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Biomedical subjects

Peter Kern

Publications and source records attributed to Peter Kern.

At least 19 recordsLinked to original sources
PubMed2006

Overweight, physical activity, tobacco and alcohol consumption in a cross-sectional random sample of German adults.

BACKGROUND: There is a current paucity of data on the health behaviour of non-selected populations in Central Europe. Data on health behaviour were collected as part of the EMIL study which investigated the prevalence of infection with Echinococcus multilocularis and other medical conditions in an urban German population. METHODS: Participating in the present study were 2,187 adults (1,138 females [52.0%]; 1,049 males [48.0%], age: 18-65 years) taken from a sample of 4,000 persons randomly chosen from an urban population. Data on health behaviour like physical activity, tobacco and alcohol consumption were obtained by means of a questionnaire, documentation of anthropometric data, abdominal ultrasound and blood specimens for assessment of chemical parameters. RESULTS: The overall rate of participation was 62.8%. Of these, 50.3% of the adults were overweight or obese. The proportion of active tobacco smokers stood at 30.1%. Of those surveyed 38.9% did not participate in any physical activity. Less than 2 hours of leisure time physical activity per week was associated with female sex, higher BMI (Body Mass Index), smoking and no alcohol consumption. Participants consumed on average 12 grams of alcohol per day. Total cholesterol was in 62.0% (>5.2 mmol/l) and triglycerides were elevated in 20.5% (> or = 2.3 mmol/l) of subjects studied. Hepatic steatosis was identified in 27.4% of subjects and showed an association with male sex, higher BMI, higher age, higher total blood cholesterol, lower HDL, higher triglycerides and higher ALT. CONCLUSION: This random sample of German urban adults was characterised by a high prevalence of overweight and obesity. This and the pattern of alcohol consumption, smoking and physical activity can be considered to put this group at high risk for associated morbidity and underscore the urgent need for preventive measures aimed at reducing the significantly increased health risk.

Adult↗
PubMed2006

Stronger host response per parasitized erythrocyte in Plasmodium vivax or ovale than in Plasmodium falciparum malaria.

OBJECTIVE AND METHODS: Fever tends to start at a lower level of parasitemia in Plasmodium vivax or ovale than in P. falciparum malaria, but hyperparasitemia and complications are more likely to occur in P. falciparum malaria. Therefore, we compared the relationship between parasitemia and host response parameters before therapy in 97 patients with P. faciparum malaria (18 with complications), and 28 with P. vivax or ovale malaria. RESULTS: In both types of malaria, parasitemia correlated with blood levels of tumour necrosis factor alpha (TNF-alpha), lactate dehydrogenase (LDH), Thrombin-antithrombin III (TAT) and elastase, and these parameters were higher in P. falciparum malaria than in P. vivax or ovale malaria. In contrast, the ratios of TNF-alpha, TAT, elastase, and LDH per parasitized erythrocyte were higher in P. vivax or ovale malaria than in uncomplicated P. falciparum malaria. They were lowest in complicated disease. Multivariate regression analysis confirmed that parasitemia did not affect these differences. CONCLUSION: The host response may reach full strength at lower parasitemia in Plasmodium vivax or ovale, than in P. falciparum malaria. With hyperparasitemia in P. falciparum malaria, the host response seems to be unable to control parasite multiplication.

Animals↗
PubMed2006

In vitro activities of itraconazole, methiazole, and nitazoxanide versus Echinococcus multilocularis larvae.

