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Biomedical subjects

S Williamson

Publications and source records attributed to S Williamson.

At least 19 recordsLinked to original sources
PubMed1997

Adverse effects of stimulant drugs in a community sample of drug users.

A sample of drug users (n = 158) were contacted and interviewed in non-clinical community settings about their use of Ecstasy, cocaine powder, and amphetamines and the adverse effects of these drugs. Subjects reported a wide range of adverse effects including anxiety problems, depression, mood swings, feelings of paranoia, and panic attacks. Sleep and appetite disturbances were the most commonly reported problems. About half of all subjects reported depression and paranoid feelings associated with their stimulant use. Many of those reporting problems stated that these were mild. However, for all drugs, a substantial minority of users reported adverse effects which they rated as 'severe'. Between 30 and 55% of the sample reported having had at least one 'severe' adverse effect (30% cocaine, 35% Ecstasy and 55% amphetamine). There were clear differences between the different drugs in the likelihood and reported severity of adverse effects. Amphetamine use was associated with significantly more adverse effects and with more severe adverse effects than Ecstasy or cocaine. Cocaine powder was associated with the least severe adverse effects. A common pattern of drug use involved the use of depressant drugs such as opiates and benzodiazepines in addition to stimulants. The stimulant and depressant users were more likely than the stimulants-only users to use stimulants by injection and more likely to report adverse effects associated with stimulant use. The stimulant and depressant users were also more likely to have been treated for a drug problem. Approximately a quarter of the sample stated that they had stopped using stimulants up to the point of interview as a result of their bad experiences.

Adolescent↗
PubMed1997

The circulating concentrations of FSH, LH and prolactin in the oestradiol-implanted ovariectomized ewe treated with caffeine.

Caffeine, a trimethylxanthine alkaloid, is a psycho-active drug that effects a wide range of physiological systems, including the reproductive system. Reports of infants with intra-uterine growth retardation and lowered birth weight as a result of in utero exposure to caffeine, are increasing. The drug is also known to alter steroidogenesis but it is not certain whether this is a direct and/or an indirect effect with the involvement of the central nervous system. Thus, an experiment was designed to determine the effect of acute caffeine administration on the circulating concentrations of gonadotrophins and prolactin in the ovariectomized oestradiol-implanted ewe. A single intravenous dose of caffeine (20 mg kg-1 bodyweight) did not affect circulating gonadotrophin concentrations with the parameters for the pulsatile secretion of luteinizing hormone (LH) and the mean concentration of follicle stimulating hormone (FSH) being similar in both experimental and control groups. Circulating prolactin levels, on the other hand, were significantly (P < 0.01) elevated following intravenous treatment with caffeine. The effect was immediate following caffeine administration with elevated concentrations being maintained over the next 3 h before their return to pre-treatment concentrations. The response was bi-phasic with peaks of prolactin concentrations at 1 and 3 h. The results of this experiment show that acute caffeine exposure does not affect the secretion of gonadotrophins from the anterior pituitary gland. Furthermore, they show that acute administration of caffeine stimulates prolactin secretion via an action that is independent of oestradiol feedback and which we suggest, may involve the ACTH/adrenal axis.

Animals↗
PubMed1997

Projections of chemically identified myenteric neurons of the small and large intestine of the mouse.

The projections of different subpopulations of myenteric neurons in the mouse small and large intestine were examined by combining immunohistological techniques with myotomy and myectomy operations. The myotomies were used to examine the polarity of neurons projecting within the myenteric plexus and showed that neurons containing immunoreactivity for nitric oxide synthase (NOS), vasoactive intestinal peptide (VIP), calbindin and 5-HT projected anally, while neurons with substance P (SP)-immunoreactivity projected orally, in both the small and large intestine. Neurons containing neuropeptide Y (NPY)- and calretinin-immunoreactivity projected locally. In the large intestine, GABA-immunoreactive neurons projected both orally and anally, with more axons tending to project anally. Myectomy operations revealed that circular muscle motor neurons containing NOS/VIP/ +/-NPY and calretinin neurons projected anally both in the small and large intestine, while SP-immunoreactive circular muscle motor neurons projected orally. In the large intestine, GABA-IR circular muscle motor neurons projected both orally and anally. This study showed that although some neurons, such as the NOS/VP inhibitory motor neurons and interneurons, SP excitatory motor neurons and 5-HT interneurons had similar projections to those in other species, the projections of other chemical classes of neurons in the mouse intestine differed from those reported in other species.

Animals↗
PubMed1997

Loss of Apc and the entire chromosome 18 but absence of mutations at the Ras and Tp53 genes in intestinal tumors from Apc1638N, a mouse model for Apc-driven carcinogenesis.

