shukoor65/lab-rag-model huggingface dataset:
Human acid maltase-deficient myogenic cell transformation with origin-defective SV40: characterization of a cloned line. A clonal human skeletal muscle cell line showing acid maltase deficiency (AMD) was established through the transfection of origin-defective SV40 DNA. The low acid alpha-glucosidase activity and glycogenosomes in this clone corresponded to AMD. This clone, in spite of loading glycogenososmes, was competent not only as to proliferation without contact inhibition but also as to myogenic differentiation to some extent. Dexamethasone promoted the formation by the transformant of multinucleated myotubes, which expressed acetylcholine receptors. The existence of glycogenosomes did not seem to affect the proliferation or differentiation of myoblasts. The aberrant acid alpha-glucosidase expressed in the transformed myogenic clone was shown to be biochemically identical to that in AMD fibroblasts. This transformant should be of great value for investigating the pathogenesis of AMD because of the possibility of supplying semi-permanently a uniform myogenic cell line expressing AMD.
Late onset Krabbe's leukodystrophy: a report of four cases. Four cases of late-onset Krabbe's leukodystrophy had varying clinical features. One sibling became wheelchair-bound while another leads an active working life. The computed tomography (CT) scan of a third patient showed occipital demyelination with contrast enhancement identical to that seen in an adrenoleucodystrophy. The fourth was the only patient with peripheral neuropathy. All patients had enzyme activity comparable to the classic infantile-onset form.
MIDAS, the Multicenter Isradipine/Diuretic Atherosclerosis Study. Design features and baseline data. The Multicenter Isradipine/Diuretic Atherosclerosis Study (MIDAS) is a randomized, double-blind, active-control trial to compare the effectiveness of two treatment regimens for the control of hypertension in reducing the rate of progression of early extracranial carotid artery atherosclerosis in hypertensive patients. The two double-blind treatment regimens are 2.5 or 5 mg isradipine twice daily and 12.5 mg or 25 mg hydrochlorothiazide twice daily. Patients whose blood pressure is not controlled with either of these regimens will receive, in addition to the highest tolerated dose of the blinded drug, 2.5 to 10 mg open-label enalapril twice daily. The MIDAS study has enrolled 883 patients to treatment with either isradipine or hydrochlorothiazide. Inclusion criteria included men and women over the age of 40 years, the presence of an atherosclerotic lesion in the extracranial carotid artery demonstrated on B-mode ultrasound scanning (maximum thickness between 1.3 and 3.5 mm), an average sitting diastolic blood pressure between 90 and 115 mm Hg, and low-density lipoprotein levels between 130 and 189 mg/dL. An assessment of each patient's blood pressure and any side effects is made every three months; a B-mode ultrasound examination of the carotid arteries was performed at baseline and every six months thereafter; an electrocardiogram was carried out at baseline and once a year thereafter; and a brief quality-of-life assessment was made at baseline and every year thereafter.
Abnormal platelet and lymphocyte calcium handling in prehypertensive rats. We have reported that the basal and stimulated cytosolic free calcium concentrations [( Ca2+]i) are elevated in platelets isolated from 12-14-week-old spontaneously hypertensive rats (SHR) as compared with normotensive Wistar-Kyoto (WKY) rats. To determine whether altered cell calcium metabolism precedes the development of overt hypertension, we measured [Ca2+]i under resting and stimulated conditions in blood platelets and thymic lymphocytes isolated from 4-week-old prehypertensive SHR and WKY rats. Blood pressure was similar in both groups (SHR 95 +/- 8 versus WKY rats 92 +/- 7 mm Hg). Basal [Ca2+]i in platelets was higher in SHR than WKY rats (63.4 +/- 3.9 versus 54.8 +/- 3.1 nM, p less than 0.003). Also the [Ca2+]i response to thrombin was greater in SHR than WKY rats in both the presence and absence of extracellular calcium. For lymphocytes, although no difference was detected in basal [Ca2+]i, the concanavalin A-induced peak [Ca2+]i was higher for SHR than WKY rats in both calcium-containing and calcium-free media. These results suggest that agonist-stimulated calcium influx and calcium discharge from intracellular stores are enhanced in both platelets and lymphocytes of 4-week-old SHR. We conclude that abnormalities in calcium metabolism in two different cell types precede the development of overt hypertension in the SHR.
