Measles Epidemics Among Children in Vietnam: Genomic Characterization of Virus Responsible for Measles Outbreak in Ho Chi Minh City, 2014.

BACKGROUND: Measles remains poorly controlled in Southeast Asia, including Vietnam. OBJECTIVES: The aim of this study was to characterize genes of virus responsible for a measles outbreak among children in Vietnam in 2014. STUDY DESIGN: Throat swab samples were collected from 122 pediatric patients with suspected measles. Furthermore, peripheral blood mononuclear cells (PBMCs) from 31 of these cases were also collected. Measles virus (MV) RNA was obtained directly from the clinical specimens, amplified by PCR, and then the N and H genes were sequenced. RESULTS: MV RNA was detectable in throat swabs from all 122 patients tested. Positive-strand viral RNA, which indicates the intermediate replicative form of MV, was also detected in PBMCs from all 31 cases from whom these cells were collected. One hundred and eighteen strains with the N gene were obtained by RT-PCR and sequenced. Using phylogenetic analysis with measles reference sequences, all of the Vietnamese strains were found to be genotype D8. However, all strains formed a distinct cluster within the genotype D8 group (D8-VNM) suggesting their own lineage. This distinct cluster was supported by a branch with a 99% bootstrap value and 3.3% nucleotide divergence in the N-450 region of the N gene from the D8 reference strain. Notably, all of the D8-VNM variant strains represented unique amino acid sequences consisting of R442, S451 and G452 in the N-450 region of the N gene. CONCLUSIONS: Measles viruses responsible for outbreaks in Southern Vietnam belonged to a genotype D8 variant group which had unique amino acid sequences in the N gene. Our report provides important genomic information about the virus for measles elimination in Southeast Asia.

Sensor-augmented pump therapy lowers HbA(1c) in suboptimally controlled Type 1 diabetes; a randomized controlled trial.

AIMS: To investigate the efficacy of sensor-augmented pump therapy vs. multiple daily injection therapy in patients with suboptimally controlled Type 1 diabetes. METHODS: In this investigator-initiated multi-centre trial (the Eurythmics Trial) in eight outpatient centres in Europe, we randomized 83 patients with Type 1 diabetes (40 women) currently treated with multiple daily injections, age 18-65 years and HbA(1c) ≥ 8.2% (≥ 66 mmol/mol) to 26 weeks of treatment with either a sensor-augmented insulin pump (n = 44) (Paradigm(®) REAL-Time) or continued with multiple daily injections (n = 39). Change in HbA(1c) between baseline and 26 weeks, sensor-derived endpoints and patient-reported outcomes were assessed. RESULTS: The trial was completed by 43/44 (98%) patients in the sensor-augmented insulin pump group and 35/39 (90%) patients in the multiple daily injections group. Mean HbA(1c) at baseline and at 26 weeks changed from 8.46% (SD 0.95) (69 mmol/mol) to 7.23% (SD 0.65) (56 mmol/mol) in the sensor-augmented insulin pump group and from 8.59% (SD 0.82) (70 mmol/mol) to 8.46% (SD 1.04) (69 mmol/mol) in the multiple daily injections group. Mean difference in change in HbA(1c) after 26 weeks was -1.21% (95% confidence interval -1.52 to -0.90, P < 0.001) in favour of the sensor-augmented insulin pump group. This was achieved without an increase in percentage of time spent in hypoglycaemia: between-group difference 0.0% (95% confidence interval -1.6 to 1.7, P = 0.96). There were four episodes of severe hypoglycaemia in the sensor-augmented insulin pump group and one episode in the multiple daily injections group (P = 0.21). Problem Areas in Diabetes and Diabetes Treatment Satisfaction Questionnaire scores improved in the sensor-augmented insulin pump group. CONCLUSIONS: Sensor augmented pump therapy effectively lowers HbA(1c) in patients with Type 1 diabetes suboptimally controlled with multiple daily injections.

The effect of GH replacement therapy on different fat compartments: a whole-body magnetic resonance imaging study.

