shukoor65/lab-rag-model huggingface dataset:
Low-dose enoximone in subjects awaiting cardiac transplantation. Clinical results and effects on beta-adrenergic receptors. During a 3-year period we administered enoximone, a phosphodiesterase inhibitor with positive inotropic and vasodilator properties, to 73 pretransplantation patients with end-stage heart failure who exhibited a clinical requirement for additional inotropic support. The clinical course and myocardial beta-adrenergic receptor status in the explanted hearts of these 73 patients was compared with results in 113 concurrently listed pretransplantation patients not requiring additional inotropic support. Only three patients required cessation of enoximone because of adverse effects, all from exacerbation of ventricular arrhythmias. Sixty-six of 73 (90.4%) enoximone-treated patients ultimately underwent cardiac transplantation a mean of 39.2 +/- 6.6 days (range 1 to 221 days) after starting enoximone, whereas seven patients (9.6%) died awaiting cardiac transplantation. The respective 1-, 3-, and 6-month pretransplantation survival rates of patients treated with enoximone calculated from their time on the waiting list for transplantation were 88.0%, 82.5%, and 82.5% compared with 92.1%, 83.8%, and 76.2% in control patients not receiving enoximone (all p = not significant). In 25 patients who received enoximone, ventricular myocardial beta-adrenergic receptors were measured at the time of transplantation and compared with values in failing ventricles from 52 pretransplantation patients not exposed to enoximone. Compared with ventricular myocardium of patients not given enoximone or intravenous beta-adrenergic agonists, total beta-adrenergic receptor (beta 1 plus beta 2) density was not decreased in patients treated with enoximone or enoximone plus intravenous beta-adrenergic agonists, but was decreased by 31% (p less than 0.05) in patients given intravenous beta-adrenergic agonists alone. Additionally, patients treated with enoximone had higher myocardial beta 2-adrenergic receptor densities than respective subgroups treated without (28% higher, p less than 0.01) or with (65% higher, p less than 0.01) intravenous beta-adrenergic agonists. Finally, isoproterenol- or calcium-mediated contractile responses in isolated right ventricular preparations from 14 patients treated with enoximone were similar to values in control patients not exposed to enoximone or intravenous beta-adrenergic agonists, suggesting that enoximone-related beta-adrenergic subsensitivity or damage to the contractile apparatus does not occur.
Long-term soft-tissue effects of biliary extracorporeal shock waves: an animal study. Although delayed effects of renal extracorporeal shock-wave lithotripsy (ESWL) have been reported, the long-term soft-tissue effects after biliary ESWL have not been investigated. We report soft-tissue effects seen up to 1 year after biliary extracorporeal shock waves were administered to 18 Yucatan pigs. The gallbladder received 4000 electromagnetic shock waves from a Siemens Lithostar overhead module. Blood samples were drawn from each pig for hematologic, coagulation, and biochemical profiles immediately before and then at prescribed time intervals after administration of shock waves. Autopsy and histopathologic examination of the gallbladder and surrounding organs were performed. Kidneys and adrenal glands also were examined in five pigs followed up for 1 year. There were no gross or microscopic abnormalities in 11 animals, including all five animals in the 1-year group in which kidneys and adrenal glands also were normal. One animal (3-week group) had two 2-mm foci of parenchymal necrosis in the right lobe of the liver, probably related to ischemia after shock-wave therapy. Transient rise in liver and pancreatic enzyme levels was seen in most animals after administration of shock waves. The levels returned to normal within 2 months in all but one animal. We conclude that biliary ESWL with the Lithostar Plus does not produce long-term histologic evidence of organ damage in Yucatan pigs.
Jolt accentuation of headache: the most sensitive sign of CSF pleocytosis. We prospectively examined the clinical signs of 54 febrile patients associated with recent-onset headache. They underwent lumbar puncture (LP) on suspicion of meningitis. The relation of each sign to cerebrospinal fluid (CSF) pleocytosis was estimated. Among 34 patients with pleocytosis, 33 had jolt accentuation (sensitivity: 97.1%), while only 5 of them had neck stiffness or Kernig's sign. Among 20 patients without pleocytosis, 12 had no jolt accentuation (specificity: 60%). We found jolt accentuation to be the most sensitive sign of CSF pleocytosis. If jolt accentuation is noted in a febrile patient associated with recent onset headache, the CSF should be examined even in the absence of neck stiffness or Kernig's sign.
