Gliadin antibody detection in gluten enteropathy

Circulating antigliadin antibody has been described in patients with gluten enteropathy although the prevalence varies in different studies. It has been suggested that the investigation for antigliadin antibody might be useful as a screening test. The object of the present study was to evaluate two different techniques for assaying these antibodies — an indirect immunofluorescent method and an enzyme-linked immunosorbent assay (ELISA). Antibodies were assayed in the sera of 102 patients in whom jejunal biopsies were also obtained. The specificity of both tests was greater than 95%, and the correlation between the presence of antibody and histology was significant (p < 0.005), though the sensitivity of each test was less than 70%.     

The Inhalation Toxicology, Genetic Toxicology, and Metabolism of Difluoromethane in the Rat

Difluoromethane (HFC32) is under development as a replacementfor chlorofluorocarbons (CFCs) in some refrigeration applications.It has been evaluated by standard studies of toxicity, developmentaltoxicity, and genotoxicity. In addition, the metabolism anddisposition of HFC32 was investigated and a physiologicallybased pharmacokinetic (PB-PK) model constructed. Inhalationof HFC32 (up to 50,000 ppm) caused no organ-specific effects,but resulted in slight maternal toxicity to the pregnant ratand rabbit and some fetotoxicity to the rat. HFC32 did not sensitizethe heart to adrenaline. The pharmacokinetics of [¹⁴C]difluoromethane(10,000 to 50,000 ppm/6 hr) revealed that about 2.1% of theinhaled HFC32 was absorbed and that steady state blood levelswere achieved within 2 hr and were proportional to dose. Carbondioxide was the major metabolite of HFC32 at all exposure levels.Carbon monoxide was not detected. The in vivo data were usedto validate a PB-PK model to describe the uptake and metabolismof HFC32. Absorption and distribution are adequately describedusing rat blood:air and tissue:air partition coefficients. Metabolism,which was linear across the dose range, was described by a firstorder rate constant (K_f=8.98 hr^–1). Of the absorbed HFC32,about 63% was metabolized at all doses; however, when metabolismwas expressed as a percentage of the inhaled dose it was muchlower, being about 1.4% of the HFC32 entering the airways. Overall,the results indicate that HFC32 is of very low toxicity andshould be an acceptable alternative to CFCs.     

Absence of effects of prolonged simvastatin therapy on nocturnal sleep in a large randomized placebo-controlled study

1It has been suggested that lipophilic HMG CoA reductase inhibitors, like lovastatin and simvastatin, may cause sleep disturbance. 2Six hundred and twenty-one patients at increased risk of coronary heart disease were randomized in a single centre to receive 40 mg daily simvastatin, 20 mg daily simvastatin or matching placebo. To assess the effects of prolonged use of simvastatin on nocturnal sleep quality and duration, a sleep questionnaire was administered to 567 patients (95% of 595 survivors) at an average of 88 weeks (range: 44–129 weeks) after randomization. 3The main outcome measures were sleep-related problems and use of sleep-enhancing medications reported during routine study follow-up visits, and responses to the sleep questionnaire about changes in sleep duration and about various sleep events during the preceding month. 4No differences were observed between the treatment groups in the frequency of sleep-related problems reported, in the proportion of follow-up visits at which such problems were reported, or in the use of sleep-enhancing medications. The numbers who stopped study treatment were similar in the different treatment groups, and no patient stopped principally because of insomnia. In response to the sleep questionnaire, there were no significant differences between the treatment groups in reports of various sleep events during the preceding month, except that slightly fewer patients allocated simvastatin reported waking often. No differences in sleep duration were observed. 5This placebo-controlled trial does not indicate any adverse effects of prolonged treatment with simvastatin on systematically sought measures of sleep disturbance.     

COMBINATION THERAPY WITH GOLD AND HYDROXYCHLOROQUINE IN RHEUMATOID ARTHRITIS: A PROSPECTIVE, RANDOMIZED, PLACEBO-CONTROLLED STUDY

We studied combination therapy with two slow-acting antirheumaticdrugs given concurrently in active rheumatoid arthritis (RA).A 12-month prospective randomized controlled trial comparedgold and hydroxychloroquine in 52 patients to gold and placeboin 49. The patients continued to receive non-steroidal anti-inflammatorydrugs and analgesics. They were selected from three rheumatologycentres in the West Midlands. Combination therapy led to a greaternumber of withdrawals due to adverse reactions (18 cases comparedto 10 receiving gold/placebo). Patients completing 12 months'therapy (27 taking gold/ hydroxychloroquine and 32 on gold/placebo)were compared using five clinical, seven laboratory, and oneradiological measure. All 13 variables favoured gold/hydroxychloroquinewith an overall advantage of 20–25% for the combination.This only reached statistical significance (at the 1% level)for C-reactive protein. An overall disease activity index wasbetter at 12 months (at the 5% level) and showed a more rapidresponse with gold/hydroxychloroquine. This is the first randomizedprospective placebo-controlled trial to show a significant advantagefrom a combination of two slow-acting drugs. There are manydifferent ways of giving such combinations and we consider theseshould be explored to maximize the effectiveness of treatmentfor RA. KEY WORDS: Rheumatoid arthritis, Treatment, Antimalarials, Sodium aurothiomalate     

Acute promyelocytic leukemia: report of a variant translocation, t(1;17)

A 4-year-old female with acute promyelocytic leukemia (APL) was found to have a variant form of the 15;17 translocation, which is diagnostic of APL. The karyotype of the malignant cells was 47,XX,t(1;11)(q25;q21),t(1;17)(p36;q21), + 8. This case is additional evidence that the breakpoint of #17 at q21 is the characteristic chromosomal aberration of APL. The present case is also unusual because of the young age of the patient.     

Role for mannose binding lectin in the prevention of Mycoplasma infection

Polymorphisms in exon 1 of the MBL-2 gene, resulting in reduced plasma levels of mannose binding lectin, were significantly overrepresented in 23 patients with primary antibody deficiency and culture-proven mycoplasma infections (P = 0.0038). This association persisted with the inclusion of a further nine suspected (doxycycline-responsive) cases (P = 0.0087). The lectin was shown to bind to three strains of mycoplasma.     

Differential effects of external pH alteration on intracellular pH in rat coronary and cardiac myocytes

Changes in extracellular pH (pH_o) induce changes in the intracellular pH (pH_i) of cardiac myocytes that are slow and attenuated. Little however is known about the effects of changing pH_o on the pH_i of the coronary smooth muscle cells. We have therefore directly compared the effects of altering pH_o on pH_i of both coronary and cardiac myocytes. Carboxy-SNARF was used in single cells to measure pH_i. Alteration of pH_o caused corresponding changes in pH_i that were large (70–80 % of pH_o) and rapid in coronary myocytes compared to cardiac myocytes. In contrast, changes of pH_i produced by weak acids or bases produced similar pH_i responses in both types of cells. It is suggested that the differential effects of pH_o on coronary and cardiac cells may be functionally significant, as it will allow rapid alteration of coronary perfusion to meet tissue needs, while maintaining cardiac output.Supported by the BHF and MRC