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G Hess

Publications and source records attributed to G Hess.

At least 19 recordsLinked to original sources

[Viral hepatitis as a traveler's disease].

At the present time, at least five different forms of viral hepatitis can be distinguished. The hepatitis A and E viruses are transmitted via a fecal-oral route, and are associated with poor hygiene. Hepatitis E is restricted to Central Africa, parts of Asia, and Central America. Hepatitis B, C and D are transmitted not via the fecal-oral route but, in the case of B and D mainly by sexual intercourse, and in the case of hepatitis C by infected blood products. Even after the introduction of interferon alpha, treatment possibilities are limited. Immune prophylaxis (hepatitis A and B) and general preventive measures are of considerable importance, not merely with respect to travelling.

Hepatitis, Viral, Human

Quantal parameters of "minimal" excitatory postsynaptic potentials in guinea pig hippocampal slices: binomial approach.

Binomial distributions of amplitudes of excitatory postsynaptic potentials (EPSPs) mixed with Gaussian noise were simulated. The objective of Monte Carlo simulations was, firstly, to study influences of sampling size (N) and noise standard deviation (Sn) on estimates of mean quantal content (m), quantal size (v) and binomial parameters (n and p) by four methods of quantal analysis (histogram, variance, failures and combined method) based on the binomial model and, secondly, to modify these methods on the basis of comparison of estimated with simulated parameters. Reliable estimates (within +/- 10% of the simulated values) were obtained for large sample sizes (N = 500-1000) with Sn less than or equal to v by the histogram (deconvolution) method and with Sn less than or equal to 2v by the other three methods. Similar results were obtained by averages from about 10 simulations if smaller samples were used (N = 50-200). In electrophysiological experiments on slices, "minimal" EPSPs were recorded from CA1 pyramidal cells after low-intensity stimuli to stratum radiatum or stratum oriens. Amplitudes of minimal EPSPs fluctuated in a manner predicted by the quantum hypothesis. Amplitude distributions of EPSPs in the non-facilitated state were adequately described either by binomial statistics with an average p equal to about 0.4 (a range of 0.3-0.7) and an average n of about 3 (range 2-6) or by Poisson statistics with m of about 1. The quantal analysis suggests that typical values of m and v for a single activated fibre in stratum radiatum might be about 0.5-1 and 300-400 microV, respectively, with low p (0.1-0.3) and n (2-4). However, the estimates of binomial parameters should be considered as coarse approximations in view of the simulation results and a possible nonuniformity of parameter p. The comparison of results of various methods based on the binomial model, in both simulation and physiological experiments, indicates the reliability of estimates of basic quantal parameters (m and v) under realistic conditions of physiological experiments. The methods are considered to be sufficiently sensitive to make use of them for studies on mechanisms of long-term synaptic plasticity.

Animals

Statistical analysis of long-term potentiation of large excitatory postsynaptic potentials recorded in guinea pig hippocampal slices: binomial model.

Excitatory postsynaptic potentials (EPSPs) were recorded in guinea pig hippocampal slices (area CA1) from 15 neurons after stimulation of stratum radiatum (str. rad.) and stratum oriens. EPSP amplitudes increased in 8 neurones (10 post-tetanic regions) recorded 15 to 45 min after tetanic stimulation of str. rad. The increase was considered to represent long-term potentiation (LTP). Quantal analysis was performed by two methods assuming binomial statistics: the histogram method using deconvolution of noise and the variance method. According to both methods, LTP was associated with an increase in mean quantal content (m) which correlated with LTP magnitude. A statistically significant increase in quantal size (v) was found only by the histogram method and the increase was not correlated with LTP magnitude. A separate analysis of EPSPs with small LTP magnitude demonstrated that with the histogram method only v was increased but not m. A smaller increase in m for the pooled data of both methods did not correlate with LTP magnitude for this EPSP subset. The increase in m for the whole EPSP set corresponds to previous results on the quantal analysis of LTP in in vivo preparations and favours a presynaptic location of major mechanisms underlying LTP maintenance. The increase in v indicates the existence of another mechanism responsible for the maintenance of a small part of LTP. This mechanism might involve either pre- or postsynaptic changes or both.

