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Biomedical subjects

P C Frei

Publications and source records attributed to P C Frei.

At least 37 records · Page 2Linked to original sources

Multicenter evaluation of new double-antigen sandwich enzyme immunoassay for measurement of anti-human immunodeficiency virus type 1 and type 2 antibodies.

A new enzyme immunoassay (EIA), the Cobas Core Anti-HIV-1/HIV-2 EIA DAGS (also referred to as Roche DAGS), for the detection of antibodies to human immunodeficiency virus type 1 (HIV-1) and HIV-2 was evaluated in four centers. The assay is based on the double-antigen sandwich (DAGS) format, which enables the detection of all classes of antibodies. The antigens consist of recombinant proteins in their native conformation and of synthetic peptides. Of a total of 5,836 negative serum samples, including 95 samples likely to produce false reactivities, 6 were false positive, resulting in a specificity of 99.9%. None of 35 sera that were from noninfected individuals but contained p24-cross-reacting antibodies as revealed by Western blot (immunoblot) analysis were reactive by the Roche DAGS assay. In samples from individuals infected with HIV-1 group M (n = 499) and HIV-2 (n = 200), the sensitivity of the assay was 100%. Although containing antigens with sequences from subtype B only, the assay was also able to correctly identify with high optical density/cutoff ratios samples from subjects infected with HIV-1 subtype O (n = 10). In 17 of 19 seroconversion panels tested, the assay detected the presence of HIV-1 antibodies as early as another sandwich EIA. Eight of these panels were also analyzed by an indirect second-generation assay, which detected antibodies 2 to 10 days later than did the DAGS assay under evaluation. The excellent specificity and sensitivity of the new Cobas Core Anti-HIV-1/HIV-2 EIA DAGS are the result of the DAGS format as well as of the native, naturally folded form of the recombinant protein used as the gag antigen.

Female↗

[Occupational activities and allergic respiratory manifestations].

The authors review aspects of occupational asthma that are important for the practitioner. Insurance problems are dealt with in the light of local regulations. Detailed chapters are devoted to baker's asthma (various aeroallergens), to plastic workers and painters (isocyanates) and to respiratory diseases among farmers. Finally, a list of other occupations in which asthma typically occurs is given. The responsibility of practitioners in charge of young patients about to choose their future profession is underlined.

Agricultural Workers' Diseases↗

Role of two-dimensional electrophoretic analysis in the diagnosis and characterization of IgD monoclonal gammopathy.

Over a period of 5 years, an isolated light chain (kappa = 9, lambda = 12) was detected in 21 sera by immunofixation electrophoresis. Further analysis with anti-delta- and anti-epsilon-specific antisera identified four delta heavy chains, all associated with a lambda light chain, and no epsilon heavy chains. For evaluation of the role of two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) in the diagnosis of IgD paraproteins, as a possible alternative or complement to immunofixation, IgD paraproteins were retrospectively analyzed by 2D-PAGE. Delta Heavy chains migrated to gel areas clearly distinguishable from other heavy chains alpha, gamma, or mu, and in a wide range of isoelectric points (pI: 5.4-8). In one serum, the monoclonal delta chain had a pI range comparable to that of albumin and was undetectable. However, all four delta chains were easily identified when analyzed from affinity-purified immunoglobulin fractions. These observations showed the following: 1) IgD paraproteins are not rare among apparently isolated monoclonal light chains detected by routine immunofixation, strongly confirming the need for further analysis with anti-delta antisera, before assumption of a light-chain disease. 2) 2D-PAGE analysis of affinity-purified immunoglobulin fractions allowed correct identification of IgD monoclonal gammopathies in all cases. 3) However, although 2D-PAGE analysis is now easy to perform, well standardized, and highly sensitive, this technique remains time-consuming and expensive, and does not appear suitable for routine practice as a first-line diagnostic procedure. 2D-PAGE should find its place as a complement to immunofixation and in the definitive demonstration, in selected ambiguous cases, of the clonal pattern of a suspected gammopathy at immunofixation.

