shukoor65/lab-rag-model huggingface dataset:
Human insulin and awareness of acute hypoglycaemic symptoms in insulin-dependent diabetes. Some insulin-dependent diabetic patients who have clear symptoms of hypoglycaemia during animal insulin treatment have reported loss of these symptoms when human insulin preparations are introduced. A survey of Mersey Region, UK, identified eleven patients whose awareness of hypoglycaemia was lost after introduction of human insulin but returned with animal insulin treatment; seven took part in the study. Acute hypoglycaemia was induced in these patients on two occasions by intravenous infusion of porcine or human soluble insulin (2.5 mU.kg-1, min-1) in random order. There was no significant difference between porcine and soluble insulin in the plasma glucose profile; mean (SEM) plasma glucose fell from 7.1 (0.4) mmol/l to a nadir of 1.5 (0.1) mmol/l with porcine insulin and from 7.1 (0.5) mmol/l to 1.6 (0.2) mmol/l with human insulin. An acute autonomic reaction occurred in all seven patients, at a similar plasma glucose concentration (1.9 [0.1] mmol/l with porcine insulin; 2.0 [0.2] mmol/l with human insulin). There were no significant differences in the frequency of symptoms or signs of hypoglycaemia between the two insulin species, nor any consistent differences in plasma glucagon, cortisol, growth hormone, adrenaline, or noradrenaline responses to hypoglycaemia. Symptomatic and hormonal responses to acute hypoglycaemia induced by porcine and human soluble insulins therefore seem to be almost indistinguishable, even in patients carefully selected for their apparent loss of hypoglycaemia awareness with human insulin.
Induction of preovulatory luteinizing hormone surge and prevention of ovarian hyperstimulation syndrome by gonadotropin-releasing hormone agonist. OBJECTIVE: To use gonadotropin-releasing hormone agonist (GnRH-a) instead of human chorionic gonadotropin (hCG) to induce oocyte maturation for in vitro fertilization (IVF). DESIGN: Pituitary and ovarian responses to GnRH-a and the outcome of IVF were studied prospectively. Data from patients injected with hCG were analyzed retrospectively. SETTING: Program of IVF at the Rambam (Governmental) Hospital, Haifa, Israel. PATIENTS AND INTERVENTIONS: One or two doses of buserelin acetate 250 to 500 micrograms were administered to six patients with moderate response (Estradiol [E2], 1,494 +/- 422 [+/- SD] pg/mL) and 8 patients with exaggerated response (E2, 7,673 +/- 3,028 pg/mL) to gonadotropin stimulation. Progesterone (P) and E2 were administered for luteal support. MAIN OUTCOME MEASURES: Gonadotropin-releasing hormone agonist effectively triggered luteinizing hormone (LH)/follicle-stimulating hormone (FSH) surge. Mature oocytes were recovered in all patients. Luteal E2 and P were lower than in patients injected with hCG. No signs of ovarian hyperstimulation syndrome were observed. RESULTS: Serum LH and FSH rose over 4 and 12 hours, respectively, and were significantly (P less than 0.05) elevated for 24 hours. Of all mature oocytes, 67% fertilized and 82% cleaved. Four pregnancies were obtained. CONCLUSIONS: A bolus of GnRH-a is able to trigger an adequate midcycle LH/FSH surge, resulting in oocyte maturation and pregnancy. Our preliminary results also suggest that it allows a more accurate control of ovarian steroid levels during the luteal phase and may prevent the clinical manifestation of ovarian hyperstimulation syndrome.
Management of perioperative hypertension using intravenous isradipine. The antihypertensive action of acute intravenous isradipine was investigated during fentanyl/pancuronium/nitrous oxide anesthesia for noncardiac surgery. An intravenous (iv) infusion of 0.5 mg isradipine (n = 10) or placebo (n = 11) was administered double-blind over 5 min if mean arterial pressure (MAP) was greater than 110 mm Hg. The number of patients with a favorable blood pressure reduction (delta MAP greater than or equal to 10% with MAP less than or equal to 110 mm Hg) was 80% with isradipine and 20% with placebo (P less than .05), and the mean MAP reduction from baseline was 26 +/- 12 and 2 +/- 16 mm Hg, respectively (P less than .001). Due to reflex activation of the sympathetic nervous system, the heart rate increased by 14 +/- 12 beats/min with acute iv isradipine. The antihypertensive effect was sustained for 45 min. Isradipine was also well tolerated. It is concluded that intravenous isradipine is an effective antihypertensive agent for the treatment of perioperative hypertension during noncardiac surgery.
