Differences in observed and self-reported compliance with 'Five Moments for Hand Hygiene' as a function of the empathy of healthcare workers.

BACKGROUND: Hand hygiene at critical time-points (as established by the World Health Organization's model 'Five Moments for Hand Hygiene') remains the leading measure for minimizing the risk of healthcare-associated infections. While many interventions have been tested to improve hand hygiene compliance (HHC) of healthcare workers (HCWs), little is known about the relationship between HHC and empathy of HCWs. AIM: To investigate the relationship between moment-specific HHC rates and empathy of HCWs at both individual and ward levels. METHODS: HHC data were collected via observation and self-report, and empathy levels were measured using an established questionnaire. The survey was conducted on 38 wards of three tertiary care hospitals in Germany. Observation data were obtained via in-house observations conducted ≤8 months before or after the survey. FINDINGS: Evidence for the expected correlation between empathy of HCWs and moment-specific HHC was found for both observed HHC (Moment 1: r=0.483, P=0.031; Moment 2: r=588, P=0.006) and self-reported HHC (Moment 1: r=0.093, P=0.092; Moment 2: r=0.145, P=0.008). In analyses of variance, the critical interaction effect between empathy (i.e. lower vs higher empathy) and designated time-point of hand hygiene (i.e. before vs after reference task) was also significant. CONCLUSION: Empathy of HCWs should be considered as an important factor in explaining differences between moment-specific HHC rates. In consequence, empathy comes into focus not only as a crucial factor for high-quality patient care, but also as an important contributor to improving HHC.

Gargle pool PCR testing in a hospital during medium and high SARS-CoV-2 incidence.

BACKGROUND: Hospitals need to be protected from SARS-CoV-2 infections to protect vulnerable patients. Thus, a safe, efficient, and cost-effective SARS-CoV-2 testing system for hospitals, in addition to standard hygiene measures and vaccination of staff, is necessary. Here we report on the feasibility and performance of a pool real-time reverse-transcriptase polymerase-chain-reaction (rRT-PCR) test system at, medium and high incidence. METHODS: We implemented a testing concept based on gargling at home and pooling of samples in the hospital before PCR testing in the laboratory. We used two PCR systems (point of care and standard 96-well plate system) to adapt to challenges in the hospital setting and respond to a rising incidence in the Omicron wave. FINDINGS: During our 10-week study period, we performed 697 pool PCRs (8793 tests in total) and identified 65 asymptomatic staff members by pool PCR and 94 symptomatic staff members by positive individual PCR. Virus loads in those detected by pool testing were significantly lower (P<0.001). The test system remained workable even during the peak of the Omicron wave and no outbreaks occurred in any specific area of the hospital during the study period. Unvaccinated individuals were over-represented in the positively tested (37% vs 22% positive tests, P=0.04). The test procedure was well accepted by a majority of the hospital staff (84%). CONCLUSION: Repeated gargle pool rRT-PCR testing can be implemented quickly in hospitals and is an effective, easily adaptable and well-accepted test system for hospitals, even during phases with very high infection rates.

A strict mask policy for hospital staff effectively prevents nosocomial influenza infections and mortality: monocentric data from five consecutive influenza seasons.

BACKGROUND: Influenza infections acquired in hospital show increased mortality, especially in elderly patients with risk factors. Nevertheless, vaccination rates are low among both high-risk patients and healthcare workers (HCWs). AIM: To more effectively prevent influenza infections in the hospital during the influenza season, a strict mouth-nose protection (MNP) requirement was introduced for all staff throughout the shift on the affected wards as an intervention and its effect on nosocomial infection rates was studied. METHODS: The present data were obtained in a retrospective, monocentric analysis over a period of four consecutive influenza seasons from 2015 to 2019. MNP for all staff during the whole shift as an intervention was introduced in 2017 and for the following seasons if at least three influenza patients were in the ward at the same time. Data from hospitalized influenza patients before and after intervention were compared with regard to nosocomial incidences and mortality. FINDINGS: In the years with strict mandatory MNP (2017-2019), the nosocomial influenza incidence fell nearly 50% (odds ratio: 0.40; 95% confidence interval: 0.28-0.56; P < 0.001) accompanied by a significant reduction in nosocomial mortality by 85% (0.15; 0.02-0.70; P = 0.007). The infectious pressure indicated by influenza incidences and patient-days at risk were comparable before and after intervention, as was the low rate of vaccine uptake by nurses. CONCLUSION: Mandatory MNP for HCWs effectively protects patients from nosocomial influenza infections and mortality.

