shukoor65/lab-rag-model huggingface dataset:
The effect of endoscopic laser therapy on survival in patients with squamous-cell carcinoma of the esophagus. Further experience. Although endoscopic laser therapy is effective for symptom palliation in esophageal cancer, few studies have investigated its effect on survival. We previously reported a 300% improvement in survival in 10 patients with squamous-cell carcinoma of the esophagus after endoscopic Nd:YAG laser energy. We now report a study to determine if the survival advantage persisted after treating an additional 26 patients. Thirty-six patients with squamous-cell carcinoma of the esophagus treated with endoscopic laser therapy were compared to 20 controls identified by our hospital Tumor Registry. There was no difference between the groups with respect to age, sex, race, location of tumor, or clinical stage. More control patients (25%) had previously undergone surgery than laser patients (0%) (p less than 0.05). Survival analysis demonstrated a significant improvement in overall survival (p less than 0.05), with an improvement in median survival from 5.7 to 9.7 months (p less than 0.05). One-year survival was 38% in laser patients, compared to 20% in control patients. Our experience continues to demonstrate that endoscopic laser therapy is effective in prolonging life as well as palliating the symptoms of patients with squamous-cell esophageal carcinoma.
Evidence for WT1 as a Wilms tumor (WT) gene: intragenic germinal deletion in bilateral WT. The inactivation of two alleles at a locus on the short arm of chromosome 11 (band 11p13) has been suggested to be critical steps in the development of Wilms tumor (WT), a childhood kidney tumor. Two similar candidate WT cDNA clones (WT33 and LK15) have recently been identified on the basis of both their expression in fetal kidney and their location within the smallest region of overlap of somatic 11p13 deletions in some tumors. These homozygous deletions, however, are large and potentially affect more than one gene. Using a cDNA probe to the candidate gene, we have analyzed DNA from both normal and tumor tissue from WT patients, in an effort to detect rearrangements at this locus. We report here a patient with bilateral WT who is heterozygous for a small (less than 11 kb) germinal deletion within this candidate gene. DNA from both tumors is homozygous for this intragenic deletion allele, which, by RNA-PRC sequence analysis, is predicted to encode a protein truncated by 180 amino acids. These data support the identification of this locus as an 11p13 WT gene (WT1) and provide direct molecular data supporting the two-hit mutational model for WT.
Effect of i.v. midazolam on the ventilatory response to sustained hypoxia in man. The ventilatory response to isocapnic, sustained hypoxia is characterized by initial hyperventilation followed by ventilatory decline. The ventilatory response to isocapnic sustained hypoxia during i.v. administration of midazolam was assessed in five healthy subjects. Compared with control experiments, the hyperventilatory effect of hypoxia was not decreased following administration of midazolam. The hypoxic ventilatory change was significantly greater with midazolam because of a decrease in tidal volume.
Hypertension as a risk factor for renal disease. Review of clinical and epidemiological evidence Renal failure is a well-recognized complication of accelerated and malignant hypertension that can be prevented by appropriate antihypertensive therapy. The risk of renal disease in patients with milder forms of hypertension is less certain. Death certificate, insurance industry, and community-based observational studies provide little information with respect to the risk of kidney damage in the hypertensive patient. Randomized controlled trials of antihypertensive drug therapy provide equivocal results. The strongest evidence in support of the hypothesis that mild hypertension increases the risk of subsequent renal disease comes from analyses of the Hypertension Detection and Follow-up Program and the Medicare End-Stage Renal Disease (ESRD) Program. The risk of blood pressure-related ESRD appears to be especially high in blacks, independent of age, sex, and prevalence of hypertension. Although these results need to be confirmed, the data raise the possibility that the effects of high blood pressure on the kidney are different in blacks than in whites. Based on current trends, it is projected that the number of beneficiaries in the Medicare ESRD Program will continue to increase during the next 30-40 years and that the diagnosis of hypertensive ESRD will become increasingly common. Additional studies to characterize the relation between mild hypertension and subsequent risk of renal disease and to confirm the corresponding benefits of antihypertensive therapy are urgently needed.
