shukoor65/lab-rag-model huggingface dataset:
Metabolic aspects of protection by glycine against hypoxic injury to isolated proximal tubules. To clarify the roles of butyrate and acylglycine formation in hypoxic proximal tubule cell injury and protection by glycine and to test the contribution of iodoacetate-suppressible metabolism to protection, (1) it was determined whether protection by glycine is fully expressed when glucose, lactate, alanine, and butyrate are replaced by alpha-ketoglutarate as the sole substrate for the tubules, (2) butyrate metabolism and acylglycine formation were directly measured in control and hypoxic preparations, and (3) it was assessed whether injury produced by iodoacetate, a potent inhibitor of glycolytic metabolism, is subject to protection by glycine. Susceptibility to hypoxic injury in medium with alpha-ketoglutarate as the sole substrate was similar to that seen in medium containing glucose, lactate, alanine, and butyrate. Tubules in alpha-ketoglutarate medium showed high degrees of protection by glycine against injury produced by 30-min of hypoxia, by iodoacetate alone, and by iodoacetate combined with hypoxia. Protection did not require preservation of cell ATP or glutathione. In glucose-lactate-alanine-butyrate medium, butyrate, measured by gas chromatography, was rapidly metabolized by oxygenated tubules and fully accounted for basal rates of oxygen consumption. Butyrate utilization stopped during hypoxia. Neither aspect of butyrate metabolism was altered by glycine. Formation of acylglycines was assessed by gas chromatography/mass spectroscopy. In preparations treated with glycine, butyrylglycine was detected under both oxygenated and hypoxic conditions; the quantities, however, were small and no other acylglycines were found. These observations indicate that protective effects of glycine are independent of short-chain acylglycine formation and glycolytic metabolism.
Low serum levels of alpha-interferon, gamma-interferon, and interleukin-2 in alcoholic cirrhosis. The existence of cellular immune deficit in alcoholic cirrhosis, together with the role of alpha- and gamma-interferon and interleukin-2 in the immune system, led us to compare serum levels of these immune system mediators in a group of 40 patients with alcoholic cirrhosis classified according to Child-Pugh's grade of severity of liver disease and 23 healthy volunteers. Serum levels of alpha-IFN, gamma-IFN, and IL-2 were significantly depressed in alcoholic cirrhotics, with no significant differences between the different degrees of hepatic damage. The results suggest a profound alteration in the immune system of alcoholic cirrhotics, which may contribute to the development of the disease and the accompanying immune system deficit.
Antithrombotic therapy for deep arterial injury by angioplasty. Efficacy of common platelet inhibition compared with thrombin inhibition in pigs. BACKGROUND. Platelet-thrombus formation is a complication of arterial wall deep injury by balloon angioplasty that may lead to acute arterial occlusion and may contribute to restenosis. METHODS AND RESULTS. Because common platelet-inhibitor drugs with a heparin bolus (100 units/kg) may be effective in inhibiting platelet-thrombus formation after arterial angioplasty, these were compared with a bolus of heparin alone (control), the specific thrombin inhibitor hirudin (1.0 mg/kg), and saline (hirudin control) in normal pigs after angioplasty of the common carotid arteries. In the presence of deep arterial wall injury (injury exposing the media), indium-111-labeled platelet deposition (x 10(6)/cm2) was 68.8 +/- 12.3 and 48.1 +/- 16.9 in the control animals. This was significantly reduced by pretreatment with low-dose aspirin (1 mg/kg/day), by high-dose aspirin (20 mg/kg/day) plus dipyridamole, and especially by thrombin inhibition with hirudin. Treatment regimens with aspirin alone (20 mg/kg/day), dipyridamole alone, or sulfinpyrazone were ineffective. Likewise, the incidence of mural thrombosis was 75% and 80% in deeply injured arteries of controls and was significantly reduced to 46% with aspirin plus dipyridamole, 25% with low-dose aspirin, and 0% with hirudin. The incidence of mural thrombosis was unchanged with high-dose aspirin (69%), dipyridamole (90%), or sulfinpyrazone (92%). This mural thrombosis could not be identified by angiography. In the presence of mild injury (deendothelialization), platelet deposition was low (less than 10 x 10(6)/cm2, a single layer) and was not changed by any therapy, including hirudin. CONCLUSIONS. These therapies do not affect platelet adhesion to deeply or mildly injured artery. These data suggest a greater role for thrombin inhibition than with thromboxane or cyclooxygenase inhibition in the pathogenesis of platelet-rich mural thrombosis after deep injury during angioplasty. Antithrombotic therapy for arterial thrombosis by thrombin inhibition appears promising.
