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S Brown

Publications and source records attributed to S Brown.

At least 271 records · Page 15Linked to original sources
PubMed1998

Comparison of single- and repeated-dose pharmacokinetics of diazepam.

PURPOSE: To determine whether repeat boluses of diazepam (DZP) lead to significant accumulation in the central nervous system and/or peripheral compartments, as repeat intravenous boluses of diazepam are commonly used in the treatment of status epilepticus (SE). METHODS: In a rat model that permits simultaneous serum and cerebrospinal fluid (CSF) sampling, we characterized the pharmacokinetics of DZP and its metabolite, desmethyldiazepam, in CSF and blood using HPLC. DZP was administered by intraperitoneal injection as either a single dose (20 or 30 mg/kg) or repeat doses (10 or 20 mg/kg x 3, 1 h apart). RESULTS: After a single intraperitoneal dose, DZP was rapidly absorbed with a time to maximum concentration of 10 min. The serum concentrations then declined biexponentially. DZP rapidly entered the CSF, the CSF to serum ratio reached equilibrium within 10 min, and was equivalent to the ratio of free to total serum concentration. Repeated DZP dosing resulted in a threefold decrease in volume of distribution and clearance (p < 0.001). This was reflected in the CSF concentration data; however, after the third dose, the ratio of CSF to serum concentration, also increased greatly, representing further persistence of DZP in the CSF compartment. CONCLUSIONS: Repeat dosing of DZP leads to substantial accumulation, and high, persistent serum and CSF concentrations, which may explain the toxic effects of repeat DZP dosing. Repeat dosing of DZP using a tapering protocol, however, may increase the effectiveness of DZP in treating SE by preventing relapses without substantially increasing toxicity.

Animals↗
PubMed1998

Down-regulation of cytochrome P450 2C family members and positive acute-phase response gene expression by peroxisome proliferator chemicals.

In this study, we show that peroxisome proliferator chemical (PPC) exposure leads to alterations in the expression of genes in rat liver regulated by the sex-specific growth hormone secretory pattern and induced during inflammation. Expression of the male-specific cytochrome P450 (P450) 2C11 and alpha2 urinary globulin (alpha2u) genes and the female-specific P450 2C12 gene was down-regulated by some PPC. Expression of P450 2C13, also under control by the sex-specific growth hormone secretory pattern, was not altered by PPC treatment, indicating that regulation of CYP2C family members does not involve perturbation of the growth hormone secretory pattern. In contrast to the increases in expression observed when inflammation was induced in male rats, two positive acute-phase response genes, alpha1-acid glycoprotein and beta-fibrinogen, were decreased by PPC exposure. The down-regulation of the P450 2C11 by WY-14,643 could be reproduced in cultured rat hepatocytes, indicating the down-regulation is a direct effect. Experiments in wild-type mice and mice that lacked a functional peroxisome proliferator-activated receptor-alpha gene showed that down-regulation by WY of alpha1-acid glycoprotein, beta-fibrinogen, and a mouse homologue of alpha2u was dependent on peroxisome proliferator-activated receptor-alpha expression. Our results demonstrate that PPC exposure leads to down-regulation of diverse liver-specific genes, including CYP2C family members important in hormonal homeostasis and acute-phase response genes important in inflammatory responses.

Acute-Phase Proteins↗
PubMed1998

Sex and relationship dysfunction in neurological disability.

OBJECTIVES: (1) to ascertain how many people with neurological disability experience sexual or relationship problems; (2) to examine the interplay of neurological disability and sexual function within the context of the dyadic relationship; (3) to consider the implications of the results for service provision. METHODS: A survey of outpatients attending Hunters Moor Regional Rehabilitation Centre, Newcastle upon Tyne over a 6 month period. Standardised measures of sexual function and concern, relationship satisfaction, disability, and mental health were used. RESULTS: Seventy people were interviewed (18% of the potential study population). Prevalence figures therefore refer to this self selected sample. Fifty one per cent had experienced a change in sexual function and 27% were concerned about this change. Of those in cohabiting relationships 25% were experiencing difficulties. Gender was significantly associated with concern about sexual function, men being more concerned. A high score on the marital adjustment scale indicating relationship dissatisfaction was the best predictor of change in and concern about sexual function. Change in sexual function and duration of illness were the most powerful predictors of relationship dissatisfaction. CONCLUSION: If concern is taken as an indication of a desire for help more than one in four of this sample required help for sexual dysfunction. Sexual and relationship functioning were very closely associated and dysfunction in either of these areas was the best predictor of dysfunction in the other area. The dyadic relationship is an important institution in the management of disability. Sexual dysfunction can be predictive of difficulties within a relationship. Any service designed to address sexual health should also address relationship issues.

