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C Kasperk

Publications and source records attributed to C Kasperk.

At least 37 records · Page 2Linked to original sources
PubMed1999

[Osteo-anabolic estrogen therapy in a transsexual man].

HISTORY AND ADMISSION FINDINGS: A 31-year-old man presented at the endocrinology out-patient clinic for the initiation of sex-change treatment. His manifestly transsexual male-to-female appearance was confirmed by a psychiatric-sexological expert report. The patient had been living as a woman for one year. Physical examination showed normal male physique with typical secondary hair growth and normal male genitals. INVESTIGATIONS: The serum testosterone level was at the upper limits of normal, that for oestrogen at the lower limit. Bone densitometry showed bone density at the upper limit of normal. Other laboratory tests were unremarkable. DIAGNOSIS, TREATMENT AND COURSE: During 30 months on cyproterone, 100 mg daily, bone mass fell at the rate of 5% per year. Bone biopsy revealed high turnover osteoporosis. Bone mass rose by 4% per year after the additional oral intake of oestradiol valerate, 2 mg daily. Osteoblastic cells, isolated from part of the biopsy tissue, with the patient's consent, was found to be stimulated by oestradiol in vitro. CONCLUSION: The described bone mass changes indicate the important role played by sex hormones in the maintenance of bone mass acquired during adolescence. The findings confirm that in males not only testosterone but also oestrogens has an anabolic effect on bone.

Adult↗
PubMed1999

The effect of pramlintide (amylin analogue) treatment on bone metabolism and bone density in patients with type 1 diabetes mellitus.

Amylin is a 37-amino-acid peptide related to CGRP and calcitonin. It is co-secreted with insulin from pancreatic beta-cells. Amylin is deficient with type 1 diabetes mellitus. To study the in vivo effects of amylin in humans, diabetic patients are an adequate model of chronic amylin deficiency. We investigated the effect of a 12 months pramlintide therapy (amylin analogue) on bone metabolism in patients with type 1 diabetes mellitus. 23 patients with type 1 diabetes mellitus (age 45.2 +/- 10.3 years, duration of diabetes mellitus 20.7 +/- 9.8 years, 13 male, 10 female) injected themselves 0.1 ml pramlintide, a human amylin analogue, four times per day for a period of 12 months. Bone mineral density measurements of the lumbar spine by dual-energy X-ray absorptiometry (DXA), and biochemical markers of bone metabolism (serum-calcium, PTH, osteocalcin, urinary pyridinium cross-links) were obtained before and one year after starting pramlintide therapy. None of the following parameters changed significantly: bone density, serum calcium, PTH, osteocalcin or pyridinium cross-links. Only osteocalcin decreased from 7.205 ng/ml to 5.825 ng/ml, but this change was not statistically significant. We conclude that a one-year pramlintide therapy does not affect bone density or bone metabolism in patients with type 1 diabetes mellitus without osteopenia (based on the markers used).

Adolescent↗
PubMed1998

Increased urinary crosslink levels in aseptic loosening of total hip arthroplasty.

The diagnosis of aseptic loosening in total hip arthroplasty is predominantly based on clinical and radiographic evaluation. Loosening is usually associated with increased bone resorption at the interface. In this study we wanted to evaluate the diagnostic value of bone markers in aseptic loosening. We compared 50 patients with proven component loosening during surgery with 50 age-, sex-, and implant-matched patients without clinical or radiological signs of loosening. We measured serum markers of bone formation (bone-specific alkaline phosphatase, osteocalcin [OC], procollagen type I propeptides) and bone resorption (collagen n-telopeptide [NTX], deoxypyridinoline [DPYD], pyridinoline [PYD]). We found significantly increased levels of NTX, DPYD, PYD, and OC in the loosening group. The other markers showed no significant difference between both groups. We conclude that determination of urinary crosslinks may offer a new and valuable diagnostic method in the detection of aseptic loosening in total hip arthroplasty.

Adult↗
PubMed1998

Regulation of interleukin-6 expression in human osteoblastic cells in vitro.

