Follicular fluid renin concentration and IVF outcome

Total renin protein concentration (TRC) was measured in stored follicular fluid (FF) samples from 42 women. Samples were selected according to their origin from follicles either without recovered ova ('empty', n = 38) or fertilized but with failed implantation ('failed', n = 36) or successful deliveries ('deliveries', n = 71). Ratios of number of embryos transferred to number of infants delivered were 2:1, 3:1 or 4:2 but 1:1 was not available. Non-parametric testing was applied to FF-TRC, volume and outcome. TRC was significantly higher in the delivery than the failed (P = 0.001) or empty (P = 0.002) categories. Assuming that the range of renin in failed follicles can identify the sub-population of unsuccessful follicles in the delivery category, then elevated FF-TRC was clearly associated with successful outcome. For individual women, the odds of infant delivery increased 17-fold as a function of average FF-TRC between 10,000 and 25,000 microIU/ml. For failed and delivery but not empty follicles, higher renin levels occurred in the smaller follicles, consistent with a burst of renin synthesis associated with the presence of an oocyte. The results suggest that FF-TRC relates to ovum viability with ovarian hyperstimulation and may have predictive use in IVF programmes.     

High-resolution analysis of genomic alterations and human papillomavirus integration in anal intraepithelial neoplasia

Anal intraepithelial neoplasia (AIN) is the likely precursor to anal cancer. AIN is associated with human papillomavirus (HPV) infection, and HPV-associated genomic instability may play an important role in the progression of squamous intraepithelial neoplasia to cancer. Microarray-based comparative genome hybridization (aCGH) was performed on DNA from AIN specimens to determine the host genomic alterations and their correlation with HPV DNA integration or rearrangement. Of 27 high-grade AIN specimens tested by CGH, 8 (30%) showed regional DNA copy number abnormalities (CNAs). Five additional cases previously identified by chromosome CGH to carry CNAs were reanalyzed by aCGH and pooled with the 8 new cases for analysis. The most common regions of gain were on chromosome arms 1p, 1q, 3q, 8p, and 20q. The most common regions of loss were on chromosome arms 2q, 7q, 11p, 11q, and 15q. HPV16 DNA integration or rearrangement correlated with CNAs in host cell DNA (P = 0.007). Although aCGH can resolve amplicons at the 1- to 2-megabase (Mb) regional resolution, the most common alteration on chromosome 3 could only be resolved to a 75-Mb region from 3q21 to qtel. Our data suggest that there may be several oncogenes in this region that are coactivated to contribute to progression to high-grade AIN.     

Peptide-based approaches to treat asthma, arthritis, other autoimmune diseases and pathologies of the central nervous system

In this review we focus on peptide- and peptidomimetic-based approaches that target autoimmune diseases and some pathologies of the central nervous system. Special attention is given to asthma, allergic rhinitis, osteoarthritis, and Alzheimer's disease, but other related pathologies are also reviewed, although to a lesser degree. Among others, drugs like Diacerhein and its active form Rhein, Pralnacasan, Anakinra (Kineret), Omalizumab, an antibody "BION-1", directed against the common beta-chain of cytokine receptors, are described below as well as attempts to target beta-amyloid peptide aggregation. Parts of the review are also dedicated to targeting of pathologic conditions in the brain and in other tissues with peptides as well as methods to deliver larger molecules through the "blood--brain barrier" by exploring receptor-mediated transport, or elsewhere in the body by using peptides as carriers through cellular membranes. In addition to highlighting current developments in the field, we also propose, for future drug targets, the components of the inflammasome protein complex, which is believed to initiate the activation of caspase- 1 dependent signaling events, as well as other pathways that signal inflammation. Thus we discuss the possibility of targeting inflammasome components for negative or positive modulation of an inflammatory response.     

HIV-1 RNA levels in an African population-based cohort and their relation to CD4 lymphocyte counts and World Health Organization clinical staging

