Melricflash/CW_MedAbstractsAlt huggingface dataset:
A double-blind comparative study of doxazosin and prazosin when administered with beta-blockers or diuretics. The antihypertensive efficacy and safety of doxazosin (once daily) and prazosin (twice daily) were compared in patients with mild or moderate essential hypertension (diastolic blood pressure [DBP] 95 to 114 mm Hg) not adequately controlled by diuretics and beta-blockers. Doxazosin produced significantly greater mean reductions in standing (p = 0.01) and supine (p = 0.04) DBP than did prazosin; there were no significant between-group differences in either mean systolic blood pressure or heart rate. The overall mean daily doses for efficacy-evaluable patients were 4.7 mg of doxazosin and 6.7 mg of prazosin. Sixteen patients (84.2%) treated with doxazosin and 13 patients (56.5%) treated with prazosin were considered therapeutic successes (decrease in standing DBP greater than or equal to 10 mm Hg or to less than or equal to 90 mm Hg with greater than or equal to 5 mm Hg reduction from baseline). Of the 19 efficacy-evaluable patients treated with doxazosin, 15 (78.9%) showed improvement in the severity category of hypertension; an improvement in severity was reported in 14 patients (60.9%) treated with prazosin. Doxazosin produced a more favorable effect on serum lipid levels than did prazosin, although no statistically significant within- or between-group differences were observed. Most side effects experienced with either doxazosin or prazosin were mild or moderate and were tolerated or disappeared with continued treatment. The overall evaluation of toleration was excellent or good for 18 (90%) doxazosin- and 21 (91%) prazosin-treated patients. Clinical efficacy was rated as excellent or good for 16 patients (80%) treated with doxazosin and 15 patients (68%) treated with prazosin. 

Category: cardiovascular diseases
Operative findings after percutaneous pulmonary balloon dilatation of the right ventricular outflow tract in tetralogy of Fallot. Since 1983 percutaneous balloon dilatation of the right ventricular outflow tract has been performed as an alternative to surgical palliation in selected cases of tetralogy of Fallot at the Royal Liverpool Children's Hospital. From 31 December 1984 to 31 December 1988, 27 of these patients underwent subsequent surgical correction. Age at operation ranged from 7 to 58 months (median 2.7 years). The mean interval between balloon dilatation and correction was 15.6 months (range 3-39 months). Two patients had a systemic pulmonary shunt operation performed before dilatation and a further five required one afterwards. Overall 20 (74%) patients had some anatomical alteration as the result of balloon dilatation, while in seven (26%) there was no discernible change in the right ventricular outflow tract. There was no consistent relation between the ratio of balloon size to pulmonary annulus diameter and the morphological findings. Balloon dilatation may obviate the need for systemic-pulmonary shunt at the expense of some structural damage, particularly to the posterior cusp. The present data suggest that dilatation does not bring about growth of the annulus to such an extent that transannular patch is no longer needed at intracardiac repair. 

Category: cardiovascular diseases
Neuroendocrine design of the gut. The enteric nervous system (ENS) can be thought of as the third component of the autonomic nervous system. It is a vast network of neurons widely dispersed throughout the gut. The ENS is a dominant regulator of gut function through the action of peptide and non-peptide neurotransmitters. The most intensively studied roles of the ENS have been the regulation of secretory processes, such as gastric acid secretion, and motility. It is clear, however, that the ENS plays a broader role in the regulation of other gut functions, including mucosal defense, the gut immune response, and sphincter function. Alterations in the regulation of gut function by the ENS are likely or suspected in a number of conditions, including achalasia, Hirschsprung's disease, inflammatory bowel disease, Chagas' disease, chronic intestinal pseudoobstruction, biliary dyskinesia, tachygastria, and irritable bowel syndrome. Improved knowledge of the pathophysiology of these troublesome conditions makes effective therapy more likely in the future. 

Category: digestive system diseases
Aneurysmal dilatation in saphenous vein bypass grafts. Three patients are reported who developed aneurysmal degeneration of a saphenous vein arterial bypass graft. All three had hypercholesterolemia and two had marked elevation of triglycerides. One bypass was for occlusive disease and two for popliteal aneurysm. There was a long lag, 3 to 7 years between graft implantation and aneurysmal degeneration. The pathology was similar for all three cases with lipid laden macrophages, loss of elastic lamina, and other atherosclerotic changes in the vein wall. While atheromatous changes and aneurysm formation in saphenous vein bypass grafts are rare, this may occur especially in patients with hypercholesterolemia and hypertriglyceridemia. Careful and prolonged follow-up plus vigorous management of the hyperlipidemic state is mandatory in these patients. 

