Biomedical subjects

G Brink

Publications and source records attributed to G Brink.

15 recordsLinked to original sources

PubMed1999

Characteristics of small breast and/or ovarian cancer families with germline mutations in BRCA1 and BRCA2.

For families with a small number of cases of breast and/or ovarian cancer, limited data are available to predict the likelihood of genetic predisposition due to mutations in BRCA1 or BRCA2. In 104 families with three or more affected individuals (average 3.8) seeking counselling at family cancer clinics, mutation analysis was performed in the open reading frame of BRCA1 and BRCA2 by the protein truncation test and mutation-specific assays. In 31 of the 104 families tested, mutations were detected (30%). The majority of these mutations (25) occurred in BRCA1. Mutations were detected in 15 out of 25 families (60%) with both breast and ovarian cancer and in 16 out of 79 families (20%) with exclusively cases of breast cancer. Thus, an ovarian cancer case strongly predicted finding a mutation (P < 0.001). Within the group of small breast-cancer-only families, a bilateral breast cancer case or a unilateral breast cancer case diagnosed before age 40 independently predicted finding a BRCA1 or BRCA2 mutation (P = 0.005 and P = 0.02, respectively). Therefore, even small breast/ovarian cancer families with at least one case of ovarian cancer, bilateral breast cancer, or a case of breast cancer diagnosed before age 40, should be referred for mutation screening.

Adult↗

PubMed1997

Hospital adaptation to risk-bearing: managerial implications of changes in purchaser-provider contracting.

A number of countries have adopted contracting reforms in which hospitals are placed at financial risk. This risk has stimulated a number of adaptive strategies to achieve organizational success. This paper presents a model of six forms of contracting relationships and reviews the adaptation strategies observed in three health systems: the USA, England and the Netherlands. These strategies include service diversification, improved management information systems, the employment of marketing and contract managers, the use of clinical pathways, case management and concurrent/retrospective review of hospital stays, quality management and quality assurance programs, pre-admission authorization, discharge planning, and physician profiling and participation in management. These adaptive strategies have three implications for managers: increased 'partnering', with purchasers, collaboration with medical staff, and assumption of managed care roles. Two groups of institutions are at risk from the changes in hospital contracting: university teaching hospitals and inner-city hospitals serving socially deprived populations. The paper ends with implications for the education of hospital managers and research on hospital management and adaptation to contracting.

Contract Services↗

PubMed1997

A high proportion of novel mutations in BRCA1 with strong founder effects among Dutch and Belgian hereditary breast and ovarian cancer families.

We have identified 79 mutations in BRCA1 in a set of 643 Dutch and 23 Belgian hereditary breast and ovarian cancer families collected either for research or for clinical diagnostic purposes. Twenty-eight distinct mutations have been observed, 18 of them not previously reported and 12 of them occurring more than once. Most conspicuously, a 2804delAA mutation has been found 19 times and has never been reported outside the Netherlands. A common haplotype spanning > or = 375 kb could be identified for each of the nine examined recurrent mutations, indicating the presence of multiple BRCA1 founder mutations in the Dutch population. The 2804delAA mutation has been estimated to have originated approximately 32 generations ago. No specific breast or ovarian cancer phenotype could be assigned to any of the common mutations, and the ovarian cancer incidence among 18 families with the 2804delAA mutation was heterogeneous.

Adult↗

PubMed1994

Self assembly of covalently anchored phospholipid supported membranes by use of DODA-Suc-NHS-lipids.

We present a novel preparation method for the self assembly of covalently anchored phospholipid supported membranes. The surface is gold covered by cysteamine. Vesicles containing DMPC and activated DODA-Suc-NHS-lipids assembled on this surface. The whole self-assembly process is monitored conveniently by Near Infrared Surface Plasmon Resonance (NIR-SPR). Comparing the data to those obtained by Ca(2+)-mediated vesicle fusion, confirmed this interpretation.

Dimyristoylphosphatidylcholine↗

PubMed1994

Spectinomycin interacts specifically with the residues G1064 and C1192 in 16S rRNA, thereby potentially freezing this molecule into an inactive conformation.

The upper stem of helix 34, consisting of the base-paired sequences C1063G1064U1065 and A1191C1192G1193, is suggested to be involved in the binding of spectinomycin. In E. coli 16S rRNA, each of the three mutations at position C1192 confers resistance to spectinomycin. In chloroplast ribosomes from tobacco plants and algae, resistance is conferred by single mutations at positions 1064, 1191, and 1193 (E. coli numbering). Since each of these mutations disrupt any of the three basepairs in the upper stem of helix 34, it has been postulated that spectinomycin can bind to this region and inhibit protein synthesis, only if its nucleotides are basepaired. We have tested this hypothesis by introducing disruptive and compensatory mutations that alter the basepair G1064-C1192. Using the specialized ribosome system, the translational activity of such mutants was determined, in the absence and presence of spectinomycin. We show that any of the three disruptive mutations A1064, C1064, and U1064 confer resistance, in accordance with the model for spectinomycin binding. Compensatory mutations A1064U1192, C1064G1192, and U1064A1192, however, maintained the resistance. This indicates that a basepaired conformation as such is not sufficient for spectinomycin binding, but rather that a G-C pair at positions 1064 and 1192 is required. In addition, we find that the translational activity of specialized ribosomes containing the mutations C1064G1192 is 5-fold lower compared to that of ribosomes containing any of the other mutations introduced, regardless whether spectinomycin is present or not. Since the introduction of C1064G1192 is expected to increase the stability of the upper stem of helix 34, we suggest that these mutations impair ribosome function by preventing the (transient) disruption of the upper stem. By analogy, we speculate that spectinomycin blocks protein synthesis by stabilizing the upper stem. In both cases, the 30S subunit would be frozen into an inactive conformation.

