shukoor65/lab-rag-model huggingface dataset:
Circadian infusion of floxuridine in patients with metastatic renal cell carcinoma. A total of 42 patients with metastatic renal cell carcinoma received floxuridine infusion for 14 days at monthly intervals. The drug was delivered via an external programmable pump on a time-modified or circadian schedule; the highest dose of 68% was given between 3 and 9 p.m. Of the 42 patients 25 (60%) had undergone prior nephrectomy. Of the 40 evaluable patients 4 (10%, 95% confidential interval 3 to 24%) achieved a partial response: 3 of the 4 had undergone prior nephrectomy, while 1 had undergone renal angioinfarction. Another 4 patients (10%) had responses at metastatic sites but no response in the primary kidney tumor. The median duration of response for these 2 groups of patients was 65 and 27 weeks, respectively, and the most responsive site was the lungs. The treatment was generally well tolerated and could be administered on an outpatient basis. Our study confirms the limited but definite activity of floxuridine infused on a circadian schedule in patients with metastatic renal cell carcinoma. We observed responses in metastasis equally in patients with or without prior nephrectomy.
Human IgE, IgG4 and resistance to reinfection with Schistosoma haematobium. A well recognized feature of the immune response to parasitic helminth infections, including schistosomiasis, is the production of large amounts of specific and nonspecific IgE1,2. Immunological pathways involving IgE can lead to damage to the developing schistosomulum and it has been suggested that responses involving IgE could have evolved as protection against helminth infections. There has been no epidemiological evidence to support this idea and the only significant IgE responses known in man are those involved in the pathogenesis of allergic disease. Here we measure serological response during reinfection with S. haematobium and demonstrate that IgE antibodies in man can be beneficial. Our results support the hypothesis that the slow build-up of IgE to high levels and the early production of IgG4 antibodies, which may block IgE pathways are responsible for delaying the development of protective immunity to S. haematobium.
The role of reperfusion-induced injury in the pathogenesis of the crush syndrome. The crush syndrome consists of the general manifestations that follow prolonged continuous pressure on the limbs. These manifestations are caused by the disintegration of muscle tissue and leakage of the contents of myocytes into the plasma. The morbidity and mortality associated with this syndrome are high. The pathophysiologic process of the derangements associated with the crush syndrome is not fully understood, but the injury induced by reperfusion is likely to be important in its development. The injury due to reperfusion involves many factors, but it is currently ascribed largely to the release of oxygen free radicals, massive accumulation of calcium in ischemic muscles, and the infiltration of neutrophils into reperfused vessels. Since ischemic muscles cannot survive without reperfusion, a strategy to salvage as much of the muscle and kidney tissue as possible in the crush syndrome must include ways of decreasing injury during ischemia and reperfusion. Various pharmacologic agents may attenuate or prevent reperfusion-induced injury to ischemic skeletal muscles and consequently to other organs, particularly the kidneys.
Results and prognostic factors of surgery in the management of non-small cell lung cancer with solitary brain metastasis. Between 1975 and 1988, 37 patients with resectable non-small cell lung cancer (NSCLC) and synchronous (within 1 month, n = 10) or metachronous (n = 27) solitary brain metastasis (SBM) underwent combined excision of their lesions. Overall 5-year and median survival were 30% and 27 months (range, 3 to 125+ months), respectively. Twenty-seven patients had a relapse, and their median disease-free interval (DFI) was 17.5 months (range, 1 to 108 months). The most frequent (78%, n = 20) site of first recurrence locally was either the ipsilateral thorax (n = 14) or brain (n = 6). In univariate analysis, age, primary tumor and lymph node status; tumor histology, size, and side; type of pulmonary resection; side and location of SBM; and onset of presentation did not affect survival and DFI. By contrast, the interval (less than or equal to versus greater than 12 months) between the two operations significantly affected survival (P = 0.0096) and DFI (P = 0.046). The DFI was also affected by the administration of adjuvant chemotherapy (AC) for the primary tumor (P = 0.02). Using the Cox model, AC was the most independent predictor of DFI. These data support the inclusion of surgery in the therapeutic armamentarium for patients with NSCLC and SBM.