Myocardial protection with Hamburg oxygenated crystalloid cardioplegic solution for multiple coronary bypass and multivalvular replacement. We evaluated myocardial protection with Hamburg oxygenated crystalloid cardioplegic solution in a double study. Part I was a prospective metabolic study, measuring myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) contents before and after ischemia in 30 coronary bypass (CABG) patients. During ischemia, CP levels decreased significantly, whereas ATP did not. After 10 minute of reperfusion, mean ATP contents were 90% of preischemic values and CP levels increased to 85% of preischemic values. Spontaneous myocardial defibrillation was seen in 93.3% of patients. Part II included evaluation of early postischemic myocardial function in 228 patients, 48 with multiple valve replacement (MUVR) and 180 with CABG. Spontaneous myocardial defibrillation was seen in 90.3%. Cardiac index, measured before and 1 and 12 hours after surgery, increased significantly in the postischemic period (from 1.95 +/- 0.9 to 2.5 +/- 0.7 l/min m2 in MUVR, p 0.04; from 2.2 +/- 0.6 to 2.7 +/- 0.7 l/min/m2 in CABG, p 0.01). Myocardial infarction frequency was 3% among CABG patients, and unrelated to the number of distal anastomosis or to aortic cross-clamp time. Early postoperative mortality was 6.2% for MUVR and 0.5% for CABG. Thus, oxygenated cardioplegia with Hamburg solution preserves high-energy phosphate compounds and prevents ischemic injury, with excellent short-term clinical results.
Dual modulation of 5-fluorouracil using leucovorin and hydroxyurea. A phase I trial. Oral hydroxyurea (HU) was added to a regimen of 5-fluorouracil (5-FU) plus leucovorin (LCV) administered as a continuous 24-hour infusion for 14 days. A previous report of the 5-FU plus LCV infusion established optimal dosages of 200 mg/m2/d and 5 mg/m2/d, respectively, for each agent. Oral HU was added to the regimen in total dosages of 0.5 g/d, 1.0 g/d, 1.5 g/d, or 2.0 g/d. Twenty-two patients received a total of 45 courses of treatment. Stomatitis was the dose-limiting side effect; it occurred in 3 of 14 courses with HU at 0.5 g/d (21%) and 9 of 17 courses with HU at 1.0 g/d (53%). Dosage escalation to 1.5 g/d or 2.0 g/d was possible in only 3 of 22 patients (17%). The median time to stomatitis was 10 days (range, 7 to 12 days). One response was observed in this heavily pretreated population. Phase II trials of HU plus LCV dual modulation of infusional 5-FU should use initial HU dosages of 0.5 g/d for the 14-day regimen described, with dose escalation as tolerated. Variable oral absorption presumably accounts for the small group of patients who can tolerate the higher doses of HU.
Immunohistochemical analysis of neural cell adhesion molecules. Differential expression in small round cell tumors of childhood and adolescence. The neural cell adhesion molecule (NCAM) was discovered in a search for cell surface antigens of chicken neurons that contribute to cell adhesion and pattern formation during development. Homologous adhesion molecules have been identified in several species, including humans. In this immunohistochemical study, the authors examine the role of human NCAM in tumor diagnosis. The authors used a monoclonal antibody (MAb), 5.1H11, to examine NCAM immunoreactivity in frozen sections of more than 450 tumors, including more than 80 small round cell tumors (SRCT) of childhood and adolescence (neuroblastomas, Ewing's sarcomas [ES], peripheral neuroepitheliomas [PN], primitive neuroectodermal tumors [PNET], esthesioneuroblastomas, malignant ectomesenchymoma, medulloblastomas, small cell osteosarcomas, mesenchymal chondrosarcomas, embryonal rhabdomyosarcomas, and lymphomas). The authors show that 1) neuroblastomas and primary brain tumors are NCAM+; 2) ES, most PN/PNETs, and melanomas are NCAM-; 3) embryonal rhabdomyosarcomas and various other sarcomas are NCAM+; 4) neuroendocrine tumors are NCAM+; 5) subsets of carcinomas of kidney, ovary, lung and other organs are NCAM+; and 6) lymphoid tumors are NCAM-. Tests with normal fetal and adult tissues indicate that these findings reflect only in part the NCAM phenotypes of corresponding normal tissues. Notably the NCAM- phenotype of ES and PN/PNET is not explained by current histogenetic models for these tumors, which suggest a primitive neuroectodermal origin. Finally the authors show that NCAM expression among SRCT has an inverse relationship with the expression of p30/32MIC2, a cell surface antigen of ES and PN/PNET detected with MAb HBA71. These results suggest that immunohistochemical assays for NCAM and p30/32MIC2 expression may aid in the further characterization of SRCT of childhood and adolescence.
