shukoor65/lab-rag-model huggingface dataset:
Presenting features and prognosis of chronic lymphocytic leukemia in younger adults. We have analyzed 117 younger patients with chronic lymphocytic leukemia (CLL) (mean age, 44.5 years; SD, 4.8; range, 19 to 49; male/female ratio, 2.08) with three main objectives: (1) to see whether these patients have distinctive presenting clinical features; (2) to investigate the impact of the disease on survival; and (3) to analyze whether already well-known prognostic factors are also useful when applied to these patients. As compared with an older age population (greater than or equal to 50 years), there were no major differences in presenting features except for an increased proportion of males (2.08 v 1.21; P less than .025) and a higher hemoglobin level (13.47 +/- 2.70 g/dL v 12.84 +/- 2.77 g/dL; P less than .05) in the younger group. Median survival is 12.3 years (expected median from a control group, 31.2 years). Clinical stages, bone marrow patterns, blood lymphocyte counts, and its doubling time are all useful to separate different risk groups of patients. Whereas patients with favorable prognostic factors have a survival probability of about 80% 14 years after diagnosis, those with poor prognostic features have a median survival of less than 3 years. It is concluded that CLL in younger adults has no major distinctive presenting features and that known prognostic factors are useful to separate different risk groups of patients. These results should be of help in planning therapy for younger persons with CLL.
Long-term efficacy and safety of terazosin alone and in combination with other antihypertensive agents. This open, multicenter phase III study was designed to assess the efficacy and long-term safety of terazosin (1 to 40 mg/day), alone or in combination with other antihypertensive drugs, in 364 patients with mild to moderate essential hypertension. Compared with baseline values, long-term terazosin monotherapy or combination therapy resulted in consistent decreases in both systolic and diastolic blood pressures, with a mean reduction in supine diastolic pressure of 12 to 14 mm Hg. The numbers of patients with controlled blood pressure at the last evaluable visit of each therapy period were as follows: terazosin alone, 106 of 245 (43%); terazosin with added diuretic, 70 of 112 (63%); diuretic with added terazosin, 47 of 88 (53%); and terazosin plus diuretic with added beta-blocker, 22 of 32 (69%). Most adverse events were mild or moderate in severity. Only pain in extremities had a higher incidence during long-term treatment (6%, 181 to 360-day period) than during initial short-term treatment (5%, 1 to 90-day period). Three of six syncopal events occurred during the initial 180 days of treatment; this 0.8% (3/364) incidence was comparable with that reported previously for short-term studies. Only one case of syncope occurred during terazosin monotherapy. Terazosin was judged to be a safe and effective long-term medication for the treatment of hypertension.
The "make/break test" as a diagnostic tool in functional weakness. Strength was measured in four major muscle groups with a hand-held dynamometer. The "make" and "break" technique was used with and without encouragement, and fatiguability was tested in patients with organic weakness and patients with functional weakness. Patients with functional weakness could be distinguished from the other two groups by an increase in strength greater than 20% with the break compared with the make technique. Additionally they tend to show larger increases in strength with encouragement and their "fatiguability" was less.
