Psoriatic arthritis: performance of rheumatologists in daily practice

OBJECTIVES: To assess, using standardised patients (SPs), how rheumatologists diagnose psoriatic arthritis, whether the diagnostic efficiency is influenced by specific characteristics of the rheumatologists, and to study the relationship with costs. METHODS: Twenty three rheumatologists were each visited by one of two SPs (one male, one female) presenting as a patient with psoriatic arthritis. SPs remained incognito for all meetings for the duration of the study. Immediately after the encounter, SPs completed case-specific checklists on the medical content of the encounter. Information on ordered laboratory and imaging tests was obtained from each hospital. RESULTS: Fourteen rheumatologists diagnosed psoriatic arthritis correctly. They inspected the skin for psoriatic lesions more often than those rheumatologists who established other diagnoses. Rheumatologists diagnosing psoriatic arthritis spent more on additional laboratory and imaging investigations. These were carried out after the diagnosis to confirm it and to record the extent and severity of the disease. No differences in type of practice, number of outpatients seen each week, working experience, or sex were found between rheumatologists who made the correct diagnosis and those who made other diagnoses. The correct diagnosis was more often missed by rheumatologists who saw the male SP, who presented with clear distal interphalangeal DIP joint arthritis only, causing confusion with osteoarthritis of the DIP joints. CONCLUSION: There is a considerable amount of variation in the delivery of care among rheumatologists who see an SP with psoriatic arthritis. Rheumatologists focusing too much on the most prominent features (DIP joint arthritis) sometimes seem to forget "the hidden (skin) symptoms".     

Cytokine profile of cervical cancer cells

OBJECTIVE: In patients with cervical carcinoma, the presence of cytokines produced by T(H)2 cells, and the presence of an eosinophilic inflammatory infiltrate, has been associated with a less effective immune response and tumor progression. In the present study, we have investigated the cytokine profile of cervical carcinoma cells. In addition, we have measured whether differences in cytokine profiles between normal and malignant cervical epithelial cells are present. METHODS: For this purpose we have determined the mRNA expression patterns of 20 relevant cytokines by RT-PCR and Southern blotting in 3 normal primary cervical epithelial cell cultures (NPE) and 10 cervical cancer cell lines (CCCL). RESULTS: TGF-beta(1), IL-4, IL-12p35, and IL-15 were produced by all CCCL and NPE. TNF-alpha, IL-10, IL-5, and RANTES were present in most NPE, but not in any of the CCCL. MCP-1 was expressed in all CCCL but in only one NPE. The presence of the anti-inflammatory cytokine TGF-beta(1) in cervical carcinomas was confirmed by RNA in situ hybridization on tissue sections of carcinomas from which the CCCL originated. CONCLUSIONS: Our results suggest that cervical carcinoma cells produce immunomodulatory cytokines and that cytokine expression patterns change after malignant transformation. The implications of locally produced cytokines by cervical cancer cells are further discussed.     

Influence of caloric restriction on the development of atherosclerosis in nonhuman primates: progress to date

Caloric restriction (CR) has been observed to retard aging processes and extend the maximum life span in rodents. In an effort to evaluate the effect of this nutritional intervention on physiologic variables in higher species, several nonhuman primate trials are ongoing. In particular, a study evaluating the independent effect of CR on the extent of atherosclerosis was initiated in 1993 in 32 adult cynomolgus monkeys. Therefore, the trial was designed to achieve identical cholesterol intake after animals were randomized to a control group or a calorie-restricted group (30% reduction from baseline caloric intake). The animals were routinely evaluated for glycated proteins, plasma insulin and glucose levels, insulin sensitivity, and specific measures for abdominal fat distribution by CT scans over a 4-year interval. The results from 4 years of intervention demonstrate that CR improves cardiovascular risk factors (such as visceral fat accumulation) and improves insulin sensitivity. In contrast to other primate studies with normolipidemic animals, CR had no independent effects on plasma lipid levels and composition in the presence of equivalent amounts of dietary cholesterol intake. Preliminary analysis of atherosclerotic lesion extent in the abdominal aorta has failed to demonstrate differences between control animals and CR animals. Follow- up studies are being conducted to determine the effect of CR on atherosclerosis extent in coronary and carotid arteries.      