Temporal association of CD40 antigen expression with discrete stages of human B-cell ontogeny and the efficacy of anti-CD40 immunotoxins against clonogenic B-lineage acute lymphoblastic leukemia as well as B-lineage non-Hodgkin's lymphoma cells. Detailed immunophenotypic analyses of immunologically classified leukemias and lymphomas showed that CD40 displays an exquisite B-lineage specificity within the human lymphopoietic system. Notably, 82% of B-lineage chronic lymphocytic leukemias (CLLs), 82% of B-lineage hairy cell leukemias (HCLs), 86% of B-lineage non-Hodgkin's lymphomas (NHLs), and 29% of B-lineage acute lymphoblastic leukemias (ALLs) were CD40+. Quantitative analyses of the correlated expression of CD40 and other B-lineage differentiation antigens on fetal lymphoid precursor cells by multiparameter two-color/three-color flow cytometry, combined with analyses of sequential antigen expression on fluorescence-activated cell fluorescence activated cell sorter (FACS) isolated immunologically distinct fetal B-cell precursor subpopulations during in vitro proliferation and differentiation, provided evidence that the acquisition of CD40 antigen in human B-cell ontogeny occurs subsequent to the expression of CD10 and CD19 antigens but before the surface expression of CD20, CD21, CD22, CD24, and surface immunoglobulin M (sIgM). Some leukemic pro-B cells from ALL patients as well as normal pro-B cell clones from fetal livers displaying germline Ig heavy chain genes were CD40+, indicating that the acquisition of CD40 antigen likely precedes the rearrangement of Ig heavy chain genes. CD40+ FACS-sorted malignant cells from B-lineage ALL as well as B-lineage NHL patients were capable of in vitro clonogenic growth, indicating the CD40 antigen is expressed on clonogenic leukemia and lymphoma cells. This hypothesis was confirmed by the ability of an anti-CD40 immunotoxin that we used as an antigen-specific cytotoxic probe to effectively kill clonogenic B-lineage ALL and NHL cells.
The C-terminal half of UvrC protein is sufficient to reconstitute (A)BC excinuclease. The UvrC protein is one of three subunits of the Escherichia coli repair enzyme (A)BC excinuclease. This subunit is thought to have at least one of the active sites for nucleophilic attack on the phosphodiester bonds of damaged DNA. To localize the active site, mutant UvrC proteins were constructed by linker-scanning and deletion mutagenesis. In vivo studies revealed that the C-terminal 314 amino acids of the 610-amino acid UvrC protein were sufficient to confer UV resistance to cells lacking the uvrC gene. The portion of the uvrC gene encoding the C-terminal half of the protein was fused to the 3' end of the E. coli malE gene (which encodes maltose binding protein), and the fusion protein MBP-C314C was purified and characterized. The fusion protein, in combination with UvrA and UvrB subunits, reconstituted the excinuclease activity that incised the eighth phosphodiester bond 5' and the fourth phosphodiester bond 3' to a psoralen-thymine adduct. These results suggest that the C-terminal 314 amino acids of UvrC constitute a functional domain capable of interacting with the UvrB-damaged DNA complex and of inducing the two phosphodiester bond incisions characteristic of (A)BC excinuclease.
Stroke-like episodes in familial mitochondrial encephalomyopathy: clinical and biochemical aspects. Acute episodes of focal neurological dysfunction are a well-recognized complication of the mitochondrial encephalomyopathies. Because of rapid remission, biochemical tests and other diagnostic procedures are mostly performed after the acute phase. We report the case of a patient suffering from mitochondrial disease manifesting primarily with seizures, progressive deafness and dementia, who experienced multiple stroke-like episodes. Other members of the family with evidence of mitochondrial dysfunction are presented briefly. EEG and biochemical findings in the acute stage are correlated with clinical symptoms, showing characteristics distinct from the chronic illness. The possible involvement of dietary factors in the provocation of stroke-like episodes is discussed and regulation of glucose intake suggested as a strategy in the prevention of stroke-like episodes.
