[Hepatosplenic localization of cat scratch disease: two cases in immunocompetent adult patients]. / Atteinte hépatosplénique de la maladie des griffes du chat : à propos de deux observations chez l'immunocompétent.

INTRODUCTION: Cat-Scratch Disease (CSD) is a well-recognized benign cause of localized lymphadenopathy, which often recovers spontaneously. However systemic clinical presentations are described in immunodeficient adults (bacillary angiomatosis, bacillary splenitis) and are less common in immunocompetent ones. EXEGESIS: We report two cases of disseminated CSD in immunocompetent patients, presenting hepatosplenic nodules, associated in the second case with an endocarditis. CONCLUSION: Bartonella serology must be achieved in case of hepatosplenic nodules with fever. Treatment of disseminated CSD in immunocompetent adults is still empirical and recovery can occur without antibiotherapy when endocarditis is not associated.

Hepatitis B vaccination in diabetic patients. Randomized trial comparing recombinant vaccines containing and not containing pre-S2 antigen.

OBJECTIVE: To investigate the immunogenicity of two recombinant hepatitis B vaccines containing S antigen alone (Engerix B) or both S and pre-S2 antigens (GenHevac B) in diabetic patients. RESEARCH DESIGN AND METHODS: Of the adult diabetic patients, 71 (26 IDDM, 45 NIDDM) were randomized to receive Engerix B or GenHevac B at 0, 1, 2, and 12 months in a single-blind clinical trial; if the antibody to hepatitis B surface antigen (anti-HBs) titers were < 10 i.u./l at month 4, a fourth injection of vaccine was given. A positive response was defined by anti-HBs titer > or = 10 IU/l at month 13. RESULTS: The anti-HBs response rate and the titers of anti-HBs did not differ significantly between the two types of vaccine. Overall, > 90% of the patients responded at month 13. In patients vaccinated with GenHevac B, anti-pre-S2 antibodies appeared earlier than anti-HBs. The anti-HBs response tended to decrease with age (P = 0.07) and tended to be higher in IDDM patients than in NIDDM patients (P = 0.06). Metabolic control, as assessed by HbA1c level, did not influence the response rate. The presence of the HLA DQ2 allele was associated with a low response. CONCLUSIONS: A large majority of diabetic patients can be efficiently vaccinated against the hepatitis B virus using a booster dose at month 4. The choice of the vaccine (with or without pre-S2 antigen) appears to have little influence, if any, on the response rate.

Expression of endogenous retroviruses in blood mononuclear cells and brain tissue from multiple sclerosis patients.

OBJECTIVES: To compare the expression of endogenous retroviruses in MS patients and controls. MATERIAL AND METHODS: Peripheral blood mononuclear cells were obtained from 22 MS patients, a corresponding number of matched healthy donors and five patients with other central nervous system disease. Also brain specimens from MS patients and controls were obtained. Transcripts of various endogenous retroviruses in these samples were detected by RNA-PCR. RESULTS: Several endogenous retroviral sequences were transcribed in peripheral blood mononuclear cells and brain tissue from MS patients as well as controls. A composite transcript of an endogenous retrovirus and a zinc finger sequence was more frequently found in healthy donors than in MS patients. CONCLUSION: Some endogenous retroviruses are normally transcribed in white blood cells and brain tissue. The significance of those findings, which concerned the composite transcripts of the zinc finger sequence and its associated endogenous retrovirus is uncertain.

Gliotoxicity, reverse transcriptase activity and retroviral RNA in monocyte/macrophage culture supernatants from patients with multiple sclerosis.

In investigating a possible link between a novel retroviral agent (provisionally called MSRV), recently characterised in multiple sclerosis (MS), and the neuropathology of MS, it was found that there was a significant correlation between gliotoxicity and reverse transcriptase activity in monocyte/macrophage culture supernatants (MMCS) unique to MS patients. MMCS from healthy controls and patients with other neurological diseases did not display either gliotoxicity or reverse transcriptase activity. The observed gliotoxic effect was an initial, intermediate filament network disorganization and subsequent cell death which was specific to astrocytes and oligodendrocytes. The reverse transcriptase activity and MSRV-specific RNA were observed during the first 2 weeks of culture in MMCS from patients with active MS. The further elucidation of the molecular form(s) of this gliotoxic factor and its original source may be crucial in elucidating important etiopathogenic mechanisms in MS.

Binding studies of macrolides, lincosamides and streptogramins to Streptococcus G group using [3H]-erythromycin.

