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Although infections are often subclinical, herpes simplex virus (HSV) can cause mild to severe diseases, especially in immunocompromised patients. There are few drugs licensed for the treatment of HSV infections. Most target the viral DNA polymerase, such as acyclovir that remains the reference treatment some thirty years after its discovery! Extensive clinical use of this drug has led to the emergence of resistant strains, mainly in immunocompromised patients, these infections can be managed with only two drugs, foscarnet and cidofovir, both much more toxic than acyclovir. This highlights the crucial need for the development of new anti-herpes drugs that can inhibit infection by both wild-type viruses and drug-resistant strains. Over the last few years, significant efforts have been made to set up a range of strategies for the identification of potential new antiviral drugs. One alternative is to develop drugs with different mechanisms of action. The present article reviews potential viral and cellular targets that are now known to be involved in HSV multiplication and for which specific inhibitors with anti-HSV activity, at least in cell culture, have been identified. These drugs inhibit viral proteins involved in viral replication (DNA polymerase, ribonucleotide reductase or helicase-primase complex). Other drugs acting on cellular proteins needed for viral replication have also been described; these drugs are targetting cyclin-dependent kinases or the polyamine biosynthetic pathway.

Resume Objectif. – Nous avons etudie de maniere retrospective une epidemie a adenovirus dans un service d’hospitalisation de nourrissons. Notre objectif etait d’en determiner les modalites de transmission et d’evaluer l’efficacite des mesures de prevention. Patients et methodes. – L’investigation a ete menee en recensant sur une periode d’un an tous les patients ayant un prelevement positif en adenovirus (AdV) et en confrontant cette liste avec celle fournie par le service lorsque l’epidemie a ete suspectee. Nous avons alors consulte les dossiers medicaux de l’ensemble des enfants ayant eu au moins un prelevement positif en AdV. Dans le meme temps, plusieurs membres du personnel ont presente les memes signes cliniques que les enfants. Seule une partie du personnel a pu etre prelevee au niveau rhinopharynge. Resultats. – Sur les neuf patients dont les recherches d’adenovirus etaient positives, six etaient infectes par le serotype 2. Six ont presente une infection nosocomiale certaine et deux une infection nosocomiale probable. Le cas index etait un enfant presentant une diarrhee febrile ayant evolue plus de 48 heures a domicile avant son hospitalisation. La contagiosite a persiste a cause de l’excretion prolongee du virus dans les selles. Les prelevements des personnels sont tous restes negatifs. L’evolution de l’infection a ete benigne chez tous les enfants. Conclusion. – Les mesures de prevention mises en œuvre apres detection de l’epidemie ont permis son eradication.

An HIV-negative infant presented with VZV primary infection during the maintenance therapy for mega-karyoblastic leukaemia. The lesions were initially vesicular and necrotic but became verrucous and hyperkerato tic. A clinical resistance to acyclovir was suspected and confirmed by histologic and virologic studies. The patient was successfully treated by foscarnet. Conclusion: resistance of VZV to acyclovir may occur after a short treatment in a non-AIDS patient. ± Acute leukaemia, acyclovir, foscarnet, Varicella zoster virus

This paper describes an image analysis method to detect and locate Salmonella colonies grown on Petri dishes, on two different media. The colonies are described using their common feature characteristics: black center surrounded by a clear halation. Morphological image analysis functions are preferred to gray levels because of the color inhomogeneity of the background even under optimal lighting. The results obtained show the good ability of this method for detecting and locating but further work is needed to validate it on a greater number of Petri dishes.

The fusarial toxicosis induced by trichothecenes is characterized by common syndromes such as vomiting, inflammation, haemorrhages, diarrhoea and haematological changes. Subchronic ingestion of trichothecenes causes a decrease in circulating white cells. This leukopenic change of animals is reported as a characteristic feature in the best known human disorder: Alimentary Toxic Aleukia (ATA). The aim of the present study was to evaluate whether the haematologic disorders imputed to trichothecenes were a result of myelotoxicity by investigating in an in vitro model. Rat haematopoietic progenitors, Colony Forming Units-Granulocytes and Macrophages (CFU-GM), were cultured in the presence of several concentrations of four trichothecenes; T-2 toxin, HT-2 toxin, diacetoxyscirpenol (DAS) and deoxynivalenol (DON). All these trichothecenes were cytotoxic to rat haematopoietic progenitor cells. It is concluded that haematological disorders observed during trichothecene intoxication of animals are caused by the destruction of haematopoietic progenitors such as CFU-GM cells.

