Carpal tunnel syndrome and gynaecomastia during growth hormone treatment of elderly men with low circulating IGF-I concentrations

OBJECTIVE We studied the relationship between plasma level of insulin-like growth hormone I (IGF-I), changes in lean body mass and in adipose mass, and adverse side-effects during human growth hormone (hGH) treatment of elderly men who had low IGF-I levels. DESIGN The first six months was a period of baseline observation. The subjects were then randomized into two groups so that during months 7–18, men in group I received hGH, and men in group II served as untreated controls. SUBJECTS Eighty-three overtly healthy elderly men, who were selected because their plasma IGF-I level was less than 0.35 units/ml. The men were randomly assigned in a ratio of three to one into group I (n= 62) or into group II (n= 21). MEASUREMENTS Plasma IGF-I level was measured monthly. Lean body mass and adipose mass were measured every six months. RESULTS Fifteen men left the study during the baseline period because of personal reasons or intercurrent medical events. In those who received drug (group I), there were a number of adverse reactions which could have been related to the hGH therapy: carpal tunnel syndrome 10, gynaecomastia 4, and hyperglycaemia 3. In total there were 27 dropouts from group I and two dropouts from group II after the six-month point, for a variety of medical and non-medical reasons, the majority probably not related to hGH therapy. During the hGH treatment of group I, plasma IGF-I increased from the range 0.10–0.35 units/ml into the range 0.5–2.2 units/ml. Among the 18 men who completed 12 months of hGH treatment without experiencing one of the three above-noted presumed hGH side-effects, mean and peak plasma IGF-I during treatment were significantly lower than among the 13 men who experienced carpal tunnel syndrome or gynaecomastia (one subject had both) while on hGH. With one exception, neither carpal tunnel syndrome nor gynaecomastia occurred in any individual with a mean IGF-I level less than 10 units/ml during hGH treatment. Twelve months of hGH treatment (group I) caused an increase in lean body mass to 106% of the initial baseline (month one of the protocol), and a reduction in adipose mass to 84% of the baseline. Meanwhile, the lean body mass of the untreated men in group II declined to 97% of the initial baseline. The body composition responses after 12 months of treatment in group I were larger in the men whose mean intra-treatment IGF-I level was 0.5–1.0 units/ ml, than in the men whose mean intra-treatment IGF-I level was 1.0–1.5 units/ml. CONCLUSIONS These observations show that when elderly men with low circulating IGF-I concentrations are treated continuously with hGH, elevation of plasma IGF-I above 10 units/ml is associated with a substantial frequency of carpal tunnel syndrome or gynaecomastia. It may be that the effects of the hormone in expanding lean body mass and reducing adipose mass can be achieved, and the side-effects avoided, by maintaining the mean IGF-I level in the range 0.5–1.0 units/ml.     

Perflubron Emulsion in Prolonged Hemorrhagic Shock: Influence on Hepatocellular Energy Metabolism and Oxygen-dependent Gene Expression

Background: Liver dysfunction as a result of impaired oxygen availability frequently occurs following hemorrhage and contributes to delayed mortality. Artificial oxygen carriers may improve oxygen supply to vital organs while avoiding the need for allogeneic transfusion.

Methods: Rats were subjected to hemorrhagic hypotension (mean arterial pressure = 35-40 mmHg for 120 min) and were subsequently resuscitated with (1) stored whole rat blood, (2) pentastarch, or (3) pentastarch combined with perflubron emulsion (PFE; 2.7 or 5.4 g/kg body weight), a second-generation artificial oxygen carrier. Recovery of liver adenosine triphosphate, hepatocellular injury, and expression of glutamine synthetase 1, a gene that is induced by exposure of hepatocytes to low partial pressure of oxygen, were studied at 4 h of resuscitation.

Results: Stored whole blood or pentastarch failed to restore liver adenosine triphosphate concentrations after prolonged shock as compared to sham controls and resulted in increased gene expression of glutamine synthetase 1. Addition of 2.7 g PFE/kg restored liver adenosine triphosphate to control, whereas 5.4 g PFE/kg resulted in adenosine triphosphate concentrations significantly above control. Improved hepatocellular oxygen supply was also confirmed by restoration of the physiologic expression pattern of glutamine synthetase 1. Serum enzyme concentrations were highest after resuscitation with stored blood, whereas addition of PFE failed to further decrease enzyme concentrations as compared to pentastarch alone.     

Lymphatic transport from normal and synovitic knees in rabbits

The resorption pattern of synovial fluid through the lymphatic system from normal and synovitic knee joints in rabbits was studied with ^99mHechnetium-rhenium-sulfur colloid injected intraarticularly and monitored for 14 hours with a gamma camera.

On the normal side the regional lymph nodes were visualized after I hour and after 14 hours still 75 percent activity remained in the knee. In the synovitic knees no lymphatic transport could be detected; and the radiotracer was unstable with rapid liberation of technetium, which was excreted in the urine. This radiolysis was not found in vitro in synovitic joint fluid.

The lymphatic transport from normal rabbit knees is low. We found a clear difference in lymphatic transport between normal and synovitic knee joints.     

