Showing papers in "Swiss Medical Weekly in 2006"

Neurological adverse events to voriconazole: evidence for therapeutic drug monitoring.

Abstract: Background: Treatment with voriconazoLe (VOR), a broad-spectrum second-generation azoLe antifungaL agent, has been shown to result in favorable outcomes in the setting of muLtipLe opportunistic fungaL infections. VOR has a considerable interpatient variation of serum concentrations, and recent observations suggest that adverse events might be close related. Objectives: Association of VOR serum Level increase (sVL) with severe neuroLogicaL adverse eve n ts. Methods E Results: In a retrospective analysis of 28 treatment courses, 6 patients presented with neuroLogicaL adverse events (nAE, haLLucination, encephaLopathy, and visual disturbance). OR per 0.1 pg/mL sVL was 2.34, (95% CI: 1.54-3.55, p<0.001). The ROC curve for nAE for each of the sVL cut points shows a very good accuracy (area under the ROC curve = 0.846). ALL nAE occurred within 3 to 22 days (median: 7 days) after start of VOR treatment or dosage adjustment. Longer duration of VOR treatment was significantLy associated with Less nAE (OR per 10 days of VOR treatment: 0.87, 95%CI: 0.78-0.96, p= 0.008). There was no correlation between sVL and creatinine (r=0.12, p=0.114), ALT (r=-0.14, p = 0.072), AST (r = 0.003, p = 0.964), aLkaLine phosphatase (r=0.03, p=0.723). Conclusions: Our findings demonstrate that the potential for emergence of neuroLogicaL adverse events is associated with elevated sVL and measurement of serum concentration could improve voMconazoLe treatment and safety.

Homocysteine as a risk factor for cardiovascular disease: should we (still) worry about?

Abstract: Cardiovascular disease (CVD) is the leading cause of death worldwide. CVD is causally related to "classical" risk factors such as elevated blood pressure, cholesterol, or glucose level and smoking. A causal role in the development of CVD is also suggested for numerous other factors, including an elevated plasma homocysteine concentration. Variation of homocysteinaemia is mainly due to genetic mutations and/or vitamin deficiency. The homocysteine concentration can be lowered with folate. Vitamin supplementation has thus been proposed in individuals with hyperhomocysteinaemia in order to reduce their CVD risk. On the other hand, population-based studies show little or no association between moderate hyperhomocysteinaemia and CVD risk. Nor has any randomised clinical trial clearly proven the efficacy of lowering the homocysteine concentration as a means of lowering the incidence of CVD. Hence at present it is inappropriate to recommend screening and treatment of hyperhomocysteinaemia in asymptomatic persons with or without other CVD risk. Until new evidence is available, clinicians should focus on better control of the "classical" risk factors for CVD.

Treatment options of invasive fungal infections in adults

Abstract: A panel of infectious disease specialists, clinical microbiologists and hospital epidemiologists of the five Swiss university hospitals reviewed the current literature on the treatment of invasive fungal infections in adults and formulated guidelines for the management of patients in Switzerland For empirical therapy of Candida bloodstream infection, fluconazole is the drug of choice in non-neutropenic patients with no severe sepsis or septic shock or recent exposure to azoles Amphotericin B deoxycholate or caspofungin would be the treatment option for patients with previous azole exposure In neutropenic patients, empirical therapy with amphotericin B deoxycholate is considered first choice In patients with severe sepsis and septic shock, caspofungin is the drug of first choice For therapy of microbiologically-documented Candida infection, fluconazole is the drug of choice for infections due to C albicans, C tropicalis or C parapsilosis When infections are caused by C glabrata or by C krusei, caspofungin or amphotericin B deoxycholate are first line therapies Treatment guidelines for invasive aspergillosis (IA) were stratified into primary therapy, salvage therapy and combination therapy in critically ill patients Voriconazole is recommended for primary (ie upfront) therapy Caspofungin, voriconazole (if not used for primary therapy) or liposomal amphotericin B are recommended for salvage therapy for refractory disease Combination therapy with caspofungin plus voriconazole or liposomal amphotericin B should be considered in critically ill patients Amphotericin B deoxycholate is recommended as initial therapy for the empirical therapy in patients with neutropenia and persistent fever with close monitoring of adverse events

Diagnosis and management of chronic pancreatitis: current knowledge.

