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Biomedical subjects

H Burger

Publications and source records attributed to H Burger.

At least 127 records · Page 7Linked to original sources

[Vertebral deformities and bone density in the elderly; the ERGO Study (Erasmus Rotterdam Health and the Elderly). ERGO Study Group].

OBJECTIVE: To assess the prevalence of vertebral deformities in men and women aged 55 years and over. DESIGN: Cross-sectional study. SETTING: A quarter in Rotterdam, The Netherlands. METHODS: As part of the 'Rotterdam elderly study', 750 responding men and 750 women underwent lateral radiography of the spine and subsequent morphometry of the vertebrae to detect presence of vertebral deformities. Grade 1 and grade 2 deformities were scored on the basis of the results of the morphometry. The entire vertebral column was classified as normal (no deformities), moderate spinal deformity (grade 1 deformities) or severe spinal deformity (grade 2 deformities). Dual Energy X-ray Absorptiometry (DXA) was used to assess the bone mineral density (BMD) at the femoral neck. RESULTS: The prevalence of moderate or severe spinal deformity was estimated to be 18% in men (12% moderate and 6% severe) and 22% in women (11% moderate and 11% severe) after adjustment for the present age distribution of the Dutch population. The prevalence of deformities increased with age, in particular for severe deformities in women aged 70 years and over. A decreasing BMD was observed with increasing severity of vertebral deformities. Men with severe spinal deformity had a 4% lower BMD whereas women with severe spinal deformity had a 6% lower BMD. CONCLUSION: Vertebral deformities are frequently present in the general population, mostly in the higher age groups. There was an association with decreased BMD. In view of the ongoing aging of the population, a future increase in the prevalence of vertebral deformities is to be expected.

Absorptiometry, Photon↗

Interleukin-3 treatment of rhesus monkeys leads to increased production of histamine-releasing cells that express interleukin-3 receptors at high levels.

To understand the hematopoietic and nonhematopoietic responses to interleukin-3 (IL-3), expression of cell-surface IL-3 receptors (IL-3R) was examined on bone marrow (BM) cells and peripheral blood (PB) cells of rhesus monkeys during the course of in vivo IL-3 treatment. Whereas IL-3R expression is low in untreated monkeys, IL-3 administration led to a gradual increase in both low- and high-affinity binding sites for IL-3. This increase reflected the total number of cells expressing IL-3Rs, as detected by flow cytometry using biotinylated IL-3. Most of these IL-3R+ cells in both BM and PB could be characterized as basophilic granulocytes that contained high levels of histamine. In contrast to the effect on these differentiated cells, IL-3 administration did not significantly alter the low level IL-3R expression on immature, CD34+ cells. Further flow cytometric analysis using biotinylated growth factors showed that the IL-3R+ basophils also expressed receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF), but not for IL-6 or Kit ligand. These findings indicated that the IL-3R+ cells included neither monocytes, which express GM-CSFRs and IL-6Rs abundantly, nor mast cells, which express c-kit. By combining flow cytometric and Scatchard data, it was calculated that the basophils contain as many as 1 to 2 x 10(3) high-affinity IL-3Rs and 15 to 30 x 10(3) low-affinity sites. The finding that in vivo IL-3 treatment leads to the production of large numbers of cells that express high levels of IL-3R and are capable of producing histamine provides an explanation for the often severe allergic reactions that occur during prolonged IL-3 administration. It also indicates that IL-3, in addition to its direct effects on hematopoietic cells, may also stimulate hematopoiesis through the release of secondary mediators such as histamine by IL-3-responsive mature cells.

Animals↗

Bone density in non-insulin-dependent diabetes mellitus. The Rotterdam Study.

