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P Pietschmann

Publications and source records attributed to P Pietschmann.

At least 37 records · Page 2Linked to original sources
PubMed2001

A comparison of quantitative computed tomography and dual X-ray absorptiometry for evaluation of bone mineral density in patients on chronic hemodialysis.

Chronic renal failure leads to a reduction of bone mineral density (BMD). Therefore, noninvasive methods to evaluate BMD are also used regularly in this patient population. In this study, we compared the results of two widely used methods, quantitative computed tomography (QCT) of the lumbar spine and dual x-ray absorptiometry (DXA) at different sites in 90 patients on chronic hemodialysis. Additionally, we also determined various clinical and biochemical data to assess their relationship to BMD at the different measurement sites. A total of 75% of our patients was found to have reduced BMD, and 25% had an average z-score below -2. Z-scores obtained by the different methods and at the different measurement sites within an individual patient varied considerably from completely normal to severely reduced values. Multivariate analyses using clinical and biochemical parameters showed lower values of BMD at all measurement sites after transplantation and marginally higher values after parathyroidectomy, which was seen only in DXA measurement at the femoral neck. We conclude from our study that determination of BMD in chronic hemodialysis patients yields highly variable results, depending on the technique used. As long as the exact clinical relevance of these results has not been determined, regular routine measurement of isolated sites of BMD cannot be advocated in this patient population.

Absorptiometry, Photon↗
PubMed2001

Characterization of a vitamin D receptor knockout mouse as a model of colorectal hyperproliferation and DNA damage.

The vitamin D receptor knockout (VDR-KO) mouse presents with a skeletal phenotype typical for complete lack of genomic 1,25-dihydroxycholecalciferol effects. Our previous data from human colorectal tissue suggest that the steroid hormone and its receptor may have protective function against tumour progression. In order to investigate the relevance of the vitamin D system for pre-malignant site-directed changes in the colon, we characterized the amount and site-specific distribution of the VDR along the large intestine in wild-type (WT), heterozygote (HT) and KO mice. We also evaluated expression of proliferating cell nuclear antigen (PCNA), of cyclin D1 and the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative stress. In colon ascendens, proliferative cells were dispersed all along the crypt and expression levels of all three markers were high in WT mice. A decrease of VDR expression did not affect expression significantly. In colon descendens, however, fewer proliferative cells were solely located in the lower third of the crypt, and an inverse relationship between VDR reduction, PCNA positivity and cyclin D1 expression was found in HT and KO mice. In parallel to enhanced proliferation a highly significant increase of 8-OHdG positivity occurred. Therefore, the sigmoid colon of VDR-KO mice, fed on an appropriate lactose/calcium-enriched diet to alleviate impaired calcium homeostasis-related phenotypic changes, is an excellent model for investigating induction and prevention of pre-malignant changes in one of the hotspots for human colorectal cancer incidence.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

[Paget disease or fibrous dysplasia of the radius?--A case report].

A 46 years old man, who showed a painful and progressive deformity of the left radius, is presented. After some months a fracture within the affected bone area occurred. The diagnostic procedures including X-ray, MRI, scintigraphy and histology were controversial. Both fibrous dysplasia and Paget's disease of bone were suspected. The critical analysis of all results concluded that the most likely diagnosis was fibrous dysplasia. Unaware of the diagnostic discrepancies, the patient received a therapy with pamidronate 3 x 60 mg intravenously, which improved symptoms. After 14 months, the patient complained again about pain in the left radius. After a second therapy with pamidronate the patient currently exhibits no symptoms. The controversial diagnostic results and the applied therapeutic procedure are discussed.

Diagnosis, Differential↗
PubMed2001

[Sex differences in joint diseases: pathophysiological basis].

Gender affects the susceptibility to many joint diseases, in particular autoimmune rheumatic disorders; women have an increased risk of rheumatoid arthritis, systemic lupus erythematosus or Sjögren's syndrome. In rheumatoid arthritis alterations of sex hormone levels such as androgen deficiency or prolactin excess might, at least in part, explain the excess incidence in women. Osteoarthritis of the hand and the knee as well as generalized osteoarthritis is more frequent in women than in men. Nevertheless, until now there is no explanation for the increased incidence of osteoarthritis in women.

Age Factors↗
PubMed2001

[Osteoporosis in the man].