Abstract: This paper reviews the current literature on chronic pancreatitis (CP). Despite marked progress in diagnostic tools, predominately imaging methods, no consensus has been reached on the nomenclature of CP, ie diagnosis, classification, staging, pathomechanisms of pain and its optimal treatment. A major problem is that no single reliable diagnostic test exists for early-stage CP except histopathology (rarely available). This stage is characterised typically by recurrent acute pancreatitis +/- necrosis (eg pseudocysts). Acute pancreatitis is a well-defined condition caused in 80% of cases by gallstones or alcohol abuse. Alcoholic pancreatitis, in contrast to biliary pancreatitis, progresses to CP in the majority of patients. However, a definite CP-diagnosis is often delayed because progressive dysfunction and/or calcification, the clinical markers of CP, develop on average 5 years from disease onset. The progression rate is variable and depends on several factors eg aetiology, smoking, continued alcohol abuse. Repeated function testing eg by the faecal elastase test, is the best alternative for histology to monitor progression (or non-progression) of suspected (probable) to definite CP. The pathomechanism of pain in CP is multifactorial and data from different series are hardly comparable mainly because insufficient data of the various variables ie diagnosis, classification, staging of CP, pain pattern and presumptive pain cause, are provided. Pain in CP is rarely intractable except in the presence of cancer, opiate addiction or extra-pancreatic pain causes. Local complications like pseudocysts or obstructive cholestasis are the most common causes of severe persistent pain which can be relieved promptly by an appropriate drainage procedure. Notably, partial to complete pain relief is a common feature in 50-80% of patients with late-stage CP irrespective of surgery and about 50% of CP-patients never need surgery (or endoscopic intervention). The spontaneous "burn-out" thesis of CP is in accordance with this observation although precise data of this phenomenon are scarce. Recent observations indicate that the progression to late-stage CP is markedly delayed in non-alcoholic compared to alcoholic CP. Therefore, spontaneous pain relief is also delayed but it occurs in close association with severe exocrine insufficiency suggesting that aetiology has a major impact on the duration of early-stage CP and that the "burn-out" thesis appears valid both in uncomplicated alcoholic and nonalcoholic late-stage CP. For treatment of steatorrhea and diabetes the reader is referred to recent reviews. Mortality and survival are closely related to aetiology with an increased death rate of about 50% within 20 years from onset in alcoholic CP compared to a markedly better prognosis in hereditary and idiopathic "juvenile" CP. The risk of pancreatic cancer is increased particularly in nonalcoholic CP based on the longer survival, whereas the risk of extra-pancreatic (smoking-related) cancer is about 12-fold higher in alcoholic CP.

Diagnostic value of signs, symptoms and laboratory values in lower respiratory tract infection.

Abstract: Background Lower respiratory tract infections (LRTI) account for the majority of all antibiotics prescribed in the clinical practice, irrespective of the fact that most cases are self-limiting Using the outcome and microbiology findings as gold standard, we determined sensitivity, specificity, positive and negative predictive values of common used signs and symptoms of bacterial LRTI requiring antibiotic therapy Patients 243 consecutive patients with suspected LRTI admitted to a tertiary care hospital Results Bacterial LRTI requiring antibiotic therapy and self-limiting LRTI were diagnosed in 32 and 86 patients, respectively Assessing these two groups, sputum, dyspnea, crackles, fever and leukocytes (WBC) were insensitive and unspecific parameters for the diagnosis of bacterial LRTI requiring antibiotic therapy Cough was sensitive (938%) but unspecific (58%) The sensitivity of infiltrates, C-reactive protein (CRP) >50 mg/L and procalcitonin (PCT) >01 ng/mL was 969%, 938% and 938%, respectively PCT >025 ng/mL showed the highest specificity (977%), followed by WBC >16 x 109/L (942%) and CRP >100 mg/L (919%) The sensitivity of WBC >16 x 109/L was low (375%) Conclusion The overall sensitivity and specificity of signs and symptoms for bacterial LRTI requiring antibiotic therapy was poor Obtaining a chest-X-ray with infiltrates and determining CRP at a cut-off value of 50 mg/L or PCT at a cutoff value of 01 ng/mL was required to ascertain the need for antibiotics in LRTI

Biomaterials-based tissue engineering and regenerative medicine solutions to musculoskeletal problems.

Abstract: Tissue engineering and regenerative medicine offer solutions to a number of compelling clinical problems that have not been adequately addressed through the use of permanent replacement devices. The challenge will be to select the optimal combination of a biomaterial scaffold, cells, and soluble regulators for a particular clinical problem. For many connective tissues of the musculoskeletal system, with microstructures that reflect the mechanical environment, it may be more advantageous to regenerate the tissue in vivo than to fully engineer the tissue in vitro for subsequent implantation. The porous material to be used as the scaffold to facilitate this regeneration needs to have certain pore characteristics, chemical composition and mechanical properties. One approach has been to employ substances that serve as analogues of the extracellular matrix of the tissue to be regenerated. For selected indications in which the supply of endogenous precursor cells is limited it may be more efficacious to employ a scaffold as a delivery vehicle for the cells rather than to inject the cells into the defect. Investigations of cell-scaffold interactions in vitro not only offer the opportunity for modification of scaffold composition and structure to improve the outcome in vivo, but also offer the opportunity to discover cell biological behaviour when cells grow in the three-dimensional tissue-like environment. Selected clinical applications may also require the implantation of regulatory proteins such as growth factors. That the action of such polypeptides released from biomaterials is short-lived has led to recent work wedding tissue engineering and gene therapy. Genes can be bound to certain biomaterial scaffolds to be released in vivo over extended periods (eg weeks) in order to genetically modify cells in the defect to produce the desired growth factors. Thus a new role for biomaterials is as a delivery vehicle for genes, as well as for cells and growth factors. These endeavours are notable particularly because there is a growing consensus that the challenge of developing biomaterials for tissue engineering, regenerative medicine, and gene therapy exceeds the challenge that was faced in the cell biological work that led to the proliferation of cells in vitro (in such a way that they retain their phenotypic characteristics) and in the genetic engineering that has led to the production of growth factors and cloning of their genes.

