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Ten-year incidence of myocardial infarction and prognosis after infarction. Department of Veterans Affairs Cooperative Study of Coronary Artery Bypass Surgery BACKGROUND. The 10-year incidence of myocardial infarction (fatal and nonfatal) and the prognosis after infarction were evaluated in 686 patients with stable angina who were randomly assigned to medical or surgical treatment in the Veterans Administration Cooperative Study of Coronary Artery Bypass Surgery. METHODS AND RESULTS. Myocardial infarction was defined by either new Q wave findings or clinical symptoms compatible with myocardial infarction accompanied by serum enzyme elevations with or without electrocardiographic findings. Treatment comparisons were made according to original treatment assignment; 35% of the medical cohort had bypass surgery during the 10-year follow-up period. The overall cumulative infarction rate was somewhat higher in patients assigned to surgery (36%) than in medical patients (31%) (p = 0.13) due to perioperative infarctions (13%) and an accelerated infarction rate after the fifth year of follow-up (average, 2.4%/yr in the surgical group versus 1.4%/yr in the medical group). The 10-year cumulative incidence of death or myocardial infarction was also higher in surgical (54%) than in medical (49%) patients (p = 0.20). According to the Cox model, the estimated risk of death after infarction was 59% lower in surgical than in medical patients (p less than 0.0001). The reduction in postinfarction mortality with surgery was most striking in the first month after the event: 99% in the first month (p less than 0.0001) and 49% subsequently (p less than 0.0001). The estimated risk of death in the absence of infarction was nearly identical regardless of treatment (p = 0.75). Exclusion of perioperative infarctions did not alter the findings. CONCLUSIONS. Although surgery does not reduce the incidence of myocardial infarction overall, it does reduce the risk of mortality after infarction, particularly in the first 30 days after the event (fatal infarctions). | 3 |
Comparative pharmacodynamics and brain distribution of E-delta 2-valproate and valproate in rats. The E-isomer of 2-unsaturated valproate (E-delta 2-VPA) is a pharmacologically active metabolite of VPA that is less teratogenic and hepatotoxic than its saturated precursor. To assess potential use of E-delta 2-VPA as an alternate to VPA, a dose-response study comparing the anticonvulsant activity and neurotoxicity of E-delta 2-VPA and VPA was conducted in rats using the intravenous (i.v.) pentylenetetrazol (PTZ)-infusion threshold seizure model. Assay of drug in whole brain and plasma allowed comparison of the drug concentration-effect relationships and the brain distribution characteristics of the two compounds. E-delta 2-VPA was two to three times more potent than VPA in elevating the clonic seizure threshold of PTZ, in reference to either plasma or whole-brain drug concentrations. Furthermore, much steeper response curves were observed with E-delta 2-VPA as compared with VPA. Within the pharmacologic concentration range (defined as EC25 to EC75), E-delta 2-VPA was less neurotoxic than VPA as assessed by behavioral tests. Therefore, E-delta 2-VPA has a much more favorable protective index than VPA. At low doses, the concentration ratios of brain to plasma for both E-delta 2-VPA and VPA increased markedly with increasing plasma drug concentration. E-delta 2-VPA and VPA were previously shown to exhibit saturable binding to rat plasma proteins. If we assume that uptake of drug into the CNS is limited to the equilibrium plasma free fraction in the brain microvasculature, much of the nonlinear brain distribution features of VPA could be accounted for by saturable drug plasma protein binding. On the other hand, more complex kinetics involving simultaneous saturation of plasma protein binding and blood-to-brain transport are proposed to explain the brain distribution of the unsaturated compound. In addition, the brain-to-free drug concentration ratios for both E-delta 2-VPA and VPA were below unity at high drug-concentration range, consistent with the presence of an efficient efflux mechanism of these compounds from brain. | 2 |
Effect of direct intracoronary administration of methylergonovine in patients with and without variant angina. The effects of intracoronary administration of methylergonovine were studied in 21 patients with variant angina and 22 patients with atypical chest pain and in others without angina pectoris (control group). Methylergonovine was administered continuously at a rate of 10 micrograms/min up to 50 micrograms. In all patients with variant angina, coronary spasm was provoked at a mean dose of 28 +/- 13 micrograms (mean +/- SD). In the control group neither ischemic ST change nor localized spasm occurred. The basal tone of the right coronary artery was significantly lower than that of the left coronary artery. The percentage of vasoconstriction of the right coronary artery was significantly higher than that of the left coronary artery. These results suggest that spasm provocation tests, which use an intracoronary injection of a relatively low dose of methylergonovine, have a high sensitivity in variant angina and the vasoreactivity of the right coronary artery may be greater than that of the other coronary arteries. | 4 |
Altered pattern of calcium kinetics in hemodialysis patients after parathyroidectomy. Six HD patients with severe secondary hyperparathyroidism (sHPT) underwent studies of calcium kinetics prior to and after parathyroidectomy (PTX) with autotransplantation. Postoperatively, patients received vitamin D and calcium supplementation. Before PTX, a markedly elevated bone turnover was found, with increased fluxes of calcium from plasma into the exchangeable calcium pool. This pool was three times larger than normal, indicating a high risk of extraosseous calcifications. Despite a marked fall in parathyroid hormone (iPTH) levels after PTX, bone cell activity was maintained, as indicated by elevated values for Ca retention. Although Ca efflux from plasma into other compartments of the exchangeable pools remained above normal, the size of the total exchangeable calcium pool markedly decreased after PTX, indicating that PTX with autotransplantation, followed by vitamin D therapy, can normalize bone turnover and shift the balance of calcium flux towards mineralized bone. Reduction in the exchangeable calcium pool may explain the clinical finding that extraosseous calcifications regress in some patients after PTX. | 4 |
Effects of changes in level and pattern of breathing on the sensation of dyspnea. Breathing during hypercapnia is determined by reflex mechanisms but may also be influenced by respiratory sensations. The present study examined the effects of voluntary changes in level and pattern of breathing on the sensation of dyspnea at a constant level of chemical drive. Studies were carried out in 15 normal male subjects during steady-state hypercapnia at an end-tidal PCO2 of 50 Torr. The intensity of dyspnea was rated on a Borg category scale. In one experiment (n = 8), the level of ventilation was increased or decreased from the spontaneously adopted level (Vspont). In another experiment (n = 9), the minute ventilation was maintained at the level spontaneously adopted at PCO2 of 50 Torr and breathing frequency was increased or decreased from the spontaneously adopted level (fspont) with reciprocal changes in tidal volume. The intensity of dyspnea (expressed as percentage of the spontaneous breathing level) correlated with ventilation (% Vspont) negatively at levels below Vspont (r = -0.70, P less than 0.001) and positively above Vspont (r = 0.80, P less than 0.001). At a constant level of ventilation, the intensity of dyspnea correlated with breathing frequency (% fspont) negatively at levels below fspont (r = -0.69, P less than 0.001) and positively at levels above fspont (r = 0.75, P less than 0.001). These results indicate that dyspnea intensifies when the level or pattern of breathing is voluntarily changed from the spontaneously adopted level. This is consistent with the possibility that ventilatory responses to changes in chemical drive may be regulated in part to minimize the sensations of respiratory effort and discomfort. | 4 |
Mixed glioblastoma multiforme and sarcoma. A clinicopathologic study of 26 radiation therapy oncology group cases. Twenty-six cases are reported of gliosarcoma (GS) retrieved from a series of 1479 glioblastomas (GBM) that were part of five consecutive, randomized Phase II or III malignant glioma protocols initiated by the Radiation Therapy Oncology Group between 1974 and 1983. The clinicopathologic features of these 26 cases, including actuarial survival times, were compared with the remaining 1453 GBM. The minimal qualitative and quantitative histologic criteria required to diagnose GS are presented. In most cases the sarcomatous component was a malignant fibrous histiocytoma; a minority were fibrosarcoma. No significant differences between GS and GBM were found with regard to age, sex, pretreatment Karnofsky performance status, tumor location, size, median survival (8.3 and 9.6 months, respectively), and actuarial survival. None of the treatment regimens, which included various combinations of radiation therapy and chemotherapy, improved the survival of GS over GBM. Selective involvement of the temporal lobe by GS was not found, and the frequency of GS was determined to be only 1.8% of all GBM. | 0 |
Erythrocyte sedimentation rate predicts early relapse and survival in early-stage Hodgkin disease. The EORTC Lymphoma Cooperative Group. OBJECTIVE: To assess the value of an elevated (greater than 30 mm/h) Westergren erythrocyte sedimentation rate (ESR) for predicting early relapse and survival after therapy in patients with clinical stage I or II Hodgkin disease. INTERVENTIONS: We studied 772 patients with early-stage Hodgkin disease who had participated in two separate multicenter clinical trials. Both trials used modern field radiotherapy and, in some patients, multi-agent chemotherapy. MAIN RESULTS: The ESR patterns were based on pretherapy and post-therapy assessments: pattern 1, always normal (n = 261); pattern 2, elevated before therapy but normal immediately after therapy (n = 121); pattern 3, elevated before therapy but normal within 3 months after therapy (n = 89); pattern 4, always elevated (n = 48); pattern 5, normal before therapy but oscillating between normal and elevated after therapy (n = 150); pattern 6, elevated before therapy but oscillating between normal and elevated after therapy (n = 130). By multivariate analysis, independent of whether or not patients received chemotherapy in the initial therapy protocol, ESR patterns 4, 5, and 6 were shown to be the best predictors for early relapse and survival when patients were stratified according to the type of chemotherapy received and the number of involved nodal areas. Patients with ESR pattern 4 had a relative risk for death seven times that of patients with patterns 1, 2, or 3. Early relapse was the second most important factor predicting death, irrespective of ESR; patients with early relapse and ESR patterns 1, 2, or 3 had a relative risk for death of 4.5, and those with early relapse and ESR patterns 4, 5, or 6 had a relative risk for death of 15. Whether or not chemotherapy was given initially did not change the relative risk, which shows that ESR, not initial therapy, was the predictor for early relapse and death due to Hodgkin disease. CONCLUSION: An unexplained elevated ESR after therapy, especially after modern radiotherapy, independent of other factors, strongly suggest the presence of aggressive and resistant Hodgkin disease. An elevated ESR is predictive of early relapse and poor prognosis; its presence justifies early aggressive therapy. | 4 |
Amniotic and thromboembolism. Embolic phenomena in pregnancy demand rapid investigation and treatment. Regardless, some patients will not survive due to the enormity of the insult. Optimally, such patients should be treated in tertiary care centers, but this is not always possible. | 4 |
Comparison of the antihypertensive efficiency of nitrendipine, metoprolol, mepindolol and enalapril using ambulatory 24-hour blood pressure monitoring. In a randomized 6-month study of 201 patients, the antihypertensive efficiency of the calcium antagonist nitrendipine, the beta 1-selective blocker metoprolol, mepindolol, the beta blocker with intrinsic activity and the angiotensin-converting enzyme inhibitor enalapril were compared as monitored by 24-hour ambulatory blood pressure (BP) measurements. The study was designed so that a comparable decrease in casual BP values was obtained with all 4 drugs. If normotension was not achieved with monotherapy, a diuretic also was administered. Pretreatment casual BP and mean 24-hour ambulatory BP values did not differ between the 4 groups. Normotension as assessed by casual BP measurements was observed in all 4 groups after 6 months of therapy, there being no significant differences between the groups. However, significantly more diuretics were required in the mepindolol (n = 14) and in the enalapril (n = 20) groups compared to the nitrendipine (n = 5) and metoprolol (n = 7) groups. Despite comparable casual BP control, the 4 groups differed significantly in their mean 24-hour measurements. The greatest systolic and diastolic BP decreases were seen in the metoprolol group. Metoprolol was also the most effective drug in decreasing the frequency of systolic pressure peaks greater than 180 mm Hg. Both beta blockers and enalapril significantly decreased the morning BP increase compared to the values before treatment, while nitrendipine did not. These data show that casual BP measurement is not a good predictor of 24-hour BP in patients taking hypertensive therapy. Despite an equal degree of "office" BP control, different antihypertensive regimens do not confer the same degree of "nonoffice" BP control. | 3 |
Medical treatment of esophageal achalasia. Double-blind crossover study with oral nifedipine, verapamil, and placebo Calcium channel blockers have been previously shown to decrease lower esophageal sphincter (LES) pressure and improve symptoms in achalasia. We performed a placebo-controlled, double-blind, crossover study to assess the effects of oral nifedipine and verapamil on LES pressure, amplitude of esophageal body contraction, and clinical symptomatology in eight patients with symptomatic achalasia diagnosed by endoscopy, barium swallow, and manometry. Patients were randomized to receive up to 20 mg nifedipine, 160 mg verapamil, or placebo and underwent esophageal manometry before (baseline) and after four weeks on each drug. Diary cards were kept to record and grade symptoms and drug plasma level determinations were correlated with manometric and clinical findings. Both nifedipine and verapamil caused a statistically significant decrease in mean LES pressure, but only nifedipine caused a significant decrease in the amplitude of contractions of the smooth muscle portion of the esophagus. No statistically significant differences in the overall clinical symptomatology were noted with any of the drugs, although some individual improvements in dysphagia and chest pain were noted. We conclude that, despite the reduction in LES pressure and contraction amplitude of the distal esophageal body, oral nifedipine and verapamil do not significantly alter the clinical symptomatology of patients with achalasia. | 1 |
