Evaluation of a peer intervention project in the hospital setting to improve the health-related quality of life of recently diagnosed people with HIV infection.

PURPOSE: This study aims to assess the impact of a peer intervention programme in the hospital setting to improve the health-related quality of life (HRQoL) of people recently diagnosed with HIV infection. METHODS: A quasi-experimental single-group study with pre- and post-measurements was conducted. The peer intervention programme consisted of four sessions that took place at the following times: (1) the day of diagnosis, (2) the day when the results of the analyses were collected and ART (antiretroviral therapy) began, (3) one month after the start of ART, and (4) four months after the start of ART. The dependent variables were HRQoL and several of its psychological predictors. Change in the dependent variables was analysed through repeated measures, variance analysis and covariance analysis. Forty-three people with HIV participated in the intervention (40 men, mean age = 39.14). RESULTS: A significant positive evolution was found in all the predictors of HRQoL, except avoidant coping (p < .05). A positive evolution was also found in all HRQoL dimensions (p < .05). There was a significant increase in CD4 cells/mm3 lymphocytes (p < .0001) and in the CD4/CD8 ratio (p < .001). The positive differential scores in the psychological health and social relationship dimensions influenced the increase in CD4 cells/mm3 lymphocytes (p = .012, p = .13). The increase in the social relations dimension score and overall health perception influenced the recovery of the CD4/CD8 ratio (p = .044; p = .068). CONCLUSIONS: Peer intervention improved the HRQoL of people recently diagnosed with HIV, and enhanced psychological health and social relationships covariate with their immunological recovery. This study represents an essential advance in evaluating peer intervention programmes for positive prevention.

New diketopiperazines as vectors for peptide protection and brain delivery: Synthesis and biological evaluation.

New strategies allowing the transfer of molecules, especially peptides, through the blood-brain barriers are a major pharmacological challenge for the treatment of brain diseases. The present study aims at evaluating in vivo the cerebral bioavailability of carrier systems, based on small and functionalizable 2,5-diketopiperazine (DKP) motifs. We studied 2 different cyclo(Lys-Lys) DKP scaffolds alone and a cyclo(Lys-Gly) DKP carrier bearing as peptide model, the tau protein hexapeptide VQIVYK sequence. The different carrier systems were synthesized and radiolabeled using one of the free domains. The stability, biodistribution, and ability to cross blood-brain barrier were investigated in vivo in mice for 99m Tc-DKP scaffolds, 99m Tc-HVQIVYK peptide alone, and 99m Tc-DKP-VQIVYK. 125 I-labelled bovine serum albumin was used as negative control for brain uptake. Both radiolabeled DKPs scaffolds and 99m Tc-DKP-VQIVYK showed a high stability, while peptide 99m Tc-HVQIVYK alone was quickly degraded in vivo. The presence of 99m Tc-DKPs scaffolds and 99m Tc-DKP-VQIVYK was observed in the ventricular and subarachnoid spaces and to a lower extent in the brain parenchyma up to 45 minutes post-injection in mice. This work highlights the potentiality of DKP scaffolds as vectors to transport peptides into the brain by limiting proteolysis and favoring cerebral bioavailability.

[Viral biosafety, biosecurity, and bioterrorism]. / Biosécurité, biosureté et bioterrorisme viral.

Intentional release of infectious agents has always been considered as a possible weapon. Today this risk has expanded from use for wartime mass destruction to small-scale terrorist acts. Viruses, some of tropical origin, constitute a special biological hazard for several reasons: great infectious potential, adaptability to the host, difficulty for diagnosis in the hospital, and absence of specific treatment for the main agents involved. Handling of the dangerous biological agents requires special biocontainment laboratories equipped and classified according to increasing risk up to level 4. This article discusses the modalities of classification.

Standardization of needlestick injury and evaluation of a novel virus-inhibiting protective glove.

Rubber surgical gloves worn as a barrier to prevent contamination from body fluids offer relative protection against contamination through direct percutaneous injuries involving needles, scalpel blades or bone fragments. To determine the main experimental parameters influencing the volume of blood transmitted by a hollow-bore needle (worst case scenario) during an accidental puncture, we designed an automatic puncture apparatus. Herpes simplex type 1 virus (HSV1), a model for enveloped viruses, was used as a 'marker' in an in-vitro gelatine model. Of the experimental parameters studied, the most critical influences were found to be needle diameter and puncture depth, whereas puncture speed, puncture angle and glove-stretching feature appeared to be less influential. A single glove reduced the volume of blood transferred by 52% compared with no glove, but double gloving offered no additional protection against hollow-bore needle punctures. Using 'standardized' puncture conditions, the virus-inhibiting surgical glove G-VIR elicited an 81% reduction in the amount of HSV1 transmitted as compared with single or double latex glove systems.

