shukoor65/lab-rag-model huggingface dataset:
Lateral parabrachial nucleus and angiotensin II-induced hypertension. The objective of this study was to determine if ablation of the lateral parabrachial nucleus (LPBN) would prevent angiotensin II-induced hypertension in rats. Thirteen male Sprague-Dawley rats were studied. Bilateral electrolytic lesions in the LPBN were produced in six rats; the remaining seven rats were subjected to sham lesion surgery only. All rats were instrumented with vascular catheters and housed in metabolism cages. Daily measurements during the 16-day protocol included arterial pressure, heart rate, water intake, urine output, and urinary sodium excretion. Periodically throughout the protocol depressor responses to ganglion blockade and to blockade of V1-type vasopressin receptors also were measured. The protocol was divided into three control-period days, 10 days of continuous (24 hr/day) angiotensin II infusion (10 ng/min i.v.), and three recovery-period days. There were no significant differences between the two groups of rats for any variable during the control period. During angiotensin II infusion, sham-lesion rats exhibited a progressive increase in arterial pressure and the depressor response to ganglion blockade and a decrease in urinary sodium excretion. No other variable was significantly changed. In rats with LPBN lesions, arterial pressure was significantly increased only on days 1 and 3 of angiotensin II infusion. No other variable was affected. It was concluded that ablation of the LPBN in rats prevented sustained hypertension during intravenous infusion of angiotensin II by interfering with neurogenic pressor mechanisms normally activated by the peptide.
Bladder and sphincter behavior in patients with spinal cord lesions. To ascertain the relationship between the clinical neurological level, and bladder and sphincter behavior, the video-urodynamic studies of 489 patients with spinal cord lesions due to a variety of causes were retrospectively analyzed. Patients were classified based on the clinical neurological level, etiology of the lesion and presence or absence of signs of sacral cord involvement. Urodynamic findings were classified as either detrusor hyperreflexia, detrusor-external sphincter dyssynergia, detrusor areflexia or normal. The results indicate that although there was a general correlation between the neurological level of injury and the expected vesicourethral function, it was neither absolute nor specific. For example, 20 of 117 cervical cord lesions had detrusor areflexia, 42 of 156 lumbar cord lesions had detrusor-external sphincter dyssynergia and 26 of 84 sacral cord had either detrusor hyperreflexia or detrusor-external sphincter dyssynergia. However, if one considers the presence of neurological abnormalities, 84% of the suprasacral cord lesions with detrusor areflexia have sacral cord signs. In contrast, all suprasacral cord lesions with no evidence of sacral cord involvement have either detrusor hyperreflexia or detrusor-external sphincter dyssynergia. The positive predictive value for positive sacral cord signs and detrusor areflexia was 87%. The positive predictive value for negative sacral cord signs and detrusor hyperreflexia/detrusor-external sphincter dyssynergia was 81%. These data suggest that the clinical neurological examination alone is not an adequate barometer to predict neurourological dysfunction and that video-urodynamic evaluation provides a more precise diagnosis for each patient.
The submandibular triangle in squamous cell carcinoma of the larynx and hypopharynx. A 15-year retrospective analysis was carried out at the University of Illinois College of Medicine, Chicago, reviewing the tumor staging and pathology data of 239 patients treated for carcinoma of the larynx and hypopharynx requiring laryngectomy alone, laryngectomy with neck dissection, or laryngopharyngectomy and neck dissection. Surgery was the primary treatment modality in 205 of the 239 cases, with the remaining 34 having surgery to treat radiation therapy failure. Primary tumors were located within the supraglottic region, the glottic region and, less commonly, the pyriform sinus. Ninety-five of the 239 patients either presented with or developed nodal metastases following initial treatment. Of these, only two had tumors within the lymph nodes of the submandibular triangle. This data corroborates impressions that tumors of the larynx and hypopharynx rarely metastasize to the submandibular triangle and that sparing this area during neck dissection for lesions of the larynx would seem justified.