The estimation of post-test probability of coronary disease following exercise testing using the sequential application of two Bayesian methods. Recent studies have revealed that Bayesian methods to estimate post-test probability following exercise testing differ in their sensitivity and specificity across the range of post-test probability. To take advantage of the relative strengths of each method, we combined two of these methods into a single method (DUAL BAYES) and compared it with the two original methods in 436 patients who underwent stress testing followed within 2 months by coronary arteriography. All patients had post-test probabilities determined using CADENZA (better sensitivity). Those CADENZA-derived probabilities greater than or equal to 50% were substituted with post-test probabilities determined by Diamond and Forrester's original TABULAR method (better specificity). Mean post-test probabilities were as follows: TABULAR 34, CADENZA 48, DUAL BAYES 37 (actual incidence 38%). Comparison of sensitivity and specificity at every fifth percentile of post-test probability revealed that the sensitivity of DUAL BAYES was better than that of TABULAR and equal to that of CADENZA at thresholds less than or equal to 10 and that the specificity was better than that of CADENZA and equal to that of TABULAR at thresholds greater than or equal to 60. Therefore using both methods as indicated above was better than using either method alone. | 3 |
Effect of hyperkalemia on experimental myocardial depression by verapamil. Three patients with systemic hypotension and sinus bradycardia that were initially refractory to conventional therapy responded well to intravenous calcium administration. Two-dimensional echocardiography revealed immediate reversal of severe left ventricular dysfunction after intravenous administration of calcium in two instances. Common factors were hyperkalemia and verapamil therapy. This interaction was examined further by evaluation of contractility, heart rate, and arterial blood pressure in anesthetized dogs. Controls (n = 9) received saline infusion, and a second group (n = 10) received saturated potassium chloride (approximately 0.2 ml/min intravenously). In control dogs, administration of verapamil (1195 +/- 181 micrograms/kg intravenously) reduced systemic arterial pressure from 113 +/- 7 mm Hg to 74 +/- 5 mm Hg, and heart rate from 147 +/- 9 beats/min to 86 +/- 11 beats/min. Potassium chloride infusion alone increased blood [K+] from 3.4 +/- 0.1 to 6.2 +/- 0.2 mEq/L, but was without hemodynamic effects. In hyperkalemic dogs, a significantly lower dose of verapamil (428 +/- 42 micrograms/kg intravenously) reduced systemic arterial pressure from 102 +/- 8 mm Hg to 36 +/- 4 mm Hg, and heart rate from 150 +/- 5 beats/min to 104 +/- 15 beats/min. Myocardial contractile function was examined with right ventricular isometric contractile force and left ventricular segment length changes. In normokalemic and hyperkalemic groups, contractility was decreased by verapamil. Effects of verapamil on arterial pressure and contractility could be reversed significantly by administration of calcium, 0.4 mEq/kg intravenously. The present results support the theory that the negative hemodynamic effects of verapamil may be exaggerated to a harmful degree by concomitant hyperkalemia. These adverse events may be reversed by calcium administration. | 3 |
Bolus versus infusion regimens of etoposide and cisplatin in treatment of non-small cell lung cancer: a study of the North Central Cancer Treatment group In an effort to test clinically the hypothesis that the duration of cellular exposure to etoposide (VP-16) and cisplatin (CDDP) is an important determinant of cytotoxicity, we performed a phase III randomized trial comparing an outpatient bolus regimen of combined VP-16 and CDDP with a sequential infusion over 72 hours of these same two drugs. All patients had stage IV non-small cell lung cancer, and survival was the primary end point. Of 113 patients randomly allocated to the study, 108 were assessable for response, survival, and toxicity. A major response was observed in 20 (37%) of 54 patients on the bolus regimen and in 16 (30%) of 54 patients receiving infusion therapy. The median time to progression was 61 and 88 days for bolus and infusion therapy, respectively. The median survival time was 148 and 157 days, respectively (P = .71). Study results were not consistent with the possibility that infusion therapy could be associated with a 50% improvement in median survival, i.e. from 5 months to 7 1/2 months. Toxicity was primarily myelosuppression and was significantly greater with the infusion regimen. We conclude that infusion therapy as tested in this protocol with VP-16 and CDDP does not offer any advantage in response rate, time to disease progression, or survival as compared with bolus therapy. In addition, infusion therapy is associated with a greater degree of neutropenia and more treatment-related deaths. | 0 |
Down-regulation of a calmodulin-related gene during transformation of human mammary epithelial cells. A human cDNA library obtained from cultured normal mammary epithelial cells (HMECs) was searched by subtractive hybridization for genes whose decrease in expression might be relevant to epithelial transformation. One clone identified by this procedure corresponded to a 1.4-kilobase mRNA, designated NB-1, whose expression was decreased greater than 50-fold in HMECs tumorigenically transformed in vitro after exposure to benzo[a]pyrene and Kirsten sarcoma virus. Sequence analysis of NB-1 cDNA revealed an open reading frame with a high degree of homology to calmodulin. NB-1 expression could be demonstrated by polymerase chain reaction amplification in normal breast, prostate, cervix, and epidermal tissues. The presence of NB-1 transcripts was variable in primary breast carcinoma tissues and undetectable in tumor-derived cell lines of breast, prostate, or other origins. NB-1 mRNA expression could be down-regulated in cultured HMECs by exposure to reconstituted extracellular matrix material, while exposure to transforming growth factor type beta increased its relative abundance. The protein encoded by NB-1 may have Ca2+ binding properties and perform functions similar to those of authentic calmodulin. Its possible roles in differentiation and/or suppression of tumorigenicity in epithelial tissues remain to be examined. | 4 |
Premalignant lesions and cancers of the skin in the general population: evaluation of the role of human papillomaviruses. To evaluate the role of human papillomaviruses (HPV) in the development of premalignant lesions and cancers of the skin in the general population, 314 biopsies obtained from 227 patients with benign neoplasms, premalignant lesions, and cancers of the skin and from 25 patients with squamous cell carcinoma of the lip were analyzed by Southern blot hybridization. DNA probes specific for various cutaneous and genital HPV types were used in hybridizations conducted under nonstringent or stringent conditions. HPV DNA sequences were only detected in eight specimens obtained from six patients: HPV 34 in one case of periungual Bowen's disease, HPV 36 and an as yet uncharacterized HPV in two cases of actinic keratosis, HPV 20 in one case of basal cell carcinoma, an as yet unrecognized HPV in one case of squamous cell carcinoma, and HPV 16 in one case of squamous cell carcinoma of the lip. None of the specimens of cutaneous horn and keratoacanthoma contained detectable HPV DNA. In contrast, HPV DNA sequences, mostly HPV 16, were detected in 13 of 23 cases of anogenital Bowen's disease and invasive Bowen's carcinoma. HPV DNA sequences were not detected in 90 cutaneous samples further analyzed by the polymerase chain-reaction technique, using amplification primers that contain conserved sequences among the genomes of HPV. These results strongly suggest that the known HPV types play only a minor role, if any, in skin carcinogenesis in the general population. | 0 |
Management of multiple risk factors for coronary heart disease in patients with hypertension. Hypertension intervention trials, which have involved mainly the use of diuretics and beta-blockers, have demonstrated a disappointing benefit in terms of reduction of coronary heart disease (CHD). Rather than suggesting that elevated blood pressure and CHD are not causally related, these data suggest that the antihypertensive agents used were not optimal for the management of hypertension and a review of the currently recommended therapies is needed. Major risk factors for CHD, which include increased blood pressure, elevated serum cholesterol levels, and smoking, are highly prevalent in the general population and appear to cluster in patients with hypertension. Therefore the treatment of hypertension demands a multifactorial approach, one that takes into consideration all the risk factors for CHD. Diuretics and beta-blockers adversely affect the serum lipid profile, and this could negate some of the CHD benefit afforded by blood pressure reduction. | 3 |
Pathologic characteristics of human T-cell lymphotropic virus (HTLV)-related extranodal orofacial lymphomas. Eleven cases of extranodal orofacial lymphomas (EOFL), consisting of four HTLV-related and seven HTLV-unrelated EOFL, were investigated with respect to the immunohistochemical and clinical features. HTLV-related EOFL were of T-cell phenotype and were associated with a poorer prognosis than HTLV-unrelated EOFL, most of which were of B-cell origin. The appearance of giant cells with cerebriform nuclei was helpful in identifying HTLV-related EOFL. The relatively high incidence of T-cell type EOFL in our series was considered to be related to the high percentage of HTLV carriers in our district, an area endemic for adult T-cell leukemia-lymphoma. | 0 |
Interferon alpha and etretinate combination treatment of cutaneous T-cell lymphoma. Eleven patients suffering from cutaneous T-cell lymphoma (mycosis fungoides) were treated with recombinant interferon alpha-2A in combination (seven patients) or alone. Two patients, one in combined treatment, went into clinical complete remission, and five experienced partial remission. Two patients progressed during therapy, and two were nonevaluable because they stopped treatment early due to side effects. Dosages of interferon were from 3 to 36 million units daily for 3 months, and thereafter 3 times weekly. Etretinate (0.7 mg/kg) was given orally. The study showed that recombinant interferon alpha-2A in combination with etretinate or alone can induce remission of cutaneous T-cell lymphoma. | 0 |
Endoscopic sclerotherapy for control of bleeding varices in children. Thirty-three children with esophageal varices due to portal hypertension underwent injection sclerotherapy over a period of 6 yr. Thirty-one completed the sclerotherapy course, and the varices were eradicated in all. In nine, the procedure was performed as an emergency because of continued bleeding and, in each case, a gastric fundal varix was the source of the blood loss. Sclerotherapy successfully controlled the bleeding in four of these, whereas five required surgical underrunning of the fundal varix. After surgery, these five continued sclerotherapy until the esophageal varices were eradicated. Complications included transient pyrexia (39%), retrosternal discomfort (30%), esophageal ulceration (18%), and esophageal stricture (12%). Rebleeding before initial eradication of the varices occurred in 12 patients but, thereafter, was very uncommon and always small in amount. Esophageal varices recurred after initial eradication in 33% of cases but were easily sclerosed with further injections. This study demonstrates that sclerotherapy is effective in reducing bleeding frequency in children with portal hypertension, but emphasizes the need for regular follow-up endoscopy after initial eradication of esophageal varices. | 4 |
Histologic similarity of murine colonic graft-versus-host disease (GVHD) to human colonic GVHD and inflammatory bowel disease. In a study designed to determine which T-cell subsets are involved in the development of murine graft-versus-host disease (GVHD), a prospective histologic analysis of gastrointestinal involvement was performed. In C57BL/6JXDBA/2F1 (B6D2F1) recipients of DBA/2 donor spleen and bone marrow cells, the colonic histologic findings were found to be similar in many respects to the histologic findings reported in human colonic GVHD and were much more severe and diffuse than were the abnormalities of the small intestine. Host irradiation before transplantation was found to play an additive or synergistic role in the development of GVHD. Furthermore the histologic features noted in DBA/2----B6D2F1 murine colonic GVHD suggest that bone marrow and spleen cell transplantation in this strain combination may be a useful model for studying the immunologic mechanisms involved in human inflammatory bowel disease. Thus severe colonic disease noted during the course of DBA/2----B6D2F1 murine GVHD was found to have significant histopathologic similarities to both human GVHD enteropathy and other inflammatory diseases of the human colon. | 1 |
Focal scleroderma and severe cardiomyopathy. Patient report and brief review. A 21-month-old infant presented with simultaneous localized scleroderma and severe cardiomyopathy with heart failure. Cardiac abnormalities and serological changes (positive rheumatoid factor assay, elevated IgM and IgG levels, and elevated erythrocyte sedimentation rate) reverted to normal with prednisone therapy, and there was substantial, though incomplete, resolution of her skin changes during the same period. To our knowledge, this is the first patient with definite, clinically significant cardiac involvement associated with focal scleroderma. The possibility of internal organ involvement, including cardiac involvement, must be considered with focal scleroderma as well as with progressive systemic sclerosis. | 3 |
U1 small nuclear RNA plays a direct role in the formation of a rev-regulated human immunodeficiency virus env mRNA that remains unspliced. rev-regulated expression of HIV-1 envelope proteins from a simian virus 40 late replacement vector was found to be dependent on the presence of a 5' splice site in the env mRNA in spite of the fact that this mRNA remains unspliced. When the 5' splice site upstream of the env open reading frame was deleted or mutated, expression of envelope protein was lost. RNA analysis of cells transfected with 5' splice-site mutants showed a dramatic reduction in the steady-state levels of env mRNA whether or not rev was present. Envelope expression could be restored in one of the 5' splice-site mutants by cotransfection with a plasmid expressing a suppressor U1 small nuclear RNA containing a compensatory mutation. These experiments show that U1 small nuclear RNA plays a direct and essential role in the formation of an unspliced RNA that is subject to regulation by rev. | 4 |
The systemic septic response: concepts of pathogenesis. Following resuscitation from shock, the clinical phase of persistent hypermetabolism is entered from which a substantial number of patients transcend into progressive organ failure and expire. The available epidemiologic, physiologic, and metabolic data are consistent with the position that a persistent degree of microcirculatory hypoxia, although it may be present in amounts that are below the sensitivity of current detection systems, becomes an increasingly less important etiologic factor as the organ failure disease progresses. Rather, aerobic metabolism appears to be the dominant mechanism of meeting the increased work loads and energy demands. There is an increasing body of evidence that cytokine release systemically, and increased cell-cell interaction through cytokines and prostanoids locally, may alter not only parenchymal function in the proximity of these mononuclear cells, but organ function at distant sites. If this latter hypothesis continues to be substantiated, it implies that the underlying cell and organ dysfunction may indeed be reversible if appropriate counter-regulatory mechanisms could be developed and the appropriate timing of their application understood. | 4 |
Restoration of sinus rhythm during two consecutive pregnancies in a woman with congenital complete heart block. In a woman with congenital complete heart block atrioventricular conduction was normal during two successive pregnancies. Pregnancy, labour, and delivery were uncomplicated on both occasions and complete heart block returned post partum. | 3 |
