shukoor65/lab-rag-model huggingface dataset:
Prediction of prognosis in primary breast cancer by detection of a high molecular weight mucin-like antigen using monoclonal antibodies DF3, F36/22, and CU18: a Cancer and Leukemia Group B study Three monoclonal antibodies (MAbs) (DF3, F36/22, CU18) were used to monitor expression of distinct epitopes present within a family of mucin-like, breast carcinoma-associated molecules. Primary tumor specimens from more than 190 stage II breast cancer patients were evaluated for expression of the high molecular weight antigens. With a median follow-up of 6 years, patients whose tumors exhibited high immunoperoxidase staining scores (greater than 50% positive cells) with MAb DF3 had a superior disease-free survival ([DFS] 56% +/- 6% v 37% +/- 5% at 6 years; P = .0088) and overall survival ([OS] 72% +/- 5% v 59% +/- 5% at 6 years; P = .025). Staining scores with the other two antibodies did not correlate with improved prognosis. For MAbs DF3 and CU18, patients whose tumors exhibited predominantly apical cellular reactivity patterns had improved DFS, although differences reached conventional levels of statistical significance only with MAb CU18. In multivariate analyses, the prognostic value of MAb DF3 staining was independent of other identified prognostic factors. Furthermore, the concordance between primary and axillary lymph node metastases staining with each MAb was 73%, 80%, and 85% for MAbs DF3, F36/22, and CU18, respectively. These results suggest that staining with MAb DF3 identifies a group of node-positive women with a relatively favorable prognosis. Expression of the DF3 mucin-like glycoprotein is related to better differentiation, and staining with MAb DF3 provides an accurate and objective estimate of clinical outcome independent of histopathologic evaluation.
Amino acid substitutions in the coat protein result in loss of insect transmissibility of a plant virus. Amino acids near the N terminus of the coat protein of tobacco vein mottling virus were deleted or altered by site-directed mutagenesis to determine the effect on aphid transmissibility of the virus. Deletion of a three amino acid sequence Asp-Ala-Gly, which is conserved in aphid-transmissible potyvirus isolates, abolished transmission. The mutation Ala----Thr in this triplet drastically reduced transmission, whereas the mutation Asp----Asn had no effect, and the mutation Asp----Lys consistently reverted to the wild-type residue. The mutation Lys----Glu, in the residue adjacent to the glycine of the triplet, drastically reduced transmission, whereas the mutation Gln----Pro, seven residues downstream from the glycine had no effect. Comparison of the sequences of other potyviruses suggests that the presence of a glycine residue at the third position of the Asp-Ala-Gly triplet is critical for aphid transmissibility and that certain changes in the residues adjacent to this position abolish or greatly reduce aphid transmissibility.
Diverticula of the female urethra: diagnosis by endovaginal and transperineal sonography. Diverticula of the female urethra can be difficult to diagnose. Invasive contrast studies (voiding cystourethrography or double-balloon urethrography) or urethroscopy are frequently required for definitive diagnosis. Although transabdominal sonography has been able to visualize large diverticula, this technique has not proved useful in routine screening. In this study, we examined the use of higher frequency (5 MHz) near-focus endovaginal or transperineal sonography for the diagnosis of urethral diverticula. Five patients with radiographically proved (three with double-balloon urethrography and two with voiding cystourethrography) urethral diverticula were examined with endovaginal (two cases) or transperineal (four cases) sonography. In all five cases, sonography showed the diverticula previously demonstrated on the contrast study. The spatial relationship of the diverticula to the urethra, an important consideration at surgery, was shown more clearly by sonography than by contrast radiography. These findings suggest that sonography may be useful as a noninvasive screening technique for urethral diverticula.