Cost-effectiveness of antihypertensive treatment. General considerations. Cost-effectiveness analysis, a set of methods for estimating the costs and health effects of medical interventions, helps decision makers to compare alternative treatments and to decide which interventions are appropriate in which situations. This article outlines some fundamental principles of cost-effectiveness analysis and discusses the characteristics necessary if alternative therapies are to be more cost-effective than traditional drug treatment for hypertension. The discussion focuses primarily on the newer drugs like angiotensin converting enzyme inhibitors, alpha-adrenergic receptor blockers, and calcium antagonists.
Quantitative analysis of signal-averaged P waves in idiopathic paroxysmal atrial fibrillation. Detailed analysis of the QRS complex can identify patients at risk from ventricular arrhythmias, but similar techniques applied to the atria have been disappointing. This study attempts to quantitate differences in the fine morphology of P waves in a group of 9 patients with paroxysmal atrial fibrillation (AF) versus 15 control subjects. Atrial triggered signal-averaging was combined with a detailed investigation of P-wave duration, high-frequency spatial voltage and spatial velocity. Signal-averaged P-wave duration was significantly increased in patients with paroxysmal AF (135 +/- 8 vs 126 +/- 4 ms, p less than 0.05). The root-mean-square voltage at frequencies greater than 35 Hz in these patients was also significantly greater (16 +/- 3 vs 12 +/- 1 microV, p less than 0.05). Similar observations were made at frequencies greater than 40 Hz (10 +/- 3 vs 7 +/- 1 microV, p less than 0.05). These differences appeared to be confined to the third quarter of the P wave (third quarter root-mean-square voltage at greater than 40 Hz expressed as a ratio of total P-wave root-mean-square voltage, 1.4 +/- 0.1 vs 1.2 +/- 0.1, p = 0.005). Spatial velocity was also increased in the paroxysmal AF group (peak spatial velocity 6.4 +/- 1.8 vs 4.6 +/- 0.5 mV/s, p less than 0.05). These observations support previous intracardiac data that implicate delay and fragmentation of intraatrial conduction in the pathogenesis of paroxysmal AF.
Evolution of the treatment of the injured colon in the 1980s. During the past 10 years, 1006 patients with colon injuries were treated in an urban trauma center. Primary repair, including suture repair and resection with anastomosis, was performed in 614 patients (61%), colostomy in 284 patients (28%), and exteriorized repairs in 83 patients (8.3%). In the remaining 25 patients (2.5%) who were exsanguinating, the colon injuries were ligated. Independent risk factors for adverse outcomes (defined as a fecal fistula, abdominal abscess, stomal complication, or death from multisystem failure) were identified using multiple logistic regression analysis. These factors were used to match patients at similar risk within different treatment groups, and odds ratios for each treatment were calculated. The odds ratios for primary repair, colostomy, and exteriorized repair were 1.0, 1.9, and 2.0, respectively. Therefore, the chance of an adverse outcome was twice as great for both exteriorized repair or colostomy as for primary repair. It is concluded that further increases in the use of primary repair are warranted.
Current and future drugs for acid-peptic disease: a plethora of opinions on possible mechanisms of action. Sixty-seven invited participants involved in the development, evaluation, and use of therapies for acid-peptic disorders participated in a meeting to discuss the scientific basis for healing actions of ulcer drugs and the prospects for future developments ("Realities of Mucosal Protection in the Upper Gastrointestinal Tract," Lausanne, Switzerland, November 8-10, 1987). Eighty-one key statements were prepared and subsequently analyzed on the basis of a voting system. Of the 45 statements that dealt with existing therapies, only 3 statements showed positive consensus (agreement of two-thirds or more of voters) about mechanisms of ulcer healing. Participants agreed that both (1) hydrogen/potassium adenosine triphosphatase inhibitors and (2) histamine H2 antagonists healed ulcers solely by acid inhibition, and (3) that sucralfate works by topical action. Substantial uncertainty about the mechanisms by which bismuth compounds and antacids heal ulcers was noted as well as their wide range of effects. The mechanism of ulcer healing by prostaglandins and the clinical relevance of antiulcer effects of drugs demonstrated in acute studies with animals were also controversial. There was greater agreement among participants about unexplored drug effects that might produce ulcer healing. Of the 36 such mechanisms surveyed, the most support went to therapies aimed at enhancement of mucosal blood flow, epithelial restitution, and mucosal alkaline secretion or inhibition of luminal pepsin activity. The diversity of opinions among participants suggests a high level of empiricism in the development of ulcer healing drugs apart from those that inhibit acid secretion. This empiricism probably arises from inadequate understanding of processes of mucosal injury and repair.
