Efficacy and Safety of Alprostadil in Patients with Peripheral Arterial Occlusive Disease Fontaine Stage IV: Results of a Placebo Controlled Randomised Multicentre Trial (ESPECIAL).

OBJECTIVES: The aim was to assess the efficacy and safety of alprostadil in patients with peripheral arterial occlusive disease (PAOD) Fontaine Stage IV. METHODS: This was a multinational, prospective, randomised, double blind, placebo controlled, parallel group trial. Patients with Stage IV PAOD were equally randomised to either 4 weeks of alprostadil treatment twice daily or to placebo treatment twice daily. The primary efficacy variables were the rate of complete healing of all necrosis and ulceration 12 weeks after the end of treatment and the frequency of major amputations 24 weeks after the end of treatment. RESULTS: A total of 840 patients were randomised between 2004 and 2013. At baseline, no major differences between treatment groups were found. The rate of "complete healing" was 18.4% in patients on alprostadil and 17.2% in patients on placebo. The rates of "major amputations" were 12.6% in patients on alprostadil and 14.6% in patients on placebo. The adjusted difference between alprostadil and placebo including their 95% confidence intervals was 1.1 (-4.0 to 6.3) for "complete healing" and -2.1 (-6.7 to 2.5) for "major amputations." In the subgroup of diabetic patients the rates of major amputations were numerically lower in the alprostadil than placebo group (10.6% vs. 17.4%). Within the total cohort a non-significant difference in "decrease in ulcer area ≥50%" was reached in 30.2% of patients on alprostadil and in 24.3% of patients on placebo at end of treatment. CONCLUSIONS: In this study, superiority of alprostadil over placebo could not be shown. Nevertheless, a slight numerical but not clinically relevant advantage for alprostadil emerged from the "area decrease of ulcers by ≥ 50%," indicating that a healing effect may have started. The results have to be considered in the light of several limitations in study design and conduct.

[Requirements for mycological diagnostics in accordance with the guideline of the German Medical Association for quality assurance of medical laboratory tests]. / Anforderungen für die mykologische Diagnostik entsprechend der Richtlinie der Bundesärztekammer (Rili-BÄK) zur Qualitätssicherung laboratoriumsmedizinischer Untersuchungen.

The ability of recognizing various clinical manifestations of mucocutaneous mycosis, making a diagnosis, and establishing a treatment is part of a dermatologist's daily routine. However, due to the fact that clinical manifestations, laboratory diagnostics, and treatment are performed in one hand, laboratory findings are properly classified and interpreted. Since new binding guidelines of the German Medical Association on quality assurance measures in medical laboratory testing came into force, there is much concern among dermatologists of how to comply with these new regulations. It is the intention of the authors to help our readers to implement these new rules in order to make sure that mycological diagnostics continue to be part of a dermatologist's professional work.

Terminators of transcription with RNA polymerase from Escherichia coli: what they look like and how to find them.

We present here a compilation of prokaryotic transcription terminator sequences (ref. 1-152). The compilation includes 49 independent terminators, 52 speculated independent terminators, 27 sites shown to function in vivo, and some 20 proven or speculated rho-dependent terminators. In addition to the well-known features of independent terminators (dyad symmetry and T-run), two consensus are found: CGGG(C/G) upstream and TCTG downstream of the termination point. A subset of the collection of sequence has been used to construct a computer algorithm to locate independent terminators by sequence analysis.

Bullous pemphigoid antigen concentration in normal human skin in relation to body area and age.

The amount of bullous pemphigoid antigen (BPA) in normal human skin on different areas of the body and in bodies of different ages was determined by making endpoint titer estimations using the indirect immunofluorescence technique. Two sera with bullous pemphigoid antibodies were tested with 36 specimens of normal human skin from six cadavers. The greatest expression of BPA was found in plantar sites, whereas the lowest endpoint titers were seen in flexural arm biopsy specimens. Age-dependent differences in BPA expression were detected as well. The oldest individuals tested produced the highest endpoint titers in contrast to the lowest endpoint titers in the youngest. This study suggests that the amount of BPA depends not only on the body region where the biopsy specimen is taken but also on the age of the donor. This is important to know in connection with indirect immunofluorescence assays for BP antibodies on human skin.