Mutations in the precore region of hepatitis B virus DNA in patients with fulminant and severe hepatitis BACKGROUND. The presence of the hepatitis B e antigen (HBeAg) in serum is known to be a marker of a high degree of viral infectivity. However, fulminant hepatitis may occur in persons who are negative for HBeAg. A single point mutation has been reported to produce a stop codon in the precore region of hepatitis B virus DNA and prevent the formation of the precore protein required to make HBeAg. To determine whether a precore-mutant virus is causally related to severe liver injury, we analyzed the entire precore region in viral strains isolated from patients with fatal cases and uncomplicated cases of hepatitis B. METHODS. Serum was obtained from 9 patients with fatal hepatitis B (5 with fulminant and 4 with severe exacerbations of chronic hepatitis) and 10 patients with acute, self-limited hepatitis B. Serum samples from a sex partner implicated as the source of the virus in one case of fulminant hepatitis were also studied. The 87 nucleotides in the precore region of the hepatitis B virus were amplified by the polymerase chain reaction and then directly sequenced. RESULTS. Of the nine patients with fatal hepatitis, seven had retrievable hepatitis B DNA. In all seven there was a point mutation from G to A at nucleotide 1896 of the precore region, converting tryptophan (TGG) to a stop codon (TAG). In contrast, this mutation was not found in the 10 patients with acute, self-limited hepatitis B. The hepatitis B DNA from the implicated source contained a sequence with the stop-codon mutation that was identical to the sequence in her partner, who had fulminant hepatitis. CONCLUSIONS. The presence of a mutant viral strain is associated with and may be involved in the pathogenesis of fulminant hepatitis B and severe exacerbations of chronic hepatitis B.
The place of oophorectomy at vaginal hysterectomy. A series of 740 vaginal hysterectomies with attempted vaginal oophorectomy is presented and compared with 700 vaginal hysterectomies without oophorectomy. Vaginal oophorectomy was successful in 94% of the patients. Factors influencing the success include obesity, nulliparity, decreased vaginal access and space, lack of uterine descent, increased uterine size and tubo-ovarian disease. These have been analysed and the recognition and management of technical difficulties are described. There was no morbidity attributable to the vaginal oophorectomy. With experience and appropriate technique suitable women can be offered prophylactic oophorectomy at the time of vaginal hysterectomy.
Hemostasis activation during esophageal variceal sclerotherapy with thrombin in cirrhotics. Sclerotherapy of bleeding esophageal varices in liver cirrhotics is a common procedure, but little is known about the possible entry of sclerosants into the systemic circulation. We injected a mixture of thrombin, sodium tetradecyl, and cefazolin and studied the effect of this sclerosant on selected hemostasis parameters. Twenty-four patients with liver cirrhosis (Child's Classification C) were studied 29 times. Blood samples were drawn before and immediately after the injection of the sclerosant. In seven patients we collected a sample 30 minutes and 24 hours after treatment. Before injection, almost all patients had elevated D-dimer, t-PA and PAI-1 levels. Fibrinogen, antithrombin, alpha-2 antiplasmin, and protein C were decreased. Only thrombin/antithrombin III complex (TAT) levels were within normal ranges. Immediately after the injection, TAT, D-dimer, and t-PA levels rose significantly (P less than 0.001, P less than 0.01, P less than 0.001), PAI-1 and PC levels decreased (P less than 0.01), while antithrombin, alpha-2 antiplasmin, and fibrinogen concentrations were unchanged. TAT and D-dimer levels were still elevated after 24 hours (P less than 0.05). These data indicate that thrombin entered the systemic circulation (elevated TAT) and that the hemostasis system was briefly systemically activated (elevated D-dimer). In spite of these changes in the hemostasis system, clinically there were no detectable thrombotic or hemorrhagic complications.
