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Biomedical subjects

H Burger

Publications and source records attributed to H Burger.

At least 55 records · Page 3Linked to original sources
PubMed2000

Cyclical etidronate use is not associated with symptoms of peptic ulcer disease.

OBJECTIVE: To investigate whether the alkylbisphosphonate etidronate is associated with an increased risk of gastrointestinal symptoms. METHODS: We conducted an observational follow-up study on a possible relationship between etidronate use and the risk of gastrointestinal symptoms in a cohort of 2754 women over 50 years of age. The study was performed with data on drug prescriptions obtained from the PHARMO database in the Netherlands. Women were included when they used either cyclical etidronate (n = 1050) or estrogen (n = 1704) for at least 14 days. They were followed-up for incident use of antiulcer drugs while on exposure medication. RESULTS: The mean ages were 72 years and 59 years in the etidronate and estrogen groups, respectively. In total, there were 95 women with incident prescriptions for gastrointestinal events after a median duration of follow-up of 2.7 months (range 0.1-19.4 months). The crude relative risk of a gastrointestinal event for etidronate compared with estrogen use was 1.2 [95% confidence interval (95% CI) 0.8-1.8]. Adjusted for baseline age, use of corticosteroids, salicylates and nonsteroidal anti-inflammatory drugs, the relative risk reversed to 0.6 (95% CI 0.4-1.2). CONCLUSION: The use of cyclical etidronate is not associated with an elevated risk of symptoms of peptic ulcer disease.

Aged↗
PubMed2000

Hip geometry, bone mineral distribution, and bone strength in European men and women: the EPOS study.

Hip geometry and bone mineral density (BMD) have been shown previously to relate, independently of each other, to risk of hip fracture. We used Lunar DPX "beta" versions of hip strength analysis (HSA) and hip axis length (HAL) software to analyze scans from ten representative age-stratified population samples in the European Prospective Osteoporosis Study (EPOS). All 1617 subjects were >50 years of age, and 1033 were women. The data were modeled with gender and center as categorical variables. The bone mineral density of the upper half of the femoral neck declined at a faster rate with age than that in the lower half. Femoral neck cross-sectional moment of inertia (CSMI), a measure of resistance to bending, showed no significant age reduction in either gender. However, height and weight effects on CSMI were significantly more beneficial in men than in women (0.002 < p < 0.012) and the weight effect appeared to be mediated by bone mineral content (BMC). Compressive stress (Cstress), defined as the stress in the femoral neck at its weakest cross section arising from a standardized fall, was higher in women. Although Cstress increased with body weight when BMC was held constant, in practice it fell through the association and statistical interaction of rising body weight with rising BMC. HAL, as expected, was strongly positively associated with male gender and also height (p < 0.0001). Hip strength-related indices were markedly center-dependent. Significant differences (p < 0.0001) were noted between the centers for all the variables investigated that related to hip geometry. Adjustment for femoral neck bone mineral content (totBMC) showed these center differences to account for >50% of center variation in hip strength, which remained highly significant (p < 0.0001). We conclude that there are substantial geographical differences in femoral neck geometry as well as in BMD. These geometric variations may contribute to the large variations in hip fracture risk across Europe. The effects of aging on hip strength need to be explored in longitudinal studies.

Age Factors↗
PubMed2000

Effects of a venous cuff at the venous anastomosis of polytetrafluoroethylene grafts for hemodialysis vascular access.

