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Biomedical subjects

A Green

Publications and source records attributed to A Green.

At least 199 records · Page 11Linked to original sources
PubMed1998

Population screening for neonatal liver disease: a feasibility study.

BACKGROUND: Extra-hepatic biliary atresia and several other causes of neonatal liver disease carry high mortality and morbidity rates, especially if not treated early in life. Despite professional recommendations, delayed referral of infants with prolonged jaundice continues to be a significant problem. One approach to reducing the age of referral and diagnosis is population screening to detect significant conjugated hyperbilirubinaemia as an index of liver dysfunction. METHODS: To investigate this possibility, and to provide reference data on bilirubin and its conjugated and unconjugated fractions in a normal newborn population, 1157 neonates were anonymously tested (median age 7 days, range 4-28 days) using surplus plasma from routinely collected neonatal screening specimens, using dry slide chemistry. RESULTS: Of 2310 specimens received, 50% were suitable for analysis. The remainder were either haemolysed or insufficient (10% and 40% of the total, respectively). Total bilirubin concentrations ranged from 9 to 428 micromol/l and conjugated bilirubin from 0 to 175 micromol/l, although the latter was rarely increased to more than 30 micromol/l (2.5th-97.5th percentile ranges 15-285 micromol/l and 0-18 micromol/l, respectively). The range of the percentage of conjugated bilirubin was 0-57% (2.5th-97.5th percentile; range 0-20%). CONCLUSION: An increased conjugated bilirubin, expressed as a concentration or as the percentage of the total bilirubin, could be used as a specific marker to screen for liver dysfunction in neonates. This approach has the potential to improve the age of referral and the prognosis of infants with neonatal liver disease.

Bilirubin↗
PubMed1998

History of tropical military service and risk of primary cutaneous melanoma in Queensland men.

A population-based case-control study was undertaken to determine whether cutaneous melanoma is associated with past military service in tropical locations. The participants were 150 male residents of southern Queensland aged 50 or over with a first diagnosis of cutaneous melanoma notified to the Queensland Cancer Registry between 1 July 1993 and 30 June 1994; 150 age-matched controls were randomly selected from the Queensland electoral roll. Data were collected from participants using a structured questionnaire. Overall, 82 (55%) cases and 80 (53%) controls reported a period of military service. Of these, 42% of both cases and controls spent part of their military service in tropical locations, with little difference in the distribution of duration of tropical service between the two groups. Compared with those who had no tropical military service, the risk of melanoma among those who had served more than 3 years in the tropics was 0.9 (0.3-2.7). Against a background level of very high risk of melanoma among Queensland men, there was no evidence that tropical military service materially increased the risk.

Aged↗
PubMed1998

Characterization of the glnK-amtB operon of Azotobacter vinelandii.

To determine whether in Azotobacter vinelandii the PII protein influences the regulation of nif gene expression in response to fluxes in the ammonium supply, the gene encoding PII was isolated and characterized. Its deduced translation product was highly similar to PII proteins from other organisms, with the greatest degree of relatedness being exhibited to the Escherichia coli glnK gene product. A gene designated amtB was found downstream of and was contranscribed with glnK as in E. coli. The AmtB protein is similar to functionally characterized ammonium transport proteins from a few other eukaryotes and one other prokaryote. glnK and amtB comprise an operon. Attempts to isolate a stable glnK mutant strain were unsuccessful, suggesting that glnK, like glnA, is an essential gene in A. vinelandii. amtB mutants were isolated, and although growth on limiting amounts of ammonium was similar in the mutant and wild-type strains, the mutants were unable to transport [14C]methylammonium.

Azotobacter vinelandii↗
PubMed1998

A comparison of disease and gene frequencies of inborn errors of metabolism among different ethnic groups in the West Midlands, UK.

OBJECTIVE: To assess birth and gene frequencies of specific autosomal recessively inborn errors of metabolism (IEM) within different ethnic groups. DESIGN: Retrospective study in a regional centre for investigation and treatment of IEM. SUBJECTS: All children born within the West Midlands NHS Region, UK, during the decade immediately preceding the 1991 National Census. METHODS: Birth frequencies for individual IEM were calculated separately for the main ethnic groups in the West Midlands using data from the West Midlands Neonatal Screening Programme, the regional register of IEM patients, and population frequencies from the National Census. Gene frequencies were calculated using previously documented observations on parental consanguinity rates and inbreeding coefficients. RESULTS: The overall incidence of recorded IEM was tenfold higher among Pakistanis compared to white children (1:318 v 1:3760), whereas only one AfroCaribbean child was identified (incidence 1:16 887). Tyrosinaemia type 1, cystinosis, mucopolysaccharidosis type 1, non-ketotic hyperglycinaemia, and hyperchylomicronaemia all occurred more frequently among Pakistanis. An increased gene frequency was only confirmed for tyrosinaemia. The incidence of phenylketonuria was similar in Pakistani and white children (1:14 452 v 1:12 611), but the gene frequency was significantly lower in Pakistanis (1:713 v 1:112). These results illustrate the interplay between gene frequency and parental consanguinity in determining disease frequencies in different populations, and indicate anticipated disease frequencies in the absence of consanguineous marriage. These figures have implications for the organisation of services for management of inborn errors, for genetic counselling, and for the assessment of gene flow in world populations.