Effect of exercise intensity and duration on regional function during and after exercise-induced ischemia. BACKGROUND. Transient reversible myocardial dysfunction has been documented after episodes of exercise-induced ischemia. This study was undertaken to determine whether the duration or intensity of exercise affects the severity of postischemic dysfunction in this setting. METHODS AND RESULTS. Ten dogs were instrumented with ultrasonic microcrystals for measurement of wall thickening, with circumflex coronary artery flow probes, and with hydraulic occluders. Dogs performed low-intensity exercise, which was sufficient to increase coronary perfusion 50% above control, and high-intensity exercise, which was sufficient to double coronary blood flow. To investigate the effects of exercise intensity on postischemic dysfunction, we had dogs perform high-intensity exercise for 5 minutes in the presence of a stenosis. On the alternate day, dogs performed low-intensity exercise for 10 minutes in the presence of a stenosis. These two protocols provide equivalent coronary flow debts. Mean transmural blood flow during high-intensity exercise without stenosis (2.61 +/- 0.54 ml/min/g) was significantly higher than that during low-intensity exercise (1.74 +/- 0.61 ml/min/g, p less than 0.002). During high-intensity exercise with coronary artery stenosis, subendocardial blood flow was significantly lower than that during low-intensity exercise with stenosis (0.64 +/- 0.40 versus 1.08 +/- 0.28 ml/min/g, p less than 0.02). This difference in subendocardial perfusion was associated with greater degrees of regional dysfunction during exercise (circumflex wall thickening was 44 +/- 23% of control for high-intensity exercise versus 60 +/- 18% of control for low-intensity exercise, p less than 0.01). In addition, from 10 to 30 minutes after exercise, wall thickening in myocardium perfused by the circumflex coronary artery remained significantly lower after high-intensity exercise than that after low-intensity exercise. To assess the effects of exercise duration on the severity of postischemic dysfunction, we had dogs perform low-intensity exercise in the presence of a coronary stenosis for 10 minutes and low-intensity exercise for only 5 minutes on alternate days. Systolic wall thickening was significantly lower after low-intensity exercise for 10 minutes than after low-intensity exercise for 5 minutes. CONCLUSIONS. High-intensity exercise results in greater degrees of subendocardial hypoperfusion and greater degrees of regional dysfunction both during and after exercise-induced ischemia than does low-intensity exercise. Second, exercise duration also exerts an effect on the severity of postischemic dysfunction, although the magnitude of this effect is less important than the effect of exercise intensity.
Association of leptomeningeal carcinomatosis in carcinoma of the breast with infiltrating lobular carcinoma. An autopsy study. We analyzed the autopsy records of 261 patients with breast carcinoma, who died at The Institute of Oncology, Ljubljana, Yugoslavia, for the presence of metastases to the central nervous system, particularly for the presence of leptomeningeal carcinomatosis. Metastases to the central nervous system were found in 41 (18.1%) of 226 patients who had metastatic cancer. In 24 cases (10.6%), metastases were seen in brain parenchyma; in 11 cases (4.9%), only dura mater was involved, and in six cases (2.6%), leptomeningeal carcinomatosis was found. All patients with leptomeningeal carcinomatosis showed some symptoms of central nervous system involvement while alive. The patients died between 2 weeks and 2 months after the onset of central nervous system symptoms. Four of six patients with such a complication presented with locally advanced or disseminated carcinoma on the first admission. With regard to histologic findings, three patients had infiltrating lobular carcinoma, two had infiltrating ductal carcinoma, and one had mixed infiltrating lobular and ductal carcinoma, with a metastasizing lobular component. Metastases to the brain parenchyma were found exclusively in infiltrating ductal carcinoma. We stress that infiltrating lobular carcinoma represents a distinctive type of breast cancer with an unusual propensity to disseminate into leptomeninges, as this occurred in almost 14% of all cases of infiltrating lobular carcinoma in our series in contrast to a 1% incidence in cases of infiltrating ductal carcinoma.
