Pulmonary toxicity with mefloquine.

This report presents a case of acute lung injury developing within hours after administration of mefloquine for a low-level Plasmodium falciparum malaria, which was persistent despite halofantrine therapy. Extensive microbiological investigation remained negative and video-assisted thoracoscopic lung biopsy demonstrated diffuse alveolar damage. The evolution was favourable without treatment. This is the second report of acute lung injury and diffuse alveolar damage caused by mefloquine. Glucose-6-phosphate dehydrogenase deficiency was present in the former case and was thought to contribute to the lung injury. However, glucose-phosphate dehydrogenase was normal in the present case, suggesting that it is not a predisposing condition to the lung injury.

Compressed Sensing Single-Breath-Hold CMR for Fast Quantification of LV Function, Volumes, and Mass.

OBJECTIVES: The purpose of this study was to compare a novel compressed sensing (CS)-based single-breath-hold multislice magnetic resonance cine technique with the standard multi-breath-hold technique for the assessment of left ventricular (LV) volumes and function. BACKGROUND: Cardiac magnetic resonance is generally accepted as the gold standard for LV volume and function assessment. LV function is 1 of the most important cardiac parameters for diagnosis and the monitoring of treatment effects. Recently, CS techniques have emerged as a means to accelerate data acquisition. METHODS: The prototype CS cine sequence acquires 3 long-axis and 4 short-axis cine loops in 1 single breath-hold (temporal/spatial resolution: 30 ms/1.5 × 1.5 mm(2); acceleration factor 11.0) to measure left ventricular ejection fraction (LVEFCS) as well as LV volumes and LV mass using LV model-based 4D software. For comparison, a conventional stack of multi-breath-hold cine images was acquired (temporal/spatial resolution 40 ms/1.2 × 1.6 mm(2)). As a reference for the left ventricular stroke volume (LVSV), aortic flow was measured by phase-contrast acquisition. RESULTS: In 94% of the 33 participants (12 volunteers: mean age 33 ± 7 years; 21 patients: mean age 63 ± 13 years with different LV pathologies), the image quality of the CS acquisitions was excellent. LVEFCS and LVEFstandard were similar (48.5 ± 15.9% vs. 49.8 ± 15.8%; p = 0.11; r = 0.96; slope 0.97; p < 0.00001). Agreement of LVSVCS with aortic flow was superior to that of LVSVstandard (overestimation vs. aortic flow: 5.6 ± 6.5 ml vs. 16.2 ± 11.7 ml, respectively; p = 0.012) with less variability (r = 0.91; p < 0.00001 for the CS technique vs. r = 0.71; p < 0.01 for the standard technique). The intraobserver and interobserver agreement for all CS parameters was good (slopes 0.93 to 1.06; r = 0.90 to 0.99). CONCLUSIONS: The results demonstrated the feasibility of applying the CS strategy to evaluate LV function and volumes with high accuracy in patients. The single-breath-hold CS strategy has the potential to replace the multi-breath-hold standard cardiac magnetic resonance technique.

Haemorrhage into the pancreatic duct (Hemosuccus pancreaticus): recognition and management.

OBJECTIVE: To highlight the clinical presentation, investigation and treatment of haemorrhage into the pancreatic duct. DESIGN: Retrospective study and review of publications. SETTING: University hospital, Switzerland. SUBJECTS: All 4 cases from 1972 to 1993. INTERVENTIONS: 2 Whipple procedures, 1 resection of the pancreatic head, 1 exploratory laparotomy. Radiological embolisation in one case. MAIN OUTCOME MEASURES: Cessation of haemorrhage and survival. RESULTS: The diagnosis was made preoperatively in three cases by gastroduodenoscopy and arteriography. Operation was the primary treatment in all patients and was effective with low morbidity and no mortality in three of them. Embolisation stopped the haemorrhage in the fourth patient, who was alcoholic and died of progressive liver insufficiency and variceal haemorrhage. CONCLUSIONS: There is no specific indication for haemorrhage into the pancreatic duct. The diagnosis is suggested by endoscopy (absence of a more common cause, or blood in the second part of the duodenum). Arteriography is essential to confirm the site of the bleeding and to attempt embolization. Operation is usually the definitive treatment.

Factor structure of the SOCRATES questionnaire in hospitalized medical patients.

The Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES), a 19-item instrument developed to assess readiness to change alcohol use among individuals presenting for specialized alcohol treatment, has been used in various populations and settings. Its factor structure and concurrent validity has been described for specialized alcohol treatment settings and primary care. The purpose of this study was to determine the factor structure and concurrent validity of the SOCRATES among medical inpatients with unhealthy alcohol use not seeking help for specialized alcohol treatment. The subjects were 337 medical inpatients with unhealthy alcohol use, identified during their hospital stay. Most of them had alcohol dependence (76%). We performed an Alpha Factor Analysis (AFA) and Principal Component Analysis (PCA) of the 19 SOCRATES items, and forced 3 factors and 2 components, in order to replicate findings from Miller and Tonigan (Miller, W. R., & Tonigan, J. S., (1996). Assessing drinkers' motivations for change: The Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES). Psychology of Addictive Behavior, 10, 81-89.) and Maisto et al. (Maisto, S. A., Conigliaro, J., McNeil, M., Kraemer, K., O'Connor, M., & Kelley, M. E., (1999). Factor structure of the SOCRATES in a sample of primary care patients. Addictive Behavior, 24(6), 879-892.). Our analysis supported the view that the 2 component solution proposed by Maisto et al. (Maisto, S.A., Conigliaro, J., McNeil, M., Kraemer, K., O'Connor, M., & Kelley, M.E., (1999). Factor structure of the SOCRATES in a sample of primary care patients. Addictive Behavior, 24(6), 879-892.) is more appropriate for our data than the 3 factor solution proposed by Miller and Tonigan (Miller, W. R., & Tonigan, J. S., (1996). Assessing drinkers' motivations for change: The Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES). Psychology of Addictive Behavior, 10, 81-89.). The first component measured Perception of Problems and was more strongly correlated with severity of alcohol-related consequences, presence of alcohol dependence, and alcohol consumption levels (average number of drinks per day and total number of binge drinking days over the past 30 days) compared to the second component measuring Taking Action. Our findings support the view that the SOCRATES is comprised of two important readiness constructs in general medical patients identified by screening.

Transduction of CpG DNA-stimulated primary human B cells with bicistronic lentivectors.

Recently, using HIV-1-derived lentivectors, we obtained efficient transduction of primary human B lymphocytes cocultured with murine EL-4 B5 thymoma cells, but not of isolated B cells activated by CD40 ligation. Coculture with a cell line is problematic for gene therapy applications or study of gene functions. We have now found that transduction of B cells in a system using CpG DNA was comparable to that in the EL-4 B5 system. A monocistronic vector with a CMV promoter gave 32 +/- 4.7% green fluorescent protein (GFP)+ cells. A bicistronic vector, encoding IL-4 and GFP in the first and second cistrons, respectively, gave 14.2 +/- 2.1% GFP+ cells and IL-4 secretion of 1.3 +/- 0.2 ng/10(5) B cells/24 h. This was similar to results obtained in CD34+ cells using the elongation factor-1alpha promoter. Activated memory and naive B cells were transducible. After transduction with a bicistronic vector encoding a viral FLIP molecule, vFLIP was detectable by FACS or Western blot in GFP+, but not in GFP-, B cells, and 57% of sorted GFP+ B cells were protected against Fas ligand-induced cell death. This system should be useful for gene function research in primary B cells and development of gene therapies.

Stochastic Population Projection for Germany - based on the Quadratic Spline approach to modelling age specific fertility rates

This contribution builds upon a former paper by the authors (Lipps and Betz 2004), in which a stochastic population projection for East- and West Germany is performed. Aim was to forecast relevant population parameters and their distribution in a consistent way. We now present some modifications, which have been modelled since. First, population parameters for the entire German population are modelled. In order to overcome the modelling problem of the structural break in the East during reunification, we show that the adaptation process of the relevant figures by the East can be considered to be completed by now. As a consequence, German parameters can be modelled just by using the West German historic patterns, with the start-off population of entire Germany. Second, a new model to simulate age specific fertility rates is presented, based on a quadratic spline approach. This offers a higher flexibility to model various age specific fertility curves. The simulation results are compared with the scenario based official forecasts for Germany in 2050. Exemplary for some population parameters (e.g. dependency ratio), it can be shown that the range spanned by the medium and extreme variants correspond to the s-intervals in the stochastic framework. It seems therefore more appropriate to treat this range as a s-interval covering about two thirds of the true distribution.

P value and the theory of hypothesis testing: an explanation for new researchers.

