[Hindfoot arthrodesis for post-infectious ankle destruction using an intramedullary retrograde hindfoot nail]. / Die Rückfußarthrodese bei postinfektiöser Sprunggelenkdestruktion mit einem intramedullären retrograden Arthrodesennagel.

BACKGROUND: Limb salvage after operations with deep infections of the ankle is often successful using arthrodesis of the hindfoot. The aim of this study was to evaluate the results of arthrodesis using a retrograde intramedullary nail following post-infectious ankle destruction. PATIENTS AND METHODS: Between 2007 and 2010 a total of 44 patients were treated with tibiotalocalcaneal (TTC) arthrodesis and 14 patients with tibiocalcaneal (TC) arthrodesis using a retrograde hindfoot nail after quieting of infection. Evaluation included the American Orthopaedic Foot and Ankle Society (AOFAS) and the short-form 12-item (SF-12) scores. RESULTS: Of the 58 patients 49 (35 male and 14 female) could be followed-up. The average time of follow-up was 18 months and the mean age was 58 years. In 85.7 % bony union could be achieved and 10.2 % suffered from reinfections. The mean results achieved in the different scores were AOFAS 56 and SF-12 39.1 (physical health summary scale) and 46.1 (mental health summary scale). Statistical analysis showed a significantly higher rate of bony fusion for TTC arthrodesis. Bony non-union showed a significant correlation to patients with reinfection and to diabetic patients. CONCLUSIONS: Hindfoot arthrodesis for treatment of septic arthritis after infections is possible by using an intramedullary nail. The results show a high rate of fusion with an acceptable reinfection rate and good patient acceptance.

Drosophila immune deficiency (IMD) is a death domain protein that activates antibacterial defense and can promote apoptosis.

We report the molecular characterization of the immune deficiency (imd) gene, which controls antibacterial defense in Drosophila. imd encodes a protein with a death domain similar to that of mammalian RIP (receptor interacting protein), a protein that plays a role in both NF-kappaB activation and apoptosis. We show that imd functions upstream of the DmIKK signalosome and the caspase DREDD in the control of antibacterial peptide genes. Strikingly, overexpression of imd leads to constitutive transcription of these genes and to apoptosis, and both effects are blocked by coexpression of the caspase inhibitor P35. We also show that imd is involved in the apoptotic response to UV irradiation. These data raise the possibility that antibacterial response and apoptosis share common control elements in Drosophila.

Cg-Rel, the first Rel/NF-kappaB homolog characterized in a mollusk, the Pacific oyster Crassostrea gigas.

We report here the identification and functional characterization of Cg-Rel, a gene encoding the Crassostrea gigas homolog of Rel/NF-kappaB transcription factors found in insects and mammals. Sequence and phylogenetic analysis showed that Cg-Rel shares the structural organization of Rel/NF-kappaB transcription factors of class II. It includes a Rel homology domain as well as a C-terminal transactivation domain (TD). Overexpression of Cg-Rel in the Drosophila S2 cell line activated the expression of a NF-kappaB-dependent reporter gene, whereas transfection with a Cg-Rel construct containing a C-terminal deletion of the TD or using a reporter gene with mutated kappaB binding sites failed to activate expression. These results suggest that Cg-Rel is a functional member of the Rel family of transcription factors, making this the sixth structurally homologous component of the Rel/NF-kappaB pathway characterized in C. gigas. Based on homology to other invertebrates' Rel/NF-kappaB cascade, the function of the oyster pathway may serve to regulate genes involved in innate defense and/or development. These findings serve to highlight a potentially important regulatory pathway to the study of oyster immunology, hence allowing comparison of the immune system in vertebrates and invertebrates, an important key issue to understand its evolution.

Sleep onset insomnia, sleep maintaining insomnia and insomnia with early morning awakening--temporal stability of subtypes in a longitudinal study on general practice attenders.