Parameters of [3H]-erythromycin binding to Streptococcus are determined in vivo using both equilibrium and kinetic methods. This binding is saturable, reversible and independent of energetic systems. Whatever the methods used, the binding parameters are identical as 14 nM for the dissociation constant of the complex erythromycin-Streptococcus and a density of binding sites of 11,865 molecules/cell. Other macrolides, streptogramins and lincosamides competitively displaced bound [3H]-erythromycin suggesting that these compounds share common binding sites on the bacteria. In parallel, the MIC values of these antibiotics against Streptococcus are determined by agar dilution method in Mueller-Hinton medium with 5% of horse blood in order to compare the binding and microbiological parameters. A strong correlation (n = 0.863) has been found between the corresponding inhibition constants and MIC values. Such binding studies could be used in conjunction with microbiological assays for primary screening of active analogous or other compounds with interfere with [3H]-erythromycin binding to the bacteria.

In vitro [3H]-erythromycin binding to Staphylococcus aureus.

Characteristics of erythromycin binding to Staphylococcus aureus were determined by using kinetics and equilibrium binding experiments. Both methods yielded identical values of the dissociation constant, i.e. 0.1 muM. This value was in accord with that found with a bacterial extract of ribosomes which are the organelles where erythromycin exerts its action. This good agreement shows that the dissociation constant of erythromycin determined with intact bacteria is a good reflect of specific bacterial receptors of macrolides, i.e. ribosomes. In addition, mechanism of uptake of the antibiotic by Staphylococcus aureus was investigated. Passive diffusion process was shown to be mainly responsible for this phenomenon.

Epstein-Barr virus infection and hepatic fibrin-ring granulomas.

Hepatic fibrin-ring granulomas were the main histological finding in the liver of a 38-year-old man with Epstein-Barr virus primary infection. The patient presented with fever, hepatomegaly, icterus, abnormal liver tests, autoimmune hemolytic anemia, and mononucleosis syndrome. There was neither enanthema nor lymphadenopathy or splenomegaly. Serologic tests disclosed an Epstein-Barr primary infection profile: anti-viral capsid antigen IgM antibodies and anti-early antigen antibodies were present, whereas anti-Epstein-Barr nuclear antigen antibodies were absent. There was no evidence for Q fever, Hodgkin's disease, or allopurinol-induced hepatitis, which are recognized causes of hepatic fibrin-ring granulomas. It is suggested that Epstein-Barr virus infection might be an additional cause of these peculiar hepatic granulomas.

Acquired ciliary abnormalities of nasal mucosa in marrow recipients.

Respiratory symptoms are frequent after bone marrow transplantation (BMT). Most studies focus on lesions of the lower respiratory tract. However, sinusitis is also common in this setting, especially after allogeneic BMT. The nasal respiratory epithelium is the first line of airway defense and is very similar to the bronchial epithelium, especially in terms of ciliary beat frequency and ultrastructural pattern of ciliated cells. We have prospectively studied the nasal respiratory epithelium of 20 marrow recipients (four autologous, 16 allogeneic) with or without sinusitis, by brushing and biopsy of the median turbinate between 2.5 and 148 months after transplant. Samples were studied for ciliary beat frequency, cytology, ultrastructural pattern and HLA-DR expression. We found that 17 of our 20 patients had abnormalities of their nasal epithelium, mainly consisting of either squamous metaplasia or heterogeneous axonemal defects of peripheral and central microtubules. No relationship between these findings and the presence of acute or chronic sinus infection, previous irradiation, graft-versus-host disease or immunosuppressive therapy could be demonstrated in this preliminary study. These abnormalities probably have multiple causes. Prospective studies are needed to determine the respective roles of treatments, infections and immune disorders associated with BMT in these abnormalities, and to know their natural evolution over time and their impact on the occurrence of upper or lower respiratory tract infections.

HIV-1 sensitivity to zidovudine: a consensus culture technique validated by genotypic analysis of the reverse transcriptase.

In order to select and standardize a reliable assay for the analysis of sensitivity of HIV isolates to AZT, we have compared two culture methods. The first assay (Cell-Associated Isolate Sensitivity Assay: CAISA) quantified AZT-resistant HIV isolates by end-point dilution cultures of peripheral blood mononuclear cells (PBMCs) in the presence of various concentrations of AZT. In the second assay (Cell-Free Isolate Sensitivity Assay: CFISA), following a conventional isolation of HIV, dilutions of infected cell-free supernatants were cultivated with fresh normal donor PBMCs in the presence of increasing concentrations of AZT. Samples from 64 untreated and AZT-treated patients were studied by CAISA (41), CFISA (43) or both assays (20). The CFISA, which allows the determination of titration parameters with respect to various kinetics patterns of viral replication was selected, and some of the CFISA phenotypically characterized isolates were further studied by nucleotide sequence analysis of the reverse transcriptase gene. CFISA showed that isolates from untreated patients were susceptible to AZT while the frequency of resistance increased with the duration of therapy. Genotypic analysis of CFISA-resistant isolates exhibited mutations at crucial positions, particularly at residue 215. We consider CFISA as a consensus culture technique for longitudinal studies of isolates from patients receiving AZT or other analogs of nucleosides.