Unlicensed and off-label drug use in a Swiss paediatric university hospital.

Abstract: BACKGROUND: Many medicines used in newborns, infants, children and adolescents are not licensed ("unlicensed") or are prescribed outside the terms of the marketing authorization ("off-label") Several studies have shown that this is a common practice in various healthcare settings in the USA, Europe and Australia, but data are scarce in Switzerland OBJECTIVES: The aim of our prospective study was to determine the proportion of unlicensed or off-label prescriptions in paediatric patients METHODS: This pilot study was conducted prospectively over a six month period in the department of paediatrics of a university hospital RESULTS: Sixty patients aged from three days to 14 years were included in the study A total of 483 prescriptions were written for the patients More than half of all prescriptions (247; 51%) followed the terms of the marketing authorization 114 (24%) were unlicensed and 122 (25%) off-label All patients received at least one unlicensed or offlabel medicine CONCLUSION: The use of unlicensed or off-label medicines to treat children was found to be common Co-operation between the pharmaceutical industry, national regulatory authorities, clinical researchers, healthcare professionals and parents is required in order to ensure that children do not remain "therapeutic orphans"

Tracheobronchial foreign body aspiration in children - diagnostic value of symptoms and signs.

Abstract: OBJECTIVE: Tracheobronchial foreign body (TFB) aspiration is a common cause of respiratory compromise in early childhood. Research indicates that a high number of children are missed with TFB aspiration. The aim of this study was to identify predictors of potential TFB aspiration. STUDY DESIGN: We analysed 370 endoscopic reports of children admitted to our emergency department who underwent explorative rigid bronchoscopy to exclude/remove a TFB (1989-2003). Patient characteristics, history, clinical, radiographic and bronchoscopic findings were noted. Sensitivities and specificities for TFB aspiration were calculated for patient history, clinical and radiographic findings. RESULTS: The median age was 1.8 years. In 59.7% of patients a TFB was found and removed. A group analysis was performed on children with symptoms less than 2 weeks (group A) and those more than 2 weeks (group B). The results showed that unilateral diminished breath sounds and unilateral overdistension on chest X-ray were the most sensitive (53-79%) and specific (68-88%) findings in both groups. The clinical triad of acute choking/coughing, wheezing and unilateral diminished breath sounds had a high specificity (96-98%) in both groups. In contrast, a positive history of acute choking/coughing in group A or a permanent cough in group B showed a low specificity (8-16%). CONCLUSION: In a paediatric respiratory compromise, the presence of unilateral diminished breath sounds, pathological chest X-ray or clinical triad is a powerful indicator for occurred TFB aspiration. Since no single or combined variables can predict TFB aspiration with full certainty, bronchoscopic exploration should be performed if TFB aspiration is suspected. Language: en

The relationship between inflammation and the coagulation system.

Abstract: Inflammation and coagulation play pivotal roles in host defence. As phylogenetically old responses, there is extensive cross-talk between inflammation and coagulation in enabling an adequate immune response against potentially injurious stimuli. Immune cells are important in the initiation of coagulation pathways, while various inflammatory mediators are capable of altering haemostasis. Vice versa, coagulation proteases have significant immunomodulatory effects. Understanding the mechanisms involved in the crosstalk between inflammation and coagulation may yield new therapeutic strategies for human diseases.

The association between impact factors and language of general internal medicine journals.

Abstract: BACKGROUND We sought to determine the associations between journal country of origin and language and journal impact factor of general medicine journals. METHODS For each "Medicine, General and Internal" journal listed in the Institute for Scientific Information (ISI) Journal Citation Reports (JCR), the 2003 impact factor, language (ie, English, multiple languages [including English], or non-English), and country of origin (ie, US or non-US) were determined. The mean log impact factors of the journals by language, country of origin, and a combination of country of origin and language were compared. RESULTS Of the 102 "Medicine, General and Internal" journals listed in the ISI JCR, 41 (40%) were published in the US and 83 (81%) were published in English. English-language journals had a significantly greater 2003 mean log impact factor than non-English journals and journals originating in the US had a significantly greater impact factor than journals originating elsewhere. However, the mean log impact factor of English-language journals originating in the US did not differ significantly from that of English-language journals originating elsewhere. CONCLUSION Journal impact factor is more associated with journal language (ie, English versus non-English), rather than journal country of origin.

