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Biomedical subjects

J Bailey

Publications and source records attributed to J Bailey.

At least 109 records · Page 6Linked to original sources
PubMed1995

Oxytocics in developing countries.

OBJECTIVES: A prospective multicenter study of obstetric practices was conducted in three developing countries (Benin, Congo and Senegal) to analyze oxytocic use during labor. One of the objectives was to assess the possible negative effects of the treatment regimens instituted during the labor monitoring phase. METHODS: Four health districts participated in the study. All women who gave birth in one of the participating health facilities over a 6-month period in Benin and Congo, and over a 3-month period in Senegal, were recruited. The number of deliveries studied in each district varied from 457 to 1048. For each case a partogram was used to assess the progress of labor and the onset of dysfunctional labor. Information was collected on the risk factors for dysfunctional labor, stillbirths and resuscitation of the neonate. RESULTS: Each of the four collaborating centers used oxytocics preferentially to treat dysfunctional labor, but even in normal labor (i.e. with a normal partogram) oxytocics were used in 4.4-21.5% of cases. In normal labor the incidence of neonatal resuscitation was higher in cases with than in those without oxytocic use: the relative risks (R.R.) varied from 1.9 to 5.6; the odds ratios varied from 2.4 to 7.0, and both were statistically significant in the four settings. In addition the stillbirth rate was always higher, though not significantly, when oxytocics were used in normal labor (R.R. 1.2-2.2). When the data of the four centers were pooled, the global relative risk for stillbirths was 1.9, and the 95% confidence interval was 1.1-3.4. Logistic regression analysis was carried out for five confounding factors (primiparity, a previous complicated delivery, presence of meconium, ruptured membranes and educational level) to adjust the odds ratio for the risk of neonatal resuscitation when oxytocics were used in normal labor. Except in the case of Abomey in Benin, where the variable 'presence of meconium' decreased the odds ratio from 6.4 to 3.4, the adjusted odds ratios remained similar to their non-adjusted values. In cases of non-dysfunctional labor, nurses and midwives used oxytocics more often than lesser trained health personnel (R.R. 4.0 [3.2-5.1]). CONCLUSION: Our results show that an obstetric treatment which is safe when used in certain well-defined indications, may have significant negative effects when used in situations where the same technical quality of care cannot be guaranteed.

Developing Countries↗
PubMed1995

Isolation of chromosome-specific genes by reciprocal probing of arrayed cDNA and cosmid libraries.

We have identified and mapped 61 novel and previously described chromosome 17 and X genes, using a human placental cDNA library. These genes were isolated using a gene identification and mapping strategy based on reciprocal probing of arrayed chromosome specific cosmid and cDNA libraries. This strategy scans gridded cosmids for nuclear genes and isolates the expressed sequence by a cosmid to cDNA filter hybridization. Inherent to this approach is the advantage of identifying the corresponding genomic cosmid clone of a particular cDNA. The genomic and cDNA reagents can be used for fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) based mapping to resolve map positions of cDNAs belonging to gene families and those associated with multiple chromosomes. The downstream utility of reagents generated by the reciprocal probing methods is demonstrated in our studies.

Base Sequence↗
PubMed1995

Characterization of npf mutants identifying developmental genes in Physarum.

In Physarum polycephalum, uninucleate haploid amoebae develop into macroscopic multinucleate plasmodia. Wild-type, sexual development is triggered when two amoebae carrying different alleles of matA fuse to form a zygote which develops into a diploid plasmodium. Mutations in the matA genetic region give rise to apogamic strains in which a single haploid amoeba can develop into a haploid plasmodium. An essential stage in both sexual and apogamic plasmodium formation is an extended cell cycle in uninucleate cells, which ends with the formation of a binucleate cell by mitosis without cytokinesis. Using a 'brute force' screening method, we have isolated mutants blocked in apogamic plasmodium development. Genetic analysis showed that the mutations we have identified were unlinked to matA, unlike mutations previously identified following an enrichment step. Most of the loci revealed by our screen were represented by only one allele, indicating that further screening should lead to the identification of additional genes required for plasmodium development. Phenotypic analysis showed that different mutants were blocked at different stages of plasmodium formation. Some of the mutations blocking apogamic development at an early stage, close to the start of the long cell cycle, failed to block sexual development in zygotes homozygous for the mutation. Since the two modes of plasmodium formation differ only in the initiation of development, these mutations presumably interfere with the initiation process. In the remaining mutants, in which both sexual and apogamic development were blocked, development first became abnormal towards the end of the long cell cycle. This suggested that the wild-type gene products were required by this time and was consistent with previous evidence that many changes in cellular organization and gene expression occur during the long cell cycle. Each of these mutants showed a different terminal phenotype and some aspects of plasmodium development occurred normally although others were blocked, suggesting that development involves multiple pathways rather than a dependent sequence of events. Phenotypic analysis of double mutants supported this conclusion and also revealed epistatic interactions, presumably due to blocks in the same pathway. In several of the mutants, terminally differentiated cells died by an apoptosis-like mechanism; since this was never observed in vegetative cells, it was presumably triggered by the failure of development. Phenotypic analyses of additional mutants will extend our understanding of the pathways involved in plasmodium development.