Bacterial load and pathogenic species on healthcare personnel attire: implications of alcohol hand-rub use, profession, and time of duty.

BACKGROUND: Since hand hygiene might prevent the risk of bacterial transmission from healthcare personnel attire (HCPA), the present study investigates the effect of alcohol-based hand rub (ABHR) use on bacterial load and pathogenic species on HCPA. METHODS: HCPA from doctors and nurses was investigated for bacterial contamination post duty. Samples from distinct areas of HCPA were obtained and analysed for bacterial load and species. A standardized questionnaire was performed regarding time of duty and profession, and ABHR from each ward was calculated according to a national standard. FINDINGS: Bacterial load on HCPA (700 samples from 200 HCPA) was found to be up to four-fold higher when wearing for more than one shift. Moreover, doctors had a lower bacterial load on attire compared to nurses. In a multivariate linear regression model, negative correlations with bacterial load on HCPA were found for ABHR (t = -2.080, P = 0.0379) and being a doctor (t = -6.009, P < 0.0001), and a positive correlation for the time of duty (t = 10.572; P < 0.0001). Detection of Staphylococcus aureus as the most prominent pathogen found on HCPA was influenced by the time of duty (odds ratio: 3.27; 95% confidence interval: 1.93-5.72; P < 0.0001) but not by ABHR (1.22; 0.30-3.42). CONCLUSION: ABHR, profession, and time of duty significantly affect the bacterial load on HCPA. Since the time of duty has the strongest impact on bacterial load, a daily change of HCPA is recommended.

Effect of two-step hygiene management on the prevention of nosocomial influenza in a season with high influenza activity.

BACKGROUND: Rapid identification of patients infected with influenza virus, precise case definition and strict hygiene measures are important for the prevention of nosocomial transmission. AIM: To prove the usefulness of a case definition for rapid identification of patients with influenza and to investigate the effect of two-step hygiene management, including the continuous use of surgical masks by hospital staff, on the rate of nosocomial infections. METHODS: All patients hospitalized between January and March 2015 with suspected influenza were enrolled. Real-time polymerase chain reaction testing for influenza was performed. Infected patients were managed according to the national hygiene guidelines, including the use of surgical masks by hospital staff during close contact with infected patients. When influenza activity increased, the continuous use of surgical masks by hospital staff was implemented as an add-on measure. FINDINGS: Most patients enrolled in this study were elderly (N=212, mean age 75 years). Frequency of cough was the only clinical parameter of respiratory infection that differed between influenza-negative and influenza-positive patients. Compared with the targeted use of surgical masks during close contact with infected patients, the continuous use of surgical masks for the entire working shift resulted in a reduction of nosocomial infections from 31% to 16%, respectively (P<0.01). CONCLUSION: Discrimination between influenza A and other respiratory infections in elderly hospitalized patients was not possible based on clinical characteristics. With regard to hygiene management, the continuous use of surgical masks by hospital staff seems to be effective for the prevention of nosocomial infections.

[Rational antibiotic treatment of mediastinitis]. / Rationale Antibiotikatherapie der Mediastinitis.