The present study investigated the temporal stability of insomnia patterns during a 4-month study period, classifying insomnia as sleep-onset insomnia, sleep-maintaining insomnia or insomnia with early morning awakening. In a longitudinal study design, 2,512 general practice attenders were investigated at the time of the first inquiry (T1) with a questionnaire. Four months later (T2), all patients complaining of difficulties in initiating and/or maintaining sleep and/or early morning awakening (n = 328) were again contacted by mail and received the same questionnaire as at T1. According to the reported symptoms, patients were assigned to the different subtypes of insomnia. The diagnosis at T1 was then compared with the diagnosis at T2 4 months later. Only about half of all patients who complained of difficulties in initiating sleep at T1 still exclusively reported sleep-onset insomnia 4 months later, whereas the remaining patients were distributed to different subtypes. The stability of sleep-maintaining insomnia and insomnia with early morning awakening was even lower. Comorbidity with a somatic or psychiatric disorder at T1 and change in hypnotic treatment did not account for the instability of the respective subgroup of insomnia. These findings illustrate that cross-sectional studies focusing on subtypes of insomnia, e.g. sleep-onset insomnia, may lead to erroneous results.

The biosynthetic pathway of ecdysone: studies with vitellogenic ovaries of Locusta migratoria (Orthoptera).

Ovaries of adult females of Locusta migratoria synthesize impressive amounts of the steroid hormone ecdysone (and related ecdysteroids) during the late phases of vitellogenesis. The present study, aimed at elucidating the sequence of the biosynthetic steps that lead from cholesterol to ecdysone, has taken benefit of this remarkable biological model by using a double approach: (1) isolation and physico-chemical identification of endogenous biogenetic intermediates; (2) metabolic study of labelled putative precursor molecules. The data presented in this paper lead us to propose the following sequence of events: conversion of cholesterol to 3 beta-hydroxy-5 beta-cholest-7-en-6-one (via several intermediates not identified in this study) followed by 14 beta-hydroxylation to 3 beta, 14 alpha-dihydroxy-5 beta-cholest-7-en-6-one; hydroxylation on the side-chain at C-25 and C-22 (in this order) to 2-deoxyecdysone; hydroxylation at C-2 to ecdysone.

Conversion of a radiolabelled ecdysone precursor, 2,22,25-trideoxyecdysone, by embryonic and larval tissues of Locusta migratoria.

A high specific activity tritiated ecdysone precursor, 2,22,25-trideoxyecdysone, was used to probe the capacity of various embryonic and larval tissues to perform the last 3 hydroxylation steps in ecdysone biosynthesis. Embryos at early stages of development, prior to the differentiation of their endocrine glands and embryonic heads, thoraces and abdomens of later stages, were found to have the capacity to hydroxylate the precursor to ecdysone. Larval epidermis and fat body are also able to transform 2,22,25-trideoxyecdysone into ecdysone; Malpighian tubules and midgut hydroxylate the precursor at C-2 but are apparently unable to hydroxylate both at C-22 and C-25. Larval prothoracic glands convert the precursor to ecdysone at a very efficient rate, which is 1-2 magnitudes higher than that of the other tissues investigated; several data argue for the existence of a privileged sequence of hydroxylations, C-25, C-22, C-2, in the larval prothoracic glands.

Combination of behaviour therapy with fluvoxamine in comparison with behaviour therapy and placebo. Results of a multicentre study.

BACKGROUND: We investigated whether the combination of multi-modal behaviour therapy (BT) with fluvoxamine is superior to BT and placebo in the acute treatment of severely ill in-patients with obsessive-compulsive disorder (OCD). METHOD: In a randomised, double-blind design, 30 patients were treated for nine weeks with BT plus placebo and 30 patients with BT plus fluvoxamine (maximum dosage 300 mg, mean dose 288.1 mg). BT included exposure with response prevention, cognitive restructuring and development of alternative behaviours. RESULTS: Both groups showed a highly significant symptom reduction after treatment. There were no significant differences between the groups concerning compulsions. Obsessions were significantly more reduced in the fluvoxamine and BT group than in the placebo and BT group. Furthermore, the group BT plus fluvoxamine showed a significantly higher response rate (87.5 v. 60%) according to a previously defined response criterion. Severely depressed patients with OCD receiving BT plus placebo presented a significantly worse treatment outcome (Y-BOCS scores) than all other groups. CONCLUSIONS: The results suggest that BT should be combined with fluvoxamine when obsessions dominate the clinical picture and when a secondary depression is present.

