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Biomedical subjects

J Brown

Publications and source records attributed to J Brown.

At least 433 records · Page 24Linked to original sources
PubMed1996

Pathophysiology and treatment of hepatitis C.

Hepatitis C virus (HCV) infection is associated with a variable disease course and response to therapy. Some infected patients may develop little or no disease for 30 to 40 years, whereas others will develop cirrhosis within 5 to 10 years. Both host and viral factors influence the rate of disease progression. The management of patients is determined by the severity of their disease assessed by liver biopsy. Those with mild hepatitis without fibrosis do not require treatment but should undergo liver biopsy every 3 years. Patients with mild hepatitis with fibrosis, or with moderate or severe hepatitis with or without fibrosis, should be offered treatment. Interferon-alpha (IFN alpha) is currently the only licensed treatment for HCV infection. Although initial response rates to IFN alpha are high, over half the patients relapse and a sustained response is achieved in only 10 to 35% of patients. Higher doses of IFN alpha and a longer treatment duration are associated with better response rates. Treatment options for those who fail to respond to IFN alpha include a second course of IFN alpha at a higher dose or IFN alpha in combination with ribavirin, phlebotomy or ursodeoxycholic acid. At present, however, there are insufficient data to routinely recommend any of these options.

Hepatitis C↗
PubMed1996

Multilocus genetic determinants of LDL particle size in coronary artery disease families.

Recent interest in atherosclerosis has focused on the genetic determinants of low-density lipoprotein (LDL) particle size, because of (i) the association of small dense LDL particles with a three-fold increased risk for coronary artery disease (CAD) and (ii) the recent report of linkage of the trait to the LDL receptor (chromosome 19). By utilizing nonparametric quantitative sib-pair and relative-pair analysis methods in CAD families, we tested for linkage of a gene or genes controlling LDL particle sizes with the genetic loci for the major apolipoproteins and enzymes participating in lipoprotein metabolism. We confirmed evidence for linkage to the LDL receptor locus (P=.008). For six candidate gene loci, including apolipoprotein(apo)B, apoAII, apo(a), apoE-CI-CII, lipoprotein lipase, and high-density lipoprotein-binding protein, no evidence for linkage was observed by sib-pair linkage analyses (P values ranged from .24 to .81). However, in addition, we did find tentative evidence for linkage with the apoAI-CIII-AIV locus (chromosome 11) (P=.06) and significant evidence for linkage of the cholesteryl ester transfer protein locus (chromosome 16) (P=.01) and the manganese superoxide dismutase locus (chromosome 6) (P=.001), thus indicating multilocus determination of this atherogenic trait.

Adolescent↗
PubMed1996

The first assistant role in PEG tube insertion.

Nurses are under pressure to take on junior doctors' tasks. Expansion of the nurse's role should be of benefit to patients and professionally appropriate. The development of the first assistant role in PEG may be an avenue for expanding nursing.

Clinical Competence↗
PubMed1996

Family study and segregation analysis of Tourette syndrome: evidence for a mixed model of inheritance.

To investigate the transmission of Tourette syndrome (TS) and associated disorders within families, complex segregation analysis was performed on family study data obtained from 53 independently ascertained children and adolescents with TS and their 154 first-degree relatives. The results suggest that the susceptibility for TS is conveyed by a major locus in combination with a multifactorial background. Other models of inheritance were definitively rejected, including strictly polygenic models, all single major locus models, and mixed models with dominant and recessive major loci. The frequency of the TS susceptibility allele was estimated to be .01. The major locus accounts for over half of the phenotypic variance for TS, whereas the multifactorial background accounts for approximately 40% of phenotypic variance. Penetrance estimates suggest that all individuals homozygous for the susceptibility allele at the major locus are affected, whereas only 2.2% of males and 0.3% of females heterozygous at the major locus are affected. Of individuals affected with TS, approximately 62% are heterozygous and approximately 38% are homozygous at the major locus. While none of the families had two parents affected with TS, 19% of families had two parents affected with the broader, phenotype, which includes TS, chronic tic disorder, or obsessive-compulsive disorder.

Adolescent↗
PubMed1996

Prostate, adrenocortical, and brown adipose tumors in fetal globin/T antigen transgenic mice.