Oscillometric finger blood pressure versus brachial auscultative blood pressure recording. In this study, a recently marketed proprietary finger blood pressure monitor, the Marshall, Astro F-88, was compared with the standard auscultative brachial mercury sphygmomanometer on 125 subjects. Measurements were undertaken according to the standards set by the American Heart Association. Sensitivity of the finger blood pressure measurement was 76% for systolic and 75% for diastolic blood pressure in diagnosis of high blood pressure (systolic greater than 140 mm Hg and diastolic greater than 90 mm Hg). Specificity was 86% for systolic and 82% for diastolic blood pressure. Positive predictive values were 58% for systolic and 38% for diastolic blood pressure in the study population in which prevalence of hypertension was 12%. The correlation coefficient (Pearson) for systolic values between devices was 0.76 (P less than .0001) and 0.57 (P less than .0001) for diastolic pressure. Values obtained by the finger monitor were found to be higher than those obtained by the mercury sphygmomanometer. Mean differences and standard deviations (paired t test) for systolic and diastolic pressures between the two devices were 2.3 +/- 14.9 mm Hg (P less than .08) and 2.9 +/- 14.5 mm Hg (P less than .02), respectively. These values are not in accordance with the proposed national standards because only 48% of the systolic and 37% of the diastolic blood pressure measurements were within 5 mm Hg of the mercury sphygmomanometer measurements. Therefore, although these differences may well be due to different techniques of monitoring employed by the devices, this device is not recommended for evaluation of blood pressure. | 3 |
Monitoring enzyme replacement treatment in exocrine pancreatic insufficiency using the cholesteryl octanoate breath test. The cholesteryl-14C-octanoate breath test was used to monitor the intraluminal enzymatic activity of pancreatin preparations in six patients with severe pancreatic insufficiency. Conventional enzyme replacement, with cimetidine as an adjunct, was compared to supplementation with enteric coated microspheres. In healthy control subjects, 14CO2 excretion rose rapidly and peaked at 90-120 minutes; mean (SD) cumulative recovery at four hours was 51 (8)%. In patients with pancreatic insufficiency on no treatment mean (SD) cumulative recovery was only 6 (4)%. After pancreatin, with previous administration of cimetidine, it increased to 27 (11)% with a time course resembling that in controls. With 2 mm enteric coated microspheres, 14CO2 excretion did not rise significantly before 120 minutes and cumulative recovery after four hours was 15 (11)%. In a control study, 2 mm radio-opaque microspheres did not empty from the stomach until two hours after ingestion. The results suggest that the cholesteryl octanoate breath test can be successfully used to monitor the intraluminal enzymatic activity after treatment with different forms of enzyme replacement in pancreatic insufficiency. In contrast to treatment with conventional pancreatin and cimetidine as an adjunct, 2 mm enteric coated microspheres did not show in vivo enzymatic activity until two hours after administration. | 1 |
Frequency and clinical implications of monoclonal antibody detection of tumor-associated antigens in serum of patients with lung cancer. We previously showed that a panel of monoclonal antibodies (MAb) (5E8, 5C7, and 1F10) that detect serum tumor-associated antigens (TAA) could distinguish patients with lung cancer from those without to a highly significant degree. However, among patients with lung cancer, the frequency and clinical importance of serum TAA expression were not established. Therefore, we analyzed the serum and initial clinical characteristics of 52 Philadelphia VA patients with newly diagnosed lung cancer seen over a 13-month period. A modified semiquantitative ELISA was employed to determine MAb reactivity. Our cohort was characterized by a mean age of 65 +/- 9 year (SD) and mean Karnovsky score of 74 +/- 10; marked weight loss was present in 28 subjects, and 39 presented with either Stage III or IV disease. The panel detected TAAs in 38 of 52 cases (sensitivity 73%; 95% Cl, 60-83%), including 13 of 22 squamous cell, 9 of 12 adenocarcinoma, 10 of 11 undifferentiated, and 6 of 7 small cell carcinomas. No significant differences were found between the reactive and nonreactive patients in terms of age, stage at presentation, histologic subtype, performance status, or weight loss. However, 1F10 and 5C7 were each associated with a greater risk of early death by Cox proportional hazard analysis (p = 0.017 and 0.006, respectively) even when other prognostic variables are accounted for. We conclude that specific serum TAA can be detected in the majority of lung cancer patients with all major histologic subtypes in a cohort with advanced tumors and poor prognostic indices. | 0 |
Acute hemodynamic effects of captopril in children with a congestive or restrictive cardiomyopathy The acute hemodynamic effects of captopril were evaluated at cardiac catheterization in 16 children (age, 0.3-18 years) with cardiomyopathy. Twelve children had congestive cardiomyopathy, whereas four had restrictive cardiomyopathy. Hemodynamic measurements were obtained 30 and 60 minutes after the oral administration of captopril (0.5 mg/kg). Blood pressures were measured in the aorta, pulmonary artery, right atrium, and pulmonary capillary wedge position; cardiac outputs were measured by the thermodilution technique. Hemodynamic data could not be obtained after the administration of captopril in one child with congestive cardiomyopathy because of an immediate, severe hypotensive response. In 11 of 12 children with congestive cardiomyopathy, cardiac index increased by 22%, from 2.3 to 2.8 l/min/m2 (p less than 0.05), and stroke volume increased by 22%, from 23 to 28 ml/m2 (p less than 0.05). Systemic vascular resistance decreased from 32 to 21 units.m2 (p less than 0.01), but the mean aortic pressure did not change significantly. In contrast, four children with restrictive cardiomyopathy had no change in cardiac output after captopril, but there was a trend toward significant arterial hypotension (mean aortic pressure decreased from 78 to 59 mm Hg). Thus, captopril acutely reduced systemic vascular resistance and increased both cardiac output and stroke volume in children with congestive cardiomyopathy. In children with restrictive cardiomyopathy, however, captopril did not affect cardiac output, but it did decrease aortic pressure. These data indicate that captopril may benefit children with a congestive cardiomyopathy but that captopril probably should not be used in children with restrictive disease. | 3 |
The role of adjuvant chemotherapy following cystectomy for invasive bladder cancer: a prospective comparative trial. We assigned 91 patients with deeply invasive, pathological stage P3, P4 or N+ and Mo transitional cell carcinoma of the bladder (with or without squamous or glandular differentiation) to adjuvant chemotherapy or to observation after radical cystectomy and pelvic lymph node dissection. For most patients chemotherapy was planned as 4 courses at 28-day intervals of 100 mg./M.2 cisplatin, 60 mg./M.2 doxorubicin and 600 mg./M.2 cyclophosphamide. A significant delay was shown in the time to progression (p = 0.0010) with 70% of the patients assigned to chemotherapy free of disease at 3 years compared to 46% in the observation group. Median survival time for patients in the chemotherapy group was 4.3 years compared to 2.4 years in the observation group (p = 0.0062). In addition to treatment groups, important prognostic factors included age, gender and lymph node status. The number of involved lymph nodes was the single most important variable. We recommend adjuvant chemotherapy for patients with invasive transitional cell carcinoma after definitive surgical resection. | 0 |
Gallbladder dynamics in patients with irritable bowel syndrome and essential dyspepsia. To assess whether gallbladder motility is altered in patients with irritable bowel syndrome (IBS) or essential dyspepsia (ED), we studied gallbladder function in 25 healthy volunteers, 20 patients with IBS, and 22 with ED. By real time ultrasonography, we studied the following parameters: (a) fasting gallbladder volume, (b) maximum percent of gallbladder emptied, (c) time required for maximal contraction, (d) residual volume after maximal contraction, and (e) percent fasting volume at 2 h. All parameters, except fasting gallbladder volume, were measured after a high-fat meal. The fasting gallbladder volume, maximum percent of gallbladder emptied, time required for maximal contraction, residual volume after maximal contraction, and percent fasting volume at 2 h in controls and patients with IBS was 19.3 +/- 8.8 ml and 24.4 +/- 9.7 ml, 67.1 +/- 10.7% and 67.6 +/- 13.5%, 41 +/- 20.6 min and 49.7 +/- 25.3 min, 6.2 +/- 3.3 ml and 7.6 +/- 5.3 ml, and 38.1 +/- 12.2% and 40.7 +/- 14.5%, respectively. The differences between the two groups were statistically not significant. The corresponding values in patients with ED were 15.5 +/- 6.3 ml, 57.6 +/- 16.5%, 51.8 +/- 29.3 min, 6.1 +/- 3.2 ml, 44.1 +/- 17%, respectively. Compared with controls there was no statistically significant difference in these parameters, except the maximum percent of gallbladder emptied, which was significantly less than that in controls (57.6 +/- 16.5% vs. 67.1 +/- 10.7%; p less than 0.05). Therefore, we could not find that patients with IBS have any abnormality of gallbladder function; postprandially, patients with ED have submaximal contraction of the gallbladder. | 1 |
Intrapartum, intranasal cocaine use and acute fetal distress. A case report. Intrapartum, intranasal cocaine was used for relief of labor pains by a healthy woman with an uncomplicated pregnancy. Fetal hypoxemia and distress followed the event. A causal relationship between the intrapartum use of cocaine and the fetal distress was postulated. Cocaine abusers could benefit from hospitalization early in labor for close surveillance and monitoring, thus avoiding exposure to cocaine and its unpredictable systemic effects. | 2 |
Time to recovery of the hypothalamic-pituitary-adrenal axis after curative resection of adrenal tumors in patients with Cushing's syndrome. The recovery time of the hypothalamic-pituitary-adrenal (HPA) axis after curative resection of adrenal tumors in patients with Cushing's syndrome is poorly documented. Eight consecutive patients were treated with a standardized hydrocortisone replacement strategy after curative resection of a cortisol-secreting tumor and the time to recovery of the HPA axis was determined. Hypercortisolism was documented by elevated 24-hour urinary free cortisol levels. Cure was documented by undetectable postoperative morning serum cortisol levels. Each patient received replacement hydrocortisone after surgery and was reevaluated every 3 to 6 months with an adrenocorticotrophic hormone (ACTH) stimulation test. Each patient was also monitored carefully for symptoms and signs of adrenal insufficiency, which was defined as symptoms consistent with this diagnosis that responded to increases in hydrocortisone levels. After surgical resection, each patient was cured of hypercortisolism. Subsequently, despite replacement hydrocortisone, each patient had symptoms of hypocortisolism, and in four of eight patients the dose of hydrocortisone was increased to relieve the symptoms. Patients required a median time of 15 months (range, 9 to 22 months) to recover a normal ACTH stimulation test and 19 months (range, 12 to 24 months) to allow discontinuation of replacement doses of hydrocortisone. The results suggest that surgical resection of a cortisol-secreting adrenal tumor will result in rapid cure of hypercortisolism, but complete recovery of the HPA axis and discontinuation of replacement steroids will require between 1 and 2 years. Normal adrenal function, as assessed by the cortisol response to ACTH, returns despite replacement doses of hydrocortisone, and replacement doses of hydrocortisone can be tapered rapidly or discontinued after a normal ACTH stimulation test. | 0 |
The role of prostanoids in the production of acute acalculous cholecystitis by platelet-activating factor. Gallbladder tissue from patients with acute acalculous cholecystitis contains increased amounts of prostanoids when compared to normal gallbladder tissue. Platelet-activating factor (PAF) is a potent stimulus of eicosanoid formation. It has been implicated as a mediator of acute inflammatory processes and systemic responses to shock. In this study the role of PAF in acute acalculous cholecystitis was evaluated. Anesthetized cats underwent gallbladder perfusion with a physiologic buffer solution containing [14C]polyethylene glycol as a nonabsorbable tracer to quantitate mucosal water absorption. Platelet-activating factor was infused into the hepatic artery for 2 hours. Control experiments were performed when vehicle alone was infused. Experiments also were performed when indomethacin was administered intravenously and when indomethacin and PAF were administered. Gallbladder mucosal absorption/secretion and perfusate and tissue prostaglandin E (PGE) and 6 keto prostaglandin F1 alpha (6-keto PGF1 alpha) levels were evaluated. Gallbladder inflammation was evaluated by beta-glucuronidase and myeloperoxidase tissue concentrations and by a histologic scoring system. Platelet-activating factor eliminated gallbladder absorption and produced net fluid secretion associated with dose-related increases in perfusate PGE concentrations and gallbladder tissue PGE and 6 keto PGF1 alpha levels when compared to control values. Platelet-activating factor produced significant inflammation in the gallbladder with increases in the histologic score of inflammation and tissue lysosomal enzyme activities. Indomethacin significantly decreased the fluid secretion, prostanoid levels, and inflammation produced by PAF. The results suggest that PAF may induce acute gallbladder inflammation associated with systemic stress through a prostanoid-mediated mechanism. | 4 |
Insulin-like growth factor-I supports proliferation of autocrine thymic lymphoma cells with a pre-T cell phenotype. We have studied the phenotypic characteristics and growth properties of murine T lymphoma cell lines derived from primary x-ray-induced thymic lymphomas at the earliest stage at which they can be detected, and well before spreading to other organs has occurred. These cell lines serve as model systems for the earliest events in T cell lymphoma induction, before tumor cell progression and spreading to other organs. We find that primary x-ray-induced T cell lymphoma lines have phenotypic characteristics of thymic pre-T cells and show no proliferative response to any of the IL tested nor to other hematopoietic growth factors. However, they do proliferate in response to insulin-like growth factor I (IGF-I) and to a small autocrine peptide distinct from IGF-I, which we term lymphoma growth factor. One of the earliest lesions in T cell lymphoma induction may therefore be an inhibition of differentiation at one of several specific points. In its early stages, T lymphoma cell growth may be restricted to an environment where local concentrations of specific growth factors such as IGF-I or lymphoma growth factor are sufficiently high. | 0 |
Aggressive oral refeeding in hospitalized patients. Malnutrition is an important clinical condition leading to increased morbidity and mortality. This report describes an aggressive oral refeeding program of high-caloric foods, which was instituted in severely anorectic patients because of their refusal to eat meals or supplements. After ascertaining a patient's favorite sweet, hospital personnel and family collaborated in providing the food. Frequently, sweets were the patient's only intake for weeks. We saw a gradual return of appetite, inclusion of other foods in the diet, and overall clinical improvement in comorbid conditions. These cases suggest that aggressive oral refeeding with high-caloric foods is an underutilized therapy for multiply impaired elderly patients. | 4 |
