In vivo fertility of bull semen following cryopreservation with an LDL (low density lipoprotein) extender: preliminary results of artificial inseminations.

A semen extender made with low density lipoproteins (LDL) has been used instead of a standard extender that is already available on the market for the cryopreservation of bovine semen. However, in order to extend its use to artificial insemination centres, in vivo fertility studies were required. Semen was taken from three bulls and frozen-thawed in two extenders: the LDL extender and a standard Tris-egg-yolk (20%) extender used by AI centres. The quality of the semen was assessed prior to artificial insemination: motility was assessed using an image analyser (Computer Assisted Semen Analysis (Hamilton Thorne)), and the integrity of the plasma membrane was assessed using the hypo-osmotic test (HOS test). For the first time, gestations were obtained following the artificial insemination of cows in the field (n=193) with semen that had been frozen-thawed in the LDL extender. No significant difference (p>0.05) was detected between the success rates of AI between the semen that had been frozen-thawed in the LDL extender (59.2%) and the control extender, Tris-20% egg yolk (65.3%). In conclusion, the in vivo fertility of semen that has been frozen-thawed in the LDL extender is maintained since gestations are obtained following AI.

Modeling and evaluation of compliance to water quality regulations in bathing areas on the Daoulas catchment and estuary (France).

The microbiological quality of waters in estuaries determines their acceptability for recreational uses. Microbiological contamination often results from urban wastewater discharges or non-point source pollution (manure spreading), and can cause bathing zones to be closed. European regulations (EC/7/2006) have proposed standards (500 E. coli/100 ml) for the acceptability areas for bathing. In this study, two models were associated to simulate contamination: SWAT on a catchment and MARS 2D in the downstream estuary. After river flow calibration and validation, two scenarios were simulated in SWAT, and E. coli fluxes obtained at the main outlet of the catchment were then introduced into MARS 2D to follow E. coli concentrations in the estuary. An annual evaluation of compliance to bathing area water quality standards was then calculated, linked with daily rainfall classes. Water quality in the estuary was below the standard on 13 days, including 5 days with rainfall superior to 10 mm, due to faecal contamination from soil leaching by rain, and 5 days with rainfall ranging from 0.1 to 5 mm/day, due to the high frequency of this level of rainfall. To conclude, this study allowed us to demonstrate the efficiency of models to gain a better understanding on water quality degradation factors.

Does selenium exert cardioprotective effects against oxidative stress in myocardial ischemia?

In the mid-1960s, a small number of scientists postulated the role of oxidative stress and oxygen-derived free radicals in the pathophysiological mechanisms underlying ischemic heart disease. However, because of the technical difficulty of measuring free radicals and quantitating oxidative damage, it was very difficult to prove that free radicals could contribute to cell pathology. The role of oxidative stress in biological systems was not definitely recognized until the early 1980s when measurement of short-lived oxygen-derived reactive species was made possible by the advent of sophisticated techniques such as EPR spectroscopy or fluorescent probes. These enabled both the study of free radical biochemistry and the acquisition of useful information about the nature and consequences of free radical-induced protein and lipid oxidation. The hypothesis that reactive oxygen species mediate cellular damage produced upon reperfusion of ischemic myocardium has gained considerable support during the past 10-15 years. Several experimental studies indicated that the administration of antioxidant enzymes or non-enzymatic antioxidants offers a significant degree of protection against ischemic damage, improving functional recovery and reducing morphological alterations to cardiomyocytes. In this context, selenium, as an essential component of glutathione peroxidase, plays a critical role in protecting aerobic tissues from oxygen radical-initiated cell injury.

Quinine pharmacokinetics and pharmacodynamics in children with malaria caused by Plasmodium falciparum.