Osteoporosis in men is a severe condition probably more frequent than generally expected. The life-time risk of a low trauma fracture in a 60 year old man is 25%; moreover, approximately one third of hip fractures occurs in men. In contrast to postmenopausal osteoporosis, osteoporosis in men is frequently a secondary condition. In approximately 50% of cases, male osteoporosis is associated with an underlying disease or condition such as hypogonadism or long-term glucocorticoid treatment. Data from our group indicate that low serum estradiol levels and elevated sex hormone binding globulin levels may play a role in the pathogenesis of idiopathic male osteoporosis. Potential treatment modalities of osteoporosis in men include calcium and vitamin D supplementation, testosterone, fluoride, bisphophonates, calcitonin and parathyroid hormone. Currently, the data available favor the use of an aminobisphosphonate for the treatment of (idiopathic or glucocorticoid induced) osteoporosis.

Aged↗
PubMed2000

Alendronate for the treatment of osteoporosis in men.

BACKGROUND: Despite its association with disability, death, and increased medical costs, osteoporosis in men has been relatively neglected as a subject of study. There have been no large, controlled trials of treatment in men. METHODS: In a two-year double-blind trial, we studied the effect of 10 mg of alendronate or placebo, given daily, on bone mineral density in 241 men (age, 31 to 87 years; mean, 63) with osteoporosis. Approximately one third had low serum free testosterone concentrations at base line; the rest had normal concentrations. Men with other secondary causes of osteoporosis were excluded. All the men received calcium and vitamin D supplements. The main outcome measures were the percent changes in lumbar-spine, hip, and total-body bone mineral density. RESULTS: The men who received alendronate had a mean (+/-SE) increase in bone mineral density of 7.1+/-0.3 percent at the lumbar spine, 2.5+/-0.4 percent at the femoral neck, and 2.0+/-0.2 percent for the total body (P<0.001 for all comparisons with base line). In contrast, men who received placebo had an increase in lumbar-spine bone mineral density of 1.8+/-0.5 percent (P<0.001 for the comparison with base line) and no significant changes in femoral-neck or total-body bone mineral density. The increase in bone mineral density in the alendronate group was greater than that in the placebo group at all measurement sites (P<0.001). The incidence of vertebral fractures was lower in the alendronate group than in the placebo group (0.8 percent vs. 7.1 percent, P=0.02). Men in the placebo group had a 2.4-mm decrease in height, as compared with a decrease of 0.6 mm in the alendronate group (P=0.02). Alendronate was generally well tolerated. CONCLUSIONS: In men with osteoporosis, alendronate significantly increases spine, hip, and total-body bone mineral density and helps prevent vertebral fractures and decreases in height.

Adult↗
PubMed2000

Successful treatment of high turnover osteoporosis in a patient with adrenocortical insufficiency.

We present a case of high-turnover osteoporosis associated with substituted adrenocortical insufficiency (Addison's disease) and its successful treatment with calcitonin and calcitriol. A 43-year-old man presented with markedly reduced bone mineral density (BMD) (lumbar spine BMD -3.46 SD below healthy young adults) after thirteen years of glucocorticoid substitution. Interestingly, his osteocalcin levels indicated an unusually high bone turnover and his alkaline phosphatase levels were also increased. Combination treatment with calcitriol and calcitonin was started. Re-evaluation after twelve months revealed a substantial increase in BMD (+6.8% for the lumbar spine, +15% for the left hip). Alkaline phosphatase levels had normalised and osteocalcin was nearly down to normal. In spite of a thorough evaluation, no other cause of osteoporosis was detected. We discuss these findings in view of the existing literature.

Addison Disease↗
PubMed2000

Surface markers and transendothelial migration of dendritic cells from elderly subjects.

Age-related changes of immune functions have been extensively investigated in both humans and animal models; nevertheless, the literature on potential alterations of dendritic cells, potent antigen presenting cells responsible for initiating immune responses, with aging is very scarce. We studied the immuno-phenotype of peripheral blood dendritic cells of elderly and young subjects by three-color flow cytometry. In addition, the capacity of transendothelial migration, an important step in inflammatory reactions, of peripheral blood dendritic cells of elderly subjects was investigated in an in vitro model. The expression of HLA-DR in the peripheral blood dendritic cells of the elderly subjects was significantly decreased when compared to the young control subjects. The expression of various other surface markers was similar in the young and elderly subjects. The ability of transendothelial migration of dendritic cells was found to be unimpaired in the elderly subjects. Both in the young and elderly subjects a significantly higher expression of CD29, CD86, HLA-DR, and HLA-DQ in the dendritic cells that had migrated through the endothelium in comparison to nonadherent, nonmigrating cells was found. In the migrating dendritic cells of the elderly subjects a significantly increased expression of CD11c was observed, whereas the expression of CD54 was significantly enhanced in the migrating dendritic cells of the young subjects only. In conclusion, our results demonstrate intact functions and a normal immunophenotype of dendritic cells derived from elderly subjects. Dendritic cells thus seem to be functional and therefore are not responsible for the well-known decline of T cell functions with aging.

