The natural history of factor VIII:C inhibitors in patients with hemophilia A: a national cooperative study. II. Observations on the initial development of factor VIII:C inhibitors

During a 4-year multicenter cooperative study of acquired factor VIII inhibitors in persons with hemophilia A, new inhibitors were detected in 31 of 1,306 patients who entered the study without an inhibitor or the history of an inhibitor. The incidence of new inhibitors was eight per 1,000 patient-years of observation. The factor VIII:C level before inhibitor development was less than or equal to 0.03 U/mL in 29 individuals and 0.06 U/mL and 0.07 U/mL in the remaining two. Factor VIII:Ag levels were measured in 27 individuals and were less than 0.03 U/mL in 23 and 0.05 to 0.11 U/mL in the remaining four. Maximum inhibitor levels ranged from 1.0 to 9,044 Bethesda U/mL. In seven patients under the age of 20, relatively weak inhibitors (none higher than 4.3 Bethesda U/mL) were detected on only a single occasion despite continued factor VIII challenge. In the other 24 patients with inhibitors detected on multiple occasions, 50% had appeared by age 20 and 71% by age 30. Seventeen of the 31 inhibitors, including 12 of 15 with maximum values greater than 10 Bethesda U/mL, developed within 75 exposure days to factor VIII.     

Recombinant vaccinia viruses for the characterization of Plasmodium falciparum-specific cytotoxic T lymphocytes: recognition of processed antigen despite limited re-stimulation efficacy

Cytotoxic T lymphocytes (CTL) have been implicated in immunity to Plasmodium falciparum infection and disease. We have previously described the use of peptides to define malaria-specific CTL epitopes. To determine whether these peptide epitopes are processed intracellularly from the whole antigen we have developed recombinant vaccinia viruses (rVV) expressing three malaria antigens: thrombospondin-related adhesive protein (TRAP), Pfs16 and the C- terminal half of liver-stage antigen (LSA)-1. Target cells infected with recombinant viruses were lysed by malaria-specific CTL from semi- immune African donors. We also tested the ability of cells infected with these recombinant vaccinia viruses to re-stimulate malaria- specific CTL in peripheral blood lymphocytes from malaria immune adults. Two other pox virus recombinants, NYVAC, an attenuated vaccinia virus, and ALVAC, a canarypox virus, both expressing malaria antigens were also evaluated for their ability to stimulate malaria-specific CTL in contrast to peptide, none of these viruses successfully re- stimulated CTL from the peripheral blood lymphocytes of semi-immune donors. The ability of human CTL from naturally exposed individuals to recognize processed antigen supports the relevance of these cells in protective immunity to malaria.      

Percutaneous dilation of benign biliary strictures

Percutaneous balloon dilation of benign biliary strictures was successful in 15 of 18 patients in whom the procedure was attempted. Successful dilation was achieved in nine of 11 patients who had biliary enteric strictures, with follow-up of 22-55 months (mean, 35.4 months) after catheter removal in seven patients. Five of six strictures in the biliary tree that developed after surgery were successfully dilated, with long-term follow-up available in two patients (58 and 42 months). A patient with an inflammatory common bile duct stricture that was successfully dilated was followed up for 18 months. Percutaneous dilation of biliary tract strictures is a promising technique with good long-term results and may be the initial treatment of choice in biliary stricture management.     

Tap water versus sterile saline solution in the colonisation of skin wounds

Irrigating wounds with tap water does not increase colonisation, but controlled studies are required for further evidence. Microbial colonisation was assessed in skin wounds, before and after irrigation with tap water, and was compared with irrigation using 0·9% sodium chloride sterile solution. The study included 120 subjects with chronic, traumatic, vascular, pressure or neuropathic wounds. A total of 60 wounds were randomly assigned to be irrigated with tap water (tap water group) and another 60 to be irrigated with 0·9% sodium chloride sterile solution (saline group), at a pressure of 0·46–0·54 PSI. Samples were collected from the centre of each wound using Levine's technique, before and after irrigation, and cultivated in thioglycollate, hypertonic mannitol agar, eosin methylene blue (EMB) agar, blood agar and Sabouraud agar at 37°C for 72 hours. There was concordance (kappa test) and discordance (McNemar test) regarding the count of positive and/or negative samples before and after irrigation in each group. The proportion of reduction of positive samples was similar for both groups in all cultures. Colony‐forming unit count before and after irrigation was similar in both groups and in all cultures, except for the culture in hypertonic mannitol agar from the tap water group, for which the count was lower after irrigation (Wilcoxon z = 2·05, P = 0·041). It is concluded that skin wound irrigation with tap water leads to further reduction of Gram‐positive bacteria compared with 0·9% sodium chloride sterile solution, with no difference in colonisation of haemolytic bacteria, Gram‐negative bacteria and fungi.     

Regional Cerebellar Volumes Predict Functional Outcome in Children with Cerebellar Malformations

The cerebellum has recently been recognized for its role in high-order functions, including cognition, language, and behavior. Recent studies have also begun to describe a functional topography of the mature cerebellum that includes organization on a mediolateral axis. However, no study to date has examined the relationship between regional cerebellar volume and developmental disabilities in children with cerebellar malformations. The objective of this study was to estimate the extent to which total and regional cerebellar volumes are associated with developmental disabilities in a cohort of children with cerebellar malformations. Children aged 1 to 6 years with a diagnosis of cerebellar malformation underwent standardized outcome measures and quantitative magnetic resonance scanning. The cerebellum was parcellated into seven mediolateral zones (three for each hemisphere plus the vermis) for regional volume analysis. In children with cerebellar malformations, decreased total cerebellar volume was associated with delays in global development, expressive language, cognition, as well as gross and fine motor function. Decreased volume in the right lateral cerebellar hemisphere was related to impaired cognition, expressive language, and gross motor function. Additionally, reduced vermis volume was associated with impaired global development, cognition, expressive language, and gross and fine motor skills, as well as behavior problems and a higher rate of positive autism spectrum screening test. These results begin to define the structural topography of functional outcome in children with cerebellar malformations and should lead to greater accuracy of prognostication as well as timely early developmental interventions.