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Biomedical subjects

P J Grob

Publications and source records attributed to P J Grob.

At least 19 recordsLinked to original sources

[Hepatitis and HIV infection in users of illegal drugs].

The prevalence of markers for ongoing or past infections with the hepatitis viruses A (HAV), B (HBV), D (HDV) and C (HCV) and with HIV are analyzed in i.v. drug users. The relevant serological parameters were measured in 1989, 1990 and 1991 in 220 to 380 sera each of drug users who frequented the open drugscene "Platzspitz" in a recreational area in the center of Zürich. The prevalence of viral markers for ongoing and past infections was many times higher in drug users than in the Swiss population. Over the three years the prevalence of HAV-markers rose from 50% to 72%, remained stable for HBV (52%, 57%, 58%) and most probably also for HCV. It slightly declined for HIV from 21% to 18% in one series and from 17% to 2% in another series. 10-34% of all individuals tested showed signs of at least one ongoing infection. Combined infections were frequently observed. The prevalence of viral markers was significantly dependent on the duration of drug use and if needle-sharing was practiced or not. Our data were analyzed in the context of the official notifications of these viral infections and related disorders to the Swiss Health Ministry. The risk of infections with the viruses analyzed here is 100-200 times higher in drug addicts than in the Swiss population. Drug users account for 42 to 52% of all infections (and clinical sequelae) notified in Switzerland. In the light of the fact that drug users also represent a potential source of spread of these viruses into the general population, the prevention effort in drug users should have first priority.

Adult

[Hepatitis serology: use and interpretation].

Presently five viruses causing hepatitis are known, the hepatitis viruses A (HAV), B (HBV), C (HCV), D (HDV) and E (HEV). The genomic structure is known of most of all these viruses as well as some of their structural and regulatory gene products. Using radio- and enzyme immunoassays viral antigens can be detected for HBV and HDV as well as specific antibodies against all the five viruses. The results of these tests are the basis for the diagnosis and the follow-up of these infections but differ in their accuracy for each given virus. Concerning HIV one can differentiate between an ongoing or recently passed infection and immunity. Concerning HBV (and HDV), an ongoing infection at various stages can be distinguished from immunity. Such distinctions are not possible with respect to HCV except when also applying the expensive and cumbersome method of the polymerase chain reaction. In this paper the most important characteristics of the hepatitis viruses are given and the behaviour of the various viral markers during the infections and their consequences are described.

Epitopes

[Antineutrophil cytoplasma antibodies (ANCA): clinical indications and experience with these new autoantibodies].

Antineutrophil cytoplasmatic autoantibodies (ANCA) have been tested in this laboratory for more than two years with a 3-fold increase in tests and positive results. The initial association with Wegener's granulomatosis has since been extended to microscopic polyarteritis and rapidly progressive glomerulonephritis. We review the published data. ANCA are not simply another laboratory test but have become an important tool for diagnosis, treatment monitoring and prevention of relapses in many vasculitis syndromes including some forms of rapidly progressive glomerulonephritis. The ANCA-associated antigens have been identified as a serin-proteinase and myeloperoxidase. This provides insights into the pathogenesis of the ANCA-related diseases.

Antibodies, Antineutrophil Cytoplasmic

[Deficiency in immunoglobulin subclasses as cause of increased infection susceptibility--a family study].

Within 3 generations 6 members of a family showed diminished serum concentrations of one or more immunoglobulin G (IgG) subclasses. In all 6 individuals IgG-2 levels were low, together with low IgG-3 and/or IgG-4 in 5, but all had normal values for total IgG. The proposita and her 2 children suffered from frequent severe respiratory infections. One child, now aged 11, has had an average of 3 such infections per year since birth, while the other, now aged 8 years, has had 4 episodes annually since birth. Recurrent infection only started at age 34 in the proposita. In these 3 patients a line immuno-binding assay showed diminished subclass-specific IgG-2 antibodies against bacterial polysaccharides. They were replaced by Sandoglobulin, an immunoglobulin for intravenous use. Under substitution by 6 g or 12 g infusions of Sandoglobulin per month no further infections occurred or the infections were clearly milder than before, and the Ig subclass levels became normal. It is concluded that in every case of recurrent respiratory infections of unusual severity suggesting an antibody deficiency, it is advisable to measure not only the total Ig classes (IgG, IgA and IgM) but also the IgG subclasses. The clinical relevance of an Ig subclass deficiency can be further substantiated by measuring subclass-specific antibodies.

