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Biomedical subjects

H Burger

Publications and source records attributed to H Burger.

At least 109 records · Page 6Linked to original sources

Double-limb support and step-length asymmetry in below-knee amputees.

The sequence of gait events and symmetry of kinematic parameters between both lower limbs are compromised in below-knee amputees. In the present study the periods of double-limb support and the step length in below-knee amputees were investigated. The symmetry of the two periods of double-limb support occurring in each stride was obviously abnormal (ratio: 0.74) among temporal and distance parameters. The time of double-limb support (0.211 +/- 0.05 seconds) measured from heel-strike of the amputated leg until toe-off of the normal leg was significantly longer (p = 0.011) when compared with the contralateral leg (0.173 +/- 0.04 seconds). The step length of the normal leg (0.709 +/- 0.07 m) was significantly (p = 0.045) shorter than that of the amputated leg (0.752 +/- 0.08 m). Most of these differences between measured kinematic parameters can be explained by the limited ability of the prosthesis ankle-foot component to reproduce the normal functions of both foot and ankle.

Adult↗

HIV type 1 RNA expression in bone marrows of patients with a spectrum of disease.

HIV-1-infected individuals at various stages of disease harbor virus in their lymphoid organs, which serve as reservoirs of viral replication throughout the course of infection. Hematologic abnormalities are extremely common in HIV-1-infected individuals and occur at all stages of disease. To determine if the bone marrow is a reservoir of HIV-1 in vivo and if active HIV-1 RNA expression in that site is related to hematologic disease in infected individuals, we examined HIV-1 RNA expression in bone marrow biopsies from 37 patients with a broad spectrum of hematologic and HIV-1-related disease. To detect HIV-1 RNA expression, we performed in situ hybridization. Double-label in situ hybridization-immunohistochemistry was used for precise identification of the type of cell expressing viral RNA. Six of 37 (16%) patients demonstrated HIV-1 RNA expression in the bone marrow. Double-label analysis performed on two marrows localized HIV-1 RNA to cells of the macrophage lineage. Active HIV-1 expression correlated with advanced HIV-1-related disease and CD4 cell depletion rather than a specific hematologic or clinical diagnosis. These data suggest that although the bone marrow does not serve as a reservoir of viral expression throughout the course of infection as do the lymphoid organs, HIV-1-expressing cells are present in the bone marrow during late stages of disease. These data also suggest that hematologic abnormalities in the majority of infected individuals may result from indirect effects of HIV-1 such as cytokine dysregulation rather than HIV-1 expression in the bone marrow itself.

Adult↗

Peripheral neuropathy in mice transgenic for a human MDR3 P-glycoprotein mini-gene.

We have generated mice transgenic for a human MDR3 mini-gene, under control of a hamster vimentin promoter. Expression of the MDR3 transgene was found in mesenchymal tissues, peripheral nerves, and the eye lens. These MDR3 transgenic mice have a slowed motor nerve conduction and dysmyelination of their peripheral nerves. An extensive dysmyelination in some transgenic strains results in a severe peripheral neuropathy with paresis of the hind legs. How expression of the MDR3 transgene causes these abnormalities is unknown. The MDR3 gene encodes a large glycosylated plasma membrane protein with multiple transmembrane spanning domains, which are involved in the translocation of the phospholipid phosphatidylcholine through the hepatocyte canalicular membrane. The ability of the MDR3 P-glycoprotein to alter phsopholipid distribution in the plasma membrane of Schwann cells may cause the damage. It is also possible, however, that the presence of a large glycoprotein in the cell membrane may be sufficient to severely disturb myelination of peripheral nerves.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Molecular cloning of full-length HIV-1 genomes directly from plasma viral RNA.

Human immunodeficiency virus type 1 (HIV-1) in plasma reflects the replicating virus population at any point in time in vivo. Studies of the relationship of the complete HIV-1 genome to pathogenesis therefore need to focus on plasma virions. Since dual infections and recombination can occur in vivo, cloning an intact plasma virus genome as a single full-length molecule is desirable. For these reasons, we developed an efficient method to clone full-length HIV-1 genomes directly from plasma viral RNA. This method used reverse transcription and long polymerase chain reaction (PCR) amplification. Virion-associated RNA was isolated from plasma samples and then reverse-transcribed to make cDNA for PCR amplification. Two different strategies were employed to amplify the full-length genome: one amplified a 9-kb fragment, and the other amplified two overlapping 5-kb fragments. Although both strategies were successful, the second was preferable for amplifying HIV-1 genomes from samples with low viral titers. By directly ligating the PCR-derived fragments into a phagemid vector, we constructed clones that comprised full-length HIV-1 RNA genomes. Using this technique, we have constructed hundreds of clones containing full-length HIV-1 genomes derived from the plasma of HIV-1-infected individuals, some of whom had low HIV-1 titers. Different HIV-1 molecular species were cloned from a single clinical sample, as demonstrated by restriction site polymorphism. This method provides a tool for studying complete HIV-1 genomes in relation to pathogenic processes.