Apart from a small number of reports from people who are based in hospitals, data on viral load in HIV-infected people in sub-Saharan Africa, where most infections occur, are lacking. We report serum HIV-1 RNA levels in a population-based cohort in rural Uganda using the nucleic acid sequence-based amplification procedure (NASBA) test kit and describe their relation to CD4 counts and World Health Organization (WHO) clinical staging. The median (interquartile range [IQR]) viral loads were 87,000 copies/ml (37,500-295,000 copies/ml) in 40 prevalent cases infected for >6 years, and 31,000 copies/ml (7800-174,000 copies/ml) in 65 incident cases with seroconversion dates within the previous 6 years. Although we found a correlation between viral load and absolute CD4 count (p < .0001), there was no evidence for an association with CD4 decline (p = .1). Overall, there was a significant trend of increasing viral load with worsening clinical stage from a median viral load of 15,000 for those in WHO stage 1 (asymptomatic) to 150,600 copies/ml for those in stage 4 (AIDS; p < .001). However, the association was seen only in incident cases. Thus, we found that the NASBA test on serum was a useful indicator of disease stage especially in persons known to be infected for <6 years. Such baseline data are important for vaccine research, and if antiretroviral drugs become available to more than a few people in Africa, it will be important that accurate viral load estimations are available at least in a proportion of people to monitor the effectiveness of treatment, and measure the compliance and emerging resistance to these drugs.     

Effect of oral creatine ingestion on parameters of the work rate-time relationship and time to exhaustion in high-intensity cycling

The relationship between work rate (W˙) and time to exhaustion (t) during intense exercise is commonly described by either a hyperbolic function (NLin), t=W ^′/(W˙?W˙ _cp), or by its linear equivalent (LinW) W _lim =W ^′+W˙ _cp(t). The parameter W˙<INF _cp (critical power) has been described as an inherent characteristic of the aerobic energy system, while W?′ has been shown to be a ralid estimate of anaerobic work capacity. Recent studies have demonstrated that oral supplementation of creatine monohydrate (CrH₂O) increases total muscle creatine stores, and have linked these increases to improved performances in intense intermittent exercise. This study was conducted to determine the effect of CrH₂O supplementation on estimates of W?′ and W˙<INF _cp derived from the NLin and LinW equations, and to determine the effect of CrH₂O on t in exhaustive constant power exercise of different intensities. Fifteen active but untrained university students completed three phases of testing on a cycle ergometer: (1) familiarization, three learning trials, (2) baseline determination of W?′ and W˙<INF _cp, four bouts performed at a W˙ selected to elicit fatigue in 90–600?s, and (3) experimental determination of W?′ and W˙ _cp, four bouts performed at the same W˙ as baseline, but performed after 5 days of ingesting either a placebo (4?×?6?g of glucose/day) or CrH₂O (4?×?5?g of CrH₂O and 1?g glucose/day). Testing was administered in a double-blind manner. Analyses of covariance revealed a significant effect for CrH₂O on both estimates of W?′ (NLin, P=0.04; LinW, P<0.01), but not on estimates of W˙ _cp (NLin, P=0.37; LinW; P=0.30). Within groups, t was significantly different for only CrH₂O at the two highest W˙s (P=0.04). It is concluded that oral ingestion of CrH₂O increases estimates of W?′ due to an improved t at the shorter, more intense exercise bouts.

     

A monoclonal blocking EIA for herpes simplex virus type 2 antibody: validation for seroepidemiological studies in Africa

A competitive type-specific enzyme-linked immunosorbent assay (ELISA) for herpes simplex virus type 2 (HSV-2) antibody was developed using an infected cell antigen and a monoclonal antibody to glycoprotein G-2. This assay has been validated for use for epidemiological studies using a large panel of sera collected in rural Uganda and a panel of 143 sera characterised previously by Western blotting, the 'gold standard' for HSV type-specific serology. This evaluation was found to have a sensitivity of 96% and a specificity of 91% in comparison with Western blot on 143 sera from clinic patients. The ELISA had a sensitivity of 93% and a specificity of 91% in comparison with Western blot on 495 sera collected in Uganda. The assay showed good reproducibility and a low percentage of sera gave equivocal results, indicating its suitability for epidemiological studies.     

Efficacy and tolerability of anti-asthma herbal medicine intervention in adult patients with moderate-severe allergic asthma