Evaluation of a Crimean-Congo hemorrhagic fever virus recombinant antigen expressed by Semliki Forest suicide virus for IgM and IgG antibody detection in human and animal sera collected in Iran.

Crimean-Congo hemorrhagic fever virus (CCHFV) is transmitted to humans by ticks or by direct contact with infected blood. It causes severe, often fatal, hemorrhagic diseases in humans but infection in animals is asymptomatic. CCHFV can spread from person to person and has caused many nosocomial outbreaks. Because the virus is very pathogenic for humans it must be manipulated in a biosafety level 4 (BSL4) laboratory, rendering the production of antigen for serological diagnosis difficult. To replace the native antigen, we produced a recombinant nucleoprotein expressed in mammalian cells via the recombinant Semliki Forest alphavirus replicon and developed an indirect immunofluorescence assay (IFA) as well as an enzyme-linked immunosorbent assay (ELISA) by immunocapture to detect IgM and IgG in human and animal serum. Using these methods, we analyzed clinical samples from human patients and sera from domestic animals collected in Iran and we show that this novel antigen provides a novel, sensitive and specific tool for CCHF diagnosis.

Nonhuman primates are relevant models for research in hematology, immunology and virology.

Nonhuman primates have been used for biomedical research for several decades. They have proved to be models that are relevant to humans because of the high level of gene homology which underlies physiological and biochemical similarities. The similarity of monkeys to humans has been used to investigate pathophysiological mechanisms in hematology, immunology and virology. New therapeutic procedures can be assessed in primates by using materials, in particular pharmacological reagents, and methods designed for humans. The relevance of these models also relies on the use of species-specific pathogens and the availability of recombinant, homologous cytokines. The introduction of more and more sophisticated cell and gene therapy protocols in hematopoietic cell transplantation and immunotherapy requires the development of preclinical trials similar to clinical settings. For several decades now, baboons and cynomolgus/rhesus monkeys have been the most useful primate models in experimental hematology, and this has contributed to numerous therapeutic advances. Primate models of AIDS have been developed to study the pathogenesis, transmission and immune responses to infection, and to test vaccines and drugs. Primate research should be restricted in quantity, and mainly designed with the aim of removing uncertainty as to the safety and clinical benefit to the patient, of new biomedical protocols.

Transient adult T-cell leukemia/lymphoma picture during varicella infection in an HTLV-1 carrier.

HTLV-1 (human T-lymphotropic virus type 1) is associated with tropical spastic paraparesis, adult T-cell lymphoma (ATL), and also with opportunistic infections. The risk for developing ATL in HTLV-1 healthy carriers is low, between 1 and 4%. Nothing is known about the events promoting the evolution from the healthy carrier state to symptomatic ATL. We describe the case of a 44-year-old French Caribbean man with a chronic and recurrent strongyloidiasis in which the occurrence of a hemorrhagic and necrotic varicella led to the discovery of an infection by HTLV-1 and an acute form of ATL. All hematological data were normal before the onset of varicella. ATL completely disappeared at the same time as the varicella healed. This leads us to hypothesize that acute infections such as the reactivation of varicella-zoster may act as a promoting factor for the development of ATL in healthy HTLV-1 carriers.

[Risk of smallpox, vaccination, bioterrorism]. / Risque de variole, vaccination et bioterrorisme.

The use of the smallpox virus as a biological weapon is very old. Confronted with a high probability of a current bioterrorist menace, counteracting strategies have been developed. One of the principle aims relies on the vaccination of teams dedicated to the management of persons infected and the stocking of vaccine for the whole population of a country. Following worldwide eradication of the disease, preventive vaccination was topped in 1978 in France for the primo-vaccination, and in 1984 for repeat vaccinations. The various strains used in the first generation vaccinations are weakened living vaccine, the natural host and origin of which is unknown. Second and third generations vaccines are under study; the principle objective is to obtain efficacy with a minimum of side effects. There are two types of adverse events, generally observed with the first generation vaccines: the first, extremely rare, can be life-threatening; the others, more frequent (10 to 15% of patients) are benign. In emergency situations, in the presence of smallpox, there should be no absolute contraindications to vaccination. In the bioterrorist context, massive vaccination campaigns of the population are unadvisable (because of the considerable risk of death and severe adverse events) in the absence of any real permit, in each case, definition of the vaccinal strategy to be adopted.

