Clinical significance of elevated alpha-fetoprotein in Alaskan Native patients with chronic hepatitis C

The clinical significance of elevated serum alpha-fetoprotein (AFP) in patients with chronic hepatitis C virus (HCV) infection is not well defined. We analysed data from a population-based cohort of patients with HCV infection to assess the prevalence of elevated serum AFP, to determine its association with clinical and virologic parameters and with clinical outcomes. We defined a slightly elevated serum AFP level as 8 to <15 and a high-AFP level as > or =15 microg/L. Among 541 HCV-RNA-positive persons, 61 (11%) had a slightly elevated or high AFP at the time of consent. AFP > or =8 microg/L was associated with the older age, aspartate aminotransferase/alanine aminotransferase ratio >1, and higher alkaline phosphatase levels, but not with heavy alcohol use, IV drug use, genotype, viral load or duration of HCV infection. Among 192 persons with an AFP at liver biopsy, 17% had an AFP > or =8 microg/L. The sensitivity/specificity of an AFP level > or =8 in detecting Ishak 3-6 fibrosis was 39%/95%. Among 372 persons with a minimum of four AFP measurements over 6 years, 5% had persistently elevated AFP >8 microg/L, 19% had both elevated and normal AFP measurements, and 76% had persistently normal AFP. Elevated AFP at consent was associated with hepatocellular carcinoma (HCC) and end-stage liver disease. Over 6 years of follow-up, persistently elevated AFP was associated with the development of HCC; no person with AFP persistently <8 microg/mL developed HCC. Serial AFP measurements appear to be useful in identifying persons with advanced fibrosis and help to determine who needs periodic screening with liver ultrasound to detect HCC.     

HIV risk and history of STDs in MCMI-III psychopathology subgroups of comorbid substance abusers

The purpose of this investigation is to investigate HIV risk-related attitudes, beliefs, expectancies, behaviors, and histories of lifetime sexually transmitted diseases in the Millon Clinical Multiaxial Inventory III (MCMI-III) defined psychopathology cluster subgroups. Hierarchical agglomerative cluster analysis, using Ward's method, was employed that led to identification of high (n = 37), medium (n = 132), and low (n = 28) MCMI-III psychopathology cluster subgroups. Members of the low psychopathology subgroup demonstrated significantly higher levels of knowledge about HIV and AIDS and less anxiety about HIV infection than high and moderate psychopathology subgroups. The high psychopathology subgroup reported greater importance of approval of condom use by partners but less sexual self-efficacy than the moderate psychopathology subgroup. This high pathology group revealed less favorable condom attitudes than did the low psychopathology subgroup and a significantly higher percentage of unprotected vaginal sex acts in the past 6 months than did members of the other two subgroups. A comparatively low rate of lifetime syphilis was reported in the low psychopathology subgroup (all ps < .05). Results are discussed in the context of a growing literature indicating distinctive treatment needs among members of high psychopathology subgroups of drug treatment participants.     

Eosinophils stimulate fibroblast DNA synthesis

Fibrosis complicates a number of chronic inflammatory diseases and occurs in some conditions following chronic hypereosinophilic syndromes. We assessed whether eosinophils might be a source of fibrogenic factors. Extracts of human and guinea pig cell populations enriched for eosinophils contained substances that stimulated tritiated thymidine incorporation by human fibroblasts. Supernatants derived from resting eosinophils and extracts prepared from eosinophil granules also contained fibrogenic factors. Our findings demonstrate a new potential role for eosinophils and suggest a causal relationship between tissue eosinophilia and scar formation in certain parasitic conditions.     

