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Biomedical subjects

M Girard

Publications and source records attributed to M Girard.

At least 127 records · Page 7Linked to original sources

Reversed-phase LC assay method for deoxycholate in influenza vaccine.

Sodium deoxycholate is used for the disruption of particles in the manufacturing of some influenza vaccines. Residual deoxycholate in inactivated vaccines is currently determined using a labour-intensive colorimetric method which lacks complete specificity. An alternative assay method for residual deoxycholate in vaccine preparations was developed using reversed-phase LC. Cholic acid was used as internal standard and the ratio of internal standard to test solute was used for all calculations. Prior to LC analysis, deoxycholic acid was concentrated by solid-phase extraction, a procedure that also removed proteinaceous material in vaccine samples. The clean-up/concentration procedure recovery was examined using untreated samples and was found to be quantitative. The linearity range of the LC method was between 3 and 200 micrograms ml-1, with a limit of detection of approximately 0.4 micrograms on column, and a lower limit of quantitation of 1.6 micrograms on column. Replicate assays during intra-and inter-day experiments gave acceptable levels of variability. The DCA content of samples from three lots of influenza vaccine varied between 10 and 16 micrograms ml-1. These values were appreciably lower than those measured spectrophotometrically, indicating the higher specificity of the LC method.

Cholic Acid↗

Percutaneous internal ureteral stent placement: review of technical issues and solutions in 50 consecutive cases.

Fifty consecutive percutaneous ureteral stent placements in 40 patients over 2 1/2 years were reviewed. Thirty-seven of 50 cases were performed following failed retrograde stenting. Antegrade stenting failed in 2/37 (5%) cases of malignant obstruction, and 4/13 (31%) cases of benign ureteral disease. Causes of failure and common technical problems included poor angulation of the percutaneous track, tortuous dilated ureters, tight obstructions, wedging of stent assembly components due to high resistance, and difficulty in positioning of the proximal pigtail. Helpful technical modifications included mid-pole rather than lower pole calyceal access, urinary decompression prior to stenting, and the routine use of a peel-away sheath (success rate 23/24 placements with sheath vs 21/26 without sheath). Stent patency rates were 95% at 3 months and 54% at 6 months. With attention to technique and appropriate modifications, success rate of percutaneous stenting remained high in this series despite the large number of cases referred after retrograde stenting had failed.

Adolescent↗

High prevalence of hepatitis C virus RNA in the supernatant and the cryoprecipitate of patients with essential and secondary type II mixed cryoglobulinemia.

Detection of hepatitis C virus RNA by polymerase chain reaction was performed in 26 patients with type II mixed cryoglobulinemia, and compared with anti-HCV antibody detection. The patients were divided into two groups according to etiology: 15 had essential type II mixed cryoglobulinemia and 11 had secondary type II mixed cryoglobulinemia. In the essential type II mixed cryoglobulinemia group, the prevalence of hepatitis C virus RNA detected by polymerase chain reaction was 60% in the supernatant and 93% in the cryoprecipitate. In the secondary type II mixed cryoglobulinemia group the prevalence of hepatitis C virus RNA was 45% in the supernatant and 55% in the cryoprecipitate. The differences between the two groups were not statistically significant. In both patient groups, detection of hepatitis C virus RNA in the cryoprecipitate was the most sensitive test for hepatitis C virus infection. These results suggest that hepatitis C virus might be involved in the origin of mixed cryoglobulinemia.

Aged↗

A novel, glycan-dependent epitope in the V2 domain of human immunodeficiency virus type 1 gp120 is recognized by a highly potent, neutralizing chimpanzee monoclonal antibody.

