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5 | Sports-related and non-sports-related sudden cardiac death in young adults. Sports-related sudden cardiac deaths were compared with non-sports-related sudden cardiac death in individuals (14 to 40 years old) who were autopsied from 1981 to 1988 at the Maryland Medical Examiner's Office. Thirty-four of 690 total cases of sudden cardiac death were sports-related, which represents 5% of sudden cardiac death in this age group. Causes of death were severe atherosclerosis (nine), hypertrophic cardiomyopathy with asymmetry (eight), coronary artery anomalies (four), idiopathic concentric left ventricular hypertrophy (three), myocarditis (two), arrhythmogenic right ventricle (one), Kawasaki disease (one), and unknown (six); two of the cases with unknown causes had tunnel arteries. Exercise-related deaths were more likely due to hypertrophic cardiomyopathy (p = 0.0007) compared with 102 age-, sex-, and race-matched controls in the non-exercise group; there was no difference in the incidence of severe atherosclerosis (p = 0.4). The mean age of individuals with hypertrophic cardiomyopathy with asymmetry was less than that of those with severe atherosclerosis (24 vs 32 years, p = 0.03). Thus exercise precipitates sudden cardiac death in younger individuals with hypertrophic cardiomyopathy. |
1 | Pelvic resections: the Rizzoli Institute experience. Materials, methods, and techniques of pelvic resections are discussed. Results, including the complications of nerve damage, infection, and vascular, visceral, and reconstructive complications are tabulated. |
1 | Combination hormonal therapy with tamoxifen plus fluoxymesterone versus tamoxifen alone in postmenopausal women with metastatic breast cancer. An updated analysis. A randomized trial was performed to determine if therapy with tamoxifen (TAM) plus fluoxymesterone (FLU) was more efficacious than TAM alone for postmenopausal women with metastatic breast cancer. Patients failing TAM could subsequently receive FLU. The dose of both drugs was 10 mg orally twice daily. Objective responses were seen in 50 of 119 (42%) TAM patients and 64 of 119 (54%) TAM plus FLU patients (two-sided P = 0.07). Time to disease progression was better for TAM plus FLU (medians: 11.6 versus 6.5 months; Cox model, P = 0.03). Duration of response and survival were similar in the two treatment arms. Among 97 patients with estrogen receptor (ER) of 10 or greater and 65 years of age or older, there were highly significant advantages for treatment with TAM plus FLU in both response rate and time to progression. Of particular note is that in this patient group TAM plus FLU showed a survival advantage (Cox model, P = 0.05). Although these data require confirmation in a prospective randomized trial, they suggest that there is a substantive therapeutic advantage for TAM plus FLU over TAM alone in elderly women with ER of 10 fmol or greater. |
5 | A new bioprosthetic cardiac valve with reduced calcification. A bioprosthetic cardiac valve cross-linked with a glycerol polyglycidyl ether polyepoxy compound (PC) was developed in order to reduce calcification and degeneration, which often occurs in bioprosthetic cardiac valves. Aortic valves harvested from dogs were treated with PC (PC valve). Right ventricle (RV)-pulmonary artery (PA) bypasses were placed in 12 dogs with PC-valved conduits, and the main PA was ligated. X-ray right ventriculography at 36 days (1 dog) and 37 days (1 dog) revealed an excellent open/close performance of the PC valve, and there was no visible thrombus in the valve. In our basic study, PC treated collagen gel disks implanted in the subcutaneous layer of growing rats showed remarkably less calcium deposition than did those treated with glutaraldehyde (GA). Biologic materials cross-linked with PC maintain their pliability, and become more hydrophilic and more hydrated than those cross-linked with GA. The hydrophilicity and hydration provide sufficient antithrombogenicity and a suitable environment for metabolism in the tissue fluid which contains oxygen, nutritive substances, and electrolytes, leading to inhibition of material degeneration. Therefore, PC valves are expected to show good valve function, sufficient antithrombogenicity, and excellent durability with less calcification, when compared to GA treated valves. |
2 | Aggravation of myasthenia gravis by erythromycin. Erythromycin is not currently recognized as causing clinical aggravation of myasthenia gravis. We report the case of a patient who experienced exacerbations of myasthenia gravis subsequent to each of several doses of intravenous erythromycin. We suggest that erythromycin can cause clinical worsening in patients with disease of the neuromuscular junction. |
3 | Intraspinal transplants. Transplants of embryonic central nervous system tissue have long been used to study axon growth during development and regeneration, and more recently to promote recovery in models of human diseases. Transplants of embryonic substantia nigra correct some of the deficits found in experimental Parkinson's disease, for example, by mechanisms that are thought to include release of neurotransmitter and reinnervation of host targets, as well as by stimulating growth of host axons. Similar mechanisms appear to allow intraspinal transplants of embryonic brainstem to reverse locomotor and autonomic deficits due to experimental spinal cord injuries. Embryonic spinal cord transplants offer an additional strategy for correcting the deficits of spinal cord injury because, by replacing damaged populations of neurons, they may mediate the restoration of connections between host neurons. We have found that spinal cord transplants permit regrowth of adult host axons resulting in reconstitution of synaptic complexes within the transplant that in many respects resemble normal synapses. Transplants of fetal spinal cord may also contribute to behavioral recovery by rescuing axotomized host neurons that otherwise would have died. Electrophysiological and behavioral investigations of functional recovery after intraspinal transplantation are preliminary, and the role of transplants in the treatment of human spinal cord injury is uncertain. Transplants are contributing to our understanding of the mechanisms of recovery, however, and are likely to play a role in the development of rational treatments. |
5 | Snoring (I). Daytime sleepiness in regular heavy snorers. Fifteen men, mean (means) age 44 years, were investigated. Their means body mass index was 21.9 kg/m2, and all of them had a respiratory disturbance index below 5 and had good nocturnal oxygen saturation. The subjects were monitored several nights both with and without the following devices: a tight-fitting facial mask, a pneumotachometer, and an esophageal balloon. They were also monitored with and without nasal continuous positive airway pressure. The Multiple Sleep Latency Test was administered after three of the experimental nights (after the baseline nights and after the second nasal CPAP night). Determination of short EEG arousals during nocturnal sleep, which lasted 2 to 10 s, was performed. The relationship between short EEG arousals, the esophageal pressure nadir, and airflow decrease was investigated. We also determined the relationship between clinical reporting of decrease in daytime alertness and MSLT results, and the relationship between MSLT results and the frequency of EEG arousals. The monitoring indicated that heavy snorers may present significant increase in Pes nadir with abrupt decrease in flow leading to EEG arousals. The frequency at which EEG arousals occur has an impact on MSLT scores. Nasal CPAP improves MSLT scores and eliminates these respiration-related EEG arousals. Some heavy snorers without obstructive sleep apnea syndrome may be at risk of having a decrease in daytime alertness. |
1 | The gastrin hypothesis. Implications for antisecretory drug selection. Newer potent and long-acting inhibitors of acid secretion, such as the proton pump inhibitor omeprazole, are becoming available for general use. These drugs promise to control acid-peptic disease effectively in patients who do not respond adequately to conventional short-acting H2-receptor antagonists. The safety of chronic administration of these drugs has come into question, however. Lifelong profound inhibition of acid secretion in rats induced by superpotent inhibitors of acid secretion or subtotal fundectomy is associated with the development of carcinoid tumors of enterochromaffin-like (ECL) cells in the gastric corpus. Available evidence supports a role of gastrin, which becomes chronically elevated in animals subjected to prolonged and profound hypochlorhydria. In humans, hypergastrinemic states such as Zollinger-Ellison syndrome and atrophic gastritis are associated with an increased risk of ECL-cell carcinoid tumors. Such observations have raised concern that humans may also be susceptible to carcinoid tumor formation in response to potent inhibitors of acid secretion. To date, however, no cases of carcinoid tumor have been attributed to the use of omeprazole in humans. If achlorhydric doses are not used, significant hypergastrinemia can be avoided while effectiveness of treatment is maintained. Such measures should minimize any risk of ECL-cell carcinoid tumors in humans taking potent long-term antisecretory drugs. |
5 | Prospective, randomized trial of the biofragmentable anastomosis ring. The BAR Investigational Group. A randomized trial was undertaken to compare the biofragmental anastomotic ring (BAR) with conventional intraperitoneal colorectal anastomotic techniques. Patients were randomized into one of two schemes: BAR versus sutured or BAR versus stapled anastomosis. There were 782 patients entered into the study and 283 patients (36%) had a sutured anastomosis, 104 patients (13%) had a stapled anastomosis, and 395 (51%) had the BAR. Comparison of the BAR with combined suture and stapled controls revealed no significant differences in wound complication, abscess rate, bleeding, anastomotic leaks, ileus, obstruction, or deaths. There were no differences in return of bowel function, return to normal diet, or hospital stay. Intraoperative difficulties occurred in 46 BAR patients (17%), and this was significantly higher (p less than 0.001) than for sutured (3%) but not for stapled anastomoses (11%). The occurrence of these problems did not adversely effect the outcome. The data suggest that the BAR is a safe, satisfactory alternative to sutured or stapled colorectal anastomoses. |
5 | Reevaluation of the periodic acid-Schiff stain in acute leukemia with immunophenotypic analyses. To determine the sensitivity and specificity of the periodic acid-Schiff (PAS) stain in the diagnosis of acute leukemia in light of the finer characterization of this disorder now available through immunophenotyping, we examined the blasts from 51 patients with newly diagnosed acute leukemia by morphological, cytochemical, and immunophenotypic analyses. The 51 patients represented every new case of acute leukemia subjected to cytochemical stains and flow cytometry between July 1987 and February 1989. By cell-surface marker analysis, 29 exhibited lymphocytic lineage, while 21 were myelocytic. One was mixed lineage. The PAS positivity, defined by the presence of blocks or coarse granules in 5% or more of the blasts, was found in 15 of 29 lymphoblastic leukemias and in four of the myeloblastic leukemias. However, PAS-positive lymphoblastic leukemias were negative with the other cytochemical stains: myeloperoxidase, Sudan black B, and alpha-naphthyl butyrate esterase. The PAS-positive myeloblastic leukemias were positive with at least one other stain. Three cases of myeloblastic leukemia exhibited greater than 10% PAS-positive blasts, with all three being acute monoblastic leukemia. Thus, the sensitivity and specificity of the PAS stain alone for lymphoblastic leukemia was 52% (15 true positives of 29) and 81% (four false positives), respectively. The sensitivity of a cytochemical-staining combination of PAS positivity and myeloperoxidase, Sudan black B, and alpha-naphthyl butyrate esterase negativity in defining cases of lymphoblastic leukemia remained at 52%; however, the specificity of this combination for lymphoblastic leukemia was 100% (no false positives). Thus, a positive PAS stain, in combination with negative myeloperoxidase, Sudan black B, and alpha-naphthyl butyrate esterase stains, continues to have a diagnostic role in the distinction between lymphoblastic and myeloblastic leukemia, and greater immunologic sophistication serves to support this position. |
3 | Motor unit discharge characteristics and short term synchrony in paraplegic humans. Frequency of firing and regularity of discharge of human motor units, and short term synchrony between pairs of motor units, have been assessed in extensor digitorum communis (EDC) and tibialis anterior (TA) muscles in control subjects and in clinically complete paraplegic subjects. The discharge pattern of TA motor units in paraplegia ranged from extremely regular to very irregular for different motor units whereas in the control population, and in EDC of both groups, there was a narrow, but intermediate, range of regularity. There was little difference in the incidence and degree of short term synchrony (STS) in EDC between paraplegic and normal subjects. In contrast, virtually no STS of motor units was observed in the TA muscles of the paraplegic group whereas control subjects exhibited approximately the same amount of STS in their TA and EDC muscles. It is concluded that the extra burden placed on arm muscles in paraplegia does not change the amount of synchronisation between motor units. Furthermore, section of the spinal cord does not increase STS as predicted from lesions of the reticulospinal tract in cats. This may reflect the coincidental removal of supraspinal synchronising inputs of motoneurons or the reorganisation of synaptic inputs in chronic paraplegia. |
4 | Doppler color-flow images from a stenosed arterial model: interpretation of flow patterns. The capability of the recently introduced Doppler color-flow mapping devices to accurately detect flow patterns in the region of an arterial stenosis was evaluated by use of an in vitro flow model. Pulsatile flow simulating that in a low-resistance vessel was induced through a straight acrylic tube, which alternatively contained axisymmetric stenoses of 0%, 20%, 40%, 60%, and 80% diameter reduction. Doppler color-flow mapper images were taken in realtime along the tube midplane from 0 to 8 diameters downstream of each stenosis. Comparison of the Doppler color-flow mapping results with similarly recorded flow visualization (hydrogen bubble) images showed a close correspondence of key features of the flow, including detection of a high-velocity, centerline jet and near-wall separated flow zones. Distinctive flow patterns exist with each stenotic case, and these should be of considerable value in diagnosing clinical disease conditions. |
5 | Salicylate poisoning from enteric-coated aspirin. Delayed absorption may complicate management. Acute salicylate poisoning with enteric-coated aspirin may result from accidental ingestion, a suicide attempt, or a complication of long-term therapy. Because absorption of enteric-coated aspirin is delayed, use of the Done nomogram to determine toxicity may lead to underestimating the severity of the poisoning. Treatment options include induction of emesis or diuresis, gastric lavage, administration of activated charcoal, and surgery. |