Risk factors for aortic valve dysfunction in children with discrete subvalvar aortic stenosis

Aortic regurgitation (AR) is a known complication of discrete subvalvar aortic stenosis (DSS), and its detection often triggers referral for surgery. However, risk factors for aortic valve dysfunction in children with DSS remain incompletely defined. The primary goal of this study was to determine independent risk factors for moderate or severe AR at mid-term follow-up in patients with DSS. Clinical records and echocardiograms of 220 patients with DSS (109 patients had DSS resection and 111 had no surgery) were analyzed. The primary outcome variable was AR grade (based on the width of the vena contracta) at latest follow-up. Age at diagnosis, gender, and duration of follow-up (median 7.2 years, range 1 to 20.4) did not differ significantly between medical and surgical patients. By multivariate analysis, independent risk factors for moderate to severe AR (n = 30) were older age at diagnosis of DSS (odds ratio [OR] for age > or =17 years 5.13, p = 0.024), previous balloon or surgical aortic valvuloplasty (OR 19.6, p <0.001), and a longer follow-up period (OR for 1-year increase 1.15, p = 0.032). Excluding patients with previous surgical or balloon aortic valvuloplasty, a higher maximal Doppler gradient was an independent risk factor for moderate to severe AR (OR for peak gradient > or =50 mm Hg 10.8, p = 0.001). Independent predictors of low-risk patients (none or trivial AR and peak gradient < or =30 mm Hg) included thin and mobile aortic valve leaflets (OR 7.86, p = 0.006) and an associated ventricular septal defect (OR 2.18, p = 0.019). These clinical and echocardiographic variables can be used to stratify risk of aortic valve dysfunction in patients with DSS and aid in timing of surgical resection.     

Effect of pravastatin on the development of diabetes and adiponectin production

In the West of Scotland Coronary Prevention Study (WOSCOPS), treatment of hypercholesterolemic men with pravastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, reduced their likelihood to progress to diabetes mellitus by 30%. However, the mechanism of this effect of pravastatin has not been investigated. In the current study, we examined the effect of pravastatin on the development of diabetes in obese diabetic mice, and on the insulin-induced glucose uptake and adiponectin production. Pravastatin treatment attenuated the development of diabetes in db/db and high fat/high sucrose diet-fed C57BL/6J mice. An in vivo glucose transport assay showed that pravastatin upregulated glucose uptake in adipose tissue. Insulin-stimulated glucose uptake was enhanced in primary adipocytes isolated from pravastatin-treated mice. Pravastatin treatment increased adiponectin production in 3T3-L1 adipocytes. Plasma adiponectin levels were significantly increased in pravastatin-treated mice. Analyses of plasma samples from the WOSCOPS biobank indicated a significant increase of plasma adiponectin levels with pravastatin treatment (placebo -0.28+/-0.34 microg/ml versus pravastatin +1.47+/-0.33 microg/ml, p=0.0003). Taken together, our findings suggest that pravastatin may have beneficial effects on adipose tissue, which may partly explain the reduction of the development of diabetes by pravastatin treatment.     

Management of ejaculatory dysfunction

Ejaculatory dysfunction is a common complaint and is often associated with a reduced quality of life for sufferer and partner. The spectrum of ejaculatory dysfunction extends from premature ejaculation (PE) to delayed ejaculation (DE) and anejaculation. Over the past 20–30 years, the PE treatment paradigm, previously limited to behavioural psychotherapy, has expanded to include drug treatment. Multiple well‐controlled, evidence‐based studies have demonstrated the efficacy and safety of selective serotonin re‐uptake inhibitors in delaying ejaculation, confirming their role as first‐line agents for the treatment of lifelong and acquired PE. More recently, there has been increased attention to the psychosocial consequences of PE, its epidemiology, its aetiology and its pathophysiology by both clinicians and the pharmaceutical industry. DE and anejaculation are probably the least common, least studied and least understood of the male sexual dysfunctions. However, their impact is significant as they may result in a lack of sexual fulfilment for both the man and his partner, an effect further compounded when procreation is among the couple's goals of sexual intercourse. The causes of DE, anejaculation and anorgasmia are manifold. Numerous psychotherapeutic treatments are described for the management of delayed or anejaculation. Although some appear to be effective, none has been properly evaluated in large‐scale samples. Treatment of DE or anejaculation with pharmacotherapy has met with limited success. No drugs have been approved by regulatory agencies for this purpose, and most drugs that have been identified for potential use have limited efficacy, impart significant side‐effects or are yet considered experimental in nature.