ECMO in premature infants. Review of factors associated with mortality. During the first few years of clinical research on neonatal extracorporeal membrane oxygenation (ECMO), 16 premature infants of less than 35 weeks gestational age were treated by the authors (RHB), and only four (25%) survived. Intracranial hemorrhage was common, prompting the authors to recommend that ECMO not be used in premature infants with respiratory failure. Since diagnostic methods, indications, and techniques of extracorporeal support have improved considerably, the records of these previous cases were reviewed in detail to determine if there was reason to believe that results might be better in the modern era. Of the 16 patients, four had pre-ECMO conditions that would now be considered contraindications and five of the remaining patients had major technical complications that are now rare. Anticoagulation and fluid management of these patients also would be handled much differently. Based on this review and on current experience with extracorporeal support in near-term infants, it is reasonable to expect that survival of moribund premature infants might be 50% or greater with extracorporeal support. New phase I trials using improved indications and technology are suggested.
Activation of phospholipase D by E-series prostaglandins in human erythroleukemia cells. Phospholipase D (PLD) can be activated by a variety of receptor agonists in different cell types. However, an effect of prostaglandins (PGs) on the activity of this enzyme has not been demonstrated previously. In this study, we found that PGE1 could stimulate PLD in human erythroleukemia cells, as measured by phosphatidylethanol formation, with an ED50 of 3.5 x 10(-7) M. PGE2 was also active, but other PGs including prostacyclin, PGD2 and PGF2, had no effect. PGE1 also elicited cyclic AMP production over the same concentration range that activated PLD. However, it is unlikely that cyclic AMP per se is responsible for PGE-induced PLD activation, because PLD could be substantially activated by PGE2 at concentrations (0.1-1 microM) which did not stimulate cyclic AMP production. Furthermore, no increase of phosphatidylethanol formation could be observed when cells were treated with other adenylyl cyclase-activating agents such as prostacyclin, forskolin and vasoactive intestinal peptide. In Ca+(+)-free medium, PLD activation by PGE1 and PGE2 was greatly reduced, indicating that their effect was through a Ca+(+)-dependent pathway. Pretreatment of cells with pertussis toxin abolished PGE1- and PGE2-stimulated PLD activity, implying the involvement of a G protein in the PGE-mediated signal transduction pathway. Our results not only indicate that E-series PGs may initiate some of their cellular effects through a novel pathway, activation of PLD, but also suggest that PGE-stimulated PLD activity in human erythroleukemia cells is Ca+(+)-dependent and is regulated via a pertussis toxin-sensitive G protein.
Angiotensin-converting enzyme inhibitor-induced renal failure: causes, consequences, and diagnostic uses. Angiotensin-converting enzyme inhibitor-induced renal failure is now a well-recognized phenomenon that appears to occur almost exclusively in patients with a preexisting reduction in renal perfusion pressure, especially those with renovascular disease. In the latter group of patients, renal failure probably results from some combination of reduced poststenotic renal perfusion pressure and a unique disturbance in the autoregulation of glomerular filtration rate. Although traditionally regarded as functional and reversible, recent animal studies suggest that angiotensin-converting enzyme inhibitor-induced reductions of glomerular filtration rate may lead to progressive renal atrophy, an observation that raises concerns about the long-term safety of these agents in patients with renovascular disease. On the other hand, the deleterious consequences of angiotensin-converting enzyme inhibition in renovascular disease have been exploited as aids in the diagnosis of this disorder. Whether the adjunctive use of angiotensin-converting enzyme inhibitors will prove to be useful in screening large populations of hypertensive patients for renovascular hypertension remains to be determined. However, such adjunctive tests appear to be useful in judging the functional significance of angiographically documented renal artery stenosis.
Pacemaker-lead puncture of the tricuspid valve. Successful diagnosis and treatment. During insertion, a transvenous pacing lead pierced the tricuspid valve in a 66-year-old man, causing progressive tricuspid insufficiency and congestive heart failure. The defect remained undiagnosed for ten years and was then repaired. To our knowledge, this is the first case in which this problem has been successfully treated rather than being diagnosed at autopsy.
