Therapy of aseptic nonunions with parathyroid hormone.

The absence of osseous consolidation of a fracture for 9 or more months with no potential to heal is defined as nonunion. Both for the patient and from a socioeconomic point of view, nonunions represent a major problem. Hypertrophic, vital nonunions are distinguished from atrophic avital ones. Risk factors for a delayed fracture healing are insufficient immobilisation, poor adaptation of the fracture surfaces or residual instability, interposition of soft tissue within the fracture gap, as well as circulation disturbances and infections. The incidence of nonunions after fractures of the long bones lies between 2.6 and 16% depending on the surgical technique used. In human and animal studies, a positive effect of parathyroid hormone (PTH) on fracture healing has been shown. PTH has a direct stimulatory effect on osteoblasts and osteoclasts. In addition, it appears to influence the effect of osseous growth factors. In this prospective study, 32 patients with nonunions were treated with teriparatide to investigate the effects of PTH on fracture healing. Definitive healing of the nonunions following PTH treatment could be observed in 95% of the cases.

[Recognition and correct classification of pressure ulcers: a position paper]. / Dekubitus erkennen und richtig klassifizieren: ein Positionspapier.

BACKGROUND: Pressure ulcers comprise serious skin and tissue damage. The correct diagnosis and classification into different categories is often difficult in daily practice. QUESTION: What procedure can be recommended to correctly diagnose and classify pressure ulcers in practice? MATERIALS AND METHODS: The society Initiative Chronische Wunden (ICW) e. V. established a group of experts who developed practical recommendations for the diagnosis and classification of pressure ulcers based on the current literature and their own expertise. RESULTS: Pressure ulcers should only be diagnosed if skin and/or tissue damage is most likely due to prolonged pressure or pressure associated with shear forces. A complete anamnesis must be performed to detect periods of previous prolonged immobility. Pressure ulcers are usually located at typical predilection sites. For category I and "suspected deep tissue damage" the tissue damage occurs under (initially) intact skin. However, the diagnosis is uncertain and the classification should be made later. The category II pressure ulcer is usually an exclusion diagnosis. The categories III and IV are pressure ulcers in the proper sense. As long as the distinction between category III and IV is not possible, the lower category should be coded. CONCLUSIONS: Currently, a relevant classification should be used uniformly for the respective setting. In accordance with the clinical picture, a most suitable diagnosis is to be made. It does not matter which classification system is used. The future WHO ICD-11 version will allow better classification of pressure ulcers.

[Orbital screwdriver injury in a toddler]. / Orbitale Schraubenzieherverletzung bei einem Kleinkind.

Presentation of a patient with an orbital intracranial penetrating screwdriver injury. The patient had been playing with the screwdriver at the time of the accident, he fell and the screwdriver penetrated his right orbit. Imaging revealed the position of the foreign body, which went from the medial orbital wall, extraconal and medial of the right internal carotid artery, through the sella turcica to the dorsum sellae. The patient had no intracranial hemorrhage. There was hardly any bleeding. The surgical removal of the screwdriver was carried out without complications.

[Health, Medical and Psychosocial Care Needs of Older Drug Addicts (40+): A Cross Sectional Study]. / Gesundheit und medizinscher und psychosozialer Versorgungsbedarf von akuten oder ehemaligen Drogenabhängigen im Alter (40+) ­ Eine Querschnittstudie.

BACKGROUND: We aimed 1) to assess health, health-related quality of life and social care needs of substance-abusing individuals aged 40+ and 2) to investigate associations between health and psychosocial care needs. METHODS: We estimated the size of the population by using capture-recapture methods. Based on this sample size estimation, we conducted a cross-sectional survey with socio-demographic data, using standardized instruments including the SF-36 (36 items), a measure of physical disorders (14 items), social support, and psychosocial and health care needs and substance abuse ("European Addiction Severity Index"). RESULTS: 37 persons participated in this study (30% women), 89% reported at least one disorder. The general health perceptions (p=0.011), vitality (p<0.001), social functioning (p<0.001), mental health (p<0.001) and physical health dimension (p=0.007) and mental health dimension (p<0.001) were significantly lower in this sample than in the German normal population (51-60 years). 54% reported having support needs. CONCLUSION: Health-related quality of life and social functioning are major problems for older substance-abusing individuals. There is a great need to have specific healthcare concepts to respond to the medical and psychosocial care needs of this group of individuals.

Improving the visualization of cryo-EM density reconstructions.