Dual effects of N-ethylmaleimide on ethanol-induced gastric lesions in rats. The effects of N-ethylmaleimide (NEM), a sulfhydryl (SH) blocker, on ethanol-induced gastric lesions were investigated in rats by varying the route of administration. Oral administration of acidified ethanol (60% ethanol in 150 mM HCl, 1 ml) produced hemorrhagic bandlike lesions in the gastric mucosa. Pretreatment of the animals with orally administered NEM (0.1-10 mg/kg) dose-dependently inhibited these lesions (the inhibition was over 80% at 1 mg/kg or greater), and the effects were partially reversed by indomethacin (5 mg/kg, subcutaneous). However, when NEM (10 mg/kg) was given subcutaneously, this agent significantly worsened the lesions. Intragastrically applied NEM produced a dose-dependent reduction of the transmucosal potential difference (PD) and the mucosal nonprotein SH levels, an increase of the volume of gastric contents, and an inhibition of gastric motility, while these parameters remained unaltered after subcutaneous administration of the agent. The microvascular permeability in the mucosa was significantly increased by both oral and subcutaneous administration of NEM (10 mg/kg) but remained unchanged in response to lower doses of orally administered (less than 3 mg/kg). These results suggest that NEM given orally is cytoprotective to the stomach against ethanol, probably by acting as a mild irritant and due to dilution of an irritant and inhibition of gastric motility (muscle relaxation), but when given subcutaneously it aggravates the lesions by unknown mechanisms.
Salmonella meningitis and infection with HIV. Patients infected with HIV demonstrate increased susceptibility to serious infections with non-typhoidal salmonellae. However, no cases of salmonella meningitis have been reported in this population. We now report three cases of salmonella meningitis which occurred in a population of 1800 patients with AIDS or AIDS-related complex at our hospitals. The incidence of meningitis complicating salmonella infection in our HIV-infected population appears to be much higher than that reported in non-AIDS patients (7.5 versus 0.15%). All had cerebrospinal fluid parameters consistent with bacterial meningitis, and two of three revealed organisms on cerebrospinal fluid Gram stain. Two presented with a fulminant illness and died despite therapy; the third developed a brain abscess associated with a relapse of meningitis. Salmonella meningitis should be considered as a cause of acute neurological deterioration in patients at risk for HIV-related disease. Relapses may occur, and mortality is high.
Early and late geometric changes after carotid endarterectomy patch reconstruction. This study examines the degree and location of vessel wall geometric changes after carotid endarterectomy-vein patch reconstruction. The external diameters of the proximal common carotid, common carotid bulb, and internal carotid arteries were measured during operation with a caliper after 349 carotid endarterectomies. There were 309 saphenous vein reconstructions, 31 synthetic patch reconstructions, and 9 primary closures. One or more B-mode ultrasound studies with cross-sectional views for common and internal carotid cursor measurements were performed from 3 months to 5 years after operation. The intraoperative-to-postoperative common carotid diameters were unchanged for the three types of reconstructions. The internal carotid diameters increased 20% to 30% for both the vein and synthetic patched arteries. This dilation was present at 3 and 6 months and progressed slightly over 5 years. Wall thickening greater than or equal to 1 mm was present in 62% of the carotid endarterectomies, with concentric stenosis in 3% and eccentric stenosis in 59%. Eccentric stenosis was present at 3 to 6 months, located on the endarterectomized posterior-medial wall of the common and internal carotid arteries, was always less than 50%, and changed very little over 5 years. No aneurysms or internal carotid occlusions were identified. Carotid endarterectomy-vein patch reconstruction results in early, mild, nonaneurysmal dilation of the internal carotid patched segment, frequent mild eccentric restenosis, and rare hemodynamically significant concentric restenosis.