Aged↗
PubMed2000

Functional and phenotypic characteristics of dendritic cells generated in human plasma supplemented medium.

One successful approach to generate dendritic cells (DC) is to cultivate peripheral blood monocytes in fetal calf serum (FCS)-containing medium in the presence of granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin (IL)-4. Because the use of xenogenic proteins has to be strictly avoided for clinical applications, alternative protocols use human plasma instead of FCS. The aim of our study was to characterize DC generated in the presence of human plasma; moreover, we describe a novel protocol to generate DC directly from peripheral blood mononuclear cells (PBMC). DC generated from purified monocytes in the presence of 1% human plasma (HP-DC) and GM-CSF and IL-4 both in the allogenic mixed leukocyte reaction (MLR) and in the tetanus presentation assay were potent stimulators of T-cell proliferation. DC generated from PBMC were equally effective stimulators in the allogenic MLR as those generated from purified monocytes. When the immunophenotype of DC generated from FCS containing medium (FCS-DC) was compared to that of HP-DC, the surface expression of CD1a and CD80 was significantly lower in HP-DC. In contrast, the expression of CD83 and CD86 was significantly higher in HP-DC than in FCS-DC. The capacity of receptor mediated endocytosis and macropinocytosis was found to be significantly lower in HP-DC when compared to FCS-DC. The differences in the immunophenotype, macropinocytosis and endocytosis between the HP-DC and the FCS-DC were observed independently of the generation of the cells from PBMC or purified monocytes. Our data indicate that HP-DC are potent stimulators of T-cell proliferation and exhibit a characteristic phenotype of intermediate maturity. Moreover, DC can be directly generated from PBMC preparations.

Antigen Presentation↗
PubMed2000

Immunology and aging.

Aging is accompanied by numerous functional and phenotypic changes in T cells, B cells and monocytes/macrophages; moreover, increases in autoimmunity, infections and occurrence of cancer have been reported in aged people. Healthy elderly persons, defined according to the criteria of the SENIEUR protocol, show various alterations in immunocompetent cells. Recent data have shown that the distribution of the subsets of peripheral blood, T-cell subtypes, is influenced by age. With increasing age, CD45RA(+) naive cells are replaced by CD45RA(-) memory CD4(+) T cells. In the CD8(+) T-cell subset, we found an increased proportion of cells co-expressing CD57. In monocytes also, some alterations of the immunophenotype, for example the expression of the adhesion molecule CD54, were observed. A relative deficit of transendothelial migration with aging was found in T cells, whereas this function was not impaired in monocytes. The immunophenotype and the function of dendritic cells do no t appear to be affected by aging. Due to their capacity to present antigens to T cells and to induce T-cell proliferation, dendritic cells may provide a useful tool for immunotherapy. In conclusion, investigations of immune functions in aging people reveal that there is an alteration of the immunophenotype of T cells and monocytes. Several functions of T-cell accompanying mechanisms, for example cytokine production and cell migration, are also affected by aging. In contrast, dendritic cells do not seem to be influenced by the aging process.

Journal Article↗
PubMed2000

Bone mineral density and biochemical parameters of bone metabolism in female patients with systemic lupus erythematosus.

OBJECTIVE: To evaluate bone mineral density and biochemical parameters of bone metabolism in ambulatory premenopausal female patients with systemic lupus erythematosus (SLE). METHODS: 30 women who fulfilled the ARA criteria for the classification of SLE were studied. Lumbar and femoral bone mineral density was determined by dual energy x ray absorptiometry. Various laboratory parameters including serum calcium, serum phosphorus, alkaline phosphatase, bone specific isoform of alkaline phophatase, propeptide of type 1 procollagen, deoxypyridinoline excretion, telopeptide of type 1 collagen, serum creatinine, osteocalcin, parathyroid hormone, 25-OH vitamin D, testosterone, progesterone, estradiol, follicle stimulating hormone and luteinotropic hormone were measured. RESULTS: According to the WHO criteria 39% of all patients with SLE studied had normal bone mineral density, 46% had osteopenia and 15% had osteoporosis at the lumbar spine; at the femoral neck 38.5% had normal bone mineral density, 38.5% had osteopenia and 23% suffered from osteoporosis. Significantly lower osteocalcin levels were found in SLE patients. All other bone resorption and formation markers measured were not statistically different, but higher serum albumin corrected calcium and lower phosphorus values were found in the SLE group. Of all sex hormones tested lower testosterone and higher follicle stimulating hormone concentrations were seen in patients with SLE. CONCLUSION: A high incidence was found of osteopenia and osteoporosis in premenopausal patients with SLE. Bone diminution in SLE seems to be attributable, at least in part, to decreased bone formation in SLE patients.