Mediastinitis occurs as a severe complication of thoracic and cardiac surgical interventions and is the result of traumatic esophageal perforation, conducted infections or as a result of lymphogenic and hematogenic spread of specific infective pathogens. Treatment must as a rule be accompanied by antibiotics, whereby knowledge of the spectrum of pathogens depending on the pathogenesis is indispensable for successful antibiotic therapy. Polymicrobial infections with a high proportion of anaerobes are found in conducted infections of the mediastinum and after esophageal perforation. After cardiac surgery Staphylococci are the dominant pathogens and a nasal colonization with Staphylococcus aureus seems to be a predisposing risk factor. Fungi are the predominant pathogens in immunocompromised patients with consumptive underlying illnesses and can cause acute or chronic forms with granulomatous inflammation. Resistant pathogens are increasingly being found in high-risk patient cohorts, which must be considered for a calculated therapy. For calculated antibiotic therapy the administration of broad spectrum antibiotics, mostly beta-lactams alone or combined with metronidazole is the therapy of choice for both Gram-positive and Gram-negative bacteria inclusive of anaerobes. For patients at risk, additional antibiotic classes with a spectrum against methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) can be administered. Increasing rates of multidrug-resistant Gram-negative bacteria (e.g. Enterobacteriaceae) and non-fermenting bacteria (e.g. Pseudomonas and Acinetobacter) in individual cases necessitates the use of polymyxins (e.g. colistin), new tetracyclines (e.g. glycylglycines) and newly developed combinations of beta-lactams and beta-lactam inhibitors. For treatment of fungal infections (e.g. Candida, Aspergillus and Histoplasma) established and novel azoles, amphotericin B and echinocandins seem to be successful; however, detection of Candida, particularly in mixed infections does not always necessitate treatment. Mediastinitis is still a severe infectious disease with a high mortality, which necessitates an early and broad spectrum antibiotic therapy; however, with respect to optimal duration of therapy and selection of antibiotics, data from good quality comparative studies are lacking.

Mean cell volume of neutrophils and monocytes compared with C-reactive protein, interleukin-6 and white blood cell count for prediction of sepsis and nonsystemic bacterial infections.

Clinicians are in need of better diagnostic markers for rapid diagnosis of severe infections. Therefore, we studied the diagnostic significance of mean cell volume of neutrophils (MNV) and monocytes (MMV) compared with Interleukin-6 (IL-6), C-reactive protein (CRP) and white blood cell count for predicting systemic clinical infection (sepsis). MNV and MMV were obtained by volume conductivity scatter (VCS) technique of the Coulter LH 750 hematology analyzer during automated differential counts, and blood samples from patients with sepsis (n = 37), nonsystemic bacterial infections (n = 39) and controls (n = 48) were studied. We observed a significant increase in MNV and MMV in the sepsis group compared with limited infections and controls. However, at a designated cut-off point of 250 pg/ml, IL-6 seemed to be the best predictor for sepsis with a sensitivity of 93% and a specificity of 76%. Compared with CRP (cut-off point 60 mg/dl), MNV at a cut-off of 150 had a comparable sensitivity and specificity and was the most predictive VCS parameter. Taken together, MNV and MMV seemed to be potential parameters to discriminate between sepsis and nonsystemic infections.

Antibiotic therapy for diabetic foot infections: comparison of cephalosporines with chinolones.

Diabetic foot complications are the most common cause of non-traumatic lower extremity amputations and uncontrolled infections represent a major risk factor. This open prospective, multicenter trial compared the efficacy of two antibiotic regimens for treatment of foot infections Wagner stage II or III in diabetic adults. Three hundred diabetic patients with severe, limb-threatening foot infection were consecutively enrolled in a prospective, observational, matched pairs controlled study to test two different antibiotic regimes (ceftriaxone vs chinolones) in addition to standard treatment of foot infection. After matching, 90 patients--each receiving ceftriaxone or chinolones--were analyzed. Our study demonstrated that treatment with a third generation cephalosporine is as effective as a treatment with chinolones. Response (reaching Wagner I or 0) was achieved in 58.0% in the ceftriaxone group and in 51.1% in the chinolone group (NS.). Fourteen days after initiation of treatment, the number of patients with microbiological isolates decreased in both groups (52 to 5 in the ceftriaxone group and 60 to 12 in the chinolone group). At hospital discharge, 66.0% of ceftriaxone and 64.4 of chinolone-treated diabetic ulcers were cured or improved. In summary, both substances proved to be effective in the primary antibiotic treatment of the diabetic foot; an early broad spectrum antibiotic treatment, that covers both gram-positive and gram negative bacteria as well as anerobes is undisputedly an imperative therapeutic intervention for the treatment of diabetic foot infection.

Contrasting effects of long-term treatment with IFN-gamma in endothelial cells: increase in IL-6 secretion versus decrease in IL-8 secretion, NF-kappa B, and AP-1 activation.