INTRODUCTION AND METHODS: The most frequent complication of polytetrafluoroethylene (PTFE) arteriovenous grafts for hemodialysis is thrombotic occlusion due to stenosis caused by intimal hyperplasia. This complication is also known for peripheral bypass grafts. Because the use of a venous cuff at the distal anastomosis improves the patency of peripheral bypass grafts, we considered that it might also improve the patency of PTFE arteriovenous grafts. Therefore, a randomized multicenter trial was carried out to study the effect of a venous cuff at the venous anastomosis of PTFE arteriovenous grafts on the development of stenoses and the patency rates. RESULTS: Of the 120 included patients, 59 were randomized for a venous cuff. The incidence of thrombotic occlusion was lower in the cuff group (0.68 per patient-year) than in the no-cuff group (0. 88 per patient-year; P =.0007). However, the primary and secondary patency rates were comparable. The cuff group tended to have fewer stenoses at the venous and arterial anastomoses when examined with duplex scan. Graft failure was higher in patients with an initial anastomosing vein diameter smaller than 4 mm (7 of 18 [39%]) than in those with a vein diameter of 4 mm or larger (16 of 88 [18%]; P =. 052). Local edema, skin atrophy, and obesity yielded a higher risk on graft failure (23% vs 11%). CONCLUSION: A venous cuff at the venous anastomosis of PTFE arteriovenous grafts for hemodialysis reduced the incidence of thrombotic occlusions; stenosis at the venous anastomosis was reduced. However, this did not result in a better patency rate. Therefore, the venous cuff should not be used routinely. Initial vein diameter and local problems (edema, obesity, or skin atrophy) appear to be the most important risk factors for graft failure.

Arteriovenous Shunt, Surgical↗
PubMed2000

Prevalence of gestational diabetes mellitus in polycystic ovarian syndrome (PCOS) patients pregnant after ovulation induction with gonadotrophins.

Our aims were: 1. To investigate if women with PCOS who become pregnant using gonadotrophins have a higher incidence of gestational diabetes mellitus (GDM) compared to spontaneously pregnant matched control women, 2. To compare the prevalence of GDM in PCOS women with that in women with hypo/eugonadotrophic hypogonadism and in unexplained infertility and 3. To investigate differences in pregnancy outcomes between the groups. This was a retrospective case-control study. Women with PCOS were matched with a control by age, BMI, and ethnicity. There were 60 women with PCOS, 11 with hypogonadotrophic hypogonadism, 6 with eugonadotrophic hypogonadism, and 12 with unexplained infertility. Control women were those who attended a major public hospital for antenatal care and delivery We found no difference in the prevalence of GDM between the PCOS (22%) and the controls (17%) or between the PCOS and other groups. Women with GDM (diet or insulin controlled) had a significantly higher BMI than women without GDM (p = 0.019). There was no difference in pregnancy outcomes between the groups. There was a significant dependence of babies' birthweight on mother's BMI (p<0.001).

Adult↗
PubMed2000

Patterns of chromosomal imbalances in muscle invasive bladder cancer.

Cytogenetic investigations of bladder cancer suggested that development and progression is characterized by specific chromosomal aberrations. In order to identify genetic changes linked to muscle invasive tumors and metastatic growth we analyzed 67 bladder carcinomas (30 pT1 and 37 pT2-4) by means of comparative genomic hybridization (CGH). The most frequent changes were gains of chromosome 1q (54%), 8q (54%), 17q (49%), 2p (30%), 12 (30%), 5p (25%), 3q (24%) and 6p (24%) as well as losses of 11p (43%), 8p (42%), 9p (36%), 11q (34%), 2q, 4q, 5q (30% each), 9q (27%) and 10q (27%). Previously not described amplifications were found at 5p11-p13, 7q21-q31, 9p24 and 17q24-q25. Gains of 3q, 7p, and 18p were markedly more frequent in pT2-4 in comparison to pT1 carcinomas but the difference did not reach statistical significance. Non-metastatic tumors showed more aberrations on average than metastatic carcinomas, although no particular change was found to be predominating in either group. Our data confirm previous findings of strong genetic similarities between minimally and deeply invasive bladder carcinomas but argue for differences between metastatic and non-metastatic disease.

Carcinoma, Transitional Cell↗
PubMed2000

Osteoporosis and salt intake.

AIM: Recently, it has been hypothesized that salt intake may be related to the risk of osteoporosis. The aim of this review was to summarize the evidence for such relationship and to discuss possible mechanisms. DATA SYNTHESIS: We performed a review of the scientific literature on osteoporosis, particularly its etiology, and then focussed on studies addressing the relation between salt intake on the one hand, and calcium balance, bone resorption, bone mineral density and fractures on the other. Although a relation between high salt intake and increased bone loss is biologically plausible, the most pertinent studies relating salt intake to bone mineral density are only suggestive of high salt consumption as a risk factor for osteoporosis. Unfortunately, studies on fracture risk and salt intake are lacking. CONCLUSION: The relationship between salt intake and osteoporosis is still controversial. A possible relation between salt intake and fracture risk should be addressed in future studies.