Backspatter from experimental close-range shots to the head

Backspatter is the ejection of biological material from a gunshot entrance wound against the line of fire. This phenomenon was investigated experimentally in transverse gunshots to the heads of calves (n = 9) using two types of 9 mm Parabellum ammunition from shooting distances of 0–10 cm. The resulting bloodstains were documented on white paper placed horizontally 60 cm below the impact site. In this report the analysis was restricted to stains with a diameter > 0.5 mm. Backspatter was documented after every gunshot. The number of stains varied from 31–324 per gunshot and appeared to be independent of the shooting distance. The maximum distance droplets travelled varied from 72–119 cm. The majority of droplets accumulated between 0 and 50 cm. The number of droplets and the distances travelled should be higher in man for anatomical reasons. The direction a single droplet can take comprises every possible angle between the most tangential ones to the skin surface. This resulted in a semi-circle of 180° covered with stains. Skin ruptures of the entrance wound were not observed. The succession of events was documented on high speed film and started with the recoil of the firearm, immediately followed by a blow-out effect of the skin. Large droplets exited approximately 0.7–4 ms after the bullet impacted the skin. The calculated minimum initial velocity of these droplets was 13–61 m/s. Backspatter from gunshots to the head likely is caused by the hot gases expanding subcutaneously and by cavitation-related intracranial overpressure and tail splashing. In three out of nine gunshots, secondary backspatter additionally occurred as a result of droplets produced by a stream of blood from the entrance wound impacting the paper surface.     

Susceptibility testing of fluconazole by the NCCLS broth macrodilution method, E-test, and disk diffusion for application in the routine laboratory

Antifungal susceptibility testing may be an important aid in the treatment of patients with life-threatening yeast infections. In order to establish the suitability of different susceptibility test methods for fluconazole with yeasts, the Rosco tablet and the E-test were compared with the gold standard NCCLS broth macrodilution method for 106 yeast strains. These included 102 clinical isolates of Candida spp., including Candida glabrata (n = 30), Candida albicans (n = 20), Candida tropicalis (n = 13), Candida parapsilosis (n = 10), Candida krusei (n = 8), plus Cryptococcus neoformans (n = 3), Saccharomyces cerevisiae (n = 2), and 16 strains belonging to other Candida spp. Four American Type Culture Collection strains of Candida were included as quality controls. The NCCLS method was found to be too complex and labor-intensive for routine testing. The E-test is an accurate alternative, but experience in determining MICs and careful attention to procedural details are critically important. The Rosco tablet showed the best agreement with the NCCLS reference method, especially when newly established breakpoints of R < or = 10 mm and S > or = 21 mm were used.     

Performance of CHROMagar MRSA medium for detection of methicillin-resistant Staphylococcus aureus

CHROMagar MRSA was evaluated for its ability to identify methicillin-resistant Staphylococcus aureus (MRSA). A well-defined collection consisting of 216 MRSA strains and 241 methicillin-susceptible Staphylococcus aureus isolates was used. The sensitivity of CHROMagar MRSA after 24 h of incubation was 95.4%, increasing to 100% after 48 h. The specificity was already 100% after 24 h.     

Proliferation and production of hemopoietic cells in two stages of disease: Preleukemia and overt leukemia

Summary The kinetics of erythropoietic and granulocytopoietic cell proliferation have been investigated in the same patient at two distinct stages: firstly in preleukemia presenting as pancytopenia with ineffective erythropoiesis, and secondly 2 years later in acute myelogenous leukemia. The method of investigation is based on determining the DNA synthesis rate of individual cells by means of quantitative¹⁴C-autoradiography after short-term incubation with¹⁴C-thymidine and fluorodeoxyuridine.Erythropoiesis was equally ineffective in the two stages, the rate of proliferation, however, slowed down towards the leukemic state. The production rate of myeloblasts was markedly reduced in preleukemia accompanied by a very low labelling index. In leukemia on the other hand the production rate was increased to such a degree that the leukemic myeoblast compartment is to be considered as prevailingly self-reproductive. The proliferation rate of myeloblasts was reduced already in preleukemia, and there was a further decrease in leukemia. From the point of view of cell kinetics the manifestation of leukemia in this patient is explained best by a change in the mode of proliferation: the myeloblasts change from steady state growth to behaving like an exponentially expanding population.Study performed under the association contract for hematology between EURATOM and GSF no. 089-72-I-BIAD Supported by the Deutsche Forschungsgemeinschaft: SFB 51/E-3     

Regulation of gelatinase B in human monocytic and endothelial cells by PECAM-1 ligation and its modulation by interferon-beta.

Platelet endothelial cell adhesion molecule-1 (PECAM-1 or CD31) and gelatinase B are coexpressed at sites of inflammation, where an intense interaction occurs between leukocytes and endothelial cells. To investigate whether a functional link exists between PECAM-1 activation and gelatinase B production, the regulatory role of PECAM-1, IFN-gamma, IFN-beta, LPS, and PMA on the production of gelatinase B (MMP-9) was studied in vitro in normal human umbilical vein endothelial cells (HUVECs), human peripheral blood mononuclear cells (PBMCs), and in a human monocytic leukemia cell line. In THP-1 cells, progelatinase B levels were slightly up-regulated by immobilized PECAM-1-specific monoclonal antibody (mAb) and soluble recombinant PECAM-1 when compared with strong induction by LPS and PMA. IFN-beta inhibited the induced and basal gelatinase B production but had no modulating effect on the expression of PECAM-1. HUVECs mainly produced progelatinase A (proMMP-2). Treatment with LPS and triggering of the endothelial cells with PECAM-1 mAb or recombinant PECAM-1 had no effect on gelatinase A or B production, whereas PMA stimulated the production of progelatinase B. IFN-beta significantly up-regulated the expression of PECAM-1 in HUVECs but did not affect gelatinase secretion. Finally, in PBMCs, progelatinase B production was increased by soluble PECAM-1 mAb, recombinant PECAM-1, LPS, and PMA, whereas IFN-beta reduced gelatinase B secretion. IFN-beta did not alter PECAM-1 expression on PBMCs. Thus, PECAM-1 and gelatinase B are differently regulated in leukocytes and endothelial cells.