OBJECTIVE: Patients with GH deficiency (GHD) are insulin resistant with an increase in visceral fat mass (FM). Whether this holds true when sedentary control subjects (CS) are matched for waist has not been documented. GH replacement therapy (GHRT) results in a decrease in FM. Whether the decrease in FM is mainly related to a reduction in visceral FM remains to be proven. The aim was to separately assess visceral and subcutaneous FM in relation to insulin resistance (IR) in GHD patients before and after GHRT and in sedentary CS. METHODS: Ten patients with GHD were investigated before and 6 months after GHRT. Sedentary CS matched for age, gender, body mass index, and waist were assessed. Exercise capacity was measured as VO(2max) using an incremental work load on a treadmill. Visceral and subcutaneous FM were measured using whole-body magnetic resonance imaging and IR by the homeostasis model assessment of IR (HOMA-IR) index. RESULTS: GHD patients had a non-significantly lower VO(2max) but did not have increased subcutaneous and visceral FM compared with CS. GHRT resulted in a similar relative decrease in subcutaneous and visceral FM. Compared with CS, GHD patients showed a lower HOMA-IR. GHRT tended to increase HOMA-IR. CONCLUSION: Matching for waist and separate assessment of visceral and subcutaneous FM may be critical in the evaluation of body composition and IR in GHD patients before and after GHRT.

Effect of growth hormone (GH) on fasting and postprandial metabolism in GH deficiency.

OBJECTIVE: Hypopituitarism with adult-onset growth hormone deficiency (GHD) is associated with increased cardiovascular morbidity and mortality due to premature and progressive atherosclerosis. An underlying cause of atherosclerosis is increased insulin resistance. Elevated fasting and postprandial glucose and lipid levels may contribute to premature atherosclerosis. We studied effects of growth hormone replacement (GHRT) on fasting and postprandial metabolic parameters as well as on insulin sensitivity in patients with adult-onset GHD. DESIGN: Using a standardized mixed meal, we studied insulin, glucose, non-esterified free fatty acid (NEFA) and triglycerides (TG) concentrations in the fasting state and during a 4 h postprandial period in 15 patients with adult-onset GHD before and after 4 months of GHRT. Identical investigations were performed in healthy matched control subjects. RESULTS: GHD patients before and after GHRT: GHRT did not result in significant changes in fasting glucose, insulin, NEFA and TG concentrations. In the postprandial period GHRT resulted in a non-significant increase in glucose and a decrease in NEFA levels in the presence of unchanged postprandial insulin and TG concentrations. GHD patients vs. control subjects: GHD patients showed similar fasting glucose, insulin and NEFA concentrations, but TG were increased. In the postprandial period GHD patients exhibited similar glucose and TG, but increased insulin and NEFA concentrations. GHRT patients vs. control subjects: Patients after GHRT had similar fasting glucose, insulin and NEFA, but increased TG concentrations. In the postprandial period patients after GHRT had increased glucose and insulin levels in the presence of similar NEFA and TG concentrations. CONCLUSIONS: While impaired insulin action in patients with GHD translates mainly by an impaired fasting TG metabolism, GHRT induced insulin resistance additionally encompasses postprandial glucose metabolism.

Metabolic syndrome and alanine aminotransferase: a global perspective from the NAVIGATOR screening population.

AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with features of the metabolic syndrome (MetS) and may be an expression of the syndrome within the liver. Using screening data from the Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) study (n = 42 149), we examined whether alanine aminotransferase (ALT), a biomarker for NAFLD, clustered with features of MetS and whether the clusters differed across global geographic regions. METHODS: Exploratory factor analysis using principle components analysis was applied to data drawn from the NAVIGATOR screening population (n = 41 111). Demographic data, anthropomorphic measurements and blood pressure (BP) collected during the screening visit, as well as blood samples analysed for ALT, total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, and fasting and 2-h glucose measures after an oral glucose tolerance test were used for our analysis. RESULTS: Two factors, interpreted as lipid (Factor 1), and BP/obesity (Factor 2) were identified, explaining approximately 50% of the variance in the overall population. Similar patterns of aggregation were reproducible across all geographic regions except Asia, where fasting glucose loaded more consistently on Factor 1. ALT loaded with mean arterial pressure, fasting glucose and waist circumference except in Asia, where it loaded only with mean arterial pressure and waist circumference. CONCLUSIONS: ALT aggregated with components of MetS, and the pattern of aggregation of ALT with other features of MetS was similar across regions except Asia, possibly indicating a different pathophysiology for NAFLD in Asia. Predictive models of NAFLD may need to be adjusted for regional and ethnic differences.

