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Biomedical subjects

J Browne

Publications and source records attributed to J Browne.

At least 37 records · Page 2Linked to original sources
PubMed1999

Characterization of the murine A1 adenosine receptor promoter, potent regulation by GATA-4 and Nkx2.5.

Adenosine acts via A1 adenosine receptors (A1ARs) in the heart and brain to potently influence mammalian physiology. A1ARs are expressed very early in embryonic development, and A1ARs are among the earliest expressed G protein coupled receptors in the heart and brain. To understand the biologic basis of A1AR expression, a genomic fragment containing the murine A1AR promoter was cloned. Reporter assay studies using DDT1 MF2 cells that express A1ARs revealed that 500 base pairs of the proximal A1AR promoter contained essential elements for A1AR gene expression. Transgenic mice with A1AR proximal promoter coupled with the beta-galactosidase reporter gene had heavy labeling of the brain and atria, consistent with normal patterns of A1AR expression. Within the proximal A1AR promoter, putative binding sites for cardiac transcription factors GATA and Nkx2.5 were identified. Co-expression studies revealed that GATA-4 and Nkx2.5 could individually drive A1AR promoter activity and act synergistically to activate A1AR expression. These observations suggest that embryonic A1AR expression involves activation of the A1AR promoter by GATA-4 and Nkx2.5.

Animals↗
PubMed1999

Topical amethocaine (Ametop) is superior to EMLA for intravenous cannulation. Eutectic mixture of local anesthetics.

PURPOSE: A eutectic mixture of local anesthetics (EMLA) is commonly used to provide topical anesthesia for intravenous (i.v.) cannulation. One of its side effects is vasoconstriction, which may render cannulation more difficult. A gel formulation of amethocaine (Ametop) is now commercially available. The aim of this study was to compare EMLA and Ametop with regard to the degree of topical anesthesia afforded, the incidence of vasoconstriction and the ease of i.v. cannulation. METHODS: Thirty two ASA I adult volunteers had a #16 gauge i.v. cannula inserted on two separate occasions using EMLA and Ametop applied in a double blind fashion for topical anesthesia. Parameters that were recorded after each cannulation included visual analogue pain scores (VAPS), the presence of vasoconstriction and the ease of cannulation, graded as: 1 = easy, 2 = moderately difficult, 3 = difficult and 4 = failed. RESULTS: The mean VAPS +/- SD after cannulation with Ametop M was 12+/-9.9 and with EMLA was 25.3+/-16.6 (P = 0.002). Vasoconstriction occurred after EMLA application on 17 occasions and twice after Ametop (P = 0.001). The grade of difficulty of cannulation was 1.44+/-0.88 following EMLA and 1.06+/-0.25 with Ametop (P = 0.023). CONCLUSIONS: Intravenous cannulation was less painful following application of Ametop than EMLA. In addition, Ametop caused less vasoconstriction and facilitated easier cannulation. Its use as a topical anesthetic agent is recommended, especially when i.v. access may be problematic.

Administration, Topical↗
PubMed1999

A gene map of the rat derived from linkage analysis and related regions in the mouse and human genomes.

We report the localization by linkage analysis in the rat genome of 148 new markers derived from 128 distinct known gene sequences, ESTs, and anonymous sequences selected in GenBank database on the basis of the presence of a repeated element. The composite linkage map of the rat contributed by our group integrates mapping information on a total of 370 different known genes, ESTs, and anonymous mouse or human sequences, and provides a valuable tool for comparative genome analysis. 206 and 254 homologous loci were identified in the mouse and human genomes respectively. Our linkage map, which combines both anonymous markers and gene markers, should facilitate the advancement of genetic studies for a wide variety of rat models characterized for complete phenotypes. The comparative genome mapping should define genetic regions in human likely to be homologous to susceptibility loci identified in rat and provide useful information for the identification of new potential candidates for genetic disorders.

Animals↗
PubMed1999

The transfer of two embryos instead of three to reduce the risk of multiple pregnancy: a retrospective analysis.