Albendazole (ABZ) and mebendazole are the only drugs licensed for treatment of human alveolar echinococcosis. In order to augment the armamentarium against this deadly disease, we tested a series of drugs for their efficacy against Echinococcus multilocularis larvae. E. multilocularis larvae grown intraperitoneally in Mongolian gerbils were transferred into tissue culture. Vesicles budded from the tissue blocks and after 6 weeks, drugs were added, and the effect on the vesicles was observed. We tested the following drugs at various concentrations: ABZ, artemether, caspofungin, itraconazole (ITZ), ivermectin, methiazole (MTZ), miltefosine, nitazoxanide (NTZ), rifampin, and trimethoprim-sulfamethoxazole. ABZ, ITZ, MTZ, and NTZ effectively destroyed parasite vesicles in this in vitro culture system. At high NTZ doses of 10 microg/ml, disintegration of all vesicles was observed after 7 days and was significantly more rapid than with ABZ at equal concentrations (21 days). After drug discontinuation, regrowth of vesicles occurred between 7 and 14 days for all four drugs, indicating a parasitostatic effect. Combination treatment with NTZ-ABZ at concentrations between 1 and 10 microg/ml for either 3 weeks, 3 months, or 6 months yielded no vesicle regrowth during 8 months after drug discontinuation. The treated larval tissue was injected intraperitoneally into gerbils, and no regrowth of larval tissue was observed, suggesting a parasitocidal effect after combined treatment. ITZ, MTZ, and NTZ are potent inhibitors of larval growth, although they proved to be parasitostatic only. The combination of NTZ plus ABZ was parasitocidal in vitro. Animal experiments are warranted for studies of dose, toxicity, and drug interactions.

Animals↗
PubMed2005

WHO classification of alveolar echinococcosis: principles and application.

Alveolar echinococcosis is caused by the larval stage of the fox tapeworm (Echinococcus multilocularis) and is frequently diagnosed as a space occupying lesion in the liver. The growth pattern resembles that of a malignant tumor with infiltration throughout the liver, spreading into neighbouring organs and metastases formation in distant organs. Thus, one of the prevailing differential diagnoses is liver cancer. Guided by the Tumor-Node-Metastasis (TNM) system of liver cancer, the European Network for Concerted Surveillance of Alveolar Echinococcosis and the WHO Informal Working Group on Echinococcosis proposed a clinical classification for alveolar echinococcosis. It was designated as PNM system (P = parasitic mass in the liver, N = involvement of neighbouring organs, and M = metastasis). As for TNM in oncology, single PNM categories were combined into four stages, I to IV. The system was developed by a retrospective analysis of 97 patients' records from two treatment centers (Besançon/France and Ulm/Germany). Recently, this WHO classification was applied to 222 patients in 4 clinical centers around the world (Besançon/France, n = 26; Urumqi/China, n = 46; Sapporo/Japan, n = 58; and Ulm/Germany, n = 92). All patients could be classified who had been diagnosed in the period from January 1998 to June 2005. The stage grouping indicated center differences, but appeared to segregate patients according to various treatment regimens. The WHO classification not only serves as a tool for the international standardization of disease manifestation but also aids to evaluate the outcome of a chosen diagnostic and treatment procedure in different treatment centers in Europe and Asia.

Animals↗
PubMed2005

Medical treatment of echinococcosis under the guidance of Good Clinical Practice (GCP/ICH).

Chemotherapy is one of the main components for the treatment of alveolar and cystic echinococcosis. Benzimidazoles are on the market since 30 years, and are used widely according to the recommendations of the 1996 WHO guidelines for treatment of cystic and alveolar echinococcosis [Bull WHO 1996; 74: 231-242.]. However, none of the two drugs (Albendazole or Mebendazole) would satisfy today the requirements for an approval by the relevant authorities, such as the European Agency for the Evaluation of Medicinal Products (EMEA) or the Food and Drug Administration (FDA). New anthelmithic drugs are in the pipeline, and some of them have already undergone preclinical testing. In addition, recent advances have been made in the definition of outcomes for clinical trials in alveolar echinococcosis. Thus, phase III studies with new active ingredients are needed to assess short- and long-term safety as well as the therapeutic value. The basic requirements for comparative drug testing are provided in the Note for Guidance on Good Clinical Practice (GCP), and are based upon the rules and regulations by International Conference on Harmonization (ICH) and the Clinical Trial Directive (Directive 2001/20/EC) of the European Commission. The application of these standards to new drug testing for echinococcosis will help to upgrade the level of evidence.

Anthelmintics↗
PubMed2005

Pregnancy is not a risk factor for gallstone disease: results of a randomly selected population sample.