Algorithms

Quantal analysis of long-term potentiation of "minimal" excitatory postsynaptic potentials in guinea pig hippocampal slices: binomial approach.

"Minimal" excitatory postsynaptic potentials (EPSPs) were recorded from 13 neurones in area CA1 of guinea pig hippocampal slices after double-pulse stimulation of stratum radiatum (str. rad.) and stratum oriens (str. or.). Amplitudes of EPSPs significantly increased in 8 neurones 5 to 55 min after 9 tetanizations in str. rad.. The increase was considered to represent long-term potentiation (LTP). Altogether 26 EPSPs (42 post-tetanic regions) were statistically analysed by four methods of the quantum hypothesis assuming the binomial model of transmitter release: the deconvolution (histogram), the variance, the failures, and the combined (variance-failures) methods. The mean quantal content (m) significantly increased after LTP induction according to all methods used. Quantal size (v) also tended to increase but according to some methods, the increase was not statistically significant and it did not correlate with LTP magnitude. However, for an EPSP subset with a LTP magnitude of less than 1.55, the increase in v correlated with LTP magnitude, whereas the increase in m did not. The relative contribution of the increase in v to LTP magnitude was larger for cases with small LTP than for the whole EPSP set. In general, the increase in m corresponds to previous studies and favours the presynaptic location of major mechanisms of LTP maintenance, i.e. an increase in the average number of transmitter quanta released by each presynaptic volley. The post-tetanic increase in v might reflect some additional mechanisms which presumably include an increase in the amount of transmitter in one quantum.

Animals

Influence of vaccination schedules and host factors on antibody response following hepatitis B vaccination.

In a prospective multicentre trial, the influence of schedule, compliance, age, sex and weight on the antibody response to hepatitis B vaccination was investigated. Comparison of the vaccination schedules 0, 1, 6 months (group 1; n = 143) and 0, 1, 2, 12 months (group 2; n = 141) was performed in months 3, 7 and 12. In addition, the antibody response was compared one month after the third and one and six months after the last vaccination. Seroprotection rates (anti-HBs greater than 10 IU/l) and antibody titres, given as geometric means (GMTs), were higher in group 1 at month 12 as well as one month after completion of three immunizations. More vaccinees of group 2, however, showed seroprotection at month 3 with higher GMTs. In addition, GMTs in group 2 were higher both one month and six months after the last vaccine dose. Determination of parallel corrected correlation factors demonstrated that age was the most important single factor, followed by body weight and sex. However, no more than 3% of the variation in the GMT can be explained by the influence of age. Due to decreased compliance with the four-dose schedule with a drop-out rate of approximately 10% of the vaccinees, the total percentage of initial vaccinees who in the end developed protective antibody levels was higher in the 0, 1, 6 months schedule. Thus, it can be concluded that subjects likely to comply will benefit from the 0, 1, 2, 12 months schedule as more rapid protection is obtained and the higher antibody levels after the booster vaccination at month 12 provide longer protection. However, vaccinees whose compliance might be questionable over a period of 12 months, should be selected for the vaccination 0, 1, 6 months schedule as compliance is at a higher level over this period and advantage can be taken of the booster effect of the third dose given in month 6.

Adolescent

Hepatitis C virus antibody secretion in vitro by peripheral blood lymphocytes.

