Predicting lethal outcome after severe head injury — A computer-assisted analysis of neurological symptoms and laboratory values

Summary A total number of 58 parameters (laboratory values, neurological symptoms, and vegetative parameters) were evaluated in 150 patients during the first seven days after severe head injury. The patients were divided into two groups, survivors and non-survivors. Eight easily evaluable routine parameters with the most significant differences between the two groups of patients were used for statistical evaluation of a no survival chance score. These highly indicative parameters are serum osmolarity and urea, blood glucose, total bilirubin, motor reaction to stimuli, body temperature, respiratory activity, and pupil reaction. A low survival chance limit was evaluated from each of these parameters by computer analysis. None of the patients in the series survived when three or more of these eight parameters had climbed beyond the limit. So far, the system is able to predict no survival chances in 50.8% of the non-survivors some six days prior to death; 80% of these predictions could be made by the fourth day after injury.     

Effect of hyperfiltration on long-term follow-up of glomerular filtration rate in male Wistar rats

It has been suggested that a prolonged course of hyperfiltration could lead to progressive deterioration of renal function. In order to test this hypothesis, the following protocol was applied to 60 male Wistar rats. At 12 weeks of life, the rats were submitted to a surgical procedure: sham operation (25 rats), unilateral nephrectomy (25 rats) or 3/4 nephrectomy (10 rats). The three groups were again divided into two subgroups: one with high-protein intake (36%) and one with a low-protein intake (12%). In order to avoid any additional traumatic procedure which could shorten the animal's life, the glomerular filtration rate (GFR) was measured without blood sampling, using a previously validated technique based on an image recorded by a gamma camera between the 9th and the 10th min after intravenous injection of^99m technetium diethylenetriaminepentaacetate (DTPA). The sum of both kidneys and bladder activity was expressed as a percentage of the injected dose. The test was performed before surgery and every month thereafter. Six weeks after surgery, the highest filtration rate was found in the rats with two kidneys/high-protein diet, followed by the two kidneys/low-protein diet, the one kidney/high-protein diet, the one kidney/low-protein diet and the 1/2 kidney. The overall GFR in the one kidney/high-protein diet rat and in the 1/2 kidney rat was respectively 80% and 55% of the pre-operative values. Until 109 weeks of age, the survival rate was comparable in the five groups of rats. At 109 weeks of age, non-significant changes in renal function were observed, the follow-up slopes of the different subgroups being more or less parallel. At that age, the lesions of glomerular sclerosis were focal and discrete, without significant differences in the five groups.     

The beneficial effect of effective control of anemia on hyperinsulinemia and hypoxemia in a hemodialysis patient with corrected transposition of the great arteries

We report the beneficial effect of control of anemia on hyperinsulinemia and hypoxemia in a hemodialysis patient with corrected transposition of the great arteries. The patients hemoglobin (Hb) level of 10.3g/dl on admission represents good control for hemodialysis (HD) patients, but it was too low for this patient with secondary polycythemia because of a right-to-left shunt. Control of anemia for a 10-month period was followed by a marked increase in Hb level (from 10.3g/dl to 13.9g/dl) and in aerobic work capacity, while the fasted insulin level decreased from 36.7µU/ml to 8.0µU/ml, without changes in leptin level, body mass index (BMI), fat mass, Kt/V, or protein catabolic rate (PCR). Additionally, hypoxemia was ameliorated, from PO₂ 33.1mmHg to PO₂ 56.2mmHg, and the hyperdynamic cardiac state was improved. The degree of anemia, together with deteriorating tissue oxygenation, may have predisposed this patient to developing insulin resistance and consequent hyperinsulinemia. The most appropriate target Hb concentration should be tailored for the clinical condition of each individual patient, bearing in mind an insulin-resistance state, especially in hemodialysis patients with hypoxemia. A more complete understanding of what regulates insulin resistance and consequent hyperinsulinemia in endstage renal disease (ESRD) awaits the elucidation of carbohydrate and insulin metabolism.     

