shukoor65/lab-rag-model huggingface dataset:
Interleukin-2 and lymphokine-activated killer cells in 15 children with advanced metastatic neuroblastoma. A phase II trial using interleukin-2 (IL2) and lymphokine-activated killer (LAK) cells was carried out in an attempt to treat children with end-stage neuroblastoma. Fifteen patients (median age, 7 years) were enrolled in the study. Twelve were in relapse after massive chemotherapy and autologous bone marrow transplantation (ABMT), and three had a primary refractory disease after conventional chemotherapy. IL2 was administered as an 18 x 10(6) IU/m2/d continuous infusion. One course consisted of a double 5-day treatment period separated by a 6-day break. Cytapheresis to harvest LAK progenitor cells was performed during the rest period. After a 4-day in vitro culture, LAK cells were reinjected during the second cycle of therapy. A phenotypic and functional analysis of immunologic parameters was conducted along with the therapeutic protocol. Toxicity was significant with two toxic deaths (cardiotoxicity and respiratory distress). The reinfusion of large amounts of LAK cells was clearly involved in one case, but this particularly severe toxicity has to be related to the patient's status (ie, heavy pretreatment). No significant clinical response was seen. The immunologic monitoring showed phenotypic and functional modifications in these patients before initiation of treatment and an unexpected absence of evolution of these parameters during IL2 therapy. Although the origin of these immune dysfunctions is not clear, they could be involved in the failure of IL2 therapy. Future studies of IL2 therapy in neuroblastoma should be undertaken earlier in the course of the disease.
Unexplained weight loss in the ambulatory elderly. Significant unexplained and unintentional weight loss was found in 45 elderly patients who were identified by computer search of the diagnostic files of seven family practice centers. We performed a case series chart review study which revealed that 24% of the 45 cases had no definitive etiology for the weight loss after two years of extensive clinical investigation. Depression was found to be the most common diagnosis made (18%) followed by cancer (16%). Only four patients died during the study period and all had cancer. The most prevalent diagnosis in this group of ambulatory elderly patients did not prove to be cancer, as often though, but rather "unexplained weight loss." CT scans were not found to be helpful as screening tests in the evaluation of weight loss. Using the data from this study, the diagnostic evaluations of elderly patients with unexplained weight loss may be more efficiently directed.
Irrationality in the management of breast cancer. I. The staging system. The historic development of breast cancer staging began early in the 20th century with the simple concept of early localized disease, spread to regional nodes, and the presence of distant metastases. This last group often was divided into patients with advanced but perhaps still curable locoregional disease and incurable patients with distant metastases. As increasing numbers of prognostic factors were recognized, efforts were made to incorporate them into the staging systems to combine patients with similar prognosis into the same stages. These attempts resulted in the development of four classifications, namely, the Columbia, Manchester, International, and American tumor-node-metastasis (TNM) staging systems. Although many benefits of staging were reported, the most important was that of permitting valid comparisons between different treatments and different institutions. Many success-limiting factors were noticed during the developmental years, and even though the TNM system has been accepted, numerous speakers and authors present their staged data in a confusing and ambiguous manner. Recommendations are made that would permit clarification of presentations to general medical audiences along with recognizable statistical validity.
Biliary bile acid profiles in familial adenomatous polyposis. Patients with familial adenomatous polyposis have an excess risk for adenomas and cancers of the upper and lower gastrointestinal tract. In the upper intestine these lesions occur mainly around the ampulla of Vater and they parallel mucosal exposure to bile. In view of this finding and of evidence that bile acids play a role in colorectal carcinogenesis, biliary bile acid profiles were determined in 29 patients with familial adenomatous polyposis (12 before colectomy, 17 after colectomy) and in 28 patients without familial adenomatous polyposis (all with colons in situ). Patients with familial adenomatous polyposis had a higher total biliary bile acid concentration than the others. The bile of patients with polyposis had a greater proportion of chenodeoxycholic acid and a lower proportion of deoxycholic acid than did the bile of patients without polyposis. The ratio of chenodeoxycholic acid and its metabolite lithocholic acid to cholic acid and its metabolite deoxycholic acid, which is related to subsequent bile acid profiles in the colon, was higher in patients with polyposis. Because bile acids influence cellular proliferation, these findings may be of importance with respect to intestinal adenoma and cancer growth.
