[A short-term diagnostic and economic impact model of neonatal screening for cystic fibrosis]. / Modellierung der kurzfristigen diagnostischen und ökonomischen Auswirkungen eines Neugeborenen-screenings auf Mukoviszidose.

BACKGROUND: Screening for cystic fibrosis (CF) is currently not a part of the neonatal screening program in Germany, but its implementation is being debated. The aim of this study was to model the short-term diagnostic and economic consequences of the implementation of such a screening. PATIENTS: Cohort of all newborns in Germany per year. METHODS: In total, 3 screening strategies were evaluated by decision modelling. The 3 screening protocols compared were alternative combinations of IRT- and DNA-testing with a final sweat test. RESULTS: All modelled screening strategies show a comparable diagnostic yield (171-175 CF-cases per year). There is a tendency of slightly higher sensitivity and shorter time to diagnosis for the "IRT-DNA with failsafe" protocol. In comparison to other strategies, the total number of screening-related visits for this protocol is lower, whereas the amount of sweat tests is the highest. All screening strategies are comparable in terms of avoided cases of extremely low height- or weight-for-age (37-38 and 13-14 cases, respectively). The incremental annual diagnostic costs (with deducted diagnostic costs without screening) are 1.13 to 1.16 million EUR. After 3 years of model runtime there is a nearly neutral total budget impact of screening (diagnostic and treatment costs) per cohort. CONCLUSION: All screening strategies lead to a considerable reduction of time to diagnosis at acceptable financial expenditures. The findings of this study broaden the current basis for discussion regarding the implementation of cystic fibrosis screening in Germany.

Pulmonary Palacos embolism: a case report.

Instrumentation with cement-augmented pedicle screws has expanded the therapeutic spectrum. This technique is useful for the palliation of bone metastases and in generalized osteoporosis. Serious complications such as pulmonary embolism have been described following percutaneous vertebroplasty, a frequently used technique. We report the case of a 55-year-old patient with a large central Palacos embolism of the right pulmonary artery after corporectomy of the lumbar vertebrae 3 and 4 and reconstruction using autologous pelvic bone. The large Palacos embolism was removed successfully from the right pulmonary artery with extracorporeal circulation.

[Efficacy and cost-effectiveness of smoking cessation courses in the statutory health insurance: a review]. / Wirksamkeit und Kosteneffektivität von Raucherentwöhnungskursen in der GKV: eine Literaturübersicht.

INTRODUCTION: Most of German health insurance funds provide and reimburse cognitive-behavioural group-based courses for smoking cessation according to section sign 20 Abs. 1 SGB V or section sign 20 a SGB V. The main goal of this study is to conduct a review of the efficacy and cost-effectiveness of these smoking cessation courses and their methodical approaches. METHODS: A literature search for available systematic reviews, meta-analyses, health technology assessments (HTA), and guidelines was conducted in relevant databases. RESULTS: Overall, six publications were included. Two sources confirm the long-term efficacy of group-based smoking cessation approach [OR (odds ratio)=1.3 and OR=2.17] with meta-analyses. The majority of available reviews or national guidelines are based on the results of these two researches. Two further reviews estimate the behaviour-based group therapy as effective. The efficacy estimation of single behavioural intervention components (skill training, problem solv-ing, relapse prevention) varies from OR=0.91 to OR=1.5. The evidence is insufficient for the internationally widespread course "Allen Carr's Easyway". No relevant publications on economic issues could be included for the courses currently made available by the statutory health insurance. CONCLUSION: The methodical approaches of smoking cessation courses offered by health insurance funds are effective and recommendable according to the available secondary literature. The efficacy of these interventions is not very high and solely covers general methodical approaches or programme components. Evaluations of current smoking cessation courses are rare and do not meet internationally accepted standards. Further research should be aimed to evaluate the established programmes with high-quality health economic studies.

Persisting muscle atrophy two years after replacement of the hip.

Muscle atrophy has been demonstrated in patients suffering from osteoarthritis of the hip, but little is known about muscular recovery after total hip replacement (THR). A total of 20 patients with unilateral osteoarthritis of the hip were assessed before, six months and two years after THR. The cross-sectional area and radiological density of the muscles of the hip, thigh, calf and back were measured using CT. We hypothesised that the muscles would not recover fully after operation. After two years comparison of the limb with the THR with the healthy limb showed that there was such a reduction in the cross-sectional area in iliopsoas (7.0%; p = 0.006) and the hip adductors (8.4%, p = 0.003) and in the radiological density in gluteus maximus (10.1 Hounsfield units; p < 0.001), gluteus medius/minimus (5.6 Hounsfield units; p = 0.011), iliopsoas (3.9 Hounsfield units; p < 0.001) and the adductors (2.4 Hounsfield units; p = 0.022). Thus, there was persistent muscle atrophy in muscles acting about the hip two years after THR. We suggest that an earlier operation or a more intensive rehabilitation may reverse these changes.