Factors affecting the rearrangement efficiency of an Ig test gene. A rearrangement test gene, pHRD, containing the mouse IgH enhancer and the metallothionein promoter, has previously been shown to rearrange efficiently after transfection into a pre-B cell line. Experiments are now reported that assess the requirements of the DNA substrate as well as of the transfected cells for efficient rearrangement. It was found that deletion of the metallothionein promoter or substitution of the IgH enhancer by the kappa enhancer did not affect rearrangement. However, deletion of the Ig enhancer reduced the efficiency. Transfection of pHRD into stable hybrids of pre-B cells and myeloma cells resulted in a high frequency of rearrangement only if certain myeloma chromosomes were lost. Furthermore, pHRD introduced into rearrangement incompetent myeloma cells upon subsequent cell fusion with pre-B cells was rearranged only very rarely and then apparently only immediately after cell fusion. Stable pre-B cell x myeloma hybrids that retained the critical myeloma chromosomes were found to have lost VDJ recombinase activity and transcripts of the RAG-1, RAG-2 and TdT genes. It is concluded that transcription, i.e., the copying of the DNA by polymerase, is probably not required for rearrangement, but that the rearrangement substrate must be in an "open" chromatin state, such as may be provided by transcriptional factors. Furthermore, the absence of rearrangement in myeloma cells is apparently due to the continued action of an inhibitor of rearrangement.
Effects of subsequent pregnancy on left ventricular function in peripartum cardiomyopathy. Pregnancy has been discouraged in patients with peripartum cardiomyopathy (PPCM) to avoid the risk of precipitating recurrent or progressive left ventricular dysfunction. We assessed left ventricular size and contractile function using echocardiography in four PPCM patients prior to pregnancy, during the third trimester, and a mean of 6 weeks postpartum. Left ventricular mean diameters at end diastole and at end systole prior to pregnancy (5.2 +/- 0.3 and 3.0 +/- 0.2 cm, respectively) did not change during pregnancy (5.2 +/- 0.3 and 3.1 +/- 0.2 cm). Similarly, left ventricular fractional shortening did not alter significantly during pregnancy or postpartum. Furthermore, no patient developed any symptoms or signs of left ventricular failure. All patients had normal babies, including one who had twins. We conclude that PPCM patients whose left ventricular function returns to normal may undertake further pregnancy with a normal fetal outcome and a low risk of recurrent left ventricular dysfunction.
Pulmonary vascular reactivity in Fischer rats. We previously reported that Fischer (F) rat lungs developed more extensive injury when challenged with oxidants than age-matched Sprague-Dawley (SD) rat lungs. We now describe a reduced pulmonary vascular response to alveolar hypoxia and angiotensin II (ANG II) in F compared with SD rats. The comparative studies were performed with isolated lungs perfused with salt solution or blood, catheter-implanted awake rats, and isolated main pulmonary arterial rings. Isolated lungs from F rats perfused with either blood or salt solution had reduced vasoconstriction in comparison with lungs from SD rats when exposed to alveolar hypoxia or challenged with ANG II. Instrumented awake F rats had a smaller mean increase in total pulmonary vascular resistance (PVR) than SD rats (35 vs. 94 mmHg.min.l-1, P less than 0.05) when challenged with 8% oxygen. The contractile response of isolated pulmonary artery but not thoracic aortic rings to KCl and ANG II was reduced in F compared with SD rats. In addition, F rats exposed to 4 wk of hypobaric hypoxia developed less pulmonary hypertension and right ventricular hypertrophy (when corrected for the hematocrit) than SD rats. We conclude that the oxidant stress-sensitive inbred F rat strain is characterized by a lung vascular bed that is relatively unresponsive to vasoconstricting stimuli. The mechanism underlying this genetic difference in lung vascular control remains to be defined.
Herniated cervical disk presenting as ischemic chest pain. Myocardial ischemia must be the first concern of every emergency physician in evaluating chest pain in the adult patient. Any suspicion of myocardial ischemia must be promptly evaluated and admitted. The American College of Emergency Physicians has recently published a standards document on the care of chest pain in the adult patient. The emergency physician must be familiar with this document. Once myocardial ischemia and other life-threatening causes are ruled out, one can consider that cervical disk disease may be the cause of chest pain. We present two cases of patients who presented to the emergency department with signs and symptoms consistent with cardiac ischemia. Both patients were found to have herniated cervical disks. Subsequent surgical repair completely relieved their symptoms. Evaluation of the literature shows that this entity was well described from 1950 to the 1960s. Most recent discussions do not mention disk herniation as even an infrequent cause of chest pain. If there is no life-threatening disease present, one should consider cervical disk disease.