Cure of bartonella endocarditis of a prosthetic aortic valve without surgery: value of serologic follow-up.

Bartonella species are emerging as an important cause of blood culture-negative endocarditis, but the optimal management of this disease has not been fully defined. We describe a case of subacute Bartonella henselae endocarditis of a prosthetic aortic valve in an immunocompetent woman that was cured with long-term antibiotic therapy alone. In addition, we demonstrate that follow-up of serologic titers against B. henselae was helpful in assessing definitive cure of the infection.

Lichen planus and hepatitis C virus--related chronic active hepatitis.

BACKGROUND AND DESIGN: An increased prevalence of chronic liver disease has been reported in patients with lichen planus (LP). We report six cases of LP associated with chronic active hepatitis and actively replicating hepatitis C virus (HCV). RESULTS: We studied six patients (three men and three women; mean age, 61 years; age range, 47 to 70 years) with various forms (cutaneous and/or mucosal) of LP and abnormal liver test results. Four patients had severe mucosal lesions. Cutaneous and mucosal lesions had a long-term evolution. Liver disease was discovered 2 to 6 years before LP in three cases and was diagnosed at the same time as LP in the three other cases. Liver biopsy performed in five patients showed chronic active hepatitis without cirrhosis in all five cases. Anti-HCV antibodies were detected in all cases by second-generation enzyme-linked immunosorbent assay and confirmed by second-generation recombinant immunoblot assay. Hepatitis C virus RNA was evidenced by means of polymerase chain reaction in the serum samples from the six patients, proving active viral replication. CONCLUSIONS: Lichen planus may be associated with HCV-related chronic active hepatitis. As interferon treatment may induce viral inactivation in some patients with HCV-related chronic liver disease, a search for HCV infection should be systematically performed in patients with chronic LP.

Seroprevalence of eight Helicobacter pylori antigens among 182 patients with peptic ulcer, MALT gastric lymphoma or non-ulcer dyspepsia. Higher rate of seroreactivity against CagA and 35-kDa antigens in patients with peptic ulcer originating from Europe and Africa.

BACKGROUND: It has been suggested that Helicobacter pylori may induce more or less severe gastroduodenal disease according to the strain virulence. DESIGN: We used Western blot to determine antigenic profiles associated with duodenal or gastric ulcer disease, MALT lymphoma and non-ulcer dyspepsia, and to identify geographical differences. METHODS: One hundred and eighty-two consecutive patients with H. pylori infection were studied. H. pylori infection was diagnosed by a rapid urease test or histological examination of gastric biopsy samples. Bacterial density and gastritis were assessed histologically by using the Sydney scoring system. Western blot was used to identify antibodies against eight antigens (CagA, VacA, urease A, heat shock protein B, and 19.5, 26.5, 30 and 35 kDa). Patients were questioned on their smoking habits and place of birth and childhood. RESULTS: There were 73 patients with duodenal ulcer, 30 with gastric ulcer, eight with erosive duodenitis, 17 with gastric MALT lymphoma and 54 with non-ulcer dyspepsia. Most (>85%) were seropositive for the heat shock protein B and 26.5-kDa antigens. The prevalence of the other antigens ranged from 45% (VacA) to 68% (urease B). The seroprevalence of CagA antigen was significantly higher (P < 0.01) in cases of gastroduodenal ulcer (84%) than non-ulcer dyspepsia (37%). Similarly, 35-kDa antigen reactivity was more frequent (P < 0.05) in duodenal ulcer patients (75%) than in those with non-ulcer dyspepsia (50%). The antigenic profiles associated with MALT gastric lymphoma and non-ulcer dyspepsia were similar. Multivariate analysis showed that only gastroduodenal ulcer was significantly associated with CagA. Gastroduodenal ulcer and a childhood spent in Africa were both associated with 35-kDa and combined CagA-35-kDa reactivity. CONCLUSIONS: This study confirms the strong seroprevalence of H. pylori CagA antigen and shows a high prevalence of the 35-kDa antigen in patients with gastroduodenal ulcer, especially those raised in Africa. There was no difference in the serological pattern between patients with non-ulcer dyspepsia and those with MALT lymphoma. Tests for antibodies to the CagA-35-kDa antigen combination might be used to select H. pylori-infected dyspeptic patients warranting treatment.