[Deep infection after treatment of proximal femur fractures--results and assessment of life quality]. / Die tiefe Infektion nach osteosynthetischer Versorgung hüftgelenknaher Femurfrakturen - Behandlungsergebnisse und Lebensqualität.

BACKGROUND: Proximal femur fractures are the second most prevalent fractures in patients older than 65 years. Despite large improvements in implant design and surgical technique, complications in fracture healing are very common. Deep infection after osteosynthetic treatment is considered to be one of the major complications with a high rate of mortality. Little is known about the adequate treatment and results in patients with infection of proximal femur fractures. The aim of this study was to evaluate the different treatment options for eradication of infection as well as to analyse the clinical outcome and quality of life. PATIENTS AND METHODS: 40 patients treated for infected proximal femur fractures between 2001 and 2010 were retrospectively analysed. Quality of life was assessed in 21 patients after an average of 40 months using the WOMAC and the SF-12 score. RESULTS: Surgical treatment included complete removal of infected implants and radical debridement. In 20 patients resection arthroplasty had to be performed. Ten patients were treated with a modular prosthesis, 4 patients were treated with a proximal femur replacement. Due to severe infection and risk-increasing comorbidities, resection arthroplasty had to be performed in the remaining 12 patients. Re-osteosynthesis could be performed in 13 patients. Average time of treatment was 67 days. At the time of follow-up the rate of mortality proved to be 15%. The rate of reinfection was 14.6%. At the time of follow-up infection was still prevalent in 2 patients. Dislocation after the hip prosthesis occurred in 3 of 14 patients. Of the 13 patients who received re-osteosynthesis one patient suffered a reinfection. Delayed fracture healing was treated with spongiosa grafts in 2 cases. 33% of the patients with resection arthroplasty died during follow-up. Statistical analysis showed better results in WOMAC and SF-12 scores in patients with hip prosthesis. Patients with re-osteosynthesis showed a larger variation in results. CONCLUSION: Deep infection after osteosynthetic treatment of proximal femur fractures is a severe complication. Radical surgical treatment and adequate local and systemic antibiotic application can help clear an infection. Quality of life is significantly reduced. Treatment should therefore be adapted to the individual patient's condition.

Insect immunity. A transgenic analysis in Drosophila defines several functional domains in the diptericin promoter.

Diptericins are antibacterial polypeptides which are strongly induced in the fat body and blood cells of dipteran insects in response to septic injury. The promoter of the single-copy, intronless diptericin gene of Drosophila contains several nucleotide sequences homologous to mammalian cis-regulatory motifs involved in the control of acute phase response genes. Extending our previous studies on the expression of the diptericin gene, we now report a quantitative analysis of the contribution of various putative regulatory elements to the bacterial inducibility of this gene, based on the generation of 60 transgenic fly lines carrying different elements fused to a reporter gene. Our data definitively identify two Kappa B-related motifs in the proximal promoter as the sites conferring inducibility and tissue-specific expression to the diptericin gene. These motifs alone, however, mediate only minimal levels of expression. Additional proximal regulatory elements are necessary to attain some 20% of the full response and we suspect a role for sequences homologous to mammalian IL6 response elements and interferon-gamma responsive sites in this up-regulation. The transgenic experiments also reveal the existence of a distal regulatory element located upstream of -0.6 kb which increases the level of expression by a factor of five.

Mental comorbidity of chronic insomnia in general practice attenders using DSM-III-R.

