Serum concentration of human alpha 2 HS glycoprotein during the inflammatory process: evidence that alpha 2 HS glycoprotein is a negative acute-phase reactant.

A nonspecific opsonin function has been ascribed to human alpha 2 HS glycoprotein. Its serum level has been shown to be decreased in trauma patients. Recent studies from this laboratory revealed a heterogeneity among the products obtained in the course of the preparation of the protein. To date, no definitive agreement existed with regard to a molecular homogeneous entity of alpha 2 HS glycoprotein (Ba-alpha 2 glycoproteins). The purpose of the current work was to study the variations in serum level of alpha 2 HS in patients suffering from an acute inflammatory process of bacterial etiology and to determine whether a decrease in alpha 2 HS was accompanied by the appearance of fragments of this protein in the serum. A method of preparing alpha 2 HS was thus developed, using an immune absorbent as a final purification step. In an intermediary step of the preparation, alpha 2 HS was found to bind zinc when metal chelate affinity chromatography was employed. Immunologically and physico-chemically pure alpha 2 HS was obtained. The protein consists of a unique polypeptide chain of about 50,000 daltons and has a unique amino-terminal residue, alanine. However, the protein maintained its molecular integrity with difficulty, and spontaneous fragments ranging from 30,000 to less than 10,000 daltons were produced in some of the preparations. No major modification in the molecular structure of the protein was noted in the sera of subjects suffering from an acute inflammatory process. Serum level of alpha 2 HS and alpha 1 antitrypsin (AT)was determined in 23 patients. When the acute-phase (AP-)reactant alpha 1 AT was increased (difference with normal mean greater than +2 or +3 SD), the sera showed a large decrease in alpha 2 HS (difference with normal mean less than -2 or -3 SD). The serum level of alpha 2 HS, albumin, alpha 2 macroglobulin, and of positive AP-reactants, orosomucoidinal study of seven patients. The results were submitted to a principal components analysis. Alpha 2 HS showed a negative correlation with the AP-reactants alpha 1 AT, orosomucoid, and haptoglobin (P less than 0.05) and a positive correlation with albumin (P less than 0.05); these findings indicate that alpha 2 HS is a negative AP-reactant. In addition, analysis of the principal components confirms thestrong analogy between alpha 2 HS and albumin and indicates that serum level behavior of the AP-reactants during the course of the disease closely depends on the protein studied.

[Disseminated aspergillosis after intra-articular corticosteroid infiltrations]. / Aspergillose disséminée à point de départ articulaire après infiltrations.

Bone and joint infections due to Aspergillus are rare and occur more commonly in immunosuppressed patients. We report the case of an 84-year-old woman who developed septic arthritis caused by Aspergillus fumigatus after corticosteroid infiltration. This patient had presented with arthritis of the left knee for several months but no microorganism had been found despite numerous arthrocenteses. This arthritis was resistant to treatment by numerous corticosteroid infiltrations. During an arthroscopy, analysis of the synovial fluid yielded A. fumigatus. Thereafter, other explorations showed disseminated aspergillosis with osteo-articular destruction, blood and urinary dissemination. A systemic treatment by voriconazole associated to intra-articular injections and surgical debridement was initiated but the patient died. Septic arthritis caused by A. fumigatus is very rare but must be considered as a differential diagnosis of septic arthritis after corticosteroid infiltration. Their complications can be very important and destructive.

[Do HIV patients know their treatment?]. / Les patients infectés par le VIH connaissent-ils leurs traitements?

UNLABELLED: Optimal adherence to antiretroviral therapy (ART) in HIV disease is one of the key factors for its efficacy. OBJECTIVE: The authors had for aim to assess HIV infected patients' knowing of their ART and the correlation with a controlled HIV viral load. DESIGN: We conducted a transversal study. Outpatients were asked at the beginning of a consultation to give the name, the dosage, and the color of their medication. RESULTS: 93 patients were included with a mean age of 45.6 years. 25.8% were AIDS patients and 82.8% had an HIV viral load under 50 copies/ml. The mean duration of treatment was 6.23 years and the latest treatment had been given for 2.26 years. They took an average of 2.6 different drugs and 5.4 pills per day. 22.6% used a pillbox. 90.3% of the patients bought their treatment by themselves and 86% prepared it. The name of all the drugs was known in 68.8%, doses in 90.3%, and colors in 83.9%. In univariate as in multivariate analysis, the use of a pillbox improves the knowledge of the dose (P = 0.01). AIDS patients know the names better (P = 0.02). In univariate and multivariate analysis, knowledge of dosage was correlated to a controlled viral load (P = 0.04). CONCLUSIONS: HIV patients know their treatment well and the knowledge of the dose could be a marker of adherence to ART as it is associated with a controlled viral load.