Proliferative and antiproliferative effects of interferon-gamma and tumor necrosis factor-alpha on cell lines derived from cervical and ovarian malignancies. Four human cell lines derived from cervical carcinomas (ME-180, SiHa, HT-3, and MS751) and three human cell lines derived from ovarian carcinomas (SK-OV-3, Caov-3, and NIH:OVCAR-3) were analyzed in vitro to determine the effect of recombinant interferon-gamma and recombinant human tumor necrosis factor-alpha on cell growth and survival. The effects of interferon-gamma, tumor necrosis factor-alpha, and both interferon-gamma and tumor necrosis factor-alpha on cell growth were measured after 24 and 72 hours of incubation by the incorporation of chromium 51. The results of this analysis showed that all seven cell lines were resistant to the antiproliferative action of tumor necrosis factor-alpha, that the growth of most cell lines was inhibited by interferon-gamma by 72 hours of incubation, and that after 72 hours of incubation all cell lines demonstrated a synergistic antiproliferative response to the combination of interferon-gamma and tumor necrosis factor-alpha. However, the effects of these cytokines on cell growth were found to differ among cell lines and varied with the concentration and the duration of incubation. The growth of one cell line (Caov-3) was stimulated by both tumor necrosis factor-alpha and interferon-gamma. These results suggest that the clinical effects of these cytokines on the growth of gynecologic cancers may be more complex than previously supposed.
Adrenal activation and the prolactin response to exercise in eumenorrheic and amenorrheic runners. Adrenocorticotropic hormone (ACTH), cortisol, and prolactin responses following maximal and submaximal (40 min at 80% maximal O2 consumption) running were studied in eumenorrheic (ER; n = 8, 29.0 +/- 1.5 yr) and amenorrheic (AR; n = 8, 24.5 +/- 2.0 yr) runners. ER were studied in the early follicular and midluteal phases of the menstrual cycle. Physical, training, and gynecological characteristics were similar, and cardiorespiratory and metabolic responses to the exercises were indistinguishable in the groups. ACTH, cortisol, and prolactin data from the follicular luteal phases in ER were combined for comparison to AR, because no differences were noted between the menstrual phases at rest. Similar preexercise ACTH levels and responses following exercise occurred in both groups, but preexercise cortisol levels were elevated (ER = 293.1 +/- 46.3, AR = 479.6 +/- 42.4 nmol/l) and cortisol responses blunted in AR. Adrenal sensitivity was blunted in AR compared with ER after submaximal (ER = 121.9 +/- 17.4, AR = 51.7 +/- 13.6) and maximal exercise (ER = 27.9 +/- 9.2, AR = 12.1 +/- 3.8). Preexercise prolactin levels were reduced (ER = 16.4 +/- 2.7, AR = 10 +/- 2.3 micrograms/l), and prolactin responses to maximal exercises were blunted in AR, despite high lactate levels (11.4 +/- 0.4 mmol/l). We conclude that 1) control for menstrual phase in ER is important in studies of prolactin responses following exercise but not in studies of ACTH and cortisol responses following exercise, 2) cortisol responses following submaximal and maximal exercise in AR are blunted at the adrenal level, 3) prolactin responses following submaximal and maximal exercise are also blunted in AR, and 4) prolactin responses following exercise may be mediated by adrenal activation.
Squamous carcinoma of the temporal bone: a revised staging. Carcinoma of the middle ear is a difficult tumour to treat. We present ten cases and discuss staging of these tumours. Our results would suggest that a revised staging system may allow better identification of patients that would benefit from surgery whilst sparing some multilating surgery that offers little to improve their quality or quantity of life.
Predictive value of brainstem evoked response in the diagnosis of acoustic neuroma. Predictive value positive is the probability that a positive test result represents a true positive finding. Twenty-six patients with brainstem evoked response findings characteristic of retrocochlear hearing loss were studied. Four acoustic neuromas were diagnosed in this group after radiologic workup. The predictive value in this population was 15%. Statistical considerations are presented.