The aim of the present study was to assess the pharmacokinetics and the efficacy of a shorter than usual 5-day quinine treatment given orally to children in Cameroon with malaria caused by Plasmodium falciparum. Quinine (8.3 mg of base per kg of body weight every 8 h) was administered as a 2% formiate salt syrup for 5 days to 30 children (age range, 0.55 to 6.7 years) with uncomplicated falciparum malaria (initial parasitemia, 1.4 x 10(3) to 1.8 x 10(5)/microl). Quinine concentrations in plasma samples (five to nine per patient) were measured by liquid chromatography on days 1 to 3. Parasitemia was counted on days 0, 1, 2, 3, 4, 7, and 14. Pharmacokinetic and pharmacodynamic data were analyzed by population approaches by using NONMEM and WinBugs, respectively. The kinetics of quinine were best described by a one-compartment model with time-varying protein binding. Clearance and the volume of distribution were positively correlated with body weight and increased over time. Parasitemia was undetectable from day 3 to 14 in all children. The time to a 4-log reduction of the initial level of parasitemia (Ter) was related to the average quinine concentration from 0 to 72 h (Cav) as Ter = Tmin [1 + (C50/Cav)s], where sigmoidicity (s) is equal to 2, Tmin is the time to eradication at infinite Cav, and C50 is the value of Cav for which Ter is twice Tmin. The C50 distribution was unimodal, and all C50 values were less than 8 mg/liter, while Cav ranged from 5.9 to 18.3 mg/liter. The median (10th to 90th percentile) Ter was 47 h (range, 39 to 76 h). The efficacy of a 5-day treatment course should be evaluated in a larger clinical trial.

Evolution of blood lead levels in urban French population (1979-1995).

BACKGROUND: The aim of the Council Directive of 29 March 1977 of the European Union was to measure non-occupational lead exposure levels in the general adult populations of European countries through biological monitoring. In France, such measurements were carried out during 1979 and 1982 in eight metropolitan areas (having more than 500 000 inhabitants), a period during which the lead content of petrol was decreased. The aim of this study conduct in 1995 was to evaluate the exposure trend to lead. METHODS: In 1995 this measurement was repeated, only in the three largest urban areas (Paris, Marseilles and Lyons). The same sampling method used in the first two campaigns was retained to ensure that the results of 1995 could be compared with those from 1979 and 1982. RESULTS: In these three metropolitan areas, the average blood lead levels decreased by the order of 60 microg/l between the beginning of the 1980's and 1995. This represents a fall of more than 50%. CONCLUSIONS: Certainly car pollution is not the only vector of dissemination of lead in the centre of urban zones, but it is there that the most sustained efforts at eradication have been made. The improvement we have observed is probably due to the policy of eliminating lead from petrol. In conclusion, the blood lead levels in French urban populations seem to have greatly decreased from those of the early 1980s.

Discontinuation of maintenance therapy for cytomegalovirus retinitis in HIV-infected patients receiving highly active antiretroviral therapy.

OBJECTIVE: To study the safety of discontinuing cytomegalovirus (CMV) maintenance therapy among patients with cured CMV retinitis receiving highly active antiretroviral therapy (HAART). METHODS: Patients with a history of CMV retinitis who were receiving anti-CMV maintenance therapy and who had a CD4 cell count > 75 x 10(6) cells/l and a plasma HIV RNA level < 30000 copies/ml while on HAART were included in a multicentre prospective study. Maintenance therapy for CMV retinitis was discontinued at enrolment and all the patients were monitored for 48 weeks by ophthalmological examinations and by determination of CMV markers, CD4 cell counts and plasma HIV RNA levels. T helper-1 anti-CMV responses were assessed in a subgroup of patients. The primary study endpoint was recurrence of CMV disease. RESULTS: At entry, the 48 assessable patients had been taking HAART for a median of 18 months. The median CD4 cell count was 239 x 10(6) cells/l and the median HIV RNA load was 213 copies/ml. Over the 48 weeks, 2 of the 48 patients had a recurrence of CMV disease. The cumulative probability of CMV retinitis relapse was 2.2% at week 48 (95% confidence interval, 0.4-11.3) and that of all forms of CMV disease 4.2%. CMV blood markers remained negative throughout follow-up. The proportion of patients with CMV-specific CD4 T cell reactivity was 46% at baseline and 64% at week 48. CONCLUSIONS: CMV retinitis maintenance therapy may be safely discontinued in patients with CD4 cell counts above 75 x 10(6) cells/l who have been taking HAART for at least 18 months.