The benefit of neutrophil exclusion from type 1 T helper cell (TH1) inflammatory processes was demonstrated in clinical studies. Increased recruitment of lymphocytes and monocytes to endothelium and impaired recruitment of polymorphonuclear neutrophils (PMNs) following interferon-gamma (IFN-gamma) treatment were described. The present study demonstrates that a 24 h treatment with IFN-gamma increases interleukin (IL)-6 release but reduces IL-8 secretion of both untreated and of tumor necrosis factor-alpha (TNF-alpha)-stimulated endothelial cells (ECs), favoring the attraction of lymphocytes but not of neutrophils. Alteration of cytokine release was accompanied by reduced basal and TNF-alpha-stimulated nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1) activity. However, IFN-gamma application neither altered gene expression of both TNF-alpha receptors (p55 and p75) nor cellular density of TNF-alpha receptor-2 (p75). Therefore, immune-modulatory action of IFN-gamma seems to be mediated by signal transduction molecules.

Expression of matrix-metalloproteinases and their inhibitors in the wounds of diabetic and non-diabetic patients.

AIMS/HYPOTHESIS: The molecular factors that cause an acute wound in diabetic patients to become chronic have not yet been established. Wound healing is known to require a balance between the accumulation of collagenous and non-collagenous extracellular matrix components and their remodelling by matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs). Our aim was to assess if the concentrations of MMPs and TIMPs were different between acute and chronic wounds in diabetic patients by analysing biopsy samples. METHODS: A 5 mm punch biopsy was taken from 20 diabetic foot ulcers of patients before initiating treatment and from traumatic wounds of 12 non-diabetic patients 2 days after injury. The concentrations of MMP-1, MMP-2(pro), MMP-2(active), MMP-8, MMP-9 and TIMP-2 were measured in detergent extracts of the biopsy homogenates using ELISAs and gelatin-zymography. RESULTS: The concentration of MMP-1 was increased 65-fold in biopsies of diabetic foot ulcers compared with the concentrations measured in biopsies of traumatic wounds. Similarly, MMP-2(pro) were increased threefold, sixfold for MMP-2(active), twofold for MMP-8 and 14-fold for MMP-9 compared to average concentrations in biopsies of traumatic wounds. Furthermore, the expression of TIMP-2 was reduced twofold in diabetic wounds compared with lesions of non-diabetic patients. CONCLUSION/INTERPRETATION: The combination of increased concentrations of MMPs with decreased concentrations of TIMP-2 in chronic diabetic foot ulcers compared with healing wounds in normal patients suggests that the increased proteolytic environment contributes to the failure of diabetic wounds to heal. New treatment strategies for healing chronic diabetic foot ulcers could be directed towards reducing concentrations of MMPs and increasing levels of TIMPs.

Regulation of mu-opioid receptor gene transcription by interleukin-4 and influence of an allelic variation within a STAT6 transcription factor binding site.

Morphine and the endogenous opioid peptide beta-endorphin exert neuromodulatory as well as immunomodulatory effects, which are transduced by mu-opioid receptors. In this report we show that stimulation with interleukin-4 induces mu-opioid receptor transcripts in human primary blood cells (T cells and polymorphonuclear leukocytes), immune cell lines (Raji, U-937, and HMEC-1), and dendritic cells. In nonstimulated immune cells this gene is silent. In addition, mu receptor transcription is up-regulated by interleukin-4 in cultures of primary rat neurons. Transient transfection experiments in Raji and SH SY5Y neuronal cells with human and rat reporter gene constructs linked the interleukin-4 effect directly to cis-active mu receptor promoter elements located at nucleotide -997 on the human gene and nucleotide -727 on the rat gene. The interleukin-4 response elements function orientation independently. They bind STAT6 transcription factors as shown by electrophoretic mobility shift assays. In the human gene, a single nucleotide polymorphism within the interleukin-4 response element reduces the trans-activating potential of this element by 50%, which may affect the phenotype of persons carrying this variation. These findings provide a molecular basis for understanding bidirectional interactions between the opioid system and the immune system.

Factors explaining the difference of total homocysteine between men and women in the European Investigation Into Cancer and Nutrition Potsdam study.