Quantitative analysis of inflammatory cell influx, procollagen type I synthesis, and collagen cross-linking in incisional wounds: influence of PDGF-BB and TGF-beta 1 therapy. Platelet-derived growth factor (PDGF-BB homodimer) and transforming growth factor-beta 1 (TGF-beta 1) are potent wound-healing hormones that accelerate incisional repair. To identify more precisely and quantitatively the stage(s) of wound healing influenced by growth-factor therapy, we investigated the three sequential tissue repair processes--inflammatory cell influx, intracellular procollagen type I (PC-I) synthesis, and collagen cross-linking--in recombinant growth factor--treated wounds. Using newly developed automated, quantitative image-analysis techniques, we observed that PDGF-BB markedly augmented the directed migration of macrophages into wounds during the first week after wounding and triggered and earlier and more sustained influx of PC-I--containing fibroblasts into the wound when compared with results in TGF-beta 1-treated or control wounds (p = 0.015 at day 2; p = 0.007 at day 21). In contrast, automated image analysis revealed TGF-beta 1-treated wound fibroblasts had a nearly twofold increase in intracellular levels of PC-I protein when compared with PDGF-BB-treated or control wound fibroblasts (p = 0.004 at day 4). However, the influence of TGF-beta 1 was transient, and the longer duration of PDGF-BB activity suggested a later influence, perhaps on the collagen remodeling phase, which is ultimately required for increased wound strength. To address this possibility, collagen cross-linking in growth factor-treated wounds was inhibited by beta-aminoproprionitrile (BAPN) treatment, and wound breaking strength was analyzed. Both PDGF-BB and TGF-beta 1 continued to enhance repair in BAPN-treated rats, indicating that they do not function primarily at the level of collagen cross-linking. Thus, PDGF-BB appears to enhance the inflammatory phase of wound healing to indirectly trigger PC-I synthesis, whereas TGF-beta 1 quantitatively enhances PC-I synthesis directly, accounting for their differing duration of activities within healing wounds.
Use of graded exercise to evaluate physiological hyperreactivity to mental stress. Physiological hyperreactivity (i.e., response in excess of metabolic requirements) to mental stress has been implicated in the etiology of coronary heart disease. This study evaluated potential hyperreactivity of cardiovascular, pulmonary, and biochemical variables to mental stress. Thirty healthy males, 19-36 yr, performed a mental arithmetic task and cycle ergometry at three powerloads. Linear regressions were calculated for each of 17 dependent variables during exercise, with oxygen uptake (VO2) serving as the independent variable. Ten variables were significantly correlated (P less than 0.003) with VO2 during exercise and, therefore, were predicted at the VO2 observed during the arithmetic task. The actual level of each variable observed during the arithmetic task was compared with the level predicted from the exercise by paired t-tests. Heart rate, systolic and diastolic blood pressure, rate-pressure product, minute ventilation, respiratory frequency, and respiratory exchange ratio were significantly greater (7-32%, P less than 0.005) during the arithmetic task than predicted from the exercise at an equivalent VO2. Plasma cortisol and serum lipid variables were not useful for evaluating hyperreactivity. Results demonstrated that graded aerobic exercise can serve as a reference for evaluating physiological hyperreactivity to mental stress for a group of ten variables which were significantly correlated with VO2 during graded exercise.
Recurrent parotitis and sialectasis in childhood. Clinical, radiologic, immunologic, bacteriologic, and histologic study. Twenty children with juvenile recurrent parotitis, between 3 months and 16 years of age at onset, were followed up over a period of 7 to 22 years. Radiologic, histopathologic, cytologic, immunologic, and bacteriologic studies were performed to investigate the cause of sialectasis, commonly found in juvenile recurrent parotitis, and the pathogenesis of the disease. It was considered that a combination of a congenital malformation of portions of the salivary ducts and infections ascending from the mouth following dehydration of the children are contributory to the pathogenesis of the disease. The results of the investigations into the cause of the disease appear to exclude an auto-immunologic response or an allergic condition, an immature immune response, mumps, a sensitivity to upper respiratory tract infection, and familial factors.