5-HT3 receptor antagonists and migraine therapy. Neuronal 5-hydroxytryptamine3 (5-HT3) receptors mediate the excitatory effects of 5-HT. They are located in pain- and nausea-modulating areas in the central nervous system and on C-fibre primary afferents in the peripheral nervous system. Consequently, these receptors mediate the painful and emetic effects of 5-HT. Selective and potent 5-HT3 receptor antagonists have been shown to block inflammatory and 5-HT induced and potentiated "vascular pain". Based on the hypothesis that 5-HT3 receptor antagonists may block neurogenic dural inflammation in the distribution area of the trigeminal nerve and, thus, could potentially prevent migraine (pain), four highly selective and potent 5-HT3 receptor antagonists have been tested in both the acute and prophylactic treatment of migraine. Unfortunately, except for a clear anti-emetic effect, none of these drugs has shown unequivocal efficacy in the treatment of migraine. This may be partly due to the complex (bell-shaped) dose-response relationship of these compounds, making exact titration of the correct dose difficult. Moreover, most 5-HT3 receptor antagonists have proved to be toxic in man on chronic administration thereby preventing further trials in migraine with adjusted doses. Short-term treatment for cytotoxic drug-induced emesis so far appears to be the only proven indication for 5-HT3 receptor antagonists.
Closure of tracheocutaneous fistula with perichondrial flap following cricothyroidotomy. A method for closure of large tracheocutaneous fistulas occurring in the cricothyroid membrane is described. Though an infrequent complication, large defects in this area can be successfully repaired with this technique.
Chemotherapy with high dose ifosfamide/mesna plus cisplatin for the treatment of ovarian cancer: a study of the Grupo de Estudio y Tratamiento Latino-Americano del Cancer. Twenty-one evaluable patients with FIGO stages II-IV epithelial ovarian cancer, median age 57 (range 47-75 years), were treated with ifosfamide (IF), 3 g/m2 diluted in 500 ml saline solution, 8 hour intravenous (i.v.) infusion on days 1-5; mesna 20% of IF dose, i.v. bolus injection, was given at hours 0 and 4; mesna 40% of IF dose by oral route at hours 8 and 12, days 1-5; plus cisplatin 20 mg/m2 diluted in 500 ml saline solution, 2 hour i.v. infusion, days 1-5. Cycles were repeated every 4 weeks. All patients had metastatic lesions (mesentery, pleura, colon, cervix, abdominal wall, lung, liver, bladder, and nodes). Toxicity ranged from mild to moderate. All patients experienced alopecia, nausea, and vomiting. Neutropenia and anemia ranged from mild to moderate. One patient experienced mild brain confusion and two patients microscopic hematuria. Ten clinically complete responses (47%) and five clinically partial responses (23%) were registered, for an overall 70% objective response. However, after a second look performance in 10 patients with clinically complete response, six of 10 patients showed a pathological complete response and four showed pathological partial response. The median duration of complete response is about 33 months, and median partial response duration is 14 months. Although the numbers are small, these data indicate that combination chemotherapy with high dose ifosfamide/mesna plus cisplatin may be an active treatment for advanced ovarian carcinoma.
Glucose uptake, perfusion, and cell proliferation in head and neck tumors: relation of positron emission tomography to flow cytometry The uptake of 18F-Deoxyglucose (FDG) was studied in vivo in relation to the proliferation rate of human head and neck tumors. Forty-two patients with histologically proven squamous-cell carcinoma of the head and neck and four patients with metastases of head and neck tumors were examined with PET and FDG prior to surgery. In 35 of these patients, a flow cytometric analysis of the DNA content and the proliferation rate was done using one-dimensional flow cytometry rate was done using one-dimensional flow cytometry (DAPI staining). In 17 cases, perfusion studies with 15O-labeled water were performed. Twenty-seven specimens were evaluable by flow cytometry. The analysis of the distribution of the FDG uptake revealed two groups, showing a high and a lower uptake pattern. In both groups the FDG uptake and the proliferation rate were correlated with an r-value of 0.64 and 0.8 respectively. However, the slope of the regression function was flat. No correlation was found between the perfusion and the proliferation rate. It is suggested that these differences in uptake in histologically identical tumor populations may correspond to differences at the molecular level, e.g., differences in the amount of the glucose carrier, perhaps caused by oncogenic transformation.