An anti-gp120 monoclonal antibody (MAb), C108G (gamma 1, kappa), was isolated from a chimpanzee that had been infected with strain IIIB of human immunodeficiency virus type 1 (HIV-1IIIB) and subsequently immunized with the recombinant glycoprotein rgp160MN. This MAb is specific for the IIIB strain of HIV-1 and related clones and exhibits very potent neutralization of these viruses; e.g., 100% neutralization of approximately 8 x 10(3) infectious units of HXB2 was achieved with 125 ng of C108G per ml. Commensurate with this potent neutralizing activity, the apparent affinity of C108G for rgp160LAI was very high, i.e., approximately 3 x 10(10) liters/mol. The C108G epitope was not destroyed by reduction of gp120 disulfide bonds but was profoundly disrupted by removal of N-linked sugars from gp120. Despite the importance of a glycan(s) in forming the C108G epitope, specific binding of C108G to synthetic peptides overlapping in amino acids 162 to 169 of the V2 region was detected, albeit with an affinity approximately 2,000-fold lower than that of C108G's binding to glycosylated envelope protein. This epitope mapping correlated with results of competition assays using MAbs of known epitope specificities. To our knowledge, this is the first description of an anti-V2 MAb raised in response to HIV-1 infection. Its potent neutralizing activity and epitope specificity indicate that the V2 domain of gp120 may be an effective target of the protective immune response and, therefore, potentially an important component of HIV vaccines.

Amino Acid Sequence↗

Synoviorthesis with colloidal 32P chromic phosphate for the treatment of hemophilic arthropathy.

Between 1977 and 1992, we performed ninety-two synoviortheses (destruction of synovial tissue by intra-articular injection of a radioactive agent) on forty-eight patients who had a severe congenital disorder of hemostasis and chronic hemophilic synovitis that was resistant to conventional treatment. Colloidal 32P chromic phosphate was injected intra-articularly: 1.0 millicurie for knees and 0.5 millicurie for other joints. The duration of follow-up ranged from one to fifteen years. The frequency and importance of bleeding decreased in most of the patients. The range of motion of half of the joints remained stable or improved and that of the other half continued to decrease. Radiographic scores worsened progressively despite the decreased frequency of hemarthrosis. In most patients, the extra-articular leakage of the radioactive agent was slight. Chromosome breakages were observed almost exclusively in patients who were seropositive for human immunodeficiency virus and in whom the CD4-lymphocyte count was decreased from normal. The patients' level of satisfaction with the results was high.

Adolescent↗

Strategically integrating hospital/home care services for improved profitability.

Because hospitals and home health agencies have been predominantly separate organizations, coordination of their efforts has not been optimized. However, with the recent proliferation of hospital-based home health agencies, opportunities to integrate these health care service delivery systems have increased. Bethesda Memorial Hospital, Boynton Beach, Fla., is a 362-bed not-for-profit community hospital with a Medicare-certified home health agency organized as a department of the hospital. Until recently, the home health agency was generally perceived as a separate entity whose services were distinct from hospital services. Progress toward integration of hospital and home care services was given impetus through collaboration of the home health agency administrator and a newly appointed director of medical affairs who was given the responsibility as medical director of the home health agency. A prime responsibility of the director of medical affairs was to reduce length of stay and hospital costs through appropriate resource management.

Cost-Benefit Analysis↗

[Can early recurrent hemorrhage in gastroduodenal ulcer be predicted?].

OBJECTIVE: To evaluate clinical, biological and endoscopic predictive factors of early recurrent bleeding from gastric or duodenal ulcers. PATIENTS AND METHODS: Seventy six patients (26 females and 50 males) with a mean age of 65.9 years (SD = 17.2) were included in a prospective study. Among the 76 patients, there were 39 NSAIDs users (51.3%). An endoscopy was performed systematically until 12 hours after admission. Treatment modalities were identical for all patients. The predictive value of 11 factors was evaluated through an univariate and multivariate analysis. RESULTS: Three factors had independent significant predictive value: a) the number of blood units used to treat a shock and to increase the haemoglobin level up to 100 g/L (P < 0.05); b) "high endoscopic risk" of recurrent bleeding including Forrest Ia, IIa and IIb ulcers (P < 0.05); c) a non steroidal anti-inflammatory treatment was associated with no recurrent bleeding contrary to the other factors (P < 0.05). Based on a second multivariate analysis including clinical factors only, a predictive score was calculated: 5 + number of blood units -5 x (NSAID = 0/1). The cut off point with maximum discrimination was 6 (specificity = 79.6%; sensitivity = 77.2%). CONCLUSION: A combination of clinical and endoscopic factors is useful to predict ulcer recurrent bleeding. Our clinical predictive score is interesting because of its simplicity. Its predictive value is of interest but have to be evaluated in another sample of patients.

Adult↗

[Is there a relationship between the presence of autoantibodies or mixed cryoglobulinemia and the clinical and histological characteristics of chronic viral hepatitis C?].