Gastroesophageal reflux in the older child: presentation, response to treatment and long-term follow-up. Much attention has been focused on the natural history of gastroesophageal reflux (GER) in neurologically normal infants which generally resolves by two years of age. In contrast, little is known of the outcome of GER diagnosed in normal older children. The charts of 32 children (21 males) without neurologic or esophageal anatomic abnormalities, age 3.5 to 16 years (mean = 9.8) at the time of diagnosis, were reviewed. Diagnosis was based on suggestive presenting symptoms and evaluation of prolonged intraesophageal pH monitoring. Esophagitis was diagnosed by histologic criteria in 16 of the 32 patients. Medical treatment consisted of prokinetic agents (metoclopramide, bethanechol) and H2-receptor antagonists. After a one to eight year follow-up period (mean +/- SD - 3.4 +/- 2.1), the symptoms in 13 children had resolved or were sufficiently improved to discontinue medication. In 13 patients, symptoms were improved but medication was required for adequate control. Four children were symptomatic without improvement in spite of medical therapy and two others required fundoplication for continued severe symptoms and refractory esophagitis. In summary, less than 50% of otherwise normal older children with GER undergo spontaneous resolution of marked improvement in symptoms and the remainder require continued long-term medical and/or surgical management.
Neurofibrillary tangles in dementia pugilistica are ubiquitinated. Ubiquitin, a protein thought to be involved in the ATP-dependent non-lysosomal degradation of abnormal proteins, has already been identified as a component of neurofibrillary tangles in Alzheimer's disease. We have examined ubiquitin immunoreactivity in a unique collection of brains from 16 ex-boxers including 11 with dementia pugilistica. Neurofibrillary tangles of dementia pugilistica were labelled with an affinity purified antiserum to ubiquitin, and BF10, a monoclonal antibody to a neurofilament epitope.
Information and referral service usage among caregivers for dementia patients. Questionnaires were mailed to 257 callers of a toll-free telephone "helpline" specializing in Alzheimer's disease and related dementing illnesses; 125 (48.6%) were completed and returned. On the average, 3.94 requests for information were made per call. The most common requests concerned services delivered to the home, general information about dementia, information about adult day care, and support group information. Results indicated that a telephone-based information and referral helpline is useful in disseminating knowledge about resources to caregivers of older community-residing adults with cognitive impairment.
Pyoderma gangrenosum associated with systemic lupus erythematosus: response to pulse steroid therapy. Pyoderma gangrenosum in a 35-year-old woman with long-standing systemic lupus erythematosus was treated with pulse steroid therapy. Significant improvement in the ulceration and control of the lupus erythematosus occurred. The unusual association of these disorders is reviewed, and the efficacy of pulse therapy in the treatment of refractory cases of pyoderma gangrenosum is discussed.
Magnetic resonance imaging signs of optic nerve gliomas in neurofibromatosis 1. We reviewed the magnetic resonance images of four children with neurofibromatosis 1 and orbital optic gliomas. The images showed double-intensity tubular thickening characteristic of perineural arachnoidal gliomatosis, elongation of the nerves, and downward kinking of the nerves in the midorbit. We believe these findings typify the orbital gliomas in patients with this disease.
Importance of histologic condition and treatment of pediatric cerebellar astrocytoma. Histologic classification and treatment of pediatric cerebellar astrocytomas is an area of controversy. At the Medical College of Wisconsin, 34 patients less than 15 years of age (median, 7.3 years of age) with cerebellar astrocytomas were seen from 1965 to 1988. Effect of histologic condition and treatment on overall survival (OS) and progression-free survival (PFS) was analyzed. Progression was defined as radiographic evidence of an enlarging mass and/or signs and symptoms indicative of advancing disease. Histologic material was reviewed and classified by the system of Winston and Gilles. Twenty-eight patients had glioma A tumors, and six patients had glioma B tumors. For patients with glioma A (n = 28), 5-year actuarial OS rate was 100%. For patients with glioma B (n = 6), 5-year actuarial OS rate was 41%. PFS rate was 66% and 0% for patients with glioma A and glioma B, respectively. The poorer PFS for patients with B histologic tumors was statistically significant (P less than 0.001). The median time to progression was 36 months and 23 months for patients with glioma A and B, respectively. Patients were retrospectively divided into total resection and observation, total resection and irradiation, subtotal resection and observation, and subtotal resection and irradiation groups, which were composed of 12, 2, 3, and 17 patients, respectively. Five-year actuarial OS rates were 100%, 50%, 50%, and 100%, respectively. PFS rates were 60%, 50%, 33% and 58%, respectively. These data support the Gilles classification as a prognostic tool because patients with B tumors had a higher incidence of disease progression and accounted for all deaths. Postoperative irradiation after subtotal resection seems to be beneficial, but additional investigation, ideally with a prospective randomized trial, will be necessary to firmly establish this.