A reduction in severe hypoglycaemia in type 1 diabetes in a randomized crossover study of continuous intraperitoneal compared with subcutaneous insulin infusion.

AIM: Continuous intraperitoneal insulin infusion (CIPII) with the DiaPort system using regular insulin was compared to continuous subcutaneous insulin infusion (CSII) using insulin Lispro, to investigate the frequency of hypoglycemia, blood glucose control, quality of life, and safety. METHODS: In this open, randomized, controlled, cross-over, multinational, 12-month study, 60 type 1 diabetic patients with frequent hypoglycemia and/or HbA1c > 7.0% with CSII were randomized to CIPII or CSII. The aim was to obtain the best possible blood glucose while avoiding hypoglycemia. RESULTS: The frequency of any hypoglycemia was similar (CIPII 118.2 (SD 82.6) events / patient year, CSII 115.8 (SD 75.7) p = 0.910). The incidence of severe hypoglycemia with CSII was more than twice the one with CIPII (CIPII 34.8 events / 100 patient years, CSII 86.1, p = 0.013). HbA1c, mean blood glucose, and glucose fluctuations were not statistically different. Treatment-related severe complications occurred mainly during CIPII: port infections (0.47 events / patient year), abdominal pain (0.21 events / patient year), insulin underdelivery (0.14 events / patient year). Weight gain was greater with CSII (+ 1.5 kg vs. - 0.1 kg, p = 0.013), quality of life better with CIPII. CONCLUSIONS: In type 1 diabetes CIPII with DiaPort reduces the number of severe episodes of hypoglycemia and improves quality of life with no weight gain. Because of complications, indications for CIPII must be strictly controlled. CIPII with DiaPort is an alternative therapy when CSII is not fully successful and provides an easy method of intraperitoneal therapy.

[Role of complementary medicine in type 1 diabetes mellitus in two Swiss centres]. / Rolle der Komplementärmedizin bei Diabetes mellitus Typ 1 in zwei Schweizer Zentren.

Insulin replacement is the only effective treatment of type 1 Diabetes mellitus (T1DM). Nevertheless, many complementary treatments are in use for T1DM. In this study we assessed by questionnaire that out of 342 patients with T1DM, 48 (14%; 13.4% adult, 18.5% paediatric; 20 male, 28 female) used complementary medicine (CM) in addition to their insulin therapy. The purpose of the use of CM was to improve general well-being, ameliorate glucose homeostasis, reduce blood glucose levels as well as insulin doses, improve physical fitness, reduce the frequency of hypoglycaemia, and control appetite. The modalities most frequently used are cinnamon, homeopathy, magnesium and special beverages (mainly teas). Thus, good collaboration between health care professionals will allow optimal patient care.

[Optimised glycaemic control and dose titration with insulin glargine (Lantus) by general practitioners in Switzerland: results of the OPTI-LAN Postmarketing Study]. / Optimierung der glykämischen Kontrolle und Dosistitration mit Insulin Glargine (Lantus) durch frei praktizierende Arzte in der Schweiz: Resultate des OPTI-LAN Praxiserfahrungsberichtes.