Vascular entrapment of intra-aortic balloon after short-term balloon counterpulsation. Prolonged, continuous intra-aortic balloon (IAB) counterpulsation for several weeks can result in balloon entrapment secondary to thrombus formation in the balloon lumen. In this report, we describe a patient who developed IAB entrapment, early (1 wk) after initiation of counterpulsation. A trace amount of blood was noted in the tubing connecting the balloon catheter to the console for 3 days prior to IAB malfunction and vascular entrapment. We suggest that the balloon catheter be removed immediately when blood is detected in the external connecting tubing even if the IAB is functioning satisfactorily. | 3 |
Tissue expansion in the treatment of pressure ulcers. The authors report their experience using skin expanders in 11 patients with severe bed sores. The expanders, with different volumes, from 250 to 1000 cc, were generally overfilled using the cutaneous tonometer. In fact, with the information revealed by this apparatus on the skin in expansion, the authors were able to reduce the filling intervals without risking ulceration. In their experience, the results obtained were satisfactory: All patients treated achieved surgical recovery. The authors see a wide future for skin-expander use in pressure-ulcer treatment. They have a working hypothesis about using expanders to progressively advance sensitive skin in areas subject to ulceration. This hypothesis is based on the possibility of reexpanding the same flap several times, as has been seen in the treatment of other types of pathology. | 4 |
Effective endothelialization of polyurethane surfaces. Response to shear stress and platelet adhesion. Biomer and Mitrathane are thromboresistant polyurethane ureas that are suitable for coating artificial valves. Degeneration of the surface coatings, however, does occur over time, and in experimental animal studies adherent thrombi have been observed as a complication. In this study, morphometric techniques applied to scanning electron microscopy were used to assess whether vascular endothelial cells harvested from jugular veins of fetal lambs could be grown to confluence on these polyurethane surfaces, whether the monolayer would remain intact under conditions of shear stress (104 dynes/cm2), and whether this would result in decreased platelet adherence of sheep platelets relative to nonendothelialized surfaces. The results have shown that both Biomer and Mitrathane could be endothelialized: 88.8 +/- 5.1% of the Biomer surface consisted of intact confluent endothelial cells, as did 95.45 +/- 1.7% of the Mitrathane surface. After 6 hr of shear stress, a significant reduction in this feature was observed (p = 0.02), but both materials still maintained a high percentage of confluent endothelial cells (78.65% for Biomer and 85.58% for Mitrathane). After 48 hr of shear stress, however, the percent confluence was similar to control values, which suggested new cell growth. Endothelialized Biomer compared with Mitrathane had fewer adherent single platelets, or small or large aggregates (p = 0.001, p = 0.01, and p = 0.05, respectively); this feature was not affected by shear stress. Whereas endothelialization of the surface clearly decreased platelet adherence on Mitrathane (p = 0.01), only a trend was seen with Biomer. These studies therefore show that endothelialization of these polyurethane surfaces is feasible. | 3 |
Essential hypertension: a sign in search of a disease. The concept of disease is of cardinal importance in medical practice. The current definition has developed over more than 200 years. It includes a distinctive natural history and identifiable cellular changes. Pickering proposed a fundamental alteration to the definition when he suggested that essential hypertension is a quantitative disease without causative cellular change distinguishing normal from abnormal. The nature of essential hypertension has been confused from the beginning because of a category error. Injury is conceptually distinguished from disease. Essential hypertension, defined as elevated blood pressure together with its cardiovascular consequences, is found to be neither an injury nor a disease according to current definitions. Instead, essential hypertension refers to a treatment group just as "the fevers" did in an earlier century. One effect on patients of the failure to resolve this diagnostic paradox is the burden of suffering from the label of "disease" rather than from a state that may be substantially due to their own behavior. A theoretical consequence of importance for psychiatric theory is that the disease status of functional disorders can no longer be defended by an appeal to the existence of a quantitative disease of blood pressure. | 3 |
Second-line platinum therapy in patients with ovarian cancer previously treated with cisplatin. In an effort to critically define the incidence and clinical characteristics of secondary responses to cisplatin-based therapy in patients with ovarian cancer previously treated with a cisplatin-based program, a retrospective review was undertaken of patients at the Memorial Sloan-Kettering Cancer Center who received greater than or equal to two cisplatin/carboplatin-based programs. Eighty-two patients were identified who met the entry criteria of having had a cisplatin-free interval (CFI) of more than 4 months between the completion of their first regimen and the institution of a second cisplatin/carboplatin program. Of the 72 assessable patients (10 had no measurable disease, and a laparotomy was not performed to assess response), 31 (43%) responded, including 10 surgically defined complete responses (S-CRs). The overall response rates (and S-CR rate), based on duration of CFI, were 5 to 12 months, 27% (5%); 13 to 24 months, 33% (11%); and more than 24 months, 59% (22%). Twenty-nine patients (35%) received noncisplatin/carboplatin-containing treatments between the cisplatin programs. Patients without any treatment for more than 24 months from the completion of their initial therapy experienced a 77% (17 of 22) response rate and a 32% (seven of 22) S-CR rate. In conclusion, secondary responses to cisplatin/carboplatin-based treatment are common in patients with ovarian cancer who have previously responded to the agents and increase in frequency with greater distance from the initial therapy. | 0 |
Surgical treatment of extramammary Paget's disease. A report of six cases and a reexamination of Mohs micrographic surgery compared with conventional surgical excision. Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy, usually on the genitalia, that almost always extends beyond clinically apparent margins. Recurrences after standard methods of surgical excision are notoriously frequent; effective treatment with Mohs micrographic surgery was first reported in 1979. It has since been suggested this malignancy may be multifocal, and reports of recurrences after resection with micrographic surgery have appeared. The authors report six cases treated with Mohs surgery, two of which recurred. They also present data on 42 additional cases obtained from a written survey of members of the American College of Mohs Micrographic Surgery and comparison cases selected from the literature. The recurrence rate after micrographic surgery appears to be at least as low as that after conventional surgical excision with vertical frozen section or paraffin section margin control. Mohs micrographic surgery allows for maximal tissue sparing of critical anatomic structures and is performed under local anesthesia as an outpatient; because of this, it may be superior to conventional surgical excision. A scheme for management of this malignancy is presented. Surgeons should be aware radical excision is not needed for most cases of extramammary Paget's disease and very long-term patient follow-up is required. | 0 |
The relationship between viral RNA, myelin-specific mRNAs, and demyelination in central nervous system disease during Theiler's virus infection. The DA strain of Theiler's murine encephalomyelitis virus (DAV) causes a chronic demyelinating disease in susceptible mouse strains. To elucidate the pathogenesis of DAV-induced demyelination, the authors investigated the spatial and chronologic relationship between virus (antigen and RNA), myelin-specific mRNAs, and demyelination in DAV-infected mice using immunohistochemistry, in situ hybridization, and slot blot hybridization analyses. In spinal cord white matter, viral RNA was detected easily in ventral root entry zones 1 to 2 weeks after infection. Viral RNA increased to maximum levels by 4 weeks after infection, which was associated with inflammation and mild demyelination. At 8 to 12 weeks after infection, when demyelination became most extensive, viral RNA was significantly decreased. Demyelination did not chronologically or spatially parallel the presence of viral RNA within the spinal cord. Decrease of myelin-specific mRNAs, including myelin-basic protein and proteolipid protein mRNAs, was observed within the demyelinating lesions with or without detectable viral RNA. These results indicate that a viral infection of white matter in the early phase of the infection initiates spinal cord disease leading to demyelination, but later an ongoing immunopathologic process contributes to the presence of extensive demyelination. | 2 |
Accidental poisoning with a superwarfarin compound (brodifacoum) in a child. The "superwarfarin" compounds are 4-hydroxy derivatives of coumarin that have increased activity and a longer duration of action than the parent compound. The superwarfarins are used widely in the United States as rodenticides and are effective against warfarin-resistant strains of rats. A chronic accidental ingestion of one of these products, brodifacoum, by a 7-year-old child who had bleeding and laboratory evidence suggestive of a vitamin K-related coagulopathy is reported. The bleeding manifestations were severe and prolonged, requiring 13 months for normalization of coagulation times. With a negative history of ingestion and despite clinical suspicion, documentation of superwarfarin poisoning was hampered by the lack of readily available assays for these compounds, even from the manufacturers. Brodifacoum was also identified in rat feces from the family home. This finding raises the concern of poisoning not only from ingestion of brodifacoum particles themselves, but also from a fecal-oral route. A review of the literature is presented and the implications of this case for the practicing physician are discussed. | 4 |
The reproducibility of intravascular ultrasound imaging in vitro. To determine which factors may affect the image quality when an intravascular ultrasound catheter is used in vivo, the influence of blood, temperature change, and contrast media were evaluated. In addition, to confirm the reproducibility of intravascular ultrasound imaging to measure cross-sectional lumen area, intraobserver and interobserver variability were determined. The findings indicated that ultrasound images in blood are mildly attenuated, that changes from room temperature to body temperature do not have a significant impact on the image quality, that contrast media attenuates the image intensity in a dose-dependent manner, and that the intravascular ultrasound imaging catheter provides a reproducible method for measuring arterial lumen area with excellent intraobserver and interobserver correlation. | 3 |
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. | 0 |
Primary balloon dilatation of coarctation of the aorta in neonates. Primary balloon dilatation of coarctation of the aorta was attempted in 10 consecutive neonates (age range 2-23 days). The coarctation site was crossed and the balloon inflated in all but one patient. In two patients with associated severe isthmal hypoplasia there was no change in the gradient after dilatation. In the remainder, the residual gradients were trivial and angiography showed complete relief of coarctation. Severe recoarctation developed 5-12 weeks after dilatation in five patients, each considered to have had an excellent initial result. The coarctation was rapidly progressive in three patients in whom Doppler studies within two weeks of the development of recoarctation had shown no significant gradient. In the other two patients progressive restenosis was charted by Doppler examinations over the course of 6-8 weeks. Three patients had a second, initially successful, dilatation procedure. One patient remained well with no residual gradient 18 weeks later. Stenosis recurred within eight weeks in the other two, and both have undergone successful surgical repair. Balloon dilatation of a native coarctation of the aorta gave excellent immediate results in most neonates. Severe isthmal hypoplasia is, however, a contraindication to balloon dilatation and early restenosis is an important problem. These results do not support the continued use of primary balloon dilatation of coarctation of the aorta in neonates. | 4 |
Stomal adenocarcinoma in Crohn's disease. Malignant change occurring at the site of a stoma in two patients with proved Crohn's disease is described. Patients with ulcerative colitis have an increased risk of colonic malignancy and Crohn's disease is also associated with both small and large bowel carcinoma. Most previous reports of stomal carcinoma have been associated with ulcerative colitis although Crohn's disease seems to carry a greater risk of associated small bowel carcinomas. This is the first report of stomal carcinoma complicating Crohn's disease. Epithelial dysplasia is associated with gastrointestinal carcinomas in both ulcerative colitis and Crohn's disease and a dysplasia-carcinoma sequence has been suggested as the origin of these tumours. In both our patients with stomal adenocarcinoma, dysplasia was identified in adjacent tissues, which suggests a similar mechanism. Malignant change should be suspected if epithelial dysplasia is discovered in a biopsy specimen from the mucosa of an ileostomy in Crohn's disease, and this risk is increased if the dysplasia is of a high grade. | 1 |
Doppler diagnostics, indications, and control of surgical treatment in patients with carotid pathology. Major stroke is a relatively common cause of death or disabling invalidism in patients with atherosclerosis. In a large percentage of cases it is caused by stenotic/thrombotic processes in carotid arteries and this emphasizes the importance of the problem of early diagnosis and treatment of carotid pathology. Recently Doppler sonography has become a leading non-invasive method of early screening of stenotic processes in carotid arteries. The aim of the present study was to ascertain the diagnostic abilities of Doppler sonography for screening of carotid pathology, assessment of extra-cranial and intracranial hemodynamics, defining of indications, and control of vascular reconstructions of carotids. | 3 |
Embolization with particles in thoracic intramedullary arteriovenous malformations: long-term angiographic and clinical results. To evaluate the long-term results of endovascular treatment with particles in the management of thoracic intramedullary arteriovenous malformations (AVMs), the authors retrospectively reviewed the angiographic and clinical findings in 35 patients. Follow-up was 1-15 years (mean, 6 years) in 28 patients and 6-10 months (mean, 7 months) in seven. A total of 158 embolization procedures were performed in 35 patients. Revascularization occurred frequently, necessitating multiple endovascular sessions. Long-term clinical evaluation showed clinical improvement, compared with the initial status before treatment, in 63% of the patients. Clinical aggravation due to embolization was observed in seven patients (20%) after 12 of the 158 endovascular sessions (8%). These results are better than those reported after surgery and indicate that embolization with particles is an efficient and safe tool in the treatment of thoracic intramedullary AVMs. | 2 |