Cryo-electron microscopy yields 3D density maps of macromolecules from single-particle images, tomograms, or 2D crystals. An optimal visualization of the density map is important for its proper interpretation. We have developed a method to improve the visualization of density maps by using general statistical information about proteins for the sharpening process. In particular, the packing density of atoms is highly similar between different proteins, which allows for building a pseudo-atomic model to approximate the true mass distribution. From this model the radial structure factor and density value histogram are estimated and applied as constraints to the 3D reconstruction in reciprocal- and real-space, respectively. Interestingly, similar improvements are obtained when using the correct radial structure factor and density value histogram from a crystal structure. Thus, the estimated pseudo-atomic model yields a sufficiently accurate mass distribution to optimally sharpen a density map.

Biological activities of selected basidiomycetes from Yemen.

In a previous paper we demonstrated the results of biological screening of Yemeni basidiomycetes. The present study was aimed to investigate the antimicrobial and the antioxidant activity of further basidiomycetes collected in Yemen. Dichloromethane, methanol and aqueous extracts of the fruiting bodies of 25 species were screened in vitro for their antibacterial activities against three Gram-positive bacteria (Staphyloccocus aureus, Bacillus subtilis, Micrococcus flavus) and two Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa), against six human fungal pathogens (Candida albicans, Candida krusei, Aspergillus fumigatus, Mucor sp., Microsporum gypseum, Trichophyton mentagrophytes) and against one non human pathogenic fungus (Candida maltosa). The results indicated that 75 extracts exhibited activity against one or more of the bacteria. The methanol extracts of Agaricus cf. bernardii, Agrocybe pediades, Chlorophyllum molybdites, Coriolopsis polyzona, Ganoderma xylonoides, Pycnoporus sanguineus, Trametes lactinea and Trametes cingulata showed activity against all tested bacteria. The highest antibacterial activity was exhibited by methanol extracts from Chlorophyllum molybdites, Ganoderma xylonoides and Trametes cingulata and Agaricus cf. bernardii, Agrocybe pediades, Coriolopsis polyzona, Pycnoporus sanguineus and Trametes lactinea. The methanol extracts of Chlorophyllum molybdites, Ganoderma xylonoides and Pycnoporus sanguineus showed considerable antifungal activities against the tested fungal strains. Strong antioxidative effects employing the DPPH assay were exhibited by methanol extracts from Chlorophyllum molybdites, Ganoderma xylonoides, Hexagonia velutina, Pycnoporus sanguineus, Trametes lactinea and Trametes cingulata. Our previous and presented studies about 48 basidiomycetes collected in Yemen provide evidence that basidiomycetes from the Arabic region so far should attract more attention as potential source for new biologically active agents.

State of the art in benefit-risk analysis: economics and marketing-finance.

All market participants (e.g., investors, producers, consumers) accept a certain level of risk as necessary to achieve certain benefits. There are many types of risk including price, production, financial, institutional, and individual human risks. All these risks should be effectively managed in order to derive the utmost of benefits and avoid disruption and/or catastrophic economic consequences for the food industry. The identification, analysis, determination, and understanding of the benefit-risk trade-offs of market participants in the food markets may help policy makers, financial analysts and marketers to make well-informed and effective corporate investment strategies in order to deal with highly uncertain and risky situations. In this paper, we discuss the role that benefits and risks play in the formation of the decision-making process of market-participants, who are engaged in the upstream and downstream stages of the food supply chain. In addition, we review the most common approaches (expected utility model and psychometrics) for measuring benefit-risk trade-offs in the economics and marketing-finance literature, and different factors that may affect the economic behaviour in the light of benefit-risk analyses. Building on the findings of our review, we introduce a conceptual framework to study the benefit-risk behaviour of market participants. Specifically, we suggest the decoupling of benefits and risks into the separate components of utilitarian benefits, hedonic benefits, and risk attitude and risk perception, respectively. Predicting and explaining how market participants in the food industry form their overall attitude in light of benefit-risk trade-offs may be critical for policy-makers and managers who need to understand the drivers of the economic behaviour of market participants with respect to production, marketing and consumption of food products.

Looking beyond borders: integrating best practices in benefit-risk analysis into the field of food and nutrition.

