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Biomedical subjects

M Williams

Publications and source records attributed to M Williams.

At least 613 records · Page 34Linked to original sources
PubMed1985

A hospital outbreak of Clostridium difficile?

An increase in numbers of patients with Clostridium difficile and its toxin in their stools at a hospital in South-west London led to closure of a ward to admissions and to an investigation of a possible nosocomial outbreak. The findings suggested that the increase was not due to an outbreak of related cases but to increased investigation. The cost of the episode both in financial terms and in the effect on patient care, was considerable. This study highlights the need for caution in interpreting the significance of Cl. difficile in stool specimens. Laboratory data can only alert clinicians to the possibility of colitis; decisions about treatment and control of spread of infection should also be based on clinical criteria.

Age Factors↗
PubMed1985

Selectivity of (+)-4-propyl-9-hydroxynaphthoxazine [(+)-PHNO] for dopamine receptors in vitro and in vivo.

The intrinsic activity of the potent dopamine (DA) agonist 4-propyl-9-hydroxynaphthoxazine [(+)-PHNO] was examined in receptor binding assays for the following receptors: DA, alpha-1 and alpha-2 adrenergic, serotonin-1 and -2, neuroleptic, beta adrenergic, anxiolytic, adenosine A-1, gamma-aminobutyric acid, muscarinic and opiate. (+)-PHNO exhibited strong to moderate potencies [IC50 (nanomolars) in parentheses] in binding to DA (24), "neuroleptic" (67), alpha-2 adrenergic (77) and serotonin-1 (277) sites. The pharmacological activity of the naphthoxazine both in vivo and in vitro was contrasted with the known DA agonists apomorphine, pergolide, lisuride and 6-ethyl-9-oxaergoline in tests of DA, alpha-2 adrenergic and serotonergic function. Each compound was examined in vitro in receptor binding assays for interactions with DA, alpha-2 adrenergic, serotonin-1 and serotonin-2 receptors and for alpha-2 adrenergic activity in inhibiting field-stimulated contractions of the vas deferens of the rat. In vivo, alpha-2 adrenergic activity was assayed via measurement of mydriasis after i.v. injections in the rat, whereas serotonin activity was assayed by measuring drug-induced inhibition of 5-hydroxytryptophan accumulation, and DA activity was assessed by quantifying stereotyped behavior after both i.p. and i.v. injections. Selectivity ratios for the DA receptor were derived from effective dose values determined in these tests and demonstrated that only apomorphine was more selective as a DA agonist than (+)-PHNO in vivo. (+)-PHNO was the least active agent at the alpha-2 receptors in the vas deferens and with serotonergic mechanisms in vivo to reduce 5-hydroxytryptophan accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Mechanism of polyuria and natriuresis in atrioventricular nodal tachycardia.

A woman with tachycardia associated with polyuria was investigated. Electrophysiological analysis showed that the tachycardia was an atrioventricular nodal re-entrant tachycardia. Programmed stimulation was then used to provoke and sustain the tachycardia for 40 minutes. Polyuria, with an appreciable increase in free water clearance, was observed. This was associated with reduction in plasma and urinary arginine vasopressin concentrations. Appreciable natriuresis also developed. These results support the hypothesis that the polyuria with increased free water clearance and the natriuresis occurring during sustained tachycardia in man are due to inhibition of secretion of vasopressin and the release of natriuretic factor.

Arginine Vasopressin↗
PubMed1984

Non-specificity of surfactant deficiency in neonatal respiratory disorders.

The phospholipid content of lung fluid taken from 77 babies during the first day of life was studied. Babies with hyaline membrane disease had low concentrations of the surfactant phospholipids phosphatidylcholine, phosphatidylinositol, and phosphatidylglycerol. The palmitic acid content in phosphatidylcholine was also lower than normal. Surfactant deficiency was not, however, specific for hyaline membrane disease, as similar phospholipid abnormalities were observed in babies with congenital pneumonia and transient tachypnoea of the newborn. These findings have important clinical implications. They are relevant to research into surfactant substitution and cast doubts on the value of the antenatal phospholipid lung profile of amniotic fluid in predicting the risk of hyaline membrane disease.

Gestational Age↗
PubMed1984

Serotonin-releasing effects of substituted piperazines in vitro.