Surgical aspects of sclerosing encapsulating peritonitis. Sclerosing encapsulating peritonitis (SEP) is associated with the administration of beta-blocking agents as well as continuous ambulatory peritoneal dialysis. The predisposing factors in the latter group are recurrent peritonitis, presence of acetate in the dialysate, and antiseptics used during bag exchanges. We report a case of SEP following chronic ambulatory peritoneal dialysis and review the literature on this benign yet potentially lethal condition. Sclerosing encapsulating peritonitis frequently leads to intestinal obstruction, small-bowel necrosis, enterocutaneous fistulas, and malnutrition. There is a high incidence of anastomotic failure when a resection and primary intestinal anastomosis is performed in patients with SEP. Although SEP is not commonly reported in the surgical literature, its importance to surgeons is indicated by the fact that the overall mortality rate is close to 60% in patients with SEP who develop surgical complications. | 4 |
Comparison of coffee intake and coffee-induced symptoms in patients with duodenal ulcer, nonulcer dyspepsia, and normal controls. Coffee and decaffeinated coffee stimulate acid secretion. In addition, many patients experience dyspepsia after coffee ingestion. Therefore, coffee is often prohibited by physicians in patients with peptic diseases. However, the association between peptic disease and symptoms remains unclear. This study compares coffee intake and the induction of symptoms by coffee in patients with duodenal ulcer disease, nonulcer dyspepsia, and normal controls. We have studied the coffee drinking habits of 58 duodenal ulcer patients, 55 nonulcer dyspepsia patients, and 55 normal controls. The use of coffee on a daily basis was not significantly different between duodenal ulcer patients (64%) and controls (56%), or between nonulcer dyspepsia patients (55%) and controls. There was also no difference between the three groups in the use of decaffeinated coffee, the number of cups per day, the method of preparation, the length of time of coffee use, or any change in coffee intake in the previous year. The intake of tea, caffeinated carbonated beverages, and aspirin or nonsteroidal anti-inflammatory drugs was also similar in the three groups. The duodenal ulcer patients were more likely to be cigarette smokers (45%) than either the controls (16%) or the nonulcer dyspepsia patients (24%). Daily alcohol intake was not significantly different in the three groups. The prevalence of coffee induction of dyspeptic symptoms was similar in duodenal ulcer patients (29%) and controls (22%), but was much more common in nonulcer dyspepsia patients (53%) than in controls (22%), p = 0.0036. In conclusion, there was no difference in coffee intake between patients with duodenal ulcer, nonulcer dyspepsia, or normal controls. However, patients with nonulcer dyspepsia, but not duodenal ulcer, were more likely to experience dyspeptic symptoms after coffee ingestion. | 4 |
The relationship of pemphigus to neoplasia. A statistically increased incidence of malignancy has been observed in patients with pemphigus. A review of the literature reveals 42 cases of nonthymic malignancies and 18 cases of thymic malignancies. A significant predominance of men, with mean age at onset of 50 years, was observed. Pemphigus vulgaris is more common in patients with nonthymic neoplasms, whereas pemphigus foliaceus or pemphigus erythematosus and pemphigus vulgaris are equally common in patients with thymic neoplasms. Lymphoreticular malignancies, especially Kaposi's sarcoma, are most frequently observed. The majority of patients with nonthymic neoplasms have pemphigus before the detection of the malignancy and have a favorable 5-year survival rate after tumor resection. The majority of the patients with thymic neoplasms have a thymoma before the development of pemphigus. In some patients pemphigus develops after thymectomy and myasthenia gravis is often associated. Overall, 37 of the 60 patients, or 61%, had a neoplasm of the immune system. | 2 |
Ras gene mutations in intraductal papillary neoplasms of the pancreas. Analysis in five cases. Five intraductal papillary neoplasms of the pancreas were analyzed for the presence of the Ras gene mutations. Three (60%) of the five neoplasms showed point mutations at K-ras codon 12. This incidence of the mutations was rather low compared with that found with ordinary pancreatic adenocarcinoma. The presence of the mutations did not correlate with the severity of cellular atypia, but was apparently related to the size of the tumor. The two neoplasms that had no mutations were smaller than the others that had mutations. The analysis suggested that Ras gene mutation is not the first genetic alteration of tumor progression, but that it occurs during the development of neoplasms of the pancreas. | 0 |
The role of endoscopic injection sclerotherapy in the management of bleeding peristomal varices. Peristomal varices usually occur in patients with enterostomies who develop portal hypertension, and represent a cause of recurrent or intractable gastrointestinal bleeding. Treatment options for such bleeding include surgical ligation of varices, stoma revision with devascularization, injection sclerotherapy, portacaval shunt, or liver transplantation. We reviewed the records of seven patients with peristomal varices, who were followed for a mean of 17 months after diagnosis. Fourteen episodes of clinically significant peristomal bleeding occurred in six patients. Surgical ligation of varices was ineffective in controlling bleeding in two of three patients, although stoma revision with devascularization was temporarily effective in two other patients. Injection sclerotherapy, used in three patients, effectively controlled acute bleeding without serious complications or need for surgery. Definitive treatment for peristomal bleeding (portacaval shunt or liver transplantation) has prevented any further bleeding in three patients for a mean of 8 months after surgery. | 4 |
Renal disease in noninsulin-dependent diabetes mellitus. Diabetic nephropathy now accounts for approximately one-third of all patients who develop end-stage renal disease. The estimated cost to supply renal replacement therapy for this population now exceeds $750 million. The relatively recent realization that half of these individuals suffer from noninsulin-dependent diabetes mellitus has sparked increased interest in attempts to understand the pathologic processes involved and how they may be similar or different from those alterations seen in insulin-dependent diabetes mellitus. Basic and clinical investigation continues in an attempt to solve the puzzle of pathogenesis, as well as answer questions about the clinical usefulness of microalbuminuria and the appropriate management of hypertension in this population. | 3 |
Abnormal differentiation of human papillomavirus-induced laryngeal papillomas. We studied the proliferation and differentiation of human laryngeal papillomas, which are benign tumors induced by human papillomaviruses. Immunofluorescent stains of tissues for a number of differentiation-specific proteins showed abnormal differentiation. Papilloma tissue fragments in vitro showed a slightly decreased fraction of proliferating cells that incorporated tritiated thymidine and a markedly reduced incorporation of tritiated uridine when compared with normal tissue. We propose that papillomavirus infection results in normal basal cell proliferation but abnormal terminal differentiation and that this abnormality significantly contributes to the hyperplasia of the papillomas. | 0 |
Are three substages of clinical B prostate carcinoma useful in predicting disease-free survival? The B1 nodule, a 1.5 cm area of induration surrounded on at least two sides by prostatic tissue of normal consistency, was defined by Jewett in 1968 as the stage of prostatic cancer best suited for treatment and cure by radical prostatectomy (RP). The area of prostatic induration suitable for RP was subsequently extended to less than one lobe (Stage B1); this extension of induration was supported by the study of Walsh and Jewett in 1980 showing a 51 percent survival free-of-disease at fifteen-year follow-up. Subsequently, clinical staging systems evolved which substaged clinical B into three categories of induration: B1N = less than 1.5 cm nodule, B1 = greater than 1.5 cm but less than one lobe, and B2 = one lobe or both lobes. To determine if digital assessment of these progressively greater degrees of induration would translate into different intervals to first progression, whether local or distant, we reviewed prostate diagrams and descriptions of all Stage B patients treated by Iodine-125 interstitial implant and external beam radiation therapy between 1974 and 1985 at our institution. Forty-six patients had B1 nodules, 78 patients B1 (less than one lobe), and 52 patients B2 (one lobe or greater). Mean follow-up was fifty-five months. We found B1N, which was also associated with well-differentiated grade and a normal acid phosphatase, to have the longest interval to progression. | 0 |
Changing arteriosclerotic disease patterns and management strategies in lower-limb-threatening ischemia. From January 1, 1974 to December 31, 1989, we treated 2829 patients with critical lower-extremity ischemia. In the last 5 years, 13% of patients had therapeutically significant stenoses or occlusions above and below the groin, while 35% had them at two or three levels below the inguinal ligament. Unobstructed arterial flow to the distal half of the thigh was present in 26% of patients, and 16% had unobstructed flow to the upper third of the leg with occlusions of all three leg arteries distal to this point and reconstitution of some patent named artery in the lower leg or foot. In the last 2 years, 99% of all patients with a threatened limb and without severe organic mental syndrome or midfoot gangrene were amenable to revascularization by percutaneous transluminal angioplasty (PTA), arterial bypass, or a combination of the two, although some distal arteries used for bypass insertion were heavily diseased or isolated segments without an intact plantar arch. Limb salvage was achieved and maintained in more than 90% of recent patient cohorts, with a mean procedural mortality rate of 3.3%. Recent strategies that contributed to these results include (1) distal origin short vein grafts from the below-knee popliteal or tibial arteries to an ankle or foot artery (291 cases); (2) combined PTA and bypass (245 cases); (3) more distal PTA of popliteal and tibial artery stenoses (233 cases); (4) use of in situ or ectopic reversed autogenous vein for infrapopliteal bypasses, even when vein diameter was 3 to 4 mm; (5) composite-sequential femoropopliteal-distal (PTFE/vein) bypasses; (6) reintervention when a procedure thrombosed (637 cases) or was threatened by a hemodynamically significant inflow, outflow, or graft lesion (failing graft, 252 cases); (7) frequent follow-up to detect threatening lesions before graft thrombosis occurred and to permit correction of lesions by PTA (58%) or simple reoperation; and (8) unusual approaches to all infrainguinal arteries to facilitate secondary operations, despite scarring and infection. Primary major amputation rates decreased from 41% to 5% and total amputation rates decreased from 49% to 14%. Aggressive policies to save threatened limbs thus are supported. | 4 |
Underestimation of treatment effect in crossover trials. In crossover trials each subject serves as his own control. For the study of cardiovascular diseases such as hypertension and angina pectoria, properly designed crossover studies are preferred to parallel studies. There is a considerable between-subject variability of symptoms in some of these conditions. Bias due to this is eliminated by the use of a crossover design. However, a problem is the so-called treatment-by-period interaction. The present study analyzes the potential influences of this on the outcome of the trial. Physical carryover effect, defined as a physical effect of the first treatment period carrying on into the second, tends to minimize differences between two consecutive treatment periods. So does the frustrating experience of an inactive agent in the first treatment period. Outside influences such as the change of the seasons may affect lengthy crossover trials in a similar way. The author concludes that the treatment effect in a crossover trial tends to be underestimated. The current concept that reports of clinical trials are generally biased toward an exaggeration of treatment effects does not seem to apply to crossover trials. | 3 |
The epidemiology of cancer among Hispanic women. The experience in Florida. To explore cancer incidence among Hispanic women living in Dade County, Florida, data were analyzed from the statewide cancer registry. For all but three sites, Hispanics had lower rates of the 15 most prevalent cancers than non-Hispanics. However, higher rates of cancer among Hispanics were noted for cancers of the gallbladder, liver, and heart and soft tissue. Subgroups of women had significantly higher rates of cervical cancer and thyroid cancer. Lower rates among Hispanics were observed for cancers of the esophagus, vagina, breast, colon, buccal cavity and pharynx, and malignant melanoma. These data suggest that most cancer sites traditionally higher among US Latino women were not higher among Dade Hispanics, and that sites more common among non-Hispanics have not yet shown an increased incidence among Hispanic women in Dade County. | 0 |
Internal mammary artery and saphenous vein graft patency. Effects of aspirin. As part of two Department of Veterans Affairs Cooperative Trials, we obtained angiographic patency data for internal mammary artery (IMA) and saphenous vein grafts to the left anterior descending (LAD) coronary artery at 1 year after coronary artery bypass surgery. Patients received either aspirin 325 mg q.d., aspirin 325 mg t.i.d., aspirin 325 mg and dipyridamole 75 mg t.i.d., or placebo. Aspirin was initiated either 12 hours before or 6 hours after operation. Patients were stratified preoperatively for extent of disease and randomized to the therapies outlined above. There was no randomization to IMA versus saphenous vein grafts to the LAD. When the patients taking placebo were compared with those taking aspirin, there were no differences in the IMA (100.0% versus 92.1%, p = 0.385) or vein graft (88.8% versus 90.4%, p = 0.675) patency rates. The patency rate, irrespective of treatment, for all IMA grafts was 92.8% (220 of 237) versus 90.1% (345 of 383) for all vein grafts to the LAD (p = 0.309). Thus, both the IMA and vein grafts had excellent patency rates at 1 year. Aspirin did not alter this at 1 year, and there were no differences between IMA and vein graft patency to the LAD. | 4 |