2 | The course of the HIV epidemic among intravenous drug users in Amsterdam, The Netherlands. To determine if behavioral changes in intravenous drug users in Amsterdam have retarded the HIV (human immunodeficiency virus) epidemic in this group in recent years, we report that: HIV-antibody seroprevalence in annual samples of injectors has been constant over the years 1986-89; HIV-antibody incidence in a cohort of injectors appears to have decreased from 1986 to 1987 and stabilized after that until 1989; acute hepatitis B incidence in all drug users in Amsterdam declined rapidly between 1985-89. It is concluded that changes in drug use behavior so far appear to have resulted in a stabilization of the epidemic among injectors, at a level with a still disturbingly high incidence rate of 5-6 per 100 person-years. |
3 | Racial differences in cerebrovascular disease hospitalizations. We studied the relationship of race to incidence of hospitalization for cerebrovascular disease among 74,096 white and 33,041 black persons who took health examinations in a prepaid health care program. Analyses were controlled for age, sex, body mass index, coffee use, smoking, alcohol use, systolic blood pressure, and baseline disease. Blacks were at higher hospitalization risk than whites for hemorrhagic cerebrovascular disease (relative risk = 2.4, 95% confidence interval = 1.3-5.8), cerebral thrombosis (relative risk = 1.9, 95% confidence interval = 1.2-2.9), and nonspecific cerebrovascular disease (relative risk = 1.6, 95% confidence interval = 1.2-2.2) but at lower hospitalization risk for extracranial occlusive disease (relative risk = 0.4, 95% confidence interval = 0.2-0.7). Blood pressure had a similar relation to all types of cerebrovascular disease in both races, but there were disparities in the relations of other atherosclerosis risk factors to different types of cerebrovascular disease. Educational attainment had little relation to hospitalization for extracranial occlusive disease, a finding that reduces the likelihood that selection bias explains the racial disparity. These data show unexplained racial differences in the type and location of cerebrovascular disease. The differences are important in understanding the pathogenesis of cerebrovascular disease and have practical clinical implications. |
2 | Diagnostic significance of carcinoembryonic antigen in the differential diagnosis of malignant mesothelioma. The histologic and cytologic distinction of malignant mesothelioma from carcinomas metastatic to the pleura or peritoneum is often problematic. For this reason immunologic methods are being increasingly used as diagnostic adjuncts. This review summarizes 40 studies on the expression of carcinoembryonic antigen in mesotheliomas and in lung and other carcinomas involving the pleura or peritoneum. Carcinoembryonic antigen was identified immunohistochemically in 11% of mesotheliomas and in 84% of carcinomas examined and immunocytochemically (in serous effusions) in 4% and 58%, respectively. In serum and in pleural or ascitic fluid, significantly elevated levels of carcinoembryonic antigen are commonly associated with (lung) carcinomas but rarely with mesotheliomas. Thus, together with identification of the antigen in serum, pleural fluid, or ascitic fluid, immunohistochemical and immunocytochemical techniques for detecting carcinoembryonic antigen provide a valuable aid for distinguishing malignant mesothelioma from metastatic carcinomas. |
1 | In vitro activity of LY264826, a new glycopeptide antibiotic, against gram-positive bacteria isolated from patients with cancer. The in vitro activity of LY264826, a novel glycopeptide antibiotic produced by Amycolatopsis orientalis, was compared with those of vancomycin, teicoplanin, and oxacillin against 311 gram-positive clinical isolates from patients with cancer, LY264826 had lower MICs for 90% of isolates (MIC90) than vancomycin for all species tested. It was active against oxacillin-resistant isolates including Staphylococcus aureus (MIC90, 0.5 micrograms/ml), Staphylococcus haemolyticus (MIC90, 2.0 micrograms/ml), Enterococcus spp. (MIC90, 0.5 micrograms/ml), Bacillus cereus (MIC90, 0.25 micrograms/ml), and Corynebacterium jeikeium (MIC90, 0.12 micrograms/ml). For S. aureus, including oxacillin-resistant isolates, the MICs of LY264826 were similar to those of teicoplanin. For coagulase-negative staphylococci, however, LY264826 had MICs that were 4- to 32-fold lower than those of teicoplanin. Against most streptococcal species the activities of LY264826 and teicoplanin were similar. Bactericidal activity against Staphylococcus spp. and most Streptococcus pyogenes isolates was less than or equal to 1 dilution of the MIC. One isolate of S. pyogenes and all Enterococcus faecalis strains tested were tolerant of LY264826, with MBCs greater than or equal to 32-fold greater than the MICs. The addition of 50% human serum resulted in a significant increase in activity only against Staphylococcus epidermidis. Variations in pH from 6.4 to 8.4 and in inoculum from 10(3) to 10(7) CFU/ml did not significantly affect the activity of LY264826. |
3 | Chronic pain--assessment of orthopedic physical therapists' knowledge and attitudes. Orthopedic physical therapists' knowledge of pain mechanisms and methods of pain management and their attitudes toward working with patients with benign chronic pain were studied. A random sample of 500 members of the American Physical Therapy Association's Section on Orthopaedics received by mail a 36-item questionnaire. Statistical analysis of scores, using frequencies, means, and correlations was performed on the 119 (23.8%) usable returns. All but 4% of the respondents preferred to work with patients who are not likely to have chronic pain. Seventy-two percent believed their entry-level education in pain management and theory was very inadequate or less than adequate to deal with an orthopedic patient population. Pain knowledge scores were low (35.8 out of 46 points), and the scores on positive attitudes toward treating patients with benign chronic pain were lower (20.5 out of 36 points). The study suggests specific deficiencies in orthopedic physical therapists' knowledge of clinical pain mechanisms and management and potentially undesirable attitudes toward treating patients with chronic pain. |
5 | Initial management of trauma. The first 5 minutes. Trauma is the leading cause of death in young Americans and is responsible for the loss of more productive years of life than heart disease and cancer combined. Initial management of trauma consists of the establishment or maintenance of a patent airway, ensurance of adequate breathing, and resuscitation of the circulation. All of these are accomplished simultaneously with a cursory survey to identify immediately life-threatening injuries and to prevent permanent disability. |
4 | Both d-cis- and l-cis-diltiazem have anti-ischemic action in the isolated, perfused working rat heart. The effect of diltiazem (d-cis-diltiazem) on the ischemic myocardium was compared with that of l-cis-diltiazem, an optical isomer having less potent calcium channel-blocking action, in the isolated, perfused working rat heart. Ischemia decreased mechanical function and tissue levels of ATP and creatine phosphate, and increased tissue levels of nonesterified fatty acids (NEFA), AMP and lactate. Reperfusion did not restore mechanical function, but restored incompletely the levels of metabolites (except NEFA) that had been altered by ischemia. The ischemia-induced changes in NEFA were prevented by d-cis-diltiazem completely and by l-cis-diltiazem incompletely. Other metabolic changes induced by ischemia were attenuated by d-cis-diltiazem but not by l-cis-diltiazem. In heart pretreated with d-cis- or l-cis-diltiazem, both the mechanical function and the levels of metabolites recovered during reperfusion, the degree of recovery with both drugs being similar. These results indicate that not only d-cis-diltiazem but also l-cis-diltiazem has an anti-ischemic action probably due to inhibition of the tissue NEFA accumulation. These results also suggest that the mechanism of the protective effect of d-cis-diltiazem on the ischemic myocardium is not entirely due to the calcium channel-blocking action. Treatment with low Ca2+ (1.0 mM CaCl2) also attenuated the ischemia-induced changes. The interval between reoxygenation and start of function in the reperfused heart that had been treated with low Ca2+ was significantly longer than that with d-cis- or l-cis-diltiazem. The effect of these isomers to shorten this interval may contribute to their common anti-ischemic action. |
1 | Results of contemporary radical cystectomy for invasive bladder cancer: a clinicopathological study with an emphasis on the inadequacy of the tumor, nodes and metastases classification. We reviewed 261 patients who underwent a radical operation at a single institution as definitive treatment of invasive bladder cancer to evaluate the survival and accuracy of the tumor, nodes and metastasis system in characterizing the prognosis. Between January 1979 and June 1987 the 261 evaluable patients underwent 1-stage radical cystectomy with pelvic node dissection and urinary diversion. No chemotherapy and/or radiation therapy was given before or after the operation. The postoperative mortality rate was 1.8%. The over-all staging error between clinical and pathological stages was as high as 44%. The over-all actuarial 5-year survival rate was 54.5%. The 5-year survival rates were 75% for stage pT1, 63% for stage pT2, 31% for stage pT3 and 21% for stage pT4 disease. A significant difference in the survival (p less than 0.002) was observed in stage pT3 by dividing tumors confined within the bladder wall (pT3a, 50%) from those extending throughout the bladder wall (pT3b, 15%). A careful evaluation of transitional cell involvement of the prostate in stage pT4a cancer led to the identification of 2 different patterns: 1) contiguous when a bladder tumor extended directly into the prostate through the bladder wall and 2) noncontiguous when a bladder tumor and a transitional cell carcinoma of the prostate were found simultaneously. These patterns had completely different (p less than 0.05) survival rates (6 versus 37%). The patients with high grade tumors had a worse prognosis in comparison with those with grades 1 and 2 tumors (41 versus 56%, p less than 0.005). The over-all 5-year survival of patients with positive nodes was 4% in comparison with 60% of those without nodal involvement (p less than 0.001). Despite current optimal surgical treatment, nearly 50% of all patients with invasive bladder cancer continue to die. The need for a modification of the current tumor, nodes and metastasis tumor classification to provide the clinician a more reliable staging system for planning treatment modalities is indeed mandatory. |
4 | Iliac artery stenosis and occlusion: preliminary results of treatment with Gianturco expandable metallic stents. Ten patients with atherosclerotic stenosis or occlusion of the iliac artery were treated with Gianturco expandable metallic stents. In the five cases of stenosis, only balloon dilation was performed prior to placement of stents. The five patients with occluded arteries were given intraarterial infusions of urokinase before balloon dilation and stent placement. Clinical symptoms improved in all patients, and no technical failures or complications occurred. Doppler ankle-brachial index studies were performed in nine cases, and in all nine cases the indexes improved after stent placement. During follow-up of 2-18 months (mean, 10.3 months), all arteries remained patent. Follow-up angiograms showed slight intimal thickening and no restenosis. Long-term follow-up and more clinical experience will be necessary to evaluate the efficacy of this stent. However, preliminary results suggest that the Gianturco expandable metallic stent is of value in the treatment of arterial occlusive disease. |
4 | Normalization of increased sodium sensitivity by maintenance hemodialysis. Blood pressure (BP) becomes more sodium and body fluid sensitive as renal function deteriorates. Thus, hypertension in chronic renal failure is mostly of the sodium sensitive type. We studied whether the increased sodium sensitivity (SS) can be restored to normal on the maintenance phase of hemodialysis (HD) therapy. Body weight (BW) and BP (specifically, mean arterial pressure [MAP]) were measured after HD and before the next HD, and the body fluid sensitivity (BFS) was calculated as the ratio of changes in these factors on both introduction and maintenance phases in HD patients (n = 56) who were not taking any antihypertensive drugs (BFS = delta MAP/delta BW). In a preliminary study, the amount of interdialytic sodium intake (QNa+) was measured (n = 30), and SS was calculated as the ratio of the change in MAP to QNa+ (SS = delta MAP/QNa+). Interdialytic BW gain (3.1 +/- 0.1 kg) was correlated with the amount of sodium intake (136 +/- 17 mEq), resulting in a positive relationship between BFS and SS (r = 0.79, P less than .0001). Therefore, BFS was used as an index of SS. As a whole, BFS decreased from the introduction to the maintenance phase (6.5 +/- 1.0 to 3.5 +/- 0.6 mm Hg/L, P less than .01). This decrease was marked (6.2 +/- 1.1 to 2.9 +/- 0.6 mm Hg/L, P less than .01) in patients (n = 46) whose BP was normalized in the maintenance phase, while not significant (7.9 +/- 1.9 to 6.3 +/- 1.3 mm Hg/L) in patients (n = 10) whose BP was still high. |
2 | Complications of Tenckhoff catheters post removal. Complications due to Tenckhoff catheters can occur at prolonged intervals after their removal. From January 1979 to October 1989, 431 patients at our center began continuous ambulatory peritoneal dialysis (CAPD), 278 of whom subsequently transferred to another form of renal replacement therapy. We identified 12 patients (4.3% or 12/278) with post removal catheter complications. There were 14 post removal complications, two each in two patients, and one in each of 12 others. The mean time to complication was 541 +/- 143 days (27-2,040). In 71% (10/14) of the complications, an abscess was found at the site of the previously removed Tenckhoff catheter. In 29% (4/14) of the complications, foreign body material consistent with a retained cuff was recovered. Documentation at the time of Tenckhoff catheter removal should include a statement regarding the presence of the Tenckhoff catheter cuffs, and patients with retained cuffs should be monitored closely for the development of abscesses or other complications. Immunocompromised patients are at high risk for these complications. |
5 | Bilateral vocal cord teflon injection. An ineffective treatment for recurrent aspiration pneumonia. Recurrent aspiration pneumonia is a potentially lethal problem, and its treatment is controversial. A variety of procedures have been advocated to prevent aspiration. These are reviewed briefly. We have been dissatisfied with established procedures because they usually require external approaches with considerable complexity and potential complications. Therefore, we attempted to obstruct the glottic airway by injecting both vocal cords with Teflon in a series of patients with recurrent aspiration pneumonia secondary to severe neurologic impairments. Since Teflon injection of the vocal cords bilaterally did not reliably prevent aspiration, we cannot recommend it for routine use in the treatment of chronic aspiration. |