Acute and sustained release of the atrial natriuretic factor prohormone N-terminus with acute myocardial infarction. This investigation was designed to determine if acute ischemic cardiac injury causes the release of the 98 amino acid (aa) N-terminus of the 126 aa atrial natriuretic factor prohormone (pro ANF). Seventeen patients with acute myocardial infarction, but without clinical evidence of congestive heart failure, had their circulating concentrations of the whole N-terminus (ie, pro ANF 1-98), the midportion of the N-terminus of the ANF prohormone (consisting of aa 31-67; pro ANF 31-67) and creatine phosphokinase (CPK) monitored daily for 14 days. All seventeen patients had elevated plasma pro ANF 1-98 and pro ANF 31-67 concentrations at the time of presentation. Maximal increase on day three post-infarction correlated with the size of infarction estimated by the maximal CPK (r = 0.675; p less than 0.05) but did not correlate with the amount of left ventricular dysfunction. Another three patients with acute myocardial infarction were treated with tissue plasminogen activator (tPA). The measured pro ANF 1-98 and pro ANF 31-67 levels in these patients were within our normal range and significantly lower (p less than 0.001) than seen in patients with acute myocardial infarction not given thrombolytic therapy. Six patients with unstable angina, likewise, had normal circulating pro ANFs 1-98 and 31-67 concentrations during prolonged episodes of chest pain. These data suggest that myocardial necrosis but not ischemia triggers the release of the entire 126 aa prohormone.
Peritonitis due to Prototheca wickerhamii in a patient undergoing chronic ambulatory peritoneal dialysis. A 72-year-old man who was undergoing chronic ambulatory peritoneal dialysis developed peritonitis due to Prototheca wickerhamii. Results of in vitro sensitivity testing revealed that the organism was sensitive to amphotericin B (MIC, 0.4 micrograms/mL) but resistant to fluconazole (MIC, greater than 80 micrograms/mL). The patient was successfully treated medically with a combination of intravenous amphotericin B and oral doxycycline.
Microvascular decompression for hemifacial spasm. Patterns of vascular compression in unsuccessfully operated patients. To determine the causative factors of unsuccessful microvascular decompression for hemifacial spasm, the follow-up results in 53 patients were assessed retrospectively. The mean follow-up period was 36 months. There were 32 patients who had compression of the seventh cranial nerve ventrocaudally by an anterior inferior cerebellar artery (AICA) or a posterior inferior cerebellar artery. Of these 32 patients, 30 (94%) had excellent postoperative results. Of 14 patients with more severe compression by the vertebral artery, nine (64%) had excellent results, three (21%) had good results, and two (14%) had poor results; in this group, three patients with excellent results experienced transient spasm recurrence. There were seven patients in whom the meatal branch of the AICA coursed between the seventh and eighth cranial nerves and compressed the dorsal aspect of the seventh nerve; this was usually associated with another artery compressing the ventral aspect of the nerve ("sandwich-type" compression). Of these seven patients, five (71%) had poor results including operative failure in one and recurrence of spasm in four. The authors conclude that the clinical outcome was closely related to the patterns of vascular compression.
Anti-anginal therapy and quality of life. A comparison of the effects of transdermal nitroglycerin and long-acting oral nitrates. A total of 112 male patients with severe effort-induced angina pectoris (New York Heart Association functional classes II and III) participated in a randomized open trial consisting of a 6 month phase with 3 month treatment cross-overs. The aim of the study was to compare the effect of transdermal nitroglycerin (TN) patches and long-acting oral nitrates (LAON) on quality of life (QL). During the cross-over period 30 patients (20 on TN and 10 on LAON) withdrew from the study, over half of them within the first month. Although the results should be interpreted with some caution, they showed that improvement in QL was present for both treatments but greater during the transdermal therapy (unadjusted p = 0.07, adjusted p = 0.03). Anginal attacks were associated with improved QL scores, and fewer attacks occurred on TN (p = 0.06). Improvement in QL was most pronounced in patients whose recorded duration of angina was less than 8 years.