Base Sequence↗

[Ultrasound assessment of the calcaneus: for the time being a conservative approach in clinical use; the ERGO study (Erasmus Rotterdam Health and the Elderly)].

OBJECTIVE: To examine whether ultrasound measurements of the calcaneus can help to identify subjects with a risk for non-vertebral fractures. DESIGN: Cross-sectional survey. SETTING: The suburb of Ommoord in Rotterdam, the Netherlands. METHODS: 1421 subjects (631 men, 790 women) underwent both ultrasound measurements of the calcaneus and bone mineral density measurement of the femoral neck by dual energy X-ray absorptiometry (DXA). At the calcaneus speed of sound (SOS in m/s) and broadband ultrasound attenuation (BUA in dB/MHz) were measured. In addition, all subjects were asked about fractures in the preceding 5 years. The frequency of non-vertebral fractures was examined per tertile of SOS and BUA. In addition, we examined whether there was a trend in the number of fractures per tertile of SOS or BUA, within tertiles of femoral neck bone mineral density. RESULTS: The measures of SOS, BUA and bone mineral density (DXA-measured) are comparable as predictors of fractures. Subjects with values of SOS, BUA or bone mineral density in the lowest tertiles were all found to report two to three times as many fractures as subjects with values for these variables in the highest tertiles. Within tertiles of bone mineral density, subjects with a low SOS reported more fractures than subjects with a high SOS. For BUA a similar but less pronounced pattern was visible. Nevertheless, the area under the receiver operating characteristic (ROC) curve was 0.63 for SOS and 0.64 for BUA, comparable to 0.62 for bone mineral density of the proximal femur. Combining ultrasound and bone mineral density measurements had limited effect on the area under the ROC curve (0.65). CONCLUSIONS: Subjects with lower values of ultrasound parameters are at increasing risk of fracture, especially if low ultrasound values are accompanied by a lower bone mineral density. It remains to be seen whether ultrasound parameters are useful for screening.

Absorptiometry, Photon↗

Association of radiographically evident osteoarthritis with higher bone mineral density and increased bone loss with age. The Rotterdam Study.

OBJECTIVE: To investigate the relationship of osteoarthritis (OA) to bone mineral density (BMD) and rate of bone loss. METHODS: The study group consisted of 2,745 persons (1,624 women) from the general elderly population. Disability was assessed by the Health Assessment Questionnaire. Femoral neck BMD was measured at baseline and, in 1,723 subjects, after 2 years of followup. Knee and hip radiographic OA was assessed on anteroposterior radiographs. RESULTS: With the exception of knee radiographic OA in men, radiographic OA was associated with significantly increased BMD (3-8%). BMD increased significantly according to the number of affected sites and the Kellgren score. Radiographic OA was also associated with significantly elevated bone loss with age (in men, only for radiographic OA of the hip). A significant increase in relation to the number of affected sites and the Kellgren score (except with regard to knee OA in men) was found, independent of disability. CONCLUSION: Radiographic OA is associated with high BMD and increased rate of bone loss. This suggests a more pronounced difference in BMD earlier in life.

Age Factors↗

A large-scale population-based study of the association of vitamin D receptor gene polymorphisms with bone mineral density.

Conflicting results have been reported on the association between restriction fragment length polymorphisms (RFLPs) at the vitamin D receptor (VDR) gene locus (i.e., for BsmI, ApaI, and TaqI) and bone mineral density (BMD). We analyzed this association in a large population-based sample (n = 1782) of men and women aged 55-80 years using a novel direct haplotyping polymerase chain reaction (PCR) test to monitor the three polymorphic sites simultaneously. The direct haplotyping test we developed demonstrated a larger degree of genetic polymorphism at the VDR gene locus than described until now. None of the individual RFLPs were associated with BMD at the proximal femur. By analyzing allele dose effects, we identified a VDR haplotype allele weakly associated with low BMD. This allele, as one representative of the group of b alleles, is different from the BsmI allele previously reported by other groups to be associated with low BMD. This suggests allelic heterogeneity at the VDR locus in relation to BMD. Our results indicate at most a small effect of the VDR genotype on BMD in this elderly population. Since anonymous polymorphisms were analyzed, alternative explanations for our results include linkage to another nearby bone-metabolism related gene.