5 | Scoliosis in trisomy 18. Patients with trisomy 18 typically present with multiple congenital anomalies and most die within the first year. However, long-term survivors are not uncommon. Seventeen patients with trisomy 18 were evaluated to study the development of scoliosis associated with this disorder. There were 13 females and 4 males with ages ranging from birth to 22 years. Twelve patients died by age 2. None developed scoliosis or had vertebral anomalies. The five patients who survived beyond age 2 developed scoliosis. Curve progression was demonstrated in the patients who returned for follow-up. Bracing was not well tolerated in two patients with curves of 48 degrees and 58 degrees. Both had poor motor control and sitting ability. One patient with a 30 degree curve was successfully managed by bracing. Another patient with a severe scoliosis was successfully fused with anterior and posterior instrumentation. Patients with trisomy 18 should be carefully evaluated for scoliosis. Scoliosis in the older child, surviving beyond age 2, may be progressive and difficult to manage. |
4 | Outlook after acute myocardial infarction in the very elderly compared with that in patients aged 65 to 75 years Little is known concerning late outcome and prognostic factors after acute myocardial infarction in the very elderly (greater than 75 years of age). Accordingly, this study compared the clinical course and mortality rate for up to 1 year in a large multicenter data base that included 702 patients greater than 75 years of age (mean +/- SD 81 +/- 4 years), with a less elderly subset of 1,321 patients between 65 and 75 years of age (mean 70 +/- 3 years). The postdischarge 1 year cardiac mortality rate was 17.6% for those greater than 75 years of age compared with 12.0% for patients between 65 and 75 years of age (p less than 0.01). There were differences in the prevalence of several factors, including female gender, history of angina pectoris, history of congestive heart failure, smoking habits and incidence of congestive heart failure during hospitalization. Multivariate analyses of predictors of cardiac death in hospital survivors selected different factors as important in the two age subgroups; age was selected in the 65 to 75 year age group but was not an independent predictor in the very elderly. The survival curves beginning at day 10 for patients 65 to 75 and in those greater than 75 years old were similar for up to 90 days but diverged later. In the very elderly, 63% of late cardiac deaths were sudden or due to new myocardial infarction, similar to the causes of 67% of deaths in the younger age group. |
3 | Diffuse axonal injury: analysis of 100 patients with radiological signs. One hundred patients with head injuries who showed diffuse axonal injury on computed tomographic scans are reported. Evaluation of the Glasgow Coma Score, pupillary signs, and computed tomographic findings on admission led to an improved ability to forecast outcomes. Our relatively good results as compared with other series, can be explained by the high proportion of children and by the liberal use of computed tomography to evaluate head injuries, thus revealing that concussion may sometimes be regarded as an early form of diffuse axonal injury. |
5 | Monitoring platelet interactions with prosthetic graft implants in a canine model. This study shows that prosthetic arterial grafts stimulate platelets for as long as 1 year after implantation in a canine model. Carotid-to-distal aorta Dacron (DuPont, Wilmington, DE) grafts (0.8 x 50.0 cm) were tunneled subcutaneously over the right dorsal side, allowing for percutaneous arterial sampling. Thromboxane B2 (TxB2) levels were evaluated at the proximal anastomosis (w), 5.0 (x), 25.0 (y), and 50.0 (z) cm distal from w, and platelet counts and mean platelet volumes were monitored at sites w and z. TxB2 levels increased after blood entered the graft and progressively increased until the blood exited at the distal anastomosis. Platelet counts did not significantly change across the graft. Over time, systemic platelet counts decreased to approximately 50% of each dog's pregraft baseline levels and remained depressed over a 1 year period. Mean platelet volumes peaked 1-3 weeks after implant and remained greater than pregraft levels. Examination of the graft luminal surface showed a developed pseudointima characteristically similar to that which develops in mature human vascular grafts. These results suggest that healed vascular grafts in canines continue to stimulate platelet release of TxB2, reduce systemic platelet counts, and increase mean platelet volumes over 1 year. These data further suggest that platelets are stimulated by the graft and consumed. |
5 | Traditional versus laparoscopic cholecystectomy. Laparoscopic cholecystectomy is a minimally invasive procedure whereby the gallbladder is removed using laparoscopic techniques. The indications are similar to those for elective traditional cholecystectomy, but selection of patients is important for success. Contraindications are currently evolving. Patients with advanced cholecystitis, abdominal sepsis, ileus, bleeding disorders, pregnancy, and morbid obesity should not undergo this procedure. The procedure requires good traditional surgical skills, as well as additional laparoscopic (and laser) skills. Operative time is slightly longer than for traditional cholecystectomy, but decreases with experience. Morbidity is low, but there is a concern about bile duct injuries. Mortality is very low (0%) and is comparable to traditional cholecystectomy (0.4%). The major advantages of laparoscopic cholecystectomy are the short hospital stay (average: 2 days) and early return to normal activity (7 days). This results in a reduction in hospital costs. Adequate training and credentialing are important processes to foster good patient outcomes. |
2 | Success of a program of routine prenatal screening for hepatitis B surface antigen: the first 2 years. Prenatal screening for hepatitis B surface antigen (HBsAg) restricted to women with defined risk factors for chronic hepatitis B virus (HBV) infection fails to identify many carriers. A centralized program of routine HBsAg screening for all pregnant women in Alberta was introduced in 1985. We collected and analysed data for the first 2 years of the program in Edmonton to determine the frequency of risk factors for HBsAg positivity, the proportion of multiparous HBsAg-positive women not identified in previous pregnancies, the efficiency and cost-effectiveness of providing immunoprophylaxis to infants at risk of HBV infection and the degree of success in inducing adequate protection. A total of 149 women (158 pregnancies) were found to be HBsAg positive. Risk factors were readily ascertainable for 85% of the women; the remaining 15% would not have been identified through risk-selective screening. The most common risk factors were Oriental ethnic origin, history of hepatitis, jaundice or multiple transfusions of blood or blood products, and occupational exposure to blood. Although 86% of the multiparous HBsAg-positive women had risk factors, only 7% had been identified in previous pregnancies. The Alberta program appears to be cost-effective. We conclude that only routine prenatal screening will identify all infants at risk of perinatal HBV infection and that a comprehensive public health program involving central laboratories, private physicians and public health staff can be highly effective and efficient in protecting infants against hepatitis B. |
4 | Experimental and clinical percutaneous angioscopy experience with dynamic angioplasty. The authors have used ultrathin angioscopes with high optical resolution to assess the effects of dynamic angioplasty in vitro and in vivo. Experimentally, angioscopy was used to study the effects of the 5F "Kensey" catheter in "normal" porcine coronary arteries (NPCA) and postmortem human coronary arteries (PMHCA). In NPCA, the catheter keeps a coaxial position. Intimal flaps (IFs) were seen in 21/23 NPCAs. They occurred with all cam rotation speeds and were usually single and small (less than 25% of lumen). Perforations in patent arteries were rare (1/23). However, when the catheter was forced against the wall by passing through a narrowing of 5F diameter (made by a band ligature), perforations were more common at higher cam speeds. The epicardium remained intact in two thirds of perforations. Angioscopy visualized perforations in only 10% of cases (1/10), the common sign being that of large and multiple intimal flaps, which were often obstructive (5/10). In PMHCAs, angioscopy was more sensitive than angiography in detecting atheromatous lesions. The authors were able to give a better assessment of the effect of dynamic angioplasty on treated lesions, including the demonstration of intimal flaps that were not visible on angiography. In vivo, they have performed percutaneous angioscopy before and after dynamic angioplasty using 8 French Kensey catheters. Angioscopy revealed features that were not shown angiographically. |
5 | Unruptured intracranial aneurysms and arteriovenous malformations: frequency of intracranial hemorrhage and relationship of lesions. Among 91 patients with unruptured intracranial arteriovenous malformations (AVM's), 16 patients had 26 unruptured intracranial saccular aneurysms. An actuarial analysis showed the risk of intracranial hemorrhage among patients with coexisting aneurysm and AVM to be 7% per year at 5 years following diagnosis compared to 1.7% for patients with AVM alone. The difference in length of survival free of hemorrhage was significant (log-rank, p less than 0.0007). Several angiographic and clinical parameters were investigated to better understand the relationship of these lesions. The aneurysms occurred in similar percentages in patients with small, medium, and large AVM's. Twenty-five aneurysms were on arteries feeding the malformation system, almost equally distributed proximally and distally. Eleven aneurysms were atypical in location, and all arose from primary or secondary branch feeders to the malformation; 24 were on enlarged feeding arteries. Eleven (16%) of the 67 patients with high-flow AVM's had associated aneurysms, compared with five (21%) of the 24 patients with low-flow AVM's. Four (16%) of 25 low-shunt malformations and 12 (18%) of 65 high-shunt malformations had associated aneurysms. All five aneurysms associated with low-shunt malformations were on a direct arterial feeder of the malformation. These data suggest that the intracranial AVM's predispose to aneurysm formation within AVM feeding systems and that the mechanism is not simply based upon the high blood flow or high arteriovenous shunt in these systems. |
5 | Hepatocyte transplantation into the lung for treatment of acute hepatic failure in the rat. The lung was investigated as a matrix for transplanted hepatocytes in the rat model. Surgically induced fulminant hepatic failure was successfully treated by injection of 5 to 7 x 10(7) isolated hepatocytes into the pulmonary parenchyma in 86% of the animals. No animal, however, survived injection of hepatocytes into the jugular vein. It was found that liver failure is a prerequisite for the intrapulmonary survival of hepatocytes. After regeneration of the native liver, the majority of hepatocytes are cleared away within 6 months. |
4 | Injuries to the cervical spine causing vertebral artery trauma: case reports. In four patients with lesions of the vertebral artery resulting from cervical spine injury, two were due to unilateral facet dislocation and two to fractures of the dens. There was one arterial occlusion with minor vertebrobasilar symptoms, and an arterial lesion with thrombosis causing embolic occlusion of the basilar artery with lethal outcome. In one patient a fresh fracture of the dens caused dislocation of C1/2 with reversible occlusion of the left and stenosis of the right vertebral artery, resulting in unconsciousness. In a patient with pseudarthrosis of the dens an aneurysm of the vertebral artery could be detected. Cerebellar or cerebral symptoms associated with cervical spine injury should be investigated by vertebral angiography because vertebral arterial injury may be more common than suspected and may simulate traumatic brain damage. |
1 | The clinical pharmacology of etoposide. Etoposide, a semisynthetic derivative of podophyllotoxin, is increasingly used to treat cancer. Etoposide is a phase-specific, cytotoxic drug acting in the late S and early G2 phases of the cell cycle. It appears to cause breaks in DNA by either an interaction with DNA-topoisomerase II or the formation of free radicals. Most studies show a biexponential decay after the intravenous (IV) administration of etoposide. The peak plasma concentrations of drug and the area under the concentration versus time curve (AUC) are linearly related to the IV dose. Considerable interpatient variability of pharmacokinetic variables exists after IV etoposide. Various metabolites of etoposide have been identified, but their detection and quantitation are disputed. Approximately 30% to 70% of an etoposide dose is excreted. The bioavailability of oral etoposide is approximately 50%, but its absorption is not linear with increasing doses within the range in clinical use. Considerable interpatient and intrapatient variability exists in the pharmacokinetics of oral etoposide. There is no evidence of etoposide accumulation after multiple consecutive doses by either the IV or oral route. The exact roles of the liver and kidney in metabolism and excretion of etoposide are uncertain. Etoposide has been shown to be a highly schedule-dependent drug in clinical studies. This, together with the phase-specific action of etoposide and its increasingly widespread use in treating cancer, makes the clinical pharmacology of this drug of great clinical importance. |
4 | Impaired insulin action on skeletal muscle metabolism in essential hypertension. Previous studies have shown that essential hypertension is frequently associated with insulin resistance. The tissues responsible for this metabolic alteration have not been defined. We tested the hypothesis that skeletal muscle is the site of insulin resistance of essential hypertension with the use of the perfused forearm technique. Eight hypertensive (age 42 +/- 3 years, body mass index 27 +/- 1 kg/m2, intra-arterial mean blood pressure 126 +/- 4 mm Hg) and seven normotensive (age 48 +/- 3 years, body mass index 26 +/- 1 kg/m2, mean blood pressure 95 +/- 4 mm Hg) male volunteers were studied. After glucose ingestion (40 g/m2), normal glucose tolerance in the patients was maintained at the expense of a heightened plasma insulin response, suggesting the presence of insulin resistance. During graded, local (intra-arterial) hyperinsulinemia encompassing the physiological range (12-120 milliunits/l), glucose uptake by forearm tissues was significantly (p less than 0.03) reduced in the hypertensive subjects as compared with the controls at each of five insulin steps, by 43% on the average. In addition, forearm lactate and pyruvate release were significantly less stimulated in the hypertensive than in the normotensive group (p less than 0.01 for both), presumably as a consequence of the decreased glucose influx. Forearm exchange of oxygen, carbon dioxide, lipid substrates (free fatty acids, glycerol, and beta-hydroxybutyrate), and potassium were similar in the hypertensive and normotensive groups in the basal state. Insulin had no effect on oxygen consumption, carbon dioxide production, and respiratory quotient in either study group, whereas it stimulated free fatty acids, glycerol, and potassium uptake to the same extent in the hypertensive and normotensive groups. |