The major aim of this study was to investigate links between chronic insomnia and mental and personality disorders using the DSM-III-R classification. Of a sample of 2512 general practice attenders, 105 with a chronic insomnia complaint over a 4-month period were evaluated for mental and personality disorders. In addition, the significance of other factors such as personality traits, social functioning and the patient's own estimation of sleep quality was studied. Sixty-six patients got a diagnosis of a current insomnia using a structured interview for DSM-III-R. Fifty percent of them had at least one additional current Axis I or II diagnosis. Affective disorders were most common as principal psychiatric diagnosis followed by substance use disorders. The general practitioners were poor in recognizing their patients' chronic insomnia complaints and the high percentage of substance abusers among them. The important role of psychopathology in chronic insomnia sufferers was indicated by the high number of patients who displayed prominent personality traits. The predominant personality pattern was characterized by a pattern of internalization of problems combined with an anxious-depressive reaction style. In summary, strong associations between chronic insomnia, mental disorders and psychopathology were confirmed by this investigation.

Prevalence of insomnia in elderly general practice attenders and the current treatment modalities.

This study aimed to assess the prevalence and treatment modalities of elderly practice attenders. A total of 330 patients aged over 65 years were investigated with a questionnaire in general practice. To assess insomnia, operationalized diagnostic criteria according to DSM-III-R were applied. Twenty-three percent of the elderly patients suffered from severe, 17% from moderate and 17% from mild insomnia. More than 80% of the patients reported suffering from insomnia for 1-5 years or longer, which indicates a chronic course. Elderly patients showed unrealistic expectations concerning duration of sleep and spend more time in bed than they realistically can expect to sleep. More than half of the elderly patients reported habitual daytime napping. Sleep-disturbed elderly patients did not differ significantly from good sleepers in their habit of taking daytime naps, but even when taking daytime naps, good sleepers slept significantly longer than the sleep-disturbed patients. A significant association was found between insomnia and mental disorders, i.e., depression and organic brain syndrome according to the diagnosis of the general physician. In about half of the cases the primary care physician was not aware that the elderly patient suffered from severe insomnia. More than half of the elderly severe insomniacs took prescribed hypnotics habitually, mainly benzodiazepines.

Expression and nuclear translocation of the rel/NF-kappa B-related morphogen dorsal during the immune response of Drosophila.

The rel/NF-kappa B-related morphogen dorsal is a maternally expressed gene which is involved in the control of the dorso-ventral axis during early embryogenesis of Drosophila. We show that this gene is also expressed in the fat body of larvae and adults of Drosophila as well as in a tumorous blood cell line: its expression is noticeably enhanced upon bacterial (or lipopolysaccharide) challenge. This challenge also induces within 15-30 min a nuclear translocation of the dorsal protein. The genes encoding inducible antibacterial peptides in Drosophila contain kappa B-related nucleotide sequences and we show that the dorsal protein can bind to such motifs and sequence-specifically transactivate a reporter gene in co-transfection experiments with a Drosophila cell line. However, in dl1 mutants, in the absence of dorsal protein, the genes encoding antibacterial peptides retain their inducibility, suggesting a multifactorial control. The results indicate that in addition to its role in embryogenesis, dorsal is involved in the immune response of Drosophila. They also strengthen the analogy between the mammalian acute phase response and the insect immune response.

Characterization of three hydroxylases involved in the final steps of biosynthesis of the steroid hormone ecdysone in Locusta migratoria (Insecta, Orthoptera).

It is most generally accepted that the last three enzymatic reactions in the biosynthetic pathway of ecdysone are, in this order, the hydroxylations at positions C-25, C-22 and C-2. Using high specific activity tritiated ecdysone precursors (2,22,25-trideoxyecdysone, 2,22-dideoxyecdysone and 2-deoxyecdysone) we have characterized the hydroxylases involved in these reactions, in the major biosynthetic tissue of ecdysone, i.e. the prothoracic glands. We show that C-2 hydroxylase is a mitochondrial oxygenase which differs from conventional cytochrome P-450-dependent monooxygenases by its relative insensitivity to CO. In contrast, C-22 and C-25 hydroxylases appear as classical cytochrome P-450 monooxygenases; C-22 hydroxylase is a mitochondrial enzyme whereas our data point to a microsomal localization of the C-25 hydroxylase.

