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Biomedical subjects

M Gregory

Publications and source records attributed to M Gregory.

At least 19 recordsLinked to original sources

Haemostatic screening and identification of zebrafish mutants with coagulation pathway defects: an approach to identifying novel haemostatic genes in man.

Zebrafish were used as a model to study haemostasis, a vertebrate function of paramount importance. A limitation of the zebrafish model is the difficulty in assaying small amounts of blood to detect coagulation mutants. We report the use of a rapid total coagulation activity (TCA) assay to screen for coagulation defects in individual adult zebrafish. We screened the TCA in 1000 gynogenetic half-tetrad diploids derived from 86 clutches. Each clutch was from a single F1 female offspring of males mutagenized with ethylnitrosourea (ENU). We found 30-50% defective zebrafish among six clutches, consistent with a heritable defect. The assay developed here provided a rapid screen to detect overall coagulation defects. However, because of the limited amounts of plasma, we could not detect defects in specific pathways. Therefore, a novel, ultra-sensitive kinetic method was developed to identify specific pathway defects. To test whether the kinetic assay could be used as a screening tool, 1500 Florida wild-type zebrafish pairs were analysed for naturally occurring coagulation defects. We detected 30 fish with extrinsic pathway defects, but with intact common and intrinsic pathways. We conclude that it is now possible to identify specific coagulation pathway defects in zebrafish.

Actins↗

The Kaiser Permanente prenatal smoking-cessation trial: when more isn't better, what is enough?

INTRODUCTION: The effectiveness of low-cost smoking interventions targeted to pregnant women has been demonstrated, although few gains in absolute cessation rates have been reported in the past decade. Under conditions of typical clinical practice, this study examined whether outcomes achieved with brief counseling from prenatal care providers and a self-help booklet could be improved by adding more resource-intensive cognitive-behavioral programs. DESIGN: Randomized Clinical Trial. SETTING: A large-group-model managed care organization. PARTICIPANTS: 390 English-speaking women 18 years of age or older who self-reported to be active smokers at their initial prenatal appointment. INTERVENTION: Participants were randomized to one of three groups: (1) a self-help booklet tailored to smoking patterns, stage of change, and lifestyle of pregnant smokers; (2) the booklet plus access to a computerized telephone cessation program based on interactive voice response technology; or (3) the booklet plus proactive telephone counseling from nurse educators using motivational interviewing techniques and strategies. No attempt was made to change smoking-related usual care advice from prenatal providers. MAIN OUTCOME MEASURE: Biochemically confirmed abstinence measured by level of cotinine in urine samples obtained during a routine prenatal visit at approximately the 34th week of pregnancy. RESULTS: Twenty percent of participants were confirmed as abstinent with no significant differences found between intervention groups. Multivariate baseline predictors of cessation included number of cigarettes smoked per day, confidence in ability to quit, exposure to passive smoke, and educational level. No differential intervention effects were found within strata of these predictors or by baseline stage of readiness to change. Cessation rates among heavier smokers were strikingly low in all intervention groups. CONCLUSION: Neither a computerized telephone cessation program nor systematic provision of motivational counseling improved cessation rates over a tailored self-help booklet delivered within the context of brief advice from prenatal providers. Innovative strategies need to be developed to increase the effectiveness of existing prenatal smoking interventions. Special attention should be paid to the needs of heavier smokers.

Adult↗

Remote village survey for agents causing hepatosplenic disease in the Republic of Yemen.

The objective of this study was to epidemiologically describe potential infectious agents among rural people in the Republic of Yemen. This would aid clinicians in designing empirical therapy and public health officials in planning disease prevention. We sought to examine evidence for the geographical distribution of pathogens causing human hepatic and splenic disease among villagers and domestic animals living in three remote areas with differing altitudes. In June 1992, a cross-sectional survey was conducted at three survey sites of differing altitudes: 3080, 1440 and 250 m above sea level. Questionnaires, parasitic and serological tests were administered to 627 human volunteers. Additionally 317 domestic animals were studied. Malaria, schistosomiasis, and hepatitis B and C infections were found to be likely causes of human hepatic or splenic disease. Additionally, evidence of human and animal infections with the agents of brucellosis and Q fever was found: IgG antibodies against hepatitis E virus were discovered in two (2.0%) of the 100 volunteers. The prevalence of markers for human and animal disease was often lowest at the village of highest elevation, suggesting that increasing altitude, as a surrogate or a true independent risk factor, was protective against infection with the agents studied.