5 | Occurrence of hypercalcemia and leukocytosis with cachexia in a human squamous cell carcinoma of the maxilla in athymic nude mice: a novel experimental model of three concomitant paraneoplastic syndromes. Hypercalcemia and leukocytosis may occur in conjunction as paraneoplastic syndromes associated with malignant disease. Here we describe a human squamous cell carcinoma of the maxilla that was associated with hypercalcemia and leukocytosis, and also cachexia. The primary tumor was surgically removed and established in permanent cell culture. When either primary tumors or cultured tumor cells were inoculated into nude mice, the nude mice developed the same paraneoplastic syndromes as those which occurred in the patient from whom the tumor was originally derived. The plasma calcium was increased two and one-half-fold and the WBC count 30-fold, and the body weight was decreased by 45% in tumor-bearing animals. Each of these paraneoplastic syndromes was alleviated by surgical excision of the tumor, indicating that the paraneoplastic syndromes were due to a factor or factors produced by the primary tumor. The development of each of these paraneoplastic syndromes in nude mice correlated positively with the other two syndromes. We examined the organs of tumor-bearing mice and found striking histopathologic abnormalities in the bones, spleen, and liver, but no infiltration with tumor cells. The bones showed marked evidence of osteoclastic bone resorption. This model of a human tumor associated with the hypercalcemia-leukocytosis paraneoplastic syndrome, together with cachexia, should make it possible to determine the mechanisms responsible for these paraneoplastic syndromes and their relationship to each other. |
4 | Renal vascular disease in African-Americans and other racial minorities. Hypertensive end-stage renal disease is about 10-fold more common nationwide in African-Americans than in Caucasians and 17-fold higher in some sections of the United States. These figures are alarming and require a much greater effort in understanding the causes of this disparity and improving blood pressure control in this population to prevent catastrophic renal damage. More information is also needed about the renovascular status of other minorities. Financial obstacles to antihypertensive care appear to be an important contributing factor to the disparities of end-stage renal disease in African-Americans and perhaps other minorities. |
1 | Current advances in the diagnosis and treatment of AIDS: an introduction. Significant progress has been made in the diagnosis and treatment of AIDS. Laboratory tests available for assessment of human immunodeficiency virus (HIV) infection include the detection of antibodies to HIV type 1, the direct detection of the virus, the identification of surrogate markers, and the phenotypic analysis of peripheral blood mononuclear cells. Clinicians have made great strides in the treatment of tumors, opportunistic infections, and complications associated with AIDS as well as in the treatment of the infection itself. In selected patients, treatment with interferon-alpha has been successful against AIDS-related Kaposi's sarcoma. Attempts to treat the leukopenia and anemia of patients with AIDS by the administration of hematopoietic growth factors have resulted in increased white blood cell counts and a decrease in erythrocyte transfusion requirements. In addition to zidovudine, several antiretroviral agents are undergoing testing, including the nucleoside analogues dideoxycytidine and dideoxyinosine, soluble CD4, and the glycosidase inhibitor N-butyldeoxynojirimycin. |
1 | Bowenoid papulosis. Bowenoid papulosis is an uncommon genital dysplasia induced by human papillomavirus infection. Clinically, it usually resembles persistent warts, but histologically it may be suggestive of squamous cell carcinoma in situ. This unusual disorder and recent advances in our understanding of it are reviewed. |
1 | Cutaneous surgery and the pregnant patient. Cutaneous surgery in 34 pregnant women is described. The main indication for surgery was the diagnosis and/or treatment of malignancy. Surgery during the period of organogenesis (15 to 56 days) should be avoided when possible. Patients should be positioned on the left side during the procedure to avoid the supine hypotensive syndrome. Monitoring of the fetal heartbeat is desirable. Local anesthetics, penicillin, and erythromycin are safe if used carefully. Acetaminophen is the analgesic of choice. Exposure to the sun should be avoided during the perioperative period. |
1 | Pheochromocytoma and acute myocardial infarction. When a pheochromocytoma is manifested as an acute myocardial illness, diagnosis may be difficult to make. If the tumor is suspected early enough, a workup can be done while the complications of the myocardial illness are being controlled (as in our case). The tumor can then be expeditiously removed before any further problems develop. The case presented here underscores the importance of maintaining a high index of suspicion for a pheochromocytoma in any patient who has an unexpected myocardial event. |
5 | The ventilator-dependent child: issues in diagnosis and management. Infants, children, and adolescents with chronic respiratory failure are surviving in increasing numbers and, thereby, producing a significant population of ventilator-dependent pediatric patients. Chronic respiratory failure can occur as a complication of a wide variety of disease states; in pathophysiologic terms, it generally results from either decreased central nervous system output or inadequate force generated by the respiratory pump. Its laboratory hallmark is hypercapnia with or without hypoxemia. Stabilization of the patient with mechanical ventilatory support may permit long-term survival. Management of the ventilator-dependent pediatric patient is a complex task that must begin with an accurate prognostication of each patient's survival and quality of life. Once a decision is made concerning the practicality and appropriateness of long-term ventilatory support, informed choices must be made with respect to need for an artificial airway, mode of ventilation, and location of care. Many younger patients, especially those with intrinsic lung disease (like bronchopulmonary dysplasia), may require a hospital setting for long-term care, whereas others with neuromuscular or central disorders may benefit from being discharged to home. The patient's family must be thoroughly educated in the child's care, and they must be involved in decision-making. A multidisciplinary team of physicians, therapists, nurses, and other professionals is required to deliver optimal care. Outcome is good for most patients who are carefully selected. |
3 | Primary leptomeningeal B-cell lymphoma in a 8-year-old child. A case of primary leptomeningeal B-cell lymphoma in an 8-year-old, previously healthy child is described. The child was found to have hypogammaglobulinemia, and the Epstein-Barr virus genome was identified in cultured tumor cells despite blood serology being negative for the virus. The patient was treated with cyclophosphamide, doxorubicin, vincristine, and dexamethasone, plus intrathecal methotrexate, and initially improved. Before the initiation of craniospinal radiation, the patient developed progressive disease, deteriorated, and died 9 months after the onset of symptoms. |
3 | Hyperprolactinemia increases and hypoprolactinemia decreases tyrosine hydroxylase messenger ribonucleic acid levels in the arcuate nuclei, but not the substantia nigra or zona incerta. The effects of experimentally produced hypoprolactinemia and hyperprolactinemia on tyrosine hydroxylase (TH) mRNA signal levels were examined in dopaminergic neurons ovariectomized rats. TH mRNA signal levels and relative TH quantity in the arcuate nuclei, zona incerta, and substantia nigra were evaluated by in situ hybridization and immunocytochemistry, respectively. The catalytic activity of TH in the stalk-median eminence (SME) was determined from the in vitro rate of 3,4-dihydroxyphenylalanine (DOPA) accumulation after inhibiting DOPA decarboxylase with brocresine. Chronic administration of bromocriptine (BROMO), a dopamine (DA) agonist, for 3 days reduced circulating rat PRL (rPRL) levels compared to those in the vehicle-treated controls. BROMO treatment decreased TH mRNA signal levels in the arcuate nuclei, the intensity of TH immunostaining in the arcuate-median eminence area, and the rate of DOPA accumulation in the SME. Concomitant administration of ovine PRL (oPRL) reversed the effects of BROMO on TH, resulting in markedly increased TH mRNA signal levels, intensity of TH immunostaining, and rate of DOPA accumulation. Treatment with oPRL by itself for 3 days increased TH mRNA signal levels in the arcuate nuclei and TH activity in the SME, compared to vehicle. Chronic treatment with haloperidol, a DA antagonist, increased circulating levels of endogenous rPRL and increased TH activity in the SME to values similar to those after oPRL treatment. However, in contrast to oPRL, mRNA levels in the arcuate nuclei of haloperidol-treated rats were similar to levels in vehicle-treated animals. To evaluate whether the effect of PRL on TH was species specific, oPRL or rPRL was continuously infused into the jugular vein using an osmotic minipump. TH mRNA levels in the arcuate nuclei were elevated above control levels by either oPRL or rPRL administration. TH mRNA levels in the DA perikarya located in the zona incerta and substantia nigra were not altered by treatment with a DA agonist, a DA antagonist, or PRL. These results indicate that hypoprolactinemia or hyperprolactinemia can selectively reduce or augment, respectively, TH mRNA levels in the tuberoinfundibular dopaminergic neurons. The alterations in TH mRNA content probably contribute to the decrease or increase in TH activity associated with hypoprolactinemia or hyperprolactinemia, respectively. |
5 | Microangiopathy in the eosinophilia-myalgia syndrome. The eosinophilia-myalgia syndrome associated with the ingestion of L-tryptophan was recognized in late 1989. We describe our pathologic study of skin, fascial, and muscle biopsies from 21 patients evaluated by light microscopy, histochemistry, and electron microscopy. A perivascular, lymphocytic infiltrate with eosinophils was present in the dermis, fascia, and skeletal muscle. Lymphocytic infiltration of arteries and arterioles was seen. Ultrastructurally, capillary and arteriolar endothelial cell thickening and necrosis was present. This microangiopathy suggests that ischemia may be a contributing factor to the findings in this syndrome. |
4 | Stress echocardiography and the human factor: the importance of being expert. The aim of this study was to evaluate how the diagnostic accuracy of a stress echocardiographic procedure, such as a dipyridamole echocardiography test, depends on the specific experience of the physician interpreting the test. Recordings of 50 consecutive dipyridamole echocardiographic tests were selected for the first part of the study. They were analyzed by 20 experienced echocardiographers with different backgrounds in stress echocardiography: 10 beginners (less than 20 stress studies interpreted with trained staff) and 10 experienced observers (greater than or equal to 100 stress studies performed). Diagnostic accuracy (true positive + true negative/total number of tests) versus the angiographic reference standard (greater than 70% coronary stenosis of at least one major coronary artery) was 62 +/- 6% for beginners and 85 +/- 3% for experienced observers (p less than 0.0001). In the second part of the study, 10 observers (5 beginners and 5 experienced observers) evaluated 2 different sets of 50 dipyridamole echocardiographic test studies before and after the training of the beginners. Before training, the accuracy of beginners was lower than that of experienced observers (61 +/- 7% versus 85 +/- 3%; p less than 0.001). After training, the accuracy gap was closed (83 +/- 3% versus 86 +/- 2%; p = NS). Therefore, interpretation of stress echocardiographic tests by an echocardiographer without specific training severely underestimates the diagnostic potential of this technique. One hundred stress echocardiographic studies are more than adequate to build the individual learning curve and reach the plateau of diagnostic accuracy that the test can yield. |
4 | The prophylactic use of octreotide in a patient with ovarian carcinoid and valvular heart disease. This case report describes the use of octreotide, a long-acting somatostatin analogue, in the management of a patient with an ovarian carcinoid tumour and severe cardiac valvular disease. This patient underwent laparotomy and tumour resection without complication. Anaesthesia was induced with midazolam, fentanyl, and vecuronium, and maintained with isoflurane as well as additional fentanyl and vecuronium. However, we feel that it was the use of octreotide that prevented a life-threatening crisis intraoperatively, and recommend its use in patients with carcinoid syndrome undergoing anaesthesia and surgery. |
5 | Nuclear DNA profiles in primary melanomas and their metastases. DNA-aneuploid primary melanomas are said to show a greater propensity to metastasize than those without an aneuploid profile. A higher aneuploid rate has also been reported in metastatic melanomas than in primary lesions. The ploidy profile was determined of 26 primary melanomas and their first subsequent secondaries on Feulgen-stained sections from routinely processed material using a computerized video image-analysis system. In 18 of 26 cases, both primary and secondary tumor showed similar corresponding DNA patterns. These were aneuploid in 13 of 18 of the cases. A hyperdiploid pattern was present in one case in both the primary and its metastasis, and a diploid pattern was seen in four cases. There were only eight cases in which a disparity between the nuclear ploidy profile in the primary and secondary tumor was evident. Although the results suggest that ploidy studies are not useful for predicting the metastatic potential of a primary melanoma, the maintenance of similar DNA profiles in the metastases in most of these cases was interesting in regard to tumor biology. |