Prospective, randomized, double-blind study of safety and tolerability of intravesical resiniferatoxin (RTX) in interstitial cystitis (IC)

Objective: To determine the safety and tolerability of intravesical resiniferatoxin (RTX) in interstitial cystitis (IC) patients. Materials and Methods: IC patients were instilled with 50 cc of test solution containing either placebo, 0.05 M or 0.10 M RTX in the bladder. Plasma concentration of RTX and its degradant resiniferonol 9-, 13-, 14-orthophenylacetate was measured. Immediate post-treatment blood sampling and cystoscopy were performed. Symptoms were evaluated before treatment, at 4- and at 12-week follow-ups, using VAS indicator for pain, voiding diary, and OLearys IC symptom/problem indices. Results: Among 22 patients observed (ten in 0.10 M RTX, eight in 0.05 M RTX, and four in placebo groups), the most commonly reported adverse event was pain during instillation (80.0%, 87.5%, and 25.0%). No serious adverse events were reported. Conclusions: Use of intravesical RTX in IC patients is associated with important tolerability issues but safe at 0.10 M and 0.05 M.     

Experimental study of drainage and granulation in response to the intra-articular injection of particles in rat knee joints

Reactive granulation and drainage of intraarticularly injected plastic particles in rat knee joints was examined by light and electron microscopy. The knee joints and associated iliac lymph nodes were excised at various intervals after the injection of latex beads (1 m) or fluoresbrite particles (0.2 m or 10 m) from 5 min until 3 months after the injection. Particles in the lymphatic or blood vessels were successfully demonstrated by an enzyme-histochemical method (5-nucleotidase staining). Five min after the injection, most of the particles were scattered on the surface of the synovial membrane, and some particles were phagocytosed by synovial lining cells. After 5 h, neutrophils had phagocytosed particles which adhered to fibrin in the joint cavity. Twelve h after the injection, after the neutrophils had died, those same particles were phagocytosed by macrophages in the joint cavity. One day after the injection, Fluoresbrite particles (0.2 m) phagocytosed by macrophages were found in the iliac lymph nodes, while latex particles (1 m) were detected in the iliac lymph nodes 3 days after the injection. Some Fluoresbrite particles (10 m) were seen in the 5-nucleotidase-positive lymphatic vessels in the synovial membrane. Three months after the injection, many macrophages filled with particles had formed granulation tissue in the synovial membrane, and macrophages containing phagocytosed particles were also seen increasingly in the iliac lymph nodes. Our findings suggested that neutrophils and macrophages phagocytosed injected particles in the joint cavity, and that the macrophages brought the particles into the deep layer of the synovial membrane. Phagocytic macrophages also carried the particles to the iliac lymph nodes through lymphatic vessels in the synovial membrane. There were no morphological differences in the processes of granulation and drainage between the two different sized plastic particles (1 m and 0.2 m), except for the behavior of the macrophages phagocytosing the particles.     

The distribution of extracellular matrix vesicles in healing of rat tibial bone three days after intramedullary injury

Summary The distribution of extracellular matrix vesicles on the third day of bone healing was studied by morphometric analysis of transmission electron micrographs. Detection and grouping of the vesicles was performed according to type, diameter, and distance from the calcified front. The different types were selected as follows: vesicles with electron-lucent contents (empty), vesicles with amorphous electron-opaque contents (amorphic), vesicles containing crystalline depositions (crystal), and vesicles containing crystalline structures with ruptured membranes (rupture). The majority of vesicles were between 0.07 µm and 0.12 m in diameter and were located at less than 3 m from the calcified front. The distribution of the empty, amorphic, crystal, and rupture vesicles was 23.2%, 74%, 2.5%, and 0.3% respectively. Their sequence of arrangement according to diameter was as follows: empty, amorphic, crystal, and rupture, the empty vesicles constituting the smallest and the rupture the largest type. Distances from the calcified front were similar for the empty, amorphic, and crystal vesicles, while the rupture type was located nearest to the front. The present observations support the widely acknowledged hypothesis on the role of extracellular matrix vesicles in mineralization. It is thought that the secretion of empty vesicles from the cell is followed by intravscular accumulation of amorphous Ca and Pi to form a hydroxyapatite crystal that, in turn, ruptures the vesicle's membrane. The maturation process is accompanied by an increase of the vesicular diameter and its approximation to the calcifying front.     

