Serum neopterin for early assessment of severity of severe acute respiratory syndrome

Neopterin and C-reactive protein (CRP) concentrations were determined in serum samples from 129 severe acute respiratory syndrome (SARS) patients and 156 healthy blood donors. In the patients with confirmed SARS, an early neopterin elevation was detected already at the day of onset of symptoms and rose to a maximum level of 45.0 nmol/L 3 days after the onset. All SARS patients had elevated neopterin concentrations (>10 nmol/L) within 9 days after the onset. The mean neopterin concentrations were 34.2 nmol/L in acute sera of SARS patients, 5.1 nmol/L in convalescent sera, and 6.7 nmol/L in healthy controls. In contrast, the mean CRP concentrations in both acute and convalescent sera of SARS patients were in the normal range (<10 mg/L). Serum neopterin level in SARS patients was associated with fever period and thus the clinical progression of the disease, while there was no significant correlation between the CRP level and the fever period. Serum neopterin may allow early assessment of the severity of SARS. The decrease of neopterin level was found after steroid treatment, which indicates that blood samples should be collected before steroid treatment for the neopterin measurement.     

Longitudinal alteration of circulating dendritic cell subsets and its correlation with steroid treatment in patients with severe acute respiratory syndrome

In this study, we found that 74 patients with severe acute respiratory syndrome (SARS) exhibited a rapid, dramatic decrease in numbers of circulating myeloid and plasmacytoid dendritic cells (mDCs and pDCs) during the first 2 weeks of illness (5.3- and 28.4-fold reductions for mDCs and pDCs compared with 25 healthy individuals, respectively), with slow return to normal cell numbers during convalescence (weeks 5–7 of illness on average). In addition, numbers of circulating CD4 and CD8 T cells exhibited milder reductions (2.1- and 1.8-fold at week 1) and earlier return to normal at a mean of weeks 3 and 4, respectively. A significant inverse correlation was found between numbers of DC and T-cell subsets and high-dose steroid treatment. Our novel findings thus suggest that the acute SARS-coronavirus infection probably contributes to the initial reduction of DC and T-cell subsets in blood, and that high-dose steroid administration may subsequently exacerbate and prolong low expression of the cell subsets. These findings will aid the framing of further studies of the immunopathogenesis of SARS.     

Lipidstatus und basale Steroidhormonspiegel nach 16 Wochen Lovastatintherapie bei primärer Hypercholesterinämie

Summary We examined the effect of a 16 week therapy with the HMG CoA reductase inhibitor lovastatin in 29 patients (mean age 43 years) with primary hypercholesterolemia. All patients had cholesterol levels above 250 mg/dl (mean 348 ±96 mg/dl) inspite of a lipid lowering diet and a therapy with conventional lipid lowering drugs during a three month screening period. After 4 weeks on placebo 20 mg lovastatin was given orally for 4 weeks. If total cholesterol exceeded 200 mg/dl the dose of lovastatin was increased monthly by 20 mg up to the maximal dose of 80mg/day. After 16 weeks lipid values changed compared with the placebo period: total-cholesterol –25%, triglycerides –8.6%, LDL-cholesterol –31%, APO B –25%, HDL-cholesterol +5.8%, APO AI +0.8%, total-cholesterol/HDL-cholesterol –25%. There was a significant improvement of lipid parameters after lovastatin therapy compared with conventional lipid lowering drugs at the end of the screening period. Lovastatin was well tolerated. A small and reversible rise of transaminases and/or creatinine kinase was observed in 6 patients. Basal levels of ACTH in the morning increased significantly during lovastatin therapy within the normal range. This observation was more frequent in females (10/12) than in males (10/ 17).

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Abkürzungen HMG Co A 3-Hydroxy-3-Methyl-Glutaryl-Coenzym A - TChol Gesamtcholesterin - LDL low density lipoprotein - HDL high density lipoprotein - TG Triglyceride - APO AI/B Apolipoprotein AI/B - ACTH Adrenocorticotropes Hormon Diese Publikation enthält Ergebnisse des Dissertationsarbeit von Frau Angela Bink.     