[Salmonella of Indian origin: pseudo-susceptibility to fluoroquinolones]. / Salmonelle d'origine indienne: attention à la fausse sensibilité aux fluoroquinolones.

We report the case of a patient presenting with typhoid fever after returning from a stay in India. This infection was not cured with a course of ciprofloxacin, due to a reduced susceptibility of the bacteria to the drug. This decreased susceptibility to fluoroquinolones was not detected by the antibiogram, but the MIC for nalidixic acid was greater than 32 mg/l. This case suggests using a third generation cephalosporin instead of a quinolone, for people coming from a high-risk zone. It also suggests that the MIC for nalidixic acid and for norfloxacin can be used as the first clue for a reduced susceptibility to fluoroquinolones.

[Reactive arthritis due to Clostridium difficile]. / Arthrite réactionnelle a Clostridium difficile.

Extracolonic manifestations of Clostridium difficile infections have rarely been reported as a cause of reactive arthritis. We report the case of a monoarticular arthritis following pseudomembranous colitis. A 45 year-old man was admitted for fever and monoarthritis of the left knee, 8 days after the onset of a C. difficile enterocolitis associated with urethritis. Samples obtained from the knee, urine, and blood cultures remained sterile. Bone scintigraphy revealed a left knee and forefoot hyperfixations. The association of arthritis and urethritis led us to the diagnosis of Fiessinger-Leroy-Reiter syndrome. Antibiotics for arthritis were ineffective and stopped, but they were continued for colitis. NSAIDs were prescribed and clinical manifestations disappeared within 24 hours, the patient resumed walking after 48 hours. Four months later there was no relapse and no sequela.

Opportunistic infections occurring during highly active antiretroviral treatment.

OBJECTIVE: To analyse the characteristics of opportunistic infections in patients receiving highly active antiretroviral treatment (HAART). DESIGN AND METHODS: A retrospective study performed in seven hospitals, included all patients starting treatment by ritonavir or indinavir between 26 March and 31 December 1996. Patients were evaluated for the development of AIDS-defining events. Clinical evaluation, plasma HIV-1 RNA quantification, CD4 cell count were recorded at baseline and at the onset of the event. RESULTS: Four hundred and eighty-six patients were included: 44.2% had a CD4 cell count below 50 x 10(6) cells/l. Fifty clinical events were recorded in 46 patients with a mean follow-up of 6.1 months, of which 34 events (68%) were observed during the first 2 months of HAART. Eighteen of these occurred despite a reduction of viral load by at least 1.5 log10) and a 100% increase of the CD4 cell count compared with that at the onset of the event, corresponding to 11 cytomegalovirus infections, five mycobacterial infections, one case of cryptococcosis, and one case of Varicella-Zoster virus-related acute retinal necrosis. Among the 16 events observed after the second month, six occurred despite a marked biological improvement, corresponding to a recurrence in five of six patients who had stopped their maintenance therapy. Events were one cytomegalovirus infection, two mycobacterial infections, one episode of oesophageal candidiasis and one cryptococcal meningitis. CONCLUSION: In patients at high risk of developing an opportunistic infection prior to the institution of a HAART regimen, prophylaxis should not be discontinued during the first 2 months of treatment, and maintenance therapy should be carried on despite a significant increase in the CD4 cell count.

Evaluation of BC-3 and BCP-1 cell lines in immunofluorescence assay to detect HHV-8 antibodies in Kaposi's sarcoma, multiple myeloma and other groups.