Adolescent↗
PubMed1999

[Hormone replacement therapy with 17 beta-estradiol dydrogesterone: results of a 3-month open-label study].

Hormone replacement therapy is well known for its beneficial effects on climacteric symptoms and is also used for the prevention of osteoporosis. In a prospective open label study we evaluated the efficacy and safety of hormone replacement therapy with 17 beta estradiol dydrogesterone (Femoston, 17 beta estradiol/continuously and dydrogesterone/sequentially). We observed 704 women who were treated with 17 beta estradiol-dydrogesterone over three months. 448 of the women previously had not used hormone replacement therapy, 224 women had been treated with a different hormone replacement therapy before they were entered into the study; for 20 women this information was not available. The physicians were asked to assess the severity of climacteric symptoms at baseline and after three months of hormone replacement therapy. In addition, the following parameters were evaluated before and at the end of the study: blood pressure, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, blood glucose, alkaline phosphatase and gamma glutamyltransferase. Twelve women did not tolerate 17 beta estradiol-dydrogesterone and therefore dropped out of the study. Climacteric symptoms clearly improved after treatment with 17 beta estradiol-dydrogesterone. During our open label prospective study, a significant decrease in blood pressure and serum levels of total cholesterol, LDL cholesterol and the LDL/HDL ratio were observed, whereas serum levels of HDL cholesterol increased significantly. Surprisingly, triglyceride levels also decreased significantly. Serum levels of alkaline phosphatase decreased significantly in women who had received a different hormone replacement therapy before they took 17 beta estradiol-dydrogesterone. We conclude that hormone replacement therapy with 17 beta estradiol-dydrogesterone is highly effective and well tolerated. Hormone replacement therapy with 17 beta estradiol-dydrogesterone appears to have a positive effect on blood pressure and the serum lipid profile. We therefore hypothesise that prolonged treatment with 17 beta estradiol-dydrogesterone may reduce morbidity and mortality secondary to cardiovascular diseases.

Alkaline Phosphatase↗
PubMed1999

[Translation of the Osteoporosis Quality of Life questionnaire (OQLQ) into German].

Osteoporosis is a major health problem affecting the quality of life. The Osteoporosis Quality of Life Questionnaire (OQLQ) is a disease-specific measure intended for use in English-speaking countries. As there is a need for measures in non English-speaking countries as well, we translated the OQLQ according to a standardised protocol into the German language. Twenty-five women suffering from osteoporosis were tested in regard of quality of life. The questionnaire appears to be especially suitable for more disabled patients.

Aged↗
PubMed1999

[Pathophysiology and therapy of osteoporosis].

Osteoporosis is a heterogeneous disease of significant socioeconomic importance. In this paper the pathogenesis of postmenopausal and senile osteoporosis, osteoporosis in men and secondary osteoporosis is reviewed. Moreover, several aspects of the diagnosis and the treatment of osteoporosis (including calcium, vitamin D, vitamin D metabolites, estrogens, SERMs, bisphosphonates, calcitonin and fluorides) are discussed.

Estrogen Replacement Therapy↗
PubMed1999

Regulatory effects of 1alpha,25-dihydroxyvitamin D3 on the cytokine production of human peripheral blood lymphocytes.