AIM: To investigate the prevalence, risk factors, and selection of the study population for cholecystolithiasis in an urban population in Germany, in relation to our own findings and to the results in the international literature. METHODS: A total of 2 147 persons (1,111 females, age 42.8+/-12.7 years; 1,036 males, age 42.3+/-13.1 years) participating in an investigation on the prevalence of Echinococcus multilocularis were studied for risk factors and prevalence of gallbladder stone disease. Risk factors were assessed by means of a standardized interview and calculation of body mass index (BMI). A diagnostic ultrasound examination of the gallbladder was performed. Data were analyzed by multiple logistic regression, using the SAS statistical software package. RESULTS: Gallbladder stones were detected in 171 study participants (8.0%, n=2,147). Risk factors for the development of gallbladder stone disease included age, sex, BMI, and positive family history. In a separate analysis of female study participants, pregnancy (yes/no) and number of pregnancies did not exert any influence. CONCLUSION: Findings of the present study confirm that age, female sex, BMI, and positive family history are risk factors for the development of gallbladder stone disease. Pregnancy and the number of pregnancies, however, could not be shown to be risk factors. There seem to be no differences in the respective prevalence for gallbladder stone disease in urban and rural populations.

Adolescent↗
PubMed2005

Impact of fluoroquinolone prophylaxis on reduced infection-related mortality among patients with neutropenia and hematologic malignancies.

BACKGROUND: Fluoroquinolone prophylaxis during neutropenia in patients with cancer has been associated with decreased incidence of gram-negative bacteremia. Bacterial antimicrobial resistance is likely to cause a progressive lack of efficacy of fluoroquinolones, but no convincing evidence from clinicoepidemiologic observations has proved this hypothesis. METHODS: This prospective observational study assessed the impact of discontinuing fluoroquinolone prophylaxis on the incidences of fever and bacteremia and on mortality among patients with neutropenia, after chemotherapy for hematologic malignancies. RESULTS: After a 12-month baseline period of levofloxacin prophylaxis, a period of discontinuation of fluoroquinolone prophylaxis was planned but was stopped prematurely after 9 neutropenic episodes over 3 weeks, because the mortality rate (33.3%) was higher than that with routine fluoroquinolone prophylaxis (2.9%) (odds ratio [OR], 16.6; 95% confidence interval [CI], 3.6-77.2). Fewer patients had gram-negative bacteremia during the baseline period (4.8%; n=15) than during the discontinuation period (44.4%; n=4) (OR, 16.9; 95% CI, 4.1-70.0). After levofloxacin therapy was reintroduced, the incidence of gram-negative bacteremia and the mortality rate were comparable to those during the first period. Escherichia coli isolated during the discontinuation period was susceptible to levofloxacin in vitro, whereas all E. coli isolates isolated during both prophylaxis periods were resistant. Bloodstream infections were caused by a single agent when the patient had received levofloxacin prophylaxis, whereas most cases of gram-negative bacteremia were polymicrobial after discontinuation. CONCLUSIONS: These findings suggest that, despite increasing rates of antimicrobial resistance, levofloxacin prophylaxis during neutropenia may have a beneficial impact on morbidity and infection-related mortality. Continued monitoring of the rate of gram-negative bacteremia is warranted for timely detection of the loss of efficacy of fluoroquinolone prophylaxis.

Amyloidosis↗
PubMed2005

Prevalence of the metabolic syndrome in southwest Germany.

The metabolic syndrome is a highly prevalent multifaceted clinical entity. Obesity, which is part of the metabolic syndrome, is the fastest growing health-related problem worldwide. Since currently prevalence data of the metabolic syndrome are lacking from Germany, we have applied ATP III-criteria in two urban and rural cohorts. Our population-based studies provide evidence that the prevalence of the metabolic syndrome increases with age. It was found to be more prevalent in a rural population and in this group it clustered in males. As a consequence of our population-based studies evidence that especially the rural population is at high risk for future macrovascular complications is substantiated. The urgent need for preventive measures aimed at reducing the significantly increased health risk is underscored.

Adolescent↗
PubMed2004

Cytomegalovirus retinitis in a patient treated with anti-tumor necrosis factor alpha antibody therapy for rheumatoid arthritis.