Enhanced detection of the t(14;18) translocation in malignant lymphoma using pulsed-field gel electrophoresis. The t(14;18) chromosomal translocation that results in the juxtaposition of the bcl-2 proto-oncogene with the heavy chain JH locus is a common cytogenetic abnormality in human lymphoma. In particular, it is seen in about 85% of follicular lymphoma (FL) and up to one-third of diffuse lymphomas (DL). The chromosome 18 breakpoints have been shown to cluster into two regions. The major breakpoint region (mbr) within the 3' untranslated region of the bcl-2 proto-oncogene accounts for approximately 60% of the cases and the minor cluster region (mcr) 30 kb 3' of bcl-2 accounts for approximately 25% of the breakpoints. Because of variability in the position of the breakpoint, detection of the t(14;18) by Southern blot analysis provides an important clonal marker for the tumor. However, conventional electrophoresis (CE) fails to detect the translocation in 15% to 25% of cases. We have applied pulsed-field gel electrophoresis (PFGE) to the detection of the t(14;18) in a series of lymphoma prospectively analyzed by CE, polymerase chain reaction (PCR), and cytogenetic analysis. PFGE readily detected t(14;18) rearrangements as indicated by comigration of bands detected with probes for the mbr region (chromosome 18) and the JH locus (chromosome 14). In a series of 40 patients with FL, this method proved to be the most comprehensive for detection of the translocation compared with standard methods; in fact, in one case only PFGE was able to detect the chromosomal rearrangement. Ten percent of the FL cases were negative by all methods tested. In a separate analysis of matched tissue specimens from cases of tumor progression of FL to diffuse lymphoma, PFGE detected a common t(14;18) rearrangement confirming a clonal origin in seven of seven cases, whereas CE detected a rearrangement in only three of seven cases. Overall, PFGE was able to detect a translocation in 8 of 12 cases that were negative by CE and four of eight negative by cytogenetic analysis. In conclusion, PFGE analysis is more comprehensive than CE, PCR, and cytogenetic analysis for the detection of the t(14;18) breakpoint in tissue biopsies of malignant lymphoma.
Small bowel tumours: yield of enteroscopy. A total of 258 patients with obscure gastrointestinal bleeding were referred for small bowel enteroscopy, a procedure which allows endoscopic evaluation of most of the small intestine. A small bowel tumour was found in 5% of patients. In 50% of patients no diagnosis could be made, but when the cause of obscure bleeding was discovered small bowel tumours were the single most common lesion in patients younger than 50 years. Small bowel tumours causing gastrointestinal bleeding may remain undetected despite extensive diagnostic evaluation. We conclude that small bowel tumours are the most common cause of obscure gastrointestinal bleeding in patients less than 50 years of age. Small bowel enteroscopy is diagnostic of small bowel tumours even when all previous diagnostic studies, including enteroclysis and angiography, are negative.
Effect of DN-1417 on photosensitivity and cortically kindled seizure in Senegalese baboons, Papio papio. The effect of DN-1417, a thyrotropin-releasing hormone (TRH) analogue, on photosensitivity and cortically kindled seizures was examined in seven Senegalese baboons (Papio papio). Intravenous (i.v.) administration of 2 mg/kg had no effect on either photosensitivity or cortically kindled seizures. When this agent was administered intracisternally, both the photomyoclonic response and cortically kindled seizures were suppressed for 4-5 days. A study of the transcallosal response also showed a long-lasting attenuation of the early positive wave (P1) amplitude (peak latency, 5-10 ms) elicited by a single stimulus after cisternal injection of DN-1417. These findings are consistent with the assumption that endogenous TRH is involved in suppression of epileptic seizures.
Comparison of extradural and intravenous diamorphine as a supplement to extradural bupivacaine. The influence of route of administration (extradural as compared with intravenous) of diamorphine 0.5 mg/hour as a supplement to extradural bupivacaine (0.125% at 15 ml/hour) was investigated in two groups of 20 patients who underwent major abdominal gynaecological surgery. Significantly more patients in the intravenous group withdrew because of inadequate analgesia (p less than 0.05). Those in the extradural group were significantly more drowsy throughout the study (p less than 0.01), but no major side effects were encountered.
Extracranial-intracranial bypass to reduce the risk of ischemic stroke. Extracranial-intracranial (EC-IC) bypass surgery is an operative procedure in which the superficial temporal artery is anastomosed to the middle cerebral artery. The operation, first described in 1969, was employed to circumvent otherwise surgically inaccessible atherosclerotic lesions high in the internal carotid system or in the middle cerebral artery. This assessment compares the findings from 13 surgical series of EC-IC bypass (1464 patients) with those reported in the only prospective, randomized, cooperative trial of this procedure (1377 patients). Analysis of the outcomes in the 1464 patients included in the surgical series produced insufficient evidence to support a conclusion that post-EC-IC bypass stroke rates were lower than the rates of either the medically or surgically treated groups in the controlled clinical trial. In the absence of reliable, objective evidence of the existence of a group of patients in whom surgical intervention is superior to medical treatment in reducing the frequency of stroke, the results of the single controlled clinical trial, which demonstrated no benefit of bypass, must be accepted as the best evidence currently available.
