Eeeaar we go again.
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Biomedical subjects
Publications and source records attributed to S Thornton.
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OBJECTIVE: To determine the effect of early labour, maternal analgesia and fetal hypoxia on circulating fetal oxytocin concentrations. DESIGN: Prospective observational study. SETTING: Delivery suite in a District General Hospital. SUBJECTS: Fifty women at term who did not require oxytocin administration or more than one form of analgesia. Study groups: vaginal delivery with (1) no analgesia, (2) pethidine, or (3) epidural analgesia. Caesarean section under regional analgesia (4) prior to, and (5) after the onset of labour. INTERVENTIONS: Samples of blood were collected from the umbilical artery (UA) and umbilical vein (UV) immediately after fetal delivery prior to placental separation or oxytocic administration. MAIN OUTCOME MEASURES: Plasma oxytocin (OT) concentration, umbilical vein pH, cystine aminopeptidase activity. RESULTS: The geometric mean UA-OT was significantly greater than UV-OT in all groups and was not altered by pethidine; however, epidural administration increased the UA-UV difference. The UA-UV difference at caesarean section was not significantly altered by the onset of labour. There was no correlation between UV pH and UA-UV plasma oxytocin. Cystine aminopeptidase activity was not detectable in UA and UV plasma. CONCLUSIONS: Fetal OT production is increased by epidural but not by pethidine analgesia. It is not influenced by the onset of labour or fetal hypoxia.
OBJECTIVE: To investigate the mechanism of action of the oxytocin (OT) antagonists, CAP 476 and F327. DESIGN: A prospective descriptional study. SUBJECTS: Women undergoing caesarean section at term or hysterectomy. INTERVENTIONS: Myometrial cells were cultured from uterine biopsies. MAIN OUTCOME MEASURES: Intracellular calcium ([Ca2+]i), determined in single cells. RESULTS: Application of OT caused a transient increase in [Ca2+]i. CAP 476 abolished and F327 reduced the response to OT but neither reduced the [Ca2+]i transient induced by cell depolarisation with 120 mmol K+. CAP 476 did not reduce transients caused by prostaglandin E2. F327 reduced the frequency of repetitive [Ca2+]i transients occurring during continuous application of OT. CONCLUSIONS: The results demonstrate that the antagonists reduce the effect of OT and that their action is relatively specific. Their mechanism of action as clinical tocolytic agents is discussed.
Intracellular calcium ([Ca2+]i) mobilization was studied in single cultured human myometrial cells in response to the agonists oxytocin and prostaglandin E2 (PGE2) using the fluorescent dye Fura-2. Oxytocin and PGE2 applications were associated with an increase in [Ca2+]i, although there was a marked intercell variation in the amplitude of the agonist-induced response. Removal of extracellular calcium ([Ca2+]o) reduced the oxytocin-induced rise and abolished the PGE2-induced rise in [Ca2+]i, thereby demonstrating that oxytocin but not PGE2 can mobilize intracellular stores of calcium. In nominally calcium-free medium, [Ca2+]i was not increased by PGE2 but subsequent application of oxytocin increased [Ca2+]i, thereby demonstrating that, within a single cell, calcium stores were mobilized by oxytocin and not PGE2. The intracellular calcium stores were completely depleted by a single application of oxytocin and not replenished in the absence of [Ca2+]o. Perfusion with calcium-containing medium for 100 s enabled store refilling. Cell depolarization by 140 mM-K+ caused a transient increase followed by a sustained elevation of [Ca2+]i on which were superimposed small fluctuations. Oxytocin caused an influx of calcium in cells depolarized by K+. This was more marked than that obtained with PGE2.
Repetitive transient increases in intracellular calcium were recorded in single cultured human myometrial cells exposed continuously to oxytocin (1 pM-1 nM). Each transient was preceded by a pacemaker-like gradual increase in baseline [Ca2+]i. Removal of extracellular Ca2+ reversibly stopped the transients although small fluctuations in [Ca2+]i were observed in seven out of eleven cells studied. In a proportion of cells (1-2%) repetitive Ca2+ transients were observed in the absence of exogenous oxytocin. The pattern of activity was similar to that seen in cells exposed to oxytocin. These spontaneous elevations in [Ca2+]i were reversibly inhibited by removing extracellular calcium. These experiments demonstrate for the first time repetitive agonist-induced and spontaneous transient increases in [Ca2+]i in single cultured human myometrial cells.