Highly sensitive Taqman PCR detection of Puumala hantavirus.

An increasing number of clinical cases of Hantavirus infections have been reported from various regions in Asia, Europe and North America. Hantaviruses (family Bunyaviridae, genus Hantavirus) are enveloped and possess a single-stranded trisegmented RNA genome of negative polarity. Rodents or insectivores are natural hosts of hantaviruses and transmit the virus to humans chiefly by aerosolisation. These viruses are the causative agents of haemorrhagic fever with renal and pulmonary syndromes. In the northeast of France, Puumala hantavirus causes, every year, more than 150 mild forms of haemorrhagic fever with a renal syndrome known as nephropathia epidemica. Serological tests may lack sensitivity for diagnosing early stages of infection and virus isolation is limited because it grows poorly in cell culture. Since reverse transcription (RT)-PCR amplification is an efficient method for detecting viral genomes in patient specimens, we developed an assay using a Taqman probe and compared it with the classical RT-PCR amplification. To achieve this goal, a Puumala strain was grown in Vero E6 cells and RNA extracted from the culture supernatant. We found that the semi-nested RT-PCR detected a minimal amount of 300 TCID(50) mL(-1), while the Taqman PCR allowed detection of less than 10 TCID(50) mL(-1 )and provided a quantitative analysis.

In vitro inhibition of Chikungunya and Semliki Forest viruses replication by antiviral compounds: synergistic effect of interferon-alpha and ribavirin combination.

Chikungunya virus (CHIKV) and Semliki Forest virus (SFV) were used in our laboratory to screen active antiviral compounds against viruses of the Alphavirus genus. Antiviral activity was estimated by the reduction of the cytopathic effect of each alphavirus on infected Vero cells and by virus titer reduction. Cytotoxicity was evaluated by determining the inhibition of Trypan blue exclusion in confluent cell cultures and by the evaluation of the inhibitory effect on cell growth. With CHIKV and SFV, the selectivity indices of human recombinant interferon-alpha and iota-carrageenan were much higher than that of ribavirin, which has been previously investigated for its inhibitory effect on alphavirus infections. Compared to ribavirin, 6-azauridine was more effective against CHIKV and showed a similar antiviral activity against SFV. IFN-alpha2b, glycyrrhizin, 6-azauridine, and ribavirin caused a concentration-dependent reduction in the virus yield with CHIKV and SFV. Moreover, the combination of IFN-alpha2b and ribavirin had a subsynergistic antiviral effect on these two alphaviruses and should be evaluated for the treatment of these infections.

Use of cRNA digoxigenin-labelled probes for detection of enteroviruses in humans and in the environment.

A dot blot hybridization test for enteroviruses is described using non-radioactive digoxigenin-labelled probes and a chemiluminescent detection. The use of a 5' non-coding riboprobe which detects all enteroviruses and a VP1 probe that detects the three serotypes of polioviruses allows the rapid detection of polioviruses and non-polio enteroviruses in human specimens or environmental water samples. The assay is strictly enterovirus specific and sensitive (800 fg RNA) and offers several advantages over conventional diagnosis or radioactive probes.

Lactate metabolism and glucose turnover in the subterranean crustacean niphargus virei during post-hypoxic recovery

Glucose and lactate metabolism were studied in a hypoxia-resistant subterranean crustacean, Niphargus virei, using an injection of l-[U-14C]lactate and tracer d-[6-3H]glucose either in normoxic conditions or after a 24 h exposure to severe hypoxic. Post-hypoxic animals (H animals) were compared with two treatment groups of normoxic animals. In the first normoxic group (NLL animals), animals were simultaneously injected with labelled and unlabelled lactate to obtain a lactate load similar to that of H animals. In the second normoxic group (N, control animals), animals were only injected with labelled lactate. During a 24 h recovery period, the incorporation of 14C and 3H into glycogen, lactate, glucose, amino acids, lipids and CO2 was measured. During recovery, glucose turnover rate was enhanced in H and depressed in NLL compared with N animals. However, when energy expenditure was taken into account, the changes were due only to a reduction of glucose turnover rate by lactate load. It was concluded that gluconeogenesis was not the main source of glyconeogenesis. Equivalent lactate loading in NLL and H animals resulted in an equivalent enhancement (fivefold) of lactate utilization in both groups when energy expenditure was taken into account. Lactate label incorporation appeared later in glycogen than in glucose, but remained high 24 h after the injection. Since glucose is mainly an extracellular metabolite, this observation may be consistent with the hypothesis of two distinct sites for glycogen restoration in hypogean crustaceans: a gluconeogenic organ (a liver equivalent) and a glyconeogenic organ (a muscle equivalent). The oxidative pathways of glucose and lactate were depressed in post-hypoxic N. virei and to a lesser extent in the NLL group. Since there is no evidence of marked protein utilization, it is postulated that, during recovery, repayment of the O2 debt relies on an increase in lipid utilization. During recovery from severe hypoxia or after a lactate load, the subterranean N. virei appeared to implement a strategy of lactate removal quite different from that observed in epigean crustaceans, favouring lactate-supported gluco- and glyconeogenesis and rapid glycogen replenishment instead of rapid lactate removal via oxidative pathways.