Short-term perfusion and “Equilibration” of canine kidneys with protective solutions

Summary Kidneys were perfused either with Euro-Collinssolution or with HTK-solution of Bretschneider. The perfusion pressure as well as the perfusion flow were measured during a six-minute perfusion. The perfusion resistance was higher in Euro-Collins-kidneys than during HTK-perfusion. The venous outflow of the kidney as well as the ureteral outflow was measured during each minute of the perfusion and has analysed for osmolality, and for sodium and potassium concentrations. In Euro-Collins-kidneys a complete equilibration of the extracellular space was not achieved, while during HTK-perfusion concentrations in the venous as in the tubular outflow, similar to those in the HTK-solution itself, could be reached. At the end of the different perfusions, tissue was analysed for biochemical parameters such as ATP, ADP, AMP and lactate as well as for morphological features. Lactate had increased and ATP had decreased during perfusion with Euro-Collins-solution, while ATP had not changed and lactate had decreased during perfusion with HTK-solution. Normal glomerular, tubular and dilated vascular structures can be seen after HTK-perfusion, while a glomerular and vascular contraction takes place during Euro-Collins-perfusion.Supported by the Deutsche Forschungsgemeinschaft, SFB 89-Kardiologie Göttingen     

Effects of Cilostazol on Human Venous Smooth Muscle

In this study, we evaluated the effect of therapeutic doses of cilostazol on human venous smooth muscle. Saphenous vein rings (two to four per patient sample) were suspended in tissue baths for isometric tension recordings. At the beginning of the experiment, optimal tension for isometric contraction was achieved for each ring in a stepwise fashion in the presence of norepinephrine (10^–2 M). Norepinepherine was then added cumulatively in half-molar increments and isometric tension developed by the rings was measured, thereby obtaining a dose-response curve. Following washout and reequilibration, the rings were precontracted with a 30-50% submaximal dose of norepinepherine determined from the dose-response curve and allowed to contract until a stable plateau was reached. Cilostazol was then added in a cumulative manner (680-2,720 g/L), and the tension generated was recorded. A total of 76 venous rings were tested, and all relaxed in the presence of cilostazol. The amount of relaxation increased as the concentration of cilostazol increased. Relaxation of 15±1.9% (mean±SEM) at low cilostazol doses (680 g/L) to 37±3% at high cilostazol doses (2,720 g/L) was demonstrated. A second finding of this study was demonstrated when the patient samples were divided according to the presence or absence of risk factors for arteriosclerosis. The specific risk factors examined included diabetes mellitus, smoking, hypercholesterolemia, and hypertension. The presence or absence of hypertension (n=52) or hypercholesterolemia (n=18) did not affect the amount of relaxation of the venous rings. Smokers (n=46) had less relaxation 16±2.4% (680 g/L) to 41±3.6% (2,720 g/L) compared to nonsmokers (n=53) who relaxed 22±3.5% (680 g/L) to 48±5.7% (2720 g/L). This did not reach statistical significance at any concentration cilostazol (p=0.11-0.18). Diabetics (n=53) did have statistically significantly less relaxation at every concentration of cilostazol compared to nondiabetics (n=11, p < 0.05). All venous rings relaxed in the presence of cilostazol. Veins of nondiabetics relaxed statistically significantly more than those of diabetics. Smokers had less relaxation than non-smokers, but this was not statistically significant. We are the first to demonstrate that human venous smooth muscle cells undergo relaxation when exposed to therapeutic concentrations of cilostazol.     