Systemic neurohumoral activation and vasoconstriction during pacing-induced acute myocardial ischemia in patients with stable angina pectoris. To identify the effect of myocardial ischemia on systemic neurohormones and vascular resistance, 32 untreated, normotensive patients with coronary artery disease underwent incremental atrial pacing until angina. Arterial and coronary venous lactate and arterial values of catecholamines and angiotensin II were determined at control, at maximal pacing rates, and at 1, 2, 5 and 30 minutes after pacing. Based on pacing-induced ST-segment depression (greater than or equal to 0.1 mV) or myocardial lactate production, or both, patients were selected as ischemic (n = 25) or nonischemic (n = 7). Baseline clinical and hemodynamic data were comparable. During pacing, chest pain was similar (20 ischemic vs 7 nonischemic patients). Also, hemodynamic measurements were comparable, except for contractility, which did not improve, and left ventricular end-diastolic pressure, which significantly increased in ischemic patients. Moreover, during ischemia arterial pressures increased significantly (13%) and systemic resistance increased from 1,470 +/- 60 (control) to 1,632 +/- 76 dynes.s.cm-5 5 minutes after pacing (p less than 0.05) in ischemic but not in nonischemic patients. Pacing did not affect neurohormones in nonischemic patients. In contrast, norepinephrine in ischemic patients increased significantly from 1.7 +/- 0.2 (control) to 2.6 +/- 0.3 (maximal pacing) and to 3.0 +/- 0.4 nmol/liter (1 minute after pacing), whereas angiotensin II levels increased from 6.2 +/- 1.4 (control) to 9.3 +/- 2.1 pmol/liter (1 minute after pacing, p less than 0.05). Epinephrine only increased during maximal rates (0.9 +/- 0.1 vs 0.6 +/- 0.1 nmol/liter at control, p less than 0.05). Thus, myocardial ischemia activates circulating catecholamines and angiotensin II, accompanied by systemic vasoconstriction.
Cigarette smoking and other vascular risk factors in vasculogenic impotence. A total of 132 consecutive patients with erectile impotence underwent extensive evaluation, including vascular evaluation with intracavernous injection of papaverine and penile duplex ultrasonography, to determine the etiology of impotence. Three vascular risk factors, smoking, diabetes mellitus and hypertension, were investigated for their impact on vasculogenic impotence. The patients were divided into four groups: one with no risk factors, one with one vascular risk factor, one with two vascular risk factors, and one with all three risk factors. The results of penile vascular evaluation in these patient groups were compared. The incidence of penile vascular impairment was found to be higher in patients with one vascular risk factor than in those with none. The proportion of abnormal penile vascular findings significantly increased as the number of risk factors increased. These data confirm the important role of vascular risk factors, smoking, diabetes mellitus, and hypertension, in the pathogenesis of organic impotence.
Failure of centralization of the fibula for congenital longitudinal deficiency of the tibia. Between 1962 and 1983, fourteen patients (twenty knees) had centralization of the fibula for congenital longitudinal deficiency: tibial, complete. Eleven of the twenty index procedures were performed on patients who were one year old or less. A progressive flexion deformity of the knee developed after all twenty index procedures. Twenty-six secondary procedures were needed, including disarticulation at the knee, posterior release, extension osteotomy, femorofibular arthrodesis, and biceps-to-quadriceps transfer, and one patient had a second attempt at centralization of the fibula. The duration of follow-up after the initial centralization of the fibula ranged from four years to twenty-two years and seven months (average, twelve years and four months). Seven patients (eight limbs) in whom the index procedure resulted in failure had a satisfactory result after disarticulation at the knee. The patients who did not have secondary disarticulation at the knee are also considered to have had a failed index procedure because they had a flexion deformity at the latest follow-up. Attempts to reconstruct the knee joint by centralization of the fibula are not warranted for patients who have congenital longitudinal deficiency: tibial, complete. Early disarticulation at the knee and fitting with a prosthesis, with close follow-up, is the treatment of choice.
Effects of a sodium-potassium ion-exchanging seaweed preparation in mild hypertension. A nonpharmacological approach in the treatment of mild hypertension is often advocated. In an attempt to decrease sodium and increase potassium intake, sixty-two middle-aged patients with mild hypertension were given a potassium loaded ion-exchanging sodium-adsorbing potassium-releasing seaweed preparation (seaweed fiber, SF). The mean blood pressure (MBP), evaluated in a double-blind crossover manner with four weeks familiarization and wash-out periods, showed a significant decrease after four weeks on 12 and 24 g/day SF but not on 6 g/day or placebo treatment. Systolic blood pressure during submaximal exercise decreased on all three SF doses. The decrease in MBP appeared to be significantly higher in sodium-sensitive (11.2 mm Hg, P less than .001) than in sodium-insensitive (5.7 mm Hg, P less than .05) patients and was in salt-sensitive patients significantly correlated to the increase in plasma renin activity (PRA). The urinary sodium excretion decreased, the urinary potassium increased and the sodium/potassium urinary excretion ratio decreased, indicating that the decrease of MBP was dependent on the decreased intestinal absorption of sodium and increased absorption of potassium released from the seaweed preparation. A sodium-potassium ion-exchanging seaweed preparation is an effective means of decreasing sodium and increasing potassium intake, and may be used for antihypertensive treatment in mild hypertension.
