Effect of conjugated estrogens on platelet function and prostacyclin generation in CRF

In a double-blind, randomized, placebo-controlled cross-over study, we investigated in seven patients with chronic renal failure the effect of conjugated estrogens (0.6 mg/kg/day for 5 days) on template bleeding time and on thromboxane A2 (TxA2), beta-thromboglobulin (beta-TG) and prostacyclin (PGI2) concentrations in blood emerging from the template bleeding time incisions. Administration of conjugated estrogens resulted in a significant shortening of the bleeding time in six out of seven patients with a maximum effect 7 and/or 14 days following treatment. Both TxA2 (measured as thromboxane B2, TxB2) and beta-TG release in bleeding time blood were significantly higher following administration of conjugated estrogens as compared to placebo administration. No difference was seen in endothelial PGI2 (measured as 6-keto-prostaglandin F1 alpha) formation when patients were treated with conjugated estrogens as compared to placebo administration over the 28 day observation period. We conclude that in patients with chronic renal failure, infusion of conjugated estrogens results in a significant shortening of the bleeding time together with an increase in platelet reactivity, as indicated by an increase of TxA2 and beta-TG concentration in the microvasculature. No effect was seen on PGI2 production, thereby excluding a major effect on vascular prostaglandin metabolism.     

Early detection of avascular necrosis of the femoral head following renal transplantation

This prospective study included 43 patients undergoing renal transplantations. Magnetic resonance imaging (MRI) and X-rays of the hip joints were produced 3 and 12 months after transplantation. In 6 hip joints of 4 patients (9.3%), we discovered femoral head necroses just 3 months after transplantation. Three of the hip joints affected were symptomatic and 3 painless. The MR images taken 12 months after transplantation revealed no additional femoral head necrosis. A core decompression was performed on 3 joints. In contrast to those with core decompression, the femoral heads without core decompression showed a progression of the necrosis in 2 of 3 cases. All 4 patients with femoral head necroses were younger than 50 years and exhibited a premature conversion of the haematopoietic marrow to fatty marrow in the area of the proximal femoral metaphysis. A similar premature conversion to fatty marrow was seen in 6 of the 22 (27.2%) patients younger than 50 years and without femoral head necroses. The doses in long-term steroid medication and the steroid doses during the rejection periods of the patients with femoral head necroses were not significantly higher than those for the patients with premature conversion to fatty marrow. The latter had also not received significantly higher doses than the patients whose MRI findings were inconspicuous.     

Micrococcus luteus: a rare pathogen of valve prosthesis endocarditis]

A rare case of prosthetic valve endocarditis caused by Micrococcus luteus is described and compared with the few cases reported in the literature, as well as the clinical features, microbiological profile, therapy, and prognosis of common prosthetic valve endocarditis. Micrococcus luteus is a constituent of the normal human buccal bacterial flora which forms yellowish colonies and appears as a gram-positive coccus typically arranged in tetrades. Although of low virulence, the germ may become pathogenic in patients with impaired resistance, colonizing the surface of heart valves. In contrast to staphylococci (for which it may easily be mistaken) it is usually penicillin-sensitive. However, the most promising antibiotic regimen proposed for treatment of Micrococcus luteus seems to be a combination of vancomycin, amikacin, and rifampicin. If the infection leads to severe hemodynamic alterations, however, valve replacement may become necessary similar to the situation in prosthetic valve endocarditis caused by more aggressive and highly resistant bacteria.     

Diffusion-weighted magnetic resonance imaging for demonstration of cerebral infarcts

Summary Forty-one patients demonstrating clinical symptoms for cerebral infarction were investigated by magnetic resonance imaging with diffusion-weighted echo-planar imaging (DWI) and T2-weighted imaging (T2WI). In 8 patients only DWI showed the cerebral lesions clearly. One patient with positive DWI and T2WI suffered from HSV encephalitis. DWI is superior to T2WI in assessment of small cortical infarcts and cerebral infarction in patients with preexisting vascular lesions. DWI is not specific, so other causes like cerebral hematoma and encephalitis have to be considered.      

Do callosal projection neurons reflect sex differences in axon number?

We have reported that female rats have more axons in the splenium of the corpus callosum than do male rats (12). To determine if the greater number of axons found in female rats might be reflected in a larger distribution of callosal projection neurons, horseradish peroxidase (HRP) was injected into the visual cortex of 55-65-day-old rats of both sexes that had been housed in a complex environment since weaning. The pattern of labeled neurons was examined in tangential sections in the cortex contralateral to the injection site, and three-dimensional reconstructions were quantified at the area 17/18a border and in area 18b. Male and female rats were found to have indistinguishable distributions of labeled callosal projection neurons. The present study failed to find an obvious difference in the distribution of projection neurons as the basis for the sex differences in axon number, but because of the limitations of tracing techniques, subtle differences cannot be excluded.     

L-arginine induces relaxation of small mesenteric arteries from endotoxin-treated rats.

The effect of arginine (Arg) was studied on norepinephrine- (1 microM) precontracted small mesenteric arteries removed from rats treated with E. coli lipopolysaccharide (LPS). The addition of L- (but not D-) Arg (1 mM) relaxed, within 3 min, the small mesenteric arteries from LPS-treated but not from control rats, the maximal relaxation (65.3 +/- 11%) being reached with less than 100 microM L-Arg. NG-Nitro-L-arginine methyl ester (1 mM) and methylene blue (10 microM) restored contractions to the level reached before addition of L-Arg. These results show that LPS induces the production of an L-Arg-derived, nitric oxide-like, relaxing factor in small mesenteric arteries.     