The Apc1638N mouse carries a targeted mutant allele at the endogenous adenomatous polyposis coli (Apc) gene and represents a unique in vivo model to study intestinal tumor formation and progression. Heterozygous Apc+/Apc1638N mice progressively develop 5-6 adenomas and adenocarcinomas of the small intestine within the first 6 months of life following a histologic sequence similar to that observed in human intestinal tumors. Here, we present the somatic mutation analysis of a total of 57 tumors. The results indicate that in > or = 75% of the lesions tested the wild type copy of the Apc gene is lost and that this LOH event extends to the entire mouse chromosome 18. Unexpectedly, mutations at the K-, N- and H-ras genes have not been found in these tumors. Immunohistochemical analysis of the Apc1638N tumors failed to detect accumulation of the Tp53 protein. Also, no mutations have been found in exons 7 and 8 of the Tp53 gene. These results indicate that, although the genetic inactivation of Apc is involved in the initiating event of the human as well as murine intestinal tumorigenesis, tumor growth and progression follow different mutational pathways in these two species.

Adenocarcinoma↗
PubMed1996

Conservation of neutralizing determinants between the sporozoite surface antigens of Theileria annulata and Theileria parva.

The sporozoite surface antigens SPAG-1 of Theileria annulata and p67 of Theileria parva are postulated to contain determinants necessary for host cell invasion and/or recognition and are both being considered as candidates for inclusion in subunit vaccines. Preliminary data suggest that these are related molecules. In this paper we describe the investigation of the relationship between these sporozoite antigens further by analysis of the immunological cross-reactivity using Mabs and sera raised against each antigen. The cross-reactions were examined by carrying out Western blots, IFA tests, and in vitro sporozoite neutralization assays. In addition, sequence comparison data which clearly establish that these surface antigens are encoded by related genes are presented. The regions of SPAG-1 identified as containing cross-reactive epitopes recognized by p67 antiserum correlated to regions of high predicted homology between p67 and SPAG-1, which are located at their respective N- and C-termini. Furthermore, p67 and SPAG-1 were found to contain cross-reactive determinants responsible for neutralization of sporozoite infectivity in vitro, and at least some of these were located in the C-termini of both molecules. The relevance of these findings to the possible roles for these molecules in host cell invasion is discussed.

Amino Acid Sequence↗
PubMed1996

GABA and nitric oxide synthase immunoreactivities are colocalized in a subset of inhibitory motor neurons of the guinea-pig small intestine.

Simultaneous immunofluorescence labelling was used to determine the patterns of colocalization of immunoreactivity for gamma-aminobutyric acid (GABA-IR) with immunoreactivity for nitric oxide synthase (NOS), vasoactive intestinal peptide (VIP) and tachykinins (TK) in nerve cells and fibres of the guinea-pig small intestine. GABA-IR nerve cell bodies were located in the myenteric plexus and varicose fibres innervated the circular and longitudinal muscle, but did not form pericellular endings in the myenteric ganglia. GABA-IR nerve cells comprised 4-5% of all nerve cells in the myenteric ganglia. Of GABA-IR myenteric nerve cells, about 85% had NOS-IR and of GABA-IR nerve fibres in both muscle layers, about 75% were NOS-IR. Conversely, 20% of NOS-IR nerve cells were GABA-IR. About 6% of GABA-IR nerve fibres innervating the circular muscle, but none innervating the longitudinal muscle, were TK-IR. Most GABA-IR fibres supplying the circular muscle, but none of those supplying the longitudinal muscle, were VIP-IR. From this study, and previous studies of projections of enteric neurons, it is concluded that most GABA-IR neurons in the guinea-pig small intestine are inhibitory motor neurons that also contain NOS-IR. A small proportion represents anally directed excitatory motor neurons that innervate the circular muscle and are also immunoreactive for TK.

Animals↗
PubMed1996

Women's satisfaction with antenatal care in a changing maternity service.

OBJECTIVES: 1) to provide a descriptive analysis of women's views of the antenatal care provided in the study centre; 2) to identify which aspects of antenatal care were important to women; 3) to assess whether or not women 'booked' for delivery at the study centre would welcome the formal introduction of a midwifery-led service and 4) to audit sources of satisfaction and dissatisfaction identified in the survey. DESIGN: descriptive survey using a self-administered questionnaire, and a self-administered audit questionnaire using a modified Measure of Satisfaction. SETTING: the antenatal clinic of one teaching hospital in the north of England between July 1993 and August 1993. The audit was conducted between December 1994 and February 1995. PARTICIPANTS: 110 women attending four 'follow up' antenatal clinics participated in the survey and 151 women participated in the audit. FINDINGS: many women felt they were already having midwifery-led care and that it was important to them to see a doctor during pregnancy. Generally the women were satisfied with antenatal care. Factors which caused dissatisfaction were, lack of continuity of care, quality of advice, waiting time and these were the focus of the audit. IMPLICATIONS FOR PRACTICE: local needs should be assessed before implementing changes in service. Elements of good practice should be identified to ensure that they are not compromised in a changing service. Further evaluation of the changing maternity service is needed to monitor satisfaction and dissatisfaction.

Adolescent↗
PubMed1996

Pharmacokinetics of caffeine in the oestrogen-implanted ovariectomized ewe.