During the year 2000 in the Rhone-Alpes region of France, 559 cases of aseptic meningitis due to enterovirus infection were recorded (approximate incidence, 10 cases per 100,000 population compared with a mean of 0.3 cases during endemic years in this region; P

The culture of human haematopoietic progenitors, Colony-Forming-Unit Granulocyte and Macrophage (CFU-GM), has been performed in the presence of four trichothecenes, T-2 toxin, HT-2 toxin, diacetoxyscirpenol (DAS), and deoxynivalenol (DON). Our results showed that trichothecenes were cytotoxic for human haematopoietic progenitors. This work and the analysis of results described in the literature allowed us to propose that the haematologic lesions observed during human intoxication could be due to a destruction of haematopoietic progenitors such as granulocytic and macrophage colony-forming cells.

Viral investigations were performed during 4 winter seasons (88/89, 89/90, 92/93, 93/94) in children attending day-care centers (DCCs) in the Rhone Département in eastern France. Over the total observation period of 4 winter seasons, 780 children were screened with a nasal swab for the presence of viruses. Of those, 230 (29.5%) had a positive viral culture. The viruses identified were respiratory syncytial virus (RSV), influenza A and B virus, parain-fluenza virus, coronavirus, rhinovirus, adenovirus and enterovirus. During that time, 83 epidemic events in 47 DCC were recorded. A particular virus was judged to be causally related to an epidemic if the identical virus was isolated in ≥ 3 children during the same outbreak of respiratory diseases. Thus, in 51 cases (61.4%) of all epidemics, the following viruses were responsible for an epidemic: RSV (n = 23), coronavirus (n = 10) (only during the season of 1993-1994), influenza A virus (n = 6), rhinovirus (n = 4), enterovirus (n = 4), adenovirus (n = 3) and parainfluenza virus (n = 1). Except for the somewhat surprising accumulation of coronavirus epidemics during the winter of 1993-1994, there were only minor seasonal variations from one year to another. As expected, RSV accounted for about one third of all respiratory tract infections in children attending DCCs and was therefore the most important single causative agent. These results are compared with data from children who did not attend a DCC and were cared for in a private practice. During the winter of 1989-1990, the viral epidemiological survey was performed at the same time and in parallel to a double-blind, placebo-controlled clinical study investigating the efficacy of OM-85 BV, an immunoactive bacterial extract. This study, enrolling 423 children attending DCCs demonstrated a protective effect of OM-85 BV in significantly reducing the risk of recurrent infections of the upper respiratory tract during the treatment period with the compound. 34% of all participating children (75 in the verum group, 70 in the placebo group) were enrolled in an additional virological study. In these patients, RSV was isolated 10 times in the placebo group, but only 5 times in the treated group (p < 0.05) and influenza A virus was present in 4 children in the placebo group, but only in 1 infant in the verum group giving a total of 14 positive virologie results in the placebo group versus 6 in the verum group (p < 0.05). Despite the small numbers of children investigated for their virologie status during respiratory infectious outbreaks, there was a statistically significant difference in the prevalence of virus carriers in favor of the children treated with OM-85 BV. These results corroborate the clinical findings.