Category: general pathological conditions
Results of primary angioplasty for acute myocardial infarction in patients with multivessel coronary artery disease. The influence of multivessel coronary artery disease on the outcome of reperfusion therapy for myocardial infarction has not been fully characterized. Direct coronary angioplasty without antecedent thrombolytic therapy was performed during evolving myocardial infarction in 285 patients with multivessel coronary artery disease at 5.2 +/- 4.2 h after the onset of chest pain. Two vessel disease was present in 163 patients (57%) and three vessel disease in 122 (43%). An anterior infarct was present in 123 patients (43%), cardiogenic shock in 33 (12%) and age greater than or equal to 70 years in 59 (21%). Angioplasty of the infarct-related vessel was successful in 256 patients (90%), including 92% with two vessel and 88% with three vessel disease (p = NS). Emergency bypass surgery was needed in six patients (2%). In-hospital death occurred in 33 patients (12%), including 13 with two vessel and 20 with three vessel disease (p less than 0.05). The mortality rate was only 4% in the subgroup of 101 patients who met entry criteria for thrombolytic trials. The in-hospital mortality rate was 45% in patients in shock and 7% in patients not in shock (p less than 0.01). Logistic regression analysis identified shock and age greater than or equal to 70 years as independently associated with in-hospital death. In 135 patients who underwent predischarge left ventriculography, global ejection fraction increased from 50% to 57% (p less than 0.001) and regional wall motion in the infarct zone improved in 59% of patients. Follow-up data were available in 251 patients (99%) at a mean of 35 +/- 19 months. 

Category: cardiovascular diseases
Orchiectomy versus oestrogen in the treatment of advanced prostatic cancer. The primary clinical efficacy of orchiectomy and the combination therapy of intramuscular polyoestradiol phosphate 80 mg monthly and oral ethinyl oestradiol 0.15 mg daily was evaluated by progression and cancer mortality rates in a series of 277 prostatic cancer patients representing part of the Finnprostate study. After a follow-up of 5 years there was a significant difference between the groups in terms of progression rate and prostatic cancer deaths. The oestrogen combination was more effective in delaying progression of the disease. The overall mortality rate was similar in both groups. About one-third of the patients were alive after 5 years. 

Category: general pathological conditions
Partial cytochrome b deficiency and generalized dystonia. An 18-year-old female had clinical features of idiopathic torsion dystonia with bilateral hypodense putaminal lesions on computed tomography. Mitochondrial encephalomyopathy was suspected because of persistent lactic acidemia and myopathy. Studies of oxidative metabolism on isolated skeletal muscle mitochondria revealed partial cytochrome b deficiency indicating a defect in the cytochrome b- c1 complex. This finding represents a unique, multisystem syndrome of progressive dystonia, putaminal degeneration, myopathy, and mitochondrial cytochrome b deficiency. Mitochondrial metabolic disorders may be a cause of torsion dystonia when other known associated factors are absent. 

Category: general pathological conditions
Quinine-induced disseminated intravascular coagulation. Recurrent disseminated intravascular coagulation occurred in 3 women after ingestion of quinine tablets for cramp. All had circulating quinine-dependent antibodies to platelets and in 2 there was initial evidence of antibody consumption, with low titres that rose steeply over the next few days and remained high for many months. 

Category: nervous system diseases
The frequency of uterine leiomyomas. As a leading cause of hysterectomy in premenopausal women. uterine leiomyomas are a major public health problem. However, very little work has been done on their epidemiology. Indeed, their true frequency has never been established using systematic and meticulous methods. In this study, gross serial sectioning at 2-mm intervals was applied as an adjunct to routine pathology processing in 100 consecutive total hysterectomy specimens. This tripled the number of leiomyomas noted in routine pathology reports. There were 649 leiomyomas in 77 of 100 uteri, with multiplicity of leiomyomas in 84%. Although leiomyomas were more numerous and larger in women with a clinical diagnosis of myomatous uterus, the incidence was no higher than in uteri removed for other reasons. The postmenopausal incidence of leiomyomas was no lower than the premenopausal incidence, although postmenopausal leiomyomas were smaller and fewer. These findings suggest that epidemiologic studies of leiomyomas may not be valid if they are based only on clinical diagnoses or routine pathology reports. 