GABA[A] receptor level changes in female hamster forebrain following in vivo estrogen progesterone and benzodiazepine treatment: a quantitative autoradiography analysis

Summary The levels of gamma amino butyric acid (GABA_A) receptors (i.e. ³H-Muscimol binding sites) were determined by quantitative neurotransmitter receptors autoradiography in ovariectomized (OVX), OVX-estradiolo (E), OVX-progesterone (P), OVX-E+P, diazepam (DZ) and DZ + Ro15-1788 treated female hamsters.The various hormonal treatments altered ³H muscimol binding in many brain areas, whereas DZ and DZ + Ro15-1788 had little influence on GABA_A receptor levels at the onset of the blocked aggressive behavioral activity. For example, E, P and E+P all significantly increased ³H muscimol binding in medial preoptic area, ventromedial hypothalamic nuclei, and vertical diagonal bandmedial septal nucleus, whereas P treatment increased binding in the caudate-putamen and decreased it in reuniens nucleus of the thalamus. E and E+P treatments increased ³H muscimol binding in the corticomedial amygdala nucleus and hippocampus. Diazepam treatment decreased the GABA_A receptor binding in the caudate-putamen and basolateral amygdala, while having no effect in the other brain regions where hormone treatment was effective. In vitro incubation of brain sections with micromolar concentrations of E or P did not change muscimol binding. These results suggest that ovarian steroids, and benzodiazepines to a lesser extent, modulate ³H muscimol binding but do so in different brain regions. The hormone effects on ³H muscimol binding in the critical reproductive centres at a time period that coincides with the onset of its behavioral effect is consistent with a genomic controlled activity.     

Impaired Leydig Cell Function In Vitro in Testicular Tissue from Human Males with "Sertoli Cell Only" Syndrome

Testicular histopathology in patients with "Sertoli Cell Only" Syndrome is characterized by absence of germinal cells. Some of these patients have high levels of LH in their peripheral blood as well as subnormal serum testosterone levels. This indicates a possible correlation between the lack of germinal cells and an impairment of Leydig cell steroidogenic activity. It has previously been shown that in vitro conversion of tritiated steroid precursors within testicular tissue indicates the Leydig cell steroidogenic activity. In this study we have investigated whether or not testicular tubular cell disorder with lack of germinal cells is related to impairment of the intratesticular steroid metabolism in vitro. Ten patients with testicular histopathology characteristic of "Sertoli cell only" syndrome were investigated and their steroid metabolism patterns were compared with those of 22 control patients. Leydig cell dysfunction was found in the group of patients with SOS; 17 alpha-hydroxylation was significantly lower and the production of 20 alpha-dihydroprogesterone was significantly higher, as compared to the control patients. The Leydig cell impairment may be due to a disturbed influence from the damaged tubules.     

The triple technique: A simple and effective outpatient procedure for the dorsal wrist ganglion

BackgroundDorsal ganglia are the most common types of wrist ganglia. Though largely asymptomatic, they can cause pain, stiffness and require treatment. The different methods described for the management have high recurrence rates even up to 70%. We describe a new method which combines 3 of these methods thus aiming to achieve the best from each of the techniques.MethodsA prospective observational study was undertaken to include patients requiring surgery for dorsal ganglion. The method involved a combination of aspiration, steroid instillation and tranfixation with silk suture for 3 weeks. Various demographic parameters, operative variables and functional criteria like QuickDASH Score and Numerical Pain Rating scale (NPRS) were used. The patients were followed up for atleast 24 months. Overall satisfaction rate was also recorded.Results83 patients were included with a mean age of 31.7 ± 12.4 years. The mean duration of surgery was 12.0 ± 4.9 min and follow up was 29.8 ± 7.1 months. 15 patients had complex multilobulated ganglia. The most common indication for surgery was cosmesis. 4 complications were encountered of which 2 were superficial infections, 1 whitish discoloration locally and 1 case of persistent pain. We achieved a success rate of 95.2% with only 4 recurrences with a mean reduction in size to be 82.2 ± 5.8%. NPRS and QuickDASH scores improved significantly. Mean satisfaction rate was 89% and 84.3% wished to have the surgery again for a similar complaint. The loss of work was 2.5 ± 1.4 days.ConclusionsTriple Technique is an effective and safe technique with <5% recurrence at 2 years.     