An integrated benefit-risk analysis aims to give guidance in decision situations where benefits do not clearly prevail over risks, and explicit weighing of benefits and risks is thus indicated. The BEPRARIBEAN project aims to advance benefit-risk analysis in the area of food and nutrition by learning from other fields. This paper constitutes the final stage of the project, in which commonalities and differences in benefit-risk analysis are identified between the Food and Nutrition field and other fields, namely Medicines, Food Microbiology, Environmental Health, Economics and Marketing-Finance, and Consumer Perception. From this, ways forward are characterized for benefit-risk analysis in Food and Nutrition. Integrated benefit-risk analysis in Food and Nutrition may advance in the following ways: Increased engagement and communication between assessors, managers, and stakeholders; more pragmatic problem-oriented framing of assessment; accepting some risk; pre- and post-market analysis; explicit communication of the assessment purpose, input and output; more human (dose-response) data and more efficient use of human data; segmenting populations based on physiology; explicit consideration of value judgments in assessment; integration of multiple benefits and risks from multiple domains; explicit recognition of the impact of consumer beliefs, opinions, views, perceptions, and attitudes on behaviour; and segmenting populations based on behaviour; the opportunities proposed here do not provide ultimate solutions; rather, they define a collection of issues to be taken account of in developing methods, tools, practices and policies, as well as refining the regulatory context, for benefit-risk analysis in Food and Nutrition and other fields. Thus, these opportunities will now need to be explored further and incorporated into benefit-risk practice and policy. If accepted, incorporation of these opportunities will also involve a paradigm shift in Food and Nutrition benefit-risk analysis towards conceiving the analysis as a process of creating shared knowledge among all stakeholders.

[Value of fall-risk tests for patients with rheumatoid arthritis]. / Wertigkeit von Sturzrisikotests bei Patienten mit rheumatoider Arthritis.

The aim of the study was to quickly and efficiently determine the risk of falling in patients with rheumatoid arthritis over the age of 46 with established methods, to discover parameters which influence the risk of falling and fractures. The study group consisted of 67 patients (median age 69±7.4 years, duration of disease <10 years 71%).With the help of the present data on fractures the performance of the chair-rising (CR) test, the timed up-and-go (TUG) test and the tandem stand (TS) test plus determination of the average daily and cumulative glucocorticoid (GC) dosage, it was possible to detect parameters which influence the risk of falling and fractures.Higher age (>60 years), overweight, deficits in muscle strength in the lower extremities and very low GC dosage (≤5 mg) were found to be associated with an increased risk of falling, which is accompanied by an increased risk of fractures.

Candidosis and aspergillosis as autopsy findings from 1994 to 2003.

We analysed the autopsy records of the Greifswald University Institute of Pathology (located in Eastern Germany) in respect of findings of candidosis and aspergillosis from 1994 to 2003. We also present eight immature aborted fetuses and premature infants with a mycosis. In a total of 2027 autopsies we found 164 cases of invasive candidosis and aspergillosis (8.1%) including a combination of both on four occasions. Other authors cited between 0.7 and 7.3%. In these 10 years in our material mycoses and in particular candidosis increased in spite of slightly decreased numbers of autopsies. The differences comparing the 5-years periods (1994-98 and 1999-2003) are highly significant for both mycoses and candidosis. They are not significant for aspergillosis. A similar relationship was observed in the distribution of mycotic organs and causative origin for candidosis alone. In the last 5 years the gastrointestinal and respiratory tracts, including the peritoneum, were more frequently infected by Candida. Non-haematological neoplasia and pneumonia as basic diseases more often appeared in cases of candidosis. All eight immature aborted fetuses and premature infants suffered from candidosis. The survey confirms the importance of autopsy as a tool for education and quality control in medical diagnostic and therapeutic activity in the field of mycoses, too.

Trichophyton rubrum-induced inflammatory tinea capitis in a 63-year-old man.

Tinea capitis caused by Trichophyton rubrum is a rare event worldwide. We report on an elderly otherwise healthy man with inflammatory fungal disease of the scalp caused by this pathogen. He had no signs of concomitant mycosis of the skin and nails and no underlying immunosuppressive disease. The fungal infection primarily had been misdiagnosed in terms of a pyoderma. Failure of antibiotic treatment, a positive mycological study and molecular diagnostics eventually led to the correct diagnosis. After systemic and local administration of terbinafine the lesion improved totally.

A patient with myelofibrosis complicated by refractory ascites and portal hypertension: to tips or not to tips? A case report with discussion of the mechanism of ascites formation.