PURPOSE: Our purpose was to investigate whether a reduction in the number of embryos transferred from three to two would help reduce the incidence of multiple pregnancies and yet leave the pregnancy rate unaffected. METHODS: Women were treated in a routine clinical in vitro fertilization program and the results analyzed retrospectively. RESULTS: There was no reduction in the pregnancy rate when two embryos were transferred compared with three. Indeed, there was actually an increase in pregnancy rate after the transfer of two embryos in those cases with one or more embryos remaining after the transfer. CONCLUSIONS: The transfer of only two embryos compared to three in women younger than 40 years of age does not compromise the chance of pregnancy. Triplets were not seen in the limited series of patients when only two embryos were transferred, but the incidence of twins remained the same. Further consideration should be given to strategies that enable the transfer of single embryos without compromising the pregnancy rate.

Adult↗
PubMed1999

A radiation hybrid map of the rat genome containing 5,255 markers.

A whole-genome radiation hybrid (RH) panel was used to construct a high-resolution map of the rat genome based on microsatellite and gene markers. These include 3,019 new microsatellite markers described here for the first time and 1,714 microsatellite markers with known genetic locations, allowing comparison and integration of maps from different sources. A robust RH framework map containing 1,030 positions ordered with odds of at least 1,000:1 has been defined as a tool for mapping these markers, and for future RH mapping in the rat. More than 500 genes which have been mapped in mouse and/or human were localized with respect to the rat RH framework, allowing the construction of detailed rat-mouse and rat-human comparative maps and illustrating the power of the RH approach for comparative mapping.

Animals↗
PubMed1999

The effects of EMLA and a topical formulation of 4% amethocaine (Ametop) on pain associated with retrobulbar injection.

Retrobulbar block is commonly performed to provide anaesthesia for cataract extraction. This technique can cause significant discomfort. A prospective, randomised, placebo-controlled trial was carried out to investigate the efficacy of a eutectic mixture of local anaesthetics (EMLA) and a 4% amethocaine topical formulation (Ametop) in reducing the pain of retrobulbar injection. Ametop and EMLA proved to be of similar efficacy, both being superior to a placebo in alleviating the discomfort of retrobulbar block. No significant side-effects were observed with the use of either formulation.

Aged↗
PubMed1999

An unusual complication of minitracheostomy.

A 72-year-old woman had a minitracheostomy inserted for sputum retention. This was undertaken by a relatively junior resident who opted to use an early model minitracheostomy kit Minitrach II. The following day the patients condition deteriorated and intubation was warranted, at which time it was apparent to senior staff that the minitracheostomy had been malpositioned. Ten days later, formal tracheostomy was performed under general anaesthesia. After incision, an abscess in the thyroid gland was found. Histology subsequently revealed a Hurthle cell tumour of the thyroid. Thyroid abscess is exceedingly rare. It typically occurs in abnormal thyroid tissue and with a focus on infection. The combination of Hurthle cell adenoma and a foreign body (the minitracheostomy) was evidently causative in this instance. This complication of minitracheostomy insertion has not to our knowledge, previously been reported.

Abscess↗
PubMed1999

A profile of the clients of male sex workers in three Australian cities.

OBJECTIVE: This paper describes the profile of clients as reported by 186 male sex workers in three Australian cities. METHOD: The data were collected using a diary which was completed after each commercial sexual encounter with a male client over a two-week period. The data reported in this study are based on reports from 2,088 sex encounters and a profile of 1,776 clients. RESULTS: The findings reveal, for example, that the most common source used for recruiting clients was advertisements, followed by escort agencies, although there were differences between the three cities; the majority of the clients were in their 40s but clients of street workers were younger; clients were most often classified as 'middle class', with differences by source of client recruitment; less than half the clients were identified as being gay and a significant number were identified as bisexual or straight; alcohol and drug use took place in a small percentage of the encounters; most workers had some information about their clients, such as occupation and home number; violence was infrequent; and unsafe sex was requested in a minority of the encounters. CONCLUSION: Overall, the results reveal that clients of male sex workers are a highly heterogeneous group. IMPLICATIONS: The paper highlights a number of issues which can further promote safety and public accountability in male sex work.

Adolescent↗
PubMed1999

Pharmacokinetics of novel erythropoiesis stimulating protein compared with epoetin alfa in dialysis patients.

