27-jähriger Reiserückkehrer mit hohem Fieber und septischem Schock im Verlauf

A 27-year-old man was admitted with high fever and shivers eleven days after returning from vacation in Indonesia. Physical examination, laboratory values, abdominal ultrasound, and chest x-ray were not conclusive. All blood cultures yielded growth of Salmonella enterica serovar Typhi, and typhoid fever was diagnosed. Subsequently, the patient developed septic shock and pulmonary edema.In this case report epidemiological, clinical, and therapeutic aspects of typhoid fever are discussed with special emphasis on criteria for severe typhoid fever, which is treated with additional glucocorticoids.     

Fracture repair during external fixation: Torsion tests of rabbit osteotomies

Bone repair was studied in the rabbit tibiofibular bone after a midshaft transverse osteotomy stabilized by external fixation and heavy compression. Both subendosteal and subperiosteal callus formation with concomitant contact healing were observed within 3 weeks, and were further succeeded by subendosteal resorption and increased porosis resulting in atrophy of the cortical bone. Subjected to the torsion test, the bones exhibited restoration of strength within 3 weeks, with maximal energy absorption and elasticity at 6 weeks. The failure of the osteotomy in the torsion test, with radiographic visibility of the osteotomy, characterized the soft-tissue type of behavior of the bones. Hard-tissue like behaviour of the bones with resistance to torsion at the osteotomy site and radiographic obliteration of the osteotomy line occurred by 12 weeks, indicating complete union of the osteotomy. Our experiments demonstrate that elastic external fixation is preferable to the rigid compression plate.     

Coxibs and heart disease: what we have learned and what else we need to know.

Since their approval in 1998, the popularity of selective cyclooxygenase-2 (COX2) inhibitors has swung from a domination of drug sales to serious disputes about their cardiovascular safety. Despite the numerous studies on COX2 inhibitors that have emerged, drawing conclusions about their cardiovascular safety has been complicated by conflicting results, underpowered clinical trials, and the lack of a placebo group and use of post hoc analyses in many trials. Nonetheless, certain conclusions can be made with reasonable accuracy. This review addresses the controversy in 3 segments. It begins with a discussion of the several mechanisms proposed to explain how selective COX2 inhibition impacts the cardiovascular system. This is followed by a recount of the several clinical studies that delved into the cardiovascular outcomes associated with COX2 inhibitors. Finally, answers to key questions are provided to assist the clinician in devising a systematic approach to the risk-benefit analysis of COX2 inhibitors in actual practice.     

Poly(ADP-ribose)polymerase-activity of chicken embryo cells exposed to nucleotoxic agents.

Poly(ADP-ribose)polymerase (PARP)-activity was assessed in vitro from the incorporation of the adenosine-diphosphate-ribose moiety of 14C-NAD+ in the acid-insoluble cell fraction. When compared to mammalian (rat) cells, chicken embryo cells exhibit an almost three- to fourfold higher constitutive PARP-activity and an about two- to threefold lower chromatin compactness as evidenced by viscometry of alkaline cell lysates and nucleoid sedimentation. X-irradiation, bleomycin and H2O2 activated PARP. Hyperthermia (43 degrees C), doxorubicin, ethidium bromide and novobiocin resulted in an inhibition of the enzyme activity. Even at the highest doses used, UV-light, monofunctionally alkylating agents and the bisbenzimide Hoechst 33258 remained without significant effects. It is suggested that, with respect to DNA-and/or chromatin-interactive agents, the chicken embryo PARP-test may be complementary to the results of morphological and biochemical studies.     

