Volume 32, Issue 4

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Vitamin D deficiency is present in approximately 50% of the world population and is mainly a consequence of reduced sun exposure (ultraviolet B radiation) of the skin that is needed for dermal vitamin D production. Dietary intake of vitamin D is usually too low to maintain a sufficient vitamin D status. It has been demonstrated over the last few years that most tissues and cells express the vitamin D receptor supporting the notion that vitamin D exerts various effects beyond its established role for maintenance of bone and skeletal health. Epidemiological data show that 25-hydroxyvitamin D levels, that are currently considered the best indicator of vitamin D status, are associated with various diseases, including cardiovascular, malignant and autoimmune diseases. However, the causality of these associations remains to be proven. Interventional trials are therefore urgently needed to elucidate whether vitamin D supplementation is useful for the prevention and/or treatment of various chronic diseases. Vitamin D supplementation has immense potential for the improvement of public health when considering the high prevalence of vitamin D deficiency and the easy, inexpensive and safe way in which vitamin D can be supplemented.

Vitamin D deficiency is present in about 50% of the world population, which is mainly a consequence of reduced sun exposure (ultraviolet B radiation) of the skin that is needed for dermal vitamin D production. Dietary intake of vitamin D is usually too low to maintain a sufficient vitamin D status. It has been demonstrated over the last few years, that most tissues and cells express the vitamin D receptor supporting the notion that vitamin D exerts various effects beyond its established role for maintenance of bone and skeletal health. Epidemiological data show that 25-hydroxyvitamin D (25[OH]D) levels, that are currently considered the best indicator of vitamin D status, are associated with various diseases including cardiovascular, malignant and autoimmune diseases. However, the causality of these associations remains to be proven. Interventional trials are therefore urgently needed to elucidate whether vitamin D supplementation is useful for the prevention and/or treatment of various chronic diseases. Vitamin D supplementation has immense potential for the improvement of public health when considering the high prevalence of vitamin D deficiency and the easy, inexpensive, and safe way in which vitamin D can be supplemented.

Plant sterols are commonly used as cholesterol lowering nutriceuticals. In subjects who regularly consume plant sterol enriched functional foods, plasma plant sterol concentration is modestly increased. Sitosterolemia, a very rare genetic disorder, is characterized by xanthomas and up to 100-fold elevation of plasma plant sterols. Because patients with sitosterolemia are at high risk to develop severe premature coronary artery disease, even modestly increased plasma plant sterols are suggested to be atherogenic. Thus, there is no consensus on the question if cardiovascular risk can be reduced by the use of plant sterol margarines. In addition to their efficacy to decrease plasma cholesterol, plant sterols together with other non-cholesterol sterols are important for the investigation of cholesterol metabolism. Analyzing plasma non-cholesterol sterols, cholesterol absorption from the intestine and endogenous cholesterol biosynthesis can be estimated. The present review offers an overview of the topic „Plant Sterols“. In particular, the role of plant sterols and cholesterol metabolism in atherogenesis is discussed. We focus on cholesterol metabolism, sitosterolemia, and the use of plant sterols as cholesterol lowering agents. Furthermore, the significance of plasma plant sterol measurement is explained.

Plant sterols are commonly used as cholesterol-lowering nutriceuticals. In subjects who regularly consume plant sterol enriched functional foods, plasma plant sterol concentration is modestly increased. Sitosterolemia, a very rare genetic disorder, is characterized by xanthomas and up to 100-fold elevation of plasma plant sterols. Because patients with sitosterolemia are at high risk to develop severe premature coronary artery disease, even modestly increased plasma plant sterols are suggested to be atherogenic. Thus, there is no consensus on the question if cardiovascular risk can be reduced by the use of plant sterol margarines. In addition to their efficacy to decrease plasma cholesterol, plant sterols together with other non-cholesterol sterols are important for the investigation of cholesterol metabolism. Analyzing plasma non-cholesterol sterols cholesterol absorption from the intestine and endogenous cholesterol biosynthesis can be estimated. The present review offers an overview of the topic “Plant Sterols”. In particular, the role of plant sterols and cholesterol metabolism in atherogenesis is discussed. We focus on cholesterol metabolism, sitosterolemia, and the use of plant sterols as cholesterol-lowering agents. Furthermore, the significance of plasma plant sterol measurement is explained.