Animals↗
PubMed1995

Sequences determining the cytoplasmic localization of a chemoreceptor domain.

The Escherichia coli serine chemoreceptor (Tsr) is a protein with a simple topology consisting of two membrane-spanning sequences (TM1 and TM2) separating a large periplasmic domain from N-terminal and C-terminal cytoplasmic regions. We analyzed the contributions of several sequence elements to the cytoplasmic localization of the C-terminal domain by using chemoreceptor-alkaline phosphatase gene fusions. The principal findings were as follows. (i) The cytoplasmic localization of the C-terminal domain depended on TM2 but was quite tolerant of mutations partially deleting or introducing charged residues into the sequence. (ii) The basal level of C-terminal domain export was significantly higher in proteins with the wild-type periplasmic domain than in derivatives with a shortened periplasmic domain, suggesting that the large size of the wild-type domain promotes partial membrane misinsertion. (iii) The membrane insertion of deletion derivatives with a single spanning segment (TM1 or TM2) could be controlled by either an adjacent positively charged sequence or an adjacent amphipathic sequence. The results provide evidence that the generation of the Tsr membrane topology is an overdetermined process directed by an interplay of sequences promoting and opposing establishment of the normal structure.

Alkaline Phosphatase↗
PubMed1995

A survey on hepatitis B vaccination policies in genitourinary medicine in UK and Ireland.

OBJECTIVE: To determine the policies applied in genitourinary medicine (GUM) departments in the United Kingdom (UK) and Ireland with regard to hepatitis B vaccination. DESIGN: All genitourinary medicine consultants were sent a questionnaire requesting information concerning their selection criteria and the management of patients offered Hepatitis B vaccine. If no response was obtained a second questionnaire was sent. The survey was carried out in 1993. SETTING: All genitourinary medicine departments in UK and Ireland. PARTICIPANTS: 234 consultants were sent the questionnaire. 153 consultants responded. RESULTS: Overall, there was a 65.4% response rate to the questionnaire. Almost all genitourinary physicians would offer the vaccine to male homosexuals and up to 74% offer it to all male homosexuals, intravenous drug users (IVDU) and prostitutes. Of the genitourinary physicians, 96% agreed that hepatitis B virus (HBV) serological markers should be checked prior to or simultaneously with vaccination, yet there was no agreement as to which marker should be performed. Up to 79% of consultants recalled the patients to check their response to vaccination but only 61% offered long term follow up after vaccination. CONCLUSION: HBV vaccine is offered to all male homosexuals, IVDU and prostitutes in GUM departments. Currently, the vaccine is not generally offered to patients who present with sexually transmitted diseases. Almost all genitourinary physicians (96%) agree that HBV serological markers should be checked prior to or simultaneously with the start of the vaccination course and 80% would request hepatitis B surface antibody levels after vaccination to identify inadequate responders and non-responders. From this survey, there appears to be a need for uniform post-vaccination HBV screening and timing and frequency of booster doses.

Consultants↗
PubMed1995

An MRI study of brain size in autism.

OBJECTIVE: This study was undertaken to obtain detailed measurements of the volume of the brain, using magnetic resonance imaging (MRI), in a carefully selected group of autistic subjects and comparison subjects. METHOD: Twenty-two male autistic subjects and 20 male volunteer comparison subjects were examined with detailed (1.5-mm slices) MRI throughout the entire brain. Total brain, total brain tissue, and total lateral ventricle volumes were measured by using manual tracing and automated techniques. RESULTS: After height and performance IQ were controlled, autistic subjects had significantly greater total brain, total tissue, and total lateral ventricle volumes than comparison subjects. CONCLUSIONS: These findings suggest that male autistic subjects have enlarged brains and that enlargement is a result of both greater brain tissue volume and greater lateral ventricle volume.