Polymeric pyelotomy

A non-toxic, soluble polymeric preparation MAG with controlled period of gelation was synthetized for the extraction of stones from the pyelocalyceal system during surgery for urolithiasis.With respect to toughness the preparation proved superior to the fibrinogenthrombin mixture, used in the so-called fibrin pyelotomy according to Dees. Its biologic testing in animals (rabbits, dogs and pigs) yielded excellent results.By analogy with fibrin pyelotomy we took the liberty to propose the term polymeric pyelotomy.     

Standardization of Ischemic Hepatic Failure in Pigs as a Model for Bioartificial Liver Assessment

Purpose. A standard protocol of ischemic liver failure in pigs was examined to establish a system for assessing the efficacy of a bioartificial liver, based on clinical practice. Methods. The portal blood flow was extracorporeally bypassed into the cervical jugular vein, using a centrifugal blood pump. The portal vein and hepatic artery were then ligated. Results. The maintenance protocol was established as follows: (1) the concentration of the inhaled anesthetic was decreased by 0.2% when the systolic blood pressure was 100mmHg; (2) the volume of an infusion containing 5% glucose was increased to 10ml/kg per hour when central venous pressure was 5mmHg; (3) 20ml of 50% glucose was injected intravenously when the blood glucose was 50mg/dl; (4) 2000 units of heparin was injected intravenously when the activated clotting time was 150s; (5) sodium bicarbonate was given when the blood pH was 7.3; (6) tidal volume was increased by 1ml/kg when the pCO₂ was 80mmHg; (7) oxygen was increased by 25% when the pO₂ was 100mmHg. No vasopressors were used in the experiment. Conclusion. Our protocol reduced the operating time and minimized the risk of data deviation that can arise from variations in operating techniques and individual animal conditions. This experimental model is also easy to use as a bridge to transplantation.     

Comparison of hemodynamic and anesthetic effects of hyperbaric bupivacaine and tetracaine in spinal anesthesia

Purpose.To compare the anesthetic and hemodynamic effects and the predictive factor of anesthesia level of commonly used preparations of hyperbaric bupivacaine and tetracaine in spinal anesthesia. Methods.Two hundred patients aged 40 to 75 years with ASA physical status I or II were anesthetized spinally via the L4–5 interspace using 0.5% hyperbaric bupivacaine in 7.27% glucose (Bupivacaine group, n = 100) or 0.5% hyperbaric tetracaine dissolved in a 10% glucose solution (Tetracaine group, n = 100) in a lateral position. The volume of anesthetic used was decided by the resident according to the surgical procedure. Patients were returned to the supine position immediately after drug injection. Blood pressure, heart rate, and anesthesia level tested by cold sensation were measured for 30min. Results.Blood pressure and heart rate decreased significantly but without any differences between the groups. The volume of drug used was significantly larger in the Bupivacaine group (2.6 ± 0.5ml) than in the Tetracaine group (2.1 ± 0.4ml) to obtain the same maximum anesthesia level. The time to reach the maximum anesthesia level was significantly longer in the Bupivacaine group (18 ± 7min) than in the Tetracaine group (15 ± 6min). The volume of the drug was the only predictive factor of the maximum anesthesia level in both groups: Level (as expressed by the number of anesthetized segments from S5 to cephalad) = 1.55 × (volume in ml) + 13.06 in the Bupivacaine group, and 2.59 × (volume) + 11.46 in the Tetracaine group. Conclusion.In spinal anesthesia, hyperbaric tetracaine in 10% glucose induced a faster and higher spread of anesthesia than hyperbaric bupivacaine in 7.27% glucose without any differences in hemodynamics.     