BACKGROUND: Anti-tumor necrosis factor alpha (anti-TNF- alpha ) antibodies have been used for the treatment of chronic inflammatory diseases such as rheumatoid arthritis (RA) and psoriasis arthritis. Such antibody therapies result in a severe interference with the patient's immune system. Increased rates of upper respiratory tract infection, reactivation of latent tuberculosis, and other systemic infectious diseases have been reported among patients receiving anti-TNF- alpha antibodies. METHODS: As a note of caution, we describe a 57-year-old woman who received therapy with anti-TNF- alpha antibodies for RA refractory to methotrexate. After almost 2 years of treatment, she developed a severe cytomegalovirus (CMV) retinitis of the right eye. RESULTS: Laboratory assays revealed an immune status with nearly total loss of the cellular immune response and partial reduction of the humoral immune response. Intravenous treatment with ganciclovir, followed by oral administration of valganciclovir, resulted in an ophthalmological remission. Cessation of immunosuppressive therapy led to partial immunological reconstitution in the patient. Six months after discontinuation of immunosuppressive therapy, CMV retinitis of the left eye occurred but was treated successfully with a second course of oral valganciclovir. CONCLUSION: In the light of this first reported case of a serious CMV infection following therapy with anti-TNF- alpha antibodies, CMV infection should be considered in symptomatic patients.

Antibodies, Monoclonal↗
PubMed2004

Screening for mutations related to atovaquone/proguanil resistance in treatment failures and other imported isolates of Plasmodium falciparum in Europe.

BACKGROUND: Two single-point mutations of the Plasmodium falciparum cytochrome b gene (Tyr268Asn and Tyr268Ser) were recently reported in cases of atovaquone/proguanil (Malarone) treatment failure. However, little is known about the prevalence of codon-268 mutations and their quantitative association with treatment failure. METHODS: We set out to assess the prevalence of codon-268 mutations in P. falciparum isolates imported into Europe and to quantify their association with atovaquone/proguanil treatment failure. Isolates of P. falciparum collected by the European Network on Imported Infectious Disease Surveillance between April 2000 and August 2003 were analyzed for codon-268 mutations, by use of polymerase chain reaction-restriction fragment-length polymorphism. RESULTS: We successfully screened 504 samples for the presence of either Tyr268Ser or Tyr268Asn. One case of Ser268 and no cases of Asn268 were detected. Therefore, we can be 95% confident that the prevalence of Ser268 in the European patient pool does not exceed 0.96% and that Asn268 is less frequent than 0.77%. In 58 patients treated with atovaquone/proguanil, Tyr268Ser was present in 1 of 5 patients with treatment failure but in 0 of 53 successfully treated patients. CONCLUSIONS: Tyr268Ser seems to be a sufficient, but not a necessary, cause for atovaquone/proguanil treatment failure. The prevalence of both codon-268 mutations is currently unlikely to be >1% in the European patient pool.

Adolescent↗
PubMed2004

Structured treatment interruption in patients with alveolar echinococcosis.

In human alveolar echinococcosis (AE), benzimidazoles are given throughout life because they are only parasitostatic. It has been a longstanding goal to limit treatment, and recent reports suggest that, in selected cases, benzimidazoles may be parasitocidal. Previously, we showed that positron -emission tomography (PET) using [(18)F]fluoro-deoxyglucose discriminates active from inactive lesions in AE. We have now performed a 3-year prospective study in 23 patients and conducted a structured treatment interruption in those without signs of PET activity. Disease progression was further assessed by ultrasound, computerized tomography, laboratory parameters, and clinical examination. We found PET-negative lesions in 15 of 23 patients and benzimidazoles were discontinued in these patients. After 18 months, patients were reevaluated, and, of the 15 initially PET-negative patients, 8 showed either new activity on PET (n = 6) or signs of clinical progression (n = 2). Reinitiation of benzimidazoles halted parasite growth again. No further progression was detected after 36 months. PET had a sensitivity of 91% for the detection of active lesions. In conclusion, despite successful suppression of metabolic activity, in most cases benzimidazoles do not kill the parasite. PET is a reliable tool for assessing metabolic activity and for timely detection of relapses. Neither duration of treatment, kind of treatment, lesion size, calcifications, or regressive changes reliably indicate parasite death. We discourage the discontinuation of benzimidazoles in inoperable AE even after many years of treatment. However, patients with a poor compliance of benzimidazole intake or patients suffering from side effects to benzimidazoles might be assessed for PET negativity. If permanent discontinuation of benzimidazoles is attempted, the course of disease should be followed by PET.