First isolation of Mycobacterium microti (Llama-type) from a dog.

We report the first isolation of Mycobacterium microti from a dog with lesions of acute peritonitis. The isolate was demonstrated to be M. microti of Llama-Type by spoligotyping. Epidemiological implications of the isolation of this possibly zoonotic agent from a dog are discussed.

Determination of binding parameters of macrolides, lincosamides, and streptogramins to Legionella pneumophila.

Parameters of [3H]erythromycin binding to Legionella pneumophila were determined in vitro using both an equilibrium and a kinetic method. Different L. pneumophila serogroups, 1-3, and a virulent strain serogroup, 1, were tested. All strains of bacteria exhibited the same binding pattern, with a dissociation constant of 0.15 microM. Other macrolides, streptogramin B-types, and lincosamides competitively displaced bound erythromycin suggesting that these compounds share common binding sites on the bacteria. Minimum inhibitory concentration (MIC) values for macrolides, streptogramin B-types, and lincosamides were determined with buffered charcoal yeast extract (BCYE) medium. A good correlation (r = 0.994) was found between the corresponding inhibition constants of these antibiotics and their MIC. It was also noted that for lincosamides the microbiological inactivity was associated with a very low bacterium affinity. Thus, it is concluded that binding parameters of these antibiotics reflect their efficacy against L. pneumophila in vitro and may serve as a useful adjunct in developing new compounds.

Tetracycline and erythromycin distribution in pathological lungs of humans and rat.

Tetracycline and erythromycin concentrate highly in pulmonary tissues in humans as well as in the rat. Their binding to the lung, whatever the species and the pathological state, is weak. Their intrapulmonary concentrations could be explained by a passive diffusion which depends on the pH variation between the intra- and extratissue compartments, the percentage of un-ionized form present, and their liposolubility. The importance of retention of tetracycline and erythromycin by plasma proteins is demonstrated by the decrease of their pulmonary index of penetration (IP, the intra- and extratissue concentrations ratio). The IP values are, respectively, 1.09 and 1.23 for tetracycline and erythromycin. These concentrations are in excess of their minimal inhibitory concentrations for bacteria responsible for pneumopathies. The lung homogenate binding of these antibiotics is weak (5% for erythromycin and 33% for tetracycline), corresponding to a nonsaturable binding to three main subcellular fractions (nucleus, mitochondria, and cytosol). Tetracycline has the same penetration in healthy or cancerous human lungs, whereas erythromycin presents a decreased IP in cancerous tissue. However, the binding of these antibiotics to healthy or cancerous lung homogenates is similar. So, the structure of cancerous cells is solely responsible for this modification of erythromycin penetration. The intrapulmonary concentration of tetracycline is increased in rat lungs infected by Legionella pneumophila. This modification is due to a great bacteria retention. In contrast, erythromycin possesses the same IP in healthy and infected rat lungs.

Binding parameters and microbiological activity of macrolides, lincosamides and streptogramins against Staphylococcus aureus.

Parameters of erythromycin binding to Staphylococcus aureus were measured in-vitro using an equilibrium method with [3H]erythromycin. The dissociation constant of the complex, erythromycin-S. aureus sensitive strain, was KD = 0.11 microM. The maximal binding, representing the density of binding sites was 14,847 molecules/cell. No binding was detectable on the constitutive resistant strain. Macrolides, streptogramins and lincosamides displaced bound [3H]erythromycin by a competitive process indicating that these compounds share common binding sites on the bacteria, i.e. 50 S ribosomal subunits. A good correlation (r = 0.99) was demonstrated between the corresponding inhibition constants (Ki) and the minimal inhibitory concentration. It is proposed that knowledge of the binding parameters provides a good indication of bacterial susceptibility and may serve as a useful adjunct in developing new compounds.

Long-lasting postmortem viability of human immunodeficiency virus: a potential risk in forensic medicine practice.

To determine the time from death when an autopsy could be carried out without any risk of contamination by human immunodeficiency virus (HIV), we cultured HIV from serial samples of blood and liquid effusion, collected as long as possible alter death from refrigerated dead bodies of HIV-infected patients. Samples were cocultivated with stimulated normal human lymphocytes and viral replication was assessed by p24 HIV1 antigen ELISA determination and by reverse transcriptase HIV1 and HIV2 activity microassay. Viable HIV was isolated from blood obtained 16.5 days postmortem, from pleural liquid effusion obtained 13.8 days postmortem, and from pericardial liquid effusion obtained 15.5 days postmortem. Viral replication was in evidence in at least one sample from all nine patients of the study. The present study did not allow us to determine a time from death when an autopsy could be carried out without any risk of contamination by HIV. We conclude that postponement of autopsies does not eliminate occupational risk of contamination by HIV.