The disposition kinetics of caffeine and its metabolites theophylline, theobromine and paraxanthine in the oestrogen-implanted ovariectomized ewe following single intravenous doses of 5, 10, 15 or 20 mg/kg caffeine are described in this paper. Blood was collected at 5, 30 and 60 min, and at 3, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192 and 240 h after dosing. Caffeine concentrations peaked within 30 min of administration but remained in a plateau phase for 3-6 h before declining over a prolonged period of time. For caffeine the mean elimination half-life was calculated to be 47 h. Detectable caffeine concentrations remained for 10 days after administration in all groups. The area under the plasma concentration-time curve (AUC) values were used to compare tissue caffeine exposure and were, approximately, linearly related to dose. Metabolite concentrations were maintained at peak and near peak concentrations for 6-24 h after caffeine administration followed by prolonged elimination. Because of significant species differences in drug elimination rates, it is concluded that the ewe is not a suitable animal model in the clinical context. However, the sheep may well provide insights into caffeine's mechanism of action of relevance to veterinary drug research.

Animals↗
PubMed1995

Transcription and translation of two glutamate decarboxylase genes in the ileum of rat, mouse and guinea pig.

gamma-Aminobutyric acid (GABA) is a major inhibitory neurotransmitter, synthesised from glutamate by glutamate decarboxylase (GAD), in the central nervous system. Two forms of GAD, designated GAD 65 and GAD 67, are encoded by distinct genes and have been demonstrated in the mammalian brain. GABA has been postulated to be synthesised in neurons of the enteric nervous system (ENS), but evidence for its role as an enteric neurotransmitter is equivocal. We therefore aimed to determine whether GAD 65 and GAD 67 messenger RNAs (mRNAs) and proteins were expressed in the ileum of mice, rats and guinea pigs. Using an RNase protection assay, both GAD 65 and GAD 67 mRNAs were detected in the rodent small intestine. Antisera specific for GAD 65 or GAD 67, used in immunoblot analyses, revealed GAD 65-like and GAD 67-like immunoreactivity in rat and guinea pig ileum. Anti-GAD 65 antisera detected a major band of 65 kDa. Anti-GAD 67 antisera detected a major band of 55 kDa, which probably represented a breakdown product, and a minor band of 67 kDa. Analysis of immunoblot extracts of rat and guinea pig ileum revealed more GAD 67-like than GAD 65-like immunoreactivity. GAD enzymatic activity was high in the rat and guinea-pig brain, and low in the whole and dissected ileum. These results demonstrate that both GAD 65 and GAD 67 genes are transcribed and translated in the ileum of three rodent species and lend indirect support to the postulate that GABA is synthesised by neurons of the ENS and intestinal endocrine cells.

Amino Acid Sequence↗
PubMed1995

Feasibility study for identifying adverse events attributable to vaccination by record linkage.

To investigate the feasibility of using a record linkage method for identifying vaccine attributable adverse events, computerized hospital admissions and vaccination records from South East Kent district were linked and checked for accuracy. Records for 90% of children under 2 years of age admitted to hospital over a 2-year period were matched with vaccination records using a computer algorithm based on name, date of birth, sex, and post-code supplemented by visual inspection. Relative to this gold standard, matching on date of birth, sex and postcode alone had a sensitivity of 60% and an incorrect match rate of 0.2% after matches to more than one vaccine recipient were excluded. Manual checking of a sample of admissions showed that only 4% had been assigned incorrect International Classification of Disease (ICD) codes. Routine record linkage of ICD admission codes to vaccination records therefore yields data of good quality which may be used for surveillance purposes.

Adverse Drug Reaction Reporting Systems↗
PubMed1995

An assessment tool for older patients.

A full and detailed assessment of older patients should include social circumstances. An assessment should identify problems of functional activity and use screening tools to aid referral to specialist multidisciplinary staff.

Activities of Daily Living↗
PubMed1994

Calretinin-immunoreactive neurons and their projections in the guinea-pig colon.

The distribution of nerve cells and fibres with immunoreactivity for the calcium-binding protein, calretinin, was studied in the distal colon of the guinea-pig. The projections of the neurons were determined by examining the consequences of lesioning the myenteric plexus. Calretinin-immunoreactive neurons comprised 17% of myenteric nerve cells and 6% of submucous nerve cells. Numerous calretinin-immunoreactive nerve fibres were located in the longitudinal and circular muscle, and within the ganglia of the myenteric and submucous plexuses. Occasional fibres were found in the muscularis mucosae, but they were very rare in the lamina propria of the mucosa. Lesion studies revealed that myenteric neurons innervated the underlying circular muscle and provided both ascending and descending processes that gave rise to varicose branches in myenteric ganglia. Calretinin-immunoreactive fibres also projected to the tertiary component of the myenteric plexus, and are therefore likely to be motor neurons to the longitudinal muscle. Varicose fibres that supplied the submucous ganglia appear to arise from submucous nerve cells. Arterioles of the submucous plexus were sparsely innervated by calretinin-immunoreactive fibres. The submucous plexus was the principal source of immunoreactive nerve fibres in the muscularis mucosae. This work shows that calretinin-IR reveals different neuronal populations in the large intestine to those previously reported in the small intestine.

Animals↗