Molecular characterization of Cryptosporidium isolates obtained from humans in France

Cryptosporidium parvum is usually considered the agent of human cryptosporidiosis. However, only in the last few years, molecular biology-based methods have allowed the identification of Cryptosporidium species and genotypes, and only a few data are available from France. In the present work, we collected samples of whole feces from 57 patients from France (11 immunocompetent patients, 35 human immunodeficiency virus [HIV]-infected patients, 11 immunocompromised but non-HIV-infected patients) in whom Cryptosporidium oocysts were recognized by clinical laboratories. A fragment of the Cryptosporidium 18S rRNA gene encompassing the hypervariable region was amplified by PCR and sequenced. The results revealed that the majority of the patients were infected with cattle (29 of 57) or human (18 of 57) genotypes of Cryptosporidium parvum. However, a number of immunocompromised patients were infected with C. meleagridis (3 of 57), C. felis (6 of 57), or a new genotype of C. muris (1 of 57). This is the first report of the last three species of Cryptosporidium in humans in France. These results indicate that immunocompromised individuals are susceptible to a wide range of Cryptosporidium species and genotypes.     

Dual effect of temperature on the human epithelial Na+ channel

The amiloride-sensitive epithelial sodium channel (ENaC) is the rate-limiting step for sodium reabsorption in the distal segments of the nephron, in the colon and in the airways. Its activity is regulated by intracellular and extracellular factors but the mechanisms of this regulation are not yet completely understood. Recently, we have shown that the fast regulation of ENaC by the extracellular [Na⁺], a phenomenon termed self-inhibition, is temperature dependent. In the present study we examined the effects of temperature on the single-channel properties of ENaC. Single-channel recordings from excised patches showed that the channel open probability (P _o, estimated from the number of open channels N·P _o, where N is the total number of channels) increased on average two- to threefold while the single-channel conductance decreased by about half when the temperature of the perfusion solution was lowered from ~30 to ~15 °C. The effects of temperature on the single-channel conductance and P _o explain the changes of the macroscopic current that can be observed upon temperature changes and, in particular, the paradoxical effect of temperature on the current carried by ENaC.     

Wagner vitreoretinal degeneration with genetic linkage refinement on chromosome 5q13-q14

· Background: It has been previously described that Wagner disease is linked to chromosome 5q13-q14. This study was carried out to describe the ophthalmological aspects and report the results of genetic linkage analysis in a large pedigree affected by Wagner disease. · Methods: Fourty members of one same family agreed to be examined. · Results: Twenty patients presented vitreoretinal degeneration in both eyes without any extra-ocular abnormalities. In young patients, visual acuity was usually normal after correction of frequent mild myopia. Presenile cataracts progressed by the third decade and required removal for visual rehabilitation. The primary disorder involved an abnormal vitreous. A few avascular vitreous bands were usually the only optical feature in the mostly empty vitreous cavity. A circumferential vitreous condensation formed in contact with the retina on many spots. Less common retinal findings included retinal detachment, abnormal retinal pigmentation, progressive atrophy of the RPE simulating choroideremia and lattice degeneration. Genetic analysis revealed a highly significant linkage (lod score >5.0) between the disease and 10 markers of the chromosome 5q13-q14 region. Two recombination events allowed us to refine the linked interval to 20 cM between the D5S650 and D5S618 markers. · Conclusion: Ophthalmological aspects of Wagner’s disease appear to progress with age. Regular ophthalmological examination is important for detecting retinal abnormalities. The gene involved in Wagner’s disease lies in a 20 cM interval on chromosome 5q13-q14. Received: 30 June 1998 Revised version received: 5 October 1998 Accepted: 6 October 1998     

Inhibition of cathepsin D by tripeptides containing statine analogs.

Various analogs of statine, a remarkable amino acid component of the protease inhibitor pepstatine, were synthesized and evaluated as tripeptide derivatives for their activity against cathepsin D and HIV-1 protease.     