Comparison by means of a computer-supported device of the enlarging characteristics of two different instruments.

Numerous studies report different results when testing endodontic instruments with similar and/or different research protocols. However, objective studies that could eliminate the factors inherent to the operator have not yet been developed. Simulated root canals in clear casting resin were used as models. The Canal Master U and Flexogate were tested by using a double exposure photographic technique. A computer-aided device capable of reproducing three-dimensional enlarging movements and irrigation of the simulated canals was developed. The enlarging movements were programmed according to the step-back and step-down techniques. The enlarging of simulated root canals with this device proved to be constant and reproducible. Standard deviations were kept low and were dependent on the degree of canal curvature. The enlarged simulated root canals showed that both instruments could be kept centered in the path of the root canal. Results showed only a few significant differences between the effective material removed and a theoretical ideal amount of removed material.

The influence of herbal ingredients on the plaque index and bleeding tendency of the gingiva.

The effectiveness of medicinal herbs in both a toothpaste and oral rinse on dental plaque, sulcus bleeding, and the pH of total saliva was investigated in a single-blind study on 50 dentistry students between the ages of 23 and 28 years. Over a period of 4 weeks, 25 students used either placebo or preparations containing medicinal herbs. Parameters measured were the approximal plaque index (API) and sulcus bleeding index (SBI). These were determined at the same time of day (12:00 P.M.), the last food intake having occurred at least 1 hour previously. Compared with the placebo preparations, the herbal ingredients significantly reduced both the API (initial value: 40.8%, final value: 23.9%) and the SBI (initial value: 33.4%, final value: 18.6%). The pH of the total saliva was significantly displaced into the alkaline range by the application of the herbal products, whereas the placebo products had a contrary effect. The results of this study suggest that herbal ingredients can be employed supportively in the therapy of periodontal diseases and for routine prophylaxis.

[Normal and induced Hg release from different amalgams]. / Normale und provozierte Hg-Freisetzung aus unterschiedlichen Amalgamen.

In an experimental investigation of 20 subjects who had no amalgam fillings, the mercury load from artificially applied, standardised amalgam surfaces was tested for one product containing gamma-2 and one free of gamma-2 respectively. The product which contained gamma-2 caused a statistically significant increase in Hg concentrations in the 24-hour urine sample. After challenge with Dimaval, an intensifying effect on the elimination rate could be detected, although all values clearly remained below a toxicologically relevant concentration. In order to avoid unnecessary exposure to heavy metals, the use of gamma-2-free amalgams and, in the long term, the development of optimised filling materials and intensification of prophylactic measures for prevention of dental caries are to be welcomed.

[The effect of the motivation of a tracing device in the hygiene phase of PA treatment]. / Zum Motivationseffekt eines Aufzeichnungsgeräts bei der Hygienephase der PA-Behandlung.

In a clinical comparative study the effectiveness of an oral hygiene motivation tool (Parograph) was evaluated. 100 patients with periodontal diseases got oral hygiene instructions with the classic clinical methods (brush-techniques) and the motivation tool. As a result, only the patients with higher plaque index showed a faster significant reduction of plaque index when motivation tool was used. The comparison between other indices used were statistically not significant.

[The effect of cyclosporin A (CyA) on the growth and metabolic activity of gingival fibroblasts]. / Einfluss von Cyclosporin A (CyA) auf Wachstum und Stoffwechselaktivität von Gingivafibroblasten.