Differential expression of transforming growth factor-β1 and β3 as well as C-FOS mRNA in normal human prostate,benign prostatic hyperplasia and prostatic cancer

Summary The discrepancy between the incidence of latent prostate cancer and that of clinically overt carcinoma suggests that there can be different courses in the biological progression of prostate cancer. As this cancer is detected increasingly at an infraclinical stage, markers are needed to indicate which lesions will progress and lead to the patient's death. To investigate the possibility that specific growth factors and/or proto-oncogenes are expressed differentially, we measured mRNA levels of transforming growth factors 1 (TGF-1), TGF-2 and TGF-3 and of the c-fos and c-jun oncogenes by Northern blotting in normal prostate, benign prostatic hyperplasia (BPH) and prostate cancer. Our data demonstrate that expression of TGF-1 increased, whereas that of TGF-3 fell to an almost undetectable level in carcinoma. Expression of c-fos followed the TGF-1 pattern, whereas no difference could be seen in c-jun expression in cancer as compared with BPH and normal prostate. The differential expression of TGF-1, TGF-3 and c-fos could possibly be used to improve the characterisation of prostate cancer. Long-term follow-up of patients may indicate whether mRNA levels of these growth factors and oncogenes correlate clinically and whether they can be used as markers for progression in human prostate cancer.     

1. Gemeinsamen Kongress Orthopädie-Unfallchirurgie 2005

Zusammenfassung Vom 19. bis 22. Oktober 2005 findet in Berlin der 1. Gemeinsame Kongress Orthopädie und Unfallchirurgie der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie, der Deutschen Gesellschaft für Unfallchirurgie sowie des Berufsverbandes der Fachärzte für Orthopädie statt.Die Abstracts des Kongresses werden als electronic supplementary material zu den Zeitschriften Der Orthopäde und Der Unfallchirurg in Springer Link veröffentlicht; sie können über die URL derorthopaede.de oder derunfallchirurg.de abgerufen werden.

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Electronic Supplementary Material Abstracts finden Sie in der elektronischen Version dieses Beitrags unter .      

Effects of calcium and temperature on tension in isolated canine coronary artery

The effects of calcium and temperature on the tension of isolated canine coronary arterial strips were studied.In 20mEq·l ^–1 K solution, the tension was significantly increased from 0mg with 0mEq·l ^–1 Ca to 33 ± 18mg with 0.2mEq·l ^–1 Ca at 37°C, from –40 ± 18mg with 0mEq·l ^–1 Ca to –17 ± 11mg with 0.2mEq·l ^–1 Ca at 30°C, from –77 ± 19mg with 0mEq·l ^–1 Ca to –52 ± 17mEq·l ^–1 with 1mEq·l ^–1 Ca at 25°C, from –88 ± 13mg with 0mEq·l ^–1 Ca to –41 ± 18mg with 2mEq·l ^–1 Ca at 20°C, from –125 ± 16mg with 0mEq·l ^–1 Ca to –116 ± 13mg with 2mEq·l ^–1 Ca at 15°C. Ca higher than 0.2mEq·l ^–1 produced a dose-dependent increase in tension between 37°C and 15°C. In spite of the presence of 4mEq·l ^–1 Ca, the development of tension was strongly supressed by lowering the temperature below 20°C, and completely inhibited at 10°C. The rate of a decrease in tension caused by cooling was about 5.5mg·°C^–1.This study demonstrated that Ca²⁺ produced a dose-dependent increase in tension in high-K solution, which was suppressed as the temperature was lowered.(Yoshida K, Fujii Y, Ina H, et al.: Effects of calcium and temperature on tension in isolated canine coronary artery. J Anesth 5: 172–176, 1991)     