BACKGROUND: Chinese herbal medicine has a long history of human use. A novel herbal formula, anti-asthma herbal medicine intervention (ASHMI), has been shown to be an effective therapy in a murine model of allergic asthma. OBJECTIVE: This study was undertaken to compare the efficacy, safety, and immunomodulatory effects of ASHMI treatment in patients with moderate-severe, persistent asthma with prednisone therapy. METHODS: In a double-blind trial, 91 subjects underwent randomization. Forty-five subjects received oral ASHMI capsules and prednisone placebo tablets (ASHMI group) and 46 subjects received oral prednisone tablets and ASHMI placebo capsules (prednisone group) for 4 weeks. Spirometry measurements; symptom scores; side effects; and serum cortisol, cytokine, and IgE levels were evaluated before and after treatment. RESULTS: Posttreatment lung function was significantly improved in both groups as shown by increased FEV(1) and peak expiratory flow findings (P<.001). The improvement was slightly but significantly greater in the prednisone group (P<.05). Clinical symptom scores, use of beta(2)-bronchodilators, and serum IgE levels were reduced significantly, and to a similar degree in both groups (P<.001). T(H)2 cytokine levels were significantly reduced in both treated groups (P<.001) and were lower in the prednisone-treated group (P<.05). Serum IFN-gamma and cortisol levels were significantly decreased in the prednisone group (P<.001) but significantly increased in the ASHMI group (P<.001). No severe side effects were observed in either group. CONCLUSION: Anti-asthma herbal medicine intervention appears to be a safe and effective alternative medicine for treating asthma. In contrast with prednisone, ASHMI had no adverse effect on adrenal function and had a beneficial effect on T(H)1 and T(H)2 balance.     

Adaptation and coping: a look at a sickle cell patient population over age 30--an integral phase of the life long developmental process

Individuals with sickle cell disease experience a variety of psychosocial issues, some of which lead to maladjustments. To gather baseline data on coping and adjustment by a group of individuals over 30 years of age, a pilot study was conducted with 30 patients followed routinely at the Duke University Comprehensive Sickle Cell Center. The purpose of the study was to characterize such psychosocial parameters as coping behaviors, education, employment, group affiliation, health beliefs, marital status, parenting and perceptions regarding the disease. Using Erickson's stage of development as a point of reference, the middle adulthood stage was used as a theoretical framework for explaining and interpreting the results of this study. Study results reflect that, on the whole, the participants employed a wide variety of life skills to promote positive psychological and physical well being. These data suggest that this population of sickle cell disease patients have attained a reasonable level of psychosocial adjustment and many are leading productive lives. However, the minority of patients, who use the health care facilities more frequently, might lead one to speculate otherwise.     

Osteochondroma and secondary synovial osteochondromatosis

Secondary synovial osteochondromatosis (SOC) is a rare disorder caused by a variety of joint disorders. Two unusual cases of secondary SOC are presented. The first patient is a 43-year-old man with extensive SOC developing within a bursa surrounding an osteochondroma of the pubic bone. The second patient is a 23-year-old man who developed florid and progressive SOC of his hip joint following excision of a femoral neck osteochondroma. SOC recurred despite three excisions over a 15-month period. Imaging was useful in pre-operative diagnosis of bursal SOC in the first patient and in detecting multiple recurrences in the second patient. Both cases illustrate prominent SOC developing secondary to osteochondroma. The different hypotheses regarding bursal and secondary SOC are reviewed. Received: 8 October 1998 Revision requested: 28 October 1998 Revision received: 13 November 1998 Accepted: 16 November 1998     

Genetic mapping of modifier loci affecting malignant hypertension in TGRmRen2 rats.

BACKGROUND: Genetic background has a major influence on the manifestation of multifactorial diseases such as hypertension in which severe complications may be caused through an interaction with additional factors, which may be genetically determined. We have previously described a genetic model of malignant hypertension (MH) in rats carrying the mouse Ren2 gene (TGRmRen2-27), in which the phenotype is dependent on the genetic background. METHODS: Using a single homozygous TGRmRen2-27 male as transgene donor, we produced two F1 populations with (a) 100% penetrance of MH in progeny heterozygous for the Fischer F344 genetic background and (b) 58.5% penetrance in progeny heterozygous for the Lewis genetic background. To identify the modifier loci affecting the phenotype, a cohort of 252 males was produced by breeding the same single male with Fischer-Lewis F1 females. The progeny were phenotyped for clinical and pathological features of MH. RESULTS: Genome-wide screening and quantitative trait loci (QTL) analysis identified two loci, on chromosome 10 (LOD 4.4) and on chromosome 17 (LOD 3.9) close to the Ace and At1 genes, respectively, which contribute to the lethal MH phenotype. Their influence on mortality was consistent with a multiplicative effect of the two loci. In addition, we found higher plasma angiotensin-converting enzyme activity in progeny receiving the Fischer allele than in progeny receiving the Lewis allele (123.5 +/- 9.5 vs. 91.8 +/- 4.9 U/liter, P < 0.01), suggesting the association of angiotensin-converting enzyme and MH. CONCLUSIONS: Our study demonstrates the application of a transgene as a "major gene" to facilitate the identification of modifier loci, which can affect the phenotype of MH, and reveals Ace and At1 as candidate genes involved in the manifestation of the MH phenotype.