Targeted oncogenesis in transgenic mice has unexpectedly produced predictable tissue-specific tumors. We previously showed that hybrid gene constructs of the human fetal G gamma- or mouse embryonic beta h1-globin promoter linked to the viral simian virus 40 T antigen (G gamma/T and beta h1/T) expressed appropriately in embryonic erythroid tissue, with some unexpected expression elsewhere. Tumors arising in the G gamma/T and beta h1/T transgenic mice were identified by histology, electron microscopy, cell culture, and RNase protection analyses. In one G gamma/T transgenic line, males developed prostate tumors that showed mixed neuroendocrine and epithelial cell features, whereas females developed adrenocortical tumors. In several other G gamma/T lines, brown adipose tumors, or hibernomas, developed in the subcutaneous interscapular neck and shoulder area, as well as internally in the periadrenal and pericardial areas. Little or no expression of T antigen was detected in adult animals before visible tumor formation. In contrast, beta h1/T transgenic mice developed only choroid plexus tumors. Transient transfection assays in prostate and adrenocortical tumor-derived cell lines showed that the G gamma-globin promoter is 7-to 10-fold more active than the beta h1-globin promoter. Activity of 5' G gamma-globin promoter-deletion DNA plasmids was analyzed by transient transfection in a variety of human prostate cancer cell lines. The G gamma-globin promoter region between -140 and -201 also showed high activity in the androgen-independent human prostate cancer cell lines DU-145 and PPC-1, but low activity in the androgen-responsive human prostate cell line LNCaP. We conclude that tumor formation in the G gamma/T transgenic lines apparently results from cryptic positive DNA cis elements active in prostate and adrenocortical cells. Because G gamma-globin promoter activity is highest in embryonic tissue, tumors in adult transgenic mice may result from expression of T antigen in embryonic prostate, adrenal glands, and brown adipose tissue.

Adrenal Cortex Neoplasms↗
PubMed1996

Antithrombotic therapy for patients with stroke symptoms. Guidelines for family physicians.

Anticoagulant therapy to halt or limit a potentially devastating stroke carries both risk and an unproven benefit. Two case reports highlight potential pitfalls. Antiplatelet agents are indicated for ischemia secondary to artery-to-artery embolism. Anticoagulation should be undertaken only when a demonstrated cardiac embolic source places a patient at ongoing risk of repeated embolic stroke. This article reviews rational approaches to anticoagulation for neurologic patients.

Anticoagulants↗
PubMed1996

Percutaneous endoscopic gastrostomy: evaluation of insertion by an endoscopy nurse practitioner.

OBJECTIVE: To evaluate the success rate and complications of percutaneous endoscopic gastrostomy (PEG) insertion performed with an endoscopy nurse practitioner, rather than a second doctor, carrying out percutaneous gastric puncture. DESIGN: A prospective evaluation of one nurse'e performance. SETTING: The endoscopy unit in a district general hospital. METHODS: An experienced endoscopy nurse, who had undergone a specific training course in PEG insertion, participated in PEG placement in 50 unselected patients over a one year period. The outcome and complications were compared with 50 PEGs inserted over the same period by medical personnel. A standard 'pull' technique was used to insert a 15Fr tube under sedation and local anaesthetic. RESULTS: The nurse was successful in PEG placement in all patients. Immediate complications from the procedure occurred in two cases in both the nurse-assisted and doctor-assisted groups. These were directly related to the gastric puncture in only one patient in each group; the others were respiratory complications related to the gastroscopy (resulting in the death of one patient). Thirty-day mortality was 8% in the nurse-assisted group and 12% following doctor-assisted PEG (mainly due to progression of the underlying condition). Outcome at 3 months was similar in the two groups, except for a slightly lower incidence of stomal infection in the nurse-assisted group. CONCLUSION: The participation of an endoscopy nurse practitioner in the gastric puncture for PEG insertion appeared to be safe and effective and offered advantages in terms of the efficient provision of a PEG placement service, increased continuity of care for the patients and an enhanced professional role for the nurse involved.

Adult↗
PubMed1996

Is the rat a suitable model for humans on studies of cereal digestion?

OBJECTIVES: To compare the extent of starch digestion from barley flake and flour in humans and rat. Is the rat a useful model? DESIGN: Four healthy male ileostomy volunteers consumed, in random order, flapjacks containing flaked barley on one occasion and barley flour on another. Ileostomy fluid was collected for analysis of starch and nonstrach polysaccharide (NSP) hourly for 12 h. The ratio of starch to NSP in ileostomy fluid was compared with that in the terminal ileum of eight randomly selected male rats consuming the flaked barley flapjack and another eight rats consuming the barley flour flapjack. RESULTS: After consuming flaked barley the terminal ileal starch-NSP ratio was 20 times lower in rats than in ileostomists and was 0.04 (s.e.m. 0.006) g/g compared with 0.89 (s.e.m. 0.05) g/g respectively. By contrast the starch-NSP ratio was very low after consuming the barley flour in both species; however the ratio was still lower in rats than in ileostomists and was 0.02 (s.e.m. 0.01) g/g compared with 0.05 (s.e.m. 0.01) g/g respectively. Using the NSP as an indigestible marker, starch from barley flake that resisted small intestinal digestion was calculated to be 0.7 (s.e.m. 0.02)% in rats compared with a higher value of 17 (s.e.m. 1)% in ileostomists. CONCLUSION: The cell walls of barley flake limit the extent of starch digestion in humans but in rats this appears not to be a limiting factor. In the present instance it was not possible to extrapolate results from rats to humans.