[Mycobacterium avium complex disease in HIV seropositive patients: incidence and risk factors before and after the introduction of highly active antiretroviral treatments. Clinical Epidemiology Group of the Information and Care Center for Human Immunodeficiency]. / Mycobacterium avium complex chez les sujets séropositifs pour le VIH: incidence et facteurs de risque avant et après l'introduction des traitements antirétroviraux hautement actifs. Groupe d'épidémiologie clinique des centres d'information et de soins de l'immunodéficience humaine (CISIH).

The objective of this study was to determine the risk factors of the first occurrence of Mycobacterium avium complex disease (MAC) infection among human immunodeficiency virus (HIV)-infected subjects during two different time periods: before and after the introduction of protease inhibitor (respectively, period 1: 1 January 1992 to 31 December 1995, and period 2: 1 January 1996 to 30 June 1998). This study was performed using the French Hospital Database on HIV (FHDH). Subjects were included when their CD4+ cell count was less than 100/mm3. If they did not die or develop MAC within the first 6 months after the inclusion, their follow-up had to be longer than 6 months to be included. Cox's model was used to calculated the relative hazards (RH) of MAC occurrence according to the age and time-dependent variables, such as CD4+ below 50/mm3, previous occurrence of tuberculosis, cytomegalovirus (CMV) infection and other acquired immunodeficiency syndrome (AIDS)-defining disease, nature of antiretroviral treatment and MAC prophylaxis. Among the 14,779 subjects followed during period 1, 1,710 (11.6%) had a diagnosis of MAC infection during their follow-up (incidence: 8.4 +/- 0.2 for 100 persons per year), while only 453 (4.4%) among 10,239 subjects presented this infection during period 2 (2.8 +/- 0.1 for 100 persons per year). Rifabutin regular prescription was a protective factor of MAC occurrence during period 1 (RH = 0.51 95% confidence interval (CI) = [0.37-0.69]), whereas this protective effect was not observed during period 2 (RH = 1.05 CI = [0.63-1.67]). Thus, during the HAART period, the results that we present do not indicate an interest into continuing MAC prophylaxis.

["Population and xenograft" investigation. Preliminary results]. / Enqu¿ete "population et x¿enogreffe". R¿esultats pr¿eliminaires.

The chronic shortage of human organs is the argument for xenotransplantation. In emergencies, acceptability is closely linked to the benefit. Little information is available on attitudes towards xenotransplantation. A poll of the attitudes was carried out, based on a questionnaire with targeted questions and background information. The goal of the study was to have a better understanding of people's attitudes towards xenotransplantation and to know the eventual changes in the answers after having been given information. For 75% of the sample, xenotransplantation would be a future biotechnology. The animal sources that would be considered for xenotransplantation were the pig and monkey. A period of ten years or more is necessary for 69% of the respondents before xenografts are performed routinely; for 19%, five years or less are needed. Human organ donation should be continued, according to 90% of the sample. Roughly, 46.4% support xenotransplantation, though in the case of a life-or-death situation acceptance reaches 65.7%. This level is higher (77%) for relatives or unknown people (71%); 74% of respondents were in favour of using normal animals and a large majority (88%) support research on xenotransplantation. A good level of confidence in medical biotechnology research and practice is suggested by this study, contrary to the results of a European survey on biotechnology.

Impact of highly active antiretroviral therapy on onset of Mycobacterium avium complex infection and cytomegalovirus disease in patients with AIDS.