Purification of the NADH reductase component of the steroid 9α-hydroxylase fromMycobacterium fortuitum

The NADH reductase component of the steroid 9α-hydroxylase fromMycobacterium fortuitum was purified to homogeneity. Recovery of the enzyme from the 50≈60% ammonium sulfate saturated fraction was 49%, with a purification factor of 100-fold. The NADH reductase has a relative molecular mass of 60 KDa as determined by SDS-PAGE. The absorption maxima at 410 and 450 nm indicate the presence of iron-sulfur group and flavin. These prosthetic groups seemed to function as redox groups that transfer electrons from NADH to the following protein. The K_M value for NADH as substrate was 68 μM. The NH₂-terminal amino acid sequence of the reductase was determined as Met-Asp-Ala-Ile-Thr-Asn-Val-Pro-Leu-Pro-Ala-Asn-Glu-Pro-Val-His-Asp-Tyr-Ala-Thr. This sequence does not show a homology with the NH₂-terminal sequences reported for the reductase component of other monooxygenases, suggesting that the NADH reductase component of the steroid 9α-hydroxylase system is novel.     

Post graft development of short children treated with growth hormone before kidney graft

Sixteen prepubertal patients with chronic renal failure (CRF) were given daily recombinant human growth hormone (rhGH) treatment (1.2 IU/kg per week) for 2.6±1.6 years until kidney transplant. Therapy was then discontinued and the patients followed for a further 3.5±1.4 years. During treatment, mean height increased from –3.0±0.9 standard deviation score (SDS) to –1.9±1.4 SDS (P<0.001) at the time of transplantation, corresponding to a mean height gain of +1.2±0.9 SDS. After discontinuation of rhGH therapy, prepubertal children continued a partial catch-up growth with a height gain of +0.5±0.8 SDS for the follow-up period. Conversely, negative changes of height were observed in pubertal transplanted children: –0.5±0.4 SDS in patients grafted at early stages of puberty (P2–P3) and –0.15±0.9 SDS in patients grafted at late stages of puberty (P4–P5). These data confirmed the benefit of rhGH therapy in CRF patients. Nevertheless, only early initiation of rhGH treatment led some of these patients to their target height at transplantation, thus preserving their potential growth. Reinitiation of rhGH therapy after transplantation should be considered in order to complete catch-up growth to target height in prepubertal children. Received: 23 July 1998 / Revised: 8 December 1998 / Accepted: 13 December 1998     

Z-350, a new chimera compound possessing α1-adrenoceptor antagonistic and steroid 5α-reductase inhibitory actions

The effects of Z-350, (S)-4-[3-(4-{1-(4-methylphenyl)-3-[4-(2-methoxyphenyl)piperazine-1-yl]propoxy} benzoyl)indole-1-yl]butyric acid hydrochloride, a newly synthesized compound possessing α₁-adrenoceptor antagonistic and steroid 5α-reductase inhibitory actions, were studied in vitro. In functional experiments, Z-350 shifted the concentration/response curve for the phenylephrine-induced contraction of rabbit prostate, urethra and aorta to the right with pA₂ values of 8.04, 7.57 and 7.13, respectively. The binding affinity of Z-350 for α₁-adrenoceptors in rabbit prostate, urethra and aorta were estimated by the displacement of [³H]prazosin. The pK _i values for this action of Z-350 were 7.53, 7.95 and 7.62 for the prostate, urethra and aorta, respectively. α₁-Adrenoceptor subtype selectivities were studied in the submaxillary gland (α_1A) and liver (α_1B) of rat. Z-350 inhibited the specific binding of [³H]prazosin to α_1A and α_1B-adrenoceptors with pK _i values of 7.82 and 7.29, respectively. Z-350 inhibited rat prostatic steroid 5α-reductase non-competitively with a pIC₅₀ of 8.42. These results indicate that Z-350 is a α₁-adrenoceptor antagonist and is a steroid 5α-reductase inhibitor. It is expected that Z-350 will be a candidate drug for the treatment of benign prostatic hyperplasia. Received: 26 January 1999 / Accepted: 2 March 1999