A recombinant polypeptide corresponding to a virus-specific cDNA clone (c100-3) serves as the antigen for a hepatitis C virus (HCV) antibody assay. Previous investigations have shown an 80% prevalence of HCV antibodies in sera of patients suffering from post-transfusional chronic hepatitis non-A, non-B, but positive results were also obtained for 30 to 70% of sera from patients with chronic hepatitis B or autoimmune hepatitis. In this study we show that HCV antibodies are secreted by peripheral blood lymphocytes (PBL) in vitro. PBL from 12/35 patients with chronic non-A, non-B hepatitis and 1/6 patients with chronic active hepatitis B spontaneously secreted HCV antibodies in cell culture supernatants. The results were confirmed by neutralisation assay and ELISAs using recombinant and synthetic polypeptides derived from the c100-3 antigen and from the HCV core antigen. Two patients suffering from non-A, non-B hepatitis were negative for HCV antibodies in serum, but their PBL produced HCV c100-3 antibodies in vitro. PBL from patients suffering from autoimmune chronic hepatitis, primary biliary cirrhosis, toxic-liver injury and healthy blood donors did not produce antibodies to HCV c100 antigen irrespective of HCV antibody test results in their sera. Polyclonal B cell activation or mitogenic stimulation of T helper cells led to increased immunoglobulin synthesis by PBL in vitro, but did not lead to enhancement of specific HCV antibody production. In addition, HCV antibody production was not induced by these stimulation procedures in control lymphocytes. This spontaneous HCV antibody production in vitro suggests persistent antigenic stimulation of the B cells in vivo.

B-Lymphocytes

Hepatitis A vaccination: schedule for accelerated immunization.

Hepatitis A vaccine, strain HM175, was investigated for immunogenicity and tolerability in a prospective multicentre trial. The following vaccination schedules and antigen contents were evaluated: days 0 and 14 with 720 ELISA units (El.U) of antigen, days 0 and 28 with 720 El.U and days 0 and 28 with 360 El.U. In all study groups, the seroconversion rates following two vaccinations were between 95 and 100%. Higher geometric mean concentrations of antibody to hepatitis A virus (anti-HAV) were reached by the vaccine containing 720 El.U of HAV antigen. The vaccine was equally well tolerated in all groups. In addition, an abbreviated schedule, in which 720 El.U of HAV antigen was given on days 0 and 14, resulted in 100% seroconversion by day 28 and a level of anti-HAV that was substantially higher than that observed after passive immunization. This implies that such a vaccine could replace immune globulin administration if time permits.

Adult

Sub-acute effects of interferon-alpha 2 on adrenocorticotrophic hormone, cortisol, growth hormone and prolactin in humans.

This study investigated the chronic effects of interferon-alpha 2 (IFN-alpha 2) on hormonal secretion in humans. Six patients suffering from chronic hepatitis B or C infection received SC doses of 3 million IU IFN-alpha 2 three times a week for 4 mo. Each patient was examined for hormone secretion four times: the day before initial IFN-alpha 2 administration (day 0), the day of the first injection (day 1), and 4 wk after start of IFN therapy on days 27 (without IFN administration) and 28 (with IFN administration). Adrenocorticotrophic hormone (ACTH), cortisol, growth hormone (hGH), and prolactin (PRL) were measured in plasma samples drawn at 30-min intervals between 1600h and 2400h. Acute administration of IFN-alpha 2 stimulated the release of ACTH to 423% (p = 0.02 vs. day 0) and cortisol to 393% (p = 0.01 vs. day 0) of control values in each patient. In five of the six patients, the plasma levels of hGH were higher on day 1 than on day 0. IFN-alpha 2 did not affect the secretion of prolactin. On day 27, the plasma levels of the four hormones were similar to the baseline levels on day 0. When IFN-alpha 2 was given on day 28, there were no significant differences in the release of ACTH (135% of control, p = 0.4) or cortisol (124% of control, p = 0.5) in comparison to day 27. These findings indicate that IFN-alpha 2 stimulation of hormone release is restricted to specific hormones.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone

Presynaptic calcium transients evoked by paired-pulse stimulation in the hippocampal slice.

The fluorescent dye Calcium Green and optical recording techniques were used to record intracellular Ca2+ transients resulting from paired-pulse stimulation in stratum moleculare of area CA1 in guinea-pig hippocampal slices. Presumed presynaptic calcium transients were recorded while glutamatergic synaptic transmission was blocked by kynurenic acid. Peak responses to paired-pulses (10-160 ms interval) were higher than responses to single pulses of same stimulation strength (42-23% increase). The isolated response to the second pulse, however, was of smaller magnitude in comparison to the first one; the difference in magnitude depended on the interstimulus interval. Thus, the residual presynaptic free calcium concentration may be responsible for paired-pulse facilitation of synaptic transmission in hippocampus. At the same time, a use-dependent inactivation of presynaptic calcium channels may occur.