OBJECTIVE: To investigate the relation between non-insulin-dependent diabetes mellitus and bone mineral density at the lumbar spine and hip. DESIGN: Population-based study with a cross-sectional survey. SETTING: A district of Rotterdam, the Netherlands. PARTICIPANTS: 5931 residents (2481 men, 3450 women) of the district aged 55 years or more. MEASUREMENTS: Participants were classified as having non-insulin-dependent diabetes mellitus if they were receiving antidiabetic medication or if they had a serum glucose level of 11.1 mmol/L or more after a nonfasting oral glucose tolerance test. Bone mineral density, measured at the lumbar spine and proximal femur using dual-energy x-ray absorptiometry and the frequency of nonvertebral fractures during the preceding 5 years were compared between persons with and without non-insulin-dependent diabetes mellitus. RESULTS: 243 men and 335 women had non-insulin-dependent diabetes mellitus. Both men and women with this condition had substantially higher mean bone mineral density values at all four sites measured than those with normal glucose tolerance. The increase could not be explained by age; obesity; use of estrogens, thiazides, or loop diuretics; impairment in abilities of daily living; smoking; or osteoarthritis. Women with non-insulin-dependent diabetes mellitus reported having had fewer fractures in the 5 preceding years than women without this condition (adjusted odds ratio, 0.63; 95% CI, 0.44 to 0.90). The frequency of fractures in men was similar for those with and without non-insulin-dependent diabetes mellitus (adjusted odds ratio, 0.96; CI, 0.60 to 1.52). CONCLUSIONS: Men and women with non-insulin-dependent diabetes mellitus have increased bone mineral density. Non-insulin-dependent diabetes mellitus in women is associated with a lower frequency of nonvertebral fractures.

Aged↗

Testosterone enhances estradiol's effects on postmenopausal bone density and sexuality.

To investigate the role of androgens in increasing bone density and improving low libido in postmenopausal women, we have studied the long-term effects of estradiol and testosterone implants on bone mineral density and sexuality in a prospective, 2 year, single-blind randomised trial. Thirty-four postmenopausal volunteers were randomised to treatment with either estradiol implants 50 mg alone (E) or estradiol 50 mg plus testosterone 50 mg (E&T), administered 3-monthly for 2 years. Cyclical oral progestins were taken by those women with an intact uterus. Thirty-two women completed the study. BMD (DEXA) of total body, lumbar vertebrae (L1-L4) and hip area increased significantly in both treatment groups. BMD increased more rapidly in the testosterone treated group at all sites. A substantially greater increase in BMD occurred in the E&T group for total body (P < 0.008), vertebral L1-L4 (P < 0.001) and trochanteric (P < 0.005) measurements. All sexual parameters (Sabbatsberg sexual self-rating scale) improved significantly in both groups. Addition of testosterone resulted in a significantly greater improvement compared to E for sexual activity (P < 0.03), satisfaction (P < 0.03), pleasure (P < 0.01), orgasm (P < 0.035) and relevancy (P < 0.05). Total cholesterol and LDL-cholesterol fell in both groups as did total body fat. Total body fat-free mass (DEXA, anthropometry, impedance) increased in the E&T group only. We concluded that in postmenopausal women, treatment with combined estradiol and testosterone implants was more effective in increasing bone mineral density in the hip and lumbar spine than estradiol implants alone. Significantly greater improvement in sexuality was observed with combined therapy, verifying the therapeutic value of testosterone implants for diminished libido in postmenopausal women. The favourable estrogenic effects on lipids were preserved in women treated with T, in association with beneficial changes in body composition.

Bone Density↗

Constitutive expression of the c-H-ras oncogene inhibits doxorubicin-induced apoptosis and promotes cell survival in a rhabdomyosarcoma cell line.