Brain Diseases↗
PubMed1998

Fluorescent in situ hybridization detection of HER-2/neu gene amplification in rhabdomyosarcoma.

Embryonal rhabdomyosarcoma is the most common malignant soft-tissue tumor in childhood, comprising 45-50% of childhood sarcomas. Cytogenetic studies of this tumor are rare. In view of the paucity of cytogenetic data on this cancer and based on the finding of HER-2/neu gene amplification in a number of cancers that was detected mostly using the traditional technique of immunohistochemistry, we decided to conduct a pilot study to investigate whether HER-2/neu gene amplification in this tumor can be detected using the newer technique of fluorescent in situ hybridization (FISH). Archival tissues of rhabdomyosarcoma were retrieved and FISH using an HER-2/neu probe was undertaken on formalin-fixed paraffin-embedded tissue sections using a protocol optimized for our laboratory at Rhode Island Hospital. Out of 9 cases of rhabdomyosarcoma studied to date, 1 case clearly showed HER-2/neu gene amplification. Thus, FISH is a sensitive technique suitable for the detection of oncogene amplification and the delineation of tumor heterogeneity in this tumor. Future experiments utilizing additional specimens from our centers as well as from other laboratories will be needed to extend the finding in the present pilot study.

Child↗
PubMed1998

People with schizophrenia and their families. Fifteen-year outcome.

BACKGROUND: This paper presents 15-year outcome data on place of residence, clinical and social morbidity and carer distress in a cohort of 179 people with schizophrenia who were living with their families in 1981-1982. METHOD: Data on morbidity and carer distress were derived from replicated patient and informant interviews using standardised research instruments. Details of residence came from patient and informant interviews corroborated by case note information. RESULTS: Thirty-nine (22%) of the original 179 patients were dead and six (3%) lost to follow-up. Of the remaining 134 patients, 74 (55%) still lived with their families, 31 (23%) lived in institutional accommodation, 26 (19%) lived alone and 3 (2%) were homeless. There was little change in the level of clinical or social morbidity or carer distress. CONCLUSIONS: These findings suggest that most people with schizophrenia who live with their families remain significantly disabled by their illness, while their carers suffer ongoing distress. Mental health services should seek to support families who want to care for relatives with schizophrenia. Appropriate alternative accommodation must be provided when family care is not possible.

Adolescent↗
PubMed1998

Corticotropin-releasing hormone directly and preferentially stimulates dehydroepiandrosterone sulfate secretion by human fetal adrenal cortical cells.

Estrogens produced by the placenta play a pivotal role in the endocrine control of pregnancy and induce many of the key changes involved in parturition. The placentae of humans and higher primates use the C19 androgen dehydroepiandrosterone sulfate (DHEA-S) supplied by the fetal adrenals as the principal substrate for estrogen synthesis. Thus, secretion of androgens by the fetal adrenals may be central to the process of primate parturition. The timing of human parturition also is correlated with placental CRH concentrations in the maternal circulation. Because the mechanisms that regulate DHEA-S production by the fetal adrenals are incompletely understood, we examined whether there is a functional relationship between CRH and steroid production by human fetal adrenal cortical cells. Using Northern blot analysis, we detected messenger RNA transcripts (2.7 kb) encoding the type-1 CRH receptor in total RNA extracted from midgestation human fetal adrenals, suggesting that the fetal adrenal cortex may be directly responsive to CRH. To test this, primary cultures of human fetal adrenal cortical cells were exposed to human CRH. Human CRH increased DHEA-S production by cultured human fetal adrenal cortical cells in a dose-dependent fashion, with an ED50 of 10-100 pmol/L. Human CRH was as effective as ACTH at stimulating DHEA-S production; however, it was 70% less potent than ACTH at stimulating cortisol production, indicating that its actions were preferentially directed toward increasing DHEA-S synthesis. Consistent with this thesis, we found that CRH increased abundance of messenger RNA encoding cytochrome P450 cholesterol side-chain cleavage and 17alpha-hydroxylase/17,20 lyase but not 3beta-hydroxysteroid dehydrogenase in adrenal cells. CRH did not alter cell number, indicating that it is not mitogenic for fetal adrenal cortical cells. These data demonstrate a direct functional interaction between CRH and the fetal adrenal. Therefore, placental CRH production, which rises exponentially during human pregnancy, may play a key role in promoting DHEA-S production by the fetal adrenals, which could lead to increasing placental estrogen synthesis and contribute to the process of parturition in humans.

Adrenal Cortex↗
PubMed1998

Colonoscopy under general anesthesia in children.