Obstructed central venous catheters. Restoring function with a 12-hour infusion of low-dose urokinase. Thrombotic obstruction frequently prohibits infusion through or withdrawal of blood from central venous catheters and can occur in conjunction with symptomatic thrombosis of the subclavian vein. Thirty catheters were radiographically proved to be obstructed by thrombus and had not responded to at least one instillation of 5000 units of urokinase. All catheters were treated with a 12-hour infusion of urokinase at the rate of 40,000 units/hour. The obstructing thrombus was either eliminated or reduced in size in all instances and full function was restored in all but one catheter. No bleeding complications were seen. Six patients with obstructed catheters also had symptoms of subclavian vein thrombosis. All patients with symptoms of subclavian vein obstruction became asymptomatic on anticoagulant therapy even though no attempt at dissolving the thrombus obstructing the subclavian vein was made. A 12-hour infusion of low doses of urokinase can safely salvage function of obstructed catheters that otherwise may require replacement. Patients with concomitant subclavian vein thrombosis become asymptomatic on anticoagulant therapy without need to dissolve the obstructing thrombus.
Diabetes mellitus and localizations of obliterating arterial disease of the lower limbs. Thirty patients with intermittent claudication (IC) and treated diabetes mellitus and 30 age- and gender-matched nondiabetic claudicants underwent a vascular examination by noninvasive ultrasound methods (continuous-wave Doppler, duplex scanner). The ankle/arm systolic pressure index did not differ in the two groups. Diabetic patients with IC had more (p less than .001) non-flow-reducing stenoses (lumen reduction less than 50%) and fewer (p less than .002) flow-reducing obstructions (lumen reduction greater than 50%) of the iliac arteries than nondiabetics had. These data are consistent with a preferentially distal (below the inguinal ligament) localization of arterial stenoses in diabetic patients, whereas iliac artery diseases are relatively more severe in nondiabetics.
A prospective evaluation of arterial intimal injuries in an experimental model. The management of arterial intimal defects remains controversial because of uncertainty concerning their natural history. We developed an experimental canine model to prospectively evaluate posterior wall intimal flaps in the superficial femoral artery. Arterial intimal flaps were constructed in 20 anesthetized dogs (40 arteries) and evaluated by arteriography, and angioscopy, and intravascular ultrasound. Postoperative patency rates at 1 (n = 20) and 3 weeks (n = 20) were compared with a control group of ten animals (n = 20, arteriotomy without intimal flap). Acute thromboses occurred in five experimental arteries with thromboses of eight additional experimental arteries at followup. Control patency was 100%, while experimental group patencies were 75% (p less than 0.05) at 1 week and 60% (p less than 0.009) at 3 weeks. All thrombosed arteries had intimal flaps with greater than 75% luminal stenosis. We conclude that intimal injuries cause arterial thromboses acutely and during subsequent followup. Intimal flaps with stenosis greater than 75% as determined arteriographically are at greatest risk for thrombosis. Angioscopy and intravascular ultrasound characterize arterial intimal defects and may delineate injuries requiring surgical or endovascular repair.
Internal biliary drainage, parenteral nutrition, and variation in the total parenteral nutrition feeding solutions: influence on the healing of colon anastomosis in jaundiced rats. The influence of preoperative internal biliary drainage and various types of total parenteral nutrition (TPN) on the healing of a colon anastomosis in 50 jaundiced rats was investigated. Jaundice was induced by division and ligation of the common bile duct. After 5 days a colon anastomosis was made. Ten days thereafter the bursting pressure of the anastomosis was measured as an assessment of wound healing. Bursting pressures were significantly lower in jaundiced rats compared with a sham-operated nonjaundiced group. Preoperative internal biliary drainage significantly improved bursting pressure (p less than 0.001) as did preoperative TPN (p less than 0.001). In the second part of the study the influence of four different feeding solutions on the healing of a colon anastomosis was tested. Solutions with and without 20% fat emulsion and a solution with branched-chain amino acids were tested as well as glucose only. No significant differences were observed among these four groups on the parameters tested.
