Autologous haematopoietic stem-cell transplantation in multiple sclerosis: benefits and risks

Autologous haematopoietic stem-cell transplantation has been evaluated over the last years as a possible new therapeutic strategy in severe forms of multiple sclerosis unresponsive to the approved therapies. Up to now, more than 400 patients have been treated and numerous are the phase I and phase II studies which addressed the feasibility of this treatment, the efficacy, side effects and transplant-related mortality. The clinical response is strongly related to the intensity of the conditioning regimen utilized as well as to the phase of the disease course in which the therapy is carried out. Rapidly evolving multiple sclerosis with a relapsing–remitting clinical course and MRI signs of activity are the cases that can take more advantage. The risk of mortality, which dropped in the last years to 2–3%, is still the main problem of this powerful therapy.     

A feasibility study of quantitative respirator fit testing by controlled negative pressure

The feasibility of using a direct measure of respirator leakage flow rate as a quantitative index of respirator face seal fit has been explored through the use of a new controlled negative pressure method. The method is based on exhausting air from a temporarily sealed respirator facepiece at a rate sufficient to generate and then sustain a constant negative pressure inside the facepiece while the wearer holds his breath. The magnitude of the negative pressure is preselected to replicate the mean inspiratory pressure inside the mask during normal wear. With the air-purifying paths into the respirator temporarily blocked, measurement of the exhaust flow rate yields a synonymous measure of the leakage flow rate into the mask during inspiration under normal use conditions. The feasibility of using the new method to quantify respirator fit was assessed in a preliminary study that compared its performance with a quantitative fit test method based on the use of dichlorodifluoromethane as a challenge agent. Study data exhibit a high degree of correlation (r greater than 0.99) and no significant difference between the two methods over a range of controlled mask leakage rates. A major advantage of the new method is that a worker can be fit tested with his assigned respirator because the method does not require a destructive sampling probe. Other significant benefits compared to current methods used to quantify respirator fit appear to include (1) ease of test administration, (2) simplicity of test components, (3) lack of a potentially toxic challenge agent, (4) a straightforward calibration procedure, (5) multiple test capability, (6) immediacy of test results, and (7) field portability of the test system.     

Human immunodeficiency virus infection in urban Rwanda. Demographic and behavioral correlates in a representative sample of childbearing women

OBJECTIVE.--To determine behavioral and demographic risk factors for human immunodeficiency virus (HIV) infection in central Africa. DESIGN.--Cross-sectional survey. SETTING.--Kigali, Rwanda. PARTICIPANTS.--A representative sample of 1458 childbearing women aged 19 to 37 years who were recruited from outpatient prenatal and pediatric clinics at the only community hospital in the city. MAIN OUTCOME MEASURE.--Antibodies to HIV assessed by enzyme immunoassay and confirmed by Western blot or indirect immunofluorescence. RESULTS.--The HIV seroprevalence was 32% overall. Infection rates were higher in women who were single, in those in steady relationships that began after 1981, and in the 33% of women reporting more than one lifetime sexual partner. Women in legal marriages or monogamous partnerships had lower rates of infection, but even low-risk women had prevalences on the order of 20%. History of venereal disease in the past 5 years, although the strongest risk factor in a multiple logistic analysis (odds ratio, 2.7; 95% confidence interval, 2.0 to 3.7), was reported by only 30% of those infected. Having a male sexual partner who drank alcohol or who had higher income were significant risk factors for HIV infection in the multivariate analysis, but use of oral contraceptives and having an uncircumcised partner were not. CONCLUSIONS.--The epidemic of the acquired immunodeficiency syndrome in Rwanda has spread beyond high-risk groups to the general population of women without known risk factors. For most of these women, a steady male partner is the source of their HIV risk and therefore a vital target for intervention efforts.     

Synthesis and antiviral activity evaluation of 3'-fluoro-3'-deoxyribonucleosides: broad-spectrum antiviral activity of 3'-fluoro-3'-deoxyadenosine

Five 3'-fluorinated ribonucleosides were prepared and evaluated for their inhibitory properties against different viruses. The synthesis of these compounds was achieved by treatment of 2',5'-di-O-tritylated nucleoside analogues possessing a xylo-configuration with diethylaminosulfur trifluoride, followed by deprotection. 3'-Fluoro-3'-deoxyadenosine was active against a broad range of viruses, encompassing both DNA viruses [pox (vaccinia)], single-stranded (+) RNA viruses [picorna (polio, Coxsackie B), toga (sindbis, Semliki Forest)] and double-stranded RNA viruses (reo). In its antiviral activity spectrum 3'-fluoro-3'-deoxyadenosine clearly differed from those adenosine analogues that are known as inhibitors of S-adenosylhomocysteine hydrolase. 3'-Fluoro-3'-deoxyadenosine also proved effective in vivo, in inhibiting tail lesion formation in mice inoculated intravenously with vaccinia virus.     