Hypoglycaemic effect of Artemisia sphaerocephala Krasch seed polysaccharide in alloxan-induced diabetic rats.

Abstract: The purpose of this study was to examine the hypoglycaemic activity of a new polysaccharide extracted from seed polysaccharide (ASP) was administered orally for 4 weeks and the blood glucose changes were determined in fasted rats. Plasma insulin, cholesterol and triglycerides levels were also determined. The ASP at a dose of 200 mg/kg body weight (bw) produced a significant decrease in blood glucose levels in diabetic rats (P <0.01). In the other hand, the effect of the ASP on the plasma cholesterol were also significant in diabetic rats (P <0.05). Furthermore, there was a significant effect of ASP on plasma triglycerides in both normal and diabetic groups. In order to characterise the active principle(s), which could be responsible for the therapeutic effect, a preliminary phytochemical analysis of the ASP was performed. The monosaccharides of ASP were composed of L-Ara, D-Xyl, D-Lyx, D-Man, D-Glc, D-Gal. Their molar proportions were 1, 4.98, 1.69, 27.86, 3.76 and 13.92, respectively.

Primary care in Switzerland--no longer attractive for young physicians?

Abstract: BACKGROUND AND OBJECTIVES A trend away from primary care (PC) to other specialties has been noted in Switzerland, as well as in the health-care systems of many other Western countries The objective of the present study was to ascertain how many third-year residents graduating in 2001/02 from medical schools in German-speaking Switzerland wanted to become PC physicians (PCPs), whether this career goal was continuously followed, and how many subjects switched to or away from PC during residency METHODS Data reported are from the third assessment of the longitudinal Swiss physicians' career development study, begun in 2001 In 2005, at the third assessment, 515 residents (538% females, 462% males) were asked what specialty qualifications and career goals they aspired to In addition, participants' socio-demographic, personality, and career-related characteristics as well as their life goals were addressed RESULTS Of n = 515 (total sample) third-year residents, 81 had not yet decided on the medical field in which they wished to specialise, while 434 had made this decision Of the latter, only 42 (97%) aspired to become PCPs Twelve of the 42 future PCPs consistently mentioned PC as a career goal from graduation throughout residency The other 30 subjects only decided on PC during the course of their residencies A switch away from PC was also noted in the case of 19 subjects who on graduation or after the first year of residency aspired to become PCPs, but abandoned this goal after three years of residency Future PCPs differ from those pursuing other specialties in terms of personal and career-related characteristics, as well as in their life goals, insofar as they are less career-orientated and regard having more time outside work a priority There are few gender-based differences between female and male future PCPs CONCLUSION Primary care seems to hold little attraction as a career goal for young physicians Residency experiences would seem to have more of an effect on choice of specialty than teaching experiences during medical school The percentage of subjects qualifying in PC is far too low to fill the need for the future generation of PCPs In addition to efforts to incorporate PC issues into medical school curricula, structured residency programs should be established to promote PC

Quality of life and psychosocial situation before and after a lung, liver or an allogeneic bone marrow transplant

Abstract: Background and objectives Only few comparative prospective studies have been published on psychosocial issues of organ transplant. This study investigated patient groups with various organ transplants with respect to their quality of life and psychosocial situation before and after surgery. Methods 76 patients receiving an organ transplant (lung n = 22, liver n = 26, allogeneic bone marrow n = 28) were investigated with regard to quality of life (SF-36), life satisfaction (FLZ), social support (F-SozU), and psychological symptoms (HADS-D) before (T0) as well as six (T1) and twelve (T2) months after transplant. Results In the pre-transplant period the values of the psychosocial variables were partly lower than those of the community normal sample. After transplant lung and bone marrow patients reported less anxiety and depression and a higher life satisfaction, and liver patients reported less depression, compared to the norms. Quality of life, life satisfaction and psychological symptoms of all patients improved significantly post-transplant, whereas the perceived social support decreased. Contrary to the other groups, the psychological well-being of liver transplant recipients was deteriorating between T1 and T2. Conclusions An organ transplant improved the patients' quality of life and psychosocial situation to a great extent. This effect was better in lung and bone marrow than in liver transplant patients.

Diagnostic yield of flexible bronchoscopy in current clinical practice.