Interleukin-6 (IL-6) is a potent stimulator of bone resorption which has been demonstrated in a variety of in vivo and in vitro models. We investigated the regulation of IL-6 secretion in primary human osteoblastic cells (HOC) in vitro by cytokines known to play an important role in coupling bone formation to bone resorption. HOC were isolated from healthy adults who underwent selective orthopedic surgery and treated with cytokines released in the bone microenvironment during coupling i.e Interleukin-1beta (IL-1beta), Tumor Necrosis Factor alpha (TNFalpha), Transforming Growth Factor beta1 and 2 (TGFbeta 1 and 2) and Endothelin-1 (ET-1). Furthermore, we determined whether systemically-acting steroid hormones of gonadal and adrenal origin as well as glucocorticoids affect the local regulation of IL-6 secretion in primary HOC. To examine the effects of different steroid hormones on IL-6 production, HOC were exposed to estradiol (E2), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA) and dexamethasone (Dexa) with and without a subsequent treatment of the HOC populations with cytokines. We observed that (1) IL-1beta and TNFalpha induced IL-6 in a dose and time-dependent fashion, (2) TGFbeta 1 and 2 enhanced basal and IL-1beta and TNFalpha induced IL-6 expression, (3) ET-1 elicited a dose-dependent stimulatory effect on IL-6 expression. (4) E2, DHT and DHEA alone and in combination with IL-1beta and TNFalpha elicited no reproducible dose-dependent effect on IL-6 production, whereas Dexa inhibited basal and IL-1beta and TNFalpha induced IL-6 expression dose dependently. In conclusion, IL-1beta, TNFalpha, TGFbeta 1 and 2 and ET-1 may participate in the regulation of bone resorption by stimulating IL-6 expression in HOC. Dexa inhibits the constitutive and cytokine stimulated IL-6 expression, whereas there is no in vitro evidence that sex steroids exert a major inhibitory effect on the osteoblastic secretion of IL-6 as demonstrated in a primary human bone cell model.

Aged↗
PubMed1997

[The Wolfram syndrome: diabetes mellitus, hypacusis, optic atrophy and short stature in STH deficiency].

HISTORY AND CLINICAL FINDINGS: A 43-year-old man was known for 3 years to have diabetes mellitus. For 2 months before admission he had symptoms of hyperglycaemia with polyuria, polydipsia, weight loss, as well as impairment of vision and declining fitness. In addition to bilateral deafness he was clearly of normally proportioned short stature (150 cm). INVESTIGATIONS: The levels of blood sugar (221 mg/dl), HbA1c(10.2%), triglycerides (496 mg/dl) and cholesterol (323 mg/dl) were raised, while the concentration of somatotropic hormone was diminished, both before and after arginine administration. Fundoscopy revealed concentric diminution of the visual fields with left amblyopia. Visual evoked potentials and colour sense testing revealed bilateral optical atrophy, and the audiogram demonstrated deafness. These findings provided the diagnosis of Wolfram syndrome, namely insulin-dependent diabetes mellitus, deafness, optical atrophy and small stature with somatotropic hormone deficiency. TREATMENT AND COURSE: On insulin treatment the metabolic state became normal (HbA1c 7.5%, normal lipid profile). It was decided that the deficiency in somatotropic hormone regulation did not require treatment. CONCLUSION: Cardinal symptoms of the autosomally recessive Wolfram syndrome are insulin-dependent diabetes and optic nerve atrophy. Several types of hormonal abnormalities are associated with it, including a deficiency in the somatotropic axis. To obtain early and adequate hormonal substitution requires extensive endocrinological diagnosis of a disease which frequently becomes manifest in childhood or adolescence.

Adult↗
PubMed1997

Skeletal site-dependent expression of the androgen receptor in human osteoblastic cell populations.