When Fever, Paracetamol? Theory and Practice in a Paediatric Outpatient Clinic

Objective: To determine how medical and nursing staff treat feverish children and compare the findings with their theoretical knowledge, evaluating how they might contribute to fever phobia in parents.Setting: Paediatric Emergency Department.Method: In the first step, we analysed prospectively the files of all children having consulted the Paediatric Emergency Department with a history of fever or of body temperature above 38 °C during a 2-week period. The second step consisted of evaluating knowledge and perception of fever of doctors and nurses using a questionnaire.Main outcome measures: Prospective study: final diagnosis (viral, non- invasive bacterial disorders, invasive bacterial disorders), site of measurement and average temperature. Evaluation of theoretical knowledge: definition of fever, site of measurement, evaluation of the child’s clinical state, antipyretic drug choice.Results: A total of 114 children under 5 years of age were enrolled and 24 caregivers (12 doctors, 12 nurses, 90 of the staff) responded to the questionnaire. The results showed good consistency in theoretical knowledge, but an excessive fear about cerebral damage was also shown by doctors. This belief likely contributes to the transmission of fever phobia to parents. In contrast, analysis of children management showed that fever was often under-treated, especially by nurses and even more so by parents. Paracetamol remained the first-line antipyretic drug yet was often administered in insufficient doses. Non-steroidal anti-inflammatory drugs were seldom used, except by parents (16 of all the children). Contrary to literature, the favourite route of administration was the rectal one. Physical methods like sponging were largely used by nurses, despite the uncertainties in their real effectiveness and their known side-effects.Conclusion: Our study showed that the management of feverish children was globally correct in the Paediatric Emergency Department, but several improvement measures have been taken (e.g. tables of normal and abnormal ranges of temperature, recommended temperature measurement techniques, dosage regimen of antipyretic drugs, guidelines to parents), justifying the implementation of a pharmaceutical follow-up.     

Effects of hemorrhagic shock, aspirin, and ethanol on secretagogue-induced experimental pancreatitis

The effects of hemorrhagic shock, aspirin, and ethanol on the biochemical and morphologic changes of experimental pancreatitis were evaluated. Pancreatitis was induced by infusing rats with a supramaximally stimulating dose (5 μg/kg/h) of caerulein. Hemorrhagic shock was established by removing sufficient blood to reduce mean arterial pressure by 30%, where it was maintained for 30 min. Aspirin (25 mg/kg) and ethanol (2 g/kg) were administered through an orogastric tube at 8-h intervals for 48 h. Hemorrhagic shock did not alter the degree of hyperamylasemia, pancreatic edema, cathepsin subcellular redistribution, or in vitro LDH leakage that characterize this model of pancreatitis. Hemorrhagic shock did, however, worsen the morphologic evidence of pancreatic injury. Administration of aspirin with ethanol did not alter the degree of hyperamy-lasemia, pancreatic edema, or subcellular cathepsin redistribution. Aspirin-ethanol pretreatment also did not alter the morphologic severity of pancreatitis.     

Prognostic value of low and high ankle-brachial index in hospitalized medical patients

BackgroundPeripheral arterial disease (PAD) is frequently underdiagnosed in the clinical practice, leading to a lack of opportunity to detect subjects at a high risk for cardiovascular (CV) death. The ankle-brachial pressure index (ABI) represents a noninvasive, objective tool to diagnose PAD and to predict adverse outcome.MethodsABI was determined by means of Doppler velocimetry, in 707 patients, aged 50 years or older, consecutively hospitalized in an internal medicine ward, who were followed-up for at least 12 months in order to assess all-cause and CV mortality.ResultsSymptomatic PAD affected 8% of the population while the prevalence of PAD, defined as ABI < 0.90, was 29%; high ABI (> 1.40) was found in 8% of the patients. After a mean follow-up period of 1.6 years, both low and high ABI were independently associated with CV mortality with a hazard ratio of 1.99 (p = 0.016) for low and 2.13 (p = 0.04) for high ABI, compared with normal ABI (0.90–1.40). High ABI also independently predicted all-cause mortality with a hazard ratio of 1.77 (p = 0.04).DiscussionABI measurement reveals a large number of individuals with asymptomatic PAD among those hospitalized in an internal medicine department. An increased mortality was observed in patients with both low and high ABI. Hospital admission for any reason may serve as an opportunity to detect PAD and start appropriate preventive actions.     

In face of the increasing efficacy of lipid-lowering therapy, is there still a place for LDL-apheresis?

Based on a large body of evidence, high LDL-cholesterol concentrations in blood is a key factor of coronary heart disease (CHD). Overall, the observational studies show a curvilinear relationship between blood cholesterol level and coronary heart disease risk. Even more relevant are the randomised trials, firmly establishing that within just a few years a cholesterol-lowering therapy confers a dramatic effect on cardiovascular morbidity and mortality. More recent studies indicate that there is a greater risk reduction in those subjects achieving lower low-density lipoprotein cholesterol (LDL-C) levels--i.e. lower is better. While this favours aggressive therapy, it is nevertheless imperative to precise patients selection for every therapy that entails a major commitment for the patient and medical community. Therefore, well-defined criteria for use of LDL-apheresis have yet to be established in the light of the expanding therapeutic armamentarium. Based on the current knowledge of the impact of statin therapy and anticipating that new options will further optimize the management of dyslipidemia in high-risk patients, we propose a reliable assessment of the effects of LDL-apheresis.