Six-year experience with a comprehensive approach to the treatment of recurrent childhood acute lymphoblastic leukemia (ALL-REZ BFM 85). A relapse study of the BFM group. Between April 1985 and March 1987 130 children and adolescents up to 18 years of age with first relapse of acute lymphoblastic leukemia (ALL) were registered on the stratified and randomized multicentric trial ALL-REZ BFM 85 designed for patients pretreated with intensive front-line therapies. Stratification criteria were time and site of relapse: bone marrow (BM) relapse on or up to 6 months after stopping front-line therapy (group A), BM relapse beyond 6 months after therapy (group B), and isolated extramedullary relapse at any time (group C). Treatment consisted of alternating courses of polychemotherapy including randomly administered high- or intermediate-dose methotrexate (HDMTX:12 g/m2 as 4-hour infusion; IDMTX: 1 g/m2 as 36-hour infusion). During maintenance therapy the patients received daily oral thioguanine and biweekly intravenous (IV) MTX. The overall second complete remission (CR) rate was 92% (groups A, B, and C: 88%, 92%, and 100%), and the probability of event-free survival (EFS) at 6 years is 0.31 +/- 0.04 (groups A, B, and C: 0.18 +/- 0.05, 0.30 +/- 0.07, and 0.72 +/- 0.11). HDMTX did not prove to be superior to IDMTX, which led to premature stopping of randomization. Risk factor analyses showed early relapse, particularly BM relapse within 18 months, and T-cell phenotype to be independent predictors of poor outcome. The incidence of central nervous system (CNS) relapses following BM relapse was 19%, indicating that reprophylaxis to the CNS with IV/intrathecal (IT) MTX was insufficient. For 17 children who received bone marrow transplantation in second CR from HLA-compatible siblings the EFS was 0.53 +/- 0.12 at 5 years. Their outcome was not influenced by the above-mentioned risk factors. With the proposed treatment regimen long-lasting second remissions can be achieved in about one third of patients even after intensive front-line treatment.
Validity of cerebrovascular mortality rates. Cerebrovascular disease (CVD) mortality rates are being increasingly used to establish a relationship with coronary heart disease risk factors. Cerebrovascular mortality rates suffer from the same general defects as coronary heart disease mortality rates but with greater diagnostic error in regard to subdivisions of CVD or stroke. These vital statistics, whether national or regional, are too inaccurate for scientific use and cannot be regarded as representing true mortality rates for any country. Moreover, clinical CVD is an inappropriate surrogate for severity of atherosclerosis, providing inexact data and allowing indeterminate overlap in epidemiologic studies.
Tumor regulation of hepatic glutamine metabolism. Fast-growing tumors are major glutamine consumers and may alter host glutamine metabolism to benefit the tumor. Previous studies from our laboratory have demonstrated that the liver switches from an organ of glutamine balance to one of glutamine release with progressive malignant growth. However, the regulation of this change is unclear. This study examined tumor modulation of hepatic glutamine metabolism by determining the activities of glutaminase, the principle enzyme of glutamine degradation, and glutamine synthetase, the principal enzyme of glutamine synthesis. Hepatic glutamine content was also determined. Rats with a fast-growing subcutaneous fibrosarcoma (TBR) and pair-fed controls were studied at 2 and 3 weeks after tumor or sham implantation, when the tumors comprised approximately 5% and 20% of total body weight. Arterial glutamine fell with progressive tumor growth (608 +/- 26 mumol/L in controls vs 494 +/- 15 in TBR, p less than 0.005) and was not attributable to a diminished food intake. Hepatic glutamine content was increased 45% (p less than 0.01) in tumor rats at 2 weeks due in part to a 35% fall in liver glutaminase activity. At 3 weeks, glutamine synthetase activity increased by 43% (0.58 +/- 0.07 mumol/mg of protein/hr in controls vs 0.83 +/- 0.04 in TBR, p less than 0.01) whereas glutaminase remained depressed (2.68 +/- 0.12 mumol/mg of protein/hr in controls vs 2.22 +/- 0.15 in TBR, p less than 0.05) and glutamine content fell compared to 2 week tumor-bearing rats, consistent with accelerated hepatic glutamine release. Tumors may alter liver glutamine metabolism by modulating hepatic enzyme activity in order to provide circulating glutamine for the growing malignancy.