von Willebrand factor and animal models: contributions to gene therapy, thrombotic thrombocytopenic purpura, and coronary artery thrombosis. Use of animal models of von Willebrand factor (vWF) deficiency, both inherited and induced, continues to advance the knowledge of vWF-related diseases. Three examples are reviewed in this article--von Willebrand's disease (vWD), thrombotic thrombocytopenic purpura, and coronary artery thrombosis. The success of gene transfer by liver and bone marrow transplantation in porcine vWD and canine hemophilia A, with a change in phenotype that establishes improved hemostasis, portends imminent testing of gene therapy in these models. With use of recombinant technology, the phenotype of hemophilia B fibroblasts has been transformed to normal, as evidenced by secretion of the normal hemostatically active protein. This result is a prelude to implantation in hemophilic animals. Thrombotic thrombocytopenic purpura is characterized by qualitative and quantitative alterations in vWF. A new animal model induced by the venom factor botrocetin, a cofactor of vWF, closely mimics the human syndrome. A proposed pathophysiologic mechanism for thrombotic thrombocytopenic purpura is outlined. The third contribution is recognition that occlusive coronary thrombosis is a vWF-dependent condition. Without vWF, as in porcine vWD or normal pigs treated with a monoclonal anti-vWF antibody, occlusive thrombi do not develop, even with luminal stenosis. The thrombogenicity of coronary atheromas, including those with fissures of the fibrous cap, is also vWF-dependent.
Persistent platelet activation by passivated grafts. Vascular grafts in canines exhibit similar healing patterns to humans in that the graft surface forms a pseudointima over time but endothelializes only near the anastomotic sites. Thus the pseudointima at the midportion of the graft may represent a nidus for persistent platelet activation. The purpose of this investigation was to examine the effect of the maturing graft surface on platelet activation. Long Dacron subcutaneous carotid to aorta grafts (50 cm x 8 mm) were placed in nine dogs. Blood samples were obtained by direct graft puncture, at the proximal and distal ends of the graft, at 1, 24, 48, 72 hours, 1, 2, 3, 4 weeks, and monthly thereafter for 8 months. Seven sham dogs had subcutaneous grafts implanted without arterial anastomoses, and blood samples were drawn from the femoral artery. Platelet counts were determined with a platelet counter. Platelet aggregation and release of adenosine triphosphate was determined with a whole blood aggregometer by use of arachidonic acid, collagen, and adenosine diphosphate as agonists. No difference was found in platelet aggregation to collagen or adenosine diphosphate stimulation across the graft, but platelets released significantly less adenosine triphosphate to collagen and adenosine diphosphate stimulation distally versus proximally. In the graft dogs a decrease in systemic platelet counts of 50% occurred from the preoperative level which persisted over 8 months (p less than 0.01). Also less response occurred to collagen and ADP stimulated platelet aggregation in the graft animals than the sham animals during the first month of study. These data suggest that significant platelet-graft interactions occur even after the graft has formed a mature pseudointima.
Evaluation of different systems for clinical quantification of varicose veins. One hundred twenty-five lower limbs with varicose veins were studied clinically, essentially by palpation. Two specialists in venous pathology scored the severity of the varicose veins from 0 to 20. Comparison between the different clinical parameters and the scores of the specialists showed that two systems of clinical quantification gave good results and were easy to use. One system is the maximum diameter of the largest varicose vein; the other system is the sum of maximum diameters over 7 sections (3 for thigh, 3 for leg, 1 for foot). This latter system gives a more precise evaluation of the clinical severity of the varicose veins.