Effects of distention and short-term grafting on vasoreactivity in rabbit external jugular veins. The relative effects of distention, intraluminal pressure, and wall tension on venous smooth muscle and endothelial cell function were examined in 40 external jugular veins from New Zealand white rabbits. Vein grafts (n = 5) were interposed in the common carotid artery and explanted after 10 minutes. Distended veins were inflated in vitro with modified Krebs' solution at 37 degrees C for 10 minutes at pressures of either 20 mm Hg (D-20; n = 5) or 80 mm Hg (D-80; n = 5). Externally supported veins (ES-80; n = 5) were inflated at 80 mm Hg pressure, but distention was prevented by covering with a 3 mm internal diameter polytetrafluoroethylene sleeve. Bradykinin-induced in vitro maximal tension was attenuated significantly in vein grafts (0.13 +/- 0.04 g) and D-80 rings (0.27 +/- 0.07 g) compared with D-20 rings (1.20 +/- 0.14 g), ES-80 rings (0.99 +/- 0.13 g), or nondistended control rings (n = 40; 1.19 +/- 0.10 g; p less than 0.001). The attenuation in contraction in the vein graft and D-80 groups was nonspecific (i.e., similar results were obtained with respect to other smooth muscle agonists). Contractile function was inversely associated with wall tension, the product of pressure and radius (r2 = 0.7438; p = 0.06). In contrast, there were no differences in endothelium-dependent or endothelium-independent relaxation among the five groups. It is concluded that, in this experimental system, (1) venous smooth muscle function is significantly attenuated after short-term in vitro distention or grafting although endothelial function is largely preserved, and (2) the decrement in contraction is due to elevated wall tension.
Differential effects of insulin-like growth factor (IGF)-I and IGF-II on the expression of IGF binding proteins (IGFBPs) in a rat neuroblastoma cell line: isolation and characterization of two forms of IGFBP-4. The isolation and hormonal regulation of two low molecular weight insulin-like growth factor binding proteins (IGFBPs) present in the conditioned medium (CM) of the rat neuroblastoma cell line B104 cells has been performed. IGFBPs were purified by ZnSO4 precipitation, insulin-like growth factor-I 1IGF-I) affinity chromatography, and reverse phase HPLC. Final isolation and N-terminal analysis was accomplished by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, electroblotting to polyvinylidene difluoride membranes, and sequencing of the bound proteins. Two IGFBPs, with apparent Mr of 28K and 24K were coisolated and sequenced. Both proteins had identical N-terminal sequences and appear to be two forms of IGFBP-4. Treatment of the IGFBPs with endoglycosidase-F caused a shift in the apparent Mr of the 28K IGFBP to 24K. However, there was no change in the apparent Mr of the 24K IGFBP. The data from this study suggest that the IGFBP-4 exists as both a glycosylated and nonglycosylated protein. Treatment of B104 cells with IGF-I increased the expression of both the 24K and 28K IGFBPs and also resulted in the appearance of IGFBP-3 and an unknown IGFBP at 29K. When added to subconfluent cells, IGF-I was also mitogenic in B104 cells. Similar to IGF-I, IGF-II treatment increased cell number and resulted in the appearance of IGFBP-3 and the 29K IGFBP. However, IGF-II treatment resulted in a significant decrease (approximately 50%) in the 24K IGFBP and also decreased the 28K IGFBP. This decrease in the expression of the 24K and 28K IGFBPs was dose-dependent and was blocked by addition of IGF-I to the cells. When an IGF-II receptor antibody was added to the cells it mimicked the effects of IGF-II on B104 cells, suggesting that the inhibitory effects of IGF-II are mediated through the type II IGF receptor. Although both IGF-I and IGF-II affected the amount of the 24K IGFBP in the CM, neither peptide affected the expression of the messenger RNA for the 24K IGFBP. In conclusion, we have isolated two IGFBPs from the CM of B104 cells. Both the 24K and 28K IGFBPs appear to be isoforms of the same protein, and sequence data suggest these proteins are two forms of IGFBP-4. IGF-I increases the expression of both of these IGFBPs, whereas IGF-II decreases their expression.(ABSTRACT TRUNCATED AT 400 WORDS).