Predictors and prevalence of obstructive sleep apnoea and snoring in 1001 middle aged men. One thousand and one men, aged 35-65 years, were identified from the age-sex register of one group general practice. Over four years 900 men were visited at home and asked questions about symptoms potentially related to sleep apnoea and snoring. Height, weight, neck circumference, resting arterial oxygen saturation (SaO2), and spirometric values were also determined. All night oximetry was then performed at home and the tracing analysed for the number of dips in SaO2 of more than 4%. Subjects with more than five dips of 4% SaO2 or more per hour were invited for sleep laboratory polysomnography. Seventeen per cent of the men admitted to snoring "often." Multiple linear regression techniques identified and ranked neck circumference (r2 = 7.2%), cigarette consumption (r2 = 3.4%), and nasal stuffiness (r2 = 2%) as the only significant independent predictors of snoring. Together these account for at least a sixfold variation in the likelihood of being an "often" snorer. Forty six subjects (5%) had greater than 4% SaO2 dip rates of over five an hour and 31 of these had full sleep studies. Three subjects had clinically obvious and severe symptomatic obstructive sleep apnoea, giving a prevalence of three per 1001 men (0.3%; 95% confidence interval 0.07-0.9%). Eighteen men had obstructive sleep apnoea only when supine and in 10 the cause of the SaO2 dipping on the original home tracing was not elucidated. The greater than 4% SaO2 dip rates correlated with the history of snoring. Multiple linear regression techniques identified and ranked neck circumference (r2 = 7.9%), alcohol consumption (r2 = 3.7%), age (r2 = 1%) and obesity (r2 = 1%) as the only significant independent predictors of the rate of overnight hypoxic dipping. This study shows that snoring in this randomly selected population correlates best with neck size, smoking, and nasal stuffiness. Obstructive sleep apnoea, defined by nocturnal hypoxaemia, correlates best with neck size and alcohol, and less so with age and general obesity.
Intramedullary nailing for impending pathological subtrochanteric fractures. We reviewed ten patients with metastatic carcinoma and impending pathological fractures of the subtrochanteric region of the femur who had prophylactic insertion of the Russell-Taylor reconstruction nail. There were no operative complications or long-term mechanical failures. This reconstruction nail has some technical and biomechanical advantages over other implants and is ideal for the management of such cases.
Effects of radiation on testicular function in long-term survivors of childhood acute lymphoblastic leukemia: a report from the Children Cancer Study Group. Testicular function was evaluated in 60 long-term survivors of childhood acute lymphoblastic leukemia (ALL). All the patients were treated on two consecutive Children Cancer Study Group protocols and received identical chemotherapy and either 18 or 24 Gy radiation therapy (RT) to one of the following fields: craniospinal plus 12 Gy abdominal RT including the gonads (group 1); craniospinal (group 2); or cranial (group 3). The median age at the time of their last evaluation was 14.5 years (range, 10.5 to 25.7), which took place a median of 5.0 years (range, 1 to 10.3) after discontinuing therapy. The incidence of primary germ cell dysfunction as judged by raised levels of follicle-stimulating hormone (FSH) and/or reduced testicular volume was significantly associated with field of RT; 55% of group 1, 17% of group 2, and 0% of group 3 were abnormal (P = .002). Leydig cell function, as assessed by plasma concentrations of luteinizing hormone (LH) and testosterone, and pubertal development, was unaffected in the majority of subjects regardless of RT field. These data indicate that in boys undergoing therapy for ALL, germ cell dysfunction is common following testicular irradiation and can occur following exposure to scattered irradiation from craniospinal RT. In contrast, Leydig cell function appears resistant to direct irradiation with doses as high as 12 Gy.