Over the period 1983-1990, 10 cases of infective native-valve endocarditis as a result of Chlamydia were seen. All patients were men, with a mean age of 42 years, and none had a history of exposure to Chlamydia psittaci. Symptoms, such as weight loss and anorexia, with fever in eight cases, had persisted for at least 2 months before admission. Haemodynamic failure was present in seven patients, and neurological signs in four. The aortic valve was involved in seven cases, the mitral valve in one and both valves in two. Vegetations, often fingerlike, were observed by echocardiography in nine cases. All patients required valve replacement, and three died in the year following diagnosis. Blood cultures were consistently negative in all cases, and no antibiotics had been given before admission. Significant titres of complement fixing anti-chlamydial antibodies were present in six cases, and micro-immunofluorescence using the three chlamydial species showed cross-reacting antibodies in all nine cases studied, with transient IgM positivity in six cases. Histologically, the leaflets were fibrosed and infiltrated by large macrophages containing dark red granules after Machiavello staining. These granules were specifically stained by immunofluorescence using monoclonal antibody to Chlamydia common antigen, but not by that specific for C. pneumoniae. No organisms were seen after Gram staining, and no positive chlamydial immunofluorescence was seen on sections of valves from patients with staphylococcal or streptococcal endocarditis.

Besides the rapid diagnostic tests based on influenza A and B antigens nucleoproteins detection, which are routinely used, the isolation of influenza strains is still required to obtain recent variant isolates for full antigenic characterization, in order to up-date the influenza vaccine composition. To increase the rapidity and the efficacy of the virus growth, we implemented a culture test in 24-well plates by centrifugation of samples on to LLCMK2 cells in the presence of trypsin. This test was routinely applied to 331 nasopharyngeal swabs collected during the influenza A outbreak in the winters 1988-1989 and to 962 in 1989-1990. The centrifugation culture assay has been compared with the direct detection of NP antigens in the clinical samples by immunofluorescence and capture ELISA tests and with the conventional virus isolation by inoculation of the samples to embryonated eggs and to LLCMK2 cell cultures. Compared with the NP antigen detection tests, the centrifugation culture assay closely correlated (r = 0.95) and the sensitivity and specificity were also excellent, 93.4% and 99.6%, respectively. Compared with the conventional culture assays, the centrifugation culture markedly increased the performance (five times) and rapidity (2 days) of influenza virus isolation and identification.

Herpes simplex virus resistant to acyclovir (ACV) is a major concern among immunocompromised patients. ACV resistance might be due to mutations located in one of the two genes involved in ACV mechanism of action, the thymidine kinase gene (TK, involved in 95% of the cases) and the DNA polymerase gene. TK gene mutations consist, in half of the cases, in nucleotide insertion or deletion, occurring most of the time in G or C homopolymers considered as hot spots. Half of the other cases involves nucleotide substitutions leading to amino acids substitutions. Studies of sensitive strains revealed a high degree of TK polymorphism, many mutations being not implied in ACV resistance. At the present time, resistance detection can be performed by phenotypic tests that require virus culture and results cannot be given to the physician before 7 to 10 days. Genotyping diagnosis performed directly from clinical samples would allow to detect resistance more rapidly, in order to switch quickly to an appropriate treatment by foscarnet or cidofovir.

Herpes simplex virus (HSV) infections are very common in the general population and among immunocompromised patients. Acyclovir (ACV) is an effective treatment which is widely used. We deemed it essential to conduct a wide and coordinated survey of the emergence of ACV-resistant HSV strains . We have formed a network of 15 virology laboratories which have isolated and identified, between May 1999 and April 2002, HSV type 1 (HSV-1) and HSV-2 strains among hospitalized subjects. The sensitivity of each isolate to ACV was evaluated by a colorimetric test (C. Danve, F. Morfin, D. Thouvenot, and M. Aymard, J. Virol. Methods 105:207-217, 2002). During this study, 3,900 isolated strains among 3,357 patients were collected; 55% of the patients were immunocompetent. Only six immunocompetent patients excreted ACV-resistant HSV strains (0.32%), including one female patient not treated with ACV who was infected primary by an ACV-resistant strain. Among the 54 immunocompromised patients from whom ACV-resistant HSV strains were isolated (3.5%), the bone marrow transplantation patients showed the highest prevalence of resistance (10.9%), whereas among patients infected by human immunodeficiency virus, the prevalence was 4.2%. In 38% of the cases, the patients who excreted the ACV-resistant strains were treated with foscarnet (PFA), and 61% of them developed resistance to PFA. The collection of a large number of isolates enabled an evaluation of the prevalence of resistance of HSV strains to antiviral drugs to be made. This prevalence has remained stable over the last 10 years, as much among immunocompetent patients as among immunocompromised patients.