Adolescent↗

The intubating laryngeal mask. Use in failed and difficult intubation.

The use of the intubating laryngeal mask in three patients is described. In two patients for whom tracheal intubation using traditional techniques had failed, the intubating laryngeal mask was used to achieve successful tracheal intubation. The trachea of one of these patients was subsequently re-intubated for a second procedure using the same technique. A third patient with a cervical spine fracture whose trachea was electively intubated using the intubating laryngeal mask is also presented.

Aged↗

Calciphylaxis mimicking dermatomyositis: ischemic myopathy complicating renal failure.

BACKGROUND: Among the complications of chronic renal failure is a syndrome of medial calcification of small- to medium-sized arteries associated with ischemic necrosis of the skin and other organ systems, leading to gangrene and a poor prognosis. The syndrome has been reviewed in the renal, dermatologic, and surgical literature under the term calciphylaxis, which describes a postulated pathogenetic mechanism whereby sensitization to an endogenous or exogenous substance (such as parathyroid hormone) predisposes to calcium deposition after exposure to a challenging agent. Myopathy has rarely been reported as the presenting feature, and the syndrome has not been discussed in the neurologic literature. METHODS: We report two patients with renal failure and systemic calciphylaxis who presented to our hospital with myopathic complaints and signs suggesting dermatomyositis. We also discuss possible disease mechanisms and treatment. CONCLUSIONS: Because early treatment (including aggressively lowering the calcium and phosphate levels and parathyroidectomy) may improve the outcome, early recognition of the syndrome of calciphylaxis is essential.

Adult↗

High mutation detection rate in the COL4A5 collagen gene in suspected Alport syndrome using PCR and direct DNA sequencing.

Approximately 85% of patients with Alport syndrome (hereditary nephritis) have been estimated to have mutations in the X chromosomal COL4A5 collagen gene; the remaining cases are autosomal with mutations in the COL4A3 or COL4A4 genes located on chromosome 2. In the present work, the promoter sequence and previously unknown intron sequences flanking exons 2 and 37 of COL4A5 were determined. Furthermore, intron sequences flanking the other 49 exons were expanded from 35 to 190 to facilitate mutation analysis of the gene. Using this information, all 51 exons and the promoter region were PCR-amplified and sequenced from DNA of 50 randomly chosen patients with suspected Alport syndrome. Mutations were found in 41 patients, giving a mutation detection rate of 82%. Retrospective analysis of clinical data revealed that two of the cases might be autosomal. Although it could not be determined whether the remaining seven cases (14%) were autosomal or X chromosome-linked, it is likely that some of them were autosomal. It is concluded that PCR amplification and direct DNA sequencing of the promoter and exons is currently the best procedure to detect mutations in COL4A5 in Alport syndrome.

Amino Acid Substitution↗

Evidence of limited capacity and noise reduction with single-element displays in the location-cuing paradigm.

Precuing a location facilitates accuracy of identification of a target at that location and reduces noise from other nontarget characters in a multicharacter field. In 5 experiments, evidence for facilitation included higher accuracy with long precue-target intervals than with short intervals and higher accuracy when a precue indicated the correct location than with short intervals and higher accuracy when a precue indicated the correct location than when it indicated the wrong location. These results were found for each target-mask condition used (1 target with 1 mask, 1 target with 4 masks, or 1 target and 3 nontargets with 4 masks) in experienced and inexperienced observers. Evidence for noise reduction was found because accuracy was higher in the 1 target-1 mask condition than in the other conditions on correctly cued trials with short-cue-target intervals and on incorrectly cued trials. Data are related to methodological factors that are important to obtaining these effects and to capacity and noise reduction models.

Adolescent↗

Plasma bupivacaine concentrations associated with continuous extradural infusions in babies.