Should elective endoscopic sphincterotomy replace cholecystectomy for the treatment of high-risk patients with gallstone pancreatitis? [editorial] Since the introduction of endoscopic sphincterotomy approximately 15 years ago, the indications for this procedure have expanded. Currently endoscopic sphincterotomy is the procedure of choice for management of retained common bile duct stones following cholecystectomy. It is also being used more frequently for choledocholithiasis with an intact gallbladder in high-risk patients and in some patients with acute gallstone pancreatitis. In patients recovering from an episode of gallstone pancreatitis, standard practice has been subsequent cholecystectomy with possible exploration of the common bile duct. To avoid surgery in high-risk patients, we propose that an elective endoscopic sphincterotomy may be a reasonable therapeutic option regardless of whether common bile duct stones are present at the time of ERCP. A prospective trial is needed to examine this issue since to date there is no literature on endoscopic sphincterotomy in the absence of choledocholithiasis for gallstone pancreatitis in patients with intact gallbladders.
A case of chronic mountain sickness diagnosed by routine pulmonary function tests. In summary, this is a patient who presented with respiratory acidosis and cor pulmonale. The major diagnostic challenge was in differentiating primary cardiopulmonary disease from a central abnormality of ventilatory drive. The arterial blood gases showed a normal A-a gradient suggesting hypoventilation as the etiology of his hypoxemia. Pulmonary function testing showed air trapping, but a relatively normal FEV1/FVC and airways resistance. The literature suggests that most altitude natives have depressed hypoxemic and hypercapnic drives with a distinct subset demonstrating a profoundly depressed drive to ventilation. This latter group has been labeled as having chronic mountain sickness or Monge's disease. As one might expect, ventilatory control during sleep is also abnormal in these patients with CMS. Our patient indeed showed typical frequent severe desaturations with hypopnea. The diagnosis of CMS in our patient was made with routine arterial blood gases and standard pulmonary function tests. Additional tests of ventilatory responsiveness to oxygen and carbon dioxide could have been performed, but are not necessary to make the diagnosis.
Possible deletion of a developmentally regulated heavy-chain variable region gene in autoimmune diseases. Several autoantibody-associated variable region (V) genes are preferentially expressed during early ontogenic development, suggesting strongly that they are of developmental and physiological importance. As such, it is possible that polymorphisms in one or more of these genes may alter susceptibility to autoimmune disease. We have searched extensively for a probe related to a developmentally regulated V gene that has the power to differentiate among highly homologous V genes in human populations. Using such a probe (i.e., Humhv3005/P1) related to both anti-DNA and anti-IgG autoantibodies, we studied restriction fragment length polymorphisms in patients with rheumatoid arthritis and systemic lupus erythematosus and found an apparent heavy-chain V (VH) gene deletion that was nearly restricted to the autoimmune patients. These data suggest that deletions of physiologically important VH genes may increase the risk of autoimmunity through indirect effects on the development and homeostasis of the B-cell repertoire.
Routine programmed electrical stimulation in survivors of acute myocardial infarction for prediction of spontaneous ventricular tachyarrhythmias during follow-up: results, optimal stimulation protocol and cost-effective screening Of 3,286 consecutive patients treated for acute myocardial infarction, electrophysiologic testing was performed in 1,209 survivors (37%) free of significant complications at the time of hospital discharge to determine their risk of spontaneous ventricular tachyarrhythmias during follow-up. Sustained monomorphic ventricular tachycardia was inducible by programmed electrical stimulation in 75 (6.2%). Antiarrhythmic therapy was not routinely prescribed regardless of the test results. During the 1st year of follow-up, 14 infarct survivors (19%) with inducible ventricular tachycardia experienced spontaneous ventricular tachycardia or fibrillation in the absence of new ischemia compared with 34 (2.9%) of those without inducible ventricular tachycardia (p less than 0.0005). During the extended follow-up period (median 28 months) of those with inducible ventricular tachycardia, 19 (25%) had a spontaneous electrical event; 37% of these first events were fatal. These results suggest that the most cost-effective strategy for predicting arrhythmia will be obtained by restricting electrophysiologic testing to infarct survivors whose left ventricular ejection fraction is less than 40% and using a stimulation protocol containing four extrastimuli. Electrophysiologic testing is the single best predictor of spontaneous ventricular tachyarrhythmias during follow-up in infarct survivors. The majority (94%) with a negative test benefit from the more reliable reassurance that all is well, whereas the 25% risk of electrical events in those with inducible ventricular tachycardia justifies a prospective trial of effective prophylactic antiarrhythmic interventions.