Herpes simplex virus (HSV) and varicella zoster virus (VZV) are susceptible to acyclovir which inhibits viral replication through two viral enzymes, thymidine kinase (TK) and DNA polymerase. Resistance may occur, it is a rare phenomenon among immunocompetent patients but resistance is more frequent and may be associated with serious complications among immunocompromised patients. Virological survey of these at risk patients is needed to detect resistant virus as soon as possible through phenotypic tests performed on virus isolated on cell cultures. Resistant virus may also be genetically characterised by detection of mutations within TK and DNA polymerase genes. Pharmacological parameters also have to be taken into consideration and a determination of acyclovir blood concentration should be performed in case of unexplained therapeutic failure. Improvement of immune system, when possible, may resolve these infections. Alternative treatments using drugs such as foscarnet or cidofovir which have a different mechanism of action compared to acyclovir, are recommended but these molecules are often more toxic than acyclovir.

We carried out a retrospective analysis of an outbreak of adenovirus (AdV) infections in a paediatric unit. The aim of the study was to analyse cases, determine the route of transmission and to evaluate the efficacy of the prevention measures.The study was performed by recollection of AdV infection cases during a period of 1 year and the results were compared with the list of clinical cases recorded during the epidemic. The clinical files of children with a positive specimen were retrospectively analysed. During that period, five members of the medical staff showed clinical signs and symptoms of AdV infection. A throat swab was collected from a subset of the staff.Among nine patients with positive AdV detection, six were infected with an Adv type 2. Six were nosocomially-acquired, the other two were only probable nosocomial infections. The index case was a child presenting a febrile diarrhoea 48 h prior to being admitted to the hospital. Nosocomial transmission was associated with the prolonged shedding of the virus with faeces of the infected cases. The specimens collected from the staff remained negative. The outcome was favourable for all children.Prevention measures, implemented when the epidemic was characterised, allowed the control of the nosocomial outbreak.

This paper presents the results of a SEE neutron evaluation carried out on five SRAM types. Sensitivity to the power supply, test pattern and memory cell structures were investigated.

Herpes simplex virus (HSV) infections are very common and may present various manifestations. Mostly asymptomatic, often mild, these infections may become life-threatening, specially in neonates. The acute and rapid diagnosis of HSV infections can prevent infections in these patients and is also helpful to confirm clinical diagnosis. The sensitivity of "classical" diagnosis methods, such as culture and antigen detection by immunofluorescence and ELISA, is highly dependent on the quality of the sample. Antigen detection techniques give results in short delays, compatible with the initiation of antiviral treatment; however their sensitivity decreases when lesions get older and they are not convenient for the diagnosis of asymptomatic infections. Isolation of HSV on cell culture remains the gold standard, because it is easy to perform and exhibits good sensitivity whatever the stage of the lesions; the isolation of the virus is required for HSV typing and to determine susceptibility to antiviral agents in case of clinical resistance to the treatment. Serodiagnosis is helpful to determine the immune status of a patient and to distinguish between primary infection and recurrence. It is now possible to differentiate HSV1 and HSV2 antibodies; the benefit of type-specific serology is clear for epidemiological surveys but may be discussed for individual follow-up, specially for genital herpes, both for the diagnosis and the prevention of HSV infections.

An HIV-negative infant presented with VZV primary infection during the maintenance therapy for megakaryoblastic leukaemia. The lesions were initially vesicular and necrotic but became verrucous and hyperkeratotic. A clinical resistance to acyclovir was suspected and confirmed by histologic and virologic studies. The patient was successfully treated by foscarnet.resistance of VZV to acyclovir may occur after a short treatment in a non-AIDS patient.

Herpes simplex virus (HSV) infections are prevalent worldwide. HSV are characterized by their ability to establish and maintain latent infections that can be reactivated. Various clinical presentations of HSV infections are described. Mostly asymptomatic, these infections may become life-threatening when occurring in neonates or when infecting the central nervous system. Accurate diagnosis of HSV infections is important and PCR is the most sensitive technique for detecting HSV. Type-specific serologies could be particularly useful for seroprevalence rates. Aciclovir is an efficient drug for the treatment of herpes simplex virus infections and resistance to this drug has been reported mainly in immunocompromised patients during the course of aciclovir treatment. There is a variety of potential vaccines for prophylaxis of HSV infection, but no vaccine is now available.