Following 3–5 days of hospital stay, Clostridium difficile is the most frequent causative agent of infectious diarrhea with high rates of diagnosis. Currently, the epidemiology of Clostridium difficile associated diarrhea (CDAD) is beginning to change. Outbreak is no longer exclusively allocated to the hospital environment, but is also seen in outpatients with increasing incidence. Further, in addition to antibiotic medication inducing the majority of cases, other medications are now known to cause CDAD. Since 2002, severe outbreaks were reported in North America, and in Canada an increased mortality for the typical over 60-year-old patient was found, with even younger patients suffering from fatal causes of the disease. There is a belief in the literature that medication with modern Fluoroquinolones may be a driver of hypervirulent isolates, which are classified 027-ribotype strains. First isolated in April 2007, in an outbreak in Germany, the spread of these hypervirulent strains is now ongoing in Germany. It seems obvious that not only the incidence and the severity of the disease in Germany will increase, but that the group of younger patients will similarly be affected. The German National Health Institute (RKI, Robert-Koch Institute, Berlin, Germany) has responded to this challenge with the obligation to report cases of 027-ribotype infection and the obligation to report fatal/severe cases. The present article focuses on historical aspects of Clostridium difficile and its toxins, and summarizes data on diagnosis, therapy and hygiene to manage the disease. Based on 10 years experience in our laboratories as the German consultant for Clostridium difficile and its diseases, we further comment on frequently asked questions from everyday practice.

Identification of bacterial resistance mechanisms is often a prerequisite for meaningful therapeutic recommendations. To infer the underlying resistance mechanism from the raw data of in vitro susceptibility tests requires recognition of typical patterns and, sometimes, additional tests. The present review provides an overview of frequent resistance mechanisms, their recognition, and of implied therapeutic consequences. Amongst others, we review methicillin (oxacillin) resistance and macrolide/lincosamide resistance in staphylococci, recognition of extended spectrum β-lactamases and AmpC β-lactamases in enterobacteria, and some general mechanisms and deductions for non-fermentative Gram-negative rods. Tables are presented relating phenotypes and interpretations. There is also a web tool that may aid in identifying resistance mechanisms (http://memiserf.medmikro.ruhr-uni-bochum.de/ResId).

Over the past few years, a dramatic increase in methicillin resistance of Staphylococcus aureus (MRSA) isolates has been observed worldwide. Infections due to MRSA cause higher rates of patient morbidity and mortality, longer hospital stays, and higher overall costs. Extensive infection control measures are necessary to prevent patient-to-patient transmission of MRSA. The sooner these infection control measures are taken, the lower is the probability of transmission between patients. Rapid identification of MRSA carriers is the fundamental task required to achieve this goal. Even sophisticated culture-based methods take at least 24 h to provide results. With the use of nucleic acid amplification technology, time-to-result periods of less than 3 h can be achieved under routine conditions. Although the originally developed PCR methods based on separate detection of the mec A gene and different S. aureus -specific markers are useful for molecular identification of MRSA, their diagnostic performance for direct detection of MRSA in clinical specimens is limited. More recently developed methods, which detect the integration event of a so-called SCC mec element (typically harbouring the mec A gene) into the S. aureus genome, are better suited for this purpose. At present, a number of different commercial and in-house PCR assays that rely on this innovative detection strategy are available. Although these assays usually display high levels of sensitivity (90–100%), specificity (93–99%) and positive predictive values (>95%), their negative predictive values are lower (80–95%). With the widespread use of these PCR assays, a number of intrinsic shortcomings have been identified that may lead to either false-positive or false-negative results. Therefore, an elaborate combination of molecular and culture-based methods should be implemented during routine laboratory workup for MRSA detection.

Over the past few years a dramatic increase in the methicillin resistance of S. aureus isolates has been observed worldwide. Infections with methicillin-resistant Staphylococcus aureus (MRSA) are accompanied by higher rates of morbidity and mortality, extended length of stay and increased overall costs. Large-scale hygienic measures are necessary to prevent the spread of the resistant isolates to patients not yet infected or colonized by MRSA. It has been demonstrated that the sooner such measures are taken, the smaller the probability of transmission to other patients. To achieve this result requires rapid identification of MRSA carriers. Even more recent culture-based detection methods can provide results only after 24 h. The use of modern PCR-supported detection methods opens the possibility to record findings within only a few hours. While the original test concepts, which are based on the separate detection of the mec A gene and various markers for S. aureus, have proven to be a good culture verification test, they are of limited usefulness for the rapid and meaningful direct detection of MRSA in clinical specimens. Recently developed, innovative test concepts based on the targeted detection of the integration of a so-called SCC mec element (a gene cluster typically also harboring the methicillin-resistance transmitting mec A-gen) in the S. aureus genome are better suited for this purpose. At present there exist a number of commercial test systems as well as a multitude of test concepts developed in-house, all of which are based on this fundamental principle. Although these assays usually display high levels of sensitivity (90–100%), specificity (93–99%) and positive predictive values above 95%, their negative predictive values are usually distinctly lower (80–95%). Meanwhile, with the increasingly broader use of these test methods several disturbance variables have been identified that can lead to false positive or false negative results. In view of these limits a combination of PCR-supported and cultural detection methods would appear to present a sensible policy.