Absorptiometry, Photon↗

Properties of musculus gluteus maximus in above-knee amputees.

The present study aimed at evaluating possible changes of the gluteus maximus muscle bulk size and in the contracting properties of gluteus maximus in the amputated above-knee limb. Seven male above-knee amputees, with a mean age of 47.4 years volunteered to participate in the present study. Twenty-one healthy subjects with a mean age of 34.0 years served as the control group. Muscle belly displacement was measured by means of a precision electromagnetic sensor dc-dc displacement transducer while performing maximal voluntary isometric contractions. The muscle twitch contraction has been quantified by the latency period (T1), time to peak tension (T2) and the slope of the record. A statistically significant decrease in muscle belly displacement on the amputated side has been observed in comparison with controls and non-amputated side. The latency period on the amputated side was significantly longer and the slope less steep than in the control group. These results indicated atrophied and slower gluteus maximus on the amputated side of above-knee amputees.

Journal Article↗

Isokinetic and isometric strength of the thigh muscles in below-knee amputees.

OBJECTIVE: The strength of the quadriceps and hamstring muscles of the amputated limb in below-knee amputees was evaluated. DESIGN: A descriptive study based on clinical measurements of muscle strength. BACKGROUND: The residual limb of below-knee amputees is less active in daily functions. As a result, atrophy of the thigh muscles in the affected limb is a common finding. Quality of standing and gait performances depend on the strength of these muscles, which activate the knee of the amputated limb. METHODS: Isokinetic concentric and eccentric, as well as isometric, strength of thigh muscles was measured by means of a dynamometer. Parameters of peak torque and maximal average torque of the quadriceps and hamstring muscles were considered. RESULTS: Significant decreases (P < 0.01) in strength of the quadriceps and hamstrings were observed in the amputated limb. Thigh muscle strength in amputees over 7 years was not significantly weaker when compared with amputees where amputation had been performed more recently. CONCLUSIONS: In below-knee amputees, the thigh muscle strength of the amputated limb decreases significantly during the first years after amputation. RELEVANCE: In so far as the ultimate goal in rehabilitation of amputees is to return the patient to an acceptable level of function, it is recommended that the amputee should be trained and encouraged in self-strengthening exercises for the thigh muscles of the amputated limb.

Journal Article↗

Hyperinsulinemia and bone mineral density in an elderly population: The Rotterdam Study.

We studied the association between insulin and glucose levels and bone mineral density (BMD) in a population based study of 5931 elderly men and women. Serum insulin was measured 2 h after a nonfasting oral glucose load in subjects not using antidiabetes medication. BMD was measured by dual-energy X-ray absorptiometry in the lumbar spine and the proximal femur. In addition, the participants were asked about fractures in the preceding 5 years. Higher bone mass was associated with higher glucose and postload insulin levels at all sites, as well as with increased waist/hip ratio and body mass index. In men, the mean age-adjusted BMD at the lumbar spine (in mg/cm2) increased 4.64 per mmol/L serum glucose (95% CI 1.46-7.82) and 0.35 per mU/L postload insulin (0.17-0.53). In women, these values were 6.88 (4.37-9.39) for glucose and 0.25 (0.11-0.39) for insulin (for all analyses: p < 0.01). The relations were essentially the same with BMD measured in the femur, as well as after adjustment for waist/hip ratio. After adjustment for body mass index, the associations were reduced and lost statistical significance in women. After excluding subjects with diabetes mellitus, the results remained the same. Subjects with a history of nonvertebral fractures had a lower BMD and lower postload insulin levels than those without. The difference in insulin levels was statistically significant in men only (12.5 mU/L, p < 0.001). Excluding men with diabetes mellitus or further adjustment for waist/hip ratio, body mass index or BMD did not change this difference. These results suggest that increased insulin levels are associated with an increased BMD and might be related to a lower fracture rate.

Absorptiometry, Photon↗

Effects of FSH on serum immunoreactive inhibin levels in the luteal phase of the menstrual cycle.