RATIONALE: National and international societies have published guidelines regarding glycaemic control in type-2 diabetes mellitus. Clinical studies have shown that glycaemic control of type-2 diabetes mellitus can be improved using simple algorithms for titration of insulin Glargine (Lantus). It is unclear, to what degree published guidelines are adopted in daily practice in Switzerland. METHODS: We performed a postmarketing study on the adoption of published guidelines regarding glycaemic control and the use of algorithms for titration of insulin Glargine doses by 77 general practitioners in Switzerland. Data collection was done prospectively over 6 months from September 2005 to September 2007. RESULTS: A total of 317 patients were included with a mean age of 63 +/- 11 years, 137 (43%) were female and 298 (94%) had type-2 diabetes. Average diabetes duration was 8 +/- 6 years. The initial average HbA1C and fasting plasma glucose were 8.9 +/- 1.6% and 10.1 +/- 3.2 mmol/l respectively. This, despite treatment with at least one oral hypoglycaemic agent (83% of patients) and/or insulin (47% of patients). As target the treating physicians chose an HbA1C < or = 7% for 284 patients (90%) and a fasting plasma glucose < or = 7 mmol/l for 245 patients (77%); thresholds that correspond to the guidelines of the Swiss Society of Endocrinology and Diabetes (SSED). The algorithm developed Riddle et al. was used by 33% of treating physicians; whereas 17% of physicians used a schedule proposed by the American Diabetes Association (ADA) and by the European Association for the Study of Diabetes (EASD) that is generally adapted by the patients themselves. During the 6-month treatment with insulin Glargine (Lantus) 196 patients (62%) achieved the SSED guidelines for glycaemic control. On average HbA1C was reduced by 2.1% (8.9 vs. 6.8%) and fasting plasma glucose by 3 mmol/l (10.1 vs. 7.1 mmol/l). On average insulin dose was increased by 14 IU (from 16 to 30 IU). Overall 91% of patients were satisfied with the way insulin doses were adapted. In 64% general wellbeing improved during the treatment period and in 27% it was unchanged. CONCLUSION: In daily practise in Switzerland the recommendations of the SSED are implemented to a high degree. Using insulin Glargine (Lantus) recommended goals of glycaemia can be rapidly and adequately achieved and patient satisfaction can be improved.

Fuel metabolism during exercise in euglycaemia and hyperglycaemia in patients with type 1 diabetes mellitus--a prospective single-blinded randomised crossover trial.

AIMS/HYPOTHESIS: We assessed systemic and local muscle fuel metabolism during aerobic exercise in patients with type 1 diabetes at euglycaemia and hyperglycaemia with identical insulin levels. METHODS: This was a single-blinded randomised crossover study at a university diabetes unit in Switzerland. We studied seven physically active men with type 1 diabetes (mean +/- SEM age 33.5 +/- 2.4 years, diabetes duration 20.1 +/- 3.6 years, HbA1c 6.7 +/- 0.2% and peak oxygen uptake [VO2peak] 50.3 +/- 4.5 ml min(-1) kg(-1)). Men were studied twice while cycling for 120 min at 55 to 60% of VO2peak, with a blood glucose level randomly set either at 5 or 11 mmol/l and identical insulinaemia. The participants were blinded to the glycaemic level; allocation concealment was by opaque, sealed envelopes. Magnetic resonance spectroscopy was used to quantify intramyocellular glycogen and lipids before and after exercise. Indirect calorimetry and measurement of stable isotopes and counter-regulatory hormones complemented the assessment of local and systemic fuel metabolism. RESULTS: The contribution of lipid oxidation to overall energy metabolism was higher in euglycaemia than in hyperglycaemia (49.4 +/- 4.8 vs 30.6 +/- 4.2%; p < 0.05). Carbohydrate oxidation accounted for 48.2 +/- 4.7 and 66.6 +/- 4.2% of total energy expenditure in euglycaemia and hyperglycaemia, respectively (p < 0.05). The level of intramyocellular glycogen before exercise was higher in hyperglycaemia than in euglycaemia (3.4 +/- 0.3 vs 2.7 +/- 0.2 arbitrary units [AU]; p < 0.05). Absolute glycogen consumption tended to be higher in hyperglycaemia than in euglycaemia (1.3 +/- 0.3 vs 0.9 +/- 0.1 AU). Cortisol and growth hormone increased more strongly in euglycaemia than in hyperglycaemia (levels at the end of exercise 634 +/- 52 vs 501 +/- 32 nmol/l and 15.5 +/- 4.5 vs 7.4 +/- 2.0 ng/ml, respectively; p < 0.05). CONCLUSIONS/INTERPRETATION: Substrate oxidation in type 1 diabetic patients performing aerobic exercise in euglycaemia is similar to that in healthy individuals revealing a shift towards lipid oxidation during exercise. In hyperglycaemia fuel metabolism in these patients is dominated by carbohydrate oxidation. Intramyocellular glycogen was not spared in hyperglycaemia.