In patients with myelofibrosis, clinically significant portal hypertension is known to be predominantly presinusoidal; however, the exact mechanisms are still controversial. The pathophysiology is particularly enigmatic in those patients without histological and angiographic evidence of significant intra- or extrahepatic obstruction to portal blood flow, respectively. Moreover, ascites formation has been reported in such cases, but in general is rare in presinusoidal portal hypertension. Here we present such a patient in which ascites developed even in the presence of unchanged serum protein levels (oncotic pressure) and was refractory to sodium restricted diet and high-dose diuretic treatment. A discussion on the parameters influencing fluid exchange and ascites formation particularly emphasizing the potential importance of the hyperdynamic circulation in this case is given. Finally, the patient was treated by implanting a transjugular intrahepatic shunt (TIPS), exerting a diuretic effect sufficient enough to avoid re-formation of ascites for several months. However, ascites re-accumulated potentially due to the appearance of ectopic peritoneal myeloid metaplasia and the patient died soon afterwards. In conclusion, TIPS may be considered as rescue management for refractory ascites secondary to portal hypertension, but caution in respect to the presence and/or development of peritoneal or other ectopic haematopoesis has to be taken.

Single-molecule fluorescence resonance energy transfer reveals a dynamic equilibrium between closed and open conformations of syntaxin 1.

Protein conformational transitions form the molecular basis of many cellular processes, such as signal transduction and membrane traffic. However, in many cases, little is known about their structural dynamics. Here we have used dynamic single-molecule fluorescence to study at high time resolution, conformational transitions of syntaxin 1, a soluble N-ethylmaleimide-sensitive factor attachment protein receptors protein essential for exocytotic membrane fusion. Sets of syntaxin double mutants were randomly labeled with a mix of donor and acceptor dye and their fluorescence resonance energy transfer was measured. For each set, all fluorescence information was recorded simultaneously with high time resolution, providing detailed information on distances and dynamics that were used to create structural models. We found that free syntaxin switches between an inactive closed and an active open configuration with a relaxation time of 0.8 ms, explaining why regulatory proteins are needed to arrest the protein in one conformational state.

Molecular and biochemical characterization of three aromatic polyketide synthase genes from Rubus idaeus.

Three polyketide synthase genes (PKS1, PKS2, PKS3) from cell suspension cultures of raspberry (Rubus idaeus L. cv. Royalty) were characterized. They showed high similarity in both their nucleotide and deduced amino acid sequences. All three proteins contain the amino acid residues identified in previous work as essential for chalcone synthase (CHS) function. Enzyme activities were investigated after heterologous expression in Escherichia coli. RiPKS1 is a typical naringenin CHS that synthesizes the chalcone as the main reaction product, and p-coumaryltriacetic acid lactone (CTAL) as a minor by-product. RiPKS3 differed from RiPKS1 in four positions (K49R, M64R, P120L, V188A), and the products in vitro were predominantly CTAL and low levels of chalcone. RiPKS2 had the same four differences from RiPKS1 as RiPKS3, but in addition two further exchanges (R259H, F344L), and the protein had no detectable enzyme activity. Experiments with RiPKS1 containing either 259H or 344L showed that each of the exchanges was sufficient to completely eliminate enzyme activity. These experiments identify amino acid residues in CHS which are important for folding of the tetraketide intermediate to the chalcone (PKS3) and which are in general essential for CHS activity (PKS2). The possible functions of these residues are discussed.

[Interferon beta-1b (Betaferon)therapy in patients with relapsing-remitting multiple sclerosis: findings of a prospective, multi-center study of disease progression]. / Interferon beta-1b (Betaferon) bei Patienten mit schubförmig-remittierender Multipler Sklerose. Ergebnisse einer prospektiven, multizentrischen Verlaufsbeobachtung.

In a survey of disease course, the efficacy and tolerability of 24-month interferon beta-1b therapy for relapsing remitting multiple sclerosis (RRMS) were evaluated in 410 patients. The investigation aimed at obtaining data from general practice and of possibly unknown, unexpected adverse reactions. In the 241 patients still on therapy, efficacy was rated after 24 months as "good" or "very good" in 75% of cases. After 24 months, 36.9% of the patients had no exacerbation (baseline 0.3%). Annual exacerbation rates dropped from 1.5 before treatment to 0.7 in the second treatment year. In the 2 years before treatment, 66.2% had worsened by at least 0.5 points on the extended disability status scale (EDSS). This proportion was reduced to 41.2% after 2 years of treatment. The safety profile corresponded to results from controlled trials. This postmarketing survey supports data from the published controlled interferon beta-1b studies and confirms the main effects of this therapy under routine conditions in general practice.

Transmission of a multiresistant Pseudomonas aeruginosa strain at a German University Hospital.