[Simvastatin-induced dermatomyositis]. / Simvastatin-induzierte Dermatomyositis.

Dermatomyositis is a rare inflammatory autoimmune disease. The association between a lipid-lowering drug like pravastatin and the development of a musculocutaneous syndrome has been reported in single case reports only. We present the first report of a simvastatin induced dermatomyositis in a 71-year-old woman with positive Mi-2-Antibodies to point out this rare side effect of the increasingly prescribed statins. In future simvastatin should be considered as a possible trigger of dermatomyositis.

Long-term effectiveness of behavioural interventions to prevent smoking among children and youth.

OBJECTIVES: To evaluate the long-term effectiveness of recent behavioural interventions in the prevention of cigarette use among children and youth and to compare the effectiveness of different school-based, community-based and multisectorial intervention strategies. METHODS: A structured search of databases and a manual search of reference lists was conducted. Randomised controlled trials published in English or German between August 2001 and August 2006 targeting youths up to 18 years of age were assessed independently by two researchers according to predefined inclusion criteria and with regard to methodological quality. Data abstraction was performed and crosschecked by two researchers. Where appropriate, pooled effect estimates were calculated and tested in sensitivity analyses. RESULTS: Of 3555 articles, 35 studies met the inclusion criteria. The follow-up duration ranged from 12 months to 120 months. Although the overall effectiveness of prevention programs showed considerable heterogeneity, the majority of studies reported some positive long-term effects for behavioural smoking prevention programs. There was evidence that community-based and multisectorial interventions were effective in reducing smoking rates; in contrast, the evidence for school-based programs alone was inconclusive. Regardless of the type of intervention, the reductions observed in smoking rates were only modest. CONCLUSIONS: The present work identified moderate evidence for the effectiveness of behavioural interventions to prevent smoking. Although evidence for the effectiveness of school-based interventions was inconclusive, evidence for the effectiveness of community-based and multisectorial interventions was somewhat stronger. Future research should investigate the effectiveness of specific intervention components and the cost-effectiveness of interventions analysed in methodologically high-quality studies.

Characterization and transcriptional regulation of the human somatostatin receptor subtype 1 gene.

Somatostatin (SRIF) exerts inhibitory effects on virtually all endocrine and exocrine secretions. At least five distinct human SRIF receptors have been identified ( SST1-SST5). Analysis of the promoter region may provide tools to understand transcriptional regulation of SSTS in various tissues, indicating specific functions. Transcriptional regulation of the human SST1 was analyzed in the present study. Total RNA from a human somatotropic pituitary tumor was reverse transcribed. 5'cDNA regions of the human SST1 were cloned using an adapted inverse PCR method. Among the 15 PCR clones analyzed, 9 demonstrated an extended 5'-utr of 266 nucleotides, determining a thymidine residue as a major transcription start site. No introns were evident in the 5'-utr region. The promoter region lacked consensus sites for TATA or CAAT boxes, YY1, or an initiator sequence, but contained two CpG islands. Different lengths of 5'-flanking regions cloned by PCR were placed upstream of the luciferase reporter gene and transiently transfected into various cell lines. The 2834 nt of the promoter region directed significant transcriptional activity in a somatotropic pituitary cell line, but neither in COS-7 monkey kidney cells nor in AtT-20 murine corticotrope cells. Transcriptional activity was not affected by incubation with various hormones. Several putative transcription factor binding sites inducing the cell-type specific activity were identified.

Clinical outcome and costs of nosocomial and community-acquired Staphylococcus aureus bloodstream infection in haemodialysis patients.