Importance of experimental models for the development of clinical trials on thromboatherosclerosis. Experimental models of vascular injury have enhanced our understanding of the pathophysiological process leading to vascular obstruction in both spontaneous and accelerated atherosclerosis. Based on experimental findings, we present and discuss a pathological classification of vascular injury or damage and its role in the pathogenesis of various vascular diseases. In addition, these animal models have provided insights into the roles of platelets and lipid metabolism in the evolution and progression of atherosclerosis and have suggested potential therapeutic applications. Thus, based on studies in the pig models, antiplatelet agents have been shown for the first time to have a beneficial effect in preventing the formation and progression of coronary atherosclerotic lesions in humans. Similarly, our findings in high density lipoprotein plasma fractions regarding inhibition and even reversal of the process of atherosclerosis in a hypercholesterolemic rabbit model have added new insights to an explosive field of lipoprotein research and provided new avenues of therapeutic strategies. our in vivo and ex vivo pig models of an extracorporeal perfusion chamber mimicking the various coronary conditions have aided in the understanding of the pathophysiology of the acute coronary syndromes and intensified our search for the ideal antithrombotic regimen in these high-risk patients. Finally, a carotid pig model of balloon angioplasty, a dog model of saphenous vein grafting, and a pig model of heart transplantation not only have provided insights into the pathophysiological process of accelerated atherosclerosis but also are allowing development of new antithrombotic and antiproliferative approaches for the prevention of these accelerated vascular diseases. In summary, we are entering an exciting era in vascular research. Significant advances in our understanding of vascular injury or damage as well as the interactions of blood cells and lipids with the vascular wall have allowed us to formulate new experimental strategies with subsequent clinical application in the prevention and progression of these vascular diseases.
Differentiation-inducing cytokine P48 exists in a membrane-associated form. P48 is a recently described 48-kDa differentiation-inducing cytokine isolated from the culture medium of the human leukemia line Reh. P48 induces differentiation and cytolytic activity in the promyelocytic cell line HL-60, and stimulates the release of TNF-alpha and IL-1 from peripheral blood monocytes. In further studies designed to examine the biosynthesis and function of P48, surface immunofluorescence flow cytometry analysis as well as 125I surface labeling and immunoprecipitation, revealed the presence of P48 on the surface of Reh cells. Triton X-114-treated Reh cells were partitioned into detergent and aqueous phases and separated by SDS-PAGE. Western blot analysis revealed that P48 partitioned exclusively into the detergent phase, suggesting an integral membrane association. Reh cells fixed with paraformaldehyde, but not K562 or P815, were able to stimulate the release of TNF-alpha from peripheral blood monocytes in a manner similar to that of secreted P48. Isolated plasma membranes from Reh cells could also stimulate TNF-alpha release. This TNF-alpha-releasing activity could be removed from detergent solubilized Reh membranes by immunoaffinity chromatography on an anti-P48 column. This study suggests that, in addition to being secreted into the culture medium, P48 is expressed on the surface of Reh cells in a biologically active form. The membrane form of P48 may be 1) a final maturation step before secretion or 2) a cell membrane-associated form that may be analogous to the membrane forms of TNF-alpha and IL-1.