Adolescent↗
PubMed1995

Post traumatic stress disorder: turning the tide without opening the floodgates.

The development of the legal concept of nervous shock represents a compromise between the need to compensate those suffering psychiatric damage and the need to protect a defendant from unlimited liability. The criteria which have developed to achieve this balance are arbitrary ones, which take little account of psychological or physiological knowledge about post traumatic stress disorder. It is suggested that recent developments in scientific understanding of this condition could usefully inform the legal process, and that some aspects of the dilemma could be avoided.

Humans↗
PubMed1995

Pharmacokinetics of all-trans-retinoic acid administered on an intermittent schedule.

PURPOSE: Administration of all-trans-retinoic acid (ATRA) on a continuous daily schedule results in a rapid and sustained decrease in plasma drug concentrations. This pharmacokinetic study was performed to determine if administration of ATRA on an intermittent schedule could overcome the rapid decrease in plasma drug concentration and provide repetitive periods of higher plasma drug exposure. MATERIALS AND METHODS: ATRA was administered on repetitive cycles of 7 consecutive days of drug followed by 7 days without drug. On the days of pharmacokinetic monitoring, following an overnight fast, a fixed single oral dose of 40 mg/m2 was administered and frequent plasma samples were obtained over 8 hours. Patients had pharmacokinetic studies performed on the first and seventh days of the first week, and on the first day of the third and eleventh weeks. ATRA was measured in plasma with a reverse-phase high-performance liquid chromatography (HPLC) assay. RESULTS: Plasma exposure to ATRA as measured by the area under the plasma concentration-time curve (AUC) decreased significantly during the first week of drug administration, from a mean of 145 +/- 26 mumol/L.min on day 1 to 18 +/- 4 mumol/L.min by day 7. Plasma ATRA concentrations at the start of weeks 3 and 11 of this every-other-week schedule were equivalent to those achieved on day 1 of treatment, with mean AUCs of 177 +/- 39 and 128 +/- 30 mumol/L.min, respectively. CONCLUSION: An intermittent schedule of ATRA administration results in repetitive periods of exposure to concentrations of ATRA normally only observed on the first day of treatment. Phase II trials to evaluate the role of intermittent schedules of administration for ATRA are planned.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Phase I/II study of intermittent all-trans-retinoic acid, alone and in combination with interferon alfa-2a, in patients with epidemic Kaposi's sarcoma.

PURPOSE: A phase I/II study of oral all-trans-retinoic acid (ATRA; tretinoin), administered every other week alone and then in combination with interferon (IFN) alfa-2a, was undertaken to evaluate the activity, toxicity, and pharmacokinetics of this regimen in patients with human immunodeficiency virus (HIV)-associated Kaposi's sarcoma (KS). PATIENTS AND METHODS: Thirteen patients with HIV-associated KS, eight of whom had more than 100 CD4 cells/microL, were entered. The protocol initially called for patients to receive 150 mg/m2/d of ATRA every other week. However, this regimen was associated with headaches, and the initial dose of ATRA was reduced to 40 mg/m2/d orally in three divided doses, increasing to a maximum of 100 mg/m2/d. After 12 weeks, IFN alfa-2a could be added. RESULTS: The principal toxicities from ATRA were headaches (12 patients) and dry skin or lip (seven patients). Of 12 assessable patients, 10 had progressive disease and two had stable disease on ATRA alone. One of eight assessable patients who went on to receive ATRA plus IFN alfa-2a had partial response (PR). There were no overall changes in the serum HIV p24 antigen (Ag) level or CD4 count during treatment with ATRA alone. Peak ATRA levels decreased during the week of continuous ATRA therapy, but rebounded when treatment was resumed after a week without the drug. CONCLUSION: Intermittent ATRA therapy was reasonably well tolerated and provided a means to circumvent the low plasma exposure found with continuous ATRA therapy. However, we were unable to document antitumor activity in patients with HIV-associated KS.

Adult↗
PubMed1994

A luciferase expression system for Physarum that facilitates analysis of regulatory elements.

We have developed a transient expression system for the protist Physarum polycephalum based on firefly luciferase. We demonstrate the utility of this system for comparing the activities of different promoters in Physarum amoebae, and also for detecting genetic elements that affect the level of gene expression. This system is likely to facilitate improvements in the stable transformation of this organism.