Recombinant allergen fragments as candidate preparations for allergen immunotherapy

Background: Lately, renewed interest has arisen in the new forms of allergen immunotherapy because they may offer alternatives for drug treatment. Objective: The purpose of this study was to develop a well-characterized preparation of the main respiratory cow dander allergen, Bos d 2, with attenuated allergenic activity. Methods: The immunologic characteristics of Bos d 2 preparations were studied by indirect IgE ELISA, ELISA inhibition, Western blotting, histamine release, skin prick tests, and the proliferation tests of allergen-specific T-cell clones. Results: The complete recombinant Bos d 2 was observed to bind effectively, IgE of cow-allergic patients in indirect ELISA. In other experiments, the IgE-binding capacity of recombinant Bos d 2 proved to be lower compared with native Bos d 2. When the two overlapping recombinant fragments of Bos d 2 (corresponding amino acids 1-131 and 81-172, respectively) covering the whole molecule were compared with the complete recombinant Bos d 2 with several methods, only a low level of residual reactivity was observed. For example, recombinant fragments could not bind antibody at all in ELISA inhibition tests retaining, however, some reactivity in skin prick tests. In contrast, the fragments were able to stimulate vigorously Bos d 2-specific T-cell clones. Conclusion: The approach we have taken may offer a simple and reproducible way to produce hypoallergenic preparations for immunotherapy, circumventing simultaneously some of the problems of other experimental methods such as individual T-cell epitope recognition in peptide-based immunotherapy. (J Allergy Clin Immunol 1997;100:721-7.)     

Non-immune therapy of IgA glomerulonephritis

Summary: The involvement of the IgA immune system and complement components in IgA glomerulonephritis (IgAGN) has prompted the use of immunosuppressive drugs in therapy, but none has so far been shown to alter the natural course of the disease. Because most patients with IgAGN present during the chronic phase of their illness, at the time when the initiating immune events may no longer be active, nonimmune therapy which targets the common pathway of progressive renal injury is likely to be more useful. There is increasing evidence that angiotensin-converting enzyme inhibitors (ACEI) reduce proteinuria and renal injury in patients with IgAGN, and this effect may be observed in both normotensive and hypertensive patients. Yet to be determined is whether this effect is specific for ACEI and whatever other effective antihypertensive drugs may achieve a similar result. Fish oil has recently been shown to retard the progression of renal failure in patients with aggressive IgAGN, but a narrow therapeutic window appears to exist for this form of treatment. Antiplatelet agents on their own appear to be ineffective but in combination with anticoagulation (low dose warfarin) have been shown to have an antiproteinuric effect and may preserve renal function in patients with progressive disease. Future directions of non-immune therapy of IgAGN include evaluation of the renoprotective effect of angiotensin II receptor antagonists, free-radical scavengers and antilipid drugs. More work should also be done to identify factors which put the patients at risk of developing progressive disease and which predict therapeutic response, as has been done recently with the identification of the deletion polymorphism of the angiotensin-converting enzyme gene as a marker of progressive disease and therapeutic response to ACEI in patients with IgAGN.     

Improved learning of Riemannian metrics for exploratory analysis.

We have earlier introduced a principle for learning metrics, which shows how metric-based methods can be made to focus on discriminative properties of data. The main applications are in supervising unsupervised learning to model interesting variation in data, instead of modeling all variation as plain unsupervised learning does. The metrics are derived by approximations to an information-geometric formulation. In this paper, we review the theory, introduce better approximations to the distances, and show how to apply them in two different kinds of unsupervised methods: prototype-based and pairwise distance-based. The two examples are self-organizing maps and multidimensional scaling (Sammon's mapping).     

Inheritance of male courtship sound characteristics inDrosophila littoralis

Males ofDrosophila littoralis vibrate their wings during courtship to deliver a love song. This consists of 25- to 50-ms-long pulses with a basic frequency of about 250–400 Hz, separated by 250- to 500-ms pauses. When recording the sounds of flies from several localities in Europe, we found that males of one strain from northern Finland displayed courtship sounds with an unusally low wing beat frequency (below 250 Hz). In a genetic analysis utilizing marker stocks, the anomalous frequency was found to be caused by genes on all major autosomes, the strongest factors being on the second chromosome. Interaction between genes on chromosome 2 and on the fused chromosome 3–4 was nonadditive. In low-frequency sounds, the number of cycles in the pulse (CN) was decreased, so that the length of the sound pulse (PL) remained more or less unchanged. We suggest that the genetically and physiologically most thoroughly controlled trait in the sound ofDrosophila littoralis is the length of the pulse.