Differentiation of intercalated cells in culture

The renal collecting duct is a heterogenous epithelium consisting of intercalated cells (ICCs) and principal cells (PCs). To test the hypothesis that the two cell types might originate from one another and to determine which one of the two is a stem cell, -ICCs and PCs were isolated by fluorescence-activated cell sorting and grown on permeable supports. Cultures of sorted PCs maintained their PC phenotype [electrogenic sodium (Na⁺) reabsorption and potassium (K⁺) secretion and expression of PC-specific antigens]. In contrast, cultures of sorted -ICCs acquired -ICC-specific functions (e.g. proton secretion) and gradually expressed functions specific for PCs (amiloride-blockable Na⁺ current and K⁺ secretion). Most cells in cultures of sorted -ICCs also acquired a central cilium, a characteristic feature of PCs. Dual-staining of -ICC cultures with cell-specific antibodies against surface antigens revealed that approximately 45% of the cells expressed only ICC-specific antigens and approximately 20% expressed only PC antigens. The remainder of the cells were ICC/PC hybrids and stained for both markers. Such hybrid cells were also observed in situ, albeit with a lower frequency, on kidney sections dualstained with cell type-specific markers. The proliferation rate of the two cell types, assessed by pulse labeling cells in S-phase with bromodeoxyuridine or staining with an antibody against a proliferation antigen (KI-67), revealed a significantly higher proliferation rate among -ICCs than PCs. In aggregate, these data suggest that -ICCs in culture are capable of differentiating into -ICCs and PCs and raise the possibility that -ICC is the stem cell of the collecting duct.     

Comparison of anesthetic effects of epidural and intravenous administration of buprenorphine during operation

Thirty six patients were received epidural anesthesia with or without buprenorphine (BPN) during upper abdominal surgery. They were divided into three groups of 12 patients as follows; G-I received 20ml of 1% lidocaine epidurally, G-II received 20ml of 1% lidocaine epidurally and 0.6mg BPN intravenously, G-III received 20ml of 1% lidocaine with 0.6mg BPN epidurally. Additional 5ml of 1% lidocaine was given to any patient if systolic blood pressure or heart rate increased 10% compared to control value. Trachea was intubated following anesthetic induction with thiopental. The lungs were ventilated with a mixture of N₂O/O₂ (33%) and pancuronium was used for muscle relaxation. The total required doses of lidocaine in G-II and G-III were decreased 60% compared to control group (G-I) (P 0.05). The mean period of time until the first administration of pentazocine for postoperative pain was 13 ± 10hr (mean ± SD) in G-II and 19 ± 24hr in G-III compared to 5 ± 4hr in G-I (P 0.001). The dose of the administration of pentazocine that was required for pain relief during the first 48 postoperative hr in G-III was 54 ± 10mg (mean ± SD) compared to 150 ± 21mg in G-I (P 0.02) and 106 ± 28mg in G-II (P 0.05). Recovery from anesthesia in G-III was more rapid than that in G-I (P 0.05). The Pa_{CO 2} values in G-II and G-III increased 15% compared to control group at about 4hr and 8hr after administration of BPN, but any clinical treatment was not needed for them. Nonrespiratory side effects, e.g., nausea, vomiting, fatigue and headache, were comparably common in all groups. Mild hematuria associated with acute hypotension occurred in two patients in G-II (17%) immediately after the intravenous injection of 0.6mg of BPN. The results showed that 0.6mg of BPN given epidurally demonstrated better anesthetic and more potent postoperative analgesic effects and lesser side effects than 0.6mg of BPN given intravenously in patients undergoing upper abdominal surgery.(Yonemura E, Fukushima K.: Comparison of anesthetic effects of epidural and intravenous administration of buprenorphine during operation. J Anesth 4: 242–248, 1990)     

An interpretation of acute changes in plasma45Ca following parathyroid hormone administration to thyroparathyroidectomized rats