5 | Methacholine challenges in the management of young children. Methacholine bronchial challenges (MBCs) have been used as an important diagnostic and management tool for physicians who treat children with chronic asthma. Despite this, children less than 5 years of age present significant diagnostic and management questions that can not easily be answered because of their inability to perform standard spirometry, and thus methacholine bronchial challenges. The present study was designed to evaluate with methacholine bronchial challenge small children (between 2 and 6 years of age) with the diagnosis of or a suspected diagnosis of asthma, utilizing a new method of evaluating airflow in small children through sound analysis, Computer Digitized Airway Phonopneumography (CDAP). There were 23 children in the study between the ages of 2 and 6 years with suspected asthma who could not perform pulmonary function tests. A control group consisting of 12 subjects between the ages of 8 and 38 years of age with a history of chronic cough and/or wheezing who could perform pulmonary function tests was also studied. Of the 12 patients over the age of 8 who had MBC, 11 of them had positive challenges with a fall in FEV1 of 19% or greater. The percent change in sound intensity levels from baseline range from 232% to 396% of baseline. There was greater than 200% change in mean intensity levels with a concentration of methacholine that produced a 19% fall in FEV1 in all of the eleven patients. For one individual who had a negative MBC there was only a 16% change in pulmonary function at 25 mg of methacholine with essentially no change in sound intensity level from baseline. |
1 | Parathyroid hormone-like peptide in normal and neoplastic human endocrine tissues. PTH-like peptide (PLP) is produced by tumors commonly associated with hypercalcemia as well as nonneoplastic tissues and several endocrine glands and tumors. To characterize the distribution of PLP in human endocrine tissues and tumors, we localized PLP in formalin-fixed paraffin-embedded material using the avidin-biotin-peroxidase technique with polyclonal antisera. Among peptide hormone-producing tissues, PLP was identified in nontumorous adenohypophysis and pituitary adenomas; medullary thyroid carcinomas; normal, hyperplastic, and adenomatous parathyroids; adrenal medulla and pheochromocytomas; normal pancreatic islets; and endocrine tumors of pancreas, gut, and lung, including small cell carcinomas. In other endocrine tissues PLP was identified in nontumorous thyroid follicular epithelium, colloid nodules, and follicular neoplasms; normal adrenal cortex, adrenocortical adenomas, and carcinomas; nontumorous testicular Leydig cells; normal ovarian granulosa and thecal cells; an ovarian thecoma and a granulosa cell tumor; placental trophoblast; and decidua. These results demonstrate that PLP is localized in many normal and neoplastic endocrine cells, including those not known to influence extracellular calcium homeostasis. The presence of PLP in a variety of endocrine tissues suggests that it may play a local physiological role in the growth or function of endocrine cells. |
5 | Vasopressin-related bullous disease of the legs. We report a 33-year-old man who developed cutaneous necrosis of the lower extremities with extensive bulla formation after i.v. administration of vasopressin for the treatment of bleeding esophageal varices. Due to its potent nonselective vasoconstrictive action, vasopressin not only may induce cardiac and gastrointestinal ischemia, but cutaneous ischemia as well. As in our patient, this may lead to extensive necrotic skin lesions at sites distant from the infusion. |
3 | Developments in 5-hydroxytryptamine receptor pharmacology in migraine. Because a satisfactory animal model for migraine does not exist, attempts to determine a common mechanism of action for effective antimigraine agents may be of benefit in elucidating the pathogenesis of this neurologic syndrome. The present review demonstrates that the clinical data that has developed over the past 30 years may allow for the elucidation of the role of specific 5-HT receptor subtypes in the pathophysiology of migraine. A large number of both acute and prophylactic antimigraine agents share an ability to interact with 5-HT receptor subtypes in human brain. As summarized in Table 3, acute antimigraine drugs (e.g., ergots, sumatriptan) share high affinity for 5-HTID receptors and somewhat lower affinity for 5-HT1A receptors. These receptors are present in certain intracranial blood vessels. 5-HT1D receptors are also located on nerve terminals where they act to inhibit the release of 5-HT and other neurotransmitters. Theoretically, 5-HTID receptor agonists may acutely inhibit the release of vasoactive or pain-inducing substances in the perivascular space. Conceivably, drugs acting at this receptor would stop the progression of this perivascular process. In addition, a number of prophylactic antimigraine drugs display a relatively high affinity for both 5-HT2 and 5-HT1C receptors in human brain. Although these receptors are also found in certain blood vessels, they are present throughout the nervous system. The receptors appear to mediate neuronal depolarizations at the cellular level. Moreover, the 5-HT2 receptor appears to play a key role in the development of inflammation in certain smooth muscle systems. Theoretically, the ability of 5-HT2 antagonists to protect perivascular inflammation may account for their efficacy in the prophylactic treatment of migraine. These data offer a novel approach to the analysis of antimigraine agents. Drugs could be selected for use in clinical migraine studies based on their selectivity for a specific 5-HT receptor subtype. For example, an agent that displays both high affinity and selectivity for 5-HT1D receptors could be clinically evaluated. Its effectiveness, or lack thereof, would indicate the importance of this specific 5-HT receptor site in the pathogenesis of migraine. Future attempts to determine a common mechanism of action for effective antimigraine agents should facilitate the elucidation of the pathogenesis of this neurologic syndrome. |
4 | A successful treatment of an intrarenal arteriovenous fistula by percutaneous embolization. A 37-year-old woman patient, known to have poorly controlled arterial hypertension that was diagnosed following a cerebrovascular accident at the age of 15 years, was referred to our outpatient clinic for investigation in 1987. An intrarenal arteriovenous fistula was diagnosed by selective renal angiography. Embolization of the fistula was performed using four 15-mm/5-cm coils, which induced thrombosis and obstructed the fistula. The vascularization of the affected kidney improved immediately. During the following 4 months, the antihypertensive treatment was stopped gradually, and the patient remained normotensive. This is an unusual case of a large intrarenal arteriovenous fistula, whose etiology was not clear, that was successfully treated by percutaneous embolization. |
5 | The malignancy-sarcoidosis syndrome. In a retrospective review of six patients with malignancy preceding sarcoidosis, we found four cases of malignant lymphoproliferative disease (LD) and one case each of ovarian cancer and breast cancer. The median interval from onset or relapse of malignancy to sarcoidosis was nine months. Of the four patients with LD, sarcoidosis appeared within six months of termination of chemotherapy for three of the patients and 15 months after allogeneic bone marrow transplantation for the fourth patient. At the time of diagnosis of sarcoidosis, there was no clinical or pathologic evidence of malignancy in the chest. We conclude that in contradistinction to the previously described syndrome of sarcoidosis preceding LD, there exists a syndrome of sarcoidosis following malignancy with or without chemotherapy. |
5 | Hemorrhoids. A practical approach to an aggravating problem. Although hemorrhoids are considered a minor medical problem, they may cause considerable discomfort and anxiety. Fortunately, treatment is often simple and surgery is rarely necessary. In this practical article, Dr Cocchiara describes internal and external hemorrhoids, a classification system, and treatment choices based on the degree of involvement. |
5 | Lumbar intervertebral disc prolapse in teenage twins. A case report and review of the literature. We report the cases of teenage twin girls presenting within months of each other with severe symptoms from lumbosacral disc prolapses, requiring laminectomy in one and chemonucleolysis in the other. CT scans showed similarities in spinal configuration, including the presence of disc bulges at the L4-5 level. This suggests a strong hereditary factor in prolapse of intervertebral discs, but a review of the literature showed little information on that aspect. |
1 | Prevention of renal disease and conservation of renal function. In summary, we have reviewed some of the most frequently encountered areas of prevention of renal failure in the elderly. They include obstruction, hypertension, drug interaction, and inappropriate use of drugs and the silent killer of the elderly, renal carcinoma. Only by a thorough understanding of the altered physiology of the aging kidney can the physician avoid making the same mistakes when new drugs are developed or new types of diseases are encountered. Proper early diagnosis and understanding the guidelines to therapy in these conditions, can save huge human costs in terms of mortality, morbidity, and money. |
1 | Prognostic factors in the treatment of hepatocellular carcinoma with transcatheter arterial embolization and arterial infusion. From January 1986 to December 1988, a prospective trial of transcatheter arterial treatment was carried out for hepatocellular carcinoma (HCC). Two hundred seventy-five patients were included. Okuda's staging system was employed. Patients with Stage I and II HCC were treated by transcatheter arterial embolization (TAE) with a gelatin sponge containing an anti-cancer agent (protocol 1a); a gelatin sponge and iodized oil mixed with an anti-cancer agent (protocol 1b); or iodized oil mixed with an anti-cancer agent (protocol 2). Patients with Stage III HCC were treated with iodized oil with anti-cancer agent (protocol 2). As an exception, patients with an unsuccessful superselective catheterization into the proper hepatic artery by Seldinger technique or obstruction of the main trunk of the portal vein were treated with percutaneous transcatheter arterial infusion into the common hepatic artery regardless of stage (protocol 3). Tumor type and extension, area of tumor involvement, portal vein involvement, method of treatment, and presence of ascites and icterus were found to be the significant factors for an initial response to therapy. Treatment method was the most important factor. Respective survival rates at 1 and 2 years were 70.9% and 55.3% for protocol 1a; 62.3% and 43.8% for protocol 1b; 37.8% and 18.3% for protocol 2; and 16.5% and 0% for protocol 3. Many factors proved to significantly influenced prognosis; however, tumor type had the most important prognostic significance followed by AFP value, ascites, treatment protocol, and area of tumor involvement. |
3 | Fulminating multiple sclerosis-like leukoencephalopathy revealing human immunodeficiency virus infection. A 66-year-old French homosexual man and a 42-year-old Brazilian man with no known risk factors for HIV infection developed headaches, asthenia, and neurologic episodes of abrupt onset. CT showed multiple hypodense, nonenhancing lesions. Serology for HIV was positive. They died respectively 2 months and 1 month after onset of the illnesses. Autopsy in both cases showed multiple, well-demarcated, demyelinating foci in the white matter of the cerebral hemispheres, brainstem, and cerebellum with histologic features characteristic of recent plaques of multiple sclerosis. There were no multinucleated giant cells or microglial nodules. Immunostaining for HIV was negative. Although a random coincidence of MS and HIV infection cannot be ruled out, the close temporal relationship between the 2 disorders suggests a possible etiologic association. |
5 | Multimodal therapy for the management of primary, nonmetastatic Ewing's sarcoma of bone: a long-term follow-up of the First Intergroup study. A total of 342 previously untreated eligible children were entered into the first Intergroup Ewing's Sarcoma Study (IESS) between May 1973 and November 1978. In group I institutions, patients were randomized between treatment 1 (radiotherapy to primary lesion plus cyclophosphamide, vincristine, dactinomycin, and Adriamycin [doxorubicin; Adria Laboratories, Columbus, OH] [VAC plus ADR]) or treatment 2 (same as treatment 1 without ADR), and group II institutions randomized patients between treatment 2 or treatment 3 (same as treatment 2 plus bilateral pulmonary radiotherapy [VAC plus BPR]). The percentages of patients relapse-free and surviving (RFS) at 5 years for treatments 1, 2, and 3 were 60%, 24%, and 44%, respectively. There was strong statistical evidence of a significant advantage in RFS for treatment 1 (VAC plus ADR) versus 2 (VAC alone) (P less than .001) and 3 (P less than .05) and also of treatment 3 versus 2 (P less than .001). Similar significant results were observed with respect to overall survival. Patients with disease at pelvic sites have significantly poorer survival at 5 years than those with disease at nonpelvic sites (34% v 57%; P less than .001). Among pelvic cases, there was no evidence of differing survival by treatment (P = .81), but among nonpelvic cases, there was strong evidence of differing survival by treatment (P less than .001). The overall percentage of patients developing metastatic disease was 44%; the percentages by treatments 1, 2, and 3 were 30%, 72%, and 42%, respectively. The overall incidence of local recurrence was 15%, and there was no evidence that local recurrence rate differed by treatment. Patient characteristics related to prognosis, both with respect to RFS and overall survival experience, were primary site (nonpelvic patients were most favorable) and patient age (younger patients were more favorable). |
4 | Anti-ischemic effects of atenolol versus nifedipine in patients with coronary artery disease and ambulatory silent ischemia. The anti-ischemic effects of atenolol and nifedipine were compared in a randomized double-blind crossover manner in 24 patients with stable exertional angina and transient silent ischemia during ambulatory electrocardiographic (ECG) monitoring. Both atenolol and nifedipine were effective (p less than 0.005) in reducing the average number and duration of transient ischemic events, but therapy with atenolol was associated with a significantly greater reduction in the mean number (p less than 0.05) and duration (p less than 0.01) of silent ischemic events. Analyses of the silent ischemic activity during the morning hours revealed that only therapy with atenolol produced a significant reduction in the average duration per patient (139 +/- 54 vs. 1,609 +/- 468 s, p less than 0.01) and in the average duration of silent ischemia per event between 6 AM and 12 noon (62 +/- 21 vs. 208 +/- 24 s, p less than 0.005). There were fewer adverse experiences during therapy with atenolol. These results show that although both atenolol and nifedipine are effective in reducing silent ischemic events, treatment with atenolol is associated with significantly greater efficacy, particularly on the morning surge of silent myocardial ischemia. |