A multi-centric study was carried out in three laboratories, to evaluate the efficiency of a standardized kit for the detection of enterovirus genome in wastewater. Twenty one samples of 20 liters of wastewater were analyzed before and after concentration through glass wool. Each sample was analyzed with the Amplicor kit as well as with techniques developed independently in each laboratory. The results show that the Amplicor kit is well suited to the detection of enterovirus genome in treated wastewater. The results may be compared to those obtained with semi-nested RT-PCR techniques used in each laboratory. However, the Amplicor kit technique is more simple and has the advantage of providing a standardized technique useful for comparative studies. During this work it was observed that the sensitivity of the detection of infectious viruses and virus genome was improved when concentrated samples were used for analysis.

Cidofovir (CDF) or Vistid is a monophosphate nucleoside analogue that inhibits the DNA polymerase of herpes viruses including the cytomegalovirus (CMV). CDF is active on GCV-resistant strains with a mutation on the phosphotransferase gene (UL97). However, DNA polymerase gene mutations that induce resistance to GCV are responsible for cross-resistance to CDF. Resistance phenotypes to GCV and CDF were determined for 57 CMV strains isolated from blood and urine samples. Sixteen strains were recovered after CDF therapy. Of the remaining 41 CDF-naive strains, 34 were susceptible and seven resistant to GCV. Fifty percent inhibitory concentrations (IC50) for CDF were in the 0.2-2.6 microM range for CDF-naive strains susceptible to GCV. For GCV-resistant strains, IC50 values for CDF wereor = 3 microM for strains with a low level of resistance to GCV (GCV IC5030 microM) andor = 6 microM for three of the five strains with a high level of resistance to GCV (GCV IC50or = 30 microM).

ELISA capture technique (ELISAc) was carried out using a rabbit hyperimmune serum attached to a solid phase for capturing mumps antigens in cerebrospinal fluid (CSF) in patients with meningitis and/or in supernatants of infected Vero cells. A biotin-labelled rabbit serum prepared from the previous serum was added and the reaction was read by an enzymatic (avidine-peroxidase) reaction by automated reading. The cut-off was calculated in 100 CSFs negative for viruses by conventional diagnosis. The specificity was evaluated in Vero cells infected with 22 CSFs collected from vaccinated children (URABE AM9 attenuated vaccine) who developed meningitis. A guinea pig hyperimmune serum confirmed the specificity. Results in culture correlated with the ELISA capture technique (ELISAc). No cross-reactivity was observed with parainfluenza 1, 2, 3 human reference strains. At least 2.5 ngs of purified mumps proteins were detected corresponding to 101.5 infectious particles per ml. ELISAc applied directly to 14 CSFs collected from unvaccinated children with meningitis diagnosed five positive cases, whereas in four cases conventional diagnosis had to be undertaken twice. ELISAc permitted the diagnosis of one additional patient. The test can be carried out in 3 h.

The substitution of methionine by either isoleucine or valine at residue 460 in the UL97 phosphotransferase has been shown to be responsible for resistance to ganciclovir (GCV) in 30% of resistant cytomegalovirus (CMV) isolates [4]. These substitutions require one nucleotide change in the gene (G-T 1 380 and A-G 1378 respectively). The aim of this study was to develop a discriminative PCR assay for rapid detection of these DNA changes. A PCR assay was duplicated in parallel for each mutation; to detect G-T 1380 each reaction mixture contained primer VSUL14 and either primer LNW to distinguish wild type residues or LNM to distinguish mutant residues, and for A-G 1378 primers were VSUL8 and either MCMW to detect wild type sequences or MCMM to detect mutated residues. For optimal discrimination, primers MCMW and MCMM were designed with a mismatch at position 3'-1. The reference strains AD169, Davis and Towne, a laboratory GCV-resistant mutant RCL1.7, and 33 CMV isolates (10 resistant, 2 indetermined and 21 sensitive) were tested by PCR. AD169, Davis and Towne, and 30 isolates were amplified only with non modified primers, and the absence of 460 mutations was confirmed by sequencing. Two isolates P1 and P2, from a transplanted patient were amplified with both MCMM and MCMW: sequencing analysis shown the presence of a mixture of strain, one of them harbouring A-G 1378 mutation. One resistant strain was amplified neither with MCMM nor with MCMW: a C-T silent mutation at nt 1368 was present. As sequencing analysis confirmed PCR results, discriminative PCR enables isolates to be rapidly assessed for the presence or absence of 460 mutations. Moreover, it can distinguish Met to Val from Met to Ile mutations, and allows the analysis of mixtures of sensitive ad resistant strains.