[Prevalence of hepatitis C virus antibodies (tests ELISA 2 and RIBA 2) in a population of pregnant women in France]. / Prévalence des anticorps dirigés contre le virus de l'hépatite C (tests ELISA 2 et RIBA 2) dans une population de femmes enceintes en France.

We studied the prevalence of anti-HCV antibodies in a population of 2,367 pregnant women attending three public Parisian suburban hospitals. Of this group, 1,614 (68 percent) were French and 753 (32 percent) were immigrant women. The geographic origin of the immigrant population was North Africa (40 percent), West Africa (33 percent), Asia (14 percent), and South Europe (13 percent). Anti-HCV antibodies were tested by the Ortho ELISA second generation test. If present, the Ortho's four-antigen RIBA test and serum alanine aminotransferase determinations were done routinely. The overall prevalence was 1.73 percent. It was 1.55 percent in French women and 2.13 percent in immigrant women. Risk factors associated with anti-HCV were found in 68 percent of the anti-HCV positive French women and in 44 percent of the positive immigrant women. Risk factors were significantly more frequent in anti-HCV positive women in both groups. Among the 41 women with a positive ELISA test, 16/25 French women (64 percent) and 8/16 immigrants (50 percent) had a positive four-antigen RIBA test. Thus, the prevalence of a positive RIBA test was similar in both groups (0.99 and 1.06 percent), due to a higher proportion of false positive ELISA tests observed in the immigrants. These results show that, in French pregnant women: a) the prevalence of anti-HCV is twice as high as that found in blood donors and is a better estimation of the actual prevalence of these antibodies in France; b) positive ELISA 2 tests are most often confirmed by a positive RIBA 2 test.(ABSTRACT TRUNCATED AT 250 WORDS)

[Monoclonal immunoglobulins in kidney transplantation. Characterisation, evolution and risk factors]. / Immunoglobulines monoclonales en transplantation rénale. Caractérisation, évolution et facteurs de risque.

Sera from 192 consecutive HIV negative renal transplant patients with more than 6 months follow-up were investigated for monoclonal or oligoclonal immunoglobulins (mIg) by immunoelectrophoresis or immunofixation. Gammapathy was present in 25 patients (13 percent). Eleven patients had only one monoclonal band, whereas 14 had two or more bands. Sixty percent were IgG K, 29 percent IgG lambda and 11 percent IgM lambda or K. Ninety percent of these mIg did not exceed 2 g/l; mIg appeared within 2-27 months following the transplantation (mean time-lag 8 +/- 6.4 months). The mIg were often transient: 20 disappeared within 1-33 months, most of them (14) being absent after 1 year of follow-up. Some risk factors for mIg could be identified: the patient's age (a risk factor only in women); the duration of dialysis; the occurrence of prior CMV infection; treatment with cyclosporine. The persistence of mIg was characterised by one or more of the followings: high titer of mIg, EBV infection or reactivation, inability to switch from IgM to IgG CMV antibodies. No significant association was found with the hepatitis B surface antigenemia, previous infection with hepatitis C or the number of rejection episodes. In 6 patients, the clinical course was characterised by severe infection or tumours. Although long-term follow ups are not yet available, patients in whom one or more mIg have been demonstrated should be carefully followed.

[Hypersensitivity syndrome during Mycoplasma pneumoniae infection]. / Syndrome d'hypersensibilité au cours d'une infection à Mycoplasma pneumoniae.

BACKGROUND: Skin manifestations have been described in 25% of patients with Mycoplasma pneumoniae infection. CASE REPORT: We report a case of Mycoplasma pneumoniae infection in a 29-year-old man who developed a polymorphous erythema-like reaction. Skin manifestations were associated with voluminous lymph node enlargement and high eosinophil levels both in serum and alveolar lavage. Seroconversion against Mycoplasma pneumoniae IgG was documented with ELISA. The clinical course was favorable with erythromycin. DISCUSSION: ELISA IgG seroconversion is sufficient to confirm the diagnosis of Mycoplasma pneumoniae infection as this test has an 80-90% specificity. This case was unusual by its clinical presentation and high eosinophil counts in serum and tissue samples, similar to what is found in drug-induced hypersensitivity.