Ethnicity↗
PubMed1998

Troglitazone inhibits progesterone production in porcine granulosa cells.

Troglitazone (a thiazolidinedione that improves insulin resistance) lowers elevated androgen concentrations in women with polycystic ovarian syndrome. In this study, we assessed the direct effects of troglitazone on steroidogenesis in porcine granulosa cells. Troglitazone inhibited progesterone production in a dose- and time-dependent manner (earliest effects at 4 h, maximum at 24 h) without affecting cell viability. Progesterone production was also inhibited by troglitazone in the presence of 25-hydroxycholesterol, indicating that the drug does not affect intracellular cholesterol transport. Troglitazone also inhibited FSH- and forskolin-stimulated progesterone secretion. The reduced progesterone production was accompanied by marked elevations of pregnenolone concentrations, suggesting inhibition of 3beta-hydroxysteroid dehydrogenase (3beta-HSD). The activity of 3beta-HSD in troglitazone-treated granulosa cells was decreased by more than 60%, compared with controls after 24 h. Troglitazone did not affect aromatase activity in porcine granulosa cells. In summary, troglitazone has direct effects on porcine granulosa cell steroidogenesis. The drug specifically inhibits 3beta-HSD activity, resulting in impaired progesterone production. The clinical relevance of this direct in vitro effect on steroidogenesis needs further investigation.

3-Hydroxysteroid Dehydrogenases↗
PubMed1998

Inhibition of protein synthesis by nitric oxide correlates with cytostatic activity: nitric oxide induces phosphorylation of initiation factor eIF-2 alpha.

BACKGROUND: Nitric oxide (NO) is cytostatic for proliferating cells, inhibits microbial growth, and down-regulates the synthesis of specific proteins. Studies were undertaken to determine the mechanism by which NO inhibits total protein synthesis and whether the inhibition correlates with established cytostatic activities of NO. MATERIALS AND METHODS: In in vitro experiments, various cell types were exposed to NO using either donors or expression of inducible NO synthase (iNOS). The capacity of NO to suppress total protein synthesis, measured by incorporation of 35S-methionine into protein, was correlated with the capacity of NO to suppress cell proliferation, viral replication, or iNOS expression. Phosphorylation of eIF-2 alpha was examined as a possible mechanism for the suppressed protein synthesis by NO. RESULTS: Both NO donors and expression of the iNOS suppressed total protein synthesis in L929 cells and A2008 human ovarian tumor cells in parallel with decreased cell proliferation. Suppressed protein synthesis was also shown to correlate with decreased vaccinia virus proliferation in murine peritoneal macrophages in an iNOS-dependent manner. Furthermore, iNOS expression in pancreatic islets or RAW264.7 cells almost completely inhibited total protein synthesis, suggesting that nonspecific inhibition of protein synthesis may be the mechanism by which NO inhibited the synthesis of specific proteins such as insulin or iNOS itself. This possibility was confirmed in RAW264.7 cells where the inhibition of total protein synthesis correlated with the decreased iNOS protein. The decrease in protein levels occurred without changes in iNOS mRNA levels, implicating an inhibition of translation. Mechanistic studies revealed that iNOS expression in RAW264.7 cells resulted in the phosphorylation of eIF-2 alpha and inhibition of the 80S ribosomal complex formation. CONCLUSIONS: These results suggest that NO suppresses protein synthesis by stimulating the phosphorylation of eIF-2 alpha. Furthermore, our observations indicate that nonspecific inhibition of protein synthesis may be a generalized response of cells exposed to high levels of NO and that inhibition of protein synthesis may contribute to many of the described cytostatic actions of NO.

Animals↗
PubMed1998

Neonatal screening: current trends and quality control in the United Kingdom.