Bone Density↗
PubMed1999

Alterations of carbohydrate and lipid intermediary metabolism during inhibition of glucose-6-phosphatase in rats.

S 4048 (1-[2-(4-Chloro-phenyl)-cyclopropylmethoxy]-3, 4-dihydroxy-5-(3-imidazo[4, 5-b]pyridin-1-yl-3-phenyl-acryloyloxy)-cyclohexanecarboxylic acid), a derivative of chlorogenic acid, specifically inhibits the glucose-6-phosphate translocating component T1 of the glucose-6-phosphatase system. Its pharmacological effect was studied on carbohydrate and lipid parameters in rats. In starved and fed rats, S 4048 caused a dose-dependent reduction of blood glucose levels with a corresponding increase in hepatic and renal glycogen and glucose-6-phosphate. The major quantitative route of carbon flux in the liver during S 4048-induced inhibition of the glucose-6-phosphatase activity seemed to be glycogenesis. Plasma free fatty acids were increased secondarily due to the S 4048-induced hypoglycemia. Hepatic triglycerides were increased possibly due to increased re-esterification of the readily available free fatty acids. Glucose-6-phosphate translocase inhibitors may be useful for experimentally studying aspects of type 1 glycogen storage disease in laboratory animals as well as for the therapeutic modulation of inappropriately high rates of hepatic glucose production in type 2 diabetes.

Animals↗
PubMed1999

CCR5 genotype and resistance to vertical transmission of HIV-1.

A human gene has been identified that affects susceptibility to HIV-1 infection. The gene codes for CCR5, the coreceptor for macrophage-tropic strains of HIV-1. Individuals who are homozygous for a deleted, mutant form of the gene, delta32, display a high degree of natural resistance to sexual and parenteral transmission of HIV-1. To investigate whether delta32 plays a role in vertical transmission, we determined the CCR5 genotype of 552 children born to infected mothers in the United States and correlated the genotypes with HIV-1 infection status. Of these children, 13% were white, 30% Latino, and 56% African American, reflecting the ethnic makeup of infected women in the United States. The delta32 gene frequency varied among these groups, ranging from 0.08 in whites to 0.02 in both Latinos and African Americans. Approximately 27% of the children in each ethnic group were infected. Four children were identified as delta32 homozygotes, two uninfected whites (3.77%) and two uninfected Latinos (1.68%). None of the infected children displayed the delta32 homozygous genotype. Among Latinos and whites, the number of uninfected children who carried the homozygous delta32 mutation was significantly greater than that predicted by the Hardy-Weinberg equilibrium (p < .001 for Latinos, p = .044 for whites). This association was noted in Latino and white children whose mothers were either treated or untreated with zidovudine. These data document the occurrence of the homozygous delta32 genotype among children of HIV-1-infected mothers and suggest that this mutant genotype may confer protection from mother-to-child transmission of HIV-1. They also suggest that sexual, parenteral, and vertical transmission all involve processes that use CCR5 as a coreceptor for primary HIV-1 infection. Therefore, blocking the CCR5 receptor may provide an additional strategy to prevent HIV-1 vertical transmission.

Alleles↗
PubMed1999

Distinct p53-independent apoptotic cell death signalling pathways in testicular germ cell tumour cell lines.