Engagement of interleukin-7 receptor stimulates tyrosine phosphorylation, phosphoinositide turnover, and clonal proliferation of human T-lineage acute lymphoblastic leukemia cells. The purposes of this study were to examine the biologic effects of the engagement of the interleukin-7 receptor (IL-7R) with recombinant human interleukin-7 (rhIL-7) in immunophenotypically distinct T-lineage acute lymphoblastic leukemia (ALL) blasts and to elucidate the biochemical nature of the IL-7R-linked transmembrane signal in rhIL-7-responsive T-lineage ALL blast populations. In the absence of costimulants, rhIL-7 stimulated the in vitro proliferation and colony formation of freshly isolated leukemic blasts from six to eight T-lineage ALL patients with a mean plating efficiency of 196 +/- 53 (background subtracted) colonies/10(5) blasts plated. Stimulation of T-lineage ALL blasts with rhIL-7 resulted in markedly enhanced tyrosine phosphorylation of six distinct phosphoproteins with molecular weights of 57, 72, 98, 123, 150, and 190 Kd, and induced a rapid increase in the production of inositol-1,4,5-trisphosphate (Ins-1,4,5-P3), which was inhibitable by the tyrosine-specific protein kinase inhibitor genistein, but not by the serine/threonine-specific protein kinase C inhibitor H7. Similarly, rhIL-7 stimulated Ins-1,4,5-P3 production in CEM-1.3 T-lineage ALL cells and this stimulation was inhibitable by the tyrosine-specific protein kinase inhibitors genistein and herbimycin A, but not by H-7. Thus, the transmembrane signal triggered by engagement of the IL-7R is intimately linked to a functional tyrosine-specific protein kinase pathway and stimulates the phosphoinositide (PI) turnover and proliferation of T-lineage ALL blasts. The presented data confirm and extend previous studies on the expression of functional IL-7R on T-lineage ALL blasts and support the hypothesis that IL-7 may play an important regulatory role in the biology of T-lineage ALL.
Late recurrent Candida endocarditis. Late recurrent Candida endocarditis (LRCE) developed on a prosthetic mitral valve 22 months after treatment for primary native mitral valve endocarditis. The LRCE was difficult to diagnose; results of two dimensional echocardiography and repeated blood cultures were negative. Only transesophageal echocardiography revealed a vegetation and only lysis centrifugation blood cultures demonstrated candidemia. Postmortem examination revealed a large Candida vegetation on the prosthetic valve and Candida in the mitral valve ring. This case and a review of the literature indicate that Candida endocarditis treated with amphotericin B and prosthetic valve replacement may recur months after treatment, and that LRCE, which is difficult to diagnose and treat, may be best prevented by lifelong antifungal suppressive therapy.
Successful excision of a juvenile-type spinal arteriovenous malformation following intraoperative embolization. Case report. The case of a 57-year-old woman with a 14-year history of progressive paraparesis is presented. Selective spinal angiography revealed a juvenile-type spinal arteriovenous malformation (AVM) with a typical large size and rapid flow. The AVM was located primarily in the retromedullary space at the cervicothoracic junction. The AVM was successfully obliterated by intraoperative embolization using isobutyl-2-cyanoacrylate and surgical excision.
