[Pathophysiology of osteoporosis and bone density determination].
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Biomedical subjects
Publications and source records attributed to H G Haas.
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Due to increasing old age and a prolonged life expectancy osteoporoses mainly of the involutional type have become very common and are thus of prime socio-medical importance. Recently considerable attention has been given to calcitonin as an aetiologic, prophylactic and therapeutic agent in osteoporosis. Since the subject is very controversial, the present study aims at critically evaluating the pertinent literature from 1980-1989: 1. A decreased stimulability of the thyroid C-cells and thus a diminished calcitonin secretion capacity has been demonstrated in white postmenopausal women. However an overt calcitonin deficiency cannot be considered to be the only or a major cause of the osteoporotic bone loss. 2. An increased bone loss (occurring in phases?) may be stopped by calcitonin(s) given either parentally or by the intranasal route. This pharmacologic calcitonin effect does not differ from the well-known osteoclast inhibiting effect in Paget's disease and seems to be similar to estrogen bone effects in the menopause. 3. An increase of total body calcium (TbCa) of 1-4% and of the bone mineral content (BMC) has been reported occurring within 18-24 months of calcitonin administration in overt osteoporosis. However a reinforcement of the bone structure has not been shown, further crash fractures of vertebras occurring despite calcitonin administration for up to 2 years. Within this observation period the bone volume assessed histomorphometrically did not increase, unless calcitonin was combined with phosphates which were known to induce secondary hyperparathyroidism. 4. Repeatedly an analgesic efficacy has been ascribed to calcitonins, presumably due to a direct hormonal effect on calcitonin receptors in the brain. Since the pain in osteoporosis is extremely variable and often self-limiting due to fracture healing the "calcitonin analgesia" has probably been over-estimated.
In cells isolated from guinea-pig or rat ventricular muscle occurrence and distribution of carbohydrate components of the surface coat were monitored using fluorochrome-coupled lectins. Fluorescence of membrane-bound lectins was assayed by an image analysis system. The lectins ConA, WGA, sWGA, LFA and RCA-I showed specific binding to the whole myocyte surface, indicating a homogeneous distribution of alpha-mannosyl, alpha-glycosyl, N-acetylglucosaminyl, N-acetylneuraminate and beta-galactosyl residues. Binding of DBA and SBA, with specific affinity for N-acetylgalactosaminyl residues, to guinea-pig cardiac myocytes was mainly at the cell poles corresponding to intercalated discs in intact tissue. Both lectins failed to interact with rat myocytes. UEA-I, specific for alpha-L-fucose, bound slightly to rat and not to guinea-pig myocytes. Binding of PNA to guinea-pig myocytes was observed only after cleaving off sialic acids from cell surface, suggesting that sialic acids mask galactosyl-beta(1,3)-N-acetylgalactosamine residues. Specificity of lectin-cell interaction was tested by an inhibition assay where free sugars were tested for their capacity to inhibit lectin binding to the myocytes. When comparing different isolation procedures based on different proteolytic enzymes, the myocytes' affinity to any lectin was found to be qualitatively unchanged. Investigation of lectin-decorated myocytes by means of confocal laser scan microscopy showed that lectin binding sites are not confined to the cell surface but are also present in sarcolemmal invaginations, i.e. transverse tubules. This suggests that the tubular system is lined with a carbohydrate layer similar to, and continuous with, that of the peripheral cell surface.
A method is presented to reinforce normal suturing techniques in median and ulnar nerve repairs at the level of the forearm or wrist. If the distance between the stumps does not exceed 20 to 30 mm the coaptation can be protected from tension by two ribbons of polydioxanone (PDS) which are sutured to the epineurium bridging the site of the suture of the nerve. PDS ribbons proved to give remarkable support to experimental nerve repairs using epineural, perineural or Tsuge suture techniques. In further experiments with tibial nerves of rats the PDS ribbon did not interfere with the nerve function or with axon sprouting. Follow-up investigations of thirty-two median and ulnar nerve injuries treated with primary or secondary interfascicular sutures using PDS ribbons of 20 mm length and 1 mm width to protect the suture line revealed satisfactory reinnervation. The late results with this method were superior to a comparable group treated with autografts.
A special hook and plate can be used to adapt small central fragments in the open reduction of Bennett's fracture-dislocation. The hook is positioned behind the small central fragment and compression exerted between the hook and a plate attached to the opposite side of the base of the first metacarpal bone using an adjustable nut, thus holding the fragments together. The reduction device simplifies X-ray controls and internal fixation with Kirschner wires.