Blotting, Western↗

Long-term evaluation of usefulness of skin and incremental challenge tests in patients with history of adverse reaction to local anesthetics.

A variety of adverse reactions to local anesthetics has been described, some of which are thought to be allergic. Different protocols of prick and intradermal skin tests as well as subcutaneous challenge tests are used to select a local anesthetic which can safely be used. Their long-term effectiveness has not yet been assessed. Twenty-eight patients with a history of adverse reaction to local anesthetics were evaluated over a 3-year period. Loss of consciousness occurred in eight patients, skin reaction in nine, and vagal symptoms in eight. Various reactions were recorded in the remaining three patients. Rapid spontaneous recovery was the rule, suggesting that immediate allergic reaction and, in particular, anaphylactic reaction were unlikely. Investigation allowed the selection of a tolerated anesthetic in all cases. Reexposure occurred in 19 patients 16-50 months after evaluation and 6.8 +/- 5.5 years after the first reaction. No patient presented a second reaction. In conclusion, adverse reactions to local anesthetics seem to be, in most cases, not allergic in nature. Evaluation protocols are effective in selecting an agent susceptible to tolerance, but are time consuming. However, they probably contribute to an important reassurance effect that is likely to increase tolerance to subsequent local anesthetic administration. Simplification of the protocols and better patient selection are proposed.

Adult↗

Anti-human immunodeficiency virus type 1 antibodies of noninfected subjects are not related to autoantibodies occurring in systemic diseases.

Indeterminate Western blot (WB) (immunoblot) patterns for anti-human immunodeficiency virus type 1 (HIV-1) antibodies are often observed when testing serum samples from noninfected individuals. We investigated here the possible involvement of some frequently occurring autoantibodies (anti-SmB/B', U1snRNP [68 kDa, A, and C], Ro/SS-A [60 and 52 kDa], and Jo-1) in the generation of such indeterminate HIV-1 WB. In particular, the role of a reported sequence homology between p24 gag and the SmB/B' autoantigen was investigated. Serum samples were obtained from 50 healthy controls, 51 patients with systemic lupus erythematosus (SLE), 46 with systemic sclerosis, 6 with Sjögren's disease, 3 with mixed connective tissue disease, and 41 healthy subjects with persistent indeterminate HIV-1 WB. Reactivity to HIV-1 p24 gag was slightly but not significantly more frequent in patients with SLE than in controls (25.5% versus 14.0%; P > 0.1), whereas reactivity to HIV-1 p17 gag was significantly more frequent in the former subjects (23.5% versus 8.0%; P = 0.03). Simultaneous reactivity to p17 and p24 was observed in patients with SLE (11.8%; P = 0.014) or systemic sclerosis (8.7%; P = 0.049) but not in controls. There was no association found between the presence of any autoantibody and the occurrence of indeterminate HIV-1 WB nor between the presence of p24-reactive antibodies and anti-SmB/B'; this indicates that most p24-reactive antibodies are directed to epitopes other than the proline-rich sequences shared by p24 gag and SmB/B'.

Aged↗

Immunogenicity of a recombinant Pre-S2-containing hepatitis B vaccine versus plasma-derived vaccine administered as a booster.

GenHevac B Pasteur is a recombinant hepatitis B vaccine derived from a mammalian cell line and containing HBs as well as pre-S2 antigens. Its immunogenicity was compared to that of the plasma-derived vaccine Hevac B Pasteur in a population primovaccinated 5.5 years earlier with four injections of the same plasma vaccine. The booster injection with either GenHevac or Hevac was administered to 295 subjects with residual anti-HBs titres below 500 IU/l (group 1: 0-9; group 2: 10-99; group 3: 100-499 IU/l). After four weeks, GenHevac had induced higher anti-HBs responses than Hevac in all groups, particularly among the low responders of group 1. Response to the vaccine occurred earlier with GenHevac. Mean anti-pre-S2 production was moderate in all groups for both vaccines (GenHevac: 60 IU/l; Hevac: 31 IU/l) and was not found in the 32 subjects who produced less than 100 IU/l anti-HBs. The results of the present study indicate that GenHevac is at least as immunogenic as Hevac.