The main aim of this study was to evaluate the clinical outcome and costs of nosocomial and community-acquired methicillin-susceptible Staphylococcus aureus (MSSA) or methicillin-resistant S. aureus (MRSA) bloodstream infection (BSI) in patients undergoing haemodialysis. A multicentre retrospective study was conducted that included 109 patients with end-stage renal disease and S. aureus BSI who were hospitalised in three German centres between 1999 and 2005. Nosocomial and community-acquired infections were analysed separately with regard to costs and outcome. Forty-nine (45%) patients had nosocomial infection. Compared to patients with community-acquired infection, these patients were more likely to have had BSI caused by MRSA (40.8% vs. 13.3%, p <0.05). BSI was the initial reason for admission for 33 (55%) patients who had community-acquired infection. The mean length of hospitalisation was 24 days for patients with community-acquired infection and 51 days for patients with nosocomial infection (p <0.05). Costs per treatment episode were 20,024 Euros for nosocomial infection vs. 9554 Euros for community-acquired infection (p <0.05). The average treatment costs for patients with MSSA BSI were <50% of those for patients with MRSA BSI (10,573 vs. 24,931 Euros, p <0.05). S. aureus BSI is an underlying cause of substantial health risk and high morbidity among the haemodialysis-dependent population, who are already at high-risk for other reasons. This study also highlighted differences according to the source of BSI, including costs arising from hospitalisation and treatment.

Identification of an upstream pituitary-active promoter of human somatostatin receptor subtype 5.

Somatostatin receptor subtype 5 (sst5) has been linked to inhibition of PRL and insulin secretion. We characterized the genomic structure of the human sst5. The transcription start site was located 94 nucleotides upstream of the initiator ATG codon. Sequence analysis of 5'-inverse PCR products revealed the presence of a 6.1-kb intron in the 5'-untranslated region. RT-PCR analysis indicated tissue-specific activation of the newly identified upstream promoter in pituitary, but not in small intestine, lung, or placenta. A -1741 promoter directed significant levels of luciferase expression in GH(4) rat pituitary cells, Skut-1B endometrium cells, and JEG3 chorion carcinoma cells, which was absent in COS-7 monkey kidney cells. A minimal -101 promoter was sufficient to allow tissue-specific expression. Its activity in COS-7 cells was not enhanced by cotransfection of the pituitary-specific transcription factor Pit-1. Analysis of deletion constructs revealed a GC-rich region immediately upstream of the transcription start site, which is necessary for promoter activity. Somatostatin led to a significant inhibition, and forskolin and thyroid hormone to a significant stimulation of pituitary-specific promoter activity. Further mapping suggested a cAMP-responsive element located between -101 and the transcription start site, and thyroid hormone-responsive elements between -1741 and -1269 and between -317 and -101. These studies identified an upstream promoter of the sst5 gene with tissue-specific activity.

Genomic structure and transcriptional regulation of the human growth hormone secretagogue receptor.

Synthetic GH secretagogues stimulate GH release through binding to a recently cloned specific GH secretagogue receptor (GHS-R). The endogenous ligand of this receptor may be part of a new endocrine pathway controlling GH secretion. Two different receptor variants, type 1a and 1b, have been described that differ in their 3'-terminal amino acids. We investigated the genomic structure and transcriptional regulation of the human GHS-R. An 18-kb genomic clone including sequences encoding for the two GHS-R variants was isolated. Sequencing revealed that the two variants originate from specific RNA processing of a single gene that spans approximately 4.1 kb. The transcription start site was defined by 5'-inverse PCR analysis at position -227. RT-PCR analysis points to differential transcriptional initiation and processing. Type 1a is encoded by two exons; 2152 bp of intronic sequence are removed by splicing at position 796/797 relative to the translation start site. Type 1b is encoded by a single exon. A putative polyadenylation signal consensus motif was identified at position +4118; 2.7 kb of the 5'-flanking region were sequenced, and putative transcription factor binding sites were identified. Transcriptional regulation was investigated by transient transfections using promoter fragments ranging in size from 168-1745 bp; 1745 bp of the GHS-R promoter directed significant levels of luciferase expression in GH(4) rat pituitary cells, whereas no activity was detected in monkey kidney COS-7 cells, human endometrium Skut-1B cells, mouse hypothalamic LHRH neuronal GT1-7 cells, or mouse corticotroph pituitary AtT20 cells. A minimal 309-bp promoter allowed pituitary-specific expression. Its activity in COS-7 cells was enhanced by cotransfection of the pituitary-specific transcription factor Pit-1. We did not find any regulation of the GHS-R promoter by forskolin, somatostatin, insulin-like growth factor I, or 12-O-tetraphorbol 12-myristate 13-acetate. Thyroid hormone and estrogen lead to a significant stimulation; glucocorticoids lead to a significant inhibition. Further mapping suggests a thyroid hormone-responsive element, an estrogen-responsive element, and a glucocorticoid-responsive element located between -309 and the translation start codon. These studies demonstrate the nature of the human GHS-R gene and identify its 5'-flanking region. Furthermore, pituitary-specific activity of the promoter and regulation by various hormones are demonstrated.

Genomic structure and transcriptional regulation of the human somatostatin receptor type 2.