Acute changes in plasma calcium and⁴⁵Ca were studied in young adult male thyroparathyroidectomized (TPTX) rats injected with moderate doses of parathyroid hormone (PTH). For plasma calcium changes, comparison was made between rats fasted or fed prior to PTH injection. For plasma⁴⁵Ca changes, the effect of the time of administration of the radionuclide was also studied; this included rats injected with PTH 1 h after radionuclide (1 h⁴⁵Ca), 18 h later (18 h⁴⁵Ca) and more than 6 days later (6 day⁴⁵Ca). The results can be summarized as follows: (1) Plasma calcium changes were greater when PTH was injected into fed rather than into fasted rats. (2) PTH always produced a relative increase (compared to controls tested concurrently) in plasma⁴⁵Ca concentrations. This increase was the same in the 1 h⁴⁵Ca and the 18 h⁴⁵Ca groups. (3) Plasma⁴⁵Ca rose at least temporarily following PTH injection in the 18 h⁴⁵Ca group. (4) The⁴⁵Ca rise following PTH was always greater in fed than in fasted groups. (5) Plasma⁴⁵Ca specific activities (S.A.) tended to rise in the 6 day⁴⁵Ca group and to fall in the 18 h⁴⁵Ca group, following PTH injection. However, the⁴⁵Ca S.A. was always higher in fed than fasted groups. (6) In a few experiments in which³²P was injected with⁴⁵Ca, specific activity changes in plasma⁴⁵Ca following PTH injection werenot accompanied by similar changes in³²P specific activity.These results could not be adequately explained by PTH effects on bone resorption, but the data supported the postulate that PTH controls plasma calcium concentrations by increasing transport of calcium through the osteocyte-lining cell (osteoblast) bone cell complex from the bone fluid compartment to the ECF.     

Skoliose,Stoffwechsel und Wirbelsäulenwachstum

Zusammenfassung Die moderne Forschung neigt immer mehr zu der Ansicht, daß bei den sog. idiopathischen Skoliosen weniger biomechanische als vielmehr biochemische Störungen ursächlich beteiligt sind. Allerdings dürfte es sich dabei nicht um eine einheitliche Ursache handeln, sondern es scheinen sich mehrere Untergruppen herauszukristallisieren.Eine prozentmäßig recht deutlich vertretene Untergruppe betrifft jene idiopathischen Skoliosen, die arachnodaktyle Symptome aufweisen. Anhand dieser Fälle läßt sich ein Denkmodell aufstellen, durch welche Zusammenhänge Stoffwechselstörungen zu Wirbelsäulenverkrümmungen führen können bzw. führen müssen.Basis dieser Hypothese ist die Tatsache, daß das enchondrale Längenwachstum und das periostale Dickenwachstum von Röhrenknochen humoral nicht gleichartig gesteuert sind und daß das enchondrale Wachstum der Wirbelkörperreihe in cranio-caudaler, das der Wirbelbogenreihe aber in anteriorposteriorer Richtung erfolgt.Ist das Gleichgewicht zwischen enchondralem und periostalem Wachstum gestört, kommt es zu typischen Veränderungen an den Röhrenknochen entweder im Sinn einer Arachnodaktylie oder im Sinn einer Chondrodystrophie.Bei der Wirbelsäule muß eine entsprechende Störung entweder zu einer relativ längeren (also höheren Wirbelbogenreihe, d. h. zu einer Kyphose) oder zu einer relativ höheren Wirbelkörperreihe (d. h. zu einer Lordose bzw. Skoliose) führen.Die Ergebnisse der bisherigen Stoffwechseluntersuchungen passen gut in dieses Bild. Ist nämlich aufgrund bestimmter Stoffwechselstörungen das Gleichgewicht zwischen chondralem und periostalem Wachstum zugunsten des ersteren gestört, mu die wachsende Wirbelsäule aufgrund der gegenüber der Bogenreihe stärker in cranio-caudaler Richtung wachsende Körperreihe in die Skoliose ausweichen.Will man die idiopathische Skoliose ursächlich in den Griff bekommen, muß man in erster Linie die entsprechenden Stoffwechselstörungen beseitigen oder paralysieren. Fernziel aller Überlegungen wäre demnach eine effektvolle chemotherapeutische Behandlung der idiopathischen Skoliose.