BACKGROUND: We describe a comparative study of an immunofluorescence assay using inducible BC-3 and BCP-1 cell lines as sources of HHV-8 antigens. STUDY DESIGN: Detection of both antibodies to proteins expressed in lytic cycle and during latency in sera from HIV-infected patients with KS, HIV-positive patients without KS, normal blood donors, HIV-negative pregnant women and HIV-negative patients with multiple myeloma. Where possible, detection of antibody was associated with nested PCR detection of HHV-8 in peripheral mononuclear cell (PBMC) samples collected from AIDS-KS patients. RESULTS: Immunofluorescence was more intense with the BC-3 cell line than with BCP-1, thus facilitating examination under the microscope. HHV-8 antibodies were detected among 82.75% of AIDS-KS patients, in 27.3% of HIV-infected homosexual men, 2% of blood donors and in 2% of pregnant women. No HHV-8 antibodies were detected in serum samples from HIV-negative patients presenting multiple myeloma. HHV-8 DNA sequences were detected and confirmed by southern blot hybridization in five out of 17 (29.4%) PBMC samples from AIDS-KS patients. Titre of antibodies to proteins expressed in lytic cycle was much higher than the titre of antibodies to proteins expressed during latency. CONCLUSIONS: Both immunofluorescence assays were found useful and HHV-8 seroprevalence rates reported in previous studies were confirmed. In addition, results obtained using these assays tend to provide evidence for a lack of epidemiological association between HHV-8 infection and development of multiple myeloma.

[Extrapulmonary tuberculosis in the central western region. Retrospective study of 217 cases (Gericco 1991-1993)]. / Tuberculose extrapulmonaire dans la région centre-ouest. Etude rétrospective de 217 cas (Gericco 1991-1993).

OBJECTIVES: To analyze the epidemiological, clinical and diagnostic characteristics of extrapulmonary tuberculosis in western France observed from 1991 to 1993 in different patients populations (HIV+ infected patients, immunosuppressed non-HIV infected patients, non-immunosuppressed patients) and according to various localizations (lymph nodes, bone and joints, genital organs, nervous system and meninges, miliary disease). METHODS: This retrospective study included 217 cases of extrapulmonary tuberculosis diagnosed from 1991 to 1993 in western France by GERICCO (Groupe d'Epidémiologie et de Recherche en Infectiologie Clinique du Centre-Ouest). Demographic, clinical, biological, microbiological and radiographic characteristics as well as clinical course on specific therapy were assessed. RESULTS: Extrapulmonary tuberculosis generally occurred most often in immunosuppressed patients but 34% of cases were observed in people without any underlying disease or risk factors. Delay to diagnosis was especially long in the non-immunosuppressed patients (mean = 96 days) but shorter in the HIV-infected patients (mean = 59 days). It was shorter in case of nervous system involvement (mean = 52 days) or military disease (mean = 80 days) than in bone and joints (mean = 120 days) and lymph nodes (mean = 102 days). Microbiologically proven tuberculosis represented only 75% of cases despite numerous investigations. Overall prognosis was good except in nervous system and meninges localizations. Failures were mainly due to death in immunosuppressed patients. CONCLUSION: Extrapulmonary tuberculosis remains frequent even in patients lacking risk factors. In 50% of cases, confirmation of diagnosis takes more than one month. In case of doubt, clinicians should not wait for laboratory results before implementing empirical specific therapy.

Cefoxitin concentrations in the cerebrospinal fluids of patients with meningitis.

The concentrations of cefoxitin in serum and cerebrospinal fluid (CSF) were measured simultaneously in three groups of patients, 12 with aseptic meningitis (group 1) and 17 and 14 with bacterial meningitis (groups 2 and 3). The patients in group 1 received a single intravenous dose of 2 g of cefoxitin without other antimicrobial therapy. In addition to conventional doses of ampicillin or benzyl penicillin, patients in groups 2 and 3 received repeated infusions of 2 g of cefoxitin every 4 h for the first 3 or 4 days of the study and again on day 10. Additionally, group 3 received probenecid in a loading dose of 1 g followed by 0.5 g every 6 or 8 h. Concentrations of cefoxitin in CSF and serum were determined 1 or 2 h after infusion in group 2 and 2 h after infusion in group 3. The concentrations of cefoxitin in CSF did not reach detectable levels (1.56 microgram/ml) in 11 of the 12 patients in group 1. A level of 2.8 microgram of cefoxitin per ml of CSF was found, with an accompanying level of 30 microgram/ml of serum, in patient 12. In the group 2 patients with bacterial meningitis, the mean CSF concentrations were 3.3, 4.7, and 2.9 microgram/ ml on days 1, 3, and 10 of treatment, with simultaneous serum levels of 8, 9, and 8 microgram/ml. At similar times periods, the mean levels of cefoxitin in group 3 patients (with concomitant probenecid) were 8.6, 12.3, and 4.3 microgram/ml of CSF and 57, 35, 27 microgram/ml of serum.