In 50 cases of pseudarthrosis of the scaphoid bone the operative technique of Matti and Russe was applied using fibrin adhesive in addition to a cortico-cancellous bone graft from the iliac crest to secure the fixation of the graft. 48 patients were re-examined. 27% showed bone consolidation after 3 months, 60% after 6 months or more. The total consolidation rate was 87%. It is not quite sure whether the better results are due to fibrin adhesive or not, especially when the consolidation took place after 6 month or more.
A method to monitor contraction of isolated myocytes by transmicroscopic photometry is illustrated. Two photodiodes are mounted inside an inverse microscope used for visual control of a cell. Illumination of one diode varies in proportion to changes in cell length. The contraction signal is amplified in a comparator circuit. Spatial resolution of the device is in the order of 1 micron which corresponds to about 5% of cell shortening in the fully activated state of contraction. The method was tested on isolated myocytes from guinea-pig ventricle. Optical records of contraction in response to action potentials or during voltage clamp compare well with the contractile behavior of multicellular preparations.
Over the period of three years 33 free latissimus dorsi-flaps and 23 pedicled myoplasties of various types for the coverage of large tissue and bone defects are performed. The operative technique of the free muscle transfer with microvascular anastomosis are described in detail. The postoperative management is outlined. The results of the free and pedicled muscle flaps are reported. In free transplantations the success-rate was 88% and in pedicled flaps 65% There is good evidence that bone consolidation and healing of the chronic bone infection can be improved by healthy vital soft tissue coverage. The indications for both procedures and the advantages and disadvantages of free and pedicled flaps are discussed.
Voltage clamp responses of a single excitable fiber were simulated using a core conductor model including a high external resistance (Rs) in series to the fiber membrane to allow for intercellular clefts in a multifiber preparation. In terms of specific resistance, Rs was between 68 and 264 omega cm2. Internal resistivity (Ri) was taken to be zero or 200 omega cm. The aim of the study was to quantify the expected antagonistic effects of external and internal resistances on Na current measurements. With Ri = 0, the external resistance was found to cause a strong depression of fast inward current compared to an ideal space clamp at command potentials between -30 and 30 mV. With Ri = 200 omega cm, the depression of inward current was partially removed. The effects of Rs and Ri on membrane current measurement were illustrated by cable analysis assuming a quasi-steady state of the fiber at peak time of inward current.
In a 71-year-old patient with osteomalacia, masked primary hyperparathyroidism was detected by vitamin D therapy for hypercalcemia. Surgery revealed a parathyroid tumor. Interpretation of total plasma calcium may be difficult unless the 25-hydroxyvitamin D levels are outside the normal range.
A theoretical model is presented for voltage clamp of a bundle of cylindrical excitable cells in a double sucrose gap. The preparation in the test node is represented by a single one-dimensional cable (length/diameter ratio approximately) with standard Hodgkin-Huxley kinetics for transmembrane Na current. Imperfections of voltage control due to internal (longitudinal) resistivity and external (radial) resistance in series to the membrane are analysed. The electrical behavior of a fiber is described by the cable equation with appropriate boundary conditions and subsidiary equations reflecting the membrane characteristics. Membrane voltage and current distribution in response to a step command was obtained by numerical integration. The results are described in two papers. The present paper deals with the effect of internal resistivity with the external resistance being neglected. The closed loop response of a fiber displays a strong tendency to oscillate. To stabilize the system a phase lead was inserted and the gain of the control amplifier was reduced. Conditions for stability were examined by Nyquist analysis. When the Na system was activated by a command pulse below ENa, a voltage gradient developed between a depolarization (relative to the command signal) at the end where voltage was monitored and a hyperpolarization at the site of current injection. In spite of a poor voltage control the total measured current appeared to have a smooth transient. With large voltage gradients a small, second inward current was seen. At a low (high) Na conductance maximum peak inward current was larger (smaller) that the current expected from ideal space clamping.
Polydioxanon-splints have been used instead of Kirschner-wires in 13 cases for the treatment of fractures of the base or head of phalanges and metacarpals and also, in conjunction with intraosseous suture wires, to stabilize the bones in replantation surgery.
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Within a period of twelve years, the authors have treated twelve patients with metacarpophalangeal joint luxations of thumb and long fingers which could not be reposed by conservative treatment. The case reports are presented in order to describe the problems posed by this relatively rare injury, the reasons hindering a reposition, and the treatment methods. This study is intended to underline the importance of early diagnosis and immediate surgical treatment in order to maintain the function of the joint.