OBJECTIVE: In children, colonoscopy is usually performed using deep sedation that may be associated with significant risks. The purpose of this study was to evaluate the safety of colonoscopy performed under general anesthesia. METHODS: All patients undergoing colonoscopy during a 3-year period were reviewed for the study. One hundred and thirty-six procedures were performed. Colonoscopies were performed by a pediatric gastroenterologist. Anesthesia was administered by a pediatric anesthetist in a gastroenterology procedure room, adjacent to the operating recovery area. RESULTS: Three patients had significant abdominal pain and tenderness after the procedure, 1 of whom suffered a perforation of the sigmoid colon. This patient had severe ulcerative colitis. The gastrointestinal complication rate was no higher than reported in adult patients undergoing colonoscopy under sedation. No significant complications relating to the administration of anesthesia were encountered. CONCLUSION: We conclude that colonoscopy performed under general anesthesia in children is a very safe procedure. It is superior to the use of sedation because the child is not placed at risk of respiratory compromise. Furthermore, the procedure is less worrisome for children when performed under a general anesthetic.

Abdominal Pain↗
PubMed1998

Photo CD for clinical imaging.

This paper examines the use of Photo CD as a source for printing clinical images for patients' medical case notes. Advantages include multiple resolutions, no capital investment in digital equipment, and professional and flexible presentation of pictures in patients' notes. Disadvantages include increased running costs for every film, a limited number of images stored on each CD and the requirement to set up a comprehensive image database to store and retrieve digital images.

CD-ROM↗
PubMed1998

Patient removals from general practitioner lists in Northern Ireland: 1987-1996.

BACKGROUND: Being struck off a general practitioner's list is a major event for patients and a subject for much media attention. However, it has not hitherto received much research attention. AIMS: To quantify the numbers of patients removed at doctors' request in Northern Ireland between 1987 and 1996. To describe the characteristics of those removed and to determine if the rate of removal has increased. METHODS: This is a descriptive epidemiological study involving a secondary data analysis of records held by the Central Services Agency. RESULTS: Six thousand five hundred and seventy-eight new patients were removed at general practitioner (GP) request between 1987 and 1996. This equated to 3920 removal decisions, a rate of 2.43 per 10,000 person-years. The very young and young adults had the highest rates of removal; most of the young being removed as part of a family. Ten point six per cent of removed patients had a repeat removal, and 16.3% of first removal decisions required an assignment to another practice. Family removals have decreased and individual removals have increased over the 10 years. Disadvantaged and densely populated areas with high population turnover were associated with higher rates of removal, though heterogeneity is evident between general practitioners serving similar areas. Compared to the period 1987 to 1991, removal rates for the years 1992 to 1993 were reduced by 20.0% (95% confidence interval (CI) for rate ratio (RR) 0.73-0.87), and those for the years 1994 to 1996 increased by 8% (95% CI = 1.01-1.16). The greatest increase was in the over-75 years age group (standardized RR = 1.60; 95% CI = 1.57-1.62). CONCLUSIONS: Removals are relatively rare events for both patients and practices, though they have been increasing in recent years. Further research is needed to understand the processes that culminate in a removal.

Adolescent↗
PubMed1998

Depressive symptoms in elderly medical-surgical patients hospitalized in community settings.

The authors examined the rates and correlates of depressive symptoms in adults over age 60 admitted to community hospital settings and compared them with patients admitted to a tertiary-care medical center. Rates of depressive symptoms in patients admitted to five different community hospitals in North Carolina were compared with each other and with a sample of 542 elderly medical patients admitted to Duke University Medical Center (DUMC). Compared with patients at DUMC, community-hospital patients were older and had more cognitive impairment, but had less severe medical illness and shorter hospital stays. The proportion of depressed community patients was significantly higher than among patients admitted to DUMC. In four of the five community hospitals, rates of significant depressive symptoms exceeded 50%. Health correlates of depression were admitting diagnoses other than cardiovascular disease, poor cognitive functioning, and severe medical illness.

Academic Medical Centers↗
PubMed1998

Visual outcome and ocular survival in patients with retinal detachments secondary to open- or closed-globe injuries.

BACKGROUND AND OBJECTIVE: A retrospective study was undertaken to establish predictive clinical features for final visual outcome and ocular survival for patients who have sustained traumatic retinal detachments (RDs). PATIENTS AND METHODS: The authors reviewed 191 cases of RD following open- or closed-globe trauma. The clinical features that were analyzed included the initial visual acuity, the location of the wound, the mechanism of injury (blunt, sharp, or projectile), and the number of quadrants of RD. RESULTS: The significant predictive factors for good visual outcome (1/200 or better) included an initial visual acuity of hand motions or better, wounds located anterior to the equator, closed-globe injuries, sharp injury in open globes, and three or fewer quadrants of RD. The factors that predicted enucleation included an initial visual acuity of light perception or no light perception, wounds located posterior to the equator, and four quadrants of RD. CONCLUSION: The significant predictive factors for final visual outcome in patients with traumatic RD were the initial visual acuity, the location of the wound, the mechanism of injury, and the number of quadrants of RD.