The induction of apoptosis by diverse apoptotic stimuli was studied in a panel of 6 testicular germ cell tumour (TGCT) cell lines with defined p53 status. Although the sensitivity to a particular stimulus varied considerably among the TGCT cell lines, the differences in response were not associated with the presence of functional p53. Mutant (mt) p53-expressing NCCIT and S2 (no p53 protein) were both readily triggered into apoptosis by cisplatin and doxorubicin, while wild-type(wt)-p53-transactivation-competent 2102 EP cells failed to undergo drug-induced apoptosis. Moreover, transactivation-deficient NCCIT cells and wtp53-expressing NT2 cells were equally sensitive to cisplatin, doxorubicin, gamma radiation, and cell-permeable C2-ceramide. Our p53 data suggest that, at least in this panel of non-isogeneic TGCT cell lines, hypersensitivity to therapeutic agents is not associated with p53 status. Next, we examined the impact of p53 inactivation on apoptosis induction in isogeneic NT2 sublines expressing human papillomavirus E6 protein. Evidently, abrogation of p53 function did not affect the hypersensitivity to apoptotic stimuli. We noted that drug-sensitive S2 cells were highly resistant to radiation-induced apoptosis, indicating distinct signalling pathways for chemotherapy and irradiation. The impaired radiation-induced apoptotic pathway in S2 and 2102 EP could not be restored by addition of cell-permeable C2-ceramide, suggesting that the blockade is downstream of ceramide generation. Ligation of Fas/APO-1/CD95 by anti-Fas effectively induced apoptosis in Fas-antigen expressing S2, 2102 EP and 833 KE. The efficient Fas-mediated activation of apoptosis in drug-, radiation-, and ceramide-resistant 2102 EP cells further suggests that diverse apoptosis-inducing factors may use distinct signalling pathways. In summary, we demonstrated the presence of distinct p53-independent apoptotic pathways in TGCT cells.

Apoptosis↗
PubMed1999

Incremental cost of medical care after hip fracture and first vertebral fracture: the Rotterdam study.

The aim of this study was to estimate the additional cost of medical care (the incremental cost) caused by incident hip and vertebral fractures, using a matched case cohort design within a longitudinal follow-up study. Incident hip fractures were recorded using the regular follow-up system of the Rotterdam Study. Incident vertebral fractures were recorded by morphometric comparison of spinal radiographs taken at intervals of 2.2 years on average. The matched control group was randomly selected from other participants of the Rotterdam Study in whom no fracture occurred during follow-up, but who were otherwise comparable at baseline. Cases were matched for age, gender, self-perceived health, ability to perform activities of daily life, living situation and general practitioner. Medical expenditure was assessed by retrieval of the general practice medical records and by recording all hospital and nursing home admissions, and all general practice and outpatient visits. Pharmaceutical consumption was recorded through the computerized records of the central pharmacy. Valid results were obtained for 44 pairs (91%) in the hip fracture and for 42 pairs (93%) in the vertebral fracture group. Cost of medical consumption in the year before the hip fracture was similar in patients and control subjects, but the incremental cost in the first year after the hip fracture was almost US$10 000. In the second year after hip fracture the incremental cost was still about $1000. Accounting for the excess mortality in hip fracture patients had little effect on cost in the first year, but cost in the second year was doubled to almost $2000. For vertebral fractures, we did not detect important acute care costs, but these fractures were associated with a yearly recurrent incremental cost of over $1000. However, almost half this difference was already present before the occurrence of the fracture, and was attributable to hospital admissions. The remainder of the incremental cost was mainly due to pharmaceutical consumption and to a lesser extent to admissions to orthopedic surgery wards. We conclude that hip fractures cause excess mortality and an important incremental cost especially during the first year, and that these could probably be avoided by prevention of hip fractures. For vertebral fractures we found no evidence of important acute care costs but we observed a yearly returning incremental cost. Part of this incremental cost, however, was pre-existing and might therefore by caused by co-morbidity.

Aged↗
PubMed1999

Added value of bone mineral density in hip fracture risk scores.

Hip fractures constitute a major health problem. For effective prevention, high-risk groups need to be identified. The objective here was to develop hip fracture risk scores while assessing the added value of bone mineral density relative to more conventional risk indicators. We prospectively followed during 4 years a cohort of 5208 persons (2193 men) aged 55 years and over from the Rotterdam Study, a population-based cohort study conducted in the Netherlands. Risk scores for hip fracture were constructed using several conventional risk indicators requiring interview and anthropometry only, and bone mineral density. During follow-up, 50 persons (14 men) suffered hip fracture. Hip fracture risk was independently determined by age, gender, height, the use of a walking aid, cigarette smoking, and either bone mineral density or weight. We developed two risk scores, with and without bone mineral density. The observed 4-year risk ranged from 3/3389 (0.1%) to 17/169 (10.1%) for the lowest and highest category of the score including bone mineral density, respectively. For the score without bone mineral density, these risks were 8/3117 (0.3%) and 16/144 (11.1%), respectively. The area under the receiver operating characteristic curve indicating discriminatory power was 0.88 for the risk score including, and 0.83 for the score excluding, bone mineral density (p for difference = 0.04). In conclusion, risk scores with and without bone mineral density measurement can be used for hip fracture risk assessment in elderly persons. While the score with bone mineral density has a modestly better performance, the score requiring interview and anthropometry only may be especially useful in primary care settings.