Perturbation of differentiated functions during viral infection in vivo. In vivo relationship of host genes and lymphocytic choriomeningitis virus to growth hormone deficiency. Retarded growth and disordered glucose metabolism secondary to growth hormone (GH) deficiency are associated with persistent lymphocytic choriomeningitis virus (LCMV) infection of GH-producing cells in the anterior lobe of the pituitary gland. Infected C3H/ST mice, which are H-2k haplotype, become GH deficient, and LCMV replicates in most (more than 90%) of their GH-producing cells. In contrast, BALB/WEHI and SWR/J mice, which are H-2d and H-2q, respectively, do not develop this GH deficiency, and less than 20% of their GH-producing cells are infected by virus. Yet all three strains infected at birth with LCMV strain Armstrong (ARM) carry equivalent amounts of virus in their blood, brain, heart, kidney, liver, spleen, and thymus throughout life. Of five additional H-2k murine strains tested, C3H/HEJ and CBA/N mice develop this GH-like disorder, whereas neither AKR/J, B10/BR, nor BALB/KAE mice do, indicating that the H-2K haplotype does not control the GH susceptibility. Furthermore C3H/SW mice, which have the H-2b haplotype on the C3H background, develop the disease, again negating any correlation with H-2k but inferring that the C3H background is responsible. One half of the hybrid offspring produced by crossing the C3H/ST GH-deficient strain with BALB/WEHI-resistant mice develop the disease, but the trait is not sex linked. F1 hybrid backcrosses with the susceptible C3H/ST parental strain or resistant BALB/WEHI strain indicate the involvement of more than two genes. Hence the development of a GH deficiency by LCMV-infected C3H/ST mice is not linked to the MHC haplotype, is not sex linked, and is not due to a dominant gene. Multiple genes are involved and these are related to C3H background. | 4 |
Renal disease in chronic arthritis of childhood. A study of urinary N-acetyl-beta-glucosaminidase and beta 2-microglobulin excretion. Urinalyses of randomly obtained samples from children with various types of chronic arthritis revealed proteinuria in 2.3% of patients, hemoglobinuria in 3.5%, erythrocyturia in 4.1%, and leukocyturia in 5.3%; these frequencies are within the range found by screening school children. However, raised urinary levels of N-acetyl-beta-glucosaminidase and/or beta 2-microglobulin (both sensitive measures of renal tubular damage) were found more frequently in children with chronic arthritis than in controls (P less than 0.0001). Abnormalities of either N-acetyl-beta-glucosaminidase or beta 2-microglobulin excretion were associated with active arthritis as measured by physician global estimate of disease activity, with a polyarticular onset of juvenile rheumatoid arthritis, and with the use of slow-acting antirheumatic drugs or the concurrent use of more than 1 nonsteroidal antiinflamtory drug. Abnormal renal tubular function appears to be common in chronic arthritis of childhood. The long-term consequences of this abnormality remain to be elucidated. | 4 |
Bone metastases: pathophysiology and management policy. The pathophysiology and options for management of bone metastases as well as criteria for determining response to therapy are reviewed. Bone metastases are frequently one of the first signs of disseminated disease in cancer patients. In the majority of patients, the primary tumor is in the breast, prostate, or lungs. Although almost all patients will die of their disease, a proportion of the patients will survive for several years. Treatment is primarily palliative: the intention is to relieve pain, prevent fractures, maintain activity and mobility, and, if possible, to prolong survival. Therapeutic options include local treatment with radiotherapy and/or surgery, and systemic treatment using chemotherapy, endocrine therapy, radioisotopes, agents such as diphosphonates, which inhibit resorption of bone, as well as analgesic and antiinflammatory drugs. The mechanisms by which pain is relieved by several of these therapies remain unclear but actions beyond a simple tumoricidal effect appear to be important. There have been few randomized trials comparing the therapeutic options, and the criteria for assessing response to therapy have, in general, been poorly defined. There is a need for rigorous clinical investigations that assess the efficacy of the various therapeutic possibilities by using well-defined and validated criteria of response. | 2 |
DNA analysis of neoplasia: an introduction for the family physician. Pathologic evaluation of a neoplastic process has traditionally consisted of microscopic examination of a stained section of tissue. Although this method is generally reliable when performed by an experienced pathologist, the morphologic features of a lesion may not consistently predict biologic behavior. The DNA content of tumors can be studied with a flow cytometer to help determine the prognosis and risk of tumor recurrence. DNA analysis of a neoplasm may provide the clinician with important prognostic information and, at some future date, may help direct chemotherapy or other treatment protocols. | 0 |
Morbidity, mortality, and quality of life for patients treated with levothyroxine In a population study of 1462 middle-aged women initiated in 1968 and 1969 we identified 29 women treated with levothyroxine from 1 to 28 years. In a 12-year follow-up in 1980 and 1981 we investigated the subjects for end-point myocardial infarction, diabetes mellitus, stroke, cancer, and death (the status of 99.7% of the initial participants was established). The women treated with levothyroxine showed no increase in morbidity or mortality. Of the 24 women still receiving levothyroxine in 1980 and 1981, 22 had serum thyrotropin and triiodothyronine concentrations with-in reference limits. These individuals were compared with the 968 women from the population study having no history of thyroid disease, and appeared identical as to laboratory and clinical data, with the exception of a slightly higher body mass, taller stature, and lower serum cholesterol concentration. The treated group did not differ in a life quality estimate based on 19 questions regarding life satisfaction and sensory function. We conclude that the levothyroxine-treated woman suffers no side effects from her life-long therapy. | 0 |
The immunoperoxidase localization of tumour markers in ovarian cancer: the value of CEA, EMA, cytokeratin and DD9. Primary tumours from 40 patients with epithelial ovarian cancer, treated at St Thomas's Hospital over a 10-year period, were studied for the immunocytochemical expression of the following tumour markers in formalin-fixed paraffin embedded material: carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), cytokeratin (CAM 5.2), and DD9. An indirect immunoperoxidase staining technique was used. All of the tumours were positive for EMA and CAM 5.2, and 30% of them were positive for both CEA and DD9. The absence of CEA and DD9 may be of value in differentiating between metastatic abdominal adenocarcinomas of ovarian origin and those of gastrointestinal origin, but no indication of prognosis was obtained using these epithelial markers. The strong and widespread staining of all the tumours for EMA suggests that this may be a useful marker for detecting metastatic or recurrent disease by immunoscintigraphy. | 0 |
A lethal complication of papaverine-induced priapism. A large series of patients was treated for impotence with intracorporeal injections of papaverine and phentolamine with no major complications and no deaths reported. We report on a 45-year-old black man with advanced multiple sclerosis who died after such therapy. When the first self-administered injection of phentolamine and papaverine failed to produce an adequate erection the patient injected a second dose that resulted in priapism and death of massive pulmonary embolism. | 3 |
Colon carcinoma associated with ureterosigmoidostomy. A patient developing a colonic adenoma 38 years following ureterosigmoidostomy is presented. The mechanisms of neoplastic transformation associated with ureterosigmoidostomy is now better understood. This knowledge is being applied to develop modifications both of the surgical technique and the management of patients with this form of urinary diversion, and is a subject of discussion. | 4 |
Esophageal involvement in pemphigus vulgaris: a clinical, histologic, and immunopathologic study. Eleven newly diagnosed patients and one patient with pemphigus vulgaris who relapsed underwent endoscopy of the upper gastrointestinal tract. Three patients had blisters or erosions and two had longitudinal lines of erythema in the esophageal mucosa. In four patients histopathologic examination showed findings of pemphigus vulgaris but direct immunofluorescence was positive in all patients. This study demonstrates that the immunopathologic disturbance in pemphigus vulgaris involves the entire length of the esophagus, although only some patients have clinical or histologic involvement. To the best of our knowledge this is the first histopathologic and direct immunofluorescence study of esophageal involvement in patients with untreated pemphigus vulgaris. | 4 |
Remodeling of myocyte dimensions in hypertrophic and atrophic rat hearts. Changes in hemodynamic load cause alterations in cardiac myocyte size, with regional variations in myocyte size distribution possible within the ventricular wall. We studied regional changes in cellular dimensions and their distribution in two models of cardiac hypertrophy and in cardiac atrophy in the rat. Combined volume-pressure overload was produced by 3,3',5-triiodo-L-thyronine (T3) treatment; atrophy was produced by heterotopic isotransplantation. Our previous data from long-term pressure overload after aortic constriction were used for comparison. Isolated ventricular myocytes were obtained after in vitro coronary perfusion with collagenase. Cell volume and its distribution were determined; cell length was directly measured by image analysis, and cross-sectional area was estimated from the cell volume/cell length ratio, assuming a cylindrical model. Myocyte hypertrophy resulting from hyperthyroidism and aortic constriction was primarily due to increased cross-sectional area. In both cases, the relative response was greater in the right ventricle than in the left ventricle. Within the left ventricle, epimyocardial myocytes enlarged the most. Aortic constriction and T3 treatment predominantly increased the size of smaller myocytes. Heterogeneity in myocyte size increased after constriction but remained relatively unaffected after T3 treatment. Atrophy of left ventricular myocytes was due to a proportional decrease in cell length and cross-sectional area, with the greatest decrease in the left ventricular endomyocardium. Atrophy predominantly affected larger myocytes, resulting in a more homogeneous overall population of smaller myocytes. We conclude that various alterations in load lead to diverse remodeling in the myocyte population throughout the ventricular wall. In general, smaller myocytes show the highest growth potential, whereas larger myocytes exhibit the highest potential to atrophy. | 4 |
Cardiovascular-sympathetic adjustments to nonexertional heat stress in mature and senescent Fischer 344 rats. The purpose of this study was to test the hypothesis that the cardiovascular-sympathetic nervous system adjustments during nonexertional heat stress are exaggerated in senescent (S, 24 mo) vs. mature (M, 12 mo) conscious unrestrained Fischer 344 rats. During two separate trials (48 h apart), each animal was exposed to an ambient temperature (Ta) of 42 degrees C until a colonic temperature (Tco) of 41 degrees C was attained and then cooled at a Ta of 26 degrees C until Tco returned to the initial control level. Trial 1: heart rate (HR), mean arterial blood pressure (MAP), and arterial plasma concentrations of norepinephrine (NE), epinephrine (E), and lactate (La) were similar between the S and M groups during the baseline (control) period. The absolute increases in HR, MAP, NE, and E from the control period to the end of heating were of similar magnitudes between groups; however, La increased more in the S than M animals (P less than 0.05). During recovery, the declines toward control levels for all variables were similar or even more rapid in the S vs. M animals (P less than 0.05). Trial 2: the changes in HR and MAP during heating were similar to those observed in trial 1 in both groups. Generally, NE and E control levels were elevated in both groups compared with those in trial 1. The absolute increases in NE during heating were similar to trial 1 in both groups, whereas E increased to a greater extent than in trial 1 in the S animals (P less than 0.05). | 4 |
Angiographic localization of spinal cord blood supply and its relationship to postoperative paraplegia. Forty-seven patients underwent selective catheterization of middle and lower thoracic intercostal and upper lumbar arteries to define the origin of the artery of Adamkiewicz. One patient had significant atheroembolism, and a second had transient lower extremity paresthesias. No other complications occurred. The origin was found in 26 (55%), and 21 patients underwent thoracoabdominal aneurysm repair with this knowledge. When the critical lumbar or intercostal artery could be included as part of a long proximal or distal anastomosis, all 12 patients could be included as part of a long proximal or distal anastomosis, all 12 patients survived, and one was paralyzed. However, if the aneurysm repair mandated a midgraft anastomosis to intercostal arteries critical to spinal cord perfusion, seven of nine patients either died or were paralyzed (p less than 0.05). In the group of 19 patients operated on in whom spinal cord blood supply was not identified three patients had a technically unsuccessful operation; two died, and one was paralyzed. Twelve of 16 patients who had an adequate, but unsuccessful attempt at localization were treated by intercostal "neglect" and survived. Late paresis developed in two patients, but they are walking now. One of the patients who died had multiple systems failure and awakened paraplegic. She had a patent, enlarged, thoracic radicular artery at T-5 which probably supplied to spinal cord and which was missed angiographically. Paralysis was associated with aneurysm extent (group 2 and III B, dissections vs group 1 & 3, p less than 0.05). Selective intercostal angiography requires further refinement, but it is safe and offers the promise of understanding the mechanisms and risks of spinal cord complications after repair of extensive thoracoabdominal aneurysms. | 2 |
Hemibody irradiation in advanced prostatic carcinoma. In summary, hemibody irradiation has developed as a safe, efficient technique for palliating multiple sites of symptomatic osseous metastases, which occur so often in advanced prostatic carcinoma. The rapidity, frequency, and duration of pain relief, as well as the convenience to the patient of a solitary treatment to multiple symptomatic areas simultaneously, make this type of treatment especially appealing. By following premedication and radiation dose guidelines, both acute and delayed side effects can be kept tolerable or at a minimal incidence. Although sequential hemibody radiation has also been explored as "systemic" therapy, the results in prostatic carcinoma have not proved dramatic, and complications have been considerable. Hormonal therapy would certainly seem to be less life-threatening and equally beneficial according to present data. As a palliative treatment, however, hemibody irradiation is a pragmatic option for relieving prostatic cancer pain. | 0 |
The butterfly rash and the malar flush. What diseases do these signs reflect? The butterfly rash and malar flush are common facial manifestations of several disorders. Systemic lupus erythematosus may produce a transient rash before any other signs. In pellagra, symmetric keratotic areas on the face are always accompanied by lesions elsewhere on the body. Erysipelas produces brawny, fiery red facial lesions, and scarlet fever causes facial eruptions as part of a generalized eruption. Lupus vulgaris and lupus pernio produce nodules that may spread in a butterfly pattern, and seborrheic dermatitis has a predilection for the malar prominences and other areas of the face. Carcinoid syndrome often causes flushing attacks that vary in duration, and facial flushing that lasts throughout treatment may accompany chemotherapy if the patient has a hypersensitivity reaction. Deep-red rashes and/or lichenoid lesions may be caused by graft-versus-host disease in a patient undergoing bone marrow transplantation. | 0 |