Drugs used in anti-cancer chemotherapy are thought to exert their cytotoxic action by induction of apoptosis. Genes have been identified which can mediate or modulate this drug-induced apoptosis, among which are c-myc, p53 and bcl-2. Since expression of oncogenic ras genes is a frequent observation in human cancer, we investigated the effects of the c-H-ras oncogene on anti-cancer drug-induced apoptosis. Apoptosis induced by a 2 h doxorubicin exposure was measured by in situ nick translation and flow cytometry in a rat cell line (R2T24) stably transfected with the c-H-ras oncogene and in a control cell line (R2NEO) transfected only with the antibiotic resistance gene neo. Both cell lines (R2T24 and R2NEO) had nearly identical growth characteristics, including cell doubling time, distribution over the cell cycle phases and plating efficiency in soft agar. Doxorubicin exposure of the R2NEO cells led to massive induction of apoptosis. In contrast, R2T24 cells, expressing the c-H-ras oncogene, showed significantly less apoptosis after doxorubicin incubation. Doxorubicin induced approximately 3- to 5-fold less cytotoxicity in the R2T24 cells than in the R2NEO cells, as determined by clonogenic assay in soft agar. No difference was observed in intracellular doxorubicin accumulation between the two cell lines, indicating that the classical, P-glycoprotein-mediated multidrug resistance phenotype is not involved in the observed differences in drug sensitivity. In conclusion, our data show that constitutive expression of the c-H-ras oncogene suppresses doxorubicin-induced apoptosis and promotes cell survival, suggesting that human tumours with ras oncogene expression might be less susceptible to doxorubicin treatment.

Animals↗

Survival of arteriovenous fistulas and shunts for haemodialysis.

OBJECTIVE: To formulate a standard for assessing functional patency of vascular access and to present long-term results of vascular access in a group undergoing dialysis, in particular the effects of percutaneous transluminal angioplasty (PTA). DESIGN: Retrospective study 1971-1980, prospective study 1980-1991. SETTING: A unit for haemodialysis in a regional hospital, The Netherlands. SUBJECTS: All 259 patients treated from 1971 to 1991 in a programme for chronic haemodialysis. INTERVENTIONS: All interventions, surgical and radiological, needed to maintain vascular access. MAIN OUTCOME MEASURES: Intervention free periods, patency of access, life expectancy of access, and early failure rate (within 4 days). Patency of access before and after PTA. RESULTS: A total of 1179 interventions were made. 407 Arteriovenous (A-V) fistulas and shunts were constructed, and there were 519 surgical reoperations and 253 PTAs. The secondary cumulative patency rate for the autogenous distal A-V fistulas (Cimino) was 79% at one year, 68% at two years, and 59% at three years. Routine use of PTA from 1986 onwards resulted in a rise in secondary cumulative patency for Cimino A-V fistulas after two years from 65% to 80% (p > 0.05). CONCLUSIONS: To describe and assess vascular access the patency rate alone is not sufficient; intervention free periods and life expectancy must also be given. Routine use of PTA with the Cimino A-V fistula resulted in an appreciable but not significant increase patency at two years.

Adolescent↗

Expression of the multidrug resistance-associated protein (MRP) gene in human cancers.

We determined the expression of a newly recognized drug resistance gene, the multidrug resistance-associated protein (MRP) gene, [Cole et al., Science (Washington DC), 258: 1650-1654, 1992], in normal human tissues and in >370 human tumor biopsies using a quantitative RNase protection assay and immunohistochemistry. MRP mRNA appeared to be ubiquitously expressed at low levels in all normal tissues, including peripheral blood, the endocrine glands (adrenal and thyroid), striated muscle, the lymphoreticular system (spleen and tonsil), the digestive tract (salivary gland, esophagus, liver, gall bladder, pancreas, and colon), the respiratory tract (lung), and the urogenital tract (kidney, bladder, testis, and ovary). The human cancers analyzed could be divided into three groups with regard to MRP expression. Group 1 consists of tumors that often exhibit high to very high MRP mRNA levels (e.g., chronic lymphocytic leukemia). Group 2 comprises the tumors that often exhibit low, but occasionally exhibit high MRP mRNA expression (e.g., esophagus squamous cell carcinoma, non-small cell lung cancer, and acute myelocytic leukemia). Group 3 comprises the tumors with predominantly low levels of MRP mRNA, comparable to the levels found in normal tissues (e.g., other hematological malignancies, soft tissue sarcomas, melanoma, and cancers of the prostate, breast, kidney, bladder, testis, ovary, and colon). Using the MRP-specific mAbs MRPr1 and MRPm6, we confirmed the elevated MRP mRNA levels in tumor tissues by immunohistochemistry. We conclude that hyperexpression of MRP is observed in several human cancers, and that additional studies are needed to assess the clinical relevance of MRP.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Quantitation of human immunodeficiency virus type 1 during pregnancy: relationship of viral titer to mother-to-child transmission and stability of viral load.