Inherited disorders of 3-methylcrotonyl CoA carboxylation

The clinical course of 4 patients who had reduced activities of 3-methylcrotonyl CoA carboxylase (also called 3-methylcrotonylglycinuria) is described. Two children presented with a metabolic acidosis, one in the neonatal period and the other with episodes of acidosis that started in the second year of life. In the other 2 children neurological symptoms were prominent, one having infantile spasms and the other developmental regression with a skin rash and alopecia. Three of the children responded well to oral biotin and dietary protein restriction but the fourth, despite a biochemical response to biotin, has a severe neurological handicap. The clinical presentation of inborn errors of 3-methylcrotonyl CoA carboxylase is variable. Metabolic acidosis may not be conspicuous and instead neurological features may predominate.     

Suspected poisoning in children. Study of the incidence of true poisoning and poisoning scare in a defined population in North East Bristol

The distinction between true and suspected poisoning in children has not been made clear in previous work on childhood poisoning. A study of suspected poisoning in children under 15 years of age in a defined population of North East Bristol from November 1970 to July 1973 carried out by the Health Education Council Medical Research Division included 53,000 child-years at risk. The number of suspected poisonings was 3-4/1000 population aged under 15 years per year, with a higher incidence in younger age groups. Detailed investigation of the circumstances of the accidents carried out by a multidisciplinary team showed that at least 65%, and possibly as many as 78% were poisoning scares and not true poisoning. The evidence used by the casualty doctor and by the parents to diagnose poisoning was explored, and in many cases was circumstantial. Children with fathers in nonmanual occupations were over-represented. This may reflect differences in patterns of utilization behaviour rather than true differences in incidence.     

Acceptability and effects of an educational leaflet on infections in type 2 diabetes patients: a randomized controlled trial in primary care

AIM: To determine the acceptability of an educational leaflet regarding the prevention and treatment of infections of the lower respiratory tract (LRTIs) and urinary tract (UTIs) and to determine the effects of the leaflet on knowledge and attitude of DM2 patients in primary care. METHOD: In a randomized controlled intervention trial 200 DM2 patients enlisted in two practices, one urban and one rural, from the Utrecht general practitioners Research Network (HNU) were selected. Per practice, 50 patients were randomly assigned to the intervention group and 50 to the control group. The intervention was a leaflet on diabetes and LRTIs and UTIs based on the results of focus group interviews. The leaflet was sent to the patients homes. The outcome measures were acceptability of the leaflet and differences in knowledge and attitude, measured by a questionnaire. RESULTS: The mean age was 68 years and 55% was male. There were no substantial differences in characteristics between the two groups. Among the intervention group, the leaflet was appreciated as understandable (100%) and inviting (79%). Compared to the control group, specific knowledge and attitude did not substantially differ. Patients in the intervention group had a slightly more positive attitude about 'being attentive to signs indicating pneumonia' (median difference, 1 point; p=.003) and they also answered 'UTI is mostly caused by a bacteria' more often correctly (risk difference, 18%; 95% CI, 4-33%, p=.016). CONCLUSION: A leaflet on prevention and treatment of LRTIs and UTIs is considered acceptable among DM2 patients, but a multi-faceted educational approach may be needed to improve health behavioral determinants.     

The prospects for renal xenotransplantation

Summary: Xenotransplantation of non-human organs into human recipients has long been proposed as a possible strategy to overcome the acute shortage of donor organs. However, vascular organ transplants to humans from phylogenetically disparate species such as the pig are not currently possible due to a rapid rejection process termed hyperacute rejection. This process is initiated by the binding of host pre-formed 'natural antibodies' to the donor vascular endothelium, activation of the host complement system and activation or injury of the donor endothelial cells, leading to intravascular coagulation and loss of the graft due to ischaemic necrosis within minutes to hours of engraftment. Prevention of natural antibody binding and complement activation is viewed as paramount to preventing hyperacute rejection. Even if hyperacute rejection can be prevented, further barriers to successful discordant xenografts such as delayed xenograft rejection and a donor-directed cell-mediated rejection process will still represent major obstacles. This review examines recent advances being made in the various areas of xenograft research and the potential clinical application of pig-to-human xenografts that these strategies may bring.