The effects of various piperazine-containing compounds on the release of endogenous serotonin (5-HT) from rat hypothalamic slices were evaluated. Incubation of hypothalamic slices with m-chlorophenylpiperazine ( mCPP ) or m- trifluoromethylphenylpiperazine ( mTFMPP ) evoked a potent, dose-dependent release of endogenous 5-HT that was similar in magnitude to that seen with tryptamine, p-chloroamphetamine, or fenfluramine. In the presence of the 5-HT uptake blockers fluoxetine or chlorimipramine, this release was reduced dramatically. Furthermore, removal of calcium from the incubation medium had little effect on the drug-induced release, suggesting that the release mechanism involved displacement of 5-HT stores and not depolarization-induced exocytosis. Trazodone, MK-212, and quipazine had only small effects on release. These studies show that several piperazine-containing compounds can evoke a potent release of endogenous stores of hypothalamic 5-HT in vitro, actions which should be considered together with their direct agonist activity when interpreting the CNS effects in vivo.

Animals↗
PubMed1984

An enzyme histochemical study of the sinuses of reactive lymph nodes.

The enzyme histochemistry of the cells lining and within the marginal and medullary sinuses of twenty human reactive lymph nodes has been studied. The sinuses contain luminal ('reticular') cells which are strongly positive for certain hydrolytic enzymes, including acid-alpha-naphthyl acetate esterase, acid phosphatase and beta-glucuronidase. In addition, the lining ('littoral') cells on both sides of the medullary sinuses are positive for these enzymes. In contrast, enzyme-containing lining ('littoral') cells of the marginal (subcapsular) sinuses are observed only on the inner aspect of the sinuses, the outer aspect being negative. Alkaline phosphatase is not present in the sinusoidal cells but 5'-nucleotidase is seen in varying amounts. These findings are supported by an ultrastructural study of three of the nodes, using a staining method for esterase activity. The different enzyme histochemical properties of the littoral cells in the marginal and medullary sinuses closely mirrors that observed when, for example, these structures are stained immunohistochemically for IgA or J chain.

5'-Nucleotidase↗
PubMed1984

Comparison of central gastric antisecretory effects of desmethylimipramine, doxepin and pirenzepine in rats.

Certain tricyclic drugs, some of which are primarily used clinically as antidepressants, have been shown to act as gastric antisecretory agents. The anatomical site(s) and mechanism(s) of action of these agents is, however, in most cases unclear. In this study, we found that desmethylimipramine (DMI) was approximately 28 times more potent in inhibiting gastric acid secretion when administered intracerebroventricularly (i.c.) than when administered intravenously (i.v.) in pylorus-ligated rats, which is indicative of a site of action in the central nervous system. Qualitatively similar results were obtained with pirenzepine where the i.c./i.v. potency ratio was 8. Doxepin also preferentially inhibited acid secretion when given i.c. at low but not at high doses. Atropine and chlorpromazine were equipotent antisecretory agents by both routes of administration. Doxepin and DMI but not pirenzepine were effective inhibitors of brain stem norepinephrine uptake in vitro thus making this an unlikely common mechanism to explain the central actions of these compounds.

Animals↗
PubMed1984

Nicotinic receptors in mammalian brain.

Nicotine has marked effects on CNS function increasing brain excitability and spontaneous activity and also has antinociceptive actions. Agonist radioligands for the nicotinic cholinergic receptor bind with high affinity in a saturable manner. Binding is however, insensitive to the ganglionic blockers, hexamethonium and mecamylamine. This suggests that agonists and antagonists bind to different sites on the receptor or that the nicotinic receptor in brain is different from that found in peripheral tissues. The nicotinic antagonist, dihydro-beta-erythroidine binds with high affinity (Kd = 4 nM) to rat brain membranes in a stereospecific, saturable, manner with a regional distribution similar to that seen with radiolabeled acetylcholine. Binding is insensitive to hexamethonium and mecamylamine. It is concluded that the nicotinic recognition sites to which dihydro-beta-erythroidine binds are neuromuscular rather than ganglionic in nature.

Animals↗
PubMed1984

Molecular aspects of the action of benzodiazepine and non-benzodiazepine anxiolytics: a hypothetical allosteric model of the benzodiazepine receptor complex.