A technique for complete oxytocinase inhibition has been combined with a rapid serial sampling strategy to determine plasma oxytocin concentrations in twelve women during the early and late first stage and in eight women throughout the second stage of labour. The progress of labour is not related to an increase in oxytocin concentration, uterine contractions are not associated with changes in plasma oxytocin concentration and hypocontractile labour does not appear to be the result of a deficit of oxytocin. The majority of patients do not demonstrate an increase in plasma oxytocin concentration during the second stage of labour; however, a minority produce a large surge immediately before delivery. The results do not support a role for oxytocin during spontaneous labour unless uterine activity is controlled by extremely low plasma hormone concentrations or the uterus becomes sensitive to a constant oxytocin concentration.
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OBJECTIVE: To compare the safety and efficacy of loperamide used in combination with ciprofloxacin or ciprofloxacin alone for the treatment of travelers' diarrhea. DESIGN: Double-blind, placebo-controlled, randomized clinical trial. SETTING: United States Army hospital in Egypt. PARTICIPANTS: United States military personnel with travelers' diarrhea (n = 104) during a military exercise in November 1989. Persons who were noncompliant, had bloody diarrhea, or had received antidiarrheal medications before entry into the study were excluded. INTERVENTIONS: All participants with travelers' diarrhea were treated with ciprofloxacin, 500 mg twice daily for 3 days. Fifty of these patients were randomly assigned to receive loperamide, a 4-mg first dose and 2 mg for every loose stool (as much as 16 mg/d), and 54 were randomly assigned to receive placebo. MEASUREMENTS: Enterotoxigenic Escherichia coli was isolated from 57% of patients; Shigella and Salmonella, seen in 4% and 2% of patients, respectively, were not common. MAIN RESULTS: After 24 hours, the symptoms of 82% of patients in the ciprofloxacin and loperamide group compared with 67% in the ciprofloxacin and placebo group had improved or fully recovered (odds ratio, 2.3; 95% CI, 0.8 to 6.3; P = 0.08). After 48 hours, the symptoms of 90% of both groups had improved or fully recovered. The mean number of stools for those receiving loperamide was not much lower than those who did not receive loperamide after 24 hours (1.9 +/- 0.2 [SE] compared with 2.6 +/- 0.2) or 48 hours (3.1 +/- 0.3 compared with 4.0 +/- 0.3) of treatment (P = 0.19). CONCLUSIONS: In a region where enterotoxigenic E. coli was the predominant cause of travelers' diarrhea, loperamide combined with ciprofloxacin was not better than treatment with ciprofloxacin alone. Loperamide appeared to have some benefit in the first 24 hours of treatment in patients infected with enterotoxigenic E. coli. Both regimens were safe.
Arginine vasopressin, oxytocin and ACTH are released from the pituitary gland in response to acute hypoglycemia. To investigate the role of alpha-adrenergic mechanisms in mediating this response, 6 non-diabetic subjects were studied during hypoglycemia induced by 0.15 IU/kg i.v. insulin under control conditions, and during non-selective alpha-adrenergic blockade with phentolamine. In the control study plasma arginine vasopressin rose from 1.6 +/- 0.8 pmol/l (mean +/- SEM) basally to a maximum of 2.5 +/- 0.8 pmol/l following hypoglycemia (p less than 0.05). An exaggerated response was found during phentolamine blockade, with a maximum plasma vasopressin of 11.5 +/- 0.4 pmol/l (by analysis of variance, p less than 0.05). The plasma oxytocin response to hypoglycemia was similarly increased during phentolamine compared to control. Plasma growth hormone rose to 94 +/- 19 mU/l, and during blockade with phentolamine the response was significantly reduced reaching a peak of 34 +/- 7 mU/l (by analysis of variance, p less than 0.05). ACTH and prolactin both increased in response to hypoglycemia, but the increases were not affected by phentolamine. An alpha-adrenergic mechanism appears to inhibit the release of arginine vasopressin and oxytocin in response to hypoglycemia, but does not appear to affect the secretion of ACTH.
A method for the theoretical prediction of the antigenic determinants and the antigen-interactive receptor sites of immunological proteins from their primary structure would constitute a useful tool for their study. Such a method developed in this laboratory uses hydrophilicity, accessibility, flexibility, and recognition profiles, together with the predicted secondary structure (alpha-helices, beta-sheets, and turns). The secondary structure is determined by a modification of the method of Lim (1974), as described below. A study of human and mouse class I and class II major histocompatibility complex (MHC) antigens, central to the regulation of immune responses and to the phenomenon of graft rejection, was carried out using the above method. Comparison of the predictions with some of the available experimental and theoretical information supports the validity and usefulness of the approach.