OBJECTIVES: To assess the impact of highly active antiretroviral therapy (HAART) on the onset of first disseminated Mycobacterium avium complex (MAC) infection and first cytomegalovirus (CMV) disease episode in HIV-infected at-risk patients. METHODS: The incidence of the two infections occurring in at-risk patients was calculated for two periods (January 1995-June 1996 and July 1996-December 1997) using the database of the HIV-infected patients followed in the Infectious Diseases Department at the Pitié-Salpêtrière Hospital in Paris. HAART was progressively introduced in late June 1996 in France. RESULTS: A total of 91 first disseminated MAC infections and 124 first CMV disease episodes were recorded. The incidence of first disseminated MAC infections fell from 13.4 per 100 person-years in the first 18-month period to 2.6 per 100 person-years in the second 18-month period. Similarly, the incidence of first CMV disease episodes fell from 20.9 to 3.5 per 100 person-years. Fourteen patients on HAART developed a first MAC infection, 12 (85.7%) within 2 months of starting HAART. Nineteen patients on HAART had a first CMV disease episode, 10 (52.6%) within 2 months of starting HAART. CONCLUSIONS: HAART led to a five-fold decrease in the incidence of first disseminated MAC infections and a six-fold decrease in first CMV disease episodes, although patients remain vulnerable to both diseases for approximately 2 months after starting HAART.

[Coxiella burnetii pneumopathy on return from French Guiana]. / Pneumopathie à Coxiella burnetii au retour de Guyane française.

Q fever is a worldwide zoonosis but is not often a common cause of fever among travellers returning from the tropics. We report a case of acute Q fever, revealed by a pneumonia and acquired by a traveller in French Guyana. The chest radiography showed alveolar opacities and pleural effusion. Biological abnormalities were elevated liver enzyme levels and thrombocytopenia. The patient improved or the third day of antibiotic treatment. She mentioned that 3 other people she lived with during her trip had been diagnosed with Q fever. A common source outbreak was then suspected. They all stayed in the same farm in French Guyana. Animal exposure occurred there, in particular with a goat and a dog (both were parturient). The disease was probably transmitted by airborne dust to our patient, as no other vectors of transmission were found. Since the clinical presentation of Q fever is not specific, in order for the physician to diagnose it, he must have an awareness of the disease. Our case emphasised that looking for risk factors of Coxiella burnetii exposures is particularly important. Amongst them, the most important seems to be contact with farm animals. The clinician should thus try to trace such a possible contact when treating a case of traveler's Q fever.

Management of CMV retinitis in the era of highly active antiretroviral therapy.

Although the epidemiological features of CMV retinitis is changing in patients receiving highly active antiretroviral therapy (HAART), continued attention must be paid to detect and treat earlier CMV infections in AIDS patients to prevent severe ophthalmic complications. Initial therapy must be based on characteristics of the CMV retinitis and patient conditions. Long term therapy of HAART must be pursued, even in patients with increased CD4 and undetectable HIV viral load, until results from large controlled studies are available. reserved.

Determinants of paradoxical CD4 cell reconstitution after protease inhibitor-containing antiretroviral regimen.

OBJECTIVES: We evaluated the parameters influencing CD4 cell reconstitution after the introduction of highly active antiretroviral therapies in real life, as well as the frequency and the determinants of the discrepancies occurring between virus and CD4 cell count evolution. DESIGN AND METHODS: A total of 317 pre-treated patients starting a protease inhibitor (PI)-containing regimen were prospectively followed for 2 years on an intent-to-treat basis for CD4 cell counts and viral loads. RESULTS: The CD4 cell counts rapidly increased from baseline (50/mm3) by a median of 50/mm3 at month 2 (+0.72 CD4 cells/mm3/day) and up to 137/mm3 at the last follow-up (second slope: +0.16 CD4 cells/mm3/day). Two independent major factors among five parameters tested significantly affected the first phase, which was negatively correlated to the slope of CD4 cell decline before PI initiation, and was positively correlated to baseline CD4 cell counts (P = 0.0001); the second phase was mostly affected by the mean viral load reduction over time (P = 0.0001). Paradoxical CD4 cell reconstitution (15% of cases) was defined by a rapid or slow CD4 cell increase contrasting with a minor or strong viral reduction, respectively. The role of previous CD4 cell decline and the low effect of viral load reduction during the first 2 months explain the early paradoxical CD4 cell responses. The major influence of viral load reduction on the long-term reconstitution, however, reduces such paradoxical responses at 2 years. CONCLUSIONS: Early paradoxical CD4 cell reconstitution after the introduction of a PI are explained by the major influence of previous disease progression on the early CD4 cell increase, whereas the magnitude of viral load reduction over time reduces such paradoxical evolutions in the long term.