Animals

Multicenter evaluation of the novel ABN Western blot (immunoblot) system in comparison with an enzyme-linked immunosorbent assay and a different Western blot.

A new, modular Western blot (immunoblot) system for human immunodeficiency virus (HIV) antibodies (ABN WesPage; Wellcome) was compared with enzyme immunoassays (Wellcome, Behringwerke, and Abbott) and with a U.S. Food and Drug Administration (FDA)-licensed Western blot (DuPont) in a multicenter study. A total of 649 serum samples from HIV patients at different stages of the disease, as well as from high-risk patients, from patients with conditions unrelated to AIDS, and from healthy blood donors, were used in the evaluation along with nine seroconversion panels. For evaluation of Western blot reactivity, both Centers for Disease Control (CDC) and FDA criteria were used. With the DuPont Western blot as the reference assay, the overall sensitivity and specificity of the ABN WesPage were 100 and 99.1%, respectively, when indeterminate results were not taken into account and when both tests were interpreted in accordance with CDC criteria. The DuPont Western blot detected significantly more antibodies to pol and gag gene products than the ABN WesPage. The ABN WesPage showed a higher positive rate of detection of viral envelope band gp160. When both Western blots were interpreted in accordance with CDC criteria, the ABN WesPage and the DuPont Western blot yielded 9.3 and 10.4% indeterminate results, respectively. When the DuPont Western blot was interpreted in accordance with the manufacturer's instructions (FDA criteria), 25.7% of the samples tested were regarded as indeterminate. The choice of interpretation criteria is of paramount importance for the evaluation of HIV Western blot patterns.

AIDS Serodiagnosis

Antiviral effect of prolonged intermittent lymphoblastoid alpha interferon treatment in chronic hepatitis B.

In a European multicentre study 40 patients with HBeAg positive chronic hepatitis B virus (HBV) infection were treated with 5 mega units of lymphoblastoid alpha-interferon daily according to the following regimen: a four week primer course, four weeks of rest and a second course lasting 16 to 30 weeks. After 52 weeks of follow up, a response (HBeAg seroconversion and HBV-DNA negativity) was observed in 22 patients (55%). HBsAg seroconversion occurred in five patients (12.5%). One patient exhibited a relapse for serum HBeAg and HBV-DNA after cessation of treatment. According to a response prediction model, the observed response rate was not related to the selection of patients likely to respond. The initial interferon course induced a reduction of the serum HBV-DNA and HBeAg levels of 87% and 18%, respectively, leading to a significantly lower level of viral replication activity at the start of the second longterm course compared with baseline. After 24 weeks of follow up (week 16 of the second course), 19 (48%) patients exhibited a response, 13 (32%) a partial response (HBeAg < 50% of initial level or HBV-DNA negative) and 8 (20%) no response. For eight of the 13 partial responders treatment was stopped at week 24 and viral replication rebounded to pretreatment values. In the last five partial responders prolongation of therapy up to week 38 led to a definite response and HBsAg seroconversion in three of the five patients. The results of this study suggest that a short primer course and prolongation of therapy may help to enhance the response rate of alpha-interferon therapy for chronic hepatitis type B.

Adolescent

[Therapy of chronic non-A, non-B hepatitis with interferon].

Alpha interferon, administered at a dose of 1 to 3 million units three times a week over a period of 24 weeks, leads to normalization of the transaminases in about 50% of patients with chronic hepatitis C. About 50% of the initial responders experience a recurrent increase in transaminases (relapse). Thus, about 20% to 25% of chronic hepatitis C patients show a lasting response to treatment with alpha interferon. A better understanding of HCV replication and the effect of interferon might possibly lead to improvements in treatment resulting in a higher response and lower relapse rates. Side effects of alpha interferon are generally mild and reversible on termination of treatment. At present, alpha interferon cannot be recommended for asymptomatic patients or those with slowly progressive liver disease.