The availability of radiolabeled benzodiazepines has resulted in the identification of high affinity receptors in the central nervous system for this class of psychotherapeutic agent which are linked to recognition sites for the inhibitory neurotransmitter, GABA. Evaluation of new, synthetic compounds in the benzodiazepine radioligand binding assay has resulted in the identification of nine classes of non-benzodiazepine putative anxiolytic agents, some of which may be more anxioselective than the benzodiazepines. At least three and possibly five subclasses of benzodiazepine receptor have been identified in mammalian tissues using radioligand binding assays. The possibility exists that one of these receptor subclasses may mediate the anxiolytic effects of the benzodiazepines while the remainder may be involved in the mediation of the sedative, ataxic and anticonvulsant properties associated with benzodiazepine-like agents. Several endogenous ligands for the benzodiazepine receptor(s) have been postulated. These include various proteins and peptides, purines and the beta-carbolines. This latter group, which competitively antagonizes the pharmacological and biochemical effects of the benzodiazepines, has the highest affinity for the benzodiazepine receptor of all compounds thus far examined; however, none of these compounds has been conclusively identified as the endogenous ligand akin to the enkephalins and endorphins at the opiate receptor. The majority of available evidence would indicate that the endogenous ligand for the benzodiazepine receptor(s) is an antagonist of the benzodiazepines and other putative anxiolytic agents.

Animals↗
PubMed1984

Modification by dexamethasone of radiation response of in vitro cultured cells.

Because of the potential clinical significance of the report that dexamethasone is a radioprotector of Chinese hamster V-79 cells, the effect of dexamethasone treatment on the radiosensitivity of five other cultured mammalian cell lines (including two human cell lines) was tested and preliminary investigations into the mechanism of protection of V-79 cells were undertaken. In agreement with the published results of others, we found that treatment of V-79 cells with dexamethasone results in a 1.3-fold increase in D0. Conversely, dexamethasone had no effect on the radiosensitivity of Chinese hamster ovary cells, murine fibrosarcoma, rat glioma cells, human diploid fibroblasts, or human mammary carcinoma cells. To study the mechanism of the radioprotective effect of dexamethasone on V-79 cells, the cell cycle was examined. Dexamethasone treatment causes a change in cell cycle distribution in V-79 cells, resulting in a dose-dependent reduced fraction of S-phase and an increased fraction of G1- and G2 + M-phase cells. However, these kinetic changes cannot explain the observed radioprotection of asynchronous populations, since purified G1 cells are more radiosensitive. Furthermore, cells synchronized in G1 by centrifugal elutriation were shown to be protected by dexamethasone to the same extent as was the unsorted population, thereby ruling out the mechanism of protection being a redistribution in the cell cycle.

Animals↗
PubMed1984

Terminal phalangeal sclerosis in rheumatoid arthritis.

The incidence of terminal phalangeal sclerosis in the hand radiographs of 150 patients with rheumatoid arthritis was compared with a control group of radiographs of non-rheumatoid patients. Terminal phalangeal sclerosis was more common in females than in males and was more common in females with rheumatoid arthritis than in female controls. In rheumatoid arthritis terminal phalangeal sclerosis may occur with or without erosive changes.

Adolescent↗
PubMed1984

Progression of cystic fibrosis lung disease as a function of serum immunoglobulin G levels: a 5-year longitudinal study.

Seventy children with cystic fibrosis were studied over a 5-year period to assess the relationship between serum immunoglobulin G levels and progression of cystic fibrosis lung disease. Patients were grouped according to their serum IgG values (low, normal, or high) and evaluated with serial pulmonary function testing, radiographic and immunologic studies, and clinical observation. The children with persistent hypogammaglobulinemia G showed significantly better lung function, better weight for age, fewer hospitalizations for pulmonary exacerbations, less colonization with Pseudomonas aeruginosa, and slower decline in pulmonary functions than did age-matched patients with normal or high IgG levels. Death occurred in five of eight (63%) patients with hypergammaglobulinemia, three of 30 (10%) with normogammaglobulinemia, and one of 32 (3%) with hypogammaglobulinemia. No deaths occurred in the 15 patients with persistent hypogammaglobulinemia. These data indicate that children with cystic fibrosis and hypogammaglobulinemia G have milder lung disease and slower deterioration in pulmonary function than do age-matched patients with normal or elevated immunoglobulin G values. The mechanisms accounting for this finding are unclear.

Agammaglobulinemia↗
PubMed1984

Synthesis of 4-substituted 2H-naphth[1,2-b]-1,4-oxazines, a new class of dopamine agonists.

A series of tricyclic oxazines, namely, the 4-substituted 2H-naphth[1,2-b]-1,4-oxazines, have been synthesized and assayed for dopamine agonist activity. One of the members of this series, compound (+)VII-15, was found to be a remarkably potent agonist in vivo when tested in the standard 6-hydroxydopamine lesioned rat assay. The absolute configuration of the compound corresponds to that found in the active isomer of apomorphine. Its activity at the alpha 2 receptor (vs. [3H]clonidine) is relatively low. It also failed to stimulate the synthesis of cAMP in the carp retina assay, thus giving the compound a highly selective profile in favor of the D2 receptor.