There are obvious sexual differences in adult skeletal morphology which for the most part are related to differences in size. Higher androgen serum levels in males exert potent osteoanabolic effects and therefore may contribute to this sexual dimorphism of the skeleton. The presence of androgen receptors (AR) in bone cells is a prerequisite for a direct osteoanabolic action of androgens. To investigate the possibility that, in addition to gender-related differences in androgen serum levels, there are also gender-related differences in the osteoblastic expression pattern of the androgen receptor, we examined AR mRNA expression, androgen binding sites, and mitogenic responses to the androgen dihydrotestosterone (DHT) in human osteoblastic cell (HOC) populations. HOCs were isolated from bone biopsy specimens derived from different skeletal sites of healthy adult males and females (2-69 years old). We found that male and female HOCs of all examined ages express similar AR mRNA levels and similar numbers of androgen binding sites. Using whole-cell-binding assays, we observed 3129-8417 androgen binding sites per femoral HOC with apparent KDs of 1.45-2.83 nM depending on the age of the investigated HOC population. Mandibular and cortical HOC of both sexes expressed higher AR mRNA levels, significantly more androgen binding sites per cell, and exhibited significantly greater mitogenic responses to DHT than iliac crest-derived and trabecular HOC of the same skeletal system and the same skeletal-site, respectively. In early adulthood, HOCs of both sexes appear to express somewhat higher AR mRNA levels and to possess more androgen binding sites than prepubertal and senescent HOC. Because sex hormone serum levels rise in puberty, we investigated the regulation of the AR mRNA expression by various steroids. We found that dexamethasone (dexa) and in some experiments also 17beta-estradiol (E2) and 1,25-dihydroxyvitamin D3 (D3) increased AR mRNA levels and androgen binding in HOC cultures. A pretreatment with dexa, E2, and D3 significantly increased the mitogenic response of HOCs to DHT. We conclude that (1) higher androgen serum levels in males together with a higher AR expression at certain skeletal sites may contribute to the development of sex-related differences in skeletal morphology, (2) glucocorticoids induce AR gene expression in HOC cultures, and (3) glucocorticoids, E2, and D3 enhance the mitogenic action of DHT.

Adolescent↗
PubMed1996

[Cicatricial small intestinal stenosis following chemotherapy for a gastrointestinal lymphoma].

HISTORY AND CLINICAL FINDINGS: 4 weeks after completing a course of chemotherapy for non-Hodgkin lymphoma of the jejunum a 45-year-old woman developed pain in the left upper abdomen and postprandial vomiting so that she could no longer take food by mouth. INVESTIGATIONS: On admission she looked cachectic and had obviously lost weight. Plain abdominal X-ray gave no evidence of perforation or ileus. Gastroduodenoscopy showed no local recurrence. But contrast jejunal radiography (after Sellink) demonstrated two severe band-like stenoses of the jejunum with prestenotic dilatation. As she had not had any previous operation or radiotherapy, cicatricial stenosis was considered as the most likely cause. As the symptoms continued and stenosing local recurrence could not be excluded, surgical resection was indicated. TREATMENT AND COURSE: Two cicatricial intramural stenoses of the proximal jejunum were found and histologically confirmed without evidence of lymphoma recurrence. After the operation the patient was again able to take food by mouth without problem. Follow-up examination 8 months later showed no recurrence and she was free of gastrointestinal symptoms. CONCLUSION: After chemotherapy for gastrointestinal lymphoma obstruction of the small intestine may occur due to chemotherapy-induced scarring.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Differential effects of glucocorticoids on human osteoblastic cell metabolism in vitro.

Clinical observations suggest that the onset and severity of glucocorticoid (GC) induced osteoporosis is dependent on the duration of the GC treatment and the applied GC compound. To test whether these in vivo observations are reflected by different in vitro effects of various synthetic GCs on human bone cell metabolism we isolated human osteoblast-like cells (HOC) from bone biopsies of healthy (no clinical symptoms of arthritis or arthrosis) adults who underwent selective orthopedic surgery. HOC were identified as bone cells by 1,25-vitamin D3-stimulated increase of specific alkaline phosphatase (ALP) activity, secretion of osteocalcin and type-I procollagen peptide, and the ability to form mineral in vitro. We investigated the effects of dexamethasone (dexa), methylprednisolone (mpred), prednisolone (pred), and deflazacort (defla) on DNA-synthesis, ALP, and osteocalcin (OC)- and type-I procollagen peptide secretion of HOC in vitro. In summary, (1) GC exposure stimulates DNA synthesis after 6-12 hour treatment periods; (2) dex and mpred strongly inhibit DNA (48-hour treatment) and collagen synthesis but stimulate ALP, whereas pred and defla exhibit smaller effects on DNA synthesis, ALP, and collagen production; and (3) all tested glucocorticoids inhibit OC secretion by HOC in vitro. Thus, the effect of GC on DNA synthesis of HOC varies with the duration of GC exposure, and dex and mpred more potently affect HOC metabolism in vitro than pred and defla.

Adult↗
PubMed1995

Human bone cell phenotypes differ depending on their skeletal site of origin.