Phase I trial of fluorouracil modulation by N-phosphonacetyl-L-aspartate and 6-methylmercaptopurine riboside: optimization of 6-methylmercaptopurine riboside dose and schedule through biochemical analysis of sequential tumor biopsy specimens. Preclinical and clinical studies demonstrate that the selective antitumor activity of fluorouracil (5-FU) is enhanced by agents which perturb certain intracellular nucleotide pools. We previously demonstrated that the combination of N-phosphonacetyl-L-aspartate (PALA), which depletes pyrimidine nucleotide pools, and 5-FU yielded a 43% response rate among 37 assessable patients with colorectal carcinoma. In preclinical tumor models, 6-methylmercaptopurine riboside (MMPR), an inhibitor of purine synthesis, elevates phosphoribosylpyrophosphate (PRPP) pools and promotes the anabolism of 5-FU to fluorinated nucleotides. In vivo, the addition of MMPR enhances the therapeutic efficacy of PALA-5-FU. In a phase I trial, we sought to determine the optimal dose and schedule of MMPR in combination with PALA (250 mg/m2 on day 1) and 5-FU (1300 mg/m2 by 24-hour infusion on day 2). MMPR (75-225 mg/m2) was given intravenously on day 1 to 27 patients with solid tumors (15 colorectal, seven breast, five other). Toxic effects were mild to moderate and included leukopenia, mucositis, nausea, or rash. Two of seven patients given MMPR at 225 mg/m2 had grade 3 diarrhea. PRPP was measured using a [14C]orotic acid 14CO2 release assay in tumor biopsy specimens obtained before and 12 hours and 24 hours after MMPR doses were given to 20 patients. The addition of MMPR elevated PRPP pools in human solid tumors. At 12 hours after treatment, two (50%) of four patients showed a twofold or greater elevation of PRPP at the MMPR dose level of 75 mg/m2; a similar elevation was observed in five (71%) of seven patients given 150 mg/m2 MMPR and in three (43%) of seven patients given 225 mg/m2 MMPR. At 24 hours after treatment, results for the respective dose levels of MMPR were two (33%) of six patients, one (20%) of five patients, and four (57%) of seven patients. Administration of the two highest MMPR dose levels appeared to result in a greater increase in tumor PRPP levels. However, toxicity was greater at the 225 mg/m2 dose level; therefore, the 150 mg/m2 dose level was favored. Tumor levels of PRPP decreased between 12 hours and 24 hours in nine (56%) of 16 patients. This time course indicates that MMPR should be administered at the beginning of the 24-hour infusion of 5-FU.
Age-dependent increase in deleted mitochondrial DNA in the human heart: possible contributory factor to presbycardia. Cardiac function deteriorates with age, and endogenous damage to mitochondrial DNA (mt DNA) is believed to be a major contributory factor to aging. Mitochondria occupy a pivotal position in energy metabolism, and mitochondria have their own DNA, which encodes 13 subunits of the mitochondrial energy transducing system. Other subunits are encoded by nuclear DNA. DNA has been shown to have a high mutation rate, and genetic mutation might primarily be ascribed to mtDNA mutation in the energy transducing system. Recent advances in gene technology, especially in polymerase chain reactions (PCR), permit us to analyze mtDNA mutations in a small quantity of tissue. We devised rapid and accurate methods to detect mitochondrial mutations--the primer shift PCR method, PCR-Southern method, the modified primer shift PCR method, and the asymmetric PCR method. With these methods, we analyzed myocardia mtDNA in human cadavers of various ages (from 3 years old to 97 years old, mean 57 years old). The 7.4 kb deletion of mtDNA was commonly detected in elderly subjects, and the proportion of deleted mtDNA to normal mtDNA increased with age. Deleted mtDNA was observed in all subjects that were over 70 years old. The mutation was based on the directly repeated sequence: 5'-CATCAA-CAACCG-3', which exists in both the adenosine triphosphatase 6 gene and the displacement loop (D-loop) region. Replication impairment occurred at that directly repeated sequence, which caused the elimination of genomes between the adenosine triphosphatase 6 gene and the D-loop region and resulted in a 7.4 kb deletion.
T-gamma-lymphoproliferative disorder arising in a background of autoimmune disease and terminating in plasma cell dyscrasia with primary amyloidosis. T-gamma-lymphoproliferative disorder, a syndrome of T-cell lymphocytosis with neutropenia has been described in patients with various autoimmune disorders, especially rheumatoid arthritis. We report a case of T-gamma-lymphoproliferative disorder occurring in a 42-year-old white woman with a long history of dermatitis herpetiformis and subsequent development of Coomb's positive autoimmune hemolytic anemia and polymyositis. The peripheral blood lymphocytes showed the T-suppressor cell phenotype (CD2-, CD3-, CD8-, and CD4-). DNA analysis of the peripheral blood lymphocytes revealed a T-cell receptor beta-chain gene rearrangement and an immunoglobulin heavy-chain gene rearrangement. The patient's course was marked by numerous bouts of infection. The unique factor in this patient was the development of a plasma cell dyscrasia and amyloidosis prior to death.