Varicella zoster virus (VZV) belongs to one of the eight herpes viruses known to infect humans. While primary VZV infection (chickenpox) is generally a disease of childhood, herpes zoster occurs primarily in elderly persons (>50 years). Herpes zoster, also called shingles, is a neurocutaneous disease resulting from reactivation of latent VZV infection within dorsal root ganglia. Severe complications may occur in elderly persons and immunocompromised of any age, including severe complication of the eye, ear, skin and internal organs, and the peripheral and central nervous systems. A progressive decline of VZV-specific cell-mediated immunity and age are associated with an increased incidence and severity of herpes zoster and postherpetic neuralgia (PHN). PHN is the most common complication of herpes zoster causing chronic, debilitating pain. In cases with characteristic signs and symptoms (presence of prodromal pain, eruptions, grouped vesicles, segmental pain), the diagnosis is almost distinctive enough and no laboratory investigations are required. However, for patients lacking no characteristic pathology, a rapid laboratory diagnosis may be helpful to begin antiviral therapy as soon as possible. Antiviral therapy should be initiated immediately within 72 h after rash onset, particularly in older patients. The main aim of treatment is to control and reduce acute zoster pain, shorten virus replication, avoid dissemination of skin lesions and prevent PHN and other severe complications. The aim of the present review is to outline advantages and disadvantages of different herpes zoster laboratory methods (microscopy, direct immunofluorescence assay, detection of viral DNA, virus isolation and serological methods). A live attenuated VZV vaccine has been developed to prevent herpes zoster and PHN in individuals >60 years of age (Shingles Prevention Study). This review summarises the epidemiology, pathogenesis, clinical aspects, complications, therapy and prevention of varicella zoster.

Varizella zoster virus (VZV) belongs to one of the eight herpes viruses known to infect humans. While primary VZV infection (chickenpox) is generally a disease of childhood, herpes zoster occurs primarily in elderly persons (>50 years). Herpes zoster, also called shingles, is a neurocutaneous disease resulting from reactivation of latent varizella zoster virus infection within dorsal root ganglia. Severe complications may occur in elderly and in immuno-compromised persons, including severe complication of the eye, the ear, the skin, internal organs, and the peripheral and central nervous system. A progressive decline of VZV-specific cell-mediated immunity and age are associated with an increased incidence and severity of herpes zoster and postherpetic neuralgia (PHN). PHN is the most common complication of herpes zoster causing chronic, debilitating pain. In cases with characteristic signs and symptoms (presence of prodromal pain, eruptions, grouped vesicles, segmental pain) the diagnosis is almost distinctive enough and no laboratory investigations are required. However, for patients lacking no characteristic pathology, a rapid laboratory diagnosis may be helpful to start antiviral therapy as soon as possible. Antiviral therapy should be initiated immediately within 72 h after onset of rash particularly in older patients. The major aim of treatment is to control and reduce the acute zoster pain, to shorten virus replication, to avoid dissemination of skin lesions and to prevent PHN and other severe complications The aim of the present review is to outline advantages and disadvantages of different laboratory methods of herpes zoster (microscopy, direct immunofluorescence assay, detection of viral DNA, virus isolation and serological methods. A live attenuated VZV vaccine has been developed to prevent herpes zoster and postherpetic neuralgia in individuals beyond 60 years of age (Shingles Prevention Study). This review summarises the epidemiology, pathogenesis, clinical aspects, complications, therapy and prevention of varizella zoster.

Introduction : Healthcare workers are exposed to bloodborne pathogens (e.g., via contaminated devices). In the healthcare environment, needlestick injuries (NSI) represent a major risk factor in the transmission of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus. Medical students are at risk of occupational exposure to bloodborne viruses following needlestick injuries during medical education. Reporting of NSI is an important step for initiating early prophylaxis or treatment. Acquisition of a bloodborne infection is acquired could result in a claim. The objective of the present study was to describe occupational blood exposure of medical students through needlestick injuries. Methods : Sixth-year medical students were invited to complete an anonymous questionnaire. Results : In our study, 58.8% (n=183/311) of medical students recalled at least one needlestick injury during their studies. Overall, 284 needlestick injuries were reported. Only 38.3% of medical students reported all NSI to the appropriate hospital personnel. The main reason (54.0%) for not reporting NSI was being ashamed of having an NSI. Conclusions : Occupational exposure to blood is a common problem among medical students. Efforts are required to ensure greater awareness among medical students about the risk of bloodborne pathogens. Proper training in procedures and how to act in the case of injury should be offered to reduce the number of NSI.