Effect of hypercapnia on total pulmonary resistance during wakefulness and during NREM sleep. We investigated the effect of different levels of hypercapnia on total pulmonary resistance (RL) in 13 subjects ranging from nonsnorers with low RL to snorers with high RL and dynamic narrowing of the upper airway during inspiration. Added CO2 was adjusted to achieve a steady-state increase in PETCO2 of +2, +4, or +6 mm Hg. RL was measured at peak inspiratory flow (RLpf), at maximal resistance within breath (RLmax), and at 10 equally spaced points within inspiration in several trials. During wakefulness, hypercapnia was associated with decreased RLmax. During steady state +6 mm Hg hypercapnia, RLmax decreased by 30% (p less than 0.01). During NREM sleep, low levels of hypercapnia did not affect RL. However, +6 mm Hg hypercapnia was associated with decreased RLmax in six of eight subjects (p = 0.07), especially in subjects with high RLmax during room air breathing. The effects of hypercapnia on RLpf paralleled its effect on RLmax. We concluded that (1) the decrease in RL during awake hypercapnia suggests an increase in upper airway dimensions and stiffness, (2) the absence of increased RL during low level NREM hypercapnia (despite the increase in inspiratory flows and collapsing pressures) also suggests an increase in upper airway dimensions and stiffness, and (3) upper airway dilating muscles appear to be recruited in a coordinated fashion with inspiratory muscles in normal humans during NREM sleep. The implications of these findings in patients with obstructive sleep apnea are not clear at this point.
Argon laser-assisted anastomoses in medium-size vessels: one-year follow-up. Laser-assisted anastomosis of medium-size vessels can be performed with satisfactory short-term patency. This study was undertaken to evaluate patency and structural integrity up to 1 year. An argon laser was used to make bilateral femoral arteriovenous anastomoses in 12 dogs compared to conventional suture method in another 8 dogs. These anastomoses were evaluated for patency and aneurysm formation at 1 hour; 1, 2, 4, and 8 weeks; and 12 months after surgery. All anastomotic sites were patent and without aneurysmal change or luminal narrowing at all harvesting intervals. Histologic examination revealed that within 1 month laser anastomotic sites were almost completely healed and without intimal hyperplasia. In suture anastomoses, foreign-body reaction remained evident up to 1 year. Use of the argon laser for medium size vessel anastomoses resulted in excellent patency without aneurysm formation or intimal hyperplasia even in the long term. These data suggest promising clinical applications.
Inhibitory effect of sandostatin on secretion of luteinising hormone and ovarian steroids in polycystic ovary syndrome. Hyperinsulinism accompanies the raised luteinising hormone (LH) concentrations in women with the polycystic ovary syndrome (PCOS). Somatostatin inhibits insulin and LH secretion in healthy adults, so the effect of treatment with a long-acting somatostatin analogue ('Sandostatin') on gonadotropin and androgen secretion in PCOS was investigated. LH pulsatility, androgen concentrations, and hormonal responses to an oral glucose load and to administration of a GnRH agonist (buserelin) were measured before and after 7 days' treatment with sandostatin 100 micrograms subcutaneously twice a day in 10 amenorrhoeic women with classic features of PCOS. Sandostatin significantly reduced integrated LH concentrations and LH pulse amplitudes, oestradiol, testosterone, and androstenedione concentrations, and LH responses to buserelin; it also suppressed insulin and C-peptide responses to an oral glucose load. Thus sandostatin inhibits pituitary and ovarian hormonal responses in part by a direct influence on pituitary activity, and the possibility of an indirect effect mediated by changes in insulin concentrations requires investigation. These findings have implications for the treatment of infertility in women with PCOS.
Stop codon in the procollagen II gene (COL2A1) in a family with the Stickler syndrome (arthro-ophthalmopathy). Linkage analysis with restriction fragment length polymorphisms for the gene for type II procollagen (COL2A1) was carried out in a family with the Stickler syndrome, or arthro-ophthalmopathy, an autosomal dominant disorder that affects the eyes, ears, joints, and skeleton. The analysis demonstrated linkage of the disease and COL2A1 with a logarithm-of-odds score of 1.51 at zero recombination. A newly developed procedure for preparing cosmid clones was employed to isolate the allele for type II procollagen that was linked to the disease. Analysis of over 7000 nucleotides of the gene revealed a single base mutation that altered a CG dinucleotide and converted the codon CGA for arginine at amino acid position alpha 1-732 to TGA, a stop codon. From previous work on procollagen biosynthesis, it is apparent that the truncated polypeptide synthesized from an allele with a stop codon at alpha 1-732 cannot participate in the assembly of type II procollagen, and therefore that the mutation would decrease synthesis of type II procollagen. It was not apparent, however, why the mutation produced marked changes in the eye, which contains only small amounts of type II collagen, but relatively mild effects on the many cartilaginous structures of the body that are rich in the same protein.