Somatostatin exerts inhibitory effects on virtually all endocrine and exocrine secretions. The somatostatin receptor subtype 2 (sst2) acts as a critical molecule for growth hormone regulation and cell proliferation. We investigated the structure and regulation of the human sst2 gene. A genomic clone including the sst2 gene was isolated, 1.5 kb of the promoter was sequenced and putative transcription factor binding sites were identified. The transcription start site was located 93 nucleotides upstream of the translation start site. The nucleotide sequences of the complete gene and 0.5 kb of 3' region were determined. A possible polyadenylation signal was identified. Transcriptional regulation was investigated by transient transfections using various promoter fragments. A -1100 sst2 promoter directed significant levels of luciferase expression in GH4 rat pituitary cells and Skut1-B endometrium cells whereas only low activity was detected in JEG3 chorion carcinoma cells or COS-7 monkey kidney cells. A minimal -252 promoter allowed cell specific expression. We did not find any regulation of the sst2 promoter by somatostatin, forskolin, TRH, TPA, T3, and 17beta-estradiol. Glucocorticoids lead to a significant inhibition of sst2 promoter activity. Further mapping suggest a glucocorticoid-responsive element between -905 and -707 and between -252 and -163. These studies demonstrate the nature of the human sst2 gene and identify its 5' and 3' flanking regions. Furthermore, specific activity of the promoter and regulation by various hormones is demonstrated.

Structure and regulation of the human growth hormone-releasing hormone receptor gene.

The GHRH receptor (GHRH-R) acts as a critical molecule for proliferation and differentiation of somatotrophic pituitary cells. A role in the pathogenesis of GH hypersecretion and GH deficiency has been implicated. We investigated structure and regulation of the human GHRH-R gene. A genomic clone including approximately 12 kb of 5'-flanking region was isolated. The gene is of complex structure consisting of more than 10 exons. Two kilobase pairs of the promoter were sequenced, and putative transcription factor binding sites were identified. The transcription start site was defined by ribonuclease protection assay. Transcriptional regulation was investigated by transient transfections using promoter fragments ranging in size from 108-1456 bp. GHRH-R promoter (1456 bp) directed high levels of luciferase expression in GH4 rat pituitary cells whereas no activity was detected in JEG3 chorion carcinoma cells or COS-7 monkey kidney cells. A minimal 202-bp promoter allowed pituitary-specific expression. Its activity in COS-7 cells is enhanced by cotransfection of the pituitary-specific transcription factor Pit-1. We did not find any regulation of the GHRH-R promoter by forskolin, phorbol-myristate-acetate, or T3. Glucocorticoids lead to a significant stimulation, and estrogen leads to a significant inhibition. Further mapping suggests a glucocorticoid-responsive element between -1456 and -1181 and an estrogen-responsive element between -202 and -108. These studies demonstrate the complex nature of the human GHRH-R gene and identify its 5'-flanking region. Furthermore, specific activity of the promoter and regulation by various hormones are demonstrated.

Comparison of photorefractive-index changes in annealed-proton-exchanged channel waveguides in MgO-doped and congruent LiNbO(3).

A quantitative comparison of the photorefractive effect in annealed proton-exchanged channel waveguides in MgO-doped and congruent LiNbO(3) at the wavelengths of 633 and 830 nm is presented. An accurate measurement technique is described to measure the refractive-index change as a function of time and the guided mode intensity for different wavelengths. The results show that doping with 7% MgO reduces the photorefractive effect at a wavelength of lambda = 633 nm by 2 orders of magnitude. The photorefractive effect in the doped substrate shows only a weak dependence on the guided power. Doping with 4 mol.% MgO has only little effect on the photorefractive effect compared with that on the congruent material. A reduced photovoltaic current is responsible for the small photorefractive effect in the 7 mol. %-doped substrate.

[Comparison of the progesterone test and uterus sonography as screening procedures in the detection of patients at risk of endometrial cancer]. / Vergleich von Progesterontest und Uterussonographie als screening-Verfahren zur Erkennung von Risikopatientinnen hinsichtlich Endometriumkarzinom.

The increasing incidence of endometrial cancer requires more attention to early detection. Postmenopausal women without symptoms were examined by progesterone challenge test (96 diabetics, 111 without diabetes) and by sonography (44 diabetics, 74 without diabetes) in order to recognize proliferation of the endometrium. The application of progesterone induced a bleeding in 4% of the women. The diagnostic curettage performed 4-6 weeks after this test revealed almost always atrophic endometrium. We found a good correspondence between abnormalities of the uterine cavity detected by sonography and the results of the pathological examination after notice pathological changes of the endometrium.