Introduction : Healthcare workers (HCWs) are exposed to bloodborne pathogens (e.g., contaminated devices). In the healthcare environment, needlestick injuries (NSI) represent a major risk factor in the transmission of hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV). Medical students are at risk of occupational exposure to bloodborne viruses following needlestick injuries during medical education. Reporting of needlestick injuries is an important step for initiating early prophylaxis or treatment. In the case of a bloodborne infection, pursuant to insure law could result in a claim. The objective of the present study was to describe occupational blood exposure of medical students through needlestick injuries. Methods : Sixth-year medical students were invited to complete an anonymous questionnaire. Results : In our study, 58.8% (n=183/311) of medical students recalled at least one needlestick injury during their studies. Overall, 284 needlestick injuries were reported. Only 38.3% of medical students reported all NSI to the appropriate hospital personnel. The main reason (54.0%) for not reporting NSI was being ashamed of having an NSI. Conclusions : Occupational exposure to blood is a common problem among medical students. Efforts are required to ensure greater awareness among medical students about the risk of bloodborne pathogens. Proper training in procedures and how to act in case of injury should be offered to reduce the number of needlestick injuries.

The hepatitis B virus (HBV) is currently estimated to chronically infect almost 400 million people worldwide of which 65 millions live on the African continent. Based on the nucleotide distance between complete genomes, the circulating hepatitis B strains have been classified into different genotypes and subtypes most of which present a specific geographic distribution. Numerous phylogenetic studies have determined the genotypes and subtypes of HBV circulating in Africa, and have revealed a surprising picture. The most prevalent genotype found was genotype E, mostly in sub-Saharan Africa followed by genotype A distributed in sub-Saharan Africa but also in the South and East of Africa, and genotype D, which was mostly found in North Africa. While the evolutionary history of genotype A has seen an obvious diversification with the appearance of several subtypes, genotype E did not undergo a similar evolutionary history. In fact, genotype E and A co-circulate in several countries but although genotype A strains show a high diversity from country to country, the diversity among genotype E strains found in the same countries is very low. While this low diversity suggests a recent appearance of genotype E in Africa it is paradoxical to the fact that the same genotype is found on more than a third of the African continent. This review summarizes the current knowledge about the HBV genotypes circulating in Africa and laboratory diagnosis. Zusammenfassung Nach Schätzungen der WHO verursacht das Hepatitis B-Virus (HBV) derzeit chronische Infektionen von annähernd 400 Millionen Menschen, von denen 65 Millionen auf dem afrikanischen Kontinent leben. Basierend auf der genetischen Distanz zwischen kompletten Genomsequenzen werden HBV-Stämme in unterschiedliche Genotypen und Subtypen eingeteilt, von denen die Mehrheit eine spezifische geografische Verbreitung aufweist. Zahlreiche phylogenetische Studien haben die Genotypen und Subtypen der in Afrika verbreiteten Stämme bestimmt und ein überraschendes Bild aufgezeigt. Der am meisten verbreitete Genotyp ist Genotyp E in Westafrika, gefolgt vom Genotyp A, verbreitet in West-, Süd- und Ostafrika und vom Genotyp D, der hauptsächlich im Norden Afrikas vorkommt. Während die in Afrika gefundenen Genotyp A-Stämme eine klare Diversifikation in unterschiedliche Subtypen aufweisen, zeigen die gefundenen Genotyp E-Stämme das Gegenteil. Obwohl Genotyp A-und E-Stämme in manchen Fällen in den gleichen Ländern vorkommen, gehören die Genotyp A-Stämme zu unterschiedlichen Subtypen, je nachdem, in welchem Land sie vorkommen, während alle Genotyp E-Stämme sich mehr oder weniger ähnlich sind. Während diese geringe Diversifikation ein erst kürzliches Erscheinen der Genotyp E-Stämme in Afrika vermuten lässt, ist sie paradoxal zu der weiten Ausbreitung des Genotyps über fast einem Drittel des afrikanischen Kontinents. Diese Übersicht fasst den momentanen Kenntnisstand über die HBV-Genotypverbreitung in Afrika und die Diagnostik zusammen.

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