Abstract: BACKGROUND Flexible bronchoscopy is a procedure commonly performed for diagnostic and therapeutic purposes. The aim of this study was to assess the diagnostic yield and the safety of routine bronchoscopy techniques including transbronchial needle aspiration and transbronchial biopsy at a university hospital in Switzerland. METHODS 616 consecutive bronchoscopies performed at the Pulmonary Medicine Department (University Hospital Basel) over a period of 6 months were analysed retrospectively using bronchoscopy reports and hospital charts. Diagnostic procedures included bronchial washings, bronchoalveolar lavage, bronchial brushings, transbronchial needle aspiration and transbronchial biopsies. RESULTS 430 bronchoscopies had a diagnostic, 186 a therapeutic indication. The overall diagnostic yield was 57% (245/430). Bronchoscopy performed for suspected tumours confirmed malignancy in 43% of cases. Bronchoscopy in suspected infection and tuberculosis identified pathogenic organisms in 46% and 27% of cases, respectively. The diagnostic yield for central and peripheral TBNA was 37.8 and 43.6%, respectively. Complications were very rare (n = 10, 1.6%) and were only minor. CONCLUSION This study demonstrates that routine bronchoscopy techniques including transbronchial needle aspiration and transbronchial biopsy are safe and have a high diagnostic yield.

The role of statins in clinical medicine--LDL--cholesterol lowering and beyond.

Abstract: In the past years, statins have emerged as the most important class of lipid lowering agents. Through inhibition of HMG-CoA reductase, they restrict the rate-limiting step of cholesterol synthesis, which leads to upregulation of LDL receptors on the cell membrane and thus reduction of atherogenic LDLs. This effect translates into clinical benefit by reducing cardiovascular events both in primary and secondary prevention settings. As an approximate rule, statin therapy leads to a relative risk reduction of 25-30% in most of the large randomised controlled trials. Stroke risk is reduced to a similar degree. Despite initial concerns, the currently available statins have a favourable safety profile; however, potential interactions with other drugs must be considered. Recently, characteristics unrelated to LDL lowering have been intensively studied. These pleiotropic statin effects result from decreased levels of isoprenoid intermediates of cholesterol synthesis. They include--among others--anti-inflammatory, anti-proliferative, and immunomodulatory actions. Pleiotropic effects favourably influence pathomechanisms of plaque formation. Furthermore, they may prove beneficial in the prevention or treatment of diseases unrelated to atherosclerosis, eg rheumatoid arthritis, multiple sclerosis, or cancer.

Risk factors for developing metastatic infection from pyogenic liver abscesses.

Abstract: Objectives The aim of this study was to identify the risk factors for developing extra-hepatic metastases from pyogenic liver abscesses. Methods We conducted a retrospective study and reviewed 225 patients (age, 19-93 years) with a discharge diagnosis of pyogenic liver abscess from a large medical centre in Taiwan, between January 1995 and June 2000. Clinical data were collected from medical records. Of the 225 patients with a pyogenic liver abscess, 24 had extrahepatic metastases and were classified into the metastatic infection group; the remaining 201 were classified into the non-metastatic infection group and served as the control group. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by exact logistic regression. Results After adjustment for age, sex, and the duration of symptoms before admission, diabetes mellitus (adjusted OR, 12; 95% CI, 3.3-67), alcoholism (adjusted OR, 5.2; 95% CI, 1.4-20), the time interval >7 days from the onset of symptoms to the time appropriate antibiotics were administered (adjusted OR, 3.9; 95% CI, 1.2-13), bacteraemia (adjusted OR, 5.4; 95% CI, 1.4-30), and infection (adjusted OR, 5.0; 95% CI, 1.1-47) were associated with the development of extra-hepatic metastases from pyogenic liver abscesses. On the other hand, fever (adjusted OR, 0.28; 95% CI, 0.089-0.92) and right upper quadrant pain/tenderness (adjusted OR, 0.091; 95% CI, 0.0020-0.50) were associated with the non-metastatic abscesses. We performed a multivariate analysis and found that diabetes mellitus (multivariate OR, 7.7; 95% CI, 2.1-29) and alcoholism (multivariate OR, 8.9; 95% CI, 2.6-30) were the independent risk factors for developing metastatic infections; yet right upper quadrant pain/tenderness (multivariate OR, 0.11; 95% CI, 0.014-0.87) was the predictor of no metastatic abscesses. Conclusions Our data suggest that diabetes mellitus and alcoholism are significant risk factors for developing metastatic infections from pyogenic liver abscesses. These findings seem to imply that underlying conditions of the host influence the development of extra-hepatic metastases from pyogenic liver abscesses.

Increased prevalence of high Body Mass Index in patients presenting with pituitary tumours: severe obesity in patients with macroprolactinoma.