Category: neoplasms
Profiles of opioid analgesia in humans after intravenous bolus administration: alfentanil, fentanyl and morphine compared on experimental pain. This report examines the relationship of plasma drug concentration to analgesic effect following bolus doses of alfentanil, fentanyl and morphine and assesses individual differences in analgesic response among volunteers. We predicted that the 3 opioids would yield disparate analgesic profiles because their physicochemical and pharmacokinetic characteristics differ. Ten healthy volunteers received intravenous bolus doses of either alfentanil, fentanyl, morphine or normal saline on different days. We stimulated their teeth electrically and measured brain evoked potential (EP) and pain report (PR) repeatedly over 2 h to assess analgesic effect. Concurrently, we drew 18 blood samples to assess opioid plasma concentrations during the test period. The relationship between opioid plasma concentration and analgesic effect was well defined for alfentanil but ambiguous for morphine. Fentanyl exhibited a marked hysteresis. We observed noteworthy individual differences in analgesic response with all 3 drugs but these differences were greatest for morphine and least for alfentanil. Inter- and intrasubject variability in analgesic response across drugs is related to the physicochemical properties of the drugs tested. 

Category: nervous system diseases
Clinical efficacy of flosequinan in heart failure. The effects of the new arterial and venous vasodilator flosequinan have been evaluated in a variety of ways in different groups of patients with chronic heart failure. Flosequinan improved the central hemodynamic effects of heart failure in one group, with benefits still apparent up to 24 hours after a single oral dose. In another group it also improved calf blood flow and, therefore, blood flow to skeletal muscle. Also, using a number of different tests, it improved the exercise performance of the patients. In a further group the improvement in exercise tolerance produced was similar to that of captopril. Flosequinan has the necessary properties of a drug that is likely to be of benefit in the treatment of patients with chronic heart failure. 

Category: cardiovascular diseases
Insulin-like growth factor binding protein secretion by breast carcinoma cell lines: correlation with estrogen receptor status. Breast tumor cell lines have been shown to secrete several distinct polypeptide growth factors, although conflicting results exist for the insulin-like growth factors (IGFs). In contrast a limited number of breast tumor cell lines have definitely been shown to secrete the high affinity IGF binding proteins (IGFBPs) that modify IGF actions. To characterize the types of IGFBPs that are secreted by breast tumor cell lines, conditioned medium was collected from seven separate tumor cell lines, three of which were estrogen receptor (ER) negative, and four of which were ER positive. All three of the ER negative cell lines, MDA-231, MDA-330, and HS578T, secreted binding proteins of 49,000 and 43,000 Mr (IGFBP-3) as well as 29,000 (IGFBP-1) and 24,000 Mr. In contrast, all four ER positive cell lines secreted 34,000 (IGFBP-2) or 24,000 Mr forms, and none secreted the 49,000 and 43,000 or 29,000 Mr forms. BT-20, a cell line that is positive for ER messenger RNA (mRNA) but negative for ER protein, secreted predominantly a 34,000 Mr protein. The amount of total IGFBP activity released in 24 h ranged between 0.4 and 5.6 nM equivalents of IGFBP-1, and there was no significant difference between the ER positive and negative cell lines. The MCF-7 cells that produced predominantly 34,000 and 24,000 Mr forms showed a 1.8-fold increase in IGFBP secretion after estrogen stimulation. Immunoblotting and a specific RIA for IGFBP-1 showed that only the ER negative lines MDA-330, MDA-231, and HS578T secreted this form. Northern blotting analysis for the mRNA encoding this protein showed that both MDA-330 and MDA-231 contained a single 1.6 kilobase mRNA species that hybridized with an IGFBP-1 complementary DNA (cDNA) probe. Immunoblotting analysis of the other cell lines showed that only the 34,000 Mr form secreted by the ER positive cell lines reacted with IGFBP-2 antisera. Exposure of the conditioned media from the three ER negative cell lines to N-glycanase revealed that the 49,000 and 43,000 Mr forms of IGFBP were glycosylated and therefore probably represent IGFBP-3. We conclude that ER negative cell lines secrete three forms of IGFBPs, IGFBP-1, IGFBP-3, and a 24,000 Mr form. In contrast, the ER positive cell lines secrete predominantly IGFBP-2 and the 24,000 Mr form but do not secrete IGFBP-3 or 1.(ABSTRACT TRUNCATED AT 400 WORDS). 