Neonatal screening for phenylketonuria (PKU) and congenital hypothyroidism (CHT) is universal across the UK using heel prick blood collected at 6-14 days of age. Additional programmes for sickle cell disorders, cystic fibrosis, Duchenne muscular dystrophy and galactosaemia are provided in some areas. The number of inherited metabolic disorders (IMDs) has greatly increased since the introduction of PKU screening, and there have been major advances in treatment, e.g. organ transplantation, drug therapy. Recent developments in technology have expanded the possibilities for screening using the heel prick blood specimen, particularly the application of tandem mass spectrometry. There is a case for introducing tandem mass spectrometry, limited to clearly defined diseases where specificity is adequate and there are satisfactory diagnostic tests. Any change in newborn screening to a much broader group of disorders must be carefully introduced and monitored preferably as a pilot study. A key component of a laboratory screening service is quality control. There are well established UK programmes for PKU and CHT. Consideration of the needs for other disorders is now an important priority.

Congenital Hypothyroidism↗
PubMed1998

Current concepts of shoulder arthroplasty.

Shoulder arthroplasty is an accepted treatment for certain proximal humerus fractures and for glenohumeral arthritis. The indications for shoulder arthroplasty are fairly well defined and the outcomes are predictable and highly successful. However, it is a technically demanding surgical procedure, with which few orthopaedic surgeons gain much experience. Most of the currently available implant systems are modifications of the original unconstrained components that were introduced by Neer. Current issues of controversy include implant modularity, glenohumeral mismatch, implant fixation, and the role of glenoid replacement in outcome.

Arthritis↗
PubMed1998

The primordial mind and the work of the negative.

This paper was given at the celebration of Bion's centennial in 1997. At the request of the organisers of this conference, the work of Bion has been brought into perspective with the author's. The author has chosen to illumine Bion's concept of the primordial mind and considers the transformation of the beta-elements into the alpha ones. He also refers to Bion's distinction of thoughts without thinker and thinking as needing thoughts to be thought by a thinker (thinking apparatus). The main point of the paper is Bion's opposition of 'nothing' and 'no thing'. The author refers to Freud's paper on 'Negation'. He recalls his own model of the double limit. He tries to show how Freud's conception of representation has a much wider field than is usually stated. He emphasises differences between Freud's and Bion's 'basic assumptions'. After having tried to clarify Bion's ideas on 'O', 'K and -K', he recalls Bion's reference to Keats's negative capability. The author then gives a short account of his own concept of the 'work of the negative', finding correspondences with Bion's own concepts. As a conclusion two Indian myths are recalled for their great symbolic value.

Defense Mechanisms↗
PubMed1998

Action STAT! The crisis nurse.

To provide quality care with limited staff and create a safer environment, managers created a new "crisis nurse" position.

Emergency Service, Hospital↗
PubMed1997

A bioluminescent assay for agonist activity at potentially any G-protein-coupled receptor.

Transient expression of apoaequorin in Chinese hamster ovary (CHO) cells and reconstitution with the co-factor coelenterazine resulted in a large, concentration-dependent agonist-mediated luminescent response following cotransfection with the endothelin ETA, angiotensin ATII, thyrotropin-releasing hormone (TRH), and neurokinin NK1 receptors, all of which interact pre-dominantly with the G alpha q-like phosphoinositidase-linked G-proteins. A substantially greater luminescence was obtained with mitochondrially targeted apoaequorin compared to cytoplasmically expressed apoaequorin. To generate a system amenable for the study of agonist activity at virtually any G-protein-coupled receptor the alpha subunit of the receptor promiscuous G-protein G alpha 16 was either transiently or stably expressed in CHO cells together with apoaequorin. In cells expressing G alpha 16, but not in its absence, agonists at a series of receptors which normally interact with either G alpha s or G alpha i were now able to cause a luminescent response from mitochondrially targeted apoaequorin. In the case of the A1 adenosine receptor, this response was clearly a result of activation of G alpha 16 and not a consequence of the release of the G alpha i-associated beta/gamma complex, as the luminescent response was unaffected by pertussis toxin treatment of the cells, whereas agonist-mediated inhibition of adenylyl cyclase activity was attenuated. These studies describe the use of coexpressed apoaequorin as a reporter for G-protein-coupled receptor-mediated calcium signaling. Furthermore, coexpression of G alpha 16 and apoaequorin provides a basis for a generic mammalian cell microplate assay for the assessment of agonist action at virtually any G-protein-coupled receptor, including orphan receptors for which the physiological signal transduction mechanism may be unknown.

Adenosine-5'-(N-ethylcarboxamide)↗
PubMed1997

Tubal sterilisation, hysterectomy and decreased risk of ovarian cancer. Survey of Women's Health Study Group.