Rapid inactivation of vaccinia virus in suspension and dried on surfaces.

A bioterrorist attack with smallpox virus would be disastrous with a 30% disease fatality rate. Such an outbreak would require biomedical laboratories for diagnosis and analyses and extensive use of clinical care facilities for patient quarantine. Safe decontamination procedures will have to be in place in order to limit the spread of the disease. In order to fulfil this need, Sanytex, a new non-corrosive commercial solution containing quaternary ammonium, aldehydes, alcohol and detergent, was tested with a view to using it in decontamination procedures. Vaccinia virus was used in this investigation as a model for smallpox virus. We determined exposure time and the concentration of Sanytex required to inactivate the virus in suspension and dried on surfaces in the presence of protein (up to 70 mg/mL). After 3 min incubation, Sanytex at a concentration of 3% led to a complete inactivation (virus titre reduction >10(4)-fold of vaccinia virus in suspension containing protein up to 30 mg/mL. A virus suspension containing 70 mg protein/mL, simulating biological fluids, was decontaminated with 10% Sanytex after 3 min. After 10 min, Sanytex at a concentration of 30%, applied on to a dried vaccinia virus contaminated surface in the presence of protein (10 mg/mL before desiccation), led to complete decontamination of the surface. Thirty minutes exposure with 30% Sanytex was necessary for a virus titre reduction of >10(4)-fold on a surface contaminated with a dried suspension of vaccinia virus in the presence of protein at 70 mg/mL. Sanytex is not corrosive, not toxic to environment and stable for up to three months even diluted. Its virucidal effect was preserved when used under pressure in a fire-hose nozzle. These results support the use of Sanytex for decontamination of biological fluids and surfaces contaminated by the smallpox virus.

Treatment of radial head fractures using a fibrin adhesive seal. A review of 15 cases.

Since 1986 we have treated 15 patients with fractures of the head of the radius limited to one or two fragments (Mason type II) by open reduction and internal fixation with the Fibrin Adhesive System. At a mean follow-up of over two years, all but one of the results were excellent. This method is recommended for the treatment of selected fractures of the radial head followed by early mobilisation.

External fixation and secondary intramedullary nailing of open tibial fractures. A randomised, prospective trial.

We performed a prospective, randomised trial in 39 patients with open tibial fractures treated initially by external fixation to compare cast immobilisation (group A) and intramedullary nailing (group B) as a sequential protocol planned from the onset of treatment. The results showed that group B achieved faster union (p < 0.05) than group A with less malunion or shortening and a greater range of movement. Patients treated by intramedullary nailing required fewer radiographs and outpatient visits (p = 0.0015) and had a more predictable and rapid return to full function. We feel that these severe fractures are better treated by delayed intramedullary nailing and that this has an acceptable rate of complications.

Kinetics of cadmium accumulation and elimination in carp Cyprinus carpio tissues.

Carp (Cyprinus carpio) were tested for cadmium accumulation and elimination during and after a simulated pollution exposure. Fish were distributed in two 1000-l indoor concrete aquaria supplied with a continuous flow (8 l min(-1)) of well water. The cadmium concentration was maintained at 53 microg l(-1) in one aquarium and 443 microg l(-1) in the other aquarium for 127 days. The exposure phase was followed by a 43-day depuration period. The cadmium accumulation in liver, kidney and muscle was measured by means of ICP-MS. The data showed that cadmium exposure produces significant cadmium uptake in tissues. Cadmium concentrations increased sharply in kidney and liver, whereas the pollutant level in muscle was only significant after 106 days. After 127 days of Cd exposure (53 microg l(-1)), the cadmium concentration in kidney was 4-fold higher than in liver and 50-fold higher than in muscle for a toxic level of 53 microg l(-1). At a Cd of 443 microg l(-1), kidney cadmium content was 2-fold higher than in liver and 100-fold higher than in muscle. In kidney and liver, the toxic concentration increased as the concentration of pollutant in water increased. During the 43 depuration days, the loss of accumulated cadmium was rapid and immediate in muscle. Conversely, no loss of cadmium was observed in kidney and liver.