Spontaneous and corticotropin-releasing factor-induced cytosolic calcium transients in corticotrophs. Spontaneous and CRF-stimulated changes in the cytosolic free calcium concentration ([Ca2+]i) were studied in two types of corticotrophs: 1) cultured human ACTH-secreting pituitary adenoma cells (hACTH cells), and 2) identified small ovoid corticotrophs cultured from normal rat pituitaries. [Ca2+]i was monitored in individual corticotrophs by dual emission microspectrofluorimetry using indo-1 as the intracellular fluorescent Ca2+ probe. In hACTH cells, [Ca2+]i measurements were carried out in combination with electrophysiological recordings obtained using whole cell patch-clamp techniques. It was shown that a single spontaneous Ca(2+)-dependent action potential led to a marked transient increase in [Ca2+]i in human tumoral corticotrophs. Spontaneous fluctuations in [Ca2+]i were also observed in unpatched corticotrophs whether derived from human pituitary tumors or normal rat tissue. Based on their striking kinetic features and their sensitivity to external Ca2+, we suggest that these spontaneous [Ca2+]i transients were the consequence of action potential firing. Under separate voltage-clamp (patch-clamp) conditions, tumor corticotrophs showed two Ca2+ current components: a low threshold, rapidly inactivating (T-type) current, and a higher threshold, slowly inactivating (L-type) current. The dihydropyridine Ca2+ channel blocker PN 200-110 (100 nM) abolished the L-type current without affecting the T-type current, while the inorganic Ca2+ channel blocker Cd2+ (200 microM) suppressed both Ca2+ currents. The Na+ channel blocker tetrodotoxin (5 microM) did not affect inward currents in tumor corticotrophs. Both L- and T-type voltage-gated Ca2+ channels were involved in controlling [Ca2+]i transients in both tumor and normal corticotrophs, inasmuch as Cd2+ (200 microM) abolished [Ca2+]i) transients, while PN 200-110 (100 nM) greatly diminished, but did not completely abolish, [Ca2+]i transients. The latter did not appear to depend on a voltage-dependent Na+ influx, since they were unaffected by tetrodotoxin (5 microM). Corticotrophs generate [Ca2+]i transients in response to the hypothalamic secretagogue CRF by acting on their membrane excitability. Indeed, we demonstrated in combined fluorescent and electrophysiological experiments that CRF (100 nM) had a coordinate action on human tumoral corticotrophs comprised of a modest depolarization and an increase in the frequency of both action potentials and subsequent [Ca2+]i transients. A coincident increase in the peak amplitude of the [Ca2+]i transient and after hyperpolarization was also observed in some CRF-stimulated cells. CRF (100 nM) evoked qualitatively similar [Ca2+]i patterns in human tumoral and normal rat corticotrophs not subjected to patch-clamping.(ABSTRACT TRUNCATED AT 400 WORDS).
Neurogenic and nonneurogenic pain and inflammatory mediators. Pain is not a simple perception. Although millions of people suffer because of it and billions of dollars are spent trying to eradicate it, we are only in our infancy of understanding the very complex interactions necessary to perceive or distort our feelings of pain. We must continue to seek a better understanding of not only our patients' macroscopic impression of pain, but we must look microscopically at each cell involved in the whole of the pain process. A time will come when our molecular understanding will provide us with the means to unlock the secrets of pain. We have come a long way since the time of Descartes in our understanding of the neurophysiology and anatomy of pain, but we have a great deal more work to do if we are going to provide our patients with better remedies in the future.
The controversy of heparin therapy as an adjunct to thrombolysis in acute myocardial infarction. Heparin is used routinely in the US as adjunct therapy for prevention of reocclusion after thrombolysis during acute myocardial infarction. A review of the literature shows controversy over the efficacy of heparin following thrombolysis. Both beneficial and a lack of beneficial effects have been reported with heparin. From a pathophysiologic viewpoint, there appears to be a need for full heparinization in the postlytic period because the residual stenosis is highly thrombogenic. However, optimal dose, time, and mode of heparin therapy has not been defined. Despite a lack of definitive data, it seems reasonable to administer intravenous heparin immediately after thrombolytic therapy to achieve a partial thromboplastin time 1.5-2.0 times control that is concurrent with an antiplatelet agent such as aspirin. These recommendations are consistent with the consensus opinion of the American College of Cardiology and the American Heart Association.
Immunohistochemical analysis of amylase isoenzymes in thyroid cancer. The expression of amylase in various histological types of thyroid cancer was studied by an immunohistochemical technique, using a polyclonal antiamylase antiserum and two monoclonal antibodies specific for salivary and pancreatic-type amylases, respectively. Amylase was expressed in 21 of 24 (88%) thyroid cancers by polyclonal antiserum analysis. Analysis by monoclonal antibodies, however, showed that only 13 (54%) cases and three (13%) cases contained salivary-type and pancreatic-type amylases, respectively. Moreover, immunoreactivity for pancreatic-type amylase was detected only in medullary carcinoma; other histological types were positive for salivary-type amylase. These results show that thyroid cancer frequently expresses amylase, and suggest that the differences between amylase isoenzymes in thyroid cancer may correlate with those found between cellular origin of tumour.