Interestingly, plasma total homocysteine (tHcy) concentration is consistently higher in men than in women. This observation deserves further investigations because elevated tHcy concentrations have been shown to be independently associated with coronary, peripheral, and cerebral vascular diseases. It was the aim of the present study to define major determinants of plasma tHcy in a healthy middle-aged German population under particular consideration of the gender factor. The study population was obtained from an ongoing recruitment procedure for a cohort study and comprised 336 men and women, aged 40 to 65 years. Exclusion criteria were elevated creatinine levels in blood, history of skin or atherosclerotic diseases, current use of vitamins or other supplements, and heavy smoking. Plasma tHcy, folate, vitamin B12, vitamin B6, creatinine, testosterone and estradiol, protein, and hematocrit were measured. Fat-free mass was assessed by skinfold thickness. The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR), a key enzyme of folate and homocysteine metabolism, was determined by polymerase chain reaction (PCR) with restriction enzyme analysis. In this population, plasma tHcy ranged from 5 to 46 micromol/L. The frequency of the T allele of the MTHFR was 0.29, which is lower than in other populations. A total of 54.2% of this population was homozygote for the wild-type, 39.6% heterozygote, and 6.2% homozygote for the mutation. tHcy correlated negatively with folate and cobalamin concentration in blood and positively with creatinine. No correlation was seen with vitamin B6. From the gender-related variables, tHyc correlated significantly with fat-free mass and testosterone and inversely with estradiol. The difference between gender with regard to tHcy was mainly explained by differences in fat-free mass, but also by estradiol concentrations. The following contributions to the variation of tHcy were seen in a multivariate regression model: plasma cobalamin (11%), creatinine (11%), plasma folate (8%), fat-free mass (5%), estradiol (2%), MTHFR polymorphisms (2%), and plasma protein (1%). We concluded that tHcy in the general population has a variety of determinants ranging from nutrition, internal metabolic parameters to gender-related variables.

Relation between homocysteinaemia and diabetic neuropathy in patients with Type 2 diabetes mellitus.

AIMS: Limited data are available on determinants of diabetic neuropathy as its pathogenesis is multifactorial. Since homocysteine exhibits toxic effects on vascular endothelial cells, the association between homocysteine and the prevalence of neuropathy in Type 2 diabetes mellitus was investigated. METHODS: A total of 65 Type 2 diabetic patients were consecutively enrolled into the study. Neuropathy was diagnosed according to clinical symptoms, clinical examination, electrophysiological sensory testing and autonomic function testing. With regard to homocysteine-related parameters, plasma homocysteine, folate, vitamin B12, vitamin B6 and renal function (creatinine, ceratinine clearance, cystatin C) were measured, and the C677T polymorphism of the methylenetetrahydrofolate reductase gene was determined. RESULTS: Forty-three of the Type 2 diabetic patients were classified as suffering from neuropathy. Both patient groups were comparable with regard to demographic data, blood pressure, glucose metabolism, renal function and homocysteine-related vitamins. In contrast, homocysteine levels (P = 0.04) and the frequency of hyperhomocysteinemia (>or= 15 micromol/l) (P = 0.01) were significantly increased in neuropathic patients. In a logistic regression model with neuropathy as dependent variable, homocysteine (adjusted for creatinine, homocysteine-related vitamins, HbA1c and duration of diabetes) was the only significant variable associated with the prevalence of neuropathy (odds ratio for homocysteine per 5 micromol/l increase: 2.60 (95% confidence interval 1.07-6.33)). CONCLUSION: The data indicate that homocysteine is independently associated with the prevalence of diabetic neuropathy in a collective of Type 2 diabetic patients. A larger, prospective study would be desirable to clarify the role of homocysteine in the pathogenesis of diabetic neuropathy.

Blastocystis hominis modulates immune responses and cytokine release in colonic epithelial cells.