Adult

[Infection with hepatitis viruses HAV, HBV and HCV as well as with AIDS virus HIV in drug addicts of the Zurich street scene--a prevalence study].

382 i.v. drug abusers were tested for a past or ongoing infection with the hepatitis viruses A (HAV), B (HBV), the newly discovered C (HCV) and with the Aids virus HIV. The cohort studied was representative for i.v. drug users of the Zurich street scene including occasional users, weekend users and severe drug addicts. 56% of the drug users tested showed HBV markers. 21% had an ongoing infection. 32% were naturally HBV immune and 4% showed immunity due to vaccination. HAV markers were detected in 50% of the individuals tested, with an ongoing infection present in 8%. 48% of the individuals tested showed signs of HCV contact. 15% of the i.v. drug users were HIV infected. 22% of these individuals were HIV-antigen positive. The data confirm that i.v. drug users have the highest rates of infection within the total population. The prevalence of viral markers correlated positively with the duration and intensity of i.v. drug use and with the practice of needle sharing. In comparison to comparable earlier studies, the present viral prevalence data were lower. This is thought to be due to an Aids prevention campaign undertaken in the Zurich street drug scene, including free distribution of injection material and condoms.

Acquired Immunodeficiency Syndrome

[Hepatitis C virus (HCV), anti-HCV and non-A, non-B hepatitis].

Our data on 559 serum samples are discussed in the light of the present knowledge on hepatitis C virus (HCV). This newly discovered virus is thought to be the main cause of the bloodborne non-A, non-B hepatitis. HCV is a single-stranded, encapsulated RNS virus. Presently one antibody, anti-HCV, is detectable, which is directed against a nonstructural viral component. This antibody appears only weeks to months after infection or onset of the disease. Within 6-9 months 60-80% of the patients with resolving non-A, non-B hepatitis become positive, with the anti-HCV usually disappearing after 1-5 years. Patients with chronic infections are positive in 70-90% of cases, with the antibody usually persisting over decades. The presence of anti-HCV offers no clue as to whether there is an ongoing or past infection and does not serve to judge infectivity or immunity. 0.34% of the blood donors in Switzerland are anti-HCV positive, with 1.3% in Southern Italy and 0.6-0.8% in Northern Italy, Great Britain, France and Germany. Anti-HCV prevalence is high in hemophiliacs (59-97%), i.v. drug users (48-92%) hemodialysis patients and polytransfused individuals (3-23%), homosexuals and promiscuous heterosexuals (1-40%) as well as in patients with non-B hepatoma (62-80%) or with alcoholic cirrhosis (27-52%). Our own data show anti-HCV in 45% of i.v. drug users, 7% of homosexuals, 13% of patients under hemodialysis or with renal transplants, and in 60% of patients with chronic non-A, non-B hepatitis.

Blood Donors

Levels of soluble interleukin-2 receptors correlate with the severity of atopic dermatitis.

Levels of soluble interleukin-2 receptors (sIL-2R) were measured as a marker of lymphocyte activation in serum of 37 patients with atopic dermatitis (AD) and of 16 patients with psoriasis vulgaris (PV), all individuals being hospitalized in the Zurich High Mountain Clinic of Davos-Clavadel (altitude 1,600 m above sea level). Measurements were performed at admission and at discharge. The PV patients served as a control group. As a further control, 20 AD patients from the Department of Dermatology in Zurich (altitude 400 m) were also evaluated. The serum sIL-2R concentration in AD patients at admission was significantly elevated in comparison with PV patients and was highly correlated with the severity of the cutaneous involvement. Comparing the 'extrinsic' and 'intrinsic' types of AD, no significant differences of sIL-2R levels were found. The sIL-2R concentrations dropped at discharge. These results suggest that the measurement of the sIL-2R level could be a marker of disease activity.

Adolescent

[Simple references of the differential blood picture in assessing the immune status of immunologically compromised severely injured patients].