Aged↗
PubMed1999

PCR-mediated recombination: a general method applied to construct chimeric infectious molecular clones of plasma-derived HIV-1 RNA.

A PCR-based approach was developed that provides a powerful tool for engineering recombinant molecules without reliance on restriction sites. DNA sequences were first amplified by high-fidelity PCR using Pfu polymerase; they were then used both as 'megaprimers' and templates in subsequent asymmetric long PCR amplifications to form chimeric clones. To demonstrate the technique, we constructed chimeric full-length HIV-1 clones derived from reverse-transcribed plasma viral RNA and proviral LTRs. Biologic characterization of these clones showed that most were infectious in tissue culture and sequence analysis demonstrated an error rate of only one base change in 20 kb of DNA sequence. For PCR-mediated recombination, it is necessary to know the sequence of the 3' and 5' overlapping regions of the desired PCR products. This method may be extended to include construction of chimeras between any DNA fragments lacking sequence homology. Such chimeras may be constructed by introducing overlapping sequences to one of the fragments. To ensure that unwanted mutations have not been introduced into the clones constructed by this method, each clone should be sequenced. Our results demonstrate that by using a high-fidelity polymerase and highly controlled PCR conditions, the PCR-introduced error rate can be greatly minimized. This new procedure may be used to construct infectious chimeras of HIV or SIV for studies of vaccines and pathogenesis. Moreover, the method is designed to exchange viral genes at precise boundaries to study individual gene products from different HIV genomes. It can also be used to construct expression vectors for production of specific proteins or delivery vectors for gene transfer and gene therapy. Finally, the technique described here provides a versatile tool to transfer genes or gene fragments from different sources for genetic investigation and engineering.

Chimera↗
PubMed1999

Mood and the menopausal transition.

This study determined which variables affect women's mood state during the menopausal transition by using six prospective annual assessments of a community-based sample of 354 Australian mid-aged women. Repeated measures multivariate analysis of covariance found that negative mood scores decreased significantly over time and were not related to natural menopausal transition, follicle-stimulating hormone, estradiol, inhibin, age, or education. The magnitude of negative mood was significantly predicted by baseline reporting of premenstrual complaints, negative attitudes to ageing and menopause, and parity of one. During follow-up, the magnitude of negative mood was significantly adversely affected by: prior experience of negative mood, experience of bothersome symptoms, poor self-rated health, negative feelings for partner, no partner, current smoking, low exercise, daily hassles, and high stress. Negative mood was reduced by decreasing symptoms, improving health, positive feelings for partner, gaining a partner, and reducing stress. The menopausal transition had an indirect effect in amplifying the effect of reducing paid work, poor health, and daily hassles.

Adult↗
PubMed1999

Estrogen receptor polymorphism predicts the onset of natural and surgical menopause.

Age at menopause and risk of hysterectomy have strong genetic components, but the genes involved remain ill defined. We investigated whether genetic variation at the estrogen receptor (ER) gene contributes to the variability in the onset of menopause in 900 postmenopausal women, aged 55-80 yr, of the Rotterdam Study, a population-based cohort study in The Netherlands. Gynecological information was obtained, and if women reported surgical menopause, validation of type and indication of surgery was accomplished by checking medical records. The ER genotypes (PP, Pp, and pp) were assessed by PCR using the PvuII endonuclease. Compared with women carrying the pp genotype, homozygous PP women had a 1.1-yr (P < 0.02) earlier onset of menopause. Furthermore, an allele dose effect was observed, corresponding to a 0.5-yr (P < 0.02) earlier onset of menopause per copy of the P allele. The risk of surgical menopause was 2.4 (95% confidence interval, 1.5-3.8) times higher for women carrying the PP genotype compared to those in the pp group, with the most prominent effect in women who underwent hysterectomy due to fibroids or menorrhagia. We conclude that genetic variations of the ER gene are related to the onset of natural menopause and the risk of surgical menopause, especially hysterectomy.