Hypertrophic cardiomyopathy without hypertrophy: two families with myocardial disarray in the absence of increased myocardial mass Two families are described in which individuals showed widespread myocardial disarray at histological examination, in the absence of macroscopic cardiac hypertrophy. In one family the clinical presentation was that of sudden unexpected cardiac death in four family members; members of the other family presented with electrocardiographic repolarisation changes and abnormalities of left ventricular diastolic function. The finding of myocardial disarray, the characteristic histological abnormality of hypertrophic cardiomyopathy, in the absence of increased cardiac mass suggests a wider range of abnormality in hypertrophic cardiomyopathy than is currently recognised. | 3 |
Effect of nicardipine on somatosensory evoked potentials in patients with acute cerebral infarction. We evaluated the effect of nicardipine, a calcium channel blocker, on somatosensory evoked potentials (SEP) in 26 patients with acute cerebral infarction. Post treatment, 58% (15/26) of the N20 and P25 latencies were prolonged in the affected hemispheres; 8% (2/26) were shortened; and 35% (9/26) did not change. The mean N20 and P25 latencies were significantly prolonged two hours post treatment in the affected hemisphere (N20, P less than 0.01, P25 P less than 0.01). Nicardipine (Ni) had no effect on SEP components in the intact hemispheres. Seventy five per cent of the 12 patients with hypertension had a decrease in blood pressure (BP) after taking nicardipine, but there were no undesirable side effects or worsening of neurological signs. Our study demonstrates that nicardipine prolongs the latencies of short-latency components of SEP in the affected hemisphere after acute ischaemic stroke and also decreases BP. These observations suggest that nicardipine therapy might impair neuronal function in the ischaemic zone. | 2 |
Axillosubclavian vein thrombosis produced by retrosternal thyroid. Several causes of axillosubclavian vein thrombosis have been described. Trauma to the subclavian vein by pacemaker wires or central venous lines as well as the so-called effort thrombosis have been recognized as frequently diagnosed precipitating factors. A patient is herein presented with thrombosis of the subclavian vein caused by a giant substernal thyroid compressing the innominate vein. | 4 |
Heart transplantation in patients with severe pulmonary hypertension and increased pulmonary vascular resistance. Irreversibly increased pulmonary vascular resistance is a contraindication for cardiac transplantation. At our hospital patients referred for recipient evaluation with systolic pulmonary artery pressure greater than 50 mmHg and pulmonary vascular resistance greater than 2 Wood units (Wu) are tested with intravenous sodium nitroprusside for reversibility. In 23 patients whose increased systolic pulmonary artery pressure (67.4 +/- 10.4 mmHg) and resistance (4.8 +/- 2.4 Wu) were reduced by nitroprusside, orthotopic heart transplantation was performed without early mortality. Right heart catheterization after transplantation revealed a significant and persistent fall of the elevated pulmonary artery pressure and pulmonary vascular resistance. We conclude that if severe pulmonary hypertension and elevated pulmonary vascular resistance are reversible with nitroprusside, the patient can safely undergo heart transplantation. | 3 |
Effect of plasmapheresis on serum and CSF autoantibody levels in CNS paraneoplastic syndromes. We compared the effect of plasmapheresis on antineuronal autoantibody titers in the serum and CSF of 3 patients with CNS paraneoplastic syndromes. Plasmapheresis reduced the serum autoantibody titer to 20% of the initial levels in the 3 patients, but the CSF autoantibody titer decreased only in the patient with severe damage of the blood-brain barrier. | 2 |
Comparison of myelography with CT follow-up versus gadolinium MRI for subarachnoid metastatic disease in children. We evaluated 17 children with primary intracranial neoplasms for subarachnoid metastatic disease (SAMD) using myelography with computed tomographic follow-up (Myelo + CT) and cerebrospinal fluid (CSF) histopathologic examination, as well as magnetic resonance imaging with gadolinium DTPA (MRI + Gd), between December 1988 and December 1989. There were 12 boys, and the median age was 5.7 years (range, 0.8 to 21.8 years). Tumor histology included 8 primitive neuroectodermal tumors (PNETs), 3 ependymomas, 2 low-grade astrocytomas, 1 anaplastic astrocytoma, 1 glioblastoma multiforme, 1 atypical rhabdoid tumor, and 1 malignant fibrous histiocytoma. Thirteen tumors originated in the posterior fossa, 2 were supratentorial, and 2 were in the spinal cord. The median interval between the 2 diagnostic tests was 2 days. MRI + Gd was positive in 11 (65%), Myelo + CT in 8 (47%), and CSF in 5 (29%) cases. MRI + Gd was superior in delineating spinal cord nodules and "sugar coating" whereas Myelo + CT more readily revealed nerve root sleeve filling defects. There was no case in which Myelo + CT was positive that MRI + Gd did not reveal SAMD. MRI + Gd is a safe, noninvasive test that should be used as the initial imaging modality for the presence of SAMD. | 0 |
Autoimmune chronic active hepatitis in a family. A positive family history of autoimmune disease is common among patients with autoimmune chronic active hepatitis, but usually autoimmunity is directed at organs other than the liver. We document for the first time the multiple occurrence of autoimmune chronic active hepatitis in a family. Out of a sibship of seven, three sisters developed this, one sister developed coeliac and autoimmune thyroid disease, one sister showed serological signs of autoimmunity, while the two brothers were well with no signs of autoimmunity. HLA typing showed that in association with the female sex DR3 seems to be more important than B8 in conferring susceptibility to autoimmune chronic active hepatitis, at least in this family. | 4 |
Thromboxane biosynthesis in cardiovascular diseases. Sudden fissuring of an atherosclerotic plaque has been suggested as the primary trigger of transient spontaneous ischemia in both the coronary and cerebral circulation. Measurements of urinary 11-dehydro-TXB2 and 2,3-dinor-TXB2, as well as results of Aspirin trials, have suggested that episodic platelet activation at the site of this acute vascular lesion is mediated, at least partly, by enhanced thromboxane (TX) A2 biosynthesis. Thus, episodic increases in metabolite excretion have been detected in unstable angina. Aspirin (75-325 mg/day) prevents about one third of all fatal and nonfatal thrombotic events in this setting. That a similar "dynamic" thrombotic process occurs during the early phase of acute myocardial infarction is suggested by thromboxane metabolite measurements and by the results of the ISIS-2 trial showing a similar impact of short-term Aspirin therapy to that seen in unstable angina. Percutaneous transluminal coronary angioplasty is associated with transiently enhanced TXA2 biosynthesis and Aspirin-suppressable periprocedural thrombotic complications. On the other hand, both non-insulin-dependent diabetes mellitus and type IIa hypercholesterolemia are associated with a relatively reproducible and persisting abnormality of TXA2-dependent platelet function. This association is likely to reflect a systemic rather than localized stimulus to platelet activation and a continuous rather than episodic alteration. Low-dose (50 mg/day) Aspirin can largely suppress thromboxane metabolite excretion in both diseases. Thus, low-dose Aspirin and/or selective prostaglandin H2/TXA2-receptor antagonists may be important tools to test the hypothesis that TXA2-dependent platelet activation represents an important transducer of the enhanced thrombotic risk associated with these metabolic abnormalities. | 3 |
Adjuvant cyclophosphamide, methotrexate, and fluorouracil in patients with axillary node-positive breast cancer: an update of the Guy's/Manchester trial. Between 1976 and 1985, 391 patients (202 premenopausal, 189 postmenopausal) with operable breast cancer and positive axillary lymph nodes were randomized after total mastectomy and axillary clearance to receive cyclophosphamide, methotrexate, and fluorouracil (CMF) (n = 193) or no adjuvant therapy (n = 198). After a median follow-up of 8 years, both relapse-free survival (RFS) and survival (S) were significantly prolonged in premenopausal patients receiving CMF (RFS, P less than .001; S, P = .003). Treatment with CMF resulted in a significant improvement in RFS in premenopausal patients both with steroid receptor-positive and steroid receptor-negative tumors and also in subgroups of premenopausal patients defined by the number of axillary nodes involved. Premenopausal patients who developed permanent amenorrhea following CMF had a significantly better RFS than those who continued to menstruate. Induction of amenorrhea following CMF was related to age, with almost all patients over 40 years becoming amenorrheic. For patients less than or equal to 40 years, development of amenorrhea following CMF did not influence outcome. No difference was detected between control and CMF groups (RFS, P = .9; S, P = .9) in postmenopausal patients nor in any subgroup of these patients. The results of this trial of the efficacy of CMF for improving RFS and S have strengthened with longer follow-up. | 0 |
Elderly patients with congestive heart failure under prepaid care. PURPOSE: Because of concern about the quality of care received by Medicare patients in health maintenance organizations (HMOs), the care of patients with congestive heart failure (CHF) in eight HMOs was compared with the care of fee-for-service (FFS) Medicare cases. PATIENTS AND METHODS: We compared the care of 170 patients with CHF enrolled in one of eight Medicare HMOs with the care of 191 similar FFS patients. Panels of expert physicians developed criteria for evaluating quality of care, and specially trained nurse clinicians abstracted medical records. RESULTS: Outpatient evaluation and management were similar in both settings, although HMO patients were significantly more likely to be advised to restrict salt intake. However, FFS patients with uncontrolled hypertension were more likely to have their medication regimens changed (62% versus 36%, p less than 0.01). Ejection fractions were obtained equally as often, and inpatient management was similar for both groups. Nonetheless, HMO providers scheduled follow-up visits within 1 week of hospital discharge more often (42% versus 27%, p less than 0.01). CONCLUSIONS: This study suggests that financial incentives of prepaid care are not detrimental to most aspects of care for CHF patients. More rapid follow-up after hospital discharge for patients with CHF suggests that HMOs may be more effective in delivering continuity of care for patients with chronic illness. | 3 |
Neurogenic inflammation of the rat trachea: fate of neutrophils that adhere to venules. The goal of this study was to determine whether neutrophils that adhere to the vascular endothelium in association with neurogenic inflammation in the respiratory tract migrate out of the blood vessels or whether they detach and reenter the circulation. We also sought to determine whether the fate of the neutrophils is influenced by neutral endopeptidase (NEP), an enzyme that degrades the tachykinins that produce neurogenic inflammation. Neutrophils in the tracheal mucosa of anesthetized pathogen-free rats were examined 5 min or 4 h after neurogenic inflammation was produced by an injection of capsaicin (100 or 200 micrograms/kg iv). In whole mounts of these tracheae stained histochemically for myeloperoxidase, adherent intravascular neutrophils had a spherical or teardrop (regular) shape and migrating neutrophils had a polarized amoeboid (irregular) shape. The number of regular neutrophils in the tracheae was increased at both times, but the increase at 4 h was only half that present at 5 min. The reduction between 5 min and 4 h was not offset by an appreciable increase in the number of irregular neutrophils, unless NEP was inhibited by phosphoramidon. We interpret these results as indicating that the rapid adherence of neutrophils to the vascular endothelium after an injection of capsaicin is followed by a gradual reentry of the neutrophils into the circulation and comparatively little neutrophil migration. However, when the effect of the stimulus is increased and/or prolonged by inhibition of NEP, some of the adherent neutrophils migrate out of the vessels. Thus the activity of NEP can regulate both the magnitude of the neutrophil adherence and the fate of the adherent cells. | 4 |
Histologic abnormalities of large and small coronary arteries, neural structures, and the conduction system of the heart found in postmortem studies of individuals dying from the toxic oil syndrome. Hundreds died and thousands were poisoned by rapeseed oil adulterated with aniline and sold illegally in Spain in 1981. The clinical manifestations, now known as the toxic oil syndrome, include pulmonary hypertension and right ventricular hypertrophy plus widespread vascular and neural lesions in other organs. Many of the late deaths ended with a scleroderma-like illness. Because scleroderma involves the heart, in this study we examined the small and large coronary arteries, neural structures, and conduction system from eight victims dying with the toxic oil syndrome. Dense fibrosis of the sinus node in two hearts resembled changes found in scleroderma. Atrionodal junctional hemorrhages and cystic degeneration of the sinus node present in the other six hearts resembled changes found in lupus erythematosus. Small and large coronary arteries exhibited focal fibromuscular dysplasia and a proliferative cystic myointimal degeneration. This latter abnormality was associated with sloughing of the inner wall and embolization of the detached fragment downstream in the same coronary artery. Every heart had many degenerative lesions within nerves, ganglia, and the coronary chemoreceptor. Both the arterial and neural abnormalities prominently involved the conduction system. Based upon observations by others with experimental feeding of rapeseed oil containing either high or low erucic acid, we suggest that this oil must remain a major suspected cause of the toxic oil syndrome, particularly in conjunction with some as yet unexplained facilitative influence by oleoanilids. If this is so, it is important to reconsider the widely recommended use of any rapeseed oil product as a suitable food for man or other animals. | 4 |
Chromatin structural analysis of the 5' end and contiguous flanking region of the myeloperoxidase gene. Myeloperoxidase (MPO) synthesis is known to be associated with the promyelocyte stage of myeloid differentiation. In particular the downregulation of MPO gene transcription is associated with myeloid cell maturation. We examined the changes in the deoxyribonuclease I hypersensitive sites within the 5' end of the MPO gene and its 5' flanking region during dimethyl sulfoxide (DMSO)-induced differentiation of HL-60 cells to determine the changes in chromatin structure that accompany this process. The locations of hypersensitive sites surrounding the 5' end of the gene in proliferating, uninduced cells were determined: three were observed in the 5' flanking region and one within the gene. Progressive changes in all sites accompanied the downregulation of MPO transcription after treatment with DMSO. No evidence of hypersensitivity was observed in the chromatin region examined after 8 days of DMSO exposure. The results provide an example of the changes that occur in the chromatin structure of a gene as it is inactivated during differentiation. | 0 |