Adult↗
PubMed2004

Update on glycopeptide use in german university hospitals.

BACKGROUND: A previous study has shown considerable variation in glycopeptide use from 1992 through 1994 among four university hospitals in southern Germany. Active antimicrobial management in one of the hospitals was associated with the containment of glycopeptide consumption in the medical and surgical service at < 1.5 defined daily doses (DDD)/100 patient days in the subsequent period. In the present study, more recent data on comparative glycopeptide use in German university hospitals were analyzed. MATERIALS AND METHODS: Hospital pharmacy records from 1998 through 2000 were evaluated. The number of DDD (definition according to the World Health Organization [WHO]/Anatomic and Therapeutic Classification [ATC] index) per 100 patient days was calculated to compare glycopeptide use in different medical and surgical service areas between eight German university hospitals. RESULTS: The 3-year averages in recent glycopeptide use for the eight hospitals ranged between 1.3 and 8.8 DDD/100 patient days in the medical services, and between 0.7 and 1.8 DDD/100 patient days in the surgical services. Only one of the eight hospitals showed medical service glycopeptide use of < 1.5 DDD/100 patient days. In most hospitals, glycopeptide use was higher in the medical intensive care units (ICU) (median 8.6; range 4.3 to 12 DDD/100 patient days, data for the year 2000) than in the surgical ICUs (median 6.7; range 1.2 to 8.6 DDD/100 patient days, data for the year 2000). High use was also observed for hematology-oncology services (median 7.5; range 2.7 to 15.7 DDD/100 patient days, data for the year 2000). CONCLUSION: These recent data from a larger hospital sample confirm large variations in glycopeptide use, identify hematology-oncology services as a significant prescribing source along with ICUs, and indicate areas of probable overuse of glycopeptide antibiotics. The data may be useful as a benchmark for further focused drug use control interventions.

Anti-Bacterial Agents↗
PubMed2004

Oligoclonal CD8+ T-cell expansion in patients with chronic hepatitis C is associated with liver pathology and poor response to interferon-alpha therapy.

The role of CD8(+) T lymphocytes in chronic hepatitis C virus (HCV) infection and in liver injury with subsequent development of fibrosis and cirrhosis is poorly understood. To address this question, we performed a follow-up study including 27 chronically HCV-infected individuals. We determined clonality and phenotypes of circulating CD8(+) T cells employing TCRBV spectratyping. Antigen specificity was tested by rMHC-peptide tetramer staining and stimulation with recombinant HCV antigens. In addition, T-cell clonality and phenotypes were followed during the variable clinical response of interferon- (IFN) alpha treatment. We could demonstrate that CD8(+) T-cell expansions were significantly associated with liver fibrosis and cirrhosis. Likewise, increased oligoclonality of circulating CD8(+) T cells in chronic HCV infection was identified as an indicator for poor clinical response to IFN-alpha therapy. Moreover, we also found that IFN-alpha therapy enhanced the differentiation of CD8(+) T cells towards a late differentiation phenotype (CD28(-) CD57(+)). In cases of virus elimination the disappearance of expanded terminally differentiated CD8(+) cells was observed. Thus, this study identifies an association of clonal expansions of circulating CD8(+) T cells with liver pathology and provides a possible explanation for the fact that response to IFN-alpha therapy diminishes with the duration of infection.

Adult↗
PubMed2004

Impeded Th1 CD4 memory T cell generation in chronic-persisting liver infection with Echinococcus multilocularis.