Lipid deposition and intimal stress and strain. A study in rats with aortic stenosis. These experiments were designed to study the topography of lipid deposition in the stenotic aorta of hypercholesterolemic rats, and to correlate it with flow conditions and intimal stresses and strains studied in a scale biophysical model and in a computer model. A 69% +/- 5% stenosis was produced with a U-shaped metal clip. One month to 8 months later, the aorta was studied en face by light microscopy after fixation and lipid staining. The intima in the throat of the stenosis was almost completely free of lipid, whereas symmetric lipid deposits occurred as bands just above and especially just below the stenosis; elsewhere lipid deposits appeared to be random. The flow data obtained from the scale model showed that the intima in the throat of the stenosis was subjected to an increase of as much as 20 times in shear stress, whereas the lipid deposits just above and just below the stenosis were associated with asymmetric flow conditions: the proximal area corresponded to a region of rapidly increasing shear stress, the distal area to a region of low to normal shear stress and separated flow. A finite element computer model based on the aortic deformations indicated that the endothelium at the inlet and outlet of the stenosis is subjected to a symmetric pattern of elevated stresses and strains. These results indicate that 1) the pattern of lipid deposition can not be adequately explained by a hypothesis based solely on flow conditions, and 2) lipid deposits can develop in areas of increased fluid shear stress, decreased fluid shear stress, and increased intimal strains.
Angioplasty of long or tandem coronary artery lesions using a new longer balloon dilatation catheter: a comparative study. To determine whether or not a new 3 cm long angioplasty balloon was more effective in treatment of long (15-25 mm) or tandem (less than 25 mm overall length) coronary lesions, 44 consecutive patients with suitable lesions were alternately assigned to treatment with shorter, standard, 2 cm length, or long, 3 cm balloons. Primary success of PTCA was achieved in 95%. Those treated with long balloons required fewer inflations (3.3 +/- 1.5 vs. 5.7 +/- 2.1, P = .0001) and showed fewer moderate or severe intimal dissections of the lesions (4/22 vs. 12/22, p = .028). The use of 3 cm PTCA balloons in long or tandem lesions appears to be efficacious and less likely to cause dissections than shorter, 2 cm length devices.
Invited review: electrodiagnostic assessment and monitoring of motor unit changes in disease. The motor unit characteristics change dynamically with disease. This is the basis for the use of neurophysiologic methods for diagnostic purposes and for long-term monitoring. A great variety of nerve conduction and EMG parameters are available to study the motor unit. They reflect different aspects of motor unit function. Therefore, the electromyographer must choose his technique and optimal parameters depending on the situation, type of condition, whether the purpose is diagnosis or monitoring, and so on. In this presentation the relationship between EMG parameters and physiologic and morphologic counterparts in some pathologic conditions will be discussed.
Myocardial biochemical and hemodynamic adaptations to chronic tachycardia. The purpose was to determine the biochemical and hemodynamic adaptations of the myocardium to chronic tachycardia. Cardiac pacemakers were implanted in Yorkshire pigs and set at a rate of 180 beats/min for a period of 35-42 days. Animals were then anesthetized with pentobarbital sodium. Myocardial blood flow and hemodynamics were determined at three different heart rates (i.e., 120, 180, and 220 beats/min). Tissue samples were then taken for microsphere and biochemical analyses. Chronically paced hearts maintained better cardiac function and had consistently higher left ventricular blood flow with a higher endocardial-to-epicardial ratio. The activities of citrate synthase and 3-hydroxyacyl-CoA dehydrogenase were 23 and 45% greater in the paced hearts, respectively. The sarcoplasmic reticulum adenosinetriphosphatase activity was 55% greater in the paced hearts, whereas the myosin adenosinetriphosphatase was the same as in the control hearts. Polyacrylamide gels of the ventricular myosin isoforms showed only the V3 type to be present in both the control and paced hearts. These findings show that the heart of a large mammal adapts to chronic tachycardia (i.e., 180 beats/min) by elevating the aerobic and calcium-sequestering capacities without altering its myosin type.