Effect of nontransmural necrosis on epicardial potential fields. Correlation with fiber direction. The effect of nontransmural necrosis on epicardial potential distributions was studied in 13 dogs. In previous studies, left ventricular epicardial pacing generated epicardial potential maps at QRS onset with a negative central area and two positive areas that faced the portions of the wavefront propagating along fibers. Subsequently, the positive areas expanded in a counterclockwise direction by 90 degrees to 120 degrees. In those studies, the rotatory expansion of the positive areas was tentatively attributed to the spread of excitation through deep myocardial layers, where fiber direction rotated counterclockwise from epicardium to endocardium. To test this hypothesis, we tried to interrupt the counterclockwise expansion of the positive area by creating localized, nontransmural necrosis at various depths in the left ventricular wall by injection of formalin or application of laser energy. Epicardial potential maps were obtained from a grid of 12 x 15 electrodes on a 44 x 56-mm area. Epicardial pacing from selected sites generated epicardial maps in which some positive areas were missing compared with controls. The direction of the straight line joining the pacing site to the site of missing positivity correlated well with the average fiber direction in the necrotic mass (r = 0.82, p less than 0.01). Angle between epicardial fiber direction and the straight line described above correlated well with the average depth of the necrosis, expressed as percent of the wall thickness (r = 0.95, p less than 0.01). These data support the hypothesis that the counterclockwise expansion of the epicardial positivity occurring after epicardial pacing results from excitation spreading along deep fibers. | 4 |
Digoxin Immune Fab therapy in the management of digitalis intoxication: safety and efficacy results of an observational surveillance study. An observational surveillance study was conducted to monitor the safety and effectiveness of treatment with Digoxin Immune Fab (Ovine) (Digibind) in patients with digitalis intoxication. Before April 1986, a relatively limited number of patients received treatment with digoxin-specific Fab fragments through a multicenter clinical trial. Beginning with commercial availability in July 1986, this study sought additional, voluntarily reported clinical data pertaining to treatment through a 3 week follow-up. The study included 717 adults who received Digoxin Immune Fab (Ovine). Most patients were greater than or equal to 70 years old and developed toxicity during maintenance dosing with digoxin. Fifty percent of patients were reported to have a complete response to treatment, 24% a partial response and 12% no response. The response for 14% of patients was not reported or reported as uncertain. Six patients (0.8%, 95% confidence interval 0.3% to 1.8%) had an allergic reaction to digoxin-specific antibody fragments. Three of the six had a history of allergy to antibiotic drugs. Twenty patients (2.8%, 95% confidence interval 1.7% to 4.3%) developed recrudescent toxicity. Risk of recrudescent toxicity increased sixfold when less than 50% of the estimated dose of antibody was administered. A total of 215 patients experienced posttreatment adverse events. The events for 163 patients (76%) were judged to result from manifestations of underlying disease and thus considered unrelated to Fab treatment. Digoxin-specific antibody fragments were generally well tolerated and clinically effective in patients judged by treating physicians to have potentially life-threatening digitalis intoxication. | 3 |
Neuroendocrine features of reactive bile ductules in cholestatic liver disease. Various cholestatic liver diseases are accompanied by a striking increase in the number of bile ductules. This so-called ductular reaction is thought to arise both from ductular metaplasia of hepatocytes and from proliferation of pre-existing bile ductules. Previous studies have shown that these reactive bile ductules differ from their normal counterpart in enzyme and immunohistochemical make-up. Using monoclonal antibodies directed to neuroendocrine markers and immunohistochemistry, we found that reactive bile ductules in cholestatic liver disease display neuroendocrine features. In all cases of primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), extrahepatic obstruction, and acute hepatitis A, reactive bile ductules expressed the neural cell adhesion molecule (N-CAM) and reacted with monoclonal antibody A2B5. Both N-CAM and the ganglioside, recognized by A2B5, are restricted to neuroendocrine cells and tissues. In all but four of these cases, the same bile ductules expressed chromogranin-A, present in the matrix of neuroendocrine granules. Furthermore, in three cases of longstanding cholestasis, scattered periportal hepatocytes expressed chromogranin-A but not N-CAM. Other neuroendocrine markers such as neuron-specific enolase, synaptophysin, or myelin-associated glycoprotein were lacking from both bile ductules and hepatocytes. The neuroendocrine phenotype of bile ductules and hepatocytes was confirmed on electronmicroscopy, demonstrating various numbers of dense-cored, neuroendocrine granules near the peripheral cell membrane in bile ductules as well as in cells intermediate between hepatocytes and bile ductular cells. In 10 cases of normal liver tissue without ductular reaction, bile ductules lacked neuroendocrine markers except in two cases in which very weak reactivity for chromogranin-A was observed. These findings illustrate the presence of a new, neuroendocrine cell type that emerges in the liver during cholestasis. Elucidation of the significance of the neuroendocrine substance(s) produced in the dense cored granules of reactive bile ductules awaits their isolation and characterization. We can speculate that this molecule plays an autocrine or paracrine regulatory role in the process of ductular metaplasia of hepatocytes or growth of bile ductules. | 4 |
Influence of untreated chronic plastic iridocyclitis on intraocular pressure in leprosy patients. The intraocular pressures of a total of 286 eyes of patients with lepromatous and borderline lepromatous leprosy who never had regular ophthalmological care or local eye treatment were measured. The patients were categorised according to the type of leprosy they had, and the eyes were categorised as without or with chronic plastic iridocyclitis. In patients with lepromatous and borderline lepromatous types of leprosy the intraocular pressure was significantly lower in eyes with chronic plastic iridocylitis 10.1 (3.6) mmHg than in both unaffected eyes 11.0 (3.2) mmHg and control eyes 13.5 (2.5) mmHg. It has been shown that chronic plastic iridocyclitis which remains untreated for years results in a lower intraocular pressure than normal. | 4 |
Intra-abdominal abscesses in Crohn's disease. We reviewed 22 patients who had intra-abdominal abscesses secondary to Crohn's disease. A total of 29 abscesses were discovered. These included superficial and deep intraperitoneal as well as pelvic and retroperitoneal abscesses. Diagnosis was aided by ultrasound and computer tomographic scanning. Barium studies continue to play an important role in delineating the extent of bowel involvement and fistulization. Treatment varied depending on the location and size of the abscess. The need for ultimate bowel resection was determined in the majority of cases by the presence of fistulization between the abscess cavity and the bowel. The terminal ileum or neoterminal ileum were almost always involved. | 4 |
Patient perception of tics and other movement disorders. To determine the subjective perception patients have of abnormal movements, 170 patients with various hyperkinesias were interviewed with questions directed at the "voluntary" or intentional versus "involuntary" aspects of their symptoms. One hundred and two of 110 patients with non-tic disorders thought that the abnormal movements were entirely involuntary. Forty-one of 60 tic disorder patients stated that all their motor and phonic tics were intentionally produced. Fifteen others had both voluntary and involuntary components, usually with the former predominating. A "voluntary" response could be used to predict the correct diagnostic category (tic versus non-tic) in 8 of 9 patients for whom the referral category was incorrect. These results suggest that a large proportion of the motor and phonic symptoms experienced by tic patients are irresistibly but purposefully executed, more akin to compulsions than to the other "involuntary" hyperkinesias with which they are commonly discussed. | 2 |
Carcinoma of the head of the pancreas. Optimal treatment for unresectable carcinoma of the pancreas remains controversial. This study was done to examine the relationship between perioperative jaundice and postoperative morbidity, and type of palliative biliary bypass and postoperative morbidity and jaundice clearance. Seventy-six patients with obstructive jaundice secondary to carcinoma of the head of the pancreas were studied. Forty-nine patients underwent one of four different types of palliative bypass: 1, cholecystojejunostomy (n = 22); 2, choledochojejunostomy (n = 11); 3, choledochoduodenostomy (n = 9), and 4, cholecystoduodenostomy (n = 7). Age, sex and preoperative health status were similar for all operative groups, as well as for those with and without postoperative morbidity. The postoperative complication rate was 33 per cent and there was one postoperative death. Length of preoperative jaundice and peak preoperative bilirubin levels were independent of morbidity. Postoperative morbidity was similar for each type of bypass used and no significant difference was found when cholecystoenteric (1 and 4) and choledochoenteric (2 and 3) bypass were compared. The results of this study support the view that postoperative morbidity is not directly related to the presence of jaundice preoperatively. Furthermore, the rate of jaundice clearance and the occurrence of postoperative complications are not dependent on the type of bypass used. | 4 |
Influence of preservation or perfusion of intraoperatively identified spinal cord blood supply on spinal motor evoked potentials and paraplegia after aortic surgery. Permanent ligation of arteries supplying blood to the spinal cord in operations for aortic aneurysm can lead to spinal cord ischemia, which can result in either paraparesis or paraplegia. This report describes a rapid method of intraoperative identification of those arteries that supply the spinal cord by use of an intrathecal platinum electrode to detect hydrogen in solution that has been injected into the aortic ostia. Preservation or perfusion of those identified arteries supplying the spinal cord may decrease the rate of postoperative neurologic complications. Of 28 porcine experiments with postoperative observation for 24 hours, there were 3 initial pilot experiments in which saline saturated with hydrogen was injected into the temporarily cross-clamped aorta. Twenty animals were then randomized to (1) preservation of only the vessels sequentially identified to supply blood to the spinal cord from T-13 to L-5 (n = 10); (2) division of the vessels supplying the spinal cord (n = 10). A further five animals underwent perfusion experiments wherein the identified cord arteries were perfused by a shunt, the other nonsupply arteries were divided, and the aorta was kept clamped for 45 minutes. Spinal motor evoked potentials were elicited with an intrathecal electrode and were highly sensitive for paralysis. Paralysis occurred in 0/3 pilot (p less than 0.013 vs division); 8/10 division; 1/10 preservation (p less than 0.0017 vs division); and perfusion 1/5 (p less than 0.025 vs division). Results of a pilot study in eight humans shows that the technique can be used to rapidly identify segmental arteries supplying the spinal cord, to determine if distal perfusion is supplying the spinal cord with blood flow, and if reattached segmental arteries are patent. | 3 |
Occult, bilateral anterior sacral and intrasacral meningeal and perineurial cysts: case report and review of the literature. None of the more than 180 cases of anterior sacral meningocele reported in the past 150 years has been bilateral, and only two have been associated with occult intrasacral meningocele. We report a unique case of bilateral anterior sacral cysts, communicating with the subarachnoid space, associated with occult intrasacral meningeal and perineurial (Tarlov's) cysts, in an asymptomatic woman. The pertinent clinical and diagnostic imaging literature is reviewed. | 2 |
Alkaline reflux gastritis. Alkaline reflux gastritis and the symptoms associated with alkaline reflux gastritis have been reported in the medical literature since shortly after Billroth successfully performed his first gastrectomy in the 1880s. The disease process is produced by, or at least is associated with, the reflux of alkaline secretions into the gastric remnant. Although it occurs after any procedure that ablates the pylorus including pyloroplasty, it would appear to be most common after a Billroth II gastrojejunostomy. How the alkaline secretions cause the gastritis is still controversial. Clearly, the most effective therapy is to reroute the secretions from the biliary tract, pancreas, and duodenum so that they will not reflux into the gastric remnant. This is most effectively accomplished by a Roux-en-Y gastrojejunostomy with the afferent limb measuring at least 18 inches (40 cm). The surgeon and the patient should be aware that the construction of such a gastric outlet channel is associated with delayed gastric emptying. The etiology of this impaired emptying is also controversial. If the patient has symptoms of dumping (either early or late), these symptoms may also be abated using the Roux limb. At least 40% of patients will have gastric outlet obstruction. Supportive therapy is appropriate in the majority of these patients. | 1 |
Solid and cystic ultimobranchial body remnants in the thyroid. In this study we determined the incidence rate (89%) and characterized the morphology of ultimobranchial body (UBB) remnants found in 18 serially sectioned neonatal thyroid glands. Although UBB remnants are often referred to as solid cell nests, we found cystic features in 55%. Ciliated columnar cells were seen in 23%. One contained a large pseudo-papilla. The UBB cells had nuclei with features reminiscent of papillary carcinoma nuclei in that they were enlarged, oval, and contained finely dispersed chromatin when compared with follicular cell nuclei. Both papillary carcinomas and UBB remnants are common, occur as tiny, solid, or cystic thyroid entities in patients of all ages, may contain papillary structures, and share some common nuclear features. Therefore, it is important to include UBB remnants in the differential diagnosis of minute thyroid entities and to recognize their morphologic features. | 0 |
Adjacent solid boundaries alter the size of regurgitant jets on Doppler color flow maps. Recent studies have attempted to predict the severity of regurgitant lesions from jet size on Doppler flow maps. Jet size is a function of both regurgitant volume and fluid entrained from the receiving chamber and, for a free jet, is a function of its momentum at the orifice. However, regurgitant jets often approach or attach to cardiac walls, potentially altering their momentum and ability to expand by entrainment. Therefore, this study addressed the hypothesis that adjacent walls influence regurgitant jet size as seen on Doppler flow maps. Steady flow was driven through circular orifices (0.02 to 0.05 cm2) at physiologic velocities of 2 to 5 m/s. At a constant flow rate and orifice velocity, orifice position was varied to produce three jet geometries: free jets, jets adjacent to a horizontal chamber wall lying 1 cm below the orifice and wall jets with the orifice at the level of the wall. Doppler color flow imaging was performed at identical instrument settings for all jets. Two long-axis views of the jet were obtained: a vertical view perpendicular to the wall, resembling that most commonly used in patients to image the length of the jet, and a horizontal view parallel to the chamber wall. Velocities along the jet were also measured by Doppler mapping. | 3 |
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