Adult↗

Efficacy of steroid withdrawal and low-dose interferon treatment in chronic active hepatitis B. Results of a randomized multicenter trial. Swiss Association for the Study of the Liver.

Fifty-six patients with biopsy-proven, chronic active hepatitis B were included in a multi-center, randomized trial comparing steroid withdrawal followed by 1.5 MU recombinant interferon alpha 2b (Intron) with placebo withdrawal followed by either 1.5 or 5 MU interferon. The patients were equally distributed between the treatment groups with respect to biochemical and histologic activity as well as with respect to DNA levels and quantitative liver function tests. One patient was lost to follow up. After 1 year of treatment, 10/18, 13/19 and 11/18 patients had lost hepatitis B virus DNA in the three groups, respectively (non-significant). Transaminase levels were normal in 27/34 of the responders but in only 4/21 of the non-responders (p < 0.0001). Both galactose elimination capacity and aminopyrine breath test improved significantly in responders, but either did not change (aminopyrine breath test) or deteriorated in non-responders (galactose elimination capacity). Biopsy score improved in both groups but this reached statistical significance only in responders. This effect was due to improvements in both inflammatory and fibrotic activity. Side effects included almost universally a flu-like syndrome, granulocytopenia (1), depression (3) and thyroid dysfunction (2). Two deaths occurred, one due to hepatocellular cancer, and the other to hepatorenal syndrome after spontaneous bacterial peritonitis. A severe cytolytic episode was observed in three patients in the steroid withdrawal group. We conclude that in patients with marked histologic activity, lower doses of interferon may be as effective as the standard dose of 5 MU.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

IgE to food allergens are highly prevalent in patients allergic to pollens, with and without symptoms of food allergy.

Serum samples from 274 patients allergic to one or more of three pollens (birch, grass, mugwort), from 36 patients allergic to cat and/or Dermatophagoides pteronyssinus but not to pollen and from 55 non-allergic controls, as well as 20 cord blood samples, were examined for specific IgE to six 'pollen-associated' food allergens by using a new sensitive assay (CAP). A questionnaire asking for reactions to food was also sent to all patients. In the pollen group, 111 patients (47%) were positive (> or = 0.71 kU/l) for a food allergen (392 positive tests). Of these, 92 were sensitive to apple, 68 to potato, 64 to carrot, 63 to celery, 61 to peach and 44 to melon. In the non-allergic group, no IgE to any of the food allergens tested was found, whereas in the group allergic to non-pollen allergens, only one individual had such an IgE. The CAP assay was found to be more sensitive than RAST for the allergens studied. A history of clinical reactions (oral symptoms in 67, rhinoconjunctivitis in 65, asthma in 42 and urticaria in 39) to the corresponding food allergen was reported mainly by patients with positive CAP. In conclusion, we found a high prevalence of IgE to some food allergens in patients allergic to pollen and the absence of such antibodies in the control groups. The new in vitro assay, being more sensitive than previous ones, indicated a high prevalence of food specific IgE in pollen allergic patients, which in many cases did not correspond to clinical symptoms of food allergy.

Adolescent↗

Prevalence of IgE antibodies specific for food allergens in patients with chronic urticaria of unexplained etiology.