Activation of electrical triggers of atrial fibrillation in hyperthyroidism.

CONTEXT: A shortening of the atrial refractory period has been considered as the main mechanism for the increased risk of atrial fibrillation in hyperthyroidism. However, other important factors may be involved. OBJECTIVE: Our objective was to determine the activity of abnormal supraventricular electrical depolarizations in response to elevated thyroid hormones in patients without structural heart disease. PATIENTS AND DESIGN: Twenty-eight patients (25 females, three males, mean age 43+/-11 yr) with newly diagnosed and untreated hyperthyroidism were enrolled in a prospective trial after exclusion of heart disease. Patients were followed up for 16 +/- 6 months and studied at baseline and 6 months after normalization of serum TSH levels. MAIN OUTCOME MEASURES: The incidence of abnormal premature supraventricular depolarizations (SVPD) and the number of episodes of supraventricular tachycardia was defined as primary outcome measurements before the start of the study. In addition, heart rate oscillations (turbulence) after premature depolarizations and heart rate variability were compared at baseline and follow-up. RESULTS: SVPDs decreased from 59 +/- 29 to 21 +/- 8 per 24 h (P = 0.003), very early SVPDs (so called P on T) decreased from 36 +/- 24 to 3 +/- 1 per 24 h (P < 0.0001), respectively, and nonsustained supraventricular tachycardias decreased from 22 +/- 11 to 0.5 +/- 0.2 per 24 h (P = 0.01) after normalization of serum thyrotropin levels. The hyperthyroid phase was characterized by an increased heart rate (93 +/- 14 vs. 79 +/- 8 beats/min, P < 0.0001) and a decreased turbulence slope (3.6 vs. 9.2, P = 0.003), consistent with decreased vagal tone. This was confirmed by a significant decrease of heart rate variability. CONCLUSION: Hyperthyroidism is associated with an increased supraventricular ectopic activity in patients with normal hearts. The activation of these arrhythmogenic foci by elevated thyroid hormones may be an important causal link between hyperthyroidism and atrial fibrillation.

QTc interval and resting heart rate as long-term predictors of mortality in type 1 and type 2 diabetes mellitus: a 23-year follow-up.

AIMS/HYPOTHESIS: We evaluated the association of QT interval corrected for heart rate (QT(c)) and resting heart rate (rHR) with mortality (all-causes, cardiovascular, cardiac, and ischaemic heart disease) in subjects with type 1 and type 2 diabetes. METHODS: We followed 523 diabetic patients (221 with type 1 diabetes, 302 with type 2 diabetes) who were recruited between 1974 and 1977 in Switzerland for the WHO Multinational Study of Vascular Disease in Diabetes. Duration of follow-up was 22.6 +/- 0.6 years. Causes of death were obtained from death certificates, hospital records, post-mortem reports, and additional information given by treating physicians. RESULTS: In subjects with type 1 diabetes QT(c), but not rHR, was associated with an increased risk of: (1) all-cause mortality (hazard ratio [HR] 1.10 per 10 ms increase in QT(c), 95% CI 1.02-1.20, p = 0.011); (2) mortality due to cardiovascular (HR 1.15, 1.02-1.31, p = 0.024); and (3) mortality due to cardiac disease (HR 1.19, 1.03-1.36, p = 0.016). Findings for subjects with type 2 diabetes were different: rHR, but not QT(c) was associated with mortality due to: (1) all causes (HR 1.31 per 10 beats per min, 95% CI 1.15-1.50, p < 0.001); (2) cardiovascular disease (HR 1.43, 1.18-1.73, p < 0.001); (3) cardiac disease (HR 1.45, 1.19-1.76, p < 0.001); and (4) ischaemic heart disease (HR 1.52, 1.21-1.90, p < 0.001). Effect modification of QT(c) by type 1 and rHR by type 2 diabetes was statistically significant (p < 0.05 for all terms of interaction). CONCLUSIONS/INTERPRETATION: QT(c) is associated with long-term mortality in subjects with type 1 diabetes, whereas rHR is related to increased mortality risk in subjects with type 2 diabetes.