One gram of aspirin per day does not reduce risk of hospitalization for gallstone disease. Data from 4524 patients in a randomized, controlled trial of aspirin were analyzed to determine if aspirin reduced the risk for hospitalization for gallstone disease. Aspirin at a dose of 1000 mg/day did not reduce the risk of hospitalization for gallstones. Hospitalization rates for gallstone disease were consistent with national rates, and the data confirmed previous associations of gallstone disease with age, elevated serum triglycerides, obesity, and female gender.
Retrograde coronary venous administration of recombinant tissue-type plasminogen activator: a unique and effective approach to coronary artery thrombolysis. Recent studies of interventional therapy by way of the coronary venous system have demonstrated that it can protect acutely ischemic myocardium. To evaluate the efficacy of coronary venous retroinfusion compared with systemic intravenous administration of recombinant tissue-type plasminogen activator (rt-PA), 14 dogs were studied with a copper coil-induced thrombus in the left anterior descending coronary artery. The rt-PA (24,000 fluorescence units/kg) was administered continuously, either intravenously (n = 8) or retrogradely (n = 6), for 30 min beginning 60 min after coronary occlusion. Thrombolysis was determined by repetitive coronary angiography. All dogs were killed 3 h after termination of rt-PA infusion and infarct size was measured by the triphenyltetrazolium chloride staining technique. Complete thrombolysis occurred in five of the six dogs in the retroinfusion group and four of the eight dogs in the systemic intravenous infusion group. Partial lysis was achieved in two dogs treated by intravenous infusion. Lysis did not occur in one dog treated with retroinfusion and in two dogs treated with intravenous infusion. Time to thrombolysis was 13.4 +/- 2.3 min in the retroinfusion group versus 27.8 +/- 4.8 min in the intravenous group (p less than 0.001). Myocardial functional recovery in the ischemic zone measured by two-dimensional echocardiography 60 min after reperfusion was significant only in the retroinfusion group (p less than 0.05).
Conventional versus thrombolytic therapy in spontaneous (effort) axillary-subclavian vein thrombosis. Effort axillary-subclavian vein thrombosis in young patients has produced long-term disability because of the failure of the thrombosed vein to recanalize. Ten consecutive patients treated in our institution were analyzed. All patients were diagnosed by venography. Four patients received thrombolytic therapy. Three of these had complete resolution and one had partial resolution of the symptoms and thrombus, that was confirmed by venography and duplex imaging. The remaining six patients were treated with conventional anticoagulant therapy. Three of these patients had no resolution, one had complete resolution of both symptoms and thrombus, and two had only partial resolution of symptoms but no resolution of thrombus. Thrombolytic therapy appears to be superior to anticoagulation in the dissolution of symptoms in effort vein thrombosis and should be considered in its management if the diagnosis is made early.
Reduction of central nervous system ischemic injury by monoclonal antibody to intercellular adhesion molecule. Activated leukocytes appear to be directly involved in potentiating ischemic central nervous system (CNS) injury. Adhesion of leukocytes to endothelium is essential for their migration and requires the binding of adhesion receptors of the leukocyte (CD 18) to an intercellular adhesion molecule (ICAM) on endothelium. Monoclonal antibodies to an ICAM can block leukocyte adhesion and transendothelial migration. To determine the efficacy of anti-ICAM antibody treatment in preserving neurological function after CNS ischemia, two animal models were used. A 1-mg/kg dose of anti-ICAM was given to rabbits 30 minutes before induction of ischemia either in the spinal cord using temporary aortic occlusion or in the brain using intra-arterial microspheres. In this study, treatment with anti-ICAM produced a significant reduction in neurological deficits in the reversible spinal cord ischemia model but not in the irreversible brain ischemia model. This protective effect supports the active role of leukocytes in CNS reperfusion ischemic injury and offers potential for future therapy.