A meta-analysis of low-dose aspirin for the prevention of pregnancy-induced hypertensive disease. BACKGROUND.--Pregnancy-induced hypertension (PIH), defined as either isolated hypertension after the 20th week of gestation or hypertension with proteinuria (preeclampsia), occurs in 5% to 15% of pregnancies and is associated with maternal and neonatal morbidity. Previous clinical trials with small numbers of patients have suggested that aspirin in doses of 60 to 150 mg/d during the second and third trimesters reduces the risk of PIH and improves maternal and neonatal outcomes. OBJECTIVE.--We performed a meta-analysis of the six published controlled trials to estimate more precisely (1) the magnitude of protection of aspirin from PIH; (2) the effect of aspirin on severe low-birth-weight infants, cesarean section, and perinatal mortality; and (3) the risk of adverse effects. METHODS.--We critically and independently evaluated study methods, assigned a quality score to each trial, and abstracted quantitative outcomes data. For each outcome, both relative risk (RR) and the number needed to be treated were calculated. RESULTS.--Among 394 subjects from six trials, the RR of PIH among women who took aspirin was 0.35 (95% confidence interval [CI], 0.22 to 0.55) and the number needed to be treated was 4.4, meaning that between four and five high-risk women would need to be treated with aspirin to prevent one case of PIH. Aspirin reduced the risk of severe low birth weight among newborns by 44% (RR = 0.56; 95% CI, 0.36 to 0.88) and reduced the risk of cesarean section by 66% overall (RR = 0.34; 95% CI, 0.25 to 0.48), although the specific indications for cesarean section were generally not described. There was no effect on fetal and neonatal death (RR = 0.88; 95% CI, 0.32 to 2.46), and there were no maternal or neonatal adverse effects associated with taking aspirin. CONCLUSION.--This meta-analysis suggests that low-dose aspirin reduces the risks of PIH and severe low birth weight, with no observed risk of maternal or neonatal adverse effects.
Relief of right ventricular angina and increased exercise capacity with long-term oxygen therapy. Long-term low-flow oxygen therapy can lead to improved exercise capacity and improved hemodynamics in selected patients with pulmonary hypertension. We report a patient who presented with severe exercise limitation and anginal chest pain that appeared to result from pulmonary hypertension and predominantly right ventricular ischemia. Acute oxygen therapy led to relief of pain but no change in exercise capacity or of pulmonary hypertension. After eight months of oxygen therapy, the patient's pulmonary hypertension was unchanged, but right ventricular hypertrophy and marked increases in exercise cardiac output and exercise capacity developed. Thus, oxygen can relieve right ventricular angina and facilitate the development of compensatory hypertrophy.
Localization of gene for familial hypertrophic cardiomyopathy to chromosome 14q1 in a diverse US population. BACKGROUND. Familial hypertrophic cardiomyopathy, an inherited primary cardiac abnormality characterized by ventricular hypertrophy, is the leading cause of sudden death in the young. Recent application of restriction fragment length polymorphism markers has provided provocative results, with localization to chromosome 18 (Japanese studies), 16 (Italian studies), 14 (US and French-Canadian studies), and two (National Institutes of Health studies) indicating genetic heterogeneity. Interpretation remains speculative until at least one of these loci is confirmed in unrelated pedigrees by independent investigators. METHODS AND RESULTS. We studied eight unrelated families of varied ethnic origins across the United States. DNA from each individual was digested with restriction enzymes TaqI or BamHI and analyzed by Southern blots followed by hybridization with probes T cell receptor alpha (TCRA), myosin heavy chain beta, D14S25, and D14S26. Multipoint linkage analysis showed a maximum lod score of 4.3, placing the locus 10 cM from D14S26 between D14S26 and TCRA, with an odds ratio of 20,000:1 and 90% confidence limits of 12 cM proximal to D14S25 to 4 cM distal to TCRA. The probability of linkage to 14q1 was more than 99%. CONCLUSIONS. These results indicate that the loci for familial hypertrophic cardiomyopathy in our families is primarily 14q1 but does not exclude other loci in a small proportion of the families. Thus, 14q1 appears to be the locus for familial hypertrophic cardiomyopathy in a significant proportion of the US population.
Post-endarterectomy headache and the role of the oculosympathetic system. A study was carried out on headache after carotid endarterectomy. A specific type of headache, similar in its characteristics to "cluster headache", occurred on the operative side in 30% of 54 patients, whereas no such headache occurred after extra-intracranial bypass or peripheral vascular surgery. This postoperative headache was not spontaneously reported by 56% of patients unless they were specifically asked about it. Pharmacological pupillary testing performed in 37 patients revealed that a decreased oculosympathetic activity (with or without adrenoceptor supersensitivity) was constantly associated with post-endarterectomy headache. Although this same abnormality was also observed in 54% of the patients without headache, a statistically significant (p less than 0.01) higher prevalence of decreased oculosympathetic responses was found in the patients with headache. The results suggest that damage to the sympathetic plexus due to the surgical procedure is involved in the development of postoperative "cluster-like" headache.