Quantitative analysis of cholesterol and cholesteryl esters in human atherosclerotic plaques using near-infrared Raman spectroscopy.

Raman spectroscopy is a non-destructive analytical technique and previous results have shown that qualitative analysis of the lipid component of human atheromatous arteries is feasible. In this paper, we describe a quantitative analytical method for cholesterol and cholesteryl esters in human atherosclerotic plaques, combined with Raman spectroscopic results, using partial least-squares (PLS) regression, a statistical multivariate method based on factorial analysis. Twenty-nine human atherosclerotic pooled samples were studied and the results of Raman spectroscopy coupled with the PLS method were compared to biochemical results. The standard error of prediction was 16.1, 13.6, 1.9, 3.3 and 3.4 mg/g for total cholesterol, free cholesterol, palmitate cholesteryl, oleate cholesteryl and linoleate cholesteryl, respectively. The repeatability of Raman spectroscopy was found to be excellent. Our results show that Raman spectroscopy is a promising technique to obtain a consistent and non-destructive quantitative analysis of cholesterol and cholesteryl esters in human atherosclerotic lesions. In situ and in vivo analysis is a possibility in the near future.

Mercury exposure in French Guiana: levels and determinants.

Mercury is used widely for gold extraction in French Guiana and throughout the entire Amazon basin. To evaluate contamination among the general population, the authors chose individuals who attended 13 health centers and maternity hospitals dispersed geographically across the territory and served Guiana's different populations. Five hundred individuals (109 pregnant women, 255 "other" adults, and 136 children) who received care at one of the centers were selected randomly for this study. Each individual answered a questionnaire and provided a hair sample. The authors determined mercury in hair with atomic absorption spectrometry. The following mean levels of mercury were observed: 1.6 microg/g (95% confidence interval [CI]=1.3, 1.9) among pregnant women; 3.4 microg/g (95% CI=3.0, 3.9) among other adults; and 2.5 microg/g (95% CI=2.1, 3.0) among children. Diet factors contributed the most to mercury levels, especially consumption of freshwater fish (mean=6.7 microg/g for individuals who ate fish more than 5 times/wk) and livers from game. Other factors, including age, dental amalgams, use of skin-lightening cosmetics, and residence near a gold-mining community, did not contribute significantly to mercury levels. Overall, 12% of the samples contained mercury levels in excess of 10 microg/g, but in some Amerindian communities up to 79% of the children had hair mercury levels that exceeded 10 microg/g. The results of this study indicated that (a) diet played a predominant role in total mercury burden, and (b) in some communities, mercury contamination exceeded safe levels.

[Opportunistic infections in patients under highly concentrated antiretroviral therapy]. / Infections opportunistes sous traitements antirétroviraux combinés.

UNLABELLED: VARIABLE RESULTS: The restoration of immunological competence following Highly Active AntiRetroviral Therapy (HAART) has led to promising results concerning cytomegalovirus viremia, atypical mycobacterium infections, and survival in patients treated for non-Hodgkin's lymphomas. The beneficial effect of introducing antiproteases is less clear for other opportunistic infections such as tuberculosis and pyogenic infections. PROPHYLAXIS: In patients with a CD4 count above 240/mm3, it would appear possible to stop primary prophylaxis against Pneumocystis carinii and toxoplasmosis.