Animals↗
PubMed1984

Maternal diabetes and neonatal respiratory distress. I. Maturation of fetal surfactant.

The phospholipid composition of amniotic fluid samples from 30 normal patients and 44 diabetic patients over the last 10 weeks of pregnancy was studied. Higher levels of phosphatidylcholine (PC) and phosphatidylinositol (PI) were found in diabetic pregnancies where there was excellent glucose control. These differences were statistically significant at 34-36 weeks. Phosphatidylglycerol (PG) appeared significantly earlier in the well controlled diabetic pregnancies, but even in the poorly controlled diabetics the levels of PC, PI and PG were comparable to those in normal pregnancies. There was no evidence of delayed appearance of fetal surfactant phospholipids in either the well or poorly controlled diabetic pregnancies. The absolute lecithin (PC)/sphingomyelin (SM) ratio in diabetic pregnancies was generally greater for any given gestational age than those in normal pregnancies. Whilst in most cases this was due to a higher PC concentration, in a few poorly controlled diabetics it was the result of a lower concentration of SM.

Amniotic Fluid↗
PubMed1984

Maternal diabetes and neonatal respiratory distress. II. Prediction of fetal lung maturity.

Fifty babies were born at less than or equal to 37 weeks to mothers with diabetes. Delivery was undertaken in all patients with the reassurance that the L/S ratio was greater than or equal to 2.0 within the preceding 72 h. Five babies (10%) developed respiratory distress syndrome (RDS). Prediction of fetal lung maturity was improved dramatically by measuring amniotic fluid concentrations of phosphatidylcholine (PC), phosphatidylinositol (PI) and phosphatidylglycerol (PG). Fourteen babies were predicted as having 'no surfactant' (PC less than 20 mg/l, PI less than 2 mg/l and PG less than 2 mg/l), five developed RDS. None of the remaining 36 babies developed the illness: they were predicted as having either 'early surfactant' (PC greater than or equal to 20 mg/l, PI greater than or equal to 2 mg/l but PG less than 2 mg/l) or 'late surfactant' (PC greater than or equal to 20 mg/l, PI greater than or equal to 2 mg/l and PG greater than or equal to 2 mg/l). Measurement of PC levels alone was the most was the most accurate method of predicting RDS. There was a significant association between low surfactant phospholipid concentrations and the development of transient tachypnoea of the newborn.

Amniotic Fluid↗
PubMed1984

Ivermectin interactions with benzodiazepine receptors in rat cortex and cerebellum in vitro.

The anthelmintic macrolide, ivermectin, enhances the binding of benzodiazepine agonist ( [3H]-diazepam) and antagonist ( [3H] beta-carboline ethyl ester) ligands to rat cortical and cerebellar membrane preparations. Enhancement of benzodiazepine agonist binding is partially additive with that of gamma-aminobutyric acid (GABA) and is inhibited by etazolate, bicuculline, and the steroid GABA antagonist R5135. Ivermectin-stimulated benzodiazepine antagonist binding is enhanced by bicuculline and inhibited by GABA and etazolate. The modulatory effects of bicuculline are chloride-dependent. The stimulatory effects of ivermectin, while quantitatively different in cortex and cerebellum, are qualitatively similar in both brain regions and are reduced in the presence of chloride. Ivermectin effects on benzodiazepine ligand binding to the benzodiazepine receptor complex and the differences in the effects of GABA, bicuculline, and R5135 on ivermectin-stimulated agonist and antagonist binding may provide evidence for distinct differences in the recognition sites for the two classes of benzodiazepine receptor ligand and their interactions with other components of the receptor complex.

Animals↗
PubMed1984

A comparison of lactate and isoproterenol anxiety states.

Both sodium lactate and isoproterenol can produce anxiety symptoms in patients with panic attacks. We administered both substances intravenously under placebo-controlled, double-blind conditions to patients with panic attacks and normal control subjects. We measured changes in anxiety levels using the Hamilton Anxiety Scale, State-Trait Anxiety Inventory, and a Panic Severity Scale. Measurements of respiratory rate and blood pH, pO2, pCO2, HCO3, and base excess were used to determine the relationship of hyperventilation to the symptoms induced by the infusions. Heart rate, epinephrine and norepinephrine levels were measured to determine whether there are changes related to palpitations and chest pain. Finger temperature and galvanic skin response were monitored to see whether any changes correlate with subject reports of hot or cold flashes and sweating. In this presentation, we will describe the clinical and biochemical changes that occur during panic attacks.

Adult↗