Adult↗
PubMed1996

Ketorolac versus meperidine for pain relief after orthopaedic surgery.

In this double-blind, randomized, multicenter study, 244 patients with at least moderate pain after major orthopaedic surgery received intramuscular Ketorolac (60 mg followed by 30 mg) or intramuscular meperidine (100 mg or placebo) every 2 to 6 hours as needed for as many as 5 days. Analgesic response was evaluated for 6 hours after initial study drug administration and thereafter each night at bedtime. Both active treatment groups had similar 3-hour summed pain intensity difference and 3-hour total pain relief scores after the first dose that were superior to placebo. The 6-hour summed pain intensity difference and total pain relief scores were significantly higher with Ketorolac than with meperidine or placebo. The mean daily categorical pain intensity scores were comparable with Ketorolac and meperidine, and both were significantly superior to placebo. Patient ratings of overall medication efficacy were significantly better with Ketorolac than with meperidine. In both patient and observer evaluations, Ketorolac was significantly better tolerated than meperidine, and the number of patients reporting adverse events was lower with Ketorolac than with meperidine. Following major orthopaedic surgery, Ketorolac provided effective analgesia that was superior to placebo and at least comparable with meperidine. Ketorolac was better tolerated than meperidine.

Adolescent↗
PubMed1995

Reduction in numerical synapse density in chick (Gallus domesticus) dorsal hippocampus following transient cerebral ischaemia.

Transient forebrain ischaemia was induced by a two-vessel occlusion method in the domestic chick. One week post-surgery, hippocampal tissue was processed for electron microscopy and synapse density assessed using the disector technique. Hippocampal volume was estimated using image analysis of serial coronal cryostat sections. The density of asymmetric synapses was significantly reduced (27%; P < 0.005) in ischaemic chicks. This appears to be a real reduction as hippocampal volume was not significantly decreased.

Animals↗
PubMed1995

A contiguous clone map over 3 Mb on the long arm of chromosome 11 across a balanced translocation associated with schizophrenia.

Forty-nine clones derived by microdissection of a schizophrenia-associated t(1;11)(q42.1;q14.3) breakpoint region have been assigned by somatic cell hybrid mapping to seven discrete intervals on the long arm of human chromosome 11. Eleven of the clones were shown to map to a small region immediately distal to the translocation breakpoint on 11q. A 3-Mb contiguous clone map of this region was established by isolation of corresponding YAC recombinants. The contig was oriented and shown to traverse the translocation breakpoint by FISH and microsatellite marker analysis. This contig will facilitate the isolation of candidate sequences whose expression may be affected by the translocation.

Base Sequence↗
PubMed1995

Isolation and characterisation of genes for sulphate activation and reduction in Aspergillus nidulans: implications for evolution of an allosteric control region by gene duplication.

A region of the Aspergillus nidulans genome carrying the sA and sC genes, encoding PAPS reductase and ATP sulphurylase, respectively, was isolated by transformation of an sA mutant with a cosmid library. The genes were subcloned and their functions confirmed by retransformation and complementation of A. nidulans strains carrying sA and sC mutations. The physical distance of 2 kb between the genes corresponds to a genetic distance of 1 cM. While the deduced amino acid sequence of the sA gene product shows homology with the equivalent MET16 gene product of Saccharomyces cerevisiae, the sC gene product resembles the equivalent MET3 yeast gene product at the N-terminal end, but differs markedly from it at the C-terminal end, showing homology to the APS kinases of several microorganisms. It is proposed that this C-terminal region does not encode a functional APS kinase, but is responsible for allosteric regulation by PAPS of the sulphate assimilation pathway in A. nidulans, and that the ATP sulphurylase encoding-gene (sC) of filamentous ascomycetes may have evolved from a bifunctional gene similar to the nodQ gene of Rhizobium meliloti.

Adenosine Triphosphate↗