At present it is conceivable to think that gene therapy represents a way to treat or even prevent the respiratory manifestations of cystic fibrosis. Consistent to such a concept, there is sufficient evidence that Ad-CFTR, a recombinant replication-deficient adenovirus expressing the human cystic fibrosis transmembrane conductance regulator cDNA, can vectorize the expression of a functional CFTR (cystic fibrosis transmembrane conductance regulator) to the nasal and airway epithelia. The clinical protocol was designed to assess the safety of single escalating doses of a replication defective adenovirus expressing the cystic fibrosis transmembrane conductance regulator gene (Ad-CFTR) when administered to the tracheobronchial portion of the airways and whether biological efficacy of CFTR delivery could be demonstrated. Six cystic fibrosis patients received nasal instillation and subsequent aerosol (Optineb, Air Liquide, Paris, France) administration of Ad-CFTR the following day. Doses (pfu) applied to the nose were 10(5) (patients SG and PB), 10(7) (patients FP and EP) and 4 x 10(8) (patients DS and FG), while aerosolised doses were 10(7) (patients SG and PB), 10(8) (patients FP and EP) and 5.4 x 10(8) (patients DS and FG), respectively. No acute toxic effects, no increase in the titer of anti-adenovirus antibodies and no spreading or shedding of Ad-CFTR were detected. In one patient Ad-CFTR DNA was found in the urine and blood two days after aerosolisation. Ad-CFTR DNA was detected in nasal and bronchial brush samples, in BAL, in saliva and tonsils 21, 8, 14 and 4 days post virus administration, respectively. Ad-CFTR mRNA (RT-PCR on bronchial cells) and CFTR protein (immunochemistry on nasal and bronchial cells) were detected up to 14 days following Ad-CFTR administration. These results show that the nebulisation of Ad-CFTR is a possible approach for treating the respiratory manifestation of cystic fibrosis.

Summary A 28-year-old man with Wiskott—Aldrich syndrome presonied with ulcerative-proliferative lesions on his face from which herpes simplex type 1 (HSV-1) was isolated. He was initially treated with 10 mg/kg of acyclovir (Zovirax®) intravenously every 8h, but his skin lesions worsened. Clinical resistance to acyclovir was suspected, and therapy with this drug was intensified. The dosage of acyclovir was increased to 45 mg/kg, administered by continuous infusion, and the lesions subsequently resolved. The strain of HSV recovered from the patient showed acyclovir-resistance in vitro, using the colorimetric method with neutral red. Herpes simplex virus resistance to acyclovir is rare. It is more common in immunocompromised patients if subtherapeutic doses are administered in the treatment of chronic persistent forms of infection. Whenever clinical resistance to acyclovir is suspected, the dosage should be increased to 2 mg/kg per h administered via an infusion pump. If no improvement is observed in the patient's condition with this regimen, a phosphorylated medication whose mechanism of action is not dependent on viral thymidine kinase, such as foscarnet (phosphonoformic acid), should be substituted.

Blood dyscrasias such as aplastic anaemia and leukopenia are described following the use of lindane for agricultural purposes or against ectoparasites in animal and human health. In order to determine the involvement of lindane in these effects, an in vitro model of haematotoxicity evaluation has been used.Culture of haematopoietic progenitors, Colony Forming Unit-Granulocyte and Macrophage (CFU-GM), have been performed in the presence of lindane with increasing concentrations.Results showed that lindane was cytotoxic for human progenitors. They were one thousand times more sensitive to the lindane than rat CFU-GM.This cytotoxicity was observed with lindane concentrations similar to those measured in human blood in cases of acute intoxication and in fat tissues of exposed populations.