Abstract: INTRODUCTION Prolactinoma has been associated with obesity. As opposed to ACTH- and GH-secreting adenoma, the mechanism by which macroprolactinoma causes obesity has not been fully understood. Having seen patients with both prolactinoma and obesity and more recent literature on brain dopamine, dopamine 2 receptors and obesity, we re-evaluated the potential relationship between prolactinoma and obesity. METHODS Data of patients with pituitary adenomas were collected retrospectively over a period of 20 years. 399 patients with well-documented pituitary adenomas and information about pre-treatment body mass index (BMI), age, sex, and tumour type were analysed. RESULTS Elevated BMI (> or = 30 kg/m2) was observed in 8/36 patients (22.2%) with ACTH-producing tumours, in 15/70 (21.4%) with GH-producing tumours, in 25/100 (25%) with macroprolactinoma, in 8/81 (9.9%) with microprolactinoma, and in 18/105 (17.1%) with inactive macroadenomas. Macroprolactinoma patients had a mean BMI value (27.5 +/- 7.7 kg/m2) similar to that of patients with Cushing's disease (27.2 +/- 5.9 kg/m2) and acromegaly (27.4 +/- 4.4 kg/m2) and on average a significantly higher BMI value compared to that of patients with inactive macroadenomas (25.8 +/- 4.4 kg/m2) (95% CI 1.2, 4.4; p-value or = 30 kg/m2 in patients with macroprolactinoma was significantly higher (95% CI 0.1, 0.29; p-value <0.001). CONCLUSIONS Average BMI in macroprolactinoma patients is significantly higher than BMI in patients with inactive adenomas. Macroprolactinoma is associated with increased frequency of obesity compared to the general population. We propose that in a subgroup of individuals obesity and macroprolactinoma may share a common basis, namely decreased dopamine 2 receptor-mediated actions.

Coronary artery disease, nitric oxide and oxidative stress: the "Yin-Yang" effect--a Chinese concept for a worldwide pandemic.

Abstract: Prevention of coronary artery disease (CAD) and reduction of its mortality and morbidity remains a major public health challenge throughout the "Western world". Recent evidence supports the concept that the impairment of endothelial function, a hallmark of insulin resistance states, is an upstream event in the pathophysiology of insulin resistance and its main corollaries: atherosclerosis and myocardial infarction. Atherosclerosis is currently thought to be the consequence of a subtle imbalance between pro- and anti-oxidants that produces favourable conditions for lesion progression towards acute thrombotic complications and clinical events. Over the last decade, a remarkable burst of evidence has accumulated, offering the new perspective that bioavailable nitric oxide (NO) plays a pivotal role throughout the CAD-spectrum, from its genesis to the outcome after acute events. Vascular NO is a critical modulator of coronary blood flow by inhibiting smooth muscle contraction and platelet aggregation. It also acts in angiogenesis and cytoprotection. Defective endothelial nitric oxide synthase (eNOS) driven NO synthesis causes development of major cardiovascular risk factors (insulin resistance, arterial hypertension and dyslipidaemia) in mice, and characterises CAD-prone insulin-resistant humans. On the other hand, stimulation of inducible nitric oxide synthase (iNOS) and NO overproduction causes metabolic insulin resistance and characterises atherosclerosis, heart failure and cardiogenic shock in humans, suggesting a "Yin-Yang" effect of NO in the cardiovascular homeostasis. Here, we will present a concise overview of the evidence for this novel concept, providing the conceptual framework for developing a potential therapeutic strategy to prevent and treat CAD.

Bone tissue engineering using fetal cell therapy

Abstract: Different cell sources for bone tissue engineering are reviewed. In particular, adult cell source strategies have been based on the implantation of unfractionated fresh bone marrow; purified, culture expanded mesenchymal stem cells, differentiated osteoblasts, or cells that have been modified genetically to express rhBMP. Several limiting factors are mentioned for these strategies such as low number of available cells or possible immunological reaction of the host. Foetal bone cells are presented as an alternative solution and review of actual treatments using these cells is presented. Finally, foetal cells used specifically for bone tissue engineering are characterised and potentially interesting therapeutic options are proposed.

Communication training and antibiotic use in acute respiratory tract infections. A cluster randomised controlled trial in general practice.

Abstract: UNLABELLED: A cluster-randomised controlled trial in general practice BACKGROUND: Physician-patient communication plays a key role in treatment decisions in primary care. We aimed to reduce the antibiotic prescription rate for acute respiratory tract infections using a short training programme in patient-centred communication. METHODS: We conducted a cluster-randomised controlled trial in 45 general practices in Switzerland. Thirty physicians received evidence-based guidelines for the management of acute respiratory tract infections; 15 physicians randomised to the full intervention additionally received training in patient-centred communication. A further 15 physicians, not randomised, served as a control to blind the physicians in the other two groups to the true comparison. The primary outcome was the antibiotic prescription rate reported by pharmacists. Secondary outcomes were patient satisfaction and enablement, re-consultation rates, days with restrictions, and days off work. 1108 adults with acute respiratory infections were screened between January and May 2004. Outcomes were measured in 837 consultations; 624 patients had follow-up interviews at 7 and 14 days. RESULTS: The antibiotic prescription rate reported by pharmacists was low in both full and limited intervention groups (13.5% and 15.7% respectively) but only half of the antibiotics were prescribed according to guidelines (53.8% and 53.1%). No significant differences were seen between the two randomised groups in primary and secondary outcomes. In both groups patient satisfaction was high (median score for both 68 out of 70). CONCLUSIONS: In this trial, patient-centred communication training did not reduce the rate of antibiotic prescriptions below an already unusually low level. Even with this low prescription rate, patient satisfaction with received care was high.