5 | Valproate in the treatment of acute mania. A placebo-controlled study. We conducted a placebo-controlled, double-blind study of valproate, a drug originally developed as an antiepileptic, in 36 patients with acute manic episodes who had previously failed to respond to or to tolerate lithium carbonate. Treatment duration was 7 to 21 days, with no other psychotropic medications permitted except lorazepam up to 4 mg/d during the first 10 days of treatment. Serum valproate concentrations were measured three times weekly; an unblinded investigator then adjusted dosage to produce serum concentrations between 50 and 100 mg/L. Valproate proved superior to placebo in alleviating manic symptoms. The 17 patients randomized to active drug demonstrated a median 54% decrease in scores on the Young Mania Rating Scale as compared with a median 5.0% decrease among the 19 patients receiving placebo. On the 100-point Global Assessment Scale of overall psychiatric functioning, patients receiving valproate improved by a median of 20 points as compared with a zero-point change with placebo. Significant differences also emerged on the Brief Psychiatric Rating Scale and in the number of supplemental doses of lorazepam required by the patients in each group. Substantial antimanic effects appeared within 1 to 4 days of achieving therapeutic serum valproate concentrations. Adverse effects were infrequent, with no adverse effect appearing significantly more frequently with valproate than with placebo. We conclude that valproate represents a useful new drug for the treatment of manic patients. |
4 | Evaluation of postprandial hyperemia in superior mesenteric artery and portal vein in healthy and cirrhotic humans: an operator-blind echo-Doppler study. In an operator-blind design, we used an echo-Doppler duplex system to examine superior mesenteric artery and portal vein hemodynamics on two consecutive mornings in 12 fasting cirrhotic patients and 12 matched controls, randomized to a standardized 355 kcal mixed-liquid meal vs. water. Cross-sectional area and mean velocity were recorded from the portal vein and superior mesenteric artery at 30 min intervals, from 0 min to 150 min after ingestion. Flows were calculated. Pulsatility index, an index related to vascular resistance, was obtained for the mesenteric artery. Baseline flows did not differ between cirrhotic patients and control patients, but pulsatility index was reduced in the cirrhotic subjects. Maximal postprandial hyperemia was attained at 30 min. Cirrhotic patients showed a blunted hyperemic response to food. In normal controls, portal vein area increased significantly after the meal from 30 min to 150 min, whereas in cirrhotic patients a significant difference occurred only at 30 min. Pulsatility index in both groups was significantly reduced after eating, and this reduction persisted up to 150 min. No changes after ingestion of water were observed. Echo-Doppler was very sensitive in detecting postprandial splanchnic hemodynamic changes and differences between cirrhotic patients and normal subjects. Mesenteric artery pulsatility index was more sensitive than flow in detecting baseline hemodynamic differences. In cirrhotic patients, portal postprandial hyperemia was mainly related to the increase in mean velocity. |
2 | Tissue distribution of 2-3 and 2-6 sialyl Lewis A antigens and significance of the ratio of two antigens for the differential diagnosis of malignant and benign disorders of the digestive tract. The authors investigated the tissue distribution of two kinds of sialylated derivatives of Lewis A (Le(a)) antigen in patients with cancers of the digestive system using specific monoclonal antibodies, and evaluated the significance of determining the 2-3 and 2-6 sialylated Le(a) antigen levels for the diagnosis of cancer. In most specimens from patients with cancers of the pancreas, biliary tract, stomach, and colon, the 2-3 sialylated Le(a) antigen was strongly expressed in cancer cells. However, 2-6 sialylated Le(a) antigen was less frequently expressed in cancer cells. The former is therefore more specific to cancer than the latter. Also, the serum level of the 2-3 sialylated Le(a) antigen was significantly higher than that of the 2-6 counterpart in patients with cancers of pancreas, biliary tract, stomach, and colon. The resulting ratio of serum 2-3/2-6 sialylated Le(a) antigens was frequently high in patients with malignancy and was low in patients with benign disorders of these digestive organs. Therefore, the 2-3/2-6 sialylated Le(a) antigen ratio is a useful for the differential diagnosis of malignant disorders in these organs. However, liver disorders were found to be exceptional in that both antigens were mostly absent in hepatocellular carcinoma (HCC) cells in immunohistologic examination, as well as in nonmalignant parenchymal liver cells. Only the epithelial cells of the intrahepatic bile ducts expressed the 2-6 sialylated Le(a) antigen strongly, and expressed the 2-3 sialylated Le(a) antigen moderately. The levels of both antigens were sometimes high in patients with liver disorders, but the ratio always remained low in patients with HCC as well as benign liver disorders such as cirrhosis or chronic hepatitis. The sialylated Le(a) antigens, which sometimes accumulate in the sera of patients with HCC, were concluded to originate from the epithelial cells of the proliferating small bile ducts, and those serum antigens cannot be considered as evidence for the presence of liver cancer cells. |
4 | Remodeling of the rat right and left ventricles in experimental hypertension. Pathological left ventricular hypertrophy in renovascular hypertension is associated with the accumulation of fibrillar collagen within the extracellular space and around intramyocardial coronary arteries. Even though the angiotensin converting enzyme inhibitor captopril was previously found to attenuate this interstitial and perivascular fibrosis, the relative importance of arterial and ventricular systolic pressures versus circulating angiotensin II (AII) and aldosterone (AL) in promoting hypertrophy and collagen accumulation in renovascular hypertension is uncertain. By drawing on the in-parallel arrangement of the right and left ventricles, with respect to their coronary circulation, and the in-series mechanical alignment of the ventricles, with a pressure-overloaded left and a normotensive right ventricle, this study sought to address this uncertainty. Three models of experimental hypertension, each having a different circulating AII and AL profile, were examined and compared with their controls: renovascular hypertension, where both AII and AL are increased; infrarenal aorta banding, where AII and AL are normal; and a chronic infusion of AL, where AII is suppressed or normal and AL is increased. In renovascular hypertension, as well as with AL, we found a significant rise in the interstitial collagen volume fraction and perivascular collagen area of the pressure-overloaded, hypertrophied left ventricle as well as the normotensive, nonhypertrophied right ventricle. This remodeling was not seen in either ventricle with infrarenal aorta banding despite comparable systemic hypertension and left ventricular hypertrophy. Thus, in experimental arterial hypertension in the rat, myocyte and nonmyocyte compartments of the myocardium are under separate controls: myocyte hypertrophy is most closely related to ventricular loading while circulating AII and AL, acting alone or in concert with other humoral factors, regulate the accumulation of collagen within the right and left ventricles. |
5 | Complications in hyperthermia treatment of benign prostatic hyperplasia. Of 435 patients treated with local hyperthermia to the prostate 27 had 29 complications, for an over-all complication rate of 6.6%. Urinary tract infections (7 cases), hematuria (6), and epididymitis (2) accounted for roughly half of the complications and could be attributed to the insertion of a catheter rather than the treatment itself but this remains to be proved. Most of the complications occurred within the first 3 treatment sessions. Despite the complication, 9 patients continued and completed the treatment course. Mean age of the study group was 73 +/- 8.3 years. Given the age of these patients, high incidence of accompanying diseases and low rate of complications, local hyperthermia should be considered a viable low risk treatment option in patients with benign prostatic hyperplasia. |
1 | The justification for surgical treatment of metastatic melanoma of the gastrointestinal tract. Fifty-six patients with symptomatic metastatic melanoma of the gastrointestinal tract (GIT) treated surgically at the Sydney Melanoma Unit between 1974 and 1989 were reviewed. The majority of these patients presented with abdominal pain or symptoms of anemia. The small intestine was the site of metastasis in more than 80 per cent. The mean over-all survival time was 11.7 months (range of one to 60 months) after surgical treatment of a first metastasis to the GIT and 3.6 months (range of zero to 12 months) postoperatively for a second GIT metastasis. Forty-four of the patients reported complete relief of their symptoms postoperatively. The results suggest that an aggressive approach to symptomatic GIT metastases from malignant melanoma is justified both to relieve distressing symptoms and to prolong life. |
3 | Botulinum toxin treatment of cranial-cervical dystonia, spasmodic dysphonia, other focal dystonias and hemifacial spasm. In the past five years, 477 patients with various focal dystonias and hemifacial spasm received 3,806 injections of botulinum A toxin for relief of involuntary spasms. A definite improvement with a global rating greater than or equal to 2 on a 0-4 scale, was obtained in all 13 patients with spasmodic dysphonia, 94% of 70 patients with blepharospasm, 92% of 13 patients with hemifacial spasm, 90% of 195 patients with cervical dystonia, 77% of 22 patients with hand dystonia, 73% of 45 patients with oromandibular dystonia, and in 90% of 21 patients with other focal dystonia who had adequate follow up. While the average duration of maximum improvement lasted about 11 weeks after an injection (range seven weeks in patients with hand dystonia to 15 weeks in patients with hemifacial spasm), some patients benefited for over a year. Only 16% of the 941 treatment visits with follow up were not successful. Except for transient focal weakness, there were very few complications or systemic effects attributed to the injections. This study supports the conclusion that botulinum toxin injections are a safe and effective therapy for patients with focal dystonia and hemifacial spasm. |
4 | Interaction of 1,25-dihydroxyvitamin D and plasma renin activity in high renin essential hypertension. Renin secretion by the kidney is inhibited by an increase in free intracellular calcium concentration. This increase in free intracellular calcium content may be augmented by serum 1,25-dihydroxyvitamin D. In 10 subjects with high renin hypertension, an increase in dietary sodium intake resulted in an increase in urinary calcium excretion (2.5 to 3.4 mmol/L, P = .011) and an increase in serum 1,25-dihydroxyvitamin D (51.2 to 61.0 pmol/L, P = .045). An inverse correlation existed between the change in vitamin D and the change in plasma renin activity (r = -0.765, P = .01). An inverse correlation also existed between the change in plasma renin activity and the change in mean arterial blood pressure (r = -0.757, P = .011). It is postulated that the increase in dietary sodium led to an increase in serum 1,25-dihydroxyvitamin D concentration, which may have contributed to an increase in intracellular calcium concentration, a decrease in renal secretion of renin, and a fall in plasma renin activity. The resultant fall in PRA in part effected the change in blood pressure to the increased sodium intake. Therefore, 1,25-dihydroxyvitamin D may be a mediator in the response of high renin hypertension to increased sodium intake. |
4 | Caliber-persistent artery of the stomach (Dieulafoy's vascular malformation). Caliber-persistent artery of the stomach (also known as cirsoid aneurysm, Dieulafoy's lesion, and submucosal arterial malformation) is clinically manifested as recurrent, massive, often fatal hematemesis. The lesion often is not seen endoscopically. Left gastric angiography in one patient with hematemesis showed a convoluted and ectatic artery in the gastric fundus, which proved to be caliber-persistent artery of the stomach on pathological examination. The tortuosity of the abnormal vessel in this condition has been attributed to artefactual contraction of the stomach following excision and formalin fixation. This is the first reported case in which a pathologically proven lesion has been clearly visualized by angiography. This demonstrates that the submucosal vessel is truly and not artifactually sinuous. It is proposed that angiographic demonstration of a nontapering, convoluted artery in the territory of the left gastric artery is highly suggestive of caliber-persistent artery of the stomach. |
4 | Application of time series analysis to circadian rhythms: effect of beta-adrenergic blockade upon heart rate and transient myocardial ischemia. Circadian variations of transient myocardial ischemia and heart rate have been identified, but the rhythms and their response to beta blockade have not been fully characterized. Time-series analysis, a mathematical technique to describe oscillatory activity occurring within a continuous data set was used, to address these issues. Nine men with coronary artery disease underwent 72 hours of ambulatory electrocardiographic monitoring during therapy with placebo or metoprolol. During administration of placebo, ischemic time and heart rate showed a primary peak with a periodicity of approximately 24 hours with a tight coupling between the 2 variables and a secondary peak with a periodicity of 5 to 8 hours. During metoprolol therapy, heart rate and ischemic variation were reduced and the 24-hour periodicity for heart rate only remained. The 24-hour periodicity for ischemia was eliminated, but the data with 5- to 8-hour periodicity became the major component of the signal. |
5 | A comparison of the efficacy and safety of pergolide and bromocriptine in the treatment of hyperprolactinemia. Pergolide is a synthetic ergoline derivative with highly potent long-acting PRL-lowering activity, allowing therapy of hyperprolactinemia with a once daily administration of the drug. The results of two open-label, randomized controlled multicenter clinical trials are reported. Pergolide (taken once a day), was compared with bromocriptine (taken two to four times daily) regarding efficacy and safety in the reduction of PRL levels, the cessation of galactorrhea and amenorrhea, the improvement in sexual function, and tumor shrinkage in hyperprolactinemia without (trial I; 61 patients) and with radiologically evident pituitary tumors (trial II; 96 patients). Both drugs were equally effective in lowering PRL levels in both trials. A median optimal dose of 50 micrograms pergolide and 5 mg bromocriptine/day suppressed PRL levels in the 61 patients of trial I by more than 80%. During the 24-week investigational period galactorrhea disappeared in 96% and 87% of patients, whereas menstruation returned in 90% and 96% of patients, respectively. An equally high efficacy (optimal median dose: 75-100 micrograms pergolide, 7.5-10 mg bromocriptine daily) was observed in trial II, although the resumption of menses was less frequent than in the patients of trial I (50% and 58% of patients, respectively). Sexual dysfunction improved similarly on both drugs in about half the patients. In addition, tumor shrinkage occurred to a similar extent with both drugs. A high incidence of adverse events was noted especially at the initiation of therapy with both compounds: nausea, dizziness, vomiting, asthenia, headache, and decrease in blood pressure occurred at a similar incidence and extent during the use of pergolide and bromocriptine. Patients in trial I treated with pergolide reported a slightly higher incidence of fever, vasodilatation, and flu syndrome. Conclusions: in these 24-week studies comprising a total of 157 hyperprolactinemic patients, a once daily administration of pergolide was shown to be as safe and effective as the two to four times daily ingestion of bromocriptine. Longer-acting dopamine agonists like pergolide that can be taken once daily, are likely to increase the ease to adherence to the therapeutic regimen. This might result in a higher compliance to medical treatment of hyperprolactinemia. |