The maximum recommended dose for extradural infusions of bupivacaine in children older than 1 month is 0.5 mg kg-1 h-1 but there are few specific reports of the associated blood concentrations during infusions in babies. Toxic symptoms can occur in children at plasma concentrations of bupivacaine as low as 2 micrograms ml-1. We attempted to measure venous plasma concentrations of total and free bupivacaine in babies aged 3-12 months during extradural infusions given at a rate commonly used in our hospital. We studied eight babies (mean age 33 weeks; mean weight 7.8 kg). After a mean initial dose of 1.2 mg kg-1 (range 1.1-1.3 mg kg-1), bupivacaine was infused at a mean rate of 0.38 (0.36-0.39) mg kg-1 h-1 for a mean of 31 (4-44) h. Blood was obtained at 4, 8, 16, 24, 32 and 40 h after starting the infusion and plasma separated by centrifugation. Total plasma bupivacaine concentration was measured using high pressure liquid chromatography (HPLC). Plasma concentrations of total bupivacaine were mostly less than 2 micrograms ml-1. One baby had a concentration of 2.02 micrograms ml-1 at 32 h and showed clear evidence of accumulation of bupivacaine. Babies can accumulate bupivacaine and achieve plasma concentrations above the threshold for toxic side effects, despite infusion rates below the currently accepted maximum. The samples size in our study was small but we believe an extradural infusion rate of 0.375 mg kg-1 h-1 is probably an absolute maximum for babies younger than 12 months.

Abdomen↗

Home enteral feeding of children in the west of Scotland.

Home enteral feeding (HEF) is increasingly used to achieve positive energy and nitrogen balance in children with chronic disease outside hospital. It should be considered when oral feeding cannot or should not be used, and when nutritional support is the sole reason for hospitalisation. In the West of Scotland 156 children (80 male, 76 female) cared for by the Royal Hospital for Sick Children in Glasgow received HEF between 1st September 1994 and 1995. They ranged in age from 0 months to 23 years. Indications for HEF were cystic fibrosis (21), cerebral palsy (17), other neurological disease (29), congenital/metabolic abnormalities (23), chronic renal failure (17), neoplastic disease (17), gastrointestinal/hepatic' disease (12), failure-to-thrive (10), and cardiorespiratory disease (10). Most children received feeds by nasogastric tube (59%) or gastrostomy (41%). One child had a jejunostomy. Feeding regimens were continuous infusion (52%), bolus feeding along (26%), and a combination of bolus and infusion (22%). 73% of patients had infusion pumps. Duration of HEF ranged from one month to 12 years. 78% of children received standard infant or enteral feeds, some receiving energy supplements. The remainder received 'disease-specific' or other special feeds. There was a 23% increase in the number of children receiving HEF during the year of the study. HEF represents an affective way of improving the nutritional status of children with chronic disease at home. It frees hospital beds and nursing resources, is well accepted by children and their families and is growing rapidly as an alternative to hospitalisation.

Adolescent↗

The Southern California Kaiser-Permanente Chemical Dependency Recovery Program evaluation: results of a treatment outcome study in an HMO setting.

This report presents the methodology and outcomes of an evaluation of the Chemical Dependency Recovery Program (CDRP) of Southern California Kaiser-Permanente, a large group model HMO. CDRP treatment includes specialized detoxification inpatient facilities, day treatment and outpatient services. Substance use outcomes in a population of 1,986 patients consecutively entering treatment were obtained via telephone at six and twelve months post intake. For patients who consumed only alcohol at baseline (N = 621), significantly higher six month point prevalence abstinence rates were found among those who remained in treatment for a minimum of three months (89%), compared to those patients who failed to return for treatment after their intake (31%). For polydrug users (N = 1365), as contrasted with patients who utilized services only on their intake date, significantly higher six month point prevalence rates were restricted to those who remained in treatment for a minimum of six months (74% versus 21%). The evaluation documented the need for CDRP services, validated program effectiveness and highlighted areas for systematic improvement.

Adult↗

Identification of 17 mutations in ten exons in the COL4A5 collagen gene, but no mutations found in four exons in COL4A6: a study of 250 patients with hematuria and suspected of having Alport syndrome.