Renal colic. Utility of the plain abdominal roentgenogram. We conducted a retrospective cohort study of 85 consecutive symptomatic patients to evaluate the sensitivity, specificity, and predictive value of plain abdominal roentgenography (PAR) compared with clinical evaluation alone in diagnosis and treatment of renal colic. With a positive intravenous pyelogram and/or actual stone retrieval used as the gold standard, 72 patients had documented stones. The calculated sensitivity and specificity for PAR were 58% (95% confidence interval, 47% to 69%) and 69% (95% confidence interval, 44% to 94%), respectively. In this population with a stone prevalence of 85%, the positive predictive value of PAR was 91%. A clinical scoring system based on signs and symptoms fared as well as PAR (sensitivity, 73%; specificity, 46%; and positive predictive value, 88%). The strategy of clinical scoring followed by selective use of intravenous pyelography was more cost-effective than strategies using PAR. We conclude that the PAR has low sensitivity and specificity and improves the predictive value only marginally, and its routine use is not cost-effective.
Rapidly progressive acute retinal necrosis secondary to herpes simplex virus, type 1. A systemically healthy 22-year-old man presented with unilateral acute retinal necrosis (ARN) that featured diffuse retinal whitening throughout the posterior retina, exudative retinal detachment, and a visual acuity of no light perception. Diagnostic vitrectomy revealed necrotic retinal cells containing intranuclear inclusions visible with light microscopy. On electron microscopy, viral particles consistent with a herpes family virus were detected. Culture of the vitrectomy specimen showed herpes simplex, type 1 (HSV 1) and rising convalescent serum ELISA titers to HSV 1 confirmed a recent infection. This case of ARN is unusual for its severity, early macular involvement, and development of exudative retinal detachment. In addition, it represents one of the few reported cases in which HSV 1 has been confirmed by both vitreous culture and serum titers as the etiologic agent. A review of the literature suggests that posterior segment inflammatory conditions secondary to HSV 1 can be associated with exudative retinal detachment, a clinical finding that may help differentiate such conditions from other infectious causes of chorioretinitis.
Choleriform syndrome and production of labile enterotoxin (CT/LT1)-like antigen by species of Salmonella infantis and Salmonella haardt isolated from the same patient. Isolates of Salmonella infantis from the stool and blood and an isolate of Salmonella haardt from the stool of a patient with choleriform diarrhea produced labile enterotoxin (CT/LT1)-like antigen. Genetic and molecular experiments indicated that the production of CT/LT1-like antigen was chromosomally encoded.
Eosinophil activation on biologic surfaces. Production of O2- in response to physiologic soluble stimuli is differentially modulated by extracellular matrix components and endothelial cells. Production of O2- in response to FMLP, TNF, IFN-gamma, platelet activating factor, LPS, substance P, and PMA by human eosinophils in suspension and in contact with polystyrene ELISA plastic (PL) or biologic surfaces was studied. Monolayers of human endothelial cells (HEC) or PL coated with FCS, fibronectin, laminin, collagen types I and IV, fibrinogen, or fibrin were used as biologic surfaces. Only PMA and FMLP stimulated O2- generation by eosinophils in suspension. Eosinophils residing on HEC monolayers, either untreated or treated with LPS, were unresponsive to all stimuli except PMA. PMA induced O2- generation by eosinophils on all surfaces; FMLP on all surfaces but HEC monolayers; TNF and platelet-activating factor only on PL, fibrinogen, and fibrin; LPS and substance P only on PL. PMA was equally effective on eosinophils on surfaces and in suspension, whereas the effect of FMLP was greater on eosinophils on surfaces than on eosinophils in suspension. IFN-gamma was ineffective on any of the surfaces tested. These results indicate that biologic surfaces may profoundly affect the ability of eosinophils to respond with a respiratory burst to physiologically relevant soluble stimuli, the effect varying according to the nature of both the stimulus and the surface. Since the respiratory burst generates products of oxygen reduction that are toxic to several tissue components, it follows that biologic surfaces may modulate eosinophil-induced tissue injury.