5 | Induction of RNA-stabilized DNA conformers by transcription of an immunoglobulin switch region A deletion DNA rearrangement is associated with immunoglobulin class switching from IgM to IgG, IgA or IgE This recombination occurs in immunoglobulin switch regions, which are complex, highly repetitive regions of DNA. As switch regions become transcriptionally active just before switch recombination, analysis of the behaviour of these sequences during transcription could elucidate the mechanism of switch recombination. Here, we report that transcription of a supercoiled plasmid containing the murine IgA switch region (S alpha) leads to a loss of superhelical turns. The resulting series of less supercoiled plasmids is stabilized by RNA-DNA hybrids formed by the nascent RNA transcripts, which remain base-paired with their DNA templates. |
3 | Excitatory amino acids in the developing brain: ontogeny, plasticity, and excitotoxicity. Besides their role as neurotransmitters, excitatory amino acids (EAAs) in the developing brain are crucially involved in plasticity and excitotoxicity which are modified by their distinct ontogeny. Along with incomplete neuritogenesis and synaptogenesis, presynaptic markers of the EAA system are immature in the developing brain; however, postsynaptic EAA system activities, particularly of the N-methyl-D-aspartate and quisqualate receptors, are transiently enhanced early in life. This transient enhancement is presumably beneficial to the immature brain because physiologic activation of the EAA system plays a critical role in plasticity of early learning and morphogenesis. At the same time, this transient hypersensitivity renders the immature brain vulnerable to pathologic excitation of the EAA system (excitotoxicity) as observed during neonatal hypoxia-ischemia. |
4 | Chinese-white differences in the distribution of occlusive cerebrovascular disease. The distribution of cerebrovascular lesions is affected by race. Blacks and Japanese have more intracranial occlusive cerebrovascular disease, while whites have more extracranial disease. Despite a high incidence of stroke in China, there are few formal studies of the distribution of vascular occlusive disease in Chinese populations. We compared clinical and angiographic features of 24 white and 24 Chinese patients with symptomatic occlusive cerebrovascular disease. In symptomatic vascular territories, whites had more severe (greater than or equal to 50% stenosis) extracranial lesions, while Chinese had more severe intracranial lesions. When we counted mild and severe lesions in a symptomatic territory, whites had more extracranial lesions while Chinese had more intracranial lesions. When we combined symptomatic and asymptomatic territories, whites had more extracranial lesions, while Chinese had more intracranial lesions. White patients reported more transient ischemic attacks. The distribution of lesions, however, was not explained by differences in incidence of transient ischemia, hypertension, diabetes, hypercholesterolemia, or ischemic heart disease between the groups. The preponderance of intracranial vascular lesions in Chinese patients is similar to that seen in blacks and Japanese. Racial differences in the occurrence of extracranial and intracranial lesions raise the possibility of a different underlying pathophysiology for the 2 locations. |
2 | Furosemide absorption in patients with cirrhosis. Twelve patients with cirrhosis (seven mild and five severe) were administered intravenous and oral furosemide in random order to assess its absorption and disposition. Total serum clearance (113 +/- 49 ml/min), volume of distribution (11.9 +/- 4.5 L), and elimination half-life (166 +/- 149 minutes) were similar to those reported previously in both healthy control subjects and patients with cirrhosis. Bioavailability of 58% +/- 17% (range, 37% to 82%) was comparable to that of previous studies, and there was no difference between patients with mild and those with severe cirrhosis. In 9 of 12 patients the mean absorption time was longer than the mean residence time determined after intravenous administration (mean for all patients, 203 +/- 86 versus 134 +/- 101 minutes; p less than 0.05), indicating that furosemide followed a "flip-flop" model in these patients. In all patients the mean absorption time was prolonged relative to normal subjects irrespective of the presence of edema. As such, the slower absorption of furosemide in edematous states, such as congestive heart failure and cirrhosis, does not appear to be a consequence of edema per se. Moreover, because similar changes occur in patients with congestive heart failure, it seems that diseases with diverse pathophysiology can slow furosemide absorption. |
1 | Preoperative cell-mediated immune function and the prognosis of patients with gastric carcinoma. The cell-mediated immune function of 83 patients with gastric carcinoma was assessed preoperatively and the results were compared to that of 52 patients with benign lesions. The data were subjected to an analysis in order to evaluate their prognostic significance. The abilities to induce allogeneic cytotoxicity and to produce interleukin 2 (IL2) in patients with stage IV carcinoma were significantly depressed, as compared to those in patients with benign lesions, whereas natural killer (NK) cell activity was not significantly impaired. There was no significant correlation among these immune functions. When the patients were stratified into two groups, those who had high (greater than the mean value in patients with benign lesions) and low (less than the same value) values of these immune reactivities, the survival of patients with high NK activity (greater than or equal to 43%) was significantly better, as compared to that of patients with low cytotoxicity (less than 43%). However, there was no correlation between the survival and allogeneic cytotoxicity in these patients. The high ability to produce IL2 (greater than or equal to 1.3 U/ml) correlated with the better survival in the patients, but not in the group of patients who underwent curative resection. |
5 | Brachial plexus block with a new local anaesthetic: 0.5 per cent ropivacaine A new local anaesthetic, ropivacaine hydrochloride, was used in a concentration of 0.5 per cent in 32 patients receiving a subclavian perivascular block for upper extremity surgery. One group (n = 15) received 0.5 per cent ropivacaine without epinephrine and a second group (n = 17) received 0.5 per cent ropivacaine with epinephrine in a concentration of 1:200,000. Anaesthesia was achieved in 87 per cent of the patients in both groups in all of the C5 through T1 brachial plexus dermatomes. Motor block was profound with 100 per cent of patients in both groups developing paresis at both the shoulder and hand and 100 per cent developing paralysis at the shoulder. There was a rapid initial onset of sensory block (a mean of less than four minutes for analgesia) with a prolonged duration (a mean of greater than 13 hr of analgesia). The addition of epinephrine did not significantly affect the quality or onset of sensory or motor block. The duration of sensory block was reduced by epinephrine at T1 for analgesia and at C7, C8, and T1 for anaesthesia. The duration of sensory block in the remaining brachial plexus dermatomes as well as the duration of motor block was not effected by epinephrine. There was no evidence of cardiovascular or central nervous system toxicity in either group with a mean dose of 2.5-2.6 mg.kg-1 ropivacaine. |
5 | Schnitzler's syndrome: a broader clinical spectrum. Schnitzler's syndrome is characterized by chronic urticaria, recurrent fever, bone pain, and lymphadenopathy in conjunction with a serum IgM M component in a concentration that is usually less than 10,000 mg/L. Complement activation and cryoprecipitation do not appear to be involved. We report two additional patients who share many of the characteristics of this entity. These patients differ from patients previously reported because of the markedly elevated IgM M-component concentration in one patient and the severity of anemia in the second patient. An increased frequency of IgG autoantibodies to interleukin-1-alpha has been reported by other investigators; it has been suggested that an antibody-mediated prolongation of the half-life of interleukin-1-alpha might account for some of the symptoms and signs of this disorder. However, neither the mediators involved in the induction of nonpruritic urticaria nor the role of the IgM M component has been established. |
5 | Acute experimental allergic encephalomyelitis in SJL/J mice induced by a synthetic peptide of myelin proteolipid protein. Clinical, histologic, and ultrastructural characteristics of acute experimental allergic encephalomyelitis (EAE) induced by sensitization with a synthetic peptide corresponding to mouse myelin proteolipid protein (PLP) residues 139-151 HCLGKWLGHPDKF were studied in SJL/J mice. Groups of mice were immunized with 20, 50, or 100 nmol of the peptide and were killed from seven to 28 days after sensitization or when they were moribund. Beginning on Day 9, the mice showed signs of EAE and the disease progressed rapidly to paralysis. Central nervous system (CNS) inflammation, edema, gliosis, and demyelination were found in all mice killed between Days 10 and 28 and white matter lesion areas correlated with clinical score at the time the mice were killed. Peripheral nerve roots and the cauda equina did not have lesions. Within the range studied, the severity of clinical or histologic disease was the same regardless of the PLP peptide dose. Two of ten mice immunized with 100 nmol and none of 14 mice given smaller doses of a synthetic peptide of mouse myelin basic protein (MBP) showed clinical EAE. These mice had small numbers of CNS lesions that were indistinguishable from those in PLP peptide-sensitized mice. These findings demonstrate that immunization of SJL/J mice with PLP peptide 139-151 produces a disease with the clinical and morphologic features of CNS tissue-, whole PLP-, whole MBP-, and MBP peptide-induced acute EAE. Thus, PLP is a major encephalitogen and immune reactions to epitopes of different myelin proteins may induce identical patterns of injury in the CNS. |
5 | Recurrent seizures in children with Shigella-associated convulsions. Fifty-five children with Shigella-associated convulsions were followed prospectively to investigate their risk of subsequent febrile or nonfebrile seizures. The duration of the follow-up period was between 6.9 and 14.1 years (9.7 +/- 3.1 years). No case of nonfebrile seizures and only 2 cases (3%) of subsequent febrile seizures were observed during this period. We conclude that although febrile and Shigella-associated convulsions share many clinical features, the natural history of these two conditions seems to be distinctly different. Shigella-related convulsions are not associated with an increased incidence of subsequent febrile or nonfebrile convulsions. |
4 | Quadricuspid aortic valve and aortic regurgitation diagnosed by Doppler echocardiography: report of two cases and review of the literature. Two cases of patients with quadricuspid aortic valve diagnosed by Doppler echocardiography are presented. Aortic regurgitation was detected by pulsed Doppler echocardiography in both patients. Because they were young patients, this aortic regurgitation indicated that aortic regurgitation is not necessarily a late-developing event, as has been thought previously. |
3 | Flecked retina associated with ring 17 chromosome. We report the case of a mentally retarded male with a ring 17 chromosome who had subretinal drusen-like deposits in each eye. This is the second report of flecked retina in a patient with ring 17 chromosome, suggesting that there may be a causal relationship between abnormalities of chromosome 17 and retinal pigment epithelial or photoreceptor dysfunction. |
3 | A review of techniques employed to estimate the number of motor units in a muscle. Being the smallest functional units under neural control, motor units play an integral role in muscle physiology. However, at the present time, there does not exist any widely accepted technique for quantifying or estimating the number of motor units in a muscle. Specifically, the existing techniques are the increment-counting technique, a technique based on spike-triggered averaging, and a macro-EMG based technique which vary in invasiveness from noninvasive to highly invasive, respectively. We discuss each of these techniques, along with their associated shortcomings, in detail. |
5 | Swan-Ganz catheter-induced massive hemoptysis and pulmonary artery false aneurysm. Swan-Ganz catheter-induced massive hemoptysis and later pulmonary artery false aneurysm occurred in a patient with prosthetic mitral regurgitation. This patient was successfully managed by double-lumen endotracheal intubation, control of pulmonary hypertension, reversal of anticoagulation, mitral valve re-replacement, and transcatheter embolization. The pertinent literature is reviewed. |
3 | Effect of parenterally administered gold therapy on the course of adult rheumatoid arthritis OBJECTIVE: To describe the course of rheumatoid arthritis over 5 years in adults and to evaluate the effect of parenterally administered gold salts on that course. DESIGN: A prospective observational study of adults with rheumatoid arthritis. Data derived from annual interviews with patients from 1983 to 1988 and from physician surveys in 1983 and 1987. SETTING: Rheumatology practices in the community. PATIENTS: The study began in 1982 with 822 adults who had rheumatoid arthritis and were under the care of rheumatologists. INTERVENTIONS: Those selected by rheumatologists in the management of their patients. MEASUREMENTS: Information describing sociodemographic and clinical characteristics, course, and therapy was collected from patients and verified by physician reports. Functional status, measured by the Health Assessment Questionnaire, and the number of painful joints were used as outcome variables. Outcome variables were adjusted for age, sex, disease duration, baseline values of the outcome variable, and the use of four disease-remittive agents other than gold. MAIN RESULTS: Multivariate repeated-measures analysis of variance showed no change in the course of rheumatoid arthritis over 5 years. The use of parenteral gold for at least 2 consecutive years at the start of the observation period produced, on average, no change in the course over 5 years in the two outcome variables. CONCLUSION: In our study of a community-based population of adults with rheumatoid arthritis who were under the care of community rheumatologists, we found that there was, on average, no statistically significant change in function or number of painful joints between 1983 and 1988. Patients receiving parenteral gold therapy for at least 2 consecutive years did not show a statistically significant difference in outcome when compared with those not receiving such therapy. |