Novel erythropoiesis stimulating protein (NESP) is a hyperglycosylated analogue of recombinant human erythropoietin (Epoetin) which has an increased terminal half-life in animal models. The aim of this study was to extend these observations to humans. Using a double-blind, randomized, cross-over design, the single-dose pharmacokinetics of Epoetin alfa (100 U/kg) and an equivalent peptide mass of NESP were compared following intravenous bolus in 11 stable peritoneal dialysis patients. This was followed by an open-label study to determine the single-dose pharmacokinetics of an equivalent peptide mass of NESP by subcutaneous injection in six of these patients. The mean terminal half-life for intravenous NESP was threefold longer than for intravenous Epoetin (25.3 versus 8.5 h), a difference of 16.8 h (95% confidence interval, 9.4 to 24.2 h, P = 0.0008). The area under the serum concentration-time curve was significantly greater for NESP (291.0 +/- 7.6 ng x h per ml versus 131.9 +/- 8.3 ng x h per ml; mean +/- SEM; P < 0.0005), and clearance was significantly lower (1.6 +/- 0.3 ml/h per kg versus 4.0 +/- 0.3 ml/h per kg; mean +/- SEM; P < 0.0005). The volume of distribution was similar for NESP and Epoetin (52.4 +/- 2.0 ml/kg versus 48.7 +/-2.1 ml/kg; mean +/-SEM). The mean terminal half-life for subcutaneous NESP was 48.8 h. The peak concentration of subcutaneous NESP was approximately 10% of that following intravenous administration, and bioavailability was approximately 37% by the subcutaneous route. The longer half-life of NESP is likely to confer a clinical advantage over Epoetin by allowing less frequent dosing in patients treated for anemia.

Adult↗
PubMed1999

Effective treatment of localized Darier's disease with adapalene 0.1% gel.

Darier's disease is an autosomal dominant disorder of keratinization that can produce unique clinical manifestations. Oral and topical retinoid products have been the mainstay therapy for this population, but local as well as systemic side effects often limit their effectiveness. A case of localized Darier's disease is presented that responded promptly and with no side effects to the topical application of adapalene 0.1% gel. A review of treatments for Darier's disease is presented.

Adapalene↗
PubMed1999

Presentation of ALS to the otolaryngologist/head and neck surgeon: getting to the neurologist.

Patients with early symptoms of bulbar amyotrophic lateral sclerosis (ALS) are usually referred to the otolaryngologist without a diagnosis. Careful examination of the speech quality and a physical exam, including the vocal cords, should be undertaken. The emotional state of the patient should be considered, and a diagnosis should not be offered before a neurologic consultation has been obtained. Patients with late symptoms of bulbar ALS almost always present with both significant speech and swallowing abnormalities. Evaluation can be difficult because many abnormalities are found on examination. Advanced progression of symptoms is a clear indication for rapid referral to a neurologist if a diagnosis has not already been made. Supportive and symptomatic care should be offered to the patient immediately. The University of Washington Neuromuscular Clinic for Speech and Swallowing Disorders has seen 600 new neurologic patients since 1986, 211 of whom were ALS patients. The introduction of percutaneous gastrostomy has greatly changed the management of ALS patients, and 75 patients have undergone this procedure (32% because of inadequate swallowing, 68% for declining vital capacity). Medical management to improve symptoms may be indicated before surgery. Surgical options for patients with late salivary presentation are uncommon and include removal of the submaxillary glands, tracheostomy, and laryngeal or salivary diversion procedures. Laryngectomy or laryngeal diversion procedures are only very rarely indicated. Although tracheostomy usually interferes with swallowing and worsens aspiration, it may rarely be indicated in patients with late airway presentation for glottic narrowing or artificial respiratory support. Symptomatic management of patients with bulbar ALS is usually best undertaken by a multidisciplinary clinic that can provide a physically and psychologically supportive environment.

Aged↗
PubMed1998

A physical map of 30,000 human genes.