Development of gastric dysplasia in pernicious anaemia: a clinical and endoscopic follow up study of 80 patients. The development of gastric dysplasia and neoplasia in patients with pernicious anaemia has been evaluated in a prospective clinical and endoscopic follow up study. After initial screening of 80 patients between 1978 and 1980, one patient underwent total gastrectomy for a gastric malignancy and 12 were kept under surveillance and underwent endoscopy at a mean interval of 14 months. In the remaining 67 patients further investigation was attempted six to seven years after the initial investigation. The continuous follow up study identified carcinoids in one patient and an adenoma with severe dysplasia in a further patient. The grade and site of mucosal dysplasia differed from one investigation to the next, but no overall progression was observed. Of the 79 patients, eight had died by the time of the reinvestigation, two of unknown cause and six of causes unrelated to pernicious anaemia. In 38 of the remaining 71 patients, clinical data only were available, with no evidence of new gastric malignancy. In 27 patients it was possible to perform an upper gastrointestinal endoscopy, when no change in the degree of dysplasia was detected. In six patients no follow up information was obtainable. In conclusion, patients with pernicious anaemia should be investigated by upper gastrointestinal endoscopy soon after diagnosis. Polyps should be removed wherever possible. In the presence of severe mucosal dysplasia or polyps that are not removed, frequent reinvestigation should be performed, provided the patient is eligible for gastric surgery. In the remaining patients, follow up endoscopies at about five year intervals would seem sufficient.
A myocutaneous flap for closure of upper arm amputations for uncontrolled axillary tumors. Tumor spread or recurrence in the axilla is usually treated with nodal dissections. At times disease recurrence is uncontrolled, causing significant morbidity including pain, bleeding, lymphedema, and neurologic symptoms. Previously, forequarter amputation has been the treatment for this problem, resulting in a significant cosmetic and functional deficit. This report describes a novel myocutaneous flap that can be used to cover soft tissue defects after major disarticulations of the upper extremity. The deltoid myocutaneous flap has been used to successfully treat three patients with uncontrolled tumors in the axilla and preserve the shoulder structures to lessen the functional deficit.
Relations between heart rate, ischemia, and drug therapy during daily life in patients with coronary artery disease. BACKGROUND. Previous studies have shown that little if any increase in heart rate occurs 1 minute before the onset of ischemia in ambulant patients with coronary artery disease. This study tested the hypothesis that there are characteristic relations between heart rate and ischemia in ambulant patients with coronary artery disease. METHODS AND RESULTS. Twenty-one patients with proven coronary disease demonstrated 212 episodes of ischemia during 504 hours of continuous monitoring of the electrocardiogram. An important increase in heart rate (from 74 +/- 11 to 90 +/- 14 beats/min, p less than 0.001) occurred between 5 and 30 minutes (not 1 minute) before the onset of ischemia. A significantly higher heart rate at onset of ischemia was seen during Bruce protocol exercise testing than during daily life (117 +/- 12 versus 95 +/- 15 beats/min, p less than 0.01). However, when a less-strenuous, but more prolonged, exercise protocol was used in a subgroup of patients (n = 12), ischemia occurred at a heart rate that was significantly lower than during the Bruce protocol (88 +/- 14 versus 103 +/- 15 beats/min, p less than 0.05) and was not significantly different from the threshold heart rate at onset of ischemia during daily life (88 +/- 14 versus 84 +/- 12 beats/min, p = NS). As part of two placebo-controlled trials, treatment with both propranolol and nitroglycerin altered the distribution of ischemic events by heart rate but in opposite directions. Although propranolol largely eliminated events occurring at high (greater than 100 beats/min) and moderate (80-100 beats/min) heart rates, the number of events at low (less than 80 beats/min) heart rates was increased. In contrast, nitroglycerin reduced episodes at low and moderate heart rates only. CONCLUSIONS. Important increases in heart rate occur before the onset of ischemia during daily life, but this increase occurs much earlier than has been reported. Duration of heart rate increase appears to influence the heart rate threshold for ischemia, and this may contribute to the occurrence of ischemia at lower heart rates during daily life than during standard exercise testing. Last, different classes of drugs appear to have characteristic effects on ischemia occurring at different heart rates that may be useful in planning therapy.