An experimental in vitro model has been developed in order to determine whether Blastocystis hominis is able to trigger inflammatory cytokine response in colonic epithelial cells. After 24 h incubation of B. hominis with the cell lines HT-29 and T-84, B. hominis cells were not able to cause cytopathic effects, but significant increases in the release of the cytokines IL-8 and GM-CSF could be observed. However, after the first 6 h of co-incubation, the production of IL-8 was not increased in HT-29 cells, and even reduced when Escherichia coli (bacteria or lipopolysaccharide) was present during co-incubation. Similar effects were observed using supernatants of B. hominis culture. These data indicate that B. hominis induces as well as modulates the immune response in intestinal epithelial cells, and we conclude that different pathophysiological events may occur during B. hominis infection.

Cardiac troponin T predicts mortality in patients with end-stage renal disease.

BACKGROUND: Patients with end-stage renal disease have a high risk of premature death, mainly as the result of cardiovascular disease (CVD), which is not sufficiently explained by the conventional risk factors. We therefore prospectively investigated total mortality and cardiovascular events in 102 patients on hemodialysis and assessed the prognostic value of baseline disease status and laboratory variables including total homocysteine and cardiac troponin T. METHODS AND RESULTS: Patients were followed for 2 years or until their first event of CVD (for outcome variable cardiovascular events, n=33) or death (for outcome variable total mortality, n=28). Survival was computed by the Kaplan-Meier method. Cox proportional hazards model was used to determine independent predictors of CVD events or total mortality. Cardiac troponin T emerged as the most powerful predictor of mortality, resulting in an almost 7-fold risk increase at concentrations >0.10 ng/mL (hazard ratio 6.85, 95% CI 3. 04 to 15.45). Total homocysteine level greater than median was also associated with mortality (hazard ratio 2.44, 95% CI 1.10 to 5.40). These hazard ratios did not change substantially after adjustment for other risk factors. Significant predictors for CVD events were baseline diabetes, cerebrovascular disease, serum glucose, and triglycerides. After adjustment, only glucose and triglycerides remained significantly related to CVD events (hazard ratio with 95% CI 1.33 [1.12 to 1.57] and 1.14 [1.04 to 1.26], respectively, for a 1-mmol/L increase in concentration). CONCLUSIONS: We conclude that total homocysteine and particularly cardiac troponin T are important predictors of mortality in patients with end-stage renal disease, whereas other laboratory variables and baseline disease status have less prognostic value.

Postprandial chylomicrons and VLDLs in severe hypertriacylglycerolemia are lowered more effectively than are chylomicron remnants after treatment with n-3 fatty acids.

BACKGROUND: n-3 Fatty acids lower plasma triacylglycerols not only in the fasting state but also in the postprandial state. However, it is not known whether chylomicrons, chylomicron remnants, and VLDLs are all affected equally or whether some lipoprotein species are lowered preferentially. OBJECTIVE: Lipoproteins, including large and small chylomicron remnants, were determined specifically with the aid of a newly developed method involving a combination of size-exclusion chromatography and fluorometric determination of retinyl palmitate, which served as a marker for exogenous fat. DESIGN: Twelve hypertriacylglycerolemic men were treated for 6 wk with 4 capsules containing 85% fish-oil concentrate/d; each capsule contained 850 mg n-3 fatty acid ethyl esters (49.1% eicosapentaenoic acid by wt and 32.2% docosahexaenoic acid by wt). Oral-fat-tolerance tests were performed before and after the treatment. Blood samples were drawn in the fasting state and until 8 h postprandially. RESULTS: Treatment with n-3 fatty acids reduced the fasting VLDL-triacylglycerol concentration by 44% (P < 0.05) and postprandial chylomicrons and VLDLs at 4, 6, and 8 h (P < 0.05) by 49-64% and 36-43%, respectively. Chylomicron remnants were reduced only in the late postprandial phase: large chylomicron remnants by 19% at 6 h and by 43% at 8 h (P < 0.05) and small chylomicron remnants by 31% at 8 h (P < 0.05). CONCLUSION: n-3 Fatty acids effectively lower chylomicrons and VLDLs, but their effect on chylomicron remnants was observed only in the late postprandial phase.

[Characteristics of the hepatitis C virus and viral predictors of therapeutic response]. / Charakteristika des Hepatitis-C-Virus und virale Prädiktoren der therapeutischen Intervention.