Exercise supplementation of dipyridamole for myocardial perfusion imaging [editorial; comment] The substitution of intravenous dipyridamole for symptom-limited treadmill exercise has provided a non-invasive means to diagnose coronary artery disease with 201Tl scintigraphy in patients unable to adequately exercise. Limitations of dipyridamole/thallium imaging are primarily due to suboptimal image quality secondary to hepatic tracer concentration and decreased test sensitivity in patients who are dipyridamole "non-responders." Low-level treadmill exercise supplementation improves image quality, whereas handgrip has little, if any, benefit. The effect of low-level exercise in augmenting coronary blood flow is unknown and reports regarding the effect of handgrip are conflicting. The diagnostic benefit of these maneuvers in improving test sensitivity and decreasing the number of "non-responders" has not been documented. The combination of maximal, symptom-limited treadmill exercise and intravenous dipyridamole is a theoretically attractive option to improve overall test sensitivity, but the physiologic consequences and potential side effects should be more thoroughly investigated.
Effect of very low birth weight and subnormal head size on cognitive abilities at school age BACKGROUND. We tested the hypothesis that very-low-birth-weight (less than 1.5 kg) infants with perinatal growth failure whose head size is not normal by eight months of age (corrected for prematurity) have significantly poorer growth and neurocognitive abilities at school age than very-low-birth-weight children with a normal head size at eight months. We also hypothesized that these differences would persist even after control for major neurologic impairment and perinatal and sociodemographic risk factors. METHODS. We have followed a cohort of very-low-birth-weight children since their birth during the period 1977 to 1979. At eight to nine years of age 249 children were evaluated with a neurologic examination and tests of intelligence; receptive and expressive language skills; speech, reading, mathematics, and spelling aptitude; visual and fine motor abilities; and behavior. Ages were corrected for premature birth. RESULTS. Among these 249 very-low-birth-weight children, head size was subnormal (less than the mean -2 SD for age) at birth in 30 (12 percent), at term in 57 (23 percent), and at eight months in 33 (13 percent). As compared with the 216 children with normal head sizes, the 33 children with subnormal head sizes at the age of eight months had significantly lower mean birth weights (1.1 vs. 1.2 kg) and higher neonatal risk scores (71 vs. 53) and at the age of eight years had a higher incidence of neurologic impairment (21 percent vs. 8 percent) and lower IQ scores (mean verbal, 84 vs. 98). Even among the children without neurologic abnormalities, a subnormal head size at eight months of age was predictive of poorer verbal and performance IQ scores at eight years of age; lower scores for receptive language, speech, reading, mathematics, and spelling; and a higher incidence of hyperactivity. In multiple regression analyses to control for socioeconomic and neonatal risk factors, intrauterine growth failure, birth weight, and neurologic impairment, a subnormal head size at eight months of age had an independently adverse effect on IQ and on scores for receptive language, speech, reading, and spelling. CONCLUSIONS. In very-low-birth-weight infants, perinatal growth failure, as evidenced by a subnormal head circumference at eight months of age, is associated with poor cognitive function, academic achievement, and behavior at eight years of age.
Prognostic significance of computed tomography of the brain in thrombotic thrombocytopenic purpura. We studied the prognostic value of computed tomography (CT) of the brain for neurologic morbidity in patients with thrombotic thrombocytopenic purpura. On review of Mayo Clinic records for 1975 through 1985, we found 32 patients with thrombotic thrombocytopenic purpura, 20 of whom had undergone CT of the brain during their hospitalization. Despite major neurologic symptoms and signs, normal CT findings were associated with complete neurologic recovery. Seventy percent of patients with normal results of CT of the brain recovered and had no neurologic deficits, whereas 80% of patients with CT abnormalities died or had permanent neurologic sequelae. A review of the literature supports these conclusions. Thus, we suggest that CT of the brain be done in any patient with thrombotic thrombocytopenic purpura and neurologic deficits. Regardless of the severity of neurologic involvement, normal CT findings should encourage continued vigorous treatment of the patient because a normal scan supports the possibility of full clinical recovery.
Alterations of ATP levels and of energy parameters in the blood of alcoholic and nonalcoholic patients with liver damage. Blood adenine nucleotides were determined in patients with alcoholic and non-alcoholic liver diseases. They included patients with alcoholic hepatitis (AH), alcoholic liver cirrhosis (ALC), non-alcoholic liver cirrhosis (NALC), and amoebic liver abscess (ALA) (28 patients). A decrease of 28% to 39% in blood ATP levels was observed among the patients with AH and the cirrhotic groups, respectively (p less than 0.05), whereas no significant changes in blood ATP levels were detected in the ALA group. Although total blood adenine nucleotides were significantly diminished in AH, ALC, and NALC groups, the AH patients retained their energy relationships within normal range. On the other hand, the cirrhotic groups, independently of their etiology, failed to maintain an adequate ATP/ADP ratio, energy charge, and phosphorylation potential in the blood, suggesting a decreased energy availability in their blood cells. Nevertheless, the mechanism involved in these effects remains to be elucidated, a failure of the damaged liver to supply purines to extra-hepatic tissues might be a major event altering the blood energy parameters.
