DERMAL NEUROVASCULAR DYSFUNCTION IN TYPE 2 DIABETES

The present article summarizes recent observations obtained in our laboratory which clearly indicate that sex steroids exert relevant effects on the peripheral nervous system. In particular, the following important points have emerged: (1) Steroids exert stimulatory actions on the synthesis of the proteins proper of the peripheral myelin (e.g., glycoprotein Po and peripheral myelin protein 22) in vivo and on the Schwann cells in culture; (2) in many cases the actions of hormonal steroids are not due to their native molecular forms but rather to their metabolites (e.g., dihydroprogesterone and tetrahydroprogesterone in the case of progesterone; dihydrotestosterone and 5 alpha-androstane-3 alpha,17 beta -diol in the case of testosterone); (3) the mechanism of action of the various steroidal molecules may involve both classical (progesterone and androgen receptors) and nonclassical steroid receptors (GABA, receptor); and finally, (4) the stimulatory action of steroid hormones on the proteins of the peripheral myelin might have clinical significance in cases in which the rebuilding of myelin is needed (e.g., aging, peripheral injury, demyelinating diseases, and diabetic neuropathy).     

用电化学检测器的高效液相色谱法测定血清及尿中速尿的含量

本文报告了用电化学检测器的高效液相色谱法测定血清及尿中速尿含量的方法。样品予处理方法:血清用乙腈除蛋白,尿用蒸馏水稀释50倍。采用作者合成的FD-Val-OH作为内标物。色谱条件为:反相柱,以含35%乙醇的5mmol/L四丁基铵水溶液为流动相(pH7.50),流速1.0ml/min;用电化学检测器,检测电压0.90V:速尿及内标物的保留时间分别为10和15min。通过计算速尿对内标物的峰高比求得速尿含量。血清及尿中的最低检测浓度分别为16和9ng/ml。标准曲线在0.25～5ng/μl(血清)、0.5～10ng/μl(尿)的浓度范围内呈线性关系。血清及尿中回收率分别为100.5%和100.6%。变异系数在4.6%以下。     

A multicenter, open-label study to assess the safety and efficacy of ciclopirox topical suspension 0.77% in the treatment of diaper dermatitis due to Candida albicans

Ciclopirox is a broad-spectrum antifungal, antibacterial, and anti-inflammatory agent. This open-label study investigated the safety and efficacy of ciclopirox topical suspension 0.77% in the treatment of diaper dermatitis due to Candida albicans (C. albicans). Forty-four male and female subjects aged 6 to 29 months were included in the study. Study medication was applied topically to the affected diaper area twice daily for 1 week. Subjects were clinically evaluated at baseline and days 3, 7, and 14 (7 days post-treatment). Safety and efficacy variables included adverse events, mycological culture studies, KOH tests, Severity Scores, and Global Evaluation of Clinical Response. All adverse events were mild to moderate and considered not related to the study medication. Treatment provided statistically significant improvement (P < .05) for both the rate of mycological cure and reduction of Severity Score at each time point compared with baseline. Ciclopirox was safe and effective in the treatment of diaper dermatitis due to C. albicans.     

cDNA cloning of a human homologue of the Caenorhabditis elegans cell fate-determining gene mab-21: expression, chromosomal localization and analysis of a highly polymorphic (CAG)n trinucleotide repeat

The two most consistent features of the diseases caused by trinucleotide repeat expansion-neuropsychiatric symptoms and the phenomenon of genetic anticipation-may be present in forms of dementia, hereditary ataxia, Parkinsonism, bipolar affective disorder, schizophrenia and autism. To identify candidate genes for these disorders, we have screened human brain cDNA libraries for the presence of gene fragments containing polymorphic trinucleotide repeats. Here we report the cDNA cloning of CAGR1, originally detected in a retinal cDNA library. The 2743 bp cDNA contains a 1077 bp open reading frame encoding 359 amino acids. This amino acid sequence is homologous (56% amino acid identify and 81% amino acid conservation) to the Caenorhabditis elegans cell fate-determining protein mab-21. CAGR1 is expressed in several human tissues, most prominently in the cerebellum, as a message of approximately 3.0 kb. The gene was mapped to 13q13, just telomeric to D13S220. A 5'-untranslated CAG trinucleotide repeat is highly polymorphic, with repeat length ranging from six to 31 triplets and a heterozygosity of 87-88% in 684 chromosomes from several human populations. One allele from an individual with an atypical movement disorder and bipolar affective disorder type II contains 46 triplets, 15 triplets longer than any other allele detected. Though insufficient data are available to link the long repeat to this clinical phenotype, an expansion mutation of the CAGR1 repeat can be considered a candidate for the etiology of disorders with anticipation or developmental abnormalities, and particularly any such disorders linked to chromosome 13.      