The purpose of this prospective work was to study a possible relationship between autoantibodies, cryoglobulinaemia and liver histologic lesions in chronic hepatitis C. Ninety three patients (mean age: 43.3 years) with histologically proven chronic hepatitis were studied. Chronic hepatitis was associated with cirrhosis in 18 cases. Auto-antibodies detection was performed in the serum of all patients and cryoglobulinaemia detection was performed in 47 patients. The prevalence of auto-antibodies was also studied in 45 blood donors (control group) and 30 patients with chronic hepatitis B. Histologic study included Knodell score and semi-quantitatively expressed histologic lesions considered as more specific of chronic hepatitis C. Twenty six of the 93 patients (28%) had at least an autoantibody with a level > or = 1/100. The autoantibodies prevalence was: smooth muscle: 15%, antinuclear: 15%, LKM 1: 1.2%, mitochondrial: 0. A mixed cryoglobulinaemia was present in 23 of 47 patients (49%). The prevalence of anti-smooth-muscle autoantibodies was significantly increased in hepatitis C patients compared with the control group (P < 0.05). The histologic Knodell score was 7.3 +/- 3.6. The histologic lesion prevalence was: portal tract lymphoid follicles: 97%, acidophil bodies: 85%, intra-sinusoidal lymphoid infiltrates: 71%, steatosis: 61%, microgranulomas: 54%, biliary duct tract damages: 53%. No statistical significant correlation was found between autoantibodies prevalence and liver histologic lesions. The Knodell score was only significantly increased in patients with mixed cryoglobulinaemia (8.4 +/- 3.6 vs 6.2 +/- 2.8) (P < 0.05). These results suggest that the autoantibodies presence in chronic hepatitis C does not change hepatic histologic lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Potential use of poliovirus as a vector.

The live attenuated Sabin strains of poliovirus have proven their efficacy at inducing a good humoral and secretory antibody response in humans. The extensive characterization of poliovirus neutralization antigenic sites and the atomic resolution of the three-dimensional structure of the viral capsid have enabled the use of the most stably attenuated poliovirus strain (the Sabin type 1 strain) as a vector for the presentation of short foreign antigenic domains in place of one of its own neutralization antigenic sites. The creation of such chimeras has been achieved by manipulating poliovirus infectious cDNA and transfecting the resulting chimeric cDNAs onto susceptible cell cultures. However, this epitope-presentation system has a limitation in terms of the sequence and size of the foreign domain that can be incorporated into the poliovirus capsid without disrupting virus viability. This has led to the construction of poliovirus hybrid genomes bearing insertions of longer heterologous sequences in place of part of the poliovirus structural genes. Upon transfection onto susceptible cells providing the poliovirus structural proteins in trans (e.g. cells previously infected with the Sabin 1 strain), stocks of encapsidated RNA replicons which expressed the foreign protein could be obtained. In addition, viable recombinant viruses bearing insertions of heterologous sequences at various places into the poliovirus genome without deleting poliovirus sequences have been reported. Potential applications of these chimeric and recombinant polioviruses in the engineering of new recombinant vaccines are discussed.

Animals↗

Substitution mutations at the putative catalytic triad of the poliovirus 3C protease have differential effects on cleavage at different sites.

Picornavirus 3C proteases are substrate-specific cysteine proteases, proposed to be homologous to the trypsin/chymotrypsin-like serine proteases on the basis of structural predictions. Substitutions at the putative active-site residues (Glu71 and Cys147) of the poliovirus 3C protease did not completely abolish proteolytic processing in vitro. The activity of mutated 3C proteases was in the following hierarchy: Glu71-Cys147 (wild type) > Asp71-Cys147 > Glu71-Ser147 > Gln71-Cys147 > Asp71-Ser147 > Gln71-Ser147 (inactive at all sites). Such mutations had differential effects on cleavage at different sites of the poliovirus polyprotein. Cleavage within the P1 region of the polyprotein was the most defective, at the 1ABC/VP1 junction and particularly at the VP0/VP3 junction. Cleavage at the 3AB/3CD and 2B/2C junctions was less affected by the mutations, and the P2/P3 and 2A/2BC junctions were cleaved efficiently by all mutants except Gln71-Ser147. All the 3C mutants gave negative results in infectivity and replication assays after transfection, indicating that mutation of Glu71 or Cys147 virtually abolishes viral replication, irrespective of the efficiency of processing of the nonstructural part of the polyprotein.

