Biochemical prognostic markers of outcome in non-paracetamol-induced fulminant hepatic failure

BACKGROUND: Fulminant hepatic failure (FHF) is associated with major metabolic disturbances, the onset and severity of which can predict clinical outcome. This study uses admission blood samples to identify early biochemical markers of clinical outcome in patients with non-paracetamol-induced FHF. PATIENTS AND METHODS: Fifty-nine patients admitted to the Scottish Liver Transplant Unit with non-paracetamol-induced FHF were studied. Plasma samples were collected at a median of 5.4 hr after admission to our unit and analyzed using conventional laboratory tests and nuclear magnetic resonance spectroscopy. RESULTS: A total of 19 patients underwent transplantation, 15 patients died without undergoing transplantation, and 25 patients survived with medical management alone. There were significantly lower levels of lactate, alanine, valine, and bilirubin and significantly higher levels of pyruvate and albumin in patients who survived spontaneously compared with the other two groups. By use of multiple logistic regression analysis, an equation was devised that best predicted clinical outcome: 0.5x(albumin [g/L])-2x(lactate [mmol/L])-36x(valine [mmol/L])-38x(pyruvate [mmol/L]). Values of less than 2 were associated with poor clinical outcome and had a positive predictive value of 91%, a negative predictive value of 86%, a sensitivity of 94%, and a specificity of 86% for death or transplantation. This algorithm can be applied on admission, thus expediting decision-making. CONCLUSION: We identified biochemical markers that may be useful in predicting outcome in patients with non-paracetamol-induced FHF and should be evaluated further in a different patient population.     

Misoprostol and pregnancy: ever-increasing indications of effective usage

PURPOSE OF REVIEW: The subject of misoprostol in the field of reproductive health care has courted much controversy. The aim of this review is to survey the literature published in this field over the past year, and to evaluate developments in this area. This article will cover termination of pregnancy, induction of labor and the issue of postpartum hemorrhage. RECENT FINDINGS: The use of misoprostol as a single agent remains of clinical value when mifepristone is unavailable. The sublingual and rectal routes are alternative modes of administration. For induction of labor, the optimum dose and route of misoprostol is still undetermined. Lower doses of between 20 microg to 40 microg may increase the safety profile for labor induction. Misoprostol may be a useful adjunct to the therapeutic options available for the prevention and treatment of postpartum hemorrhage. SUMMARY: There are many potential uses for misoprostol in pregnancy. However clinicians must judge the evidence and the emotive debate surrounding this field and decide how it will influence their clinical practice depending on the priorities of their own clinical circumstances.     

Insulin-like growth factor-1 and insulin-like growth factor binding protein-3 for prostate cancer detection in patients undergoing prostate biopsy

PURPOSE: Laboratory and epidemiological studies suggest that high circulating insulin-like growth factor (IGF)-1 and low IGF binding protein-3 are associated with increased prostate cancer risk. However, the usefulness of serum IGF-1 or IGF binding protein-3 for predicting pathology results in men undergoing prostate biopsy is unclear. We examined the relationships of serum IGF-1, IGF binding protein-3 and the results of prostate biopsy. MATERIALS AND METHODS: A total of 652 consecutive patients with elevated serum prostate specific antigen (PSA) or abnormal digital rectal examination who were referred for transrectal ultrasound sextant prostate needle biopsy underwent blood sampling before biopsy. PSA, free PSA, IGF-1 and IGF binding protein-3 were measured. There were 244 men (37.4%) with cancer and 408 controls with benign conditions. RESULTS: Mean IGF-1 plus or minus SD in the cancer and control groups was 176.1 +/- 58.3 and 178.7 +/- 54.7 ng./ml., respectively (p = 0.57). Mean IGF binding protein-3 in the cancer and control groups was 2,724 +/- 647 and 2,673 +/- 589 ng./ml., respectively (p = 0.3). Adjustment for age and PSA showed significantly lower IGF-1 in cancer cases, while IGF binding protein-3 was not significant. ROC values were significantly higher for free-to-total PSA and PSA than for crude and age adjusted IGF-1 and IGF binding protein-3. CONCLUSIONS: Our data indicate that serum IGF-1 or IGF binding protein-3 does not predict the results of prostate biopsy in men with elevated PSA or abnormal digital rectal examination. This finding implies that while there is evidence that the IGF-1 level is a risk factor for prostate cancer, neither IGF-1 nor IGF binding protein-3 can be used as a tumor marker for this disease.     

Use of oral misoprostol in the prevention of postpartum haemorrhage

Objective To investigate the use of the oral prostaglandin E₁ analogue, misoprostol in the prevention of postpartum haemorrhage.
Design A prospective observational study.
Setting A university teaching hospital.
Participants Two hundred and thirty-seven consecutive women undergoing vaginal delivery.
Methods All the women were given 600 μg oral misoprostol just after delivery.
Main outcome measures Rates of postpartum haemorrhage; need for therapeutic oxytocic drugs; retained placenta and length of the third stage of labour.
Results Postpartum haemorrhage occurred in 6% of the women; the need for therapeutic oxytocics in 5%, retained placenta in 2% and the median length of the third stage was 5 min. Vomiting and diarrhoea in the first hour after delivery occurred in 8% and 3% respectively and shivering in 60%.
Conclusions Misoprostol may be effective in the prevention of postpartum haemorrhage, and has few side effects. A double blind randomised trial is required.     

Genomewide association analysis of warfarin dose requirements in Middle Eastern and North African populations

To date, there has been no genomewide association study (GWAS) from the Middle East and North African (MENA) region to identify genetic variants associated with warfarin dose variability using this approach. In this study, we aimed to conduct the first GWAS of warfarin dose requirements in patients from the MENA region. A total of 132 Qatari (discovery) and 50 Egyptians (replication) were genotyped using Illumina Multi‐Ethnic Global BeadChip Array. A GWAS was performed on log‐transformed weekly warfarin dose in the studied population, adjusting for clinical characteristics and ancestry. The genomewide signals from the discovery cohort were tested in the Egyptian cohort. A GWAS meta‐analysis, including the Qatari and Egyptian cohorts, was also performed and the output from this analysis was used in a gene‐based analysis. The discovery analysis in Qatari identified five genomewide single‐nucleotide polymorphisms (SNPs) in chromosome 16. These signals were replicated in the Egyptian cohort. Combining the two data through a GWAS meta‐analysis strengthened the association in chromosome 16 with VKORC1 rs9934438 being the lead genomewide signal (β = −0.17, 6 × 10⁻¹⁵). Other SNPs were identified in chromosome 10 at a p value less than 1 × 10⁻⁵. The genetic variants within VKORC1 rs9934438 and CYP2C9 rs4086116 explained 39% and 27% of the variability in the weekly warfarin dose requirement in the Qatari and Egyptians, respectively. This is the first GWAS of warfarin dose variability in the MENA region. It confirms the importance of VKORC1 and CYP2C9 variants in warfarin dose variability among patients from the MENA region.