Over 15 months, 60 patients at a German University Hospital became infected or colonized by a multiresistant Pseudomonas aeruginosa strain, which was isolated from tracheal secretions, blood, urine, venous catheters, ascites and several wounds. Most patients had undergone invasive treatment (surgery, cancer therapy). The genetic relationship of the isolates was investigated by pulsed field gel electrophoresis. The isolates were resistant to beta-lactam antibiotics, including carbapenems and aztreonam, to aminoglycosides and quinolones. The only in vitro susceptibility was to polymyxin B. Extensive sampling was carried out to identify contaminated medical devices, surfaces or media (water, food). Samples were taken from doctors and nursing staff and various treatment procedures were observed for several weeks. The handling of respirators, resuscitation tubes, urine bottles, and bedpans resulted in the contamination of the patients' environment, although most devices were cleaned and disinfected with automatic washer/disinfectors. Several wash basins on the intensive care unit were contaminated, but none of the drinking water samples showed any growth of P. aeruginosa. We recommend the strict use of gloves and strict application of alcoholic hand disinfectants immediately after discarding the gloves. The chain of infection ceased after strict cohort isolation and the subsequent introduction of the specific hygiene regime.

Immune response after adenoviral gene transfer in syngeneic heart transplants: effects of anti-CD4 monoclonal antibody therapy.

BACKGROUND: E1-deleted adenoviral vectors are frequently used for in vivo gene therapy. However, gene expression after adenovirus-(ad) mediated gene transfer is known to be transient due to the generation of an immune response against virus-infected cells. In this study, we asked whether an anti-CD4 mAb (RIB 5/2) treatment may improve the gene transfer into rat cardiac grafts. METHODS: We injected recombinant ad-constructs encoding for Escherichia coli beta-gal into syngeneic rat heart transplants via the proximal aorta. One-half of the recipients of genetically modified grafts received the anti-CD4 mAb RIB 5/2, whereas the other half received no monoclonal antibody treatment. Genetically unmodified isografts without any treatment of the recipients were used as additional controls. At different time points hearts were harvested and analyzed for reporter gene expression, intragraft cellular infiltration, and cytokine gene expression (quantitative "real time" reverse transcriptase polymerase chain reaction). Serum samples were analyzed for anti-ad-Ig using enzyme-linked-immunosorbent-assay. RESULTS: In control animals the beta-gal reporter gene expression slowly increased until day 7 and then declined. The immunohistological and reverse transcriptase polymerase chain reaction intragraft analyses revealed a strong inflammatory response (cellular infiltration, cytokine expression) in ad-transfected grafts that may explain the delayed expression and fast down-regulation of the transgene. Treatment with RIB 5/2 mAb resulted in a faster and prolonged reporter gene expression, reduced graft infiltration, reduced anti-ad-Ig titers and less interferon-gamma up-regulation. CONCLUSIONS: Our results indicate that modulation of the anti-ad immune response using a nondepleting anti-CD4 mAb may increase the efficiency of ad-vectors for gene therapy in the transplant setting.

Ischemia/reperfusion injury-mediated down-regulation of adenovirus-mediated gene expression in a rat heart transplantation model is inhibited by co-application of a TNFRp55-Ig chimeric construct.

E1-deleted adenoviral vectors are efficient vectors for somatic gene therapy. Recently, we have shown that intratracheal application of an adenoviral reporter construct leads to significant reporter gene expression in rat lungs within 24 h. In contrast, reporter gene expression in syngeneic rat heart transplants after adenovirus-mediated gene transfer was delayed. Since the adenovirus cannot replicate, down-regulation of the hCMV-IE promoter controlled reporter gene expression in initially infected cells by cytokines, which are released as a result of ischemia/reperfusion injury, might be involved. In order to investigate the role of proinflammatory cytokines, eg TNF-alpha in affecting hCMV-IE promoter-driven reporter gene expression, transient blockade of TNF-alpha was achieved by local co-application of an Ad-construct encoding for a soluble TNFRp55-Ig chimeric molecule in a syngeneic rat heart transplantation model. Co-application of the reporter construct together with the TNFRp55-Ig chimeric molecule significantly increased the early reporter gene expression after transplantation. Moreover, infiltration of inflammatory cells (T cells, macrophages, NK cells) and production of TNF-alpha in the transplant was markedly reduced. Our results indicate that: (1) proinflammatory cytokines are involved in down-regulation of reporter gene expression in ischemia/reperfusion injured tissues; and (2) inhibition of TNF-alpha might be a useful tool to increase early gene expression in gene therapy protocols, particularly in transplantation. Gene Therapy (2000) 7, 1238-1243.