Prevalence of developmental dysplasia of the hip in children with clubfoot

Purpose

The relationship between congenital talipes equinovarus (CTEV) and developmental dysplasia of the hip (DDH) remains uncertain. The role of routine hip screening in children with CTEV is debated. A recent study has found a high incidence of DDH in patients with CTEV. The aim of our study was to determine the true prevalence of radiographic hip dysplasia and identify the need for routine hip screening in patients treated for CTEV.

Methods

From a single centre database of 165 children consisting of 260 CTEV, a prospective radiological prevalence study of 101 children was performed over a period of 3 months. A single anterior-posterior pelvic radiograph was performed at a minimum age of 5 months. The DDH was determined by a single senior investigator based on the age-adjusted acetabular index (AI) as described by Tonnis.

Results

There were no dislocations or subluxations. According to the age-adjusted AI, 16 children had ‘light’ dysplasia and one child had ‘severe’ dysplasia. The child with severe dysplasia was known to have DDH and had already undergone treatment. The 16 children with light dysplasia did not require any form of treatment.

Conclusion

Out of one hundred and one children with CTEV, only one had DDH requiring treatment. This is consistent with the majority of the literature supporting the premise that there is no true association between CTEV and DDH. We, therefore, feel that routine hip screening for children with CTEV is not supported by current evidence and cannot be recommended.     

Proteolytic inactivation of human factor VIII procoagulant protein by activated human protein C and its analogy with factor V

Purified human factor VIII procoagulant protein (VIII:C) was treated with purified human activated protein C (APC) and the loss of VIII:C activity correlated with proteolysis of the VIII:C polypeptides. APC proteolyzed all VIII:C polypeptides with mol wt = 92,000 or greater, but not the doublet at mol wt = 79-80,000. These results and our previous thrombin activation studies of purified VIII:C, are analogous with similar studies of factor V and form the basis for the following hypothesis: activated VIII:C consists of heavy and light chain polypeptides [mol wt = 92,000 and mol wt = 79-80,000 (or 71-72,000), respectively] which are similar in Mr to the heavy and light chains of activated factor V. Thrombin activates VIII:C and V by generating these polypeptide chains from larger precursors and APC inactivates both molecules by cleavage at a site located in the heavy chain region of activated VIII:C and V.     

Variation in blood sample collection for determination of hemodialysis adequacy. Council on Renal Nutrition National Research Question Collaborative Study Group

Inadequate dialysis has been associated with high morbidity and mortality in end-stage renal disease (ESRD) patients receiving maintenance hemodialysis. The accurate estimation of dialysis adequacy, measured either as a calculated urea kinetics (Kt/V) or a simple urea reduction ratio (URR) is dependent on the proper collection of blood samples for predialysis and postdialysis blood urea nitrogen (BUN) determination. Because no established protocol exists for blood sampling, we surveyed the study cohort of dialysis centers participating in the National Kidney Foundation Council on Renal Nutrition National Research Question Collaborative Study to determine the comparability of BUN data that were collected to calculate URR to determine adequacy of dialysis. Surveys were completed by 100% of the 202 units participating: 195 in the United States (from 43 states) and seven from Canada, treating approximately 15,000 hemodialysis patients in total. The distribution of the sample by the type of facility mirrored that of 1996 United States Renal Data System (USRDS) Annual Report facilities data. Results showed a 5.0% error in predialysis blood draw and an 8.4% to 41.6% error in the postdialysis counterpart. There was a large variability in the observed postdialysis methods in general. Dilution of predialysis sample with either heparin or saline will falsely underestimate Kt/V and URR. The presence of access-derived, recirculated blood in the postdialysis sample will falsely overestimate Kt/V and URR. Excessive delay in drawing postdialysis sample will reduce Kt/V and URR because of urea rebound. Adoption by all dialysis providers of a uniform blood sample draw procedure will result in a consistency necessary to allow reliable and valid comparison of adequacy of dialysis parameters within and between ESRD patients, units, and clinical trials.