Conditions for polymerase chain-reaction amplification of ten exon regions (Exons 3, 7, 11 through 13, and 15 through 19) of the collagen COL4A5 gene and four exon regions (Exons 2, and 12 through 14) of the COL4A6 gene were sequenced and established in this study. These Type IV collagen genes contain 51 and 48 exons, respectively. The sequences of these exons were determined in the two genes in 250 male patients with hematuria and suspected Alport syndrome. Seventeen mutations were found in nine of the ten exons studied in the COL4A5 gene in 17 patients, whereas no mutations were identified in COL4A6. One mutation was identical in two patients known to be unrelated. The results indicate that mutations in COL4A5 that leading to renal failure are more frequent than those involved in classic Alport syndrome, and also that mutations in COL4A6 are not likely to cause this disease. Furthermore, mutations in COL4A5 are distributed quite randomly and no "hot spots" were found.

Adolescent↗

Flux analysis of microbial metabolic pathways using a visual programming environment.

This paper describes the use of a visual programming environment (LabVIEW) for the flux analysis of metabolic pathways. Representations of metabolic pathways are constructed in software from individual reaction elements (icons) which are linked together to indicate potential flux routes. Off-line bioprocess data are then used to supply the inputs and outputs to the metabolic pathway and the pathway fluxes are calculated. The metabolic system can be modelled at different levels of complexity and new pathways can be inserted into existing models. To illustrate this, flux analyses are performed on three Escherichia coli mutants with metabolic pathway deletions and insertions. The first analysis looks at organic acid production and the second at the effect of the presence in E. coli of an engineered pathway for toluene degradation.

Acetates↗

Ritual slaughter.

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Abattoirs↗

Fibroblast growth factor-2 (FGF-2) is present in maternal and cord serum, and in the mother is associated with a binding protein immunologically related to the FGF receptor-1.

Fibroblast growth factor-2 (FGF-2) is expressed in human fetal tissues and placenta. We, therefore, determined whether FGF-2 appeared in either fetal or maternal circulations during normal pregnancies [fetuses appropriate for gestational age (AGA)] or those complicated by fetal growth restriction (small for gestational age). Cordocentesis was performed, and matched maternal blood was collected between 19-39 weeks gestation, whereas maternal and cord blood and amniotic fluid (AF) were collected at term. FGF-2 was extracted from maternal serum (MS), cord serum (CS), and AF by heparin-Sepharose affinity chromatography and subjected to Western blot analysis or quantified by specific RIA. Western blot analysis of MS, CS, and AF revealed, in each case, a single immunoreactive FGF-2 species of 18 kilodaltons (kDa), although this was not present in nonpregnant serum. In AGA pregnancies, immunoreactive FGF-2 was present in MS from at least 18 weeks gestation and rose to maximum values at the end of second trimester (weeks 28-31; mean +/- SEM, 342 +/- 62 pmol/L), but by term had declined (weeks 40-42; 104 +/- 24 pmol/L). In CS, FGF-2 immunoreactivity was highest at weeks 18-20 of gestation (662 +/- 144 pmol/L), but thereafter, slowly declined to term (weeks 40-42; 119 +/- 28 pmol/L). Immunoreactive FGF-2 levels in MS and CS of small for gestational age pregnancies in the second trimester tended to be lower than those in AGA pregnancies, but differences were not statistically significant. AF also contained immunoreactive FGF-2 at term (91 +/- 35 pmol/L). Neutral gel chromatography on Sephadex G-200 revealed that FGF-2 immunoreactivity eluted as a broad peak with an apparent molecular size of 55-160 kDa. These same fractions contained peptides of 55-60, 90-95, and 120-130 kDa, which were recognized by antisera against the extracellular domain of the high affinity FGF receptor, FGFR1, after Western blot. Ligand blot analysis of the same nitrocellulose filters using 125I-labeled FGF-2 revealed that the 55- to 60-kDa species specifically bound FGF-2. This binding species was not recognized during Western blot analysis using an antiserum raised against the intracellular tyrosine kinase domain of FGFR1, suggesting that it represents a truncated receptor form. Similar FGFR1 immunoreactive species were present in nonpregnant female and male sera, but were barely detectable in term CS or AF.(ABSTRACT TRUNCATED AT 400 WORDS)

Amniotic Fluid↗