1 | Evaluation of the serum level of immunosuppressive substance in oral cancer patients. The serum level of immunosuppressive substance (IS) was studied in 40 patients with primary oral cancer and in 79 patients without cancer. Its usefulness was evaluated as a parameter for monitoring therapy as well as recurrence of the tumors. Mean values for serum IS in patients with cancer and patients without were 687 +/- 284 micrograms/mL and 464 +/- 153 micrograms/mL, respectively. Normal healthy controls had a mean value of 431 +/- 105 micrograms/mL, with the cutoff value set at 641 micrograms/mL (mean +2 SD). Patients without cancer who had a severe infectious disease showed conspicuously high serum IS levels, and these values were closely correlated with their C-reactive protein values. The positive rate of IS increased in all patients with oral cancer was 58%. The mean level of serum IS in cancer patients was significantly higher than that of the controls (P less than .01), and the level was found to be more elevated as the stage of the disease advanced (stage I to III, 48%; stage IV, 68%). Histologic analysis of the tumor cells in patients with squamous cell carcinoma (SCC) showed that the mean serum IS level of those who had poorly differentiated SCC was much higher (937 +/- 181 micrograms/mL) than that of patients with well-differentiated SCC (616 +/- 159 micrograms/mL). Patients who had recurrent or metastatic cancer, or those who died from the cancer exhibited marked elevation of the serum IS levels, whereas patients who remained free of cancer in the follow-up period showed significantly lower serum IS levels. The rise and fall of the serum IS level was closely correlated with the disease progression and/or remission. These data strongly suggest that serum IS is a useful parameter for monitoring the disease stage as well as the effect of therapy on patients with oral cancer. |
2 | Dietary predictors of symptom-associated gallstones in middle-aged women. In 1980, 88,837 women aged 34-59 y completed a semiquantitative food frequency questionnaire and were followed for 4 y. Four hundred thirty-three women reported a cholecystectomy for recent cholecystitis, and 179 reported unremoved, newly symptomatic gallstones diagnosed by ultrasound or x ray. Among the 59,306 women with Quetelet's index of relative weight less than 25 kg/m2, inverse associations were observed between intakes of vegetable fat and vegetable protein and the risk of reportedly symptomatic gallastones, after adjusting for age, Quetelet's index in 1980, weight change between 1976 and 1980, energy intake, and alcohol intake. The relative risk in the highest quintile of vegetable fat intake, as compared with the lowest quintile, was 0.6 [95% confidence interval (CI), 0.4-0.9], and the corresponding relative risk for vegetable protein intake was 0.7 (95% CI, 0.6-0.9). No significant associations were found with energy-adjusted intakes of cholesterol, animal fat, animal protein, carbohydrate, or sucrose. |
1 | Palliative treatment of bile duct tumoral compression by an endoprosthesis: clinical results. The palliative therapy of stenoses of the biliary tract is a difficult choice. Because percutaneous or endoscopic drainage methods are fraught with complications, an endoprosthesis for surgical intubation of the biliary tract has been developed. Thirty patients were treated by this method. After choledochotomy, the endoprosthesis is positioned surgically above the sphincter of Oddi, thereby avoiding ascending cholangitis. Twenty-nine patients (13 with gallbladder cancer, 11 with cholangiocarcinomas, 5 with metastases) presented with neoplastic compression, and one patient had an early postoperative stricture with loss of substance after right hepatectomy for hepatic metastases. The operative mortality was 3.3% (one pulmonary complication). Resolution of jaundice was obtained in all but two patients, and pruritus always resolved. The mean survival time for the patients with cholangiocarcinoma was 12.2 months and 6.33 months for those with gallbladder cancer. Indices of satisfaction (Bismuth's method) were 71% (gallbladder cancer), 93.5% (hilar cholangiocarcinoma), and 92% (metastatic compressions). This new type of surgical endoprosthesis is an alternative in the palliative treatment of neoplastic hilar compression because it is well tolerated, has a low rate of operative mortality or morbidity, and affords an acceptable quality of life for the patients. |
4 | Experimental retinal branch vein occlusion in miniature pigs induces local tissue hypoxia and vasoproliferative microangiopathy. In miniature pigs, retinal veins were experimentally occluded using argon laser coagulation. Microvascular modifications leading to retinal hemorrhages and retinal edema were observed some hours after the occlusion. These lesions resolved progressively within 3 weeks after the occlusion, but in most cases ischemic retinal territories persisted. Preretinal partial pressure of oxygen (PO2) measurements, using double barrelled O2-sensitive microelectrodes, showed that all the ischemic areas were indeed hypoxic. In half of the experiments, preretinal and intravitreal new vessels grew on the ischemic territories. Tissue hypoxia appears to be a key step in triggering neovascularization. However, the critical level of hypoxia was not determined. |
5 | Obstructive sleep apnea presenting with nocturnal angina, heart failure, and near-miss sudden death. An obese woman with a one-year history of episodic nocturnal chest pain was admitted because of shock and pulmonary edema. A clinical diagnosis of acute myocardial infarction and cardiogenic shock was made. She was ventilated and successfully resuscitated. Subsequent investigations showed no evidence of cardiac dysfunction or coronary disease, but sleep study confirmed the diagnosis of obstructive sleep apnea syndrome (OSAS). We suggest that the nocturnal angina and heart failure in this patient might have resulted from extreme hypoxemia produced by OSAS. This case raised the possibility that the high cardiovascular mortality rate reported in OSAS might not necessarily relate to underlying coronary artery disease. Further investigations are required to delineate the true incidence of coronary disease in patients with OSAS. |
2 | Anorectal surgery in the HIV+ patient: update. Anorectal surgery in HIV+ patients historically has been viewed with a great deal of nihilism. Advances in medical therapy and better understanding of unique pathophysiologic processes have afforded the colorectal surgeon the ability to treat better and sometimes cure the anorectal complications of AIDS. We present a series of 75 consecutive surgical procedures (1-year accrual) on HIV+ (40) and CDC AIDS (22) patients. Surgical procedures, perioperative T cell counts, and outcome will be presented; 53 percent of procedures resulted in complete healing of anal wounds; 30 percent resulted in partial healing with symptomatic relief; 17 percent resulted in symptomatic relief or tissue diagnosis without appreciable wound healing. The healing rate was significantly higher in the HIV+ group (69 percent) compared to the AIDS group (26 percent). Perioperative T cell counts did not have predictive value on outcome. No patients suffered significant unexpected morbidity, mortality, or incontinence. Pathophysiologic mechanisms of several disease processes unique to HIV+ patients and data from our ongoing investigation using RNA hybridization are presented. |
5 | Chancroid and the role of genital ulcer disease in the spread of human retroviruses. Chancroid is the most prevalent form of genital ulcer disease in developing countries and is undergoing a resurgence in industrialized countries. As a result of a nonspecificity of the clinical findings, the etiologic diagnosis of genital ulcer disease requires laboratory support. Genital ulcer disease is a risk factor for the transmission of human retroviral infections. An understanding of this interaction is emerging and will impact on the treatment and control programs for the agents causing genital ulcer disease. |
5 | Transient cyst-like cortical defects following fractures in children. Medullary fat within the subperiosteal haematoma. Asymptomatic cyst-like cortical defects appearing after fractures in children have been occasionally reported. Typically, these defects appear during fracture consolidation, within the newly formed subperiosteal bone, proximal to the fracture line, do not enlarge, and progressively disappear. We have previously shown a fatty density on CT scan within the early cortical defect. We now present two additional cases in which early CT scans appeared to confirm that these transient cortical defects may consist of fat, and probably result from the inclusion of medullary fat within the subperiosteal haematoma. |
5 | Interleukin-6 (IL-6) is an intermediate in IL-1-induced proliferation of leukemic human megakaryoblasts. We have examined the in vitro effects of recombinant human (rh) interleukin-1 (IL-1) on the growth of purified megakaryoblasts obtained from patients with acute megakaryoblastic leukemia. We demonstrate that both IL-1 alpha and IL-1 beta treatment of these cells led to stimulation of DNA synthesis (as shown by increase of 3H-thymidine incorporation up to 35-fold) and also resulted in colony formation of leukemic megakaryoblasts. However, the stimulatory effect of IL-1 was dependent on endogenous production of IL-6, because addition of neutralizing monoclonal antibody (MoAb) to IL-6 abrogated the stimulatory activity of IL-1. In contrast, neutralizing MoAbs to granulocyte (G)-colony stimulating factor (CSF), granulocyte-macrophage (GM)-CSF, and macrophage (M)-CSF failed to counteract the growth-enhancing effects of IL-1. Leukemic megakaryoblasts accumulated IL-6 mRNA and released IL-6 protein into their culture supernatant when exposed to rh IL-1 but failed to disclose transcripts for G-, GM-, and M-CSF under these conditions. Analysis of IL-6 receptor (IL-6R) transcript levels demonstrated that megakaryoblasts constitutively expressed IL-6R mRNA and that these transcripts are down-regulated to undetectable levels upon exposure to IL-1 and IL-6. Increase of 3H-thymidine incorporation by megakaryoblasts could be duplicated by exogenous IL-6 that could be blocked by neutralizing MoAb to IL-6. In conclusion, our results suggest that leukemic megakaryoblasts could produce and secrete IL-6, and express IL-6R, and that the growth-enhancing effect of IL-1 on these cells is indirect, via production of IL-6 by leukemic cells. |
1 | Leukemia and non-Hodgkin's lymphoma and residential proximity to industrial plants. The risks of developing leukemia and non-Hodgkin's lymphoma from living near industrial facilities were evaluated among men from Iowa and Minnesota in a population-based, case-control study. We found a statistically significant increase in the risk of developing non-Hodgkin's lymphoma (RR = 1.4) and a slight, nonsignificant excess for leukemia (RR = 1.2) among individuals who lived .8-3.2 km (1/2-2 miles) from a factory. Risks were greater for certain histologic types: follicular lymphoma (RR = 1.5), acute lymphocytic leukemia (RR = 5.4), and acute myelocytic leukemia (RR = 2.2). For non-Hodgkin's lymphoma (but not for leukemia), the relative risks for those living within .8 km (1/2 mile) of a factory were similar or slightly larger than for those living .8-3.2 km (1/2-2 miles) from a factory. Risks did not increase with duration of residence near a factory. The elevated risks of non-Hodgkin's lymphoma were particularly associated with residing near stone, clay, or glass industry facilities. The risk of developing leukemia was greater among persons who resided near chemical and petroleum plants. These preliminary findings raise the possibility that general environmental exposure associated with certain industrial activities may elevate the risk of developing leukemia and non-Hodgkin's lymphoma. Evaluation of data on proximity to industrial plants from studies in other geographic locations is needed to determine whether our results represent a meaningful association. |
5 | Ciliary motility in two patients with yellow nail syndrome and recurrent sinopulmonary infections. The yellow nail syndrome (YNS) is described as a combination of yellow nails, chronic lymphedema, pleural effusions, and recurrent sinopulmonary infections, but all these features need not be present for the diagnosis. The mechanism that renders patients with this syndrome susceptible to respiratory infections is not known. To determine whether abnormal ciliary motility is a predisposing factor, in vitro ciliary beat frequency (CBF) was measured in two patients with YNS and recurrent respiratory infections. In each case, the CBF was within normal limits (12 Hz). These data suggest that abnormal ciliary motility is not a pathophysiologic mechanism of recurrent sinopulmonary infections in YNS. |
4 | The effects of etomidate on cerebral metabolism and blood flow in a canine model for hypoperfusion. The effects of etomidate, a nonbarbiturate cerebral metabolic depressant, on cerebral metabolism and blood flow were studied in 29 dogs during cerebral hypoperfusion. Three groups of animals were studied during a 45-minute normotensive and a 30-minute hypotensive period: 10 control animals without etomidate, 11 animals receiving a 0.1-mg/kg etomidate bolus followed by an infusion of 0.05 mg/kg/min etomidate (low-dose group), and eight animals receiving doses of etomidate sufficient to suppress electroencephalographic bursts (high-dose group). The mean arterial pressure fell to similar levels (p less than 0.05) during hypotension in all three groups (40 +/- 5, 38 +/- 3, and 27 +/- 6 mm Hg, respectively). The mean cerebral oxygen extraction fraction rose (p less than 0.05) from 0.23 +/- 0.02 to 0.55 +/- 0.08 in the five control animals tested and from 0.33 +/- 0.02 to 0.53 +/- 0.02 in the seven animals tested in the low-dose group, but did not increase (p greater than 0.05) in the four animals tested in the high-dose group (0.24 +/- 0.03 to 0.23 +/- 0.05). Mean cerebral blood flow levels decreased in all groups during hypotension (p less than 0.05): 42 +/- 3 to 21 +/- 4 ml/100 gm/min (52% +/- 12% decrease) in the five animals tested in the control group, 60 +/- 8 to 24 +/- 6 ml/100 gm/min (56% +/- 13% decrease) in the four animals tested in the low-dose group, and 55 +/- 8 to 22 +/- 3 ml/100 gm/min (60% +/- 4% decrease) in the four animals tested in the high-dose group. In summary, the cerebral oxygen extraction fraction increased in the control animals and low-dose recipients during hypotension, suggesting the presence of threatened cerebral tissue. In contrast, the cerebral oxygen extraction did not change during hypotension when high-dose etomidate was administered. It is concluded that high-dose etomidate may preserve the cerebral metabolic state during hypotension in the present model. |
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