[Long-term follow up after antithyroid drug treatment in Graves' disease]. / Langzeitverlauf nach thyreostatischer Therapie bei Basedow-Hyperthyreose.

BACKGROUND AND OBJECTIVE: In Europe antithyroid drug (ATD) therapy is the preferred initial treatment for patients with a first episode of Graves' disease. Results of long-term recurrence rates following ATD therapy are conflicting. The main goal was to assess long-term recurrence rate after ATD treatment. Secondarily we tried to verify chemical and clinical findings (thyrotropin receptor antibodies (TRAb), duration of primary treatment, age and goitre size) as predictive factors. PATIENTS AND METHODS: Records of 94 patients with a first episode of Graves' disease (1990-1995) treated by ATD were retrospectively analyzed. 18 patients were lost for follow up investigations, the remaining 76 (65 women, 11 men, age 16-76 years) patients were followed for 99 (+/- 22) months (mean +/- SD). To verify the predictive factors a logistic regression analysis was done. RESULTS: Among the 76 patients 16 underwent near-total resection (n = 5) or radioiodine therapy (n = 11) after initial ATD treatment. Sixty patients were treated during 19 +/- 16 months (mean +/- SD) with ATDs and were euthyroid when treatment was stopped. Thirteen of the 60 patients (21.7%) remained in remission after discontinuation of ATD therapy, in 42 patients (70%) hyperthyroidism recurred, in four patients (6.7%) ATD could not be stopped, one patient (1.7%) had a persistent hypothyroidism after discontinuation of ATD. Relapse rate was inversely correlated with duration of primary ATD treatment (p < 0.05), but not with TRAb titer at the time of diagnosis nor at the time of ATD discontinuation. Also, no correlation could be noticed with goitre size at the time of diagnosis. An inverse correlation of the age at the time of diagnosis with relapse rate was of only borderline significance (p = 0.055). CONCLUSIONS: Initial successful treatment with ATD is followed by a high recurrence rate in our population. Two possible negative predictors of relapse are short duration of primary ATD treatment and young age at the time of diagnosis. TRAb titer at the time of diagnosis or at the time of ATD discontinuation and goitre size seem to have no influence on the outcome.

Apolipoprotein B as a long-term predictor of mortality in type 1 diabetes mellitus: a 15-year follow up.

OBJECTIVES: To evaluate the association of apolipoprotein B (apo B) with mortality due to all causes, to cardiac disease and to ischaemic heart disease (IHD) in subjects with type 1 diabetes mellitus. SUBJECTS: 165 subjects with type 1 diabetes included in the Swiss Cohort of the WHO Multinational Study of Vascular Disease in Diabetes were followed for 14.7+/-0.45 years. METHODS: Causes of death were obtained from death certificates, hospital records and postmortem reports. Using a parametric proportional hazards model the association of apo B with mortality rates was assessed by time-to-event analysis, including the absolute cumulative mortality risk over time for various apo B levels at baseline. RESULTS: Apo B was positively associated with all-cause mortality [hazard ratio (HR) 2.65 per g L-1 increase of apo B, 95% CI: 1.11-6.36, P=0.029], cardiac mortality (HR 11.64, 1.03-131.11, P=0.047) and IHD mortality (HR 9.36, 1.26-69.66, P=0.029). An apo B>or=0.96 g L-1 translated into a duplication of overall mortality hazard (HR 1.93, 1.00-3.72, P=0.050), and a sevenfold increase of mortality because of cardiac disease or IHD (HR 7.44, 1.44-38.42, P=0.017 and HR 7.38, 0.78-69.82, P=0.081). A baseline apo B of 1.5 g L-1 predicted an absolute cumulative risk to die over the next 10 years of 12.1% (5.2-31.7) for male and of 10.4% (4.7-26.1) for female subjects whereas risks were 6.3% (1.8-21.4) and 5.4% (0.8-15.8) for an apo B of 0.8 g L-1. CONCLUSION: Apo B is consistently associated with an increased mortality in type 1 diabetes.

Efficacy of drug eluting stents in patients with and without diabetes mellitus: indirect comparison of controlled trials.

OBJECTIVE: To examine whether polymer based coronary stents eluting sirolimus or paclitaxel are