Cyclosporine A (CyA) is a powerful nonsteroidal immunosuppressive agent in organ and bone marrow transplants. It may cause nephro- and hepatotoxicity and may lead to generalized fibrous hyperplasia of gingiva by a yet unknown mechanism. In order to study the pathophysiology of this side effect human gingival fibroblast cultures derived from normal gingiva were studied under the influence of CyA. During short time incubation of 72 h a significant increase of 3H-thymidine incorporation was noted while 14C-glucosamine incorporation remained unchanged. Long term incubation over 6 weeks, however, resulted in a significant increase of both cell proliferation and synthesis of the extracellular matrix. These findings demonstrate a powerful growth stimulation of gingival fibroblasts by CyA under in-vitro conditions and show that the observed fibrous hyperplasia of the gingiva under CyA therapy is the result of a direct effect on gingival cells.

MALDI-TOF MS imaging of controlled release implants.

MALDI-TOF MS (matrix-assisted laser desorption/ionization time-of-flight mass spectrometry) imaging is used to characterize novel lipid implants allowing for controlled drug delivery. Importantly, this innovative technique provides crucial information on the inner structure of the implants before and after exposure to the release medium and does not require the addition of marker substances. Implants were prepared by extrusion at room temperature. Thus, in contrast to hot-melt extruded systems, the risks of drug inactivation and solid state transformations of the lipid matrix former are reduced. Hydrogenated/hardened soybean oil and glyceryl tristearate were studied as lipids and propranolol hydrochloride and theophylline as drugs, exhibiting significantly different solubility in water. The implants were also characterized by optical microscopy, differential scanning calorimetry, water uptake and lipid erosion studies, mathematical modeling as well as in vitro drug release measurements. Importantly, broad spectra of drug release patterns with release periods ranging from a few days up to several months could easily be provided when varying the initial drug content and type of lipid, irrespective of the type of drug. The diameter of the implants can be as small as 1mm, facilitating injection. MALDI-TOF MS imaging revealed homogeneous macroscopic drug distributions within the systems, but steep drug concentration gradients in radial and axial direction at the lower micrometer level, indicating drug- and lipid-rich domains. As the implants do not significantly swell, local irritation upon administration due to mechanical stress can be expected to be limited. Good agreement between experimentally measured and theoretically calculated drug release kinetics revealed that diffusional mass transport plays a major role for the control of drug release from this type of advanced drug delivery systems.

Preparation of regular arrays of bimetallic clusters with independent control of size and chemical composition.

Regular arrays of bimetallic clusters have been prepared by atomic deposition, under UHV, on a nanostructured ultrathin alumina film. The alumina films are obtained by oxidation at 1000 K of a Ni3Al (111) surface. They present two regular hexagonal superstructures with lattice parameters of 2.4 and 4.1 nm. Pd clusters nucleate exclusively on the 4.1 nm superstructure forming regular arrays of clusters extending on the whole (1 cm2) substrate. Gold deposited on a previously formed Pd clusters array, condenses exclusively on the Pd clusters in forming a regular array of bimetallic AuPd clusters with a narrow size distribution. The size and the composition of the AuPd clusters can be controlled independently. Gold clusters nucleates also on the 4.1 nm superstructure but they can escape from the nucleation sites and coalesce with other gold clusters. By condensing Pd on the preformed Au clusters, PdAu clusters are formed together with pure Pd clusters nucleated on the free sites of the 4.1 nm superstructure of the alumina film.

Tinea capitis: ringworm of the scalp.

The guideline tinea capitis, as passed by three German medical societies, is presented in the present study.

Onychomycosis.

The guideline on onychomycosis, as passed by the responsible German medical societies, is presented in the present study.

[Comparative studies on periodontal indexes with particular to the Periotest method]. / Bergleichende Untersuchungen über Parodontal-Indizes unter besonderer Berücksichtigung des Periotestverfahrens.

40 patients from both gender were examined to determine if there is a correlation between periodontal indices and periotest values. As a result we were able to show that the pocket depth correlates with the periotest values for all tooth groups. On the other hand SBI correlates with the periotest values only for the premolars in upper and the front in lower jaw.