Cutaneous herpes simplex virus infections. Affecting millions of Americans each year, herpes simplex virus infections are among the most common human viral infections. Many clinical forms exist, depending on the site of infection and the patient's age and immune status. Clinical evaluation and laboratory studies help establish the diagnosis. Acyclovir is the drug most often used to treat herpes simplex virus infections, although newer agents, such as phosphonoformate trisodium, may be required for acyclovir-resistant infections.
Effects of media conditions, insulin, and dexamethasone on insulin-receptor mRNA and promoter activity in HepG2 cells. Numerous physiological agents and conditions modulate cellular insulin sensitivity by downregulating or upregulating total cellular insulin receptors. In this study, we examined the effects of replacing complete medium in the absence or presence of insulin on the regulation of insulin-receptor gene expression in cultured human hepatoma cells (HepG2). Failure to replace complete medium resulted in growth arrest of HepG2 cells and a six- to sevenfold increase in insulin-receptor mRNA due to the prolongation of insulin-receptor mRNA half-life. Northern analysis revealed multiple insulin-receptor mRNA species; the largest species (11 kilobases) was disproportionately increased in growth-arrested cells. High concentrations of insulin (500 ng/ml) induced a 33.8% decrease in the abundance of insulin-receptor mRNA (n = 14). At lower concentrations, a trend of inhibition was observed but was not statistically significant. Insulin (500 ng/ml) did not affect insulin-receptor mRNA stability. The effect of conditioned media, insulin, and dexamethasone on insulin-receptor promoter activity was also examined. Various constructs of the 5'-flanking region of the insulin-receptor gene were attached immediately upstream to a chloramphenicol acetyltransferase (CAT) reporter gene and transiently transfected into HepG2 cells via a pBR322-derived plasmid (pCAT). In cells replaced with complete medium, 12 and 118% of the promoter activity was contained within 578 and 877 base pairs, respectively, from the major translational initiation site. Conditioned media from growth-arrested cells in culture for 7 days increased promoter activity approximately twofold in 48 h. However, this increase failed to localize to any specific region on the insulin-receptor promoter.
A prospective comparison of neuropsychologic performance of children surviving leukemia who received 18-Gy, 24-Gy, or no cranial irradiation. To compare the late neuropsychologic toxicities of CNS prophylaxis for childhood acute lymphoblastic leukemia (ALL), longitudinal assessments were performed on three groups of patients: those who received repeated courses of moderate-dose (1 g/m2) intravenous (IV) and intrathecal methotrexate (IT MTX) without cranial irradiation (MTX group, n = 26), those who received IT MTX and 18 Gy cranial irradiation (18-Gy group, n = 23), and those who received IT MTX and 24 Gy cranial irradiation (24-Gy group, n = 28). All patients were free of CNS leukemia at diagnosis and had remained in continuous, complete remission 5 to 11 years (median, 7.4 years) following CNS prophylaxis. An analysis of serial intelligence quotient (IQ), achievement, and neuropsychologic studies revealed no significant influence of either age at CNS prophylaxis or CNS prophylaxis group on any neuropsychologic outcome measure. After adjusting for changes in IQ test versions that were necessitated by advancing patient age, no statistically significant declines in Verbal, Performance, or Full Scale IQs were noted for the three CNS treatment groups. However, comparisons of group means masked declines in individual children; 22% to 30% of children exhibited a clinically significant deterioration (greater than or equal to 15 points) in uncorrected IQ values over the study period. Female sex was associated with an increased risk of deterioration in Verbal IQ, but we were unable to identify risk factors associated with other declines in intellect and achievement. The inability to reliably predict individual patients at risk for clinically significant neuropsychologic toxicities on the basis of age at diagnosis or specific method of CNS prophylaxis suggests that other etiologic factors must be explored as the basis for these changes, such as ecologic factors and chemotherapy during the continuation phase of treatment.