Method and theory of monophasic action potential recording. MAP recordings have been at the cradle of cardiac electrophysiology but only recently, through safer and simpler technology, have gained wider access to clinical electrophysiology. In contrast to conventional electrode catheter recordings, MAP recording devices provide precise information not only of the local activation time but of the entire local repolarization time course as well. Although the MAP does not reflect the absolute amplitude or upstroke velocity of transmembrane action potentials, it delivers highly accurate information on the action potential duration and configuration, including early afterdepolarizations as well as relative changes in transmembrane diastolic and systolic potential changes. Based on available data, the MAP probably reflects the transmembrane voltage of cells within a few millimeters of the exploring electrode. MAPs can be recorded by catheter technique from the endocardial surface and by special probes from the epicardium in the operating room. The contact electrode technique is preferable over suction electrodes because it is safer and simpler to use in patients and because it produces more stable, longer-lasting signals. A modified contact MAP catheter incorporates pacing electrodes and permits simultaneous assessment of action potential duration and refractoriness. This not only facilitates the use of MAP catheters in routine electrophysiological studies but also is important for assessing the voltage-independent effects of antiarrhythmic drugs on refractoriness. MAP recordings offer the opportunity to study, in the in situ heart, a variety of pertinent electrophysiological phenomena including, for example, effects of cycle length changes and antiarrhythmic drugs on action potential duration or the role of afterdepolarizations in the genesis of triggered arrhythmias. Due to vigorous heart beating, movement artifacts may occur and need to be distinguished from true abnormalities in the action potential time course. With these limitations in mind, MAP recordings are a valuable addition to clinical electrophysiological studies.
Screening for sleep apnea using pulse oximetry and a clinical score. Confirmation of the diagnosis of OSA currently requires overnight polysomnography. This study evaluates the usefulness of pulse oximetry together with a clinical score in identifying OSA. Forty patients were assigned a clinical score based on the presence or absence of loud snoring, observations of interrupted breathing during sleep, hypersomnolence, obesity and essential hypertension. Each underwent a night of domiciliary pulse oximetry followed by nocturnal polysomnography. Significant OSA was confirmed in 26. All 15 patients with positive pulse oximetry tracings had significant OSA (apnea index greater than or equal to 10). Five of eight with negative tracings were also shown to have significant OSA along with six of the seven patients with inadequate or indeterminate tracings. Clinical scores were significantly different for those with and without OSA. This study confirms the usefulness of nocturnal pulse oximetry in establishing the diagnosis of OSA and highlights the value of a clinical score in improving its sensitivity as a screening tool.
Hemodynamic and metabolic responses to graded microvascular occlusion. The hemodynamic and metabolic consequences of microvascular occlusion, often present in the runoff bed of distal arterial reconstructions, have been difficult to quantitate clinically. To investigate these pathophysiologic relationships, a porcine hindlimb model was developed in which arteriolar patency, which we term outflow capacity, may be quantitatively defined and reduced by serial distal microembolization with 70 microns flow-directed glass bubbles. In 10 anesthetized adult pigs, hindlimb perfusion was limited to femoral artery flow (FAF) by collateral ligation. Serial measurements of outflow resistance (OR), femoral artery flow, and resting muscle pH (mpH), a metabolic index of tissue perfusion, were made as relative outflow capacity (ROC) underwent graded reduction from 1.0 (baseline) to 0 (complete occlusion). Femoral artery flow decreased linearly (FAF = 87 ROC - 3), and outflow resistance increased in hyperbolic fashion (OR = 1.66/ROC) in response to graded peripheral microembolization, whereas resting muscle pH followed a more complex relationship (In mpH = 0.055 ROC + 1.95). An integrated analysis of these results suggests that a 50% to 60% reduction in arteriolar patency represents a critical point beyond which outflow resistance rises rapidly and hindlimb flow decreases to levels that are inadequate to support the metabolic demands of resting tissues.
The fibromyalgia impact questionnaire: development and validation. An instrument has been developed to assess the current health status of women with the fibromyalgia syndrome. The Fibromyalgia Impact Questionnaire (FIQ) is a brief 10-item, self-administered instrument that measures physical functioning, work status, depression, anxiety, sleep, pain, stiffness, fatigue, and well being. We describe its development and validation. This initial assessment indicates that the FIQ has sufficient evidence of reliability and validity to warrant further testing in both research and clinical situations.