Prevalence and treatment of insomnia in general practice. A longitudinal study.

The aim of the study was to assess prevalence and treatment modalities of insomnia in general practice. To investigate the course of insomnia, a longitudinal study design was adopted. Two thousand five hundred and twelve patients (age 18-65 years) were investigated with a questionnaire in general practice (T1). Four months later (T2) and again 2 years later (T3) a questionnaire was sent to all patients who had complained about severe insomnia at the time of the first inquiry. To assess insomnia, operationalized diagnostic criteria were applied (DSM-III-R). Eighteen point seven percent suffered from severe, 12.2% suffered from moderate and 15% suffered from mild insomnia. In the course of 2 years insomnia appeared as a chronic health problem. A high comorbidity of severe insomnia was found with chronic somatic and psychiatric disorders, especially with depression. Of the severely insomniac patients, 23.9% used prescribed hypnotics habitually, mainly benzodiazepines. The use of prescribed hypnotics remained rather stable during the whole study period. More than half of the patients reported a daily use of the hypnotics for 1-5 years or longer, but only 22% of the severely insomniac patients reported at the time of the third inquiry a significant improvement of insomnia due to the administration of sleeping pills. Thus, the long-term administration of benzodiazepine hypnotics seems to be an inadequate treatment strategy in chronic insomnia. Whether the occurrence of rebound insomnia after benzodiazepine withdrawal may be one of the main factors for chronic hypnotic use requires discussion.(ABSTRACT TRUNCATED AT 250 WORDS)

Insect immunity. Two 17 bp repeats nesting a kappa B-related sequence confer inducibility to the diptericin gene and bind a polypeptide in bacteria-challenged Drosophila.

The Drosophila diptericin gene codes for a 9 kDa antibacterial peptide and is rapidly and transiently expressed in larvae and adults after bacterial challenge. It is also induced in a tumorous Drosophila blood cell line by the addition of lipopolysaccharide (LPS). The promoter of this gene contains two 17 bp repeats located closely upstream of the TATA-box and harbouring a decameric kappa B-related sequence. This study reports that the replacement of the two 17 bp repeats by random sequences abolishes bacteria inducibility in transgenic fly lines. In transfected tumorous blood cells, the replacement of both or either of the 17 bp motifs reduces dramatically LPS inducibility, whereas multiple copies significantly increase the level of transcriptional activation by LPS challenge. A specific DNA-protein binding activity is evidenced in cytoplasmic and nuclear extracts of induced blood cells and fat body. It is absent in controls. It is proposed that induction of the diptericin gene mediated by the two 17 bp repeats occurs via a mechanism similar to that of mammalian NF-kappa B.

Insect immunity: the diptericin promoter contains multiple functional regulatory sequences homologous to mammalian acute-phase response elements.

We are using the diptericin gene as a model system to study the control of expression of the genes encoding antibacterial peptides during the Drosophila immune reaction. In order to investigate the putative regulatory regions in the diptericin promoter, we performed DNaseI footprinting experiments combined with gel-shift assays in two inducible systems: the larval fat body and a tumorous Drosophila blood cell line. Our results confirm the importance of kappa B-like elements previously described in the immune response of insects and reveal for the first time the involvement of other regions containing sequences homologous to mammalian acute-phase response elements.

Ecdysteroids and ovarian development in the shore crab, Carcinus maenas.

Mature ovaries of the shore crab Carcinus maenas contain large concentrations of three major ecdysteroids which we have identified by physicochemical methods as ecdysone, 20-hydroxyecdysone and ponasterone A. The fluctuations of ovarian and blood ecdysteroid concentrations are presented in relation to the various stages of ovarian development.