To develop strategies to prevent mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1), it is important to define the factors determining it. We examined the relationship between maternal HIV-1 titer and the occurrence of mother-to-child transmission. In addition, we quantitated HIV-1 longitudinally in mothers during pregnancy, at delivery, and up to 1 year postpartum. To examine transmission, we prospectively studied 19 mother-child pairs; in 5 pairs, HIV-1 transmission occurred. We used endpoint dilution culture of peripheral blood mononuclear cells to determine maternal viral titer and found that although 4 of 6 (67%) women with viral titers of > or = 125 HIV-1 infectious units per 10(6) cells transmitted HIV-1 to their infants, only 1 of 13 (7.6%) women with lower viral titers transmitted (P = 0.01). Twelve of the 19 mothers had HIV-1 loads determined serially 3-8 times over periods ranging from 18 to 65 weeks. Viral titers varied greatly between the 12 women, but the viral load in each woman remained stable over time. In this cohort, HIV-1 viral load remained stable during pregnancy and the greater the maternal viral burden, the more likely that transmission occurred. These two related findings suggest that determination of HIV-1 titers early in pregnancy may predict which women are at high risk of transmitting to their infants and may be used to counsel HIV-1-infected women of childbearing age. These data identify maternal viral titer as a major determinant of mother-to-child HIV-1 transmission and thereby provide the scientific rationale for therapeutic strategies designed to interrupt transmission by lowering viral load.

Acquired Immunodeficiency Syndrome↗

Cloning and expression of interleukin-3 genes of chimpanzee and New World monkeys.

Interleukin-3 (IL-3) genes were cloned from chimpanzee (Pan troglodytes), tamarin (Saguinus oedipus) and marmoset (Callithrix jacchus) and expressed in COS cells. Although the IL-3 gene structure is well conserved in these primate species, sequence analysis revealed extensive base substitutions. The chimpanzee IL-3 protein, which is highly homologous (98.5% identity) to human IL-3, stimulated proliferation of human cells dependent on IL-3. In contrast, due to the numerous amino acid substitutions in the New World monkey IL-3 species, no stimulation of human cells was observed, illustrating the extensive evolutionary divergence of IL-3.

Amino Acid Sequence↗

J-shaped relation between change in diastolic blood pressure and progression of aortic atherosclerosis.

The J-shaped relation between diastolic blood pressure and mortality from coronary heart disease continues to provoke controversy. We examined the association between diastolic blood pressure and progression of aortic atherosclerosis in a population-based cohort of 855 women, aged 45-64 years at baseline. The women were examined radiographically for calcified deposits in the abdominal aorta, which have been shown to reflect intimal atherosclerosis. After 9 years of follow-up, slight progression of atherosclerosis was noted in 19% of women and substantial progression in 16%. The age-adjusted relative risk of substantial atherosclerotic progression in women with a decrease in diastolic pressure of 10 mm Hg or more was 2.5 (95% CI 1.3-5.6), compared with the reference group of women who had a smaller decrease or no change. The excess risk in this group was confined to women whose increase in pulse pressure was above the median (3.9 [1.5-9.9] vs 1.1 [0.3-4.2] in women with an increase in pulse pressure below the median). The relative risks for women with rises in diastolic pressure of 1-9 mm Hg and 10 mm Hg or more were 2.2 (1.1-4.3) and 3.5 (1.6-8.0), respectively. These findings suggest that a decline in diastolic blood pressure indicates vessel wall stiffening associated with atherosclerotic progression. They support the hypothesis that in low-risk subjects progression of atherosclerosis may be accompanied by a decrease in diastolic blood pressure rather than the opposing idea that low diastolic blood pressure precipitates the occurrence of atherosclerotic events.