We have examined the effect of tubal sterilisation and hysterectomy on risk of ovarian cancer in a large case-control study in eastern Australia involving 824 women aged 18-79 years, diagnosed with epithelial ovarian cancer between 1990 and 1993, and 855 controls randomly selected from the electoral roll. Relative risks for ovarian cancer were estimated using multiple categorical regression to adjust for age, parity, oral contraceptive use and other risk factors. Tubal sterilisation was associated with a 39% reduction in risk of ovarian cancer (RR 0.61, 95% CI 0.46-0.85) and hysterectomy with a 36% reduction (RR 0.64, 95% CI 0.48-0.85). Risk remained low 25 years after surgery and was reduced irrespective of sterilisation technique, and estimates were similar among various types of epithelial ovarian cancer. The greatest reduction (74%) was observed among women with primary peritoneal tumours. Pelvic infection and use of vaginal sprays or contraceptive foams were not related to ovarian cancer, while use of talc in the perineal region slightly but significantly increased risk among women with patent fallopian tubes. Reportedly heavy or painful menses, perhaps associated with retrograde flow, were associated with ovarian cancer, and reduction in risk of disease after hysterectomy was greatest among women who had heavy periods. Our findings support the theory that contaminants from the vagina, such as talc, and from the uterus, such as endometrium, gain access to the peritoneal cavity through patent fallopian tubes and may enhance the malignant transformation of ovarian surface epithelium. Surgical tubal occlusion may reduce the risk of ovarian cancer by preventing the access of such agents.

Adolescent↗
PubMed1997

Population based study of prevalence of islet cell autoantibodies in monozygotic and dizygotic Danish twin pairs with insulin dependent diabetes mellitus.

OBJECTIVE: To study the comparative importance of environment and genes in the development of islet cell autoimmunity associated with insulin dependent diabetes mellitus. DESIGN: Population based study of diabetic twins. SETTING: Danish population. SUBJECTS: 18 monozygotic and 36 dizygotic twin pairs with one or both partners having insulin dependent diabetes. MAIN OUTCOME MEASURES: Presence of islet cell antibodies, insulin autoantibodies, and autoantibodies to glutamic acid decarboxylase (GAD65) in serum samples from twin pairs 10 years (range 0-30 years) and 9.5 years (2-30 years) after onset of disease. RESULTS: In those with diabetes the prevalence of islet cell antibodies, insulin autoantibodies, and autoantibodies to glutamic acid decarboxylase in the 26 monozygotic twins was 38%, 85%, and 92%, respectively, and in the dizygotic twins was 57%, 70%, and 57%, respectively. In those without diabetes the proportions were 20%, 50%, and 40% in the 10 monozygotic twins and 26%, 49%, and 40% in the 35 dizygotic twins. CONCLUSION: There is no difference between the prevalence of islet cell autoantibodies in dizygotic and monozygotic twins without diabetes, suggesting that islet cell autoimmunity is environmentally rather than genetically determined. Furthermore, the prevalence of islet cell antibodies was higher in the non-diabetic twins than in other first degree relatives of patients with insulin dependent diabetes. This implies that the prenatal or early postnatal period during which twins are exposed to the same environment, in contrast with that experienced by first degree relatives, is of aetiological importance.

Adolescent↗
PubMed1997

[Incidence of juvenile-onset diabetes in Denmark. A prospective registration in the counties of Fyn, Ribe, Sønderjylland and Vejle].

To provide contemporary figures of the incidence of childhood onset diabetes mellitus in Denmark, a prospective routine registration system has been established. The present study covered the population of children aged 0-14 years in four Danish counties, observed during the calendar years 1989 through 1993 concerning new cases of the disease. A total of 201 cases (113 boys and 88 girls) were registered, corresponding with a sex- and age-adjusted incidence rate of 17.4 per 100,000 person-years. Based on a validation analysis the study material is considered virtually complete. Overall, the incidence among boys was slightly higher than among girls, but not statistically significantly so. The incidence rate increased with age for both boys and girls. The results confirm that the incidence of childhood onset diabetes in Denmark is relatively high. Compared with previous Danish studies there has been an increase of about 20-25% in the incidence during the last 20 years. Our study stresses the importance of a continuous registration of new cases of childhood diabetes in Denmark, thereby providing clues for further aetiological studies as well as providing reference values for the planning of the diabetes health care. Our results indicate that at least two independent ascertainment sources must be employed to ensure complete registration in studies that rely upon voluntary registration as the primary reporting source.

Adolescent↗