Base Sequence↗

PubMed1986

Comparison of cefixime and co-trimoxazole in acute uncomplicated urinary tract infection. A double-blind general practice study.

Five hundred and twenty-eight patients with presumptive acute uncomplicated urinary tract infection (UTI) were randomly assigned to receive cefixime 400 mg once daily, cefixime 200 mg twice daily or co-trimoxazole 2 tablets twice a day for 10 days; 477 completed at least 5 days of therapy. Of the patients 342 (65%) had positive baseline urine cultures, yielding 353 pathogens. A microbiological response was determined for 280 pathogens (79%), eradication being observed in over 94% of isolates; 153 pathogens (43%) were sensitive to both cefixime and co-trimoxazole and eradication was observed in over 96% of cases. Clinical response correlated well with microbiological response. The incidence of diarrhoea and stool changes was higher (P less than 0.005) in the patients who received cefixime once daily than in the other groups. There was a significantly higher incidence of stool changes with cefixime twice daily than with co-trimoxazole (P less than 0.05), but these did not necessitate discontinuation of therapy. Nausea was commoner with co-trimoxazole (P less than 0.05). The majority of pathogens isolated were Escherichia coli, Proteus mirabilis and staphylococci. Approximately 24% of E. coli were resistant in vitro to co-trimoxazole (P less than 0.005). Cefixime 200 mg twice daily is an effective and safe alternative to co-trimoxazole in the management of acute uncomplicated UTI.

Adult↗

PubMed1986

Circadian rhythm and diurnal excursion of plasma cortisol in diabetic pregnant women.

The effect of type I and II diabetes in pregnancy on the circadian rhythm and diurnal excursion of plasma cortisol was studied in the second and third trimesters and post partum. Cosignor analysis demonstrated persistence during gestation of the significant circadian rhythm of the nonpregnant state. As previously reported in control pregnancies, plasma cortisol levels (24-hour mean, nadir, peak, and nadir-peak excursion) increased during gestation while the relative excursion of cortisol (expressed as the percent deviation from the 24-hour mean) was blunted. No significant difference was found between diabetic groups or when diabetic groups were compared with control subjects. Nocturnal hypoglycemia was common among diabetic women during pregnancy and post partum. Although these episodes were usually asymptomatic, the mean concomitant cortisol levels were increased over the corresponding cortisol levels of nonhypoglycemic diabetic and control subjects. We conclude that differences between control and type I and II diabetic subjects in carbohydrate tolerance or glycemic excursion are not explained by differences in cortisol levels or rhythm. The pregnancy-associated blunting of the excursion of cortisol is consistent with an autonomous source of adrenocorticotropin. Asymptomatic nocturnal hypoglycemia is common in insulin-requiring diabetic women and is associated with increased cortisol secretion.

Circadian Rhythm↗

PubMed1983

Qualitative and quantitative assessment of the circadian rhythm of cortisol in pregnancy.

The effect of pregnancy on the circadian rhythm and diurnal excursion of plasma cortisol and urinary free corticoids was examined in a sequential study during the second and third trimester and 6 to 12 weeks post partum. Hourly blood samples from six subjects and 8-hour urine collections from eight subjects were obtained around the clock. While the circadian rhythm was maintained during gestation, plasma cortisol levels (24-hour mean, nadir, peak, and nadir-peak excursion) increased. The relative excursion of plasma cortisol (expressed as the percentage of deviation from the 24-hour mean) exhibited remarkable blunting compared with postpartum values. This pregnancy-associated blunting of plasma cortisol excursion was indicated by a significant reduction in the: (1) mean peak and nadir excursion, (2) integrated area between the percent deviation curve and the 24-hour mean, and (3) mean slope of the major incremental and decremental segments of the percent deviation curve. The circadian rhythm and diurnal excursion of plasma cortisol were reflected in urinary free corticoid values. Mean 24-hour urinary free corticoid concentrations increased 180% during gestation over nonpregnant levels. Nadir concentrations of urinary free corticoids in pregnancy exceeded peak nonpregnant levels. The gestational rise of metabolically active free cortisol and adrenocorticotropin (ACTH), and the pregnancy-associated blunting of the excursion of plasma cortisol may be explained by an autonomous source of ACTH during gestation.

Adolescent↗

PubMed1980