The trk proto-oncogene product: a signal transducing receptor for nerve growth factor The trk proto-oncogene encodes a 140-kilodalton, membrane-spanning protein tyrosine kinase (p140prototrk) that is expressed only in neural tissues. Nerve growth factor (NGF) stimulates phosphorylation of p140prototrk in neural cell lines and in embryonic dorsal root ganglia. Affinity cross-linking and equilibrium binding experiments with 125I-labeled NGF indicate that p140prototrk binds NGF specifically in cultured cells with a dissociation constant of 10(-9) molar. The identification of p140prototrk as an NGF receptor indicates that this protein participates in the primary signal transduction mechanism of NGF.
Duodenal somatostatinoma with congenital pseudoarthrosis. We describe a previously unreported association between somatostatinoma and congenital pseudoarthrosis. Because pseudoarthrosis is part of von Recklinghausen's disease, in turn with an association with somatostatinoma, we speculate on a link between pseudoarthrosis and somatostatinoma.
Repeat infusion of recombinant tissue-type plasminogen activator in patients with acute myocardial infarction and early recurrent myocardial ischemia. When conventional treatment of patients with early clinical reinfarction after thrombolytic therapy fails, mechanical revascularization may be attempted. An alternative strategy, repeat thrombolytic infusions, is reported. Fifty-two patients with acute myocardial infarction were treated with one or two additional thrombolytic infusions of recombinant tissue-type plasminogen activator (rt-PA) because of nonsustained ischemia after initial treatment with rt-PA or streptokinase. Thirty-five patients received the second infusion within 1 h of the first; 13 patients received the second infusion 1 to 72 h after the first and 4 patients received it later during their hospitalization. Bleeding complications occurred in 10 patients (19%); however, most of these were minor (no intracranial bleeding) and only 2 patients required blood transfusion. In 14 patients in whom the decrease in fibrinogen and plasminogen levels was measured after the first and second infusions, this decrease was only 25% and 63%, respectively--only slightly higher than the 22% and 53% decreases measured in 63 patients who had only one rt-PA infusion. In 44 patients (85%), the acute ischemia resolved completely within 1 h after initiation of the second infusion. In 23 patients (44%), pain and ST segment elevation did not recur and invasive coronary intervention was avoided. Thus, repeat rt-PA infusions can stabilize a substantial number of patients with acute reinfarction and, even when relief is temporary, repeat rt-PA infusions can minimize myocardial damage while patients await mechanical revascularization.
Assessment of quality of life. Assessment of quality of life has emerged in recent years as an important part of the overall evaluation of drug therapy and health care in general. Measurement techniques for this difficult assessment range from simple unqualified questions on patient well-being to complex statistical analyses of a wide range of lifestyle and activity variables. The factors that influence quality of life during chronic drug therapy differ in the treatment of symptomatic (e.g., heart failure) vs asymptomatic (e.g., hypertension) disease, and include drug side effects, relief of symptoms, improved prognosis, return to work, physical activity and the need for further hospital treatments. The manifestation of quality of life varies for different people leading to lack of agreement on the precise definition. The absence of standardization of methods of measurement also contributes to this and leads to lack of comparability of studies and unreasonable claims by some drug manufacturers. Further complicating issues in multicenter trials across countries include language problems and interethnic differences in "sickness" behavior. The recently introduced quality-adjusted life year (QALY) index, designed to take account of both the quality and duration of life in assessing the outcome of treatments, may avoid some of these problems. By classifying illness states (the Rosser index) on the basis of disability and distress, and comparing outcomes in terms of improved prognosis, QALYs have already been used for cost/benefit analyses of a number of new and expensive therapies. Like other methods, QALYs have problems related to variability in individual appreciation of life values. To date, a perfect method of quality of life assessment remains elusive.