[Seroprevalence of HBV, HCV and HDV hepatitis markers in 500 patients infected with the human immunodeficiency virus]. / Séroprévalence des marqueurs des virus des hépatites B, C et D chez 500 patients infectés par le virus de l'immunodéficience humaine.

The serological status for both hepatitis B, C and D viruses was analyzed for 500 HIV seropositive patients and for 1037 of a control group. The prevalence was 31.4% for anti HCV, 13.8% for HBs Ag and 69.0% for one or more HBV markers in HIV positive patients and respectively 2.5%, 2.7% and 13.1% in control group. The markers for hepatitis D were founded among 21% of the HBs Ag carriers (patients and control group), correlated with drug i.v. use. The prevalence of anti-HCV was 71.6% in subjects who had blood-borne HIV infection and 1.5% in those with sexually acquired infection. The prevalence in control group was 10.2% and 1.7% respectively according to the same risk factors. The prevalence of HBs Ag was higher among HIV positive patients with sexual risk (17.5%) than with blood exposition (9.9%) and a variation in the same direction is observed in control group (3% v.s. 1%). The relation between markers for hepatitis B and hepatitis C was negative.

Enteric prevalence of adenovirus in human immunodeficiency virus seropositive patients.

To evaluate the prevalence of adenovirus strains in human immunodeficiency virus (HIV)-positive patients and to investigate their possible role in the onset of diarrhea, a total of 103 stools from HIV-seropositive patients at various stages of infection and 200 stools from sex and age cross-matched control subjects were examined. Adenovirus prevalence was measured by ELISA as well as conventional and rapid cell culture techniques. Results were compared between patients suffering from diarrhea and those without diarrhea. Adenovirus prevalence was statistically greater in HIV-seropositive cases than controls (8.7%, 2.5%, respectively). No significant difference was found between HIV-positive patients with diarrhea and those without gastrointestinal complications (P > 0.05). However, a significant difference in adenovirus prevalence was found between HIV-positive patients with diarrhea and control subjects with diarrhea (P = 0.02). Although viral prevalence varied with the different stages of HIV infection, differences were not statistically significant. In conclusion, although current opinion considers adenoviruses to be no more than opportunistic pathogens, the results of this large-scale study do not exclude a potential reactivation of latent adenovirus in HIV infection and suggest that further effort should be directed to elucidating such a mechanism if it exists as well as investigating the specific role of certain adenovirus serotypes in provoking diarrhea during later stages of HIV infection.

[The use of antibiotic treatment in osteoarticular infections]. / L'utilisation du traitment antibiotique dans les infections ostéo-articulaires.

The authors emphasise the interest of identification of the germ during bone and joint infections, and recall the main data, often fragmentary, one the diffusion of antibiotics into bone. Concerning the practical use of antibiotics, they emphasise the necessity of basing their treatment on bacteriological examinations before choosing an association of two antibiotics, the effect of which will be regularly assessed by a study of the bactericidal power of the serum.

[Multifocal tuberculosis. Apropos of 49 cases in the midwest region. GERICCO (Group for Epidemiology and Research in Clinical Infections of the Central West of France), 1991-1993]. / Tuberculose multifocale. A propos de 49 cas dans la région Centre-Ouest (Géricco, 1991-1993).

Diffuse or multifocal tuberculosis (TB) accounts for 9% to 10% of cases of extrapulmonary TB and carries a poor prognosis with a mortality rate of 16% to 25%. Forty-nine cases of multifocal TB defined as involvement of two extrapulmonary sites with or without pulmonary TB were reviewed. Mean patient age (+/- SD) was 50 +/- 18 years. Twenty-three per cent of patients were immigrants. A history of TB and contact with a TB patient were found in 23% and 18% of cases, respectively. Of the 52% of immunocompromised patients, 38% were HIV-positive. The skin tuberculin test was positive in 67% of cases. Mean time from symptom onset to admission was 80 +/- 77 days (median, 58 days). The 49 patients had a total of 128 TB foci. Six patients had positive blood cultures. The tubercle bacillus was recovered from the extrapulmonary sites in 88% of cases. Mean treatment duration was nine months. Recovery from the TB was achieved in 64% of cases. The overall mortality rate was 47%, and 33% of patients died as the direct result of TB. Most deaths occurred in immunocompromised patients. A high index of suspicion for multifocal TB should be maintained in immunocompromised patients, even those who test negative for the HIV.