Simulation of high-resolution QRS complex using a ventricular model with a fractal conduction system. Effects of ischemia on high-frequency QRS potentials. Recent studies have analyzed the high-fidelity surface electrocardiographic signal, and efforts have been made to increase the diagnostic sensitivity of the electrocardiogram by observing its high-frequency components. It was found that the high-frequency (150-250-Hz) electrocardiogram appears to detect evidence of transient ischemia with greater sensitivity than visual inspection of the surface electrocardiogram. A finite-element three-dimensional model of the ventricles with a self-similar (fractal) conduction system has been introduced as a bridge to the understanding of electrocardiographic phenomena related to high-frequency potentials. The model was activated, and the dipole potential generated by adjacent activated and resting cells was calculated to obtain a high-resolution QRS complex. Normal and ischemic activation processes was stimulated by regional reduction in conduction velocity. It was found that although the resulted low-frequency QRS complex was not significantly altered from normal conditions, the high-frequency components exhibited morphological changes similar to the ones observed during animal experiments and human studies. Based on the results obtained from the model, it can be concluded that these morphological changes can be attributed to a slowing of conduction velocity in the region of ischemia and that the model is adequate for meeting the challenges imposed by the requirements of high-frequency methods applied in clinical cardiology.
Recurring catamenial pneumothorax treated with a Gn-RH analogue. We report a case of recurring catamenial pneumothorax with concurrent pelvic endometriosis. Thoracoscopy revealed a blue-like lesion on top of the dome of the right hemidiaphragm. Microscopic examination of biopsy specimens showed endometriosis. The patient was treated with a Gn-RH analogue and remains well without further evidence of pneumothorax after six months.
Cerebral circulation: humoral regulation and effects of chronic hypertension. New concepts have emerged in recent years concerning regulation of cerebral circulation. The purpose of this review is to summarize briefly several of these concepts. First, humoral mechanisms may have important effects on cerebral blood vessels and blood flow to choroid plexus. Recent evidence suggests that several vasoactive peptides may have major effects on fluid and ion balance in the brain by altering blood flow to the choroid plexus and possibly the production of cerebrospinal fluid. Second, chronic hypertension produces structural remodeling and hypertrophy of cerebral blood vessels and a shift in the relationship of cerebral blood flow to systemic blood pressure. Third, endothelium-dependent responses of cerebral arterioles to receptor and nonreceptor mediated agonists are impaired during chronic hypertension. Alterations in endothelium-dependent responses of cerebral arterioles during chronic hypertension appears to be due to release of an endothelium-derived contracting factor.
Ischemic necrosis: a hypothesis to explain the pathogenesis of spontaneously ruptured enterocystoplasty. Spontaneous enterocystoplasty rupture represents a devastating and potentially fatal late complication. Previously proposed mechanisms of rupture include catheter trauma, chronic infection, avulsion of adhesions between the bowel patch and peritoneum, and chronic overdistension with elevated intravesical pressures. We have witnessed this complication 4 times in 3 patients 5 weeks to 46 months postoperatively. Tissue specimens from 3 episodes in 2 patients with detubularized sigmoid enterocystoplasties were available for histological examination. All patients had a neurogenic bladder from myelomeningocele, all had an AMS800 artificial urinary sphincter and all had a documented history of chronic distension from inadequate emptying of the augmented bladder. At exploration, all of the ruptures were found within the bowel segment near the bladder apex in an area remote from the anastomotic line. In each case tissue specimens from the rupture site showed marked vascular congestion, intramural hemorrhage, abundant hemosiderin laden macrophages, myofiber atrophy and intravascular thrombi. These features are interpreted to reflect the sequelae of vascular compromise and ischemia. We propose that enterocystoplasty rupture results from ischemia, possibly due to chronic overdistension and subsequent vascular compromise. This mechanism may account for many of the previously reported cases of enterocystoplasty rupture.