Hepatitis C

Tumor necrosis factor and interferon as prognostic markers in human immunodeficiency virus (HIV) infection.

Peripheral blood cells were obtained from patients at different stages of their human immunodeficiency virus (HIV) infection. It was found that the capacity to generate interferon alpha was reduced already at Walter Reed stage 2 (WR) while the interferon gamma capacity remained largely unaffected until WR stage 4. Endogenous tumor necrosis factor (TNF) alpha production increased as the HIV disease progressed. The data obtained add to our knowledge on destruction of the immune system by the HIV. Moreover TNF and acid labile interferon alpha might contribute to HIV replication and disease progression. Nevertheless the tests performed are too time-consuming to be introduced into routine analysis of HIV infection or for monitoring its therapy and can so far not be used for intervention strategies. Further studies are needed.

Biomarkers

Treatment of chronic hepatitis C.

alpha-Interferon given subcutaneously at doses between 1-3 million units leads to responses in about 50% of patients suffering from chronic hepatitis C. A 24-week treatment is frequently (approx. 50%) followed by relapses reducing the percentage of lasting responders to approx. 20%. The patients who relapse are sensitive to retreatment with interferon-alpha. A better understanding of HCV replication and of the interferon action in this viral disease might help to further improve treatment schedules. Side effects of interferon were frequently mild and readily reversible after cessation of treatment. At present interferon treatment should not be recommended in asymptomatic patients or individuals with slowly progressive liver disease.

Chronic Disease

Serum hyaluronate and type III procollagen aminoterminal propeptide concentration in chronic liver disease. Relationship to cirrhosis and disease activity.

To analyse the relationship between the presence of liver cirrhosis and hepatic inflammation and the serum concentrations of the aminoterminal propeptide of procollagen type III (P-III-NP) and of hyaluronic acid (HA) in chronic liver disease, we measured P-III-NP and HA concentrations in paired serum samples from 133 patients with various chronic liver diseases, from 22 patients with acute hepatitis and from 50 healthy age-matched controls. In 24 (of the 133) patients with autoimmune chronic liver disease, follow-up determination was performed during therapeutic treatment with immunosuppressive drugs. Compared with controls P-III-NP concentrations (medians) were significantly elevated in 65% of patients with chronic active hepatitis (P = 0.00097) and in 79% of patients with active liver cirrhosis (P = 0.0126) but not in patients with chronic persistent hepatitis (P = 0.06). Serum concentrations (medians) of HA were increased (P = 0.0058) in 32% of patients with chronic active hepatitis and in 91% of patients with active cirrhosis (P less than 6 x 10(-7)). The difference of HA serum concentrations but not that of P-III-NP serum concentrations in patients with chronic active hepatitis and in patients with active cirrhosis was statistically significant. HA and P-III-NP serum concentrations were significantly elevated in 22 patients with acute hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Interferon-alpha-2-induced stimulation of ACTH and cortisol secretion in man.

Short-term effects of interferon-alpha 2 on plasma concentrations of adrenocorticotrophic hormone (ACTH) and cortisol were measured in man in relation to interferon absorption. Interferon-alpha 2 was given subcutaneously at a dose of 3 x 10(6) IU at 17.00 h to 2 female and 5 male patients who suffered from chronic hepatitis B infection and who had not previously been treated with interferon. Plasma levels of ACTH, cortisol and interferon-alpha were determined at 30-min intervals between 16.00 and 24.00 h. In each patient a similar cortisol, ACTH and interferon-alpha profile was determined on a day, when no interferon-alpha treatment was given. Interferon-alpha plasma levels peaked around 21.30 h, i.e. 4.7 h after injection. In each patient ACTH and cortisol levels were increased. As calculated from the areas under the curves, ACTH release was increased by an average of 332% (maxima at about 22.00 h, i.e. 5.2 h post injection); cortisol release was increased by an average of 311% (maxima at about 23.00 h, 5.8 h post injection). These actions were not related to side effects like fever or other flu-like symptoms. Our findings confirm that in man as in animals interferon-alpha 2 can act as a mediator between the immune and endocrine system.

Adrenocorticotropic Hormone