Age Factors↗

Age-associated changes in ultrasound measurements of the calcaneus in men and women: the Rotterdam Study.

Broadband ultrasound attenuation (BUA) and speed of sound (SOS) of the os calcis were measured in a sample of 1405 persons (628 men), aged 55-93 years, from the cohort of the Rotterdam Study, a population-based study of diseases in the elderly. We studied the effect of age, body mass index, age at menopause, current use of thiazides, loop diuretics, and estrogens, smoking, and disability on SOS and BUA. Comparisons were made between ultrasound measurements and bone mineral density (BMD) measurements of the lumbar spine and proximal femur using DXA. We found a significant decline with age in SOS and BUA in men (-0.4 and -0.1 %/year, respectively) and women (-1.3 and -0.4%/year, respectively), which persisted after adjustment for body mass index. Age at menopause was not associated with SOS or BUA. Pack-years of smoking was negatively related to SOS in both sexes and to BUA in men. Severe disability was associated with lower SOS and BUA in men, but not in women. Despite the small number of exposed persons, current corticosteroid use was associated with lower BUA in men. The other risk factors examined did not affect the ultrasound measurements. We observed modest correlations between SOS or BUA, on the one hand, and BMD of the lumbar spine, on the other hand (r = 0.32-0.42). Similar correlations were found between ultrasound measurements and BMD measurements of the proximal femur. We conclude that in persons 55 years or over (1) there is a significant age-related decline of BUA and SOS, which is about three times higher in women compared with men, and (2) ultrasound measurements are not able to predict low BMD in hip or spine.

Absorptiometry, Photon↗

Molecular evolution of interleukin-3.

Chimpanzee, tamarin, and marmoset interleukin-3 (IL-3) genes were cloned, sequenced, and expressed. Western blot analysis demonstrated that functional genes were isolated. IL-3 sequences were compared with those of mouse, rat, rhesus monkey, gibbon, and man. Multiple alignment of the IL-3 coding regions showed that only a few regions had been conserved during mammalian evolution, which are likely associated with functional domains of the IL-3 protein. Substitution rates for the various lineages were calculated and the numbers of synonymous and nonsynonymous substitutions were estimated separately. Distance matrices of the IL-3 coding regions were used to construct phylogenetic trees which revealed large differences in IL-3 evolution rate as well as a more rapid substitution rate for rodents and a rate slowdown during hominoid evolution. Extremes were rhesus monkey IL-3, which accumulated few synonymous substitutions, and gibbon IL-3, which had almost exclusively synonymous substitutions. In rhesus monkey IL-3, nonsynonymous substitutions outnumbered synonymous substitutions, which could not be readily explained by a random process of substitutions. We assume that during evolution of IL-3, the majority of the amino acid replacements and the impaired interspecies functional cross-reactivity originate from selection mechanisms with the most likely selective force being the structure of the heterodimeric IL.3 cell-surface receptor. Insight into IL-3 architecture and structural analysis of the IL-3 receptor are needed to analyze the unusually fast evolution of IL-3 in more detail.

Animals↗

The treatment-seeking woman at menopause.