Category: neoplasms
Neurohormonal factors in functional dyspepsia: insights on pathophysiological mechanisms. Neurohormonal factors were investigated in 10 patients with functional dyspepsia who had normal or slow upper gut transit and 10 age- and sex-matched healthy controls. Gastric and small bowel motility and transit, jejunal responses to luminal distention and IM neostigmine, gut hormones, and vagal and sympathetic functions were studied. Slow upper gut transit was defined by a gastric emptying slope less than 0.3%/min or 10% small bowel transit time greater than 300 minutes. Four patients with slow transit had reduced postprandial antral motility and gut hormone responses. Two of the four patients had vagal and sympathetic dysfunction. In 6 patients with normal transit, balloon distention in the jejunum was perceived at a lower volume (32.7 +/- 5.9 mL) than in controls (46.6 +/- 3.0 mL). Pressure responses to balloon distention were reduced in 5 and exaggerated in 1 patient; abnormal efferent vagal (2 patients) and sympathetic (1 patient) function were also documented. In view of the normal transit, motility, and jejunal pressure responses to neostigmine in all 6 patients, the abnormal response to distention suggests afferent dysfunction. Functional dyspepsia is a heterogenous disorder. Abnormal transit is sometimes associated with disorders of extrinsic neural control, but the latter are also found in patients with normal transit. Increased perception of intraluminal stimuli in those with normal transit suggests a disturbance in afferent function. 

Category: general pathological conditions
Transforming growth factor beta 1 suppresses acute and chronic arthritis in experimental animals. Systemic administration of the cytokine, TGF beta 1, profoundly antagonized the development of polyarthritis in susceptible rats. TGF beta 1 administration (1 or 5 micrograms/animal), initiated one day before an arthritogenic dose of streptococcal cell wall (SCW) fragments, virtually eliminated the joint swelling and distortion typically observed during both the acute phase (articular index, AI = 2.5 vs. 11; P less than 0.025) and the chronic phase (AI = 0 vs. 12.5) of the disease. Moreover, TGF beta 1 suppressed the evolution of arthritis even when administration was begun after the acute phase of the disease. Histopathological examination of the joint revealed the systemic TGF beta 1 treatment greatly reduced inflammatory cell infiltration, pannus formation, and joint erosion. Consistent with the inhibition of inflammatory cell recruitment into the synovium, TGF beta 1 reversed the leukocytosis associated with the chronic phase of the arthritis. Control animals subjected to the same TGF beta 1 dosing regimen displayed no discernable immunosuppressive or toxic effects even after 4 wk of treatment. These observations not only provide insight into the immunoregulatory effects of TGF beta, but also implicate this cytokine as a potentially important therapeutic agent. 

Category: general pathological conditions
Patient evaluation for cardiac transplantation. The aim for cardiac transplantation is to improve the quality of life and the survival in patients with end-stage heart failure. Given the scarcity of donor organ availability, the expense of the transplantation process and follow-up care, as well as the tremendous emotional burden the process places on a patient and his/her family, it is essential to carefully screen potential candidates for their symptomatic, functional, hemodynamic, and psychosocial eligibility, and to rule out coexisting hemodynamic or comorbid conditions that would jeopardize successful transplantation and immunosuppression. Comprehensive screening of potential transplant candidates, which is best accomplished by a multidisciplinary team approach working closely with patients and their families, is essential to insure that maximum benefit is derived from this scarce and valuable resource. 