Aged↗
PubMed1999

Factors affecting sexual functioning of women in the mid-life years.

OBJECTIVE: To model the interaction of hormones, symptoms and psychosocial factors on women's sexuality during the menopausal transition. DESIGN AND METHODS: A prospective, observational study was carried out of a community-based sample of 438 Australian-born women aged 45-55 years at baseline. The study comprised six annual assessments in the women's own homes utilizing a core questionnaire, with rating scales for well-being and daily hassles, and a Personal Experiences Questionnaire as a measure of sexual functioning. Levels of follicle stimulating hormone (FSH), estradiol and inhibin were measured annually. Statistical analysis was performed by structural equation modelling. RESULTS: The retention rate was 90% (final sample size after exclusions, n = 354). The normal fit index for the global model obtained was 0.92. There is a significant direct effect of menopausal status on vaginal dryness/dyspareunia, and an indirect effect on sexual responsivity via a direct effect of menopausal status on symptoms, which then affect well-being. Menopausal status reflects hormonal status. Feelings for the partner and the partner's sexual problems have direct effects on different aspects of sexual functioning. Other social variables such as paid work, interpersonal stress, daily hassles and educational level affect sexual functioning indirectly via effects on symptoms and well-being. CONCLUSIONS: Psychosocial factors, symptoms and the menopausal transition affect women's sexual functioning during the mid-life years.

Aging↗
PubMed1998

Expression of p53, p21/WAF/CIP, Bcl-2, Bax, Bcl-x, and Bak in radiation-induced apoptosis in testicular germ cell tumor lines.

PURPOSE: Testicular germ cell tumors (TGCTs) represent one of the few tumor types that are curable by antineoplastic therapy, probably due to the high sensitivity of this neoplasm to induction of apoptosis by chemotherapeutic agents and/or ionizing radiation. Here, we tested cell susceptibility to radiation-induced apoptosis in a panel of TGCT cell lines and attempted to correlate this with the known potentially relevant molecular determinants (p53 gene status and Bcl-2 family proteins) of apoptosis. METHODS AND MATERIALS: Induction of apoptosis by gamma-radiation was morphologically recognized in NT2, NCCIT, S2, and 2102 EP using Hoechst/PI staining and additionally confirmed by Western blot analysis of PARP cleavage. The p53 gene status was estimated by sequence analysis. Expression of p21/WAF/CIP was determined by Northern blot analysis and immunoblotting was used to monitor p53, Bax, Bcl-2, Bcl-x, and Bak protein levels. In vitro colony formation was studied to establish clonogenic survival curves. RESULTS: NT2 and NCCIT appeared to be susceptible for radiation-induced apoptosis, contrasting 2102 EP and S2 which were highly resistant. Sequence analysis showed that NT2, S2, and 2102 EP are homozygous for wild-type p53 (wtp53), whereas NCCIT contains mutant p53 (mtp53). NT2 and 2102 EP cells showed radiation-induced p53 upregulation, while NCCIT (mtp53) and S2 (no p53 protein) cells did not. Consistently, gamma-radiation-induced DNA damage resulted in a p53-dependent transactivation of the p21/WAF/CIP gene in NT2 and 2102 EP, but not in mtp53-containing NCCIT cells and p53 nonexpressing S2 cells. Constitutive expression of Bax, Bcl-2, Bcl-x, and Bak was not affected by radiation and showed no correlation with cell susceptibility to radiation-induced apoptosis. A discrepancy was found between apoptosis and reproductive death. CONCLUSIONS: The present study revealed that: i) the presence of wtp53 may not be absolutely required for the hypersensitivity for radiation-induced apoptosis in TGCT cell lines, ii) the molecular mechanism underlying the unique radiosensitivity was independent of the expression of Bcl-2 family proteins, and iii) cell susceptibility to apoptosis induction is not sufficiently informative to predict intrinsic radiosensitivity as determined by clonogenic survival.

Apoptosis↗