Quantitative assessment of ALZ-50 immunoreactivity in Alzheimer's disease.

A quantitative assay for ALZ-50 immunoreactivity was evaluated in samples of superior temporal gyrus taken at autopsy from 13 Alzheimer patients and 11 controls. The assayable immunoreactivity appears to be stable for at least 24 hours postmortem but was lost with formalin fixation. The mean value of the Alzheimer patients was tenfold higher than that of the controls (P less than .002). The values of four Alzheimer samples overlapped with the low levels seen in controls, but no controls had elevated levels. In this sample population, therefore, the assay had a sensitivity of 69% and specificity of 100%.     

Mechanics and function in heart morphogenesis.

For years, biomechanical engineers have studied the physical forces involved in morphogenesis of the heart. In a parallel stream of research, molecular and developmental biologists have sought to identify the molecular pathways responsible for embryonic heart development. Recently, several studies have shown that these two avenues of research should be integrated to explain how genes expressed in the heart regulate early heart function and affect physical morphogenetic steps, as well as to conversely show how early heart function affects the expression of genes required for morphogenesis. This review combines the perspectives of biomechanical engineering and developmental biology to lay out an integrated view of the role of mechanical forces in heart development.     

Activity measurements of the high-energy pure beta-emitters 89Sr and 90Y by the TDCR efficiency calculation technique.

The absolute activities of the pure beta-emitters 89Sr and 90Y have been determined by a direct method, namely the triple-to-double coincidence ratio (TDCR) efficiency calculation technique. This undertaking has extended further the number of radionuclides that have been standardized by this non-extrapolation liquid scintillation (LS) method. Both measurements were carried out within the framework of international key comparisons under the auspices of the International Bureau of Weights and Measures (BIPM). The TDCR results agreed well with those of other participating national laboratories, most using alternative (tracer) methods.     

The importance of standardization of creatinine in the implementation of guidelines and recommendations for CKD: implications for CKD management programmes.

BACKGROUND: In an attempt to reduce late referral and to improve the care of patients with chronic kidney disease (CKD), different organizations have issued guidelines on when to refer patients to the nephrologist. Most suggest referral of patients with a GFR below 60 ml/min/1.73 m2, and demand referral if the GFR is below 30 ml/min/1.73 m2. It is recommended to use the abbreviated MDRD equation to estimate GFR. This formula is, however, sensitive to the creatinine assay methodology. In addition, the impact of the implementation of such guidelines on the nephrology practice has never been evaluated. This study (i) identifies the true burden of CKD in a population and simulates the effects of a 100% implementation of the guidelines on the nephrology work load, and (ii) evaluates the validity of the estimated GFR using the abbreviated MDRD formula when routinely provided. METHODS: Different laboratories (both hospital and private) in our region were asked to report on all the serum creatinine values performed during the first week of December 2004. If patients had more than one determination, only the lowest serum creatinine value was retained. Patients already known to a nephrology unit were not included. GFR was calculated using the abbreviated MDRD, using the serum creatinine as reported by these laboratories, or after correction to the MDRD-standard using different published equations. RESULTS: 20,108 patients, with a mean age of 53.4+/-16.2 years, 48% females, had at least one serum creatinine determination in the observation period. According to the K/DOQI CKD classification, 20.2, 1.6 and 0.8% of females and 13.3, 1.6 and 0.6% of males were in stage 3, 4 and 5, respectively, when the abbreviated MDRD formula was used with the serum creatinine value as reported by the laboratories. Important differences in classifications were obtained when the different correction formulae for creatinine were applied. According to the current recommendations, this would lead to a mandatory referral of 1650-2400 CKD stage 4 patients per 100 000 inhabitants and a suggested referral of another 4100-15 360 CKD stage 3 patients per 100,000 inhabitants to a nephrology unit. CONCLUSION: Implementation of the current guidelines for referral of CKD patients to nephrologists would lead to an overload of the nephrology care capacities. Large differences in estimated GFRs with different corrections for serum creatinine are observed, resulting in important CKD classification differences. Standardization of serum creatinine assays is mandatory before guidelines, and especially the routine provision of the estimated GFR by the abbreviated MDRD formula, can be implemented in clinical practice.