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Scoliosis, metabolism and growth of the vertebral column

Summary Modern investigators incline to the opinion, that more biochemical than biomechanical disorders take part in cause of the idiopathic scolioses. It seems, however, that there is not only one cause but more in some subgroups.Idiopathic scolioses, which have symptomes of arachnodactyly, seem to be a big one of these subgroups. These cases allow to state a hypothesis, in which kind a disordered metabolism leads to a deviation of the spine.This hypothesis is basing on the fact, that the enchondral growth in the length and the periostal growth in the width of long bones are not regulated in the same endocrinological kind and that the enchondral growth of the vertebral-bodies-column happens in cranio-caudal direction, the enchondral growth of the vertebral-archies-column, however, in anterior-posterior direction.If the balance between enchondral and periostal growth is disturbed, you can see typical chances on the long bones, which resemble either an arachnodactyly or a chondrodysplasy.The same disturbance will cause a kyphosis respectively a lordosis (or scoliosis) on the vertebral spine; either the bodies-column or the archies-column will become longer (higher).The results of metabolism research are suitable to these facts. If the balance between enchondral and periostal growth,—basing on a dysbolism,—is disturbed in such a kind, that the vertebral-bodies-column is growing faster than the vertebral-archies-column, the vertebral spine is forced to change into a lordosis respectively into a scoliosis.If you want to cure an idiopathic scoliosis, you first have to remove or to paralyse the dysbolism. The aim of all research has to be to find an effective chemotherapeutical treatment of mindst a part of all idiopathic scolioses.

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Herrn Prof. Ph. Erlacher zum 90. Geburtstag gewidmet.     

Dexamethasone regulates IL-1β and TNF-α-induced interleukin-8 production in human bone marrow stromal and osteoblast-like cells

We have investigated both constitutive- and cytokine-induced secretion of interleukin-8 (IL-8) and its regulation by dexamethasone and 17-estradiol in normal human bone marrow stromal (HBMS), osteoblast-like cells (hOB), and osteosarcoma MG-63 cells. Although HBMS cells secrete low levels of IL-8 constitutively, treatment with IL-1 and tumor necrosis factor- (TNF-) induced IL-8 secretion. Their effects were synergistic but IL-8 production was not affected by 17-estradiol. Human osteosarcoma MG-63 cells also secreted low levels of IL-8 constitutively; the production was induced by IL-1 and TNF- and was also not affected by 17-estradiol. The magnitude of the response to cytokine stimulation of IL-8 in MG-63 cells was much lower than that of HBMS and hOB cells, indicating differences in response in normal and osteoblastic osteosarcoma cells. Dexamethasone (10^-7 M) significantly inhibited IL-1 plus TNF- stimulated IL-8 production in HBMS, MG-63, and hOB cells. The accumulated results demonstrate that IL-8 is secreted by HBMS, MG-63, and hOB cells, suggesting that IL-8 may play a role in the regulation of bone cell function. These data also emphasize the importance of glucocorticoids in controlling cytokine secretion in HBMS, hOB, and MG-63 cells.     

Cytokines in human milk: Properties and potential effects upon the mammary gland and the neonate

Epidemiologic and immunologic studies of breastfed and nonbreastfed infants and investigations of certain biologic activities in human milk led to the identification of immunomodulating agents in human milk. Among them were the cytokines interleukin-1 (IL-1); IL-6, IL-8, IL-10, granulocyte-colony stimulating factor, macrophage-colony stimulating factor (M-CSF), tumor necrosis factor-, interferon-, epithelial growth factor (EGF), transforming growth factor- (TGF-), and TGF-2. Inteferon- may originate from T cells in milk; EGF, TGF-, TGF-, M-CSF, IL-6, and IL-8 may be produced by mammary gland epithelium. Based upon their known functions, we hypothesize that cytokines influence the development and immunologic function of the mammary gland and the neonate. Thosein vivo functions remain to be defined by future investigations.