Digital rectal examination and carcinoma of the prostate. Urologists have considered themselves to be the experts in the use of digital rectal examination for the evaluation of diseases of the prostate. However, without close attention to the teaching of this examination, it probably is inaccurate and unreliable. Moreover, many patients who are destined to die of prostate cancer never develop a palpable abnormality. In patients with prostate cancer, a palpable abnormality usually indicates the presence of carcinoma, but the majority of patients will be upstaged by pathologic examination. In patients undergoing a digitally guided biopsy, it appears critical that those with a negative biopsy be followed closely, as they have a measurable risk of developing overt carcinoma. It is unclear how transrectal ultrasound will interface with digital rectal examination because of the multiple echo patterns this disease can exhibit.
Quantitative cervical flexor strength in healthy subjects and in subjects with mechanical neck pain. Although weakness of anterior cervical muscles is postulated to contribute to persistent neck pain in patients with mechanical neck pain, quantitation of weakness has never been reported. We compared anterior cervical muscle strength in 30 subjects with mechanical neck pain and in 30 asymptomatic control subjects. Testing was performed with the subject supine, chin retracted, and neck flexed. Assessment was made using a hand-held dynamometer with head held at the midline and with rotation left and right within a pain-free range. Analysis with Wilcoxon scores showed that patients with neck pain had significantly less (p less than .05) strength (N.Kg-1) in all three positions than controls (1.16 +/- 0.49 vs 1.71 +/- 0.42, sagittally; 1.01 +/- 0.52 vs 1.47 +/- 0.41, rotation left; .99 +/- 0.46 vs 1.43 +/- 0.43 rotation right; neck pain vs control, respectively.) This weakness and its role in persistent neck pain should be recognized. The efficiency and effect of cervical muscle strengthening in treatment of chronic neck pain should be further defined.
A phase I, II study of high-dose 5-fluorouracil and high-dose leucovorin with low-dose phosphonacetyl-L-aspartic acid in patients with advanced malignancies. Twenty-eight patients with refractory advanced malignancies were treated with a 24-hour infusion of 5-fluorouracil (5-FU), leucovorin (LV), and N-(phosphonacetyl)-L-aspartic acid (PALA) weekly. Twenty-seven patients were evaluable to assess toxicity and antitumor activity. The PALA was administered as an intravenous bolus over 15 minutes at a fixed dose (250 mg/m2) 24 hours before the start of the 5-FU and leucovorin infusions. Initially the dose of 5-FU was 750 mg/m2; this was increased incrementally to 2600 mg/m2. The LV was administered in a fixed dose of 500 mg/m2 concurrently with the 5-FU over a 24-hour period. This regimen was repeated weekly. Diarrhea, stomatitis, nausea, and vomiting were among the dose-limiting toxicities. Others were hand-foot syndrome, hair loss of the scalp and eyelashes, overall weakness, rhinitis, and chemical conjunctivitis. The maximum tolerated dose of 5-FU in this combination and schedule was 2600 mg/m2. Seven of 14 patients treated with 2600 mg/m2 were able to tolerate the chemotherapy on a weekly basis without interruption. The other seven patients required dose reductions, but most received 5-FU at a dose of 2100 mg/m2. Twenty-three of 27 patients were treated previously. Eight patients had a partial response; five of these were treated previously. A complete response was observed in one patient with pancreatic carcinoma, previously untreated. The overall response rate for patients treated with 2100 or 2600 mg/m2 of 5-FU was nine of 18 patients (50%). Three of four previously untreated patients with pancreatic cancer responded to this treatment (two responded partially, and one had a complete response). One of three heavily pretreated patients with non-small cell lung cancer had a partial response as did a patient with breast cancer. Four of ten patients with colorectal cancer responded to the treatment (four partial responses), of whom three had been treated previously.