In the 1920s, Ronald Fisher developed the theory behind the p value and Jerzy Neyman and Egon Pearson developed the theory of hypothesis testing. These distinct theories have provided researchers important quantitative tools to confirm or refute their hypotheses. The p value is the probability to obtain an effect equal to or more extreme than the one observed presuming the null hypothesis of no effect is true; it gives researchers a measure of the strength of evidence against the null hypothesis. As commonly used, investigators will select a threshold p value below which they will reject the null hypothesis. The theory of hypothesis testing allows researchers to reject a null hypothesis in favor of an alternative hypothesis of some effect. As commonly used, investigators choose Type I error (rejecting the null hypothesis when it is true) and Type II error (accepting the null hypothesis when it is false) levels and determine some critical region. If the test statistic falls into that critical region, the null hypothesis is rejected in favor of the alternative hypothesis. Despite similarities between the two, the p value and the theory of hypothesis testing are different theories that often are misunderstood and confused, leading researchers to improper conclusions. Perhaps the most common misconception is to consider the p value as the probability that the null hypothesis is true rather than the probability of obtaining the difference observed, or one that is more extreme, considering the null is true. Another concern is the risk that an important proportion of statistically significant results are falsely significant. Researchers should have a minimum understanding of these two theories so that they are better able to plan, conduct, interpret, and report scientific experiments.

Comparison of transhiatal laparoscopy versus blind closed-chest cervicotomy and laparotomy for esophagectomy in children.

BACKGROUND: Esophageal replacement for caustic stenosis in children poses a challenging surgical problem. Blind removal of the injured esophagus without thoracotomy through a left cervical and transhiatal approach followed by an orthotopic esophageal replacement using either the colon or the stomach is a difficult procedure and can be dangerous in children. We performed our first total laparoscopic transhiatal esophagectomy in February 2007. We aim to compare this new technique to the previously applied method of blind closed-chest esophagectomy through a cervicotomy and laparotomy. METHODS: We analyzed the surgery and follow-up of 40 children operated upon for extensive irreversible caustic burns of the esophagus. The first 20 esophageal replacements were performed following a blind dissection of the mediastinum through a cervical incision and a laparotomy for esophagectomy (Group I). The last 20 esophageal replacements were performed after laparoscopic transhiatal dissection in the mediastinum and cervicotomy in the neck for esophagectomy (Group II). All operations were performed under the supervision of the same senior surgeon. RESULTS: Average age at the time of surgery was the same in both groups. Total esophagectomy was achieved in 45.0% of cases in Group I versus in 90.0% of cases in Group II. Colon was used in 80.0% of cases in Group I and in 90.0% in Group II. The mean duration of surgery was one hour longer in the laparoscopy group. One vascular injury was reported in the blind laparotomy group. Pneumothorax was more frequent in Group II without significant consequences besides drainage. Average time of extubation was about the same in both groups (1.8days). CONCLUSION: Laparoscopic transhiatal esophagectomy for caustic burns before esophageal replacement in children is safe and effective. It could avoid vascular and bronchial mediastinal injuries as the dissection is performed under direct visual control. The routine use of laparoscopic assistance by a senior surgeon improves the safety of esophageal dissection and reduces life-threatening complications.

Foxm1 expression in prostate epithelial cells is essential for prostate carcinogenesis.

The treatment of advanced prostate cancer (PCa) remains a challenge. Identification of new molecular mechanisms that regulate PCa initiation and progression would provide targets for the development of new cancer treatments. The Foxm1 transcription factor is highly up-regulated in tumor cells, inflammatory cells, and cells of tumor microenvironment. However, its functions in different cell populations of PCa lesions are unknown. To determine the role of Foxm1 in tumor cells during PCa development, we generated two novel transgenic mouse models, one exhibiting Foxm1 gain-of-function and one exhibiting Foxm1 loss-of-function under control of the prostate epithelial-specific Probasin promoter. In the transgenic adenocarcinoma mouse prostate (TRAMP) model of PCa that uses SV40 large T antigen to induce PCa, loss of Foxm1 decreased tumor growth and metastasis. Decreased prostate tumorigenesis was associated with a decrease in tumor cell proliferation and the down-regulation of genes critical for cell proliferation and tumor metastasis, including Cdc25b, Cyclin B1, Plk-1, Lox, and Versican. In addition, tumor-associated angiogenesis was decreased, coinciding with reduced Vegf-A expression. The mRNA and protein levels of 11β-Hsd2, an enzyme playing an important role in tumor cell proliferation, were down-regulated in Foxm1-deficient PCa tumors in vivo and in Foxm1-depleted TRAMP C2 cells in vitro. Foxm1 bound to, and increased transcriptional activity of, the mouse 11β-Hsd2 promoter through the -892/-879 region, indicating that 11β-Hsd2 was a direct transcriptional target of Foxm1. Without TRAMP, overexpression of Foxm1 either alone or in combination with inhibition of a p19(ARF) tumor suppressor caused a robust epithelial hyperplasia, but was insufficient to induce progression from hyperplasia to PCa. Foxm1 expression in prostate epithelial cells is critical for prostate carcinogenesis, suggesting that inhibition of Foxm1 is a promising therapeutic approach for prostate cancer chemotherapy.