NATURAL HISTORY OF HEPATITIS C-INFECTION AND VIRAL CHARACTERISTICS: Hepatitis C-virus (HCV) infection is a major cause of non-A, non-B-hepatitis and, additionally, is associated with liver cirrhosis and hepato-cellular carcinoma. The high degree of chronificity of HCV-infection is reasonable due to antigenic variability of neutralizing epitopes leading to incomplete immunoresponse with subsequent virus persistence. Besides genetic variants of HCV within a virus population (quasispecies nature of HCV), different genotypes are classified being genetically and phenotypically distinct, and geographically restricted in part. Genotyping of HCV is not only important for phylogenetic and epidemiological studies, but also a predictive marker for pathogenesis and therapy. VIRAL PREDICTORS OF HCV THERAPY: In a meta-analysis of 18 therapeutical studies of chronical HCV infections, genotype 1 and high levels of viremia determined markedly the response to interferon therapy. In this context, clinical trials have proven the effect of a combined therapy with interferon and ribavirin. Especially patients with HCV genotype 1 or high levels of viremia had a real benefit from combined antiviral therapy in comparison to monotherapy with interferon. CONCLUSION AND FUTURE CONCEPTS: Besides recent concepts improving the therapeutical response to HCV infection, further effort is necessary to develop more successful strategies for eradication of hepatitis C virus. In this context, variations of interferon therapy should be evaluated (e.g. higher and daily doses, longer duration of interferon therapy, "retarded" interferon (PEG-IFN). In addition, new therapeutical concepts should be performed including a combination of interferon with other known antiviral agents (amantadine), a combination with immunomodulators (GM-CSF, thymosin alpha 1), the development of new antiviral agents (inhibitors of viral proteases, helicases and polymerases) and the exploration of anti-viral, molecular strategies (specific ribozymes, antisense oligonucleotides and DNA-vaccination). Nevertheless, the development of an effective vaccination should be the most important challenge for the future.

Analysis of the Gly40Ser polymorphism in the glucagon receptor gene in a German non-insulin-dependent diabetes mellitus population.

A heterozygous polymorphism changing GGT40 (Gly) to AGT40 (Ser) in the glucagon receptor gene (GCG-R) was reported to be associated with non-insulin-dependent diabetes mellitus (NIDDM). A possible involvement of this polymorphism in impaired glucose tolerance was also suggested in a French population. However, the prevalence of this polymorphism differs markedly among different ethnic groups, whereby the results in German populations were found to be contradictory. We thus investigated the association of this mutation with NIDDM and healthy subjects in 508 German subjects (196 NIDDM, and 312 controls). None of the control subjects, but one of the NIDDM patients demonstrated the Gly40Ser polymorphism. Since no first-degree relative of the index patient had this genetic variance, a de novo mutation is suggested. Although the frequency of the Gly40Ser polymorphism in NIDDM observed in France is not confirmed in our population, this genetic variance is also evident in Germany.

Supplementation with vitamin B12 decreases homocysteine and methylmalonic acid but also serum folate in patients with end-stage renal disease.

Hyperhomocysteinemia is frequently found in patients with end-stage renal disease (ESRD). Plasma total homocysteine (tHcy) concentrations may be reduced by supplementation with folic acid or combinations of folic acid, vitamin B12, and vitamin B6. Supplementation studies with vitamin B12 alone in patients with ESRD have not yet been published. In this study, we investigated the effects of intravenous injection of cyanocobalamin (1 mg/wk for 4 weeks) in ESRD patients (N = 14) with low serum cobalamin concentrations (<180 pmol/L). All patients had elevated levels of plasma tHcy, methylmalonic acid (MMA), and cystathionine before supplementation. After supplementation, plasma tHcy and MMA decreased 35% and 48%, respectively; however, cystathionine levels were unchanged. The extent of the plasma tHcy reduction tended to be influenced by the C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR). Serum cobalamin increased significantly upon supplementation, whereas serum folate levels were substantially reduced by 47%. In contrast, red blood cell (RBC) folate was unchanged. This study shows that vitamin B12 supplementation effectively decreases both MMA and plasma tHcy in ESRD patients with low B12 levels. Furthermore, it illustrates the close interrelation between vitamin B12 and folate metabolism.