Therapy and management of systemic AL (primary) amyloidosis.

Abstract: The optimal treatment of immunoglobulin light chain amyloidosis (AL) patients requires early diagnosis, correct amyloid typing, effective treatment and careful supportive therapy. In the last few years the therapeutic arsenal for the management of AL has been considerably enriched. Cardiac dysfunction can be accurately monitored by measuring the serum concentration of natriuretic peptide type-B and cardiac troponins and the quantitative test for circulating free light chains allows an easy assessment of haematological response to chemotherapy. These new tools can be combined in order to maximise the improvement of organ dysfunction and minimise toxicity, adapting the intervention to each patient.

Cardiac resynchronization therapy in chronic heart failure.

Abstract: Cardiac resynchronisation therapy (CRT) has emerged as a treatment option for patients with severe, drug-refractory heart failure and signs of intraventricular dyssynchrony. In clinical trials CRT reduced the overall mortality, improved symptoms, exercise tolerance, and left ventricular function, as compared with optimised medical therapy alone. One of the challenging fields in patient selection for CRT is to identify the 20-30% of heart failure patients with bundle branch block that will not respond to this novel therapy. Other fields of uncertainty, such as CRT in patients with atrial fibrillation or chronic right ventricular stimulation as well as the role of a back-up defibrillator will be discussed.

ECG changes amongst patients with alcohol withdrawal seizures and delirium tremens

Abstract: Introduction Alcohol withdrawal seizures and delirium tremens (DT) are serious complications of alcohol dependence. The prevalence of arrhythmias and other electrocardiographic (ECG) changes occurring in these clinical situations is not well studied. Methods We performed a retrospective analysis of clinical data and ECG's from patients discharged between 1995 and 2005 with the diagnosis of DT (ICD-Code F10.4) or alcohol withdrawal seizures (F10.3). Measurement of the ECG intervals was done in lead II. The corrected QT interval (QTc) was obtained using Bazett's formula. Results 49 patients (38 males; 11 females) with a mean age of 48 years were included in the study. 23 patients with DT and 16 with convulsions were admitted to the hospitals. Ten patients developed DT while being hospitalised for other reasons. The QTc interval was prolonged (>440 ms and >460 ms in males and females, respectively) in 31 patients (63%). Five patients (10%) developed tachyarrhythmias (two torsade de pointes, one sustained ventricular tachycardia, two supraventricular tachycardia, one atrial fibrillation). All returned to sinus rhythm after appropriate treatment. Conclusions Tachyarrhythmias are common amongst patients with severe alcohol withdrawal syndromes. The majority of the patients had an acquired long QT syndrome which led to a torsade de pointes in two cases. No patient died in the hospital and all were discharged in sinus rhythm. Clinicians should possibly avoid QT prolonging drugs and carefully monitor the rhythm in patients with severe alcohol withdrawal syndromes.

Stem cells with potential to generate insulin producing cells in man.

Abstract: Replacement of insulin-producing cells represents an almost ideal treatment for patients with diabetes mellitus type 1. Transplantation of pancreatic islets of Langerhans--although successful in experienced centres--is limited by the lack of donor organs. Generation of insulin-producing cells from stem cells represents an attractive alternative. Stem cells with the potential to differentiate into insulin-producing cells include embryonic stem cells (ESC) as well as adult stem cells from various tissues including the pancreas, liver, central nervous system, bone marrow and adipose tissue. The use of human ESC is hampered by ethical concerns and the inability to create patient specific ESC with therapeutic cloning. Among adult stem cells mesenchymal stem cells appear to have a particular developmental plasticity ex vivo that include their ability to adopt a pancreatic endocrine phenotype. The present review summarises the current knowledge on the development of insulin-producing cells from stem cells with special emphasis on human mesenchymal stem cells isolated from the pancreas and adipose tissue.

Satisfaction of patients on chronic haemodialysis and peritoneal dialysis.

Abstract: BACKGROUND: In contrast to quality of life, patient satisfaction on chronic haemodialysis (HD) and peritoneal dialysis (PD) has only rarely been studied. PATIENTS AND METHODS: All chronic HD and PD patients of the 19 centres located in western Switzerland were asked to complete a specific questionnaire, assessing dialysis centre characteristics, treatment modalities, and information received before and during dialysis treatment. Comparison between satisfaction with PD and HD was carried out on the patients in the nine centres offering both treatment modalities. RESULTS: Of the 558 questionnaires distributed to chronic HD patients, 455 were returned (response rate 82%). Fifty of 64 PD patients (78%) returned the questionnaire. The two groups were similar in age, gender, and duration of dialysis treatment. Completion rates were >90% for a majority of questions, with the lowest rate for information on sexuality (49% in HD and 54% in PD respectively). The lowest scores were recorded for information received about complications and costs of dialysis, and impact of end-stage kidney disease on sexuality. Satisfaction was lower in anonymous questionnaires. Satisfaction of PD patients was significantly better in 50% of the questions, particularly session tolerance (p<0.001), information about dialysis sessions (p=0.007), and complications (p=0.006). CONCLUSIONS: PD patients were on average more satisfied with their treatment than HD patients. Satisfaction could be improved with more information about potential adverse treatment effects.