Current cardiovascular risk management patterns with special focus on lipid lowering in daily practice in Switzerland.

Background: There may be a considerable gap between LDL cholesterol (LDL-C) and blood pressure (BP) goal values recommended by the guidelines and results achieved in daily practice. Design Prospective cross-sectional survey of cardiovascular disease risk profiles and management with focus on lipid lowering and BP lowering in clinical practice. Methods: In phase 1, the cardiovascular risk of patients with known lipid profile visiting their general practitioner was anonymously assessed in accordance to the PROCAM-score. In phase 2, high-risk patients who did not achieve LDL-C goal less than 2.6 mmol/l in phase 1 could be further documented. Results: Six hundred thirty-five general practitioners collected the data of 23 892 patients with known lipid profile. Forty percent were high-risk patients (diabetes mellitus or coronary heart disease or PROCAM-score >20%), compared with 27% estimated by the physicians. Goal attainment rate was almost double for BP than for LDL-C in high-risk patients (62 vs. 37%). Both goals were attained by 25%. LDL-C values in phase 1 and 2 were available for 3097 high-risk patients not at LDL-C goal in phase 1; 32% of patients achieved LDL-C goal of less than 2.6 mmol/l after a mean of 17 weeks. The most successful strategies for LDL-C reduction were implemented in only 22% of the high-risk patients. Conclusion: Although patients at high cardiovascular risk were treated more intensively than low or medium risk patients, the majority remained insufficiently controlled, which is an incentive for intensified medical education. Adequate implementation of Swiss and International guidelines would expectedly contribute to improved achievement of LDL-C and BP goal values in daily practice.

Zins-Spreads als Einnahmequelle für Kantone : Die Abhängigkeit des Passivzinssatzes von den Bruttoschulden und damit einhergehende Renditemöglichkeiten am Kapitalmarkt

Über eine längere Zeitdauer betrachtet, weisen staatliche Schulden tendenziell tiefere Zinssätze respektive Renditen auf als andere auf dem Markt gehandelte papiere, was teilweise durch das geringere Risiko erklärt werden kann (Mehra & Prescott, 2003: S.892). Indem die Abhängigkeit der Schuldzinssätze von den Schuldenquoten der Schweizer Kantone modelliert und in Beziehung zu einer adäquaten Marktrendite gebracht wird, zeigt diese Arbeit, welches Einnahmepotential sich aus diesem Zins-Spread für die Schweizer Kantone ergibt. Zur Schätzung der Zinskurve wird vom Marktgleichgewicht ausgegangen, bei welchem die investoren mit einem Default Premium für einen möglichen Ausfall des Kantons als Schuldner, im Vergleich zu einer risikolosen Anlage, abgegolten werden müssen (Bayoumi, Goldstein und Woglom, 1995: S. 1048-1051). Dazu werden die für den Schweizer Kontext spezifischen Determinanten für die Ausfallswahrscheinlichkeit identifiziert (Daldoss und Foraita, 2003: S. 87). Empirisch überprüft wird dieses Modell anhand eines quantitativen Ansatzes, wobei in erster Linie die Generalisierte Momenten-Methode (GMM) angewandt wird. Als Datenbasis dient hauptsächlich die Finanzstatistik der Eidgenössischen Finanzverwaltung (EFV), wobei alle 26 Schweizer Kantone im Zeitraum von 1981 bis 2011 betrachtet werden. Als Marktrendite wird die durchschnittliche Rendite der Schweizer Pensionskassen verwendet. Mit den verwendeten Daten und Modellen kann die Form der Zinskurve jedoch nicht eindeutig bestimmt werden, was grösstenteils auf die Endogenitätsproblematik zurückzuführen ist. Diese kann aufgrund ungenügender und mangelhafter Instrumente ohne zusätzliche Daten nicht überwunden werden. Folglich kann auch keine optimale Schuldenquote bestimmt werden. Die quantitativen Resultate deuten dennoch auf ein gewisses Einnahmepotential hin. Wie das Fallbeispiel Kanton Aargau zeigt, kann dieses punktuell auch gebraucht werden und findet in der Praxis Anwendung (Anonymer Interviewpartner, 2013).