Adolescent↗
PubMed1998

Early obstetric discharge: does it make a difference to health outcomes?

Clinicians in several countries have expressed concerns about possible adverse effects of shortening obstetric length of stay. A population-based survey of 1366 mothers who gave birth in Victoria, Australia, in 1993 was used to investigate social and obstetric characteristics of mothers discharged home 'early', and to assess whether shorter stays were associated with adverse health outcomes, or a lesser degree of satisfaction, or both. Women's views and experiences of length of hospital stay were gathered via a statewide postal survey of women who gave birth in a 2-week period; 62.5% (n = 1336) responded. Assessment of the relationship between length of stay (1-2 days vs. > or = 5 days, and 3-4 days vs. > or = 5 days) and four main outcome measures (infant feeding at 6 weeks, period prevalence of feeding problems, maternal confidence and depression) showed no association between these variables and length of stay after adjusting for other obstetric and social factors in separate regression analyses. For stays of 3-4 days, the adjusted odds ratio (OR) for formula feeding at 6 weeks was 1.35 [95% confidence interval (CI) 0.9-1.9]; for feeding problems OR = 0.87 [0.7-1.2]; for lacking confidence OR = 0.81 [0.6-1.2]; and for depression OR = 0.96 [0.7-1.4]. Large randomised trials of early obstetric discharge are required to resolve continuing uncertainties about the safety, and possible benefits of shorter hospital stays.

Breast Feeding↗
PubMed1998

[Evaluation of super dwarf wheat growth and development in greenhouse "Svet" during cultivation in inhabited pressurized chamber].

Goals of the 3-month experiment GREENHOUSE using the equipment of greenhouse SVET (ECO-PSY-95) were to feature growth and development of wheat through the entire cycle of ontogeny under the maximally mimicked MIR environment, and to try out the procedures and timeline of space experiment GREENHOUSE-2 as a part of the fundamental biology investigations within the MIR/NASA space science program. Irradiation intensity (PAR) was 65 W/m2 and 38 W/m2 in the experiment and laboratory control, respectively. Values of other environmental parameters were MIR average (18-25 degrees C, relative air humidity in the interval between 40% and 75%, total gas pressure of about 660 to 860 mm Hg, partial oxygen pressure within the range from 140 to 200 mm Hg, partial carbon dioxide pressure up to 7 mm Hg). Experimental results showed that wheat cultivation in inhabited chamber under a modified lighting unit providing greater irradiation of the crop area produced more plant mass although seed production dropped. Low grain content in ears could be the aftermath of the gaseous trace contaminants in the chamber atmosphere.

Air Pressure↗
PubMed1997

Identification of a novel member of the TGF-beta superfamily highly expressed in human placenta.

While conducting a gene discovery effort targeted to transcripts of the prevalent and intermediate frequency classes in placenta throughout gestation, we identified a novel member of the TGF-beta superfamily that is expressed at high levels in human placenta. Hence, we named this factor 'Placental Transforming Growth Factor Beta' (PTGFB). The full-length sequence of the 1.2-kb PTGFB mRNA has the potential of encoding a putative pre-pro-PTGFB protein of 295 amino acids and a putative mature PTGFB protein of 112 amino acids. Multiple sequence alignments of PTGFB and representative members of all TGF-beta subfamilies evidenced a number of conserved residues, including the seven cysteines that are almost invariant in all members of the TGF-beta superfamily. The single-copy PTGFB gene was shown to be composed of only two exons of 309 bp and 891 bp, separated by a 2.9-kb intron. The gene was localized to chromosome 19p12-13.1 by fluorescence in-situ hybridization. Northern analyses revealed a complex tissue-specific pattern of expression and a second transcript of 1.9 kb that is predominant in adult skeletal muscle. Most importantly, the 1.2-kb PTGFB transcript was shown to be expressed in placenta at much higher levels than in any other human fetal or adult tissue surveyed.

Adult↗
PubMed1997

Localization of mGluR4 protein in the rat cerebral cortex and hippocampus.

The cellular distribution of the rat metabotropic glutamate receptor type 4 (mGluR4) was examined in the adult rat cerebral cortex and hippocampus. Antibodies were raised against amino acid residues located in the extracellular amino terminal domain that is common to both the mGluR4a and mGluR4b splice variants, and used for an immunohistochemical investigation. The affinity-purified antibodies on immunoblot analysis specifically detected mGluR4 protein in transfected mammalian cells, showing no cross-reactivity with other members of the mGluR family. At the light microscope level intense mGluR4-like immunoreactivity was detected in the CA2 region of Ammon's horn in the hippocampus. In the cerebral cortex numerous non-pyramidal cells were strongly immunolabelled.

Animals↗