Animals↗
PubMed1994

Epidermal growth factor receptor-dependent stimulation of amphiregulin expression in androgen-stimulated human prostate cancer cells.

Amphiregulin is a heparin-binding epidermal growth factor (EGF)-related peptide that binds to the EGF receptor (EGF-R) with high affinity. In this study, we report a role for amphiregulin in androgen-stimulated regulation of prostate cancer cell growth. Androgen is known to enhance EGF-R expression in the androgen-sensitive LNCaP human prostate carcinoma cell line, and it has been suggested that androgenic stimuli may regulate proliferation, in part, through autocrine mechanisms involving the EGF-R. In this study, we demonstrate that LNCaP cells express amphiregulin mRNA and peptide and that this expression is elevated by androgenic stimulation. We also show that ligand-dependent EGF-R stimulation induces amphiregulin expression and that androgenic effects on amphiregulin synthesis are mediated through this EGF-R pathway. Parallel studies using the estrogen-responsive breast carcinoma cell line, MCF-7, suggest that regulation of amphiregulin by estrogen may also be mediated via an EGF-R pathway. In addition, heparin treatment of LNCaP cells inhibits androgen-stimulated cell growth further suggesting that amphiregulin can mediate androgen-stimulated LNCaP proliferation. Together, these results implicate an androgen-regulated autocrine loop composed of amphiregulin and its receptor in prostate cancer cell growth and suggest that the mechanism of steroid hormone regulation of amphiregulin synthesis may occur through androgen upregulation of the EGF-R and subsequent receptor-dependent pathways.

Amino Acid Sequence↗
PubMed1994

Analysing general practitioners' referral decisions. I. Developing an analytical framework.

Despite a large volume of research, understanding the influences on general practitioner referral behaviour remains limited. This paper argues for the value of an approach to this area based on the analysis of individual referral decisions, rather than aggregated referral statistics. A framework for analysing referral decisions is described, developed from a study that collected accounts of 167 referral decisions from 28 general practitioners. The framework enables referral decisions to be examined at three levels of analysis of increasing generality. It also encompasses factors that influence general practitioners against making a referral as well as those that influence them towards referral, as it was found that both types of influence can be discerned in most cases. The types of study in which the framework would be a useful analytical tool are discussed.

Adolescent↗
PubMed1994

Analysing general practitioners' referral decisions. II. Applying the analytical framework: do high and low referrers differ in factors influencing their referral decisions?

An analytical framework of the referral decision was applied to the question of whether general practitioners (GPs) with relatively high and relatively low referral rates differed in the types of factors that influenced their referral decisions. Interview data from six high referring and six low referring GPs were compared at all levels of the framework, using both quantitative and qualitative content analysis. High referrers were found to mention significantly more negative factors than low referrers, i.e. they referred 'in spite of' reasons against referral. In particular, they referred patients in spite of having doubts about treatment effectiveness. Low referrers mentioned factors related to interpersonal processes significantly more often than high referrers, for example, GP-patient communication as an influence. Possible interpretations of these findings are discussed.

Adolescent↗
PubMed1994

Metabolic responses to nephrosis: effect of a low-protein diet.

To determine whether dietary protein restriction (LPD) causes protein catabolism in adriamycin nephrosis, nephrotic and control rats were paired by weight and gavage fed an 8.5% protein diet for 3 days (protocol 1) or 12 days (protocol 2). Fasting whole body protein turnover was then measured using a constant infusion of L-[1-14C]leucine. After 3 days of LPD, proteinuria decreased slightly and body weight did not change in either group. In contrast, leucine oxidation and urinary urea nitrogen excretion in nephrotic rats decreased by 18% and 37%, respectively (P < or = 0.05). After 12 days of LPD, weight loss did not differ between groups. In contrast to protocol 1, proteinuria decreased by 45% in nephrotic rats fed LPD for 12 days, and leucine oxidation rats increased to the level of control rats. Rates of whole body protein synthesis (PS) and degradation (PD) did not differ between nephrotic and control rats receiving LPD for 3 or 12 days, but were significantly lower than rates measured in rats fed 22% protein. We conclude that 1) proteinuria stimulates protein conservation even when dietary protein intake is restricted; 2) the decrease in amino acid oxidation was dependent on moderate proteinuria, since prolonged LPD ameliorated nephrosis and leucine oxidation rates increased to control levels; and 3) since weight loss and rates of whole body PS and PD in nephrotic and control animals were indistinguishable, moderate proteinuria did not increase protein catabolism.

Animals↗