3C Viral Proteases↗

Impact of screening donor blood for alanine aminotransferase and antibody to hepatitis B core antigen on the risk of hepatitis C virus transmission.

The transfusion-related risk of transmission of hepatitis C virus (HCV) was evaluated in France for the periods before and after exclusion of donor blood units with the surrogate markers elevated alanine aminotransferase (ALT) levels and antibody to hepatitis B core antigen (anti-HBc). A total of 1,412 blood recipients undergoing surgery were followed up prospectively in the period from 1986 to 1989. The stored serum samples were tested for antibodies to HCV by an enzyme immunoassay (EIA) and the result in reactive sera confirmed by a recombinant immunoblot assay (RIBA). The risk of HCV transmission was estimated by the maximum likelihood method for a subpopulation of 892 recipients divided into three groups. Of 55 (3.9%) EIA positive patients, 56.4% were found to be positive prior to transfusion. HCV seroconversion (positive RIBA) occurred in 22 patients (1.6%). The risk of HCV transmission per 1,000 transfused blood units decreased significantly from 4.11 in Group 1 (receiving non-screened blood) to 3.43 in Group II (receiving ALT screened blood) and to 1.40 in Group III (receiving ALT and anti-HBc screened blood). These results demonstrate that screening of donors for surrogate markers had reduced the risk of HCV transmission before the introduction of a systematic anti-HCV screening policy in France in March 1990.

Adolescent↗

[The use of magnesium sulfate during surgery of pheochromocytoma: apropos of 2 cases].

Maintenance of haemodynamic stability during anaesthesia for phaeochromocytoma resection is still a challenge. If magnesium sulfate is widely used for the control of arterial pressure during preeclampsia, its use during phaeochromocytoma resection has only been published by one author. We describe two cases where magnesium sulfate is the main agent used to control arterial pressure during resection of a phaeochromocytoma. Magnesium sulfate's hypotensive, antiarrhythmic and antiadrenergic properties are reviewed. The total doses administered were 11 g and 12 g, given as an infusion and boluses. Magnesium sulfate could be part of the anaesthetist's pharmacopoeia during phaeochromocytoma resection.

Adrenal Gland Neoplasms↗

The needs and hopes for an AIDS vaccine.

This article reviews the many difficulties met in the development of an effective vaccine against human immunodeficiency virus (HIV), including the considerable antigenic variability of the virus, its intracellular mode of transmission, its mucosal port of entry, and the persistent nature of the infection. Progresses in the development of prototype vaccines in animal models are discussed together with the results of initial clinical trials in human volunteers.

AIDS Vaccines↗

[A sickle cell homozygote with transfusion deadlock. Favorable outcome with hydroxyurea treatment].

Alloimmunization following multiple transfusions, a frequently observed complication in sickle cell anemia patients, may make subsequent transfusion attempts extremely hazardous. The case of a young woman with sickle-cell anemia is reported; she was hospitalized for the treatment of extensive invalidating leg ulcers. The transfusion program that was initiated as a prerequisite to skin allografts had to be stopped, due to rapid occurrence of multiple alloimmunization. Broad spectrum alloantibodies precluded further selection of compatible blood units. In an attempt to get round this impossibility, a treatment with Hydroxyurea was initiated in order to boost synthesis of F-hemoglobin. After one year under this treatment, the patient's clinical status has clearly improved without requiring any new blood transfusion.

Adult↗

High viral load in lymph nodes and latent human immunodeficiency virus (HIV) in peripheral blood cells of HIV-1-infected chimpanzees.

We have examined human immunodeficiency virus type 1 (HIV-1) infection in chimpanzees by analyzing HIV-1 DNA and RNA in lymph nodes and peripheral mononuclear cells (PBMCs). Like certain asymptomatic HIV-infected persons, these chimpanzees had no detectable viral replication in their PBMCs. However, viral replication and a high viral load were observed in the lymphatic tissue. Despite the absence of viral replication in PBMCs, 1/1,000 to 1/10,000 of the PBMCs contained HIV-1 proviral DNA, and HIV transcription could be rapidly induced in these cells in vitro. These results provide direct evidence of cellular latency of HIV in vivo and suggest that HIV infection in chimpanzees may be a useful model for clinical latency of HIV infection in humans.

Animals↗