Bone tissue engineering using foetal cell therapy.

Abstract: Different cell sources for bone tissue engineering are reviewed. In particular, adult cell source strategies have been based on the implantation of unfractionated fresh bone marrow; purified, culture expanded mesenchymal stem cells, differentiated osteoblasts, or cells that have been modified genetically to express rhBMP. Several limiting factors are mentioned for these strategies such as low number of available cells or possible immunological reaction of the host. Foetal bone cells are presented as an alternative solution and review of actual treatments using these cells is presented. Finally, foetal cells used specifically for bone tissue engineering are characterised and potentially interesting therapeutic options are proposed.

The expanding role of hospitalists in the United States.

Abstract: Hospitalists are the most rapidly growing group of providers in the United States; in a few years, there will be more hospitalists than cardiologists in the U.S. While early growth in the field was driven by financial demands on hospitals, more recent incentives include a growing focus on improving the quality and safety of care. With current evidence suggesting both financial and educational benefits from the increased presence of hospitalists in both teaching and non-teaching settings, the environment is ripe for further expansion. Hospitalists are likely to embrace a number of additional clinical and non-clinical roles in the coming years. They will serve as change agents, hospital leaders and experts in both quality improvement activities and research initiatives around improving inpatient care delivery. As their skills sets and unique competencies become more clearly outlined, the next step will likely be the development of an independent specialty with its own board certification.

Clinical experiences with bisphopsphonate induced osteochemonecrosis of the jaws.

Abstract: Question Bisphosphonates are frequently used drugs in the adjuvant therapy of bone metastases and tumour-induced hypercalcaemia, but also for osteoporosis or Pagets disease. Several publications within the last three years considered osteonecrosis of the jaws to be connected with bisphosphonate therapy. Until today possible treatment strategies contain antibiotics, hyperbaric therapy and operative treatment. The tendency of healing however seems to be extremely poor. All clinicians should be aware of this new kind of side effect of bisphosphonate therapy. Methods 14 patients with this new kind of osteonecrosis were admitted to the department of Cranio-Maxillofacial Surgery of the University Hospital of Zurich. 8 men and 6 women all received bisphosphonates for cancer therapy. A complete analysis of patients' data was performed. Results Of 14 patients in 7 the underlying disease disease was multiple myeloma. In one patient it was prostate cancer and in all female patients it was breast cancer. All of them had prior dental treatment and showed inflammatory signs and bacterial colonisation with localisation in the upper or lower jaw or in both. Conclusion The infectious part of the bisphosphonate-induced osteonecrosis (ONJ) is considered to be more important than thought before. We presume that antimicrobial treatment is of utmost importance in the treatment of this kind of osteonecrosis. Patients with current or previous bisphosphonate therapy should be treated multidisciplinary to assure ideal prevention and treatment.

Secular trends in legal and illegal substance use among 16 to 20 year old adolescents in Switzerland.

Abstract: BACKGROUND Data targeting trends in legal and illegal substance use by adolescents are scarce. Using the data from two similar large national surveys run in 1993 and 2002, this paper assesses secular trends in rates of substance use among 16-20-year-old Swiss adolescents. METHODS Self-reported regular use of tobacco, alcohol misuse, regular cannabis use (01 occasion over last 30 days) and lifetime use of psychoactive medication, LSD, ecstasy, cocaine and heroine were assessed through identical questions using an anonymous self-administered questionnaire. 9268 (1993) and 7428 (2002) high school students and apprentices were included in the analyses. RESULTS There is a higher proportion of regular smokers among apprentices than among students (p <0.001). Between 1993 and 2002 the increase in regular tobacco consumption was significant among both female and male apprentices (p <0.001) but not among students. Between 1993 and 2002 alcohol misuse significantly increased in all four groups (p <0.001). It is more prevalent among males than among females (p <0.001) and higher among apprentices than among students (p <0.001). Regular use of cannabis has increased in the four groups (p <0.0001). It is higher among males than among females (p <0.001), while it is largely the same among students and apprentices. While the increase in ecstasy use is highly significant in all four groups (p <0.001), the increase in LSD and cocaine use is significant among apprentices only (p <0.001). Use of LSD, ecstasy and cocaine is more prevalent among males than among females (<0.001) and higher among apprentices than among students (p <0.001). CONCLUSION The secular increase in psychoactive substance use among older Swiss adolescents calls for the implementation of effective strategies both from individual and public health viewpoints.