Improvement of psoriatic arthritis in a patient treated with bromocriptine for hyperprolactinemia. We describe a woman with psoriatic arthritis who experienced a remarkable improvement of her skin and joint disease while only taking bromocriptine therapy. She was treated with bromocriptine for primary infertility due to hyperprolactinemia. The improvement in joint symptoms appeared to parallel that of the skin. More studies are required to determine the reproducibility of this observation.
Recovery of costal and crural diaphragmatic contractility from partial paralysis. Since the two muscles (costal and crural) that constitute the diaphragm are separate and histologically different, their individual recovery pattern from neuromuscular blockade also may be different. Therefore, we studied the recovery of force and shortening in the in vivo diaphragm from atracurium-induced neuromuscular blockade in seven pentobarbital anesthetized dogs to assess segmental differences. Transdiaphragmatic pressure (Pdi), shortening of costal and crural segments, integrated electromyogram (EMG), and tidal volume (VT) were measured during spontaneous breathing. After atracurium had reduced VT to 30% of control, breathing parameters were followed until recovered to 90% of control values. In addition, force-frequency curves generated by supramaximal tetanic stimuli of the phrenic nerve were measured. Recovery times for tidal Pdi, tidal EMG, tidal shortening, low-frequency shortening, and twitch Pdi were twice as fast as for VT (40 +/- 4 min), reflecting a slower rate of recovery of accessory inspiratory muscles. High-frequency recovery was typically slower than that of VT. During tidal breathing and tetanic stimulation, costal and crural shortening recovered simultaneously. On the other hand, comparison between costal and crural by analysis of pressure-shortening relationships showed a segmental difference (crural shortened 30% more than costal at the same Pdi), which implied reduced afterload on the crural segment. However, since shortening and pressure were linearly related during paralysis and recovery, measurements of Pdi alone can accurately reflect changes in contractile mass when heterogeneity and afterload are controlled.
Trends in the pathophysiology and pharmacotherapy of spasticity [editorial] Spasticity develops after supraspinal or spinal lesions of descending motor systems, with obligate involvement of the corticospinal tract. Spasticity is characterized by an increase in muscle tone, which, in contrast to many other types of enhanced muscle tone, shows a marked velocity-dependent increase when the muscle is passively stretched. The pathophysiological mechanisms underlying this spastic muscle tone remain obscure. Three major causes are currently considered possible: (1) changes in the excitability of spinal interneurones; (2) receptor hypersensitivity; (3) formation of new synapses by sprouting. The latter mechanism could account for the long time course over which spastic muscle tone develops in hemiplegic or paraplegic patients, but there is no experimental evidence for this hypothesis. The electromyographic (EMG) gait analysis of patients with spasticity has thrown doubt on the common belief that the velocity-dependent increase in spastic muscle tone is evoked by stretch reflex activity and has led to the idea that spastic muscle tone resides in the muscle fibres themselves. While such a mechanism may contribute to the slowness of active movements in spastic patients, recent experiments on patients with spastic arm paresis have confirmed the classical view that the spastic muscle tone is related to the EMG activity evoked in the passively stretched muscle. This pathological EMG activity is seen during the entire range of the dynamic phase of the stretch, during which a normal muscle exhibits only an early, phasic burst at the highest stretch velocities employed. For the pharmacological treatment of spasticity, substances with different central or peripheral actions are available. Their assumed receptor actions are described, together with their main indications and side-effects.
Fatal brainstem stroke following internal jugular vein catheterization. Neurologic complications of central venous catheterization are uncommon, and there are no reports of cerebrovascular events. We report a case of massive postoperative vertebrobasilar territory stroke following internal jugular vein cannulation due to inadvertent vertebral artery injury. Autopsy revealed thrombosis at the site of puncture wound in the right vertebral artery, with emboli present in the distal basilar artery.