We studied the possible regulatory effects of 1alpha,25-dihydroxyvitamin D3 [1alpha,25-(OH)2D3] on cytokine production and differentiation of subsets of CD4+ [T helper 1 (Th1) and Th2] and CD8+ [T cytotoxic 1 (Tc1) and Tc2] lymphocytes at the single cell level. PBMC from healthy donors were cultured with or without 1alpha,25-(OH)2D3 for up to 21 days. On days 0, 7, 14, and 21, the percentage of cytokine-producing T lymphocytes was analyzed by intracellular cytokine detection with mAb and flow cytometry. Simultaneous staining for cell surface markers allowed discrimination of CD4+ and CD8+ T cell subsets. After culture with 1alpha,25-(OH)2D3 (10(-8) mol/L), no significant effects on the proportion of interferon-gamma (IFNgamma)- or interleukin-4 (IL-4)-producing cells were detected, whereas reduced frequencies of IL-2-producing cells in the CD4+ as well as in the CD8+ population were found. An increase in the low percentage of CD4+ and CD8+ T cells producing the Th2 cytokine IL-13 was noticed. Most interestingly, IL-6-producing CD4+ and CD8+ T cells could only be detected in cultures with 1alpha,25-(OH)2D3, reaching a plateau after 14 days. The percentage of IL-6-producing T cells induced by 1alpha,25-(OH)2D3 after a given time period remained stable for at least 7 weeks. Studies of cytokine coexpression revealed that about 70% of IL-6-producing CD4+ and CD8+ cells were also positive for IL-2, but more than 90% were negative for IFNgamma, IL-4, or IL-13, respectively. This suggests that the IL-6-producing population does not match the Th1/Tc1-like (IFNgamma+) or Th2/Tc2-like (IL-4+ or IL-13+) subset. The influence of 1alpha,25-(OH)2D3 on cytokine production by lymphocytes is probably an important point of intersection between the endocrine and the immune system.

Adult↗
PubMed1999

[Pathophysiology of osteoporosis].

Osteoporosis must be viewed as a pathological condition which affects the entire skeleton and is characterized by a low bone mass in combination with microarchitectural changes particularly of cancellous bone, both adding to the fragility of bone at distinct sites of the axial as well as the perpendicular skeleton. The two major determinants of bone mass and mineral density in later life in both sexes, i.e., (i) the extent of the peak bone mass in early adulthood as well as (ii) the rate of involutional bone loss thereafter, both are governed by a complex interaction of genetic, age-related, hormonal, nutritional, environmental and life style factors in the regulation of systemic calcium and phosphate homeostasis and, equally important, of local bone remodeling processes. Osteoporosis results from an imbalance of bone resorption (osteoclast activity) and bone formation (osteoblast activity). Based on pathophysiological concepts, effective strategies for prevention and treatment of osteoporosis can be designed. Thus, modification of nutritional (calcium and/or vitamin D deficiency), endocrine (estrogen deficiency) and life style factors (physical activity) are important principles not only for prevention of osteoporotic bone loss but also for treatment of the overt disease which can be aided by a variety of drugs that either inhibit bone resorption or increase bone formation.

Bone Remodeling↗
PubMed1998

The effect of alendronate on cytokine production, adhesion molecule expression, and transendothelial migration of human peripheral blood mononuclear cells.

Since both osteoclasts and macrophages belong to the mononuclear phagocytic system it is conceivable that bisphosphonates not only affect bone metabolism but also inflammatory responses. The migration of mononuclear cells into perivascular tissue is a central event in inflammatory reactions. We studied the effects of the aminobisphosphonate alendronate on the transendothelial migration of human peripheral blood mononuclear cells in an in vitro model. Alendronate (at a concentration of 100 microM) significantly increased the percentage of peripheral blood mononuclear cells that migrated through endothelial cell monolayers. Similar results were obtained with another aminobisphosphonate, viz, pamidronate. An overnight treatment of the endothelial cell monolayers with alendronate did not alter the rate of peripheral blood mononuclear cells that subsequently migrated. The overnight cultivation of the peripheral blood mononuclear cells in the presence of alendronate resulted in an increased surface expression of CD54 (intercellular adhesion molecule-1, ICAM-1) in both CD14(+) and CD3(+) cells; in CD14(+) cells also the expression of CD49d (alpha4 subunit of late activation antigen-4, VLA-4) increased after alendronate treatment. Alendronate treatment of peripheral blood mononuclear cells also resulted in an increased production of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma). We conclude that alendronate has a distinct effect on the transendothelial migration of human peripheral blood mononuclear cells in vitro. Alendronate may either directly or indirectly, e.g., by augmenting the production of proinflammatory cytokines, influence the expression of certain adhesion molecules and thereby facilitate transendothelial migration. These effects could be related to the transient leukopenia reported following intravenous administration of relatively high doses of aminobisphosphonates for the treatment of hypercalcemia of malignancy.

Alendronate↗