This report describes skeletal site-related differences in human osteoblastic cell metabolism in studies of four patients. Northern analyses of the constitutive growth factor messenger ribonucleic acid (mRNA) expression pattern in mandibular and iliac crest-derived human osteoblastic cells (based on within-patient comparisons) revealed higher mRNA levels for strong mitogenic growth factors such as basic fibroblast growth factor (bFGF) and insulin-like growth factor II (IGF-II) in the rapidly proliferating and less alkaline phosphatase (ALP)-expressing mandibular osteoblastic cells compared to those in the lower bFGF and IGF-II mRNA levels in slowly proliferating iliac human osteoblastic cells exhibiting a higher ALP expression level. In contrast, transforming growth factor-beta (TGF beta) mRNA was more abundant in iliac human osteoblastic cells than in mandibular osteoblastic cells. Furthermore, we found that there was a proportionality, based on data from both sites, between the level of constitutive TGF beta mRNA and the response to exogenously administered bFGF or IGF-II. A comparable pattern of growth characteristics and mRNA expression was also observed in transformed human osteoblastic cells that had been subcloned in sublines expressing high and low levels of the human osteoblastic differentiation marker ALP. These findings are consistent with 1) skeletal site-related differences in human bone cell phenotypes, and 2) decreased IGF-II and bFGF expression and increased TGF beta expression and responsiveness to bFGF and IGF-II in human bone cells exhibiting a high ALP expression.

Alkaline Phosphatase↗
PubMed1992

[Endocrinously active parathyroid cysts. Their diagnosis by the determination of intact parathormone in the cyst fluid].

A 53-year-old woman with recurrent nephrolithiasis was found to have hypercalcaemia of 3.12 mmol/l and an intact parathormone level of 166 pg/ml, indicating primary hyperparathyroidism. Preoperative ultrasound examination to localize the parathyroid adenoma revealed a clear fluid-containing cyst in the right lobe of the thyroid. The aspirated fluid had an intact parathormone level of 306 pg/ml, twice that in serum. The cyst was removed surgically. 14 days postoperatively calcium and parathormone levels in serum had become normal without any calcium administration. Measuring the concentration of intact parathormone in the aspirated cyst fluid made possible not only the distinction from a thyroid cyst but also the precise preoperative localization of the parathyroid cyst.

Body Fluids↗
PubMed1990

Studies of the mechanism by which androgens enhance mitogenesis and differentiation in bone cells.

Recently, we reported a direct effect of androgens on murine and human bone cells to stimulate bone cell proliferation and differentiation. To test whether this effect of androgenic steroids might be mediated by growth factors, we measured relative concentrations of insulin-like growth factor-I and -II (IGF-I and IGF-II) and transforming growth factor-beta (TGF beta) in the conditioned medium from androgen-treated murine calvarial cell cultures. Only the concentration of TGF beta was increased. Consistent with the increased secretion of TGF beta in the mouse calvarial cell system, we observed an increased expression of TGF beta mRNA in a normal human osteoblastic cell system. We also determined whether androgens alter the response to growth factors. We found that dihydrotestosterone (DHT) treatment enhanced the mitogenic effects of fibroblast growth factor (FGF) and IGF-II but not those of IGF-I. The enhanced effect of FGF and IGF-II after DHT pretreatment was not affected by addition of TGF beta-blocking antibodies or by changing the culture medium. This indicated that in addition to increased release of TGF beta, another mechanism might be involved in the action of DHT on human and murine bone cells. Thus, we investigated the binding of human IGF-II to human osteoblastic cells and observed an increase in IGF-II binding after DHT treatment. Our results are consistent with a mechanism of action of androgens on bone cells that involves the induction of TGF beta and, in addition, may sensitize the cells to show an enhanced response to FGF and IGF-II, possibly by changing the receptor binding of mitogenic growth factors.

Androgens↗
PubMed1988

Algae-derived (phycogene) hydroxylapatite. A comparative histological study [corrected and issued with original paging in Int J Oral Maxillofac Surg 1988 Oct;17(5)].

3 granular hydroxylapatite (HA) biomaterials, solid, coralline and phycogene HA (obtained from calcifying algae), differing widely in their relative amounts of specific surfaces and their origin, were examined with regard to their effects on bone healing in rats. Trephine drill holes were produced in the rat femur and filled with the HA granules. Each biomaterial produced a characteristic pattern of bone healing. Bioceramics with a small surface area showed random bone-implant contacts. Biomaterials offering large surface areas showed a dense bone-implant interface. Evidence is presented to suggest that a large specific surface favours osteoneogenesis and cell spreading on and into an implant.

Animals↗