Improved anchorage in osteoporotic vertebrae with new implant designs.

The goal of our study was to evaluate two newly developed implant designs and their behavior in terms of subsidence in lumbar vertebral bodies under cyclic loading. The new implants were evaluated in two different configurations (two small prototypes vs. one large prototype with similar load-bearing area) in comparison to a conventional screw-based implant (MACS TL). A pool of 13 spines with a total of 65 vertebrae was used to establish five testing groups of similar bone mineral density (BMD) distribution with eight lumbar vertebrae each. In additional to BMD assessment via dual-energy X-ray absorptiometry, cancellous BMD and structural parameters were determined using a new generation in vivo 3D-pQCT. The specimens were loaded sinusoidally in force control at 1 Hz for 1000 cycles at three load levels (100, 200, and 400 N). A survival analysis using the number of cycles until failure (Cox regression with covariates) was applied to reveal differences between implant groups. All new prototype configurations except the large cylinder survived significantly longer than the control group. The number of cycles until failure was significantly correlated with the structural parameter Tb.Sp. and similarly with the cancellous BMD for three of five implants. In both large prototypes the cycle number until failure significantly correlated with the preoperative distance to the upper endplates. Although the direct relationship between bone structure or density and mechanical breakage behavior cannot be conclusively proven, all the prototypes adapted for poor bone structure performed better than the comparable conventional implant.     

Cardiac atrophy in women following bed rest

Both chronic microgravity exposure and long‐duration bed rest induce cardiac atrophy, which leads to reduced standing stroke volume and orthostatic intolerance. However, despite the fact that women appear to be more susceptible to post‐spaceflight presyncope and orthostatic hypotension than male astronauts, most previous high‐resolution studies of cardiac morphology following microgravity have been performed only in men. Because female athletes have less physiological hypertrophy than male athletes, we reasoned that they also might have altered physiological cardiac atrophy after bed rest. Magnetic resonance imaging was performed in 24 healthy young women (32.1±4 years) to measure left ventricular (LV) and right ventricular (RV) mass, volumes, and morphology accurately before and after 60 days of 6° head‐down tilt (HDT) bed rest. Subjects were matched and then randomly assigned to sedentary bed rest (controls, n=8) or two treatment groups consisting of (1) exercise training using supine treadmill running within lower body negative pressure plus resistive training (n=8), or (2) protein (0.45 g/kg/day increase) plus branched‐chain amino acid (BCAA) (7.2 g/day) supplementation (n=8). After sedentary bed rest without nutritional supplementation, there were significant reductions in LV (96±26–77±25 mL; P=0.03) and RV volumes (104±33–86±25 mL; P=0.02), LV (2.2±0.2–2.0±0.2 g/kg; P=0.003) and RV masses (0.8±0.1–0.6±0.1 g/kg; P<0.001), and the length of the major axis of the LV (90±6–84±7 mm. P<0.001), similar to what has been observed previously in men (8.0%; Perhonen M.A., Franco F., Lane L.D., Buckey J.C., Blomqvist Zerwekh J.E., Peshock R.M., Weatherall P.T., Levine B.D. J Appl Physiol 2001: 91: 645–653). In contrast, there were no significant reductions in LV or RV volumes in the exercise‐trained group, and the length of the major axis was preserved. Moreover, there were significant increases in LV (1.9±0.4–2.3±0.3 g/kg; P<0.001) and RV masses (0.7±0.1–0.8±0.2 g/kg; P=0.002), as well as mean wall thickness (9±2–11±1 mm; P=0.02). The interaction between sedentary and exercise LV and RV masses was highly significant (P<0.0001). Protein and BCAA supplementation led to an intermediate phenotype with no change in LV or RV mass after bed rest, but there remained a significant reduction in LV volume (103±14–80±16 mL; P=0.02) and major‐axis length (91±5–88±7 mm; P=0.003). All subjects lost an equivalent amount of body mass (3.4±0.2 kg control; 3.1±0.04 kg exercise; 2.8±0.1 kg protein). Cardiac atrophy occurs in women similar to men following sedentary 60 days HDT bed rest. However, exercise training and, to a lesser extent, protein supplementation may be potential countermeasures to the cardiac atrophy associated with chronic unloading conditions such as in spaceflight and prolonged bed rest.     

Alteration of visual evoked potentials and electroretinograms in Parkinson's disease

A group of 24 patients with Parkinson's disease (PD) with normal fundi and normal visual acuities was examined electrophysiologically. Checkerboard reversal VEPs and ERGs (P-ERGs) at various contrast levels as well as photopic and scotopic luminance ERGs were recorded and compared with an age-matched group of controls. Earlier reported latency increases of the VEPs of the patients were confirmed for patterns of high contrast only. Scotopic and photopic luminance ERGs of the patients showed normal latencies, but at all light intensities the amplitudes of the scotopic and photopic b wave, as well as the amplitudes of the photopic a waves, were significantly reduced, P-ERG amplitudes were reduced at 50% contrast. Identical results were obtained in patients under dopaminergic treatment (n = 17) and in patients who did not receive any treatment (n = 7). These results suggest that alterations occur already at the retinal level where dopamine receptors have been found. Thus the reported changes of the VEP are not caused by the visual cortex alone.