We investigated whether some cases of chronic urticaria of unexplained cause might be related to food allergy which had remained undetected during routine examination. This investigation was undertaken as the consequence of the availability of a new in vitro assay for specific IgE with increased sensitivity. The following three groups of subjects were studied: 1) a control group of 60 nonatopic subjects, 2) 60 patients with allergy to perennial aeroallergens without skin involvement, and 3) 60 patients suffering from chronic urticaria with no evidence of any triggering factor despite careful clinical investigation. Specific IgE against 19 food allergens frequently involved in urticaria were investigated in all subjects with the new CAP System (Pharmacia). Positive results (CAP > 0.70 kU/l) for one or more food allergens were found in none of the nonatopic controls, in six of the subjects with respiratory allergy, and in 16 of the urticaria patients. The use of an in vitro test with an increased sensitivity allowed us to detect a significant prevalence of IgE specific for food allergens in patients with chronic urticaria of unknown origin. This suggests that, in several of those patients, chronic urticaria might be triggered by a food allergy undetected by the usual methods.

Adolescent↗

Evaluation of third-generation assays for detection of anti-hepatitis C virus (HCV) antibodies and comparison with presence of HCV RNA in blood donors reactive to c100-3 antigen.

We tested serum samples from blood donors by using first-, second-, and third-generation enzyme immunoassays or recombinant immunoblot assays. Second- and third-generation assays gave comparable results. Circulating hepatitis C virus RNA was found in a high proportion of reactive samples. A lack of reactivity or low-level reactivity predicted the absence of hepatitis C virus RNA in 100% of the cases.

Antigens, Viral↗

Simultaneous active and passive immunization against hepatitis A studied in a population of travellers.

Three hundred travellers, seronegative for hepatitis A, were enrolled into this study to evaluate a new inactivated hepatitis A vaccine. Three injections, each containing at least 720 ELISA units, were administered intramuscularly at months 0, 1 and 6. The subjects were distributed into three groups: 100 received vaccine only; 100 received a single injection of immunoglobulin enriched in HAV antibody; and the 100 remaining travellers received the vaccine and immunoglobulin administered simultaneously with the first vaccine dose. In both vaccinated groups, the rate of seroconversion was found to be higher than 90% at month 1, reaching 100% and 97.8% at month 2 in groups 1 and 3, respectively, and 100% at month 7. In the group receiving both vaccine and immunoglobulin, antibody production was somewhat slower and the final titres were, on average, slightly lower than those obtained in the group with the vaccine alone (GMT 2488 and 3614 mIU ml-1 respectively; p = 0.02). The vaccine appeared to be highly immunogenic in all subjects and was also well tolerated. The slight inhibition of antibody production, induced by the concurrent administration of immunoglobulin, does not affect the overall protection afforded by the vaccine. We conclude that simultaneous active and passive hepatitis A immunizations can be recommended.

Adolescent↗

Comparison of two in vitro assays, RAST and CAP, when applied to the diagnosis of anaphylactic reactions to honeybee or yellow jacket venoms. Correlation with history and skin tests.

We compared the results obtained with a new specific IgE assay (Pharmacia CAP system) to those of RAST and intradermal skin tests (ST) performed in 87 patients with a history of generalized reaction to honeybee or yellow jacket venom. When CAP and RAST were compared with positive ST performed with honeybee venom, CAP sensitivity was not significantly higher (98%) than that of RAST (95%). When yellow jacket venom was tested, CAP sensitivity (93%) was clearly superior to that of RAST (40%). When we compared the specificities of RAST and CAP to bee venom, RAST was positive in 21% of the 24 subjects with negative ST, and CAP in 42%. Among the 29 patients with negative ST to yellow jacket venom, RAST was positive in 17% and CAP in 28%. These results do not reflect a lower specificity of CAP, because CAP positivities could be inhibited in vitro, and because, in three patients with a history of anaphylactic reaction (one to honeybee, two to yellow jacket), CAP was the only positive test confirming the clinical observation. Among the 53 patients who were able to identify the offending insect (honeybee, 31; yellow jacket, 22), the cause of the anaphylactic reaction was usually confirmed by ST and CAP: honeybee venom 97% for both ST and CAP; yellow jacket venom 82% for ST, 86% for CAP. This was not the case for RAST, which confirmed honeybee venom hypersensitivity in 87% and yellow jacket venom hypersensitivity in only 41%. Thus, CAP is both more sensitive and more rapid than RAST, without losing specificity.