Memory T cells of the CD4 lineage coordinate immune responses against pathogens via the antigen-induced secretion of potent effector cytokines. The efficacy of these responses is thought to depend on both the overall number of pathogen-specific memory T cells and the particular array of cytokines that these cells are programmed to secrete. It is unknown to what extent cellular immunity can be induced by Echinococcus multilocularis infection. To examine the immunological memory provided by the adaptive cellular immune system in control of the chronic-persisting infection, peripheral lymphocytes of patients with alveolar echinococcosis (AE) were studied ex vivo. Stimulation of memory cells was performed with E. multilocularis vesicular fluid, purified protein derivative as recall antigen and phytohemagglutinin. Cytomegalovirus latency served as disease control. Frequencies of circulating CD4(+) T cells secreting IFN-gamma, IL-2, tumor necrosis factor-alpha, IL-4, IL-5 and IL-10 were determined by both cytokine flow cytometry and ELISPOT assays. Most strikingly, in chronic AE the frequencies of E. multilocularis antigen-specific cells committed to T(h)1-cytokine production were low (mean 0.5% of CD4(+) T cells). However, an E. multilocularis-specific response of CD4(+) T cells at frequencies of >/=0.1% was detected in the majority of AE patients (68%). Low numbers of cells committed to T(h)1 cytokine secretion were invariably seen in patients with active and inactive disease. Interestingly, the number of specific CD4(+) memory T cells was not increased in cured AE patients after complete surgical removal of the metacestode. Hyporesponsiveness during the chronic helminth infection was E. multilocularis specific. Thus, our results demonstrate that antigen-specific memory function against E. multilocularis is markedly different from that against viral or bacterial pathogens. Whether the antigen-specific cellular hyporesponsiveness with impeded T(h)1 CD4(+) memory T cell generation is a cause or a result of the progressive metacestode activity remains to be determined.

Adult↗
PubMed2004

Risk factors for alveolar echinococcosis in humans.

We conducted a case-control study to investigate risk factors for acquiring autochthonous alveolar echinococcosis in Germany. Forty cases and 120 controls matched by age and residence were interviewed. Patients were more likely than controls to have owned dogs that killed game (odds ratio [OR] = 18.0), lived in a farmhouse (OR = 6.4), owned dogs that roamed outdoors unattended (OR = 6.1), collected wood (OR = 4.7), been farmers (OR = 4.7), chewed grass (OR = 4.4), lived in a dwelling close to fields (OR = 3.0), gone into forests for vocational reasons (OR = 2.8), grown leaf or root vegetables (OR = 2.5), owned cats that roamed outdoors unattended (OR = 2.3), and eaten unwashed strawberries (OR = 2.2). Sixty-five percent of cases were attributable to farming. Measures that prevent accidental swallowing of possibly contaminated material during farming or adequate deworming of pet animals might reduce the risk for alveolar echinococcosis.

Adolescent↗
PubMed2003

Echinococcus granulosus infection: clinical presentation, medical treatment and outcome.

BACKGROUND: Chemotherapy of cystic echinococcosis became a treatment option 25 years ago, when new anthelminthic drugs were introduced. Benzimidazole carbamates were shown to kill the entire metacestode stage of the parasite, and praziquantel exhibited an effect on protoscoleces. Continuous or intermittent treatment with albendazole is recommended for a period of up to 6 months, and praziquantel may enhance the effect, in particular in the case of cyst spillage. Degenerative changes in the cysts occur in approximately 75% of the patients by the end of the treatment period. Benzimidazoles have to be applied in high daily doses, and adverse effects are observed, such as leucopenia, elevation of liver transaminases, and alopecia. Unfortunately, prospective randomized trials on the efficacy of chemotherapy versus surgery are not available. New treatment methods, such as percutaneous puncture, aspiration, injection of scolicidal agents and re-aspiration (PAIR) or modified PAIR-based techniques, have received much attention, and in experienced hands these approaches yield rates of cure and relapse equivalent to those following surgery. Adjunct treatment with benzimidazoles is the cornerstone of the interdisciplinary approach in cystic echinococcosis. CONCLUSION: The recent ultrasound WHO consensus classification of hepatic cysts is a major achievement, since on the basis of this classification prospective clinical trials can be initiated. The results of such studies may provide the basis for a stage-specific appropriate medical, interventional or surgical therapy, or even guide the clinicians to opt for 'watch and wait' by close observation without specific treatment.

Albendazole↗