The "ultraperipheral" revascularization in arteriosclerotic obstruction of tibial vessels. Experimental study. In arteriosclerotic obstruction of the main tibial arteries, the tibial collateral vessels are usually patent, and about 70% of these arteries are potentially suitable for surgical revascularization. The present study aimed at investigating the practical feasibility of a selective revascularization procedure on these tibial muscular arteries (ultraperipheral revascularization). Six lower limbs amputated at thigh level for arteriosclerotic gangrene with complete obstruction of the main tibial arteries, were studied: the tibial collateral muscular vessels showed patency in 65% of cases. The authors propose a surgical technique for the revascularization of these peripheral vessels with the use of a vascular prosthesis. The "post-operative" angiographic studies showed that revascularization of these peripheral muscular arteries was possible.
Increased prevalence of hereditary metabolic diseases among native Indians in Manitoba and northwestern Ontario. OBJECTIVE: To compare the prevalence of hereditary metabolic diseases in the native and non-native populations of Manitoba and northwestern Ontario. DESIGN: Retrospective analysis. SETTING: Children's Hospital, Winnipeg. PATIENTS: Patients were selected by three methods: laboratory tests designed to screen patients suspected of having a metabolic disease, laboratory investigation of newborn infants with abnormalities detected through screening, and investigation of near relatives of probands with disease. RESULTS: A total of 138 patients with organic acid, amino acid and carbohydrate disorders were seen from 1960 to 1990. Of these, 49 (36%) were native Indians (Algonkian linguistic group). This was in sharp contrast to the proportion of native Indians in the total study population (5.8%). Congenital lactic acidosis due to pyruvate carboxylase deficiency (13 patients), glutaric aciduria type I (14 patients) and primary hyperoxaluria type II (8 patients) were the most common disorders detected. Other rare disorders included glutaric aciduria type II (one patient), 2-hydroxyglutaric aciduria (one patient) and sarcosinemia (one patient). Underreporting, especially of glutaric aciduria type I and hyperoxaluria type II, was likely in the native population. CONCLUSIONS: Hereditary metabolic diseases are greatly overrepresented in the native population of Manitoba and northwestern Ontario. We recommend that native children who present with illnesses involving disturbances of acid-base balance or with neurologic, renal or liver disease of unknown cause by investigated for a possible metabolic disorder.
Plasma catecholamine levels in cyclic antidepressant overdose. Cyclic antidepressant overdose is a major cause of morbidity and mortality in self-poisoned patients. The major cause of mortality with cyclic antidepressant overdose is cardiotoxicity. We determined plasma catecholamine levels in 41 symptomatic acute overdose patients to identify interactions between QRS duration (a marker for cardiotoxicity) and a presumed hyper-adrenergic state. Using a linear multivariable regression analysis, QRS duration correlated with the presence of cyclic antidepressant, plasma norepinephrine levels, the ratio of norepinephrine to epinephrine level, and pulse rate (p less than 0.001, r2 = 0.42). Commensurate physiologic changes were not found in the presence of elevated catecholamine levels in the cyclic antidepressant overdose group. One possible explanation for the blunted systemic response to the elevated catecholamine levels is adrenergic desensitization. Investigation of serial catecholamine levels during cyclic antidepressant overdose may lead to modification of our current theories of cardiotoxicity and therapy.
Diastolic time in diabetes. Impairment of diastolic time during dynamic exercise in type 2 diabetes with retinopathy. To evaluate the effect of microangiopathic complications and autonomic dysfunction on diastolic time (DT) during dynamic exercise, 19 patients with type 2 diabetes and ten normal subjects were studied using ear densitography. All subjects had neither an ischemic electrocardiographic response nor chest pain during maximal treadmill exercise. The DT and heart rate (HR) had an inverse nonlinear relation, and electromechanical systole (QS2) and HR had an inverse linear relation during exercise. When the exercise DT-HR and QS2-HR relations were compared, a significant lengthening of QS2, with a consequent shortening of DT, was observed in diabetic patients with retinopathy, compared to patients without retinopathy and normal subjects (p less than 0.005), while no significant differences were found between diabetic patients without retinopathy and normal subjects; however, there were no significant differences in the exercise DT-HR and QS2-HR relations among diabetic patients with and without autonomic dysfunction and normal subjects. A more prominent abbreviation in the diastolic perfusion time observed in patients with retinopathy would be meaningful because microangiopathy might already have limited subendocardial blood flow. Thus, patients with type 2 diabetes who have retinopathy have a potential risk of aggravation of left ventricular function through the deterioration of myocardial blood flow.