Adolescent↗

[Chronic urticaria: evaluation and long-term follow-up].

Two major difficulties occur as soon as one is confronted to a patient suffering from chronic urticaria: the determination of an etiology that might be amenable to treatment and the establishment of an efficient treatment and satisfying follow-up for the patient. After having reviewed the different possible etiologies of chronic urticaria, this paper attempts to propose a logical diagnostic approach for the primary care physician. This will allow him to identify the etiologies that are the most common and responsive to a specific treatment and then to detail the modalities of this treatment.

Chronic Disease↗

Clonality of cold agglutinins in patients with hemolytic anemia: an analysis by high-resolution two-dimensional gel electrophoresis.

High-resolution two-dimensional gel electrophoresis (2-DGE) was used to analyse plasma samples and partially purified cold agglutinins (CA) obtained from two selected patients. Both presented an acute hemolytic anemia with CA of high thermal amplitude, normal immunoglobulin levels, no detectable paraproteinemia, and no clinical evidence of a malignant B-cell disorder. The electrophoretograms of their plasma showed evident alternations of the "normal" protein profile, which were directly related to hemolysis (absence of the spots of haptoglobin and in one case of those of hemopexin), but no monoclonal gammopathy. The electrophoretograms of their purified CA revealed two clearly different spot patterns respectively corresponding to a monoclonal IgM and to polyclonal IgM. These results show that the clonality of CA associated with hemolytic anemia can be easily determined by 2-DGE. This technique may be very useful to discriminate chronic cold agglutinin disease in the early phase from "parainfectious" CA.

Adult↗

Hepatitis B virus, alpha-fetoprotein synthesis, and hepatocellular carcinoma in Zaire.

We investigated the epidemiology of hepatocellular carcinoma (HCC) in Zaire, and evaluated the association between exposure to hepatitis B virus (HBV) and the development of HCC. Two hundred and twenty-three consecutive cases of HCC diagnosed over 19 years (1966-1985) were reviewed. HCC represented 8.32% of all carcinomas and 5.56% of all cancers. Frequency was higher in males (75.7%) than in females (24.3%); a sex ratio of 3/1. The majority (82.1%) of patients were aged 14 to 55 years with a peak occurrence in the fourth decade (28.6%). The mean age in males (41.27 +/- 17.5 years) and females (37.40 +/- 15.16 years) was significantly different (p < 0.02). Sera from 40 patients and 68 age and sex-matched controls were analyzed for markers of HBV infection: patients and controls had comparable rates of exposure (96% vs 72.1%, respectively). However, patients had significantly higher HBsAg carrier rates (56.7% vs 7.35%; p < 0.001), and lower anti-HBsAg seroconversion rates (25% vs 63.2%, p < 0.05). Using immunohistochemical analysis, the livers of patients were evaluated for HBsAg and HBcAg. These HBV antigens were more frequent in non-tumourous hepatocytes (53.3% vs 23.3%, respectively) than in HCC cells (13.3% vs 3.3%). Serum alpha-fetoprotein (AFP) was abnormal (> 20 ng/ml) in 90% of patients. The geometric mean (GM) AFP was 7273.8 ng/ml. AFP levels were significantly higher in HBsAg-positive HCC cases (GM: 19,322.6 ng/ml; 95% confidence interval (CI): [3639.2, 102,565.2]) than in antigen negative cases (GM: 1939.5 ng/ml; 95% CI: [182.8, 19,952.6]), but did not correlate with HBV replication. Immunohistochemical detection of AFP revealed a similar correlation between AFP and HBsAg. Neither AFP level nor HBsAg production correlated with cellular atypia or tumor grade.

Adolescent↗