The authors report 4 cases of African histoplasmosis in Zaïrans. The diagnostic was based ou cutaneous (4 patients), bones (3), lymph-nodes (2), and bowel-localizations (1) and was confirmed by the presence of Histoplasma duboisiis yeasts in cutaneous biopsy (4 patients), in pus of abscess or cutaneous lesions (3) and in stools (1). Two HIV seronegatives patients had a good outcome with amphotericin B. One patient died without any treatment. One HIV-1 and HTLV-1 seropositive patient had successful short-term outcome with ketoconazole. Seven others cases of association between African histoplasmosis and AIDS are noted in the literature. They suggest the opportunistic nature of this deep mycosis.

Some pesticides are hematotoxic and cause aplastic anemia, agranulocytosis, neutropenia, and thrombopenia. In order to evaluate hematopoietic progenitor cultures in the exploration of pesticide hematotoxicity, human and rat colony-forming unit-granulocyte and macrophage (CFU-GM) were cultured in the presence of different concentrations of pesticides, known to be either hematotoxic or innocuous for blood cells. The results were compared to the control culture of the same sample. Four insecticides (lindane, azinphos, mevinphos, parathion methyl), three herbicides, (2,4,5, T, bromacil, MCPA), and two fungicides (fosethyl-aluminum, DNOC) were tested and exhibited the following data: 1) Pesticides, known to be hematotoxic, inhibited the development of progenitors. Different phenomena were observed and suggested different mechanisms: cell destruction, block in mitosis, decrease or delay in mitosis. 2) Difference in sensitivity to molecules between human and rat progenitors was observed. Human progenitors were more sensitive to pesticides, except for 2,4,5 T.

Summary The authors review the biological properties of enteroviruses and the pathogenic features of the neuromeningeal infections caused by them, and describe the value and methods of interpretation of diagnostic procedures. They then outline the place of the enteroviruses in infectious viral diseases of the nervous system (meningitis, encephalitis, paralytic syndromes) and the epidemiology of these infections, basing their conclusions on W.H.O. statistics and their personal experience of such cases in the Rhone-Alpes region. Epidemiological data concerning meningitis epidemics is often incomplete, and almost inexistent for encephalitic and sporadic paralytic syndromes. In many cases, the etiological diagnosis is not made as this requires a very complete virological diagnosis and precise epidemiological surveys. Fecal excretion of these resistant viruses and their dissemination in water supplies means that epidemiological studies of the environment and the population are necessary, and should be made regularly.

An immunocapture ELISA test for the diagnosis of human and animal influenza A and/or B is described. A monoclonal anti-nucleoprotein (NP) antibody was used to capture the NP antigen and the captured antigen was detected by an anti-NP polyclonal rabbit antiserum. Compared with the usual diagnostic method by cultivation in embryonated eggs, this test had a high specificity (97%) and sensitivity when used for diagnosis using clinical nasopharyngeal samples obtained from patients and animals. Immunocapture ELISA permitted an easier reading than the indirect immunofluorescence technique. It also permitted diagnosis in frozen samples (-20 degrees C) or in infected LLCMK2 cells mixed with uninfected nasopharyngeal cells and kept at 20 degrees C for one week. This test can be carried out in 3 h.

We saw 5 young infants with severe pneumonias due to RS virus (diagnosed serologically). Three of these infants were born as premature babies. Artificial ventilation was necessary in two cases. After the case reports follows a discussion of the most important problems of epidemiology, diagnostics and therapy of RS virus infections in young infants.

