[Haemorrhagic shock and calciumhomeostasis in rats (author's transl)].
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Biomedical subjects
Publications and source records attributed to B Krempien.
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Uremic women on hemodialysis with metabolic bone disease (hyperparathyroidism, osteomalacia resulting from defective vitamin D metabolism) and anemia (erythropoietin deficiency) are known to give birth to infants without bone disease or anemia. Therefore, skeletal development (enchondral and desmal bone formation) and hepatic erythropoiesis were evaluated in fetuses of uremic rats. These fetuses failed to show defective mineralisation or evidence of bone disease. Bolus injection of high doses of exogenous PTH into the maternal or fetal organism did not affect fetal bone histology. In addition, no apparent defect of bone mineralisation or bone formation was found in fetuses of ricketic rats. Normal mineralisation in the offspring of uremic rats may be explained by fetal hyperphosphatemia and/or insensitivity of fetal (woven) bone mineralisation to vitamin D. Absence of fetal anemia (normal hematocrits, normal density of hematopoietic cells in the liver) in the presence of maternal anemia is presumably due to the insensitivity of fetal erythropoiesis to erythropoietin.
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Stable long-term chronic renal failure in the growing Sprague Dawley rat causes marked bone disease with impaired mineralization (i.e. rickets) and evidence of increased parathyroid hormone activity. Although significant bone disease is present, the rate of longitudinal growth is not diminished in preterminal renal failure. However, it is significantly diminished in terminal renal failure, when uremic rats are compared with sham-operated control rats at identical levels of food intake. At identical levels of food intake, weight gain is also diminished in rats with terminal uremia as compared with sham-operated control rats, suggesting increased calorie cost for growth.
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Longitudinal growth; bone and growth zone histology; growth cartilage and bone mineralization (tetracycline technique); bone Ca content (neutron activation analysis); bone radiology; serum and urine chemistry; urinary cAMP and serum 25-OH-vitamin D3 were studied in a long-term model of experimental uremia in the rat. Uremia was induced by two-stage subtotal nephrectomy with irradiation of the remaining parenchyma. Ccr in the experimental group was 113 +/- 5.8 micron1/min X 100 g (19.8% of controls) and serum creatinine 1.67 +/- 0.04 mg% (5.1 X control value). Uremic animals were pair-fed with sham-operated controls. In the proximal tibia delayed transformation of cartilage into primary spongiosa with appearance of chondro-osteoid and delayed transformation of primary spongiosa into secondary spongiosa was observed (rickets). Increased amounts of osteoid were present although 25-OH-vitamin D3-levels were high. There were only modest signs of secondary hyperparathyroidism (osteoclast counts; urinary cAMP). In spite of the presence of bone disease, longitudinal growth was not reduced in uremic animals as compared with pair-fed sham-operated animals, but was significantly reduced as compared with ad lib fed control animals. In contrast, weight gain was significantly diminished in uremic animals as compared with pair-fed sham-operated control animals. It is concluded that diminished intake of food is the major determinant of growth retardation in preterminal experimental renal failure.
Differential counts and electron microscopical studies of osteocytes were performed on rats immobilized by spinal cord severing, plaster cast and ischiatic nerve dissection. In undecalcified ground sections of tibia and femur (100 micron) stained with basic fuchsin, osteocytes were differentiated into small (metabolically inactive) osteocy es enlarged (metabolically activated) osteocytes and empty lacunae. In rats (immobilizedfor' three weeks) with functioning parathyroid glands, but not after parathyroidectomy, the number of activated cells is markedly increased, whereas the number of small osteocytes is reduced. In animals with spinal cord severing the number of empty lacunae is also increased. Electron microscopical studies of undecalcified tibiae taken from rats immobilized for ten days showed a periosteocytic osteolysis with destruction of the lacunar wall, fragmentation of collagen fibres and loss of mineral crystals. The cytoplasmic seams of osteocytes were broadened, mitochondria were enlarged, and the cytoplasma showed vacuoles containing amorphous material which could be found in the pericellular space. Deep invaginations of the cytoplasma and an increase of the cell processes were typical findings. The results of the investigation point to an activation of osteocyte metabolism by immobilization. The osteocytes thus play an important part at the onset of immobilization osteoporosis. Periosteocytic osteolysis can be inhibited by parathyroidectomy. Therefore, the response of osteocytes to endogenous parathyroid hormone must be altered under conditions of immobilization.