Passive electrical parameters of bullfrog atrial trabeculae were measured in a single gap arrangement. Attention was focussed on the resistance of internal longitudinal pathway. The influence of external Ca2+ depletion was tested using EGTA as chelating agent. Morphometry of trabeculae, fine structure of junctional complexes, and distribution of membrane-bound Ca were investigated by light and electron microscopic methods. The specific internal resistance to longitudinal current flow was 523 omega cm with normal Ringer as perfusing fluid and 1140 omega cm in EGTA-containing solution. These values are considered to represent the sum of myoplasmic and junctional resistivity. Morphometrical studies indicated an interstitial space of 12%, a mean cell length of 358 micron, and a mean cell diameter of 3.2 micron. In freeze-fractured preparations junctional structures were observed in the form of "atypical gap junctions" consisting of 10 nm particles arranged in a circular or linear array. The number of gap junctions was estimated to range between 20 and 50/cell which is equivalent to a junctional area of 0.01 or 0.03% of total surface area. A mean number of 55 particles/gap junction was calculated. After 20 min of exposure to EGTA the majority of junctional complexes were converted to clusters; the number of particles/gap junction was not significantly altered. The fluorescent dye CTC was used as a probe for membrane-bound Ca of isolated living cells. In normal Ringer a strong fluorescence was seen at the cell surface and in different intracellular compartments. With EGTA both superficial and internal fluorescence disappeared completely. From a combination of electrical and morphometrical data the resistance of intercellular junctions was calculated. Under normal conditions the specific resistance of junctional membrane amounted to 0.4 omega cm2 and the resistance of an individual connection was of the order of 10(11) omega. With EGTA, the respective values were increased by about 230%. The mechanism underlying this depression of junctional conductance is not clear. It seems not related to a rise of cytoplasmic free Ca2+. The EGTA-induced increase in internal resistance was reflected by a decrease of the length constant of a bundle. The nature of "atypical gap junctions" and their relation to tight junctions are discussed. It is concluded that the junctions observed in frog atrial muscle are analogous to gap junctions of insect or mammalian cells in spite of the different size and arrangement of the particles. A theoretical model is presented for the electrical behaviour of a bundle in a single gap arrangement.(ABSTRACT TRUNCATED AT 400 WORDS)
1. In primary hyperparathyroidism an increased bone turnover is seen, accompanied by osteitis fibrosa (= fibroosteoclasia, FO) in severe forms of the disease. Both types of bone reaction may be detected by microradioscopy X-rays of the hand, extensive striation of metacarpal cortical bone indicating increased bone turnover and subperiosteal resorption of phalanges pointing to FO. 2. In the present study 65 patients with proven PHPT were evaluated before and 39 after operation. Microradioscopy was combined with biochemical assessment of hyperparathyroidism including alkaline serum phosphatase (aPh) as an index of osteoblastic activity, hydroxyprolin excretion (HyPro) reflecting bone turnover, immunoreactive parathyroid hormone levels (PTH), serum calcium (SCa), urinary calcium (UCa), serum inorganic phosphorus (SP) and clearance of phosphate (Cp). A comparison was made with the incidence of renal stone disease and the degrees of metacarpal striation (StG) and subperiosteal resorption (UG) were followed after operation. 3. Preoperative X-rays of 60% of the PHPT subjects showed increased StG and/or UG, and in 41,5% the diagnosis of PHPT was possible from the X-ray findings only. There existed a significant correlation between StG and UG on one hand and aPh, HyPro and PTH on the other. No correlation, either positive or negative, was seen between FO and the incidence of renal stones. After surgery, subperiosteal bone lesions disappeared in all patients, while intracortical striations persisted in half of the subjects despite the normalised bone turnover. Thus, primary hyperparathyroidism may not only lead to endosteal bone loss but to an irreversible intracortical bone deficit as well.
Rapid and preferential uptake of 47 calcium 87m Strontium by the multinodular calcareous masses was seen in a patient with tumoral calcinosis. Using 87m Strontium, scintigraphic imaging of the tumors was achieved, while the skeleton was barely visible. More intense accumulation of 87m Sr. in one tumor suggested a higher rate of calcium depostion. This was in agreement with the observation that this tumor showed less tendency to decrease in size during calcium and phosphorus deprivation therapy. Quantitative measurements of the uptake of bone seeking tracers by the tumors may be of value in estimating calcium turnover in the calcified masses.