Hydroxyethyl starch induced acquired von Willebrand's disease

Hydroxyethyl starch (HES) (Hespan, DPont) is a widely used synthetic volume expander which in standard doses of up to 1.51 in 24 h has no significant effect on coagulation (Munsch et al. 1988). However, the data sheet states that in large volumes HES may alter the coagulation mechanism. We now report a case of HES induced acquired von Willebrand's disease (vWD) in which severe bleeding occurred.     

Short report: treatment of Helicobacter pylori-associated duodenal ulcer with omeprazole plus antibiotics

Omeprazole heals most duodenal ulcers after 4 weeks of treatment but relapse is common. Eradication of Helicobacter pylori is associated with reduced rate of ulcer relapse. This study investigates the effect of omeprazole with antibiotics in H. pylori-associated duodenal ulceration. Forty-three patients with endoscopically proven duodenal ulcer and H. pylori entered this study. Treatment consisted of 20 mg omeprazole daily (four weeks) and seven days (first week) treatment with 400 mg metronidazole t.d.s. and 500 mg tetracycline t.d.s. Four weeks after completing the treatment, 81 % (35143) had a healed duodenal ulcer, and 58% (25/43) had H. pylori eradication. In those who healed, at one year 21 remained H. pylori-negative, 12 had persistent H. pylori infection and 2 had re-infection. The ulcer relapse rate at one year was 26%: of the 9 who relapsed, 6 had persistent infection, 2 were re-infected, and only 1 was H. pylori-negative. This combination therapy of antibiotics with omeprazole successfully eradicates Helicobacter pylori and has a lower ulcer replase than omeprazole alone.     

Development and reproducibility of a tool to assess school food-purchasing practices and lifestyle habits of Australian primary school-aged children

Objective: To describe the development and reproducibility of a self‐report instrument, for use with children in years 4–6, to identify sources of food eaten during the day, and type and frequency of food purchases at school. Design: Tool development stages included formulation of content and format, expert review, piloting and a test–retest study. Subjects/setting: The pilot study included school students (n = 20) in years 4 and 5 (seven girls, mean age 9.7 ± 0.7 years) attending an Australian public primary school. The test–retest study was performed in a large metropolitan public primary school (n = 245 children, 52% female, mean age 10.7 ± 0.91 years) including children from years 4 (n = 88), 5 (n = 84) and 6 (n = 73). Statistical analysis: A Kappa statistic was used to assess level of agreement between the two time periods separated by 1 week. The results were analysed using SAS version 8.2 with each question compared at time 1 and 2. Results: The mean kappa was 0.529 using pairings from 17 questions. Values ranged from 0.18 to 0.71 (CI 0.46–0.60). Conclusions and applications: The School Eating Habits and Lifestyle Survey has been developed and pilot‐tested in primary school‐aged children and shown to have moderate stability over time. The results show that each phase of development, particularly those spent in consultation and testing, led to progressive improvement of this instrument. This process improved the quality of information produced and gave insights to self‐report of dietary intake and behaviours among children.     

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     

Intravenous and intracoronary fibrinolytic therapy in acute myocardial infarction: Overview of results on mortality, reinfarction and side-effects from 33 randomized controlled trials

During the past 25 years, 24 randomized trials of intravenous(IV) fibrinolytic treatment have been reported, involving atotal of some 6000 patients in the acute phase of myocardialinfarction. Most tested IV streptokinase (SK), but a few testedIV urokinase (UK). In the past 2 or 3 years numerous small randomizedtrials of intracoronary (IC) SK have been started, 9 of which,involving a total of about 1000 such patients have been reported.Because all of these IV and IC trials were small (the largestincluding only 747 patients), their separate results appearcontradictory and unreliable. But, an overview of the data fromthese trials indicates that IV treatment produces a highly significant(22%±5%, (P<0.001) reduction in the odds of death,an even larger reduction in the odds of reinfarction, and anabsolute frequency of serious adverse effects to set againstthis that is much smaller than the absolute mortality reduction.The apparent size of the mortality reduction in the IV trialswas similar whether anticoagulants were compulsory or optional,whether treatment was in a coronary cure unit or an ordinaryward and, surprisingly, whether treatment began early ( <6h from onset of symptoms) or late (generally 12–24 h).In addition, there was no evidence that UK was more effectivethan the less expensive SK, or that, despite their technicalcomplexity, the new IC regimes were more effective than theold IV regimes. Even the IV schedules that have been studied in randomized trialswere, however, quite complex, and the IC schedules were farmore so. Perhaps partly because of this, none of them is widelyused. If so, then some much simpler, and hence more widely practicable,IV SK regimes should be developed and tested. For example, asimple one hour high-dose IV SK infusion, without anticoagulation,will successfully convert virtually all of the available plasminogeninto plasmin. But, it may be several years before the net effectson mortality of any more widely practicable IV SK regimes canbe agreed unless many of the hospitals that do not wish routinelyto use IC regimes or the complex previous IV regimes will collaboratein multicentre randomized trials that can, if necessary, continuerapid intake until some tens of thousands of patients have beenrandomized, and some thousands of deaths have been observedamong the control and treated patients. The same, of course,may be true for any other fibrinolytic regimes (e.g. infusionof tissue plasminogen activator) if their net effects on mortalityare comparable to those of IV SK.     

Syndrome X in women is associated with oestrogen deficiency

This study was undertaken to ascertain whether gynaecologicalhistory or a reduction in ovarian hormones are triggers of anginain menopausal women with a positive exercise test and normalcoronary arteries. The majority of patients with angina pectoris,a positive exercise test and normal coronary arteries are female,suggesting that the female gender may be important in the aetiology.We studied the gynaecological features of 107 women (age 53±9 years) with syndrome X, taken from a population of134 patients including 27 males. Cardiological investigationswere undertaken and detailed gynaecological history obtainedfrom all the female patients. Menopausal status was confirmedby plasma levels of oestradiol-17ß100 pmol. l^–1. In 95 of the 107 female patients, chest pain began either duringthe perimenopausal period (32) or after the menopause (63).Of the 63 menopausal patients, 43 had undergone hysterectomyat an average of 8 ± 6 years prior to the onset of chestpain. The incidence of hysterectomy in the study population(40%) was four times greater than that of an age-matched population.These findings confirm that the majority of patients with syndromeX are women in whom the chest pain began after the onset ofmenopause. Ovarian hormone deficiency may, therefore, play arole in the onset of syndrome X in female patients.     

SULPHASALAZINE-INDUCED AUTOIMMUNE ABNORMALITIES IN PATIENTS WITH RHEUMATIC DISEASE

Sulphasalazine is a commonly used second line agent in rheumatoidarthritis (RA) and other inflammatory joint diseases and isreported to be one of the least toxic of this group of drugs.Recently a severe allergic reaction and cases of lupus-likedisease have been described in patients with RA after treatmentwith sulphasalazine. We describe five patients, all with inflammatoryarthropathy who developed cutaneous vasculitis, lupus-like diseaseor atypical serology after exposure to sulphasalazine. Threeof four cases investigated were found to have the slow acetylatorphenotype. These reactions can complicate the diagnosis anddelay discontinuation of the drug. Moreover, present guidelinesfor the diagnosis of drug-induced lupus do not apply to themajority of patients with sulphasalazine-induced lupus. KEY WORDS: Sulphasalazine-induced lupus, Rheumatoid arthritis, dsDNA antibodies, Vasculitis