Effect of salbutamol on gastroesophageal reflux in healthy volunteers and patients with asthma. The aim of this work was to establish whether beta-adrenergic agonists promote or increase gastroesophageal reflux in patients with asthma. Ten healthy individuals and eight patients with asthma were studied on 2 different days. One day they received a placebo, and the other day they received 4 mg of salbutamol by mouth. Complete measurements of esophageal manometry were performed before and every 30 minutes for 210 minutes after the administration of the drugs. Esophageal pH was measured continuously for the duration of the experiment. The results demonstrate that (1) salbutamol had no effect on the lower esophageal sphincter pressure gradient, the peak esophageal contraction pressure, or the number and duration of reflux episodes in patients with asthma and normal individuals, and (2) patients with asthma have a resting lower esophageal sphincter pressure higher than healthy subjects. We conclude that the administration of salbutamol does not affect esophageal function.
Emergency department presentation of renal dialysis patients: indications for EMS transport directly to dialysis centers. To determine the pattern of emergency department (ED) utilization by renal dialysis (RD) patients, a prospective study was conducted of dialysis patients presenting to the ED of a regional dialysis center. The most common presenting complaints were shortness of breath (SOB), chest pain, abdominal pain, and vomiting; the most common diagnoses were congestive heart failure, chest wall pain, and electrolyte abnormalities. Interventional dialysis (ID), defined as emergent dialysis required to treat the patient's presenting complaint, was required for 30 patients, with the most common presenting complaints of these patients being shortness of breath, weakness, and chest pain. Only SOB was statistically significant in predicting the need for ID (P less than 0.001), with a positive predictive value of 0.63 and a negative predictive value of 0.85. Prehospital implications of these data suggest that RD patients with a chief complaint of SOB should be transported directly to a facility capable of dialysis on an emergent basis.
Nuclear magnetic resonance imaging for assessment and follow-up of patients with valve disease. Nuclear magnetic resonance (NMR) imaging now offers a powerful means of assessing a variety of clinically important parameters in patients with valvular heart disease. NMR approaches will probably be most useful in patients with chronic valvular regurgitation, in which there continues to be uncertainty regarding the optimum timing for surgical intervention. In these patients it is possible to simultaneously assess both the valvular regurgitation and the resulting changes in myocardial structure and function. In patients with aortic stenosis, NMR can be applied to the assessment of left ventricular mass, both before and after valvuloplasty or valve replacement. In mitral stenosis, NMR may be applied to the assessment of right ventricular volumes and function. NMR may be used for the detection of prosthetic valve regurgitation when Doppler studies are equivocal. Finally, NMR imaging may be applied in patients with congenital or aortic root disease to evaluate valvular function in addition to diagnostic assessment of such patients. The future development of isotropic three-dimensional acquisition approaches, ultrafast imaging strategies, automated surface detection techniques, and more rapid function and flow analysis could considerably enhance the use of the current NMR approaches. The application of spectroscopic techniques could provide a means of monitoring myocardial metabolic abnormalities in ventricles exposed to chronic overload. Meanwhile, in patients with valvular regurgitation and stenosis, it would seem timely to initiate long-term serial NMR studies to further define natural history and the effects of various medical regimens and to ultimately help determine optimum medical and interventional regimens.
Calcium antagonists: an overview. Calcium antagonists reduce the influx of calcium ions through the calcium channels. This causes a reduction in myocardial contractility or a fall in vascular resistance because of a lowering of vascular smooth muscle tone. Therefore, the net effect is a fall in blood pressure. The three major classes of calcium antagonists, the dihydropyridines, papaverine derivatives, and benzothiazepines, differ in molecular structure and their binding characteristics to the calcium channels. Furthermore, newer antagonists, particularly the dihydropyridines such as nicardipine, have a high affinity for vascular tissue and are highly selective for vascular smooth muscle. These compounds also have a favorable effect on hypertension mainly because of lowering of vascular resistance. In addition, they do not cause potentially negative metabolic effects on glucose or lipid levels and are generally well tolerated. Based on these findings, the Joint National Committee in the United States and the World Health Organization/International Society of Hypertension Committee on the Management of Mild Hypertension recommended the use of calcium antagonists as first-line treatment in hypertension.