Recent studies suggest that health care utilisation by women during menopause transition in general is highly idiosyncratic, despite the widespread advocation of prophylactic hormone therapy and increased health vigilance. The Melbourne Women's Midlife Health Study, a community-based cross-sectional study of 2001 urban Australian-born women aged 45-55 years, evaluated women's physical and emotional experiences, past and present health status, attitudes and beliefs about menopause, health behaviours and current menopausal status in a 30-min telephone interview. This paper reports on those factors related to help-seeking and health care utilisation. Findings show that treatment utilisers, in contrast to non-utilisers, reported a wider range of general symptoms, but reports on vasomotor symptoms did not contribute to the regression analysis. Treatment utilisers were further identified as problem-related or prevention-related utilisers. In three-way analyses, the past and present social and physical health of the problem-related treatment user was reportedly worse than either the prevention-related utiliser or non-utiliser. These findings suggest that medical and societal views about the health of middle-aged women during menopausal transition are likely to be based on the experiences of a particular segment of the population only. It is proposed that biased views of menopause as a time of considerable distress and ill-health are being perpetuated and over-generalised. This perspective appears to have little relevance for the majority of middle-aged women.

Australia↗

The association between age and bone mineral density in men and women aged 55 years and over: the Rotterdam Study.

In this cross-sectional study, bone mineral density (BMD) measurements were performed in 1762 ambulatory subjects (678 men and 1084 women) aged 55 years and over from the Rotterdam Study, a population based study of diseases in the elderly. BMD measurements of the proximal femur and lumbar spine were performed using dual energy X-ray absorptiometry. No age-related decline in BMD could be observed in the lumbar spine. Yearly percentage BMD reduction in women and men was -0.6% and -0.3% in the femoral neck, -0.8% and -0.5% in the Ward's triangle, and -0.4% and -0.3% in the trochanter, respectively. Late menopause was associated with high BMD in Ward's triangle and lumbar spine. We conclude that: (1) accurate assessment of age-related bone reduction in the spine is impossible from cross-sectional studies since BMD measurements in the elderly may be influenced by spinal osteoarthritis; and (2) the rate of age-related bone reduction in the femoral neck appears to be approximately two times higher in women than in men.

Absorptiometry, Photon↗

High expression of the multidrug resistance-associated protein (MRP) in chronic and prolymphocytic leukaemia.

The expression of the multidrug resistance-associated protein (MRP), a new glycoprotein involved in drug resistance, was investigated in tumour samples from 80 patients with chronic B-cell malignancies by a quantitative RNase protection assay. In B-cell chronic lymphocytic leukaemia (B-CLL) (n = 32), either treated (n = 18) or untreated (n = 14), a high percentage of patients (20/32: 63%) had relatively high expression levels of the MRP gene (25U or more). In addition, hyperexpression of the MRP gene was demonstrated in 4/10 (40%) untreated patients with B-cell prolymphocytic leukaemia (B-PLL). In contrast, low MRP mRNA expression levels were detected in hairy cell leukaemia (n = 7), non-Hodgkin's lymphoma (n = 13) and multiple myeloma (n = 18). Statistical analysis of MRP expression in untreated CLL (mean +/- SD 29.2 +/- 18.5 U) versus treated CLL (mean +/- SD 26.7 +/- 13.7 U) did not show significant differences in MRP expression between the two groups. Southern blot analysis did not reveal amplification of the MRP gene in the leukaemia samples with elevated MRP mRNA levels. We conclude that B-PLL and B-CLL frequently display high MRP expression and that this hyperexpression is probably due to transcriptional activation and/or increased mRNA stability.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Upper limb prosthetic use in Slovenia.

The article deals with the use of different types of upper limb prostheses in Slovenia. Four hundred and fourteen upper limb amputees were sent a questionnaire on the type of their prosthesis, its use and reasons for non-use, respectively. The replies were subject to statistical analysis. Most of the questioned upper limb amputees (70%) wear a prosthesis only for cosmesis. The use of a prosthesis depends on the level of upper limb amputation, loss of the dominant hand, and time from amputation. Prosthetic success appears to be unrelated to age at the time of amputation and the rehabilitation programme. The most frequent reason for not wearing a prosthesis is heat and consequent sweating of the stump. More than a third of amputees are dissatisfied with their prostheses.

Activities of Daily Living↗