Infectious complications threaten the survival of severe traumatized patients in the intensive care unit. Major cause is a secondary immunodeficiency syndrome as a consequence of overloading the immune system by tissue debris and microbial antigens. Antigen presenting cells of the monocyte-macrophage line become activated unspecifically and produce immunosuppressive monokines, which modulate the T- and B-cell systems and weaken the specific immune response to antigens. In 150 severe injured patients (mean ISS 31; 15 patients died due to infections) we found that a decrease of lymphocytes below 1000/microliters and an increase of monocytes up to more than 1000/microliters within the first 24 hours correlate with developing infection in such a manner, that the lymphocyte/monocyte-quotient on day 1 was 2.0 in survivors and 0.9 in subjects, who died due to infections.

Cross Infection

[The natural history and laboratory parameters of HIV infection].

Since 1983 the morbidity and mortality rates as well as results of haematological, immunological and (later) HIV serological tests were recorded prospectively for 497 HIV-positive patients during 1837 clinic visits at least twice within at most six months for a median period of observation of 18 months (range 6-64 months). The rate of progression to a higher stage was calculated according to the method of Kaplan-Meier. The rate for asymptomatic patients was 16% after one and 33% after two years; for patients with persisting generalized lymphadenopathy it was 13% and 21%, respectively, for those with AIDS-related complex 28% and 47%, respectively, and for those with AIDS 33% and 82%, respectively. As for results of laboratory tests, patients with progressive disease had significantly lower titres of anti-HIV nuclear antibodies, as well as a higher incidence of HIV-p24 antigen. Haemoglobin levels, platelet and lymphocyte counts and number of CD-4-positive lymphocytes were significantly lower, Neopterin and beta 2-microglobulins higher (P less than 0.01).

AIDS-Related Complex

[Tumor markers and immunomodulator substances in ascites--their value as screening and diagnosis parameters].

The object of this study was to determine the known laboratory parameters, tumor markers and immunomodulatory substances in 69 ascites of various etiology, and to test their diagnostic significance. The usual parameters such as protein content, LDH ratio, albumin quotient and albumin gradient, fibronectin, cholesterol and cell count did not reliably differentiate the etiology in each particular case, although the mean values of the various groups differed significantly. Even cytological investigation was negative in 6 out of 29 malignant ascites. Neither were the immunomodulatory substances such as neopterin, beta 2-microglobulin and interleukin-2 receptors suitable for differentiation. In patients with carcinoma of the prostate the values of prostate-specific antigen were significantly increased in ascites. The best separation between benign hepatic or cardiac ascites and malignant ascites was provided by ferritin (sensitivity 97%, specificity 100%). The values in benign hepatic or cardiac ascites were lower than 150 ng/ml and those in malignant ascites higher than 170 ng/ml.

Adjuvants, Immunologic

[Immunologic changes and infection in severely injured patients].

The severity of major surgery determines the extent of immunodeficiency which follows. The most pronounced immunodepression is found after severe blunt trauma; in polytraumatized patients the alterations of many measured parameters correlate with the injury severity score (ISS) i.e. with the severity of the injuries. Infection is also followed by many changes in the immune response. A score including serum concentrations of IgA, beta 2-microglobulin and percentage of monocytes was found to be predictive for the first 3 days after trauma with regard to subsequent occurrence of infection. In the first post-trauma day the lymphocyte-monocyte ratio correlates with the probability of survival or death by infection. Pneumonia occurred in 47% and septicemia in 22% of 150 polytraumatized patients ventilated artificially for more than 24 hours. The first signs of these infections were already present during the first 5 days, i.e. in the period of the most severe immunodeficiency. The preliminary results of a pilot study with immunomodulation by thymopentin are encouraging and show a significant decrease in the frequency of infections.

Humans

[Immunosuppression caused by surgery and severe trauma].

The present prospective study was performed to describe physiological immunosuppressive effects dependent on minor surgical interventions and an immunodeficiency syndrome after major surgery and severe trauma. Parameters of cellular and humoral immunity were monitored in 64 patients of the Department of Surgery of the University Hospital Zurich preoperatively and on days 1, 2, 3 and 4 after selective surgery or polytrauma. 22 patients were multiply traumatized (mean ISS 34.7 +/- 13), 14 patients underwent Y-grafting of the abdominal aorta, 11 resection of colorectal carcinoma, 8 cholecystectomy and 9 inguinal herniotomy. There could be seen a decrease of parameters of cellular immunity (absolute lymphocyte count, CD-4-/CD-8-cell-ratio and release of IL2-receptors), a decrease of humoral defense (immunoglobulins and complement factors) and an increase of macrophage activation (serum levels of neopterin).

Humans