OBJECTIVE: FSH causes a dose-related increase in circulating immunoreactive inhibin (INH) in the follicular phase of the menstrual cycle, while LH is the major stimulus to INH secretion by the corpus luteum. The present study was undertaken to assess whether FSH can also stimulate INH production during the luteal phase. DESIGN: Normal volunteers were treated with a single injection of LH-free FSH (Metrodin, 150 units) or saline as control, during the early, mid- or late luteal phase of the cycle, with subsequent hormone measurements. PATIENTS: The 21 volunteers were aged 19-29. Seven subjects given FSH and 8 controls were studied in the early luteal phase, 1-4 days post ovulation. Eight FSH treated subjects and 10 controls were studied in the midluteal phase, 5-9 days post ovulation, and 6 each, respectively, were studied in the late luteal phase. MEASUREMENTS: Oestradiol (E2), progesterone (P), and INH were measured by previously described radio-immunoassays. RESULTS: In both the early and mid-luteal phases, FSH caused a significant rise in INH (early, from 778 to 922 U/l, mid-luteal 1553 to 2090 U/l) and E2 (early 371 to 545 pmol/l, mid-luteal 528 to 636) while there was no significant change in P. No significant changes occurred in the saline treated subjects. In the late luteal phase FSH prevented the significant fall in INH seen in the controls, whilst there was no effect on E2 or P. CONCLUSIONS: It was concluded that both FSH and LH are capable of modulating inhibin production during the luteal phase of the menstrual cycle. FSH may exert its actions on the corpus luteum or alternatively on developing follicles. The present study cannot clearly distinguish between these possibilities.

Adult↗

Expression of the multidrug resistance-associated protein (MRP) gene in primary non-small-cell lung cancer.

BACKGROUND: One of the major problems in the cure of advanced non-small-cell lung cancer (NSCLC) is its lack of response to cytotoxic drug treatment, and the mechanisms underlying this intrinsic drug resistance are unclear. PATIENTS AND METHODS: We determined the expression of a newly recognised drug resistance gene, the Multidrug Resistance-associated Protein (MRP) gene, in normal lung tissue and in tumour biopsies from 35 surgically resected NSCLCs (11 adenocarcinomas, 24 squamous cell carcinomas). MRP mRNA levels were quantitated by RNase protection assay and expression of the MRP Mr 190,000 glycoprotein was estimated by immunohistochemistry. RESULTS: Using the MRP-specific monoclonal antibody MRPr1, MRP expression was detected by immunohistochemistry in epithelial cells lining the bronchi in normal lung. In NSCLC approximately 35% of the samples showed elevated MRP mRNA levels. Based on MRP-specific immunohistochemical staining the tumours were divided into 4 groups: 12% were scored as negative (-), 14% showed weak cytoplasmic staining of the tumour cells (+/-), 40% had a clear cytoplasmic staining (+), and in 34% a strong cytoplasmic as well as membranous staining was observed (++). MRP expression, as estimated by immunohistochemistry, correlated with the MRP mRNA levels quantitated by RNase protection assay (correlation coefficient = 0.745, p = 0.0009), with MRP mRNA levels (mean +/- SD) of 3.0 +/- 1.0 U, 3.5 +/- 0.7 U, 7.5 +/- 5.9 U, and 19.3 +/- 10.7 U, in the (-), (+/-), (+), and (++) immunohistochemistry expression groups, respectively. Among the squamous cell carcinomas a correlation was observed between MRP staining and tumour cell differentiation: the strongest MRP staining was predominantly found in the well differentiated tumours. CONCLUSIONS: Hyperexpression of MRP is frequently observed in primary NSCLC, especially in the well differentiated squamous cell carcinomas. Further studies are needed to assess the role of MRP in the mechanism of clinical drug resistance in NSCLC.

ATP-Binding Cassette Transporters↗

Stump length as related to atrophy and strength of the thigh muscles in trans-tibial amputees.

Stump length and the thigh muscles strength of the amputated limb are among the major factors influencing outcome of prosthetic rehabilitation of trans-tibial amputees. In the present study the authors evaluated and compared the strength of quadriceps and hamstrings muscles of both limbs in trans-tibial amputees, as measured by means of an electrical dynamometer. The obtained results showed that the thigh muscles of the sound limbs are significantly stronger than those of the amputated limbs (p < 0.01). The results obtained for amputees with shorter stumps were compared with those with longer stumps. In the group of amputees (n = 9) with a stump shorter than 15.1 cm, values of peak torque (in isokinetic contraction) and maximal average torque (in isometric contraction) were significantly (p < 0.5) weaker when compared to those (n = 9) with a stump longer than 15.1 cm. The results obtained for amputees with a higher rate of thigh muscle atrophy were compared to those with lesser atrophy. In the group of amputees where muscle atrophy was accompanied by decrease in thigh girth of over 5.9 cm, muscles strength did not significantly decrease (p < 0.5) as compared to amputees where thigh girth decrease was less than 5.9 cm. It is concluded that atrophy of the thigh muscles of trans-tibial amputees is accompanied with a significant decrease in strength. In amputees with a short stump, the short lever action provided by the stump interferes with the ability of the thigh muscles to control the prosthesis efficiently during daily activities such as standing and walking.