A bioglass-coated fully dense alumina total hip was evaluated in sheep without using polymer bone "cement." After 3 months following surgery, both the acetabular cup and femoral stem component were firmly attached to bone. Histologic and radiographic analysis of the bone-implant interface showed regions of woven and even lamellar bone formation where high load transmission occurred. In regions of low loading or poor fit, a pseudosynovial fibrous lining was present.
A biomechanical concept of interface maturation around cement-free implanted alumina-ceramic hip endoprostheses in sheep is explained. Provided there is rigid primary stability of the implant within the bone bed, hard tissue formation along the support areas of the implant is mainly dependent on implant shape and main local stress direction. Three subsequent phases of interface maturation can be distinguished, finally resulting in firm fixation of the implant by mechanical interlocking of supporting bone and ceramic. A new composite alumina-metal hip endoprosthesis for partial cement-free implantation (cup) is presented. The technique, postoperative care, and encouraging early results in 5 patients are demonstrated. A new ceramic femoral component for cement free implantation is proposed.
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Four different acetabular replacement designs and 2 femoral head replacement designs made out of high density alumina ceramic have been tested in sheep with postoperative survival times of up to 11 months (Frialit 99: Al2O3 99.6%, MgO 0.4%). It can be concluded from these experiments that a cement free implantation technique with alumina requires a primary rigid fixation of the implant to bone, with the possibility for new bone growth along the ceramic and into grooves and macroscopic holes for further interdigitation. Three different solutions for the acetabular component can be recommended for human application. In addition, an all ceramic femoral prosthesis has been tested for bending strength in its neck region. Twenty prostheses have been factured, all of which showed values for bending strength far higher than the physiological neck fracture level (900 kp/cm2). The present state of development of all ceramic prostheses is discussed. Up to now, the development of fibrous tissue between the bone and the ceramic implant has caused reservations with human implantation. The direct definite anchorage problem has to be resolved first.
In femoral cortical bone of 16 uremic patients with long standing renal insufficiency an increased fraction of woven bone was found both in Haversian and in interstitial bone. Either partly resorbed Haversian systems were replaced by non lamellar woven bone or single Haversian systems showed partly well organized lamellar bone and partly disorganized non lamellar texture without signs of antecedent resorption. The replacement of lamellar bone by woven bone was measured morphometrically in undecalcified ground sections. Woven bone was defined by its lack of structural birefringence under polarized light. In advanced cases of secondary hyperparathyroidism more than 60% of cortical bone were composed of woven bone. The substitution of immature less organized woven bone for mature well orfanized lamellar bone has important implications for the biomechanical properties of the skeleton.
Clinical, biochemical, roentgenological, and histological features of slipped epiphyses (epiphysiolysis) in 11 out of 112 children with renal osteodystrophy have been analysed. Characteristic age-related patterns of involvement of different epiphyses are described. Quantitative measurements of iliac bone histology, serum parathyroid hormone levels, and clinical history show the presence of more advanced osteitis fibrosa in children with epiphysiolysis than in those without. A good correlation was found between serum parathormone levels and osteoclastic resorption, endosteal fibrosis as well as osteoid. Histological studies show that the radiolucent zone between the epiphyseal ossification centre and the metaphysis in x-rays is not caused by accumulation of cartilage and chondro-osteoid (as usually found in vitamin D deficiency rickets) but by the accumulation of woven bone and/or fibrous tissue. The response to vitamin D therapy in most cases was good. Parathyroidectomy was required in only one case.