Psychiatric disorder is reported to occur in a large proportion of patients with irritable bowel syndrome (IBS) and psychological treatment methods have been advocated for this patient group. In a sample of 25 out-patients with intractable IBS, only four patients with psychiatric disorder were identified. The majority did not have elevated levels of anxiety or depression nor was there evidence of significant abnormal illness behaviour. Electrodermal activity did not show the extremes of responding and habituation associated with anxiety, depression or chronic pain. It is suggested that, when accurate diagnostic criteria are employed, a specific relationship between IBS and psychopathology is no longer evident.
Campylobacter coli VC167, which undergoes an antigenic flagellar variation, contains two full-length flagellin genes, flaA and flaB, that are located adjacent to one another in a tandem orientation and are 91.5% homologous. The gene product of flaB, which has an Mr of 58,946, has 93% sequence homology to the gene product of flaA, which has an Mr of 58,916 (S. M. Logan, T. J. Trust, and P. Guerry, J. Bacteriol. 171:3031-3038, 1989). Mutational analyses and primer extension experiments indicated that the two genes are transcribed under the control of distinct promoters but that they are expressed concomitantly in the same cell, regardless of the antigenic phase of flagella being produced. The flaA gene, which was expressed at higher levels than the flaB gene in both phases, was transcribed from a typical sigma 28-type promoter, whereas the flaB promoter was unusual. A mutant producing only the flaB gene product did not synthesize a flagellar filament and was nonmotile. Southern blot analysis indicated that flagellar antigenic variation involves a rearrangement of flagellin sequence information rather than the alternate expression of the two distinct genes.
The metabolic clearance rate (MCR) of oxytocin (OT) was determined by use of constant infusion techniques to achieve low and high plasma OT concentrations in 10 women in late pregnancy and again 8-10 wk postpartum (mean plasma oxytocinase activity was 2.1 IU/ml plasma at term and less than 0.1 IU/ml plasma 8-10 wk postpartum). At the lower plasma OT concentrations (5.0 and 5.2 pg/ml, pregnant and postpartum, respectively) produced by infusion of 17.9 ng/min in pregnancy and 4.3 ng/min postpartum, mean MCR of OT was increased fourfold during pregnancy (5.7 +/- 0.6 and 1.3 +/- 0.1 l/min, pregnant and postpartum, respectively; P less than 0.001). At the higher plasma OT concentrations (8.0 and 8.0 pg/ml, pregnant and postpartum, respectively) produced by infusion of 35.7 ng/min in pregnancy and 8.5 ng/min postpartum, mean MCR of OT was likewise markedly increased during pregnancy compared with postpartum values (7.1 +/- 1.9 and 1.4 +/- 0.1 l/min, respectively; P less than 0.01). The MCR of OT was independent of plasma concentration (between 5 and 8 pg/ml) during pregnancy and in the postpartum period. It is concluded that the MCR of OT is increased markedly during human pregnancy. This may be due to concomitant increases in in vivo cystine aminopeptidase activity or other less specific pregnancy-associated metabolic changes.
1. Histones from Anopheles albimanus adults were prepared by a combination of techniques including chromatin isolation and selective extractions. 2. The anopheline histones were identified on acid urea gels by comparing their electrophoretic profile with that of calf thymus histones and histones isolated from other tissue. 3. Excellent separation of histones was obtained after the extractions by a single electrophoretic run. 4. In addition to the five major classes of histones found in eukaryotes, a sixth class was detected and tentatively identified as histone H5. 5. This is the first report of histone H5 and its function in insects.
Santoquin (0.25% by weight) in the diets of mice receiving adequate dietary selenium (1.0 parts/10(6] reduced the humoral immune response, as monitored by the plaque-forming cell assay, to levels exhibited by mice maintained on selenium-deficient diets (0.005 parts/10(6)). Mice exhibiting this suppression of immunity had levels of blood glutathione peroxidase, serum selenium, and liver DNA, RNA and protein similar to mice receiving selenium only. Therefore, it was concluded that Santoquin is not immunosuppressive by interfering with selenium metabolism or general tissue function, but by other unknown mechanisms.