Effects of small ruminal boluses used for electronic identification of lambs on the growth and development of the reticulorumen.

Fifty-four male lambs were used to study the effects of two types of small electronic boluses on the dimensions and epithelial characteristics of their reticulorumen. Newborn lambs were assigned according to bolus type and age of application to the following treatments: 1) control (C, n = 21), without bolus; 2) mini (M, n = 21), identified with a 9.3 x 37.4-mm, 5.2-g bolus during the first week after birth; and 3) small (S, n = 12), identified with a 15.0 x 39.1-mm, 20-g bolus after weaning at wk 5, when lambs weighed more than 12 kg. After weaning, lambs were given ad libitum access to concentrate and barley straw. Six lambs were euthanized at the start of the experiment to measure initial reticulorumen characteristics. Ten lambs (five from M and five from C treatments) were slaughtered at weaning and 24 (eight per treatment) were slaughtered when they reached 24 kg. After bolus recovery, the reticulorumen was emptied and filled with polyurethane foam to obtain reticulorumen casts. Weight of the emptied reticulorumen and volume of the casts were measured. Four representative lambs from each treatment were also slaughtered at 24 kg, and their reticulorumen used to evaluate papillae size, number of dead cells, and degree of keratinization of both the reticulum wall and the rumen wall epithelia. Weight at weaning (13.8 kg), age at the end of fattening (65 d), and mortality rate (4%) did not differ among treatments. Retention rate for M and S boluses was 82.4 and 100%, respectively. Fresh weight and volume of the reticulorumen did not differ among treatments at weaning (130 g and 1,679 mL) or at the end of the fattening period (640 g and 5,931 mL). Lambs in the M treatment had greater (P < 0.05) rumen papillae size and lower (P < 0.10) keratinization than C lambs; values in the S lambs were intermediate between M and C lambs. Neither the M nor S type of bolus affected dimensions of the reticulorumen, but the earlier presence of M boluses induced a greater papillae size, with no negative effects on health and fattening performances of young lambs.

Stabilization of the lower thoracic and lumbar spine with the internal spinal skeletal fixation system and a cross-linkage system. First results of treatment.

Since 1986, 19 patients with 21 fractures of the thoracic and lumbar spine have been treated with the AO Internal Spinal Skeletal System. Of these fractures, 17 were burst fractures, 2 were seatbelt fractures and 2 were fracture-dislocations. All the patients in the series had a minimum follow-up of 12 months. There were 4 important losses of correction and two deep infections. In the majority of patients the postoperative reduction deteriorated during follow-up. The addition of 1 or 2 DTT appears to give the system more stability.

[Incidence of nosocomial infections in a military hospital]. / Incidence des infections nosocomiales dans un hôpital des armées.

Over a 2-year period, 479 cases of nosocomial infections were identified in our hospital by a surveillance method based on the bacteriological laboratory results. The monthly incidence rate ranged from 1.8 to 4 percent of all in-patients. With this method, a 2 percent background noise and a 4 percent alarm threshold could be defined. The most frequent nosocomial infections were urinary tract infections (77 percent), purulent skin infections (12 percent) and septicaemias (10 percent). Compared during 15 days with the most sensitive surveillance method of the National Nosocomial Infections Surveillance System, our method proved insufficient to detect nosocomial lung infections and superficial surgical wound infections. On the other hand, it was highly satisfactory to watch for urinary tract infections and septicaemias. Improvements that would not put a heavy burden on the work of clinical departments are suggested.

[Malaria: chloroquine resistance]. / Paludisme: la résistance a la chloroquine.

Chloroquine remains the most commonly antimalaric drug utilized all around the world (340 t in 1988). Its efficiency is linked to its action on the digestive vacuole of plasmodium. Since 1957, the areas of resistance are spreading over of an alarming way, striking all continents. 3,000 cases of malaria are imported in France each year, and 90% of the strains tested in vitro by incorporating tritium hypoxanthine are resistant to chloroquine. The resistant parasites are able to exclude chloroquine from their cytoplasm and produce in great number two genes to synthetize a glycoprotein, probable agent of cellular exclusion of the antimalaric drug. Despite of it, to prescribe chloroquine in prophylaxis remains indispensable, because the risk of severe malaria due to some sensitive strains of Plasmodium falciparum.