Activities of Daily Living↗

Influence of speed on gait parameters and on symmetry in trans-tibial amputees.

Normal gait is characterised by a high level of inter-leg symmetry of gait parameters. Therefore, efforts in rehabilitation of amputees are directed at the construction of a prosthesis which provides normal leg function and allows a more symmetrical gait. Analysis of the gait of trans-tibial amputees was performed when they were ambulating at their own freely selected speed and at a faster speed. The effect of speed on selected gait parameters in each leg was evaluated and the influence on symmetry established by comparing the inter-leg changes for each of the selected parameters. The faster gait trail affected significantly all temporal and distance parameters in both legs but not the level of symmetry between legs. At the faster speed, the hip angles at heel-strike and during swing and the knee angle during load response, in the normal leg, and the knee angle during swing in the amputated leg, all increased significantly. Speed of gait significantly affected symmetry between knee angles as reflected by the increased differences measured during load response (from 2.62 +/- 5.2 to 7.06 +/- 4.2 degrees) and during toe-off (from 1.80 +/- 7.4 to 9.50 +/- 9.1 degrees). Timing and sequence of selected gait events, as related to stride time, were not significantly affected by speed of gait. These results might contribute to a better understanding of gait characteristics in trans-tibial amputees and provide design guidance for prosthetic components.

Adult↗

Multidrug resistance-associated protein (MRP) in haematological malignancies.

The presence of multidrug resistant cells, either acquired or de novo, severely limits treatment outcome in haematological malignancies. Although expression of the Mr 170,000 P-glycoprotein drug pump is likely to play a role in multidrug resistance (MDR) in haematological malignancies, it is now evident that other MDR mechanisms may be operational as well in leukaemias, lymphomas, and multiple myeloma. We determined the expression of a newly recognised drug resistance gene, the Multidrug Resistance-associated Protein (MRP) gene, in peripheral blood cells from healthy volunteers and from patients with haematological malignancies. Expression of MRP mRNA and its Mr 190,000 glycoprotein were estimated by RNase protection assay and immunocytochemistry, respectively. MRP appeared to be ubiquitously expressed at low levels in all nonmalignant haemopoietic cell types. However, some leukaemias showed elevated levels of MRP, probably due to transcriptional activation or increased mRNA stability. High to very high MRP expression levels were frequently found in chronic lymphocytic leukaemia and prolymphocytic leukaemia. Acute myelocytic leukemia often exhibited low but occasionally high MRP expression levels, while in the other acute and chronic leukaemias, lymphomas, and multiple myeloma, predominantly low, basal levels of MRP were found. We conclude that hyperexpression of MRP is observed in leukaemias, and that further studies are needed to assess the clinical relevance of MRP.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Maternal plasma human immunodeficiency virus type 1 RNA level: a determinant and projected threshold for mother-to-child transmission.

To prevent mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission, it is important to identify its determinants. Because HIV-1 RNA levels can be reduced by antiviral therapy, we examined the role of maternal plasma HIV-1 RNA level in mother-to-child transmission. We used quantitative competitive PCR to measure HIV-RNA in 30 infected pregnant women and then followed their infants prospectively; 27% of the women transmitted HIV-1 to their infants and maternal plasma HIV-1 RNA level correlated strikingly with transmission. Eight of the 10 women with the highest HIV-1 RNA levels at delivery (190,400-1,664,100 copies per ml of plasma) transmitted, while none of the 20 women with lower levels (500-155,800 copies per ml) did (P = 0.0002). Statistical analysis of the distribution of HIV-1 RNA loads in these 30 women projected a threshold for mother-to-child transmission in a larger population; the probability of a woman with a viral RNA level of < or = 100,000 copies per ml not transmitting is predicted to be 97%. Examination of serial HIV-1 RNA levels during pregnancy showed that viral load was stable in women who did not initiate or change antiviral therapy. These data identify maternal plasma HIV-1-RNA level as a major determinant of mother-to-child transmission and suggest that quantitation of HIV-1 RNA may predict the risk of transmission.

Acquired Immunodeficiency Syndrome↗