Category: cardiovascular diseases
Hirudin interruption of heparin-resistant arterial thrombus formation in baboons. To determine the role of thrombin in high blood flow, platelet-dependent thrombotic and hemostatic processes we measured the relative antithrombotic and antihemostatic effects in baboons of hirudin, a highly potent and specific antithrombin, and compared the effects of heparin, an antithrombin III-dependent inhibitor of thrombin. Thrombus formation was determined in vivo using three relevant models (homologous endarterectomized aorta, collagen-coated tubing, and Dacron vascular graft) by measuring: (1) platelet deposition, using gamma camera imaging of 111In-platelets; (2) fibrin deposition, as assessed by the incorporation of circulating 125I-fibrinogen; and (3) occlusion. The continuous intravenous infusion of 1, 5, and 20 nmol/kg per minute of recombinant hirudin (desulfatohirudin) maintained constant plasma levels of 0.16 +/- 0.03, 0.79 +/- 0.44, and 3.3 +/- 0.77 mumol/mL, respectively. Hirudin interrupted platelet and fibrin deposition in a dose-dependent manner that was profound at the highest dose for all three thrombogenic surfaces and significant at the lowest dose for thrombus formation on endarterectomized aorta. Thrombotic occlusion was prevented by all doses studied. In contrast, heparin did not inhibit either platelet or fibrin deposition when administered at a dose that maximally prolonged clotting times (100 U/kg) (P greater than .1), and only intermediate effects were produced at 10-fold that dose (1,000 U/kg). Moreover, heparin did not prevent occlusion of the test segments. Hirudin inhibited platelet hemostatic function in concert with its antithrombotic effects (bleeding times were prolonged by the intermediate and higher doses). By comparison, intravenous heparin failed to affect the bleeding time at the 100 U/kg dose (P greater than .5), and only minimally prolonged the bleeding time at the 1,000 U/kg dose (P less than .05). We conclude that platelet-dependent thrombotic and hemostatic processes are thrombin-mediated and that the biologic antithrombin hirudin produces a potent, dose-dependent inhibition of arterial thrombus formation that greatly exceeds the minimal antithrombotic effects produced by heparin. 

Category: cardiovascular diseases
Inhibition of cell mediated cytotoxicity by sulphasalazine: effect of in vivo treatment with 5-aminosalicylic acid and sulphasalazine on in vitro natural killer cell activity. Decreased cell mediated cytotoxicity occurs frequently in inflammatory bowel disease, particularly in patients with active disease. It is not clear, however, whether this decrease is caused by the disease or is a consequence of the medical treatment. In this study we evaluated the effect of in vivo treatment with 5-aminosalicylic acid and sulphasalazine on the in vitro natural killer cell activity in five patients with inflammatory bowel disease in remission and in four healthy control subjects in a double blind randomised crossover trial preceded and separated by four weeks of treatment with placebo. The natural killer cell activity was significantly impaired in 67% (six of nine subjects) after four weeks' sulphasalazine treatment and tended to be related to subjects with a slow acetylator phenotype. In contrast, 5-aminosalicylic acid treatment caused only a marginal reaction in the natural killer cell activity in 22% (two of nine subjects). The inhibitory effects were found to be reversible since the decreased natural killer cell activity was completely restored after placebo treatment in all subjects. In conclusion, in vivo treatment with sulphasalazine inhibits the in vitro natural killer cell activity and this seems to be mediated by the sulphapyridine moiety. This phenomenon may contribute to the low natural killer cell activity found in patients with active inflammatory bowel disease. 

Category: digestive system diseases
Detection of bcr-abl fusion in chronic myelogeneous leukemia by in situ hybridization. Chronic myelogeneous leukemia (CML) is genetically characterized by fusion of the bcr and abl genes on chromosomes 22 and 9, respectively. In most cases, the fusion involves a reciprocal translocation t(9;22)(q34;q11), which produces the cytogenetically distinctive Philadelphia chromosome (Ph1). Fusion can be detected by Southern (DNA) analysis or by in vitro amplification of the messenger RNA from the fusion gene with polymerase chain reaction (PCR). These techniques are sensitive but cannot be applied to single cells. Two-color fluorescence in situ hybridization (FISH) was used with probes from portions of the bcr and abl genes to detect the bcr-abl fusion in individual blood and bone marrow cells from six patients. The fusion event was detected in all samples analyzed, of which three were cytogenetically Ph1-negative. One of the Ph1-negative samples was also PCR-negative. This approach is fast and sensitive, and provides potential for determining the frequency of the abnormality in different cell lineages. 

Category: neoplasms