In human hyperplastic prostate, 5α-dihydrotestosterone results from the 5α-reduction of testosterone and is transformed into epimeric 5α-androstanediols by the 3α- and 3β-hydroxysteroid dehydrogenases. Kinetics of these enzymic transformations were studied with labelled testosterone and 5α-dihydrotestosterone substrates in NADPH-supplemented homogenates from six hyperplastic prostate glands. Estradiol-17β interfered only with the prostatic 5α-reduction of testosterone. In contrast, other estrogenic substances found in food (zearalenone and zearalanol) inhibited only the 3α- and 3β-hydroxysteroid dehydrogenases. Increase in Km in all cases and no statistically different increase of Vmax pointed toward competitive types of inhibition. Since these in vitro studies only apply to NADPH-dependent enzymic activities, the inhibitory action of estradiol-17β on the prostatic 5α-reductase may occur in vivo. Nevertheless, effects of estradiol-17β and zearalenone or zearalanol on the NADH-dependent reductions of 5α-dihydrotestosterone and oxidations of the 5α-androstanediols need to be known before one of these compounds could be implicated in changes in levels of endogenous prostatic 5α-dihydrotestosterone.

Because of the possible serological cross reactions frequently described in the literature between L. pneumophila and M. pneumoniae or between L. pneumophila and Chlamydia, we decided to determine their frequency with our sera and our own methods. The anti M. pneumoniae and Chlamydia antibodies were researched in 162 sera samples from 46 cases of legionellosis serologically diagnosed and in 51 sera from 26 hyperimmunised rabbits. Conversely, anti L. pneumophila antibodies were researched in 165 sera from mycoplasmosis (61) or chlamydiosis (25 cases). None of the sera from mycoplasmosis or chlamydiosis tested by IFA and MA had antilegionella antibodies. None of the rabbits' sera hyperimmunised with Legionella had anti M. pneumoniae or Chlamydia antibodies. On the contrary, by complement fixation and IFA, out of the 46 cases of legionellosis under study, 6 showed a seroconversion in M. pneumoniae and 2 in Chlamydia. The Ig class determination did not show IgM titers in 7 of these 8 sera. The mechanisms of these cross reactions are discussed: antigens and methods used, booster effect during legionellosis, concurrent mycoplasmosis or chlamydiosis.

Prophylaxis with high-titered anti CMV globulins was studied in 2 pilot trials using 2 different schedules. Results were compared with a historical group without prophylaxis.

The poliomyelitis survey was started in 1976 in Bahrain and Kuwait. For each paralytic case, diagnosis was done by virus isolation, neutralizing antibody titration and specific IgM characterization. More than 90% of the infants who were ill were less than 2 years old. In Bahrain, 17 paralytic cases in 1976 and 12 in 1977 occurred between January and July (annual incidence was respectively 7.7 and 5.4/100,000). The first epidemic was due to poliovirus type 2, the second one to poliovirus type1. From 29 cases, 13 occurred in vaccinated infants of which 9 received 3 or 4 oral vaccine doses. For 3 infants, paralysis occurred less than one month after vaccination. All the isolates were wild polioviruses (rct). In Kuwait, 119 cases were examined, and of them, 57 occurred between August 76 and May 77 (incidence 5.7/100,000). Poliovirus type 1 was responsible for 61% of cases, type 2 for 5% and type 3 for 12%. From October 1976 to December 1977, 350 stools samples were collected from contacts: 19% of them carried poliovirus (12% type 1, 1% type 2 and 6% type 3). All the viruses isolated from both paralytic cases and contacts were wild strains (rct). Of 119 cases, 35 occurred in vaccinated infants from which 4 had received 3 or 4 oral vaccine doses. For 11 infants paralysis occurred less than one month after vaccination. The virus spread was evaluated (i) just before vaccination in 337 infants or children from June to December 76: 8% carried poliovirus Sabin-like strains (and 18% non polioviruses), and (ii) one month after vaccination in 75 infants: 37% carried poliovirus Sabin-like strains.

The antiviral activity of a novel biological response modifier (murabutide MDP derivative) has been investigated in 3-week-old OF1 mice infected with influenza (A/Texas/1/77) virus. In each experimental and control group, 10 mice were infected intranasally with a viral dose producing 50% mortality in 5 days and received murabutide via the subcutaneous or intranasal route at various doses either in a simple or in daily repeated administration. All experiments were done in triplicate. Significant prophylactic or therapeutic effects were observed when murabutide was administered the same day as virus, 4 days or 2 days before virus, and 2 days later. These effects varied with the route of administration and the doses of the compound.