[Studies of patient motivation during systematic periodontal treatment]. / Untersuchungen uber die Motivation des Patienten bei der systematsichen PA-Behandlung.

Motivated patients are essential for successful periodontal therapy. The intention of this investigation was to determine the success of motivational attempts. 100 patients were examined and separated into two groups according to sex and age. As a result there was no significant difference between gender groups as well as age groups concerning the motivation.

New standards, new dilemmas--reflections on managing medical mistakes.

This article describes one hospital's development of a proactive, patient centered program, which emphasizes total honesty in dealing with all aspects of patient care. This process includes the full and timely disclosure of errors which affect the patient's health and well being. The article describes the process by which the medical facility identifies errors and works with healthcare providers to arrive at a consensus on the management of these errors. Included is a step by step analysis of how disclosure can be successfully accomplished.

[Allergic contact eczema and vitiliginous depigmentations caused by paratertiary butylphenol]. / Allergisches Kontaktekzem und vitiligoartige Depigmentierungen durch paratertiäres Butylphenol.

Allergic contact eczema and vitiliginous depigmentations caused by paratertiary butylphenol. In a case of allergic contact eczemas due to an occupational contact with paratertiary butylphenol, vitiliginous depigmentations appeared after a latency period of several years. Disorders of cellular immune reactions, struma and hepatosis were absent. Paratertiary butylphenol might have been absorbed by the epidermis. It is suggested for prophylactic purposes to declare the components of adhesives in order to avoid occupational contacts with dangerous substances.

The EMBL data library.

The EMBL Data Library was the first internationally supported central resource for nucleic acid sequence data. Working in close collaboration with its American counterpart, GenBank (1), the library prepares and makes available to the scientific community a comprehensive collection of the published nucleic acid sequences. This paper describes briefly the contents of the database, how it is available, and possible future enhancements of Data Library services.

[The effects of herbal agents on dental plaque and sulcus bleeding index]. / Der Einfluss von pflanzlichen Wirkstoffen auf Plaqueindex und Blutungsneigung der Gingiva.

This study was designed to examine the efficacy of plant-derived active substances in a combined application of toothpaste and mouth rinse on dental plaque and sulcus bleeding index and the pH values of the saliva. 50 healthy students of dentistry without periodontal diseases took part in this study. Over a period of 4 weeks half of the group used herbs, while the other half used a placebo preparation. The data of the oral examination were always obtained at 12 a.m., with the last food intake at least 1 hour before. The results revealed a significant reduction of plaque accumulation and bleeding signs under herbal extracts in contrast to the placebo preparation. The salivary pH values were shifted to the alkaline range in the herbal extract group whereas the placebo product showed the opposite effect. Our data demonstrate the usefulness of herbal extracts as an adjunct in the treatment of periodontal disease and in a routine preventive regimen.

[Modulation of glycosaminoglycan- and collagen synthesis of human gingival fibroblasts by progesterone]. / Untersuchungen zur Progesteronwirkung auf die Glykosaminoglykan- und Kollagensynthese in Gingivafibroblasten.

Hormonal changes occuring during pregnancy are known to induce periodontal changes and may therefore influence preexisting periodontal diseases negatively. Since glycosaminoglycans (GAG) and collagen are the principal constituents of the matrix, the influence of progesterone on their synthesis was chosen as an assay system. Confluent human gingival fibroblast cultures grown under standard conditions were preincubated with progesterone levels ranging from 0.05 to 0.5 microgram/ml for 48h before GAG synthesis was assayed by incorporation of 14C-glucosamine. The GAG fraction was detemined by ion-exchange-chromatography and fractionated precipitation. Collagen-synthesis was monitored by 14C-proline-incorporation. Progesterone concentrations corresponding to those seen in the third trimenon of pregnancy were able to lower GAG-synthesis; the synthesis of all GAG-species was affected in a similar way. Collagen synthesis was only affected by unphysiologicaly high hormone doses. The observed clinical changes may therefore be due to the influence of progesterone on GAG synthesis.