A map of 30,181 human gene-based markers was assembled and integrated with the current genetic map by radiation hybrid mapping. The new gene map contains nearly twice as many genes as the previous release, includes most genes that encode proteins of known function, and is twofold to threefold more accurate than the previous version. A redesigned, more informative and functional World Wide Web site (www.ncbi.nlm.nih.gov/genemap) provides the mapping information and associated data and annotations. This resource constitutes an important infrastructure and tool for the study of complex genetic traits, the positional cloning of disease genes, the cross-referencing of mammalian genomes, and validated human transcribed sequences for large-scale studies of gene expression.

Animals↗
PubMed1998

Quality of life of elderly patients with isolated systolic hypertension: baseline data from the Syst-Eur trial. Syst-Eur Trial Investigators.

OBJECTIVE: To describe measures of quality of life of elderly patients with isolated systolic hypertension at entry to a placebo-controlled randomized trial of antihypertensive treatment and to investigate factors associated with these. DESIGN: Cross-sectional analyses at entry to a randomized controlled trial. SETTING: Patients attending hypertension clinics or general practitioners' surgeries at 30 centres in 10 European countries. PATIENTS: Six hundred and thirty-one patients aged 60 years or more, with a sitting systolic blood pressure during the run-in phase of 160-219 mmHg, a sitting diastolic blood pressure below 95 mmHg and a standing systolic blood pressure of 140 mmHg or more. MAIN OUTCOME MEASURES: Cognitive function tests (Reitan Trail Making A and B), Brief Assessment Index (a measure of depressed mood) and four subscales from the Sickness Impact Profile (Ambulation, Social Interaction, Sleep and Rest and Housework). RESULTS: Poor quality of life was generally associated with increasing age, previous treatment with antihypertensive drugs, presence of cardiovascular complications and, among women, high diastolic blood pressure, higher consumption of alcohol and high body mass index. CONCLUSIONS: At entry to the trial there was considerable heterogeneity of patients in terms of measures of quality of life and cognitive performance. It remains to be determined whether these influence subsequent quality of life during randomized treatment.

Age Factors↗
PubMed1997

Location of the first genetic locus, PKDr1, controlling autosomal dominant polycystic kidney disease in Han:SPRD cy/+ rat.

The Han:SPRD cy/+ strain develops a form of slowly progressive disease that appears similar in many respects to that seen in the autosomal dominant polycystic kidney disease (ADPKD) in humans. We have performed a total genome scan in an experimental backcross population derived from affected Han:SPRD cy/+ rat (PKD) and non-affected Wistar Ottawa Karlsburg rat (WOK) using 117 microsatellite markers. The genetic dissection of PKD allowed us to map on rat chromosome 5, a quantitative trait locus (QTL) controlling PKD, kidney mass and plasma urea concentration. The homology region is likely to reside on human chromosome 8. The gene responsible for PKD in Han:SPRD cy/+ rat is neither PKD1, localised on human chromosome 16, nor PKD2, localised on human chromosome 4. Therefore, we propose that this new locus be denoted PKDr1. The detection of the PKDr1 locus and associated QTL should accelerate research into the genetic causes of ADPKD.

Animals↗
PubMed1997

Identification of a major susceptibility locus on chromosome 6p and evidence for further disease loci revealed by a two stage genome-wide search in psoriasis.

Psoriasis is a common chronic inflammatory disorder of the skin. To further understand the pathogenesis of psoriasis we have chosen to investigate the molecular genetic basis of the disorder. We have used a two-stage approach to search the human genome for the location of genes conferring susceptibility to psoriasis, using a total of 106 affected sibling pairs identified from 68 independent families. As over a third of the extended kindreds included affected relatives besides siblings, in addition to an analysis of allele sharing between affected sibling pairs, a novel linkage strategy was applied that extracts full non-parametric information. Four principal regions of possible linkage were identified on chromosomes 2, 8, 20 (p <0.005) and markers from the MHC region at 6p21 (p <0.0000006) for which significant evidence of linkage disequilibrium was also observed (p <0.00002). Whilst data from limited case control associations exist to implicate the MHC, the results of this genome wide analysis demonstrate that, at least in the population studied, a gene or genes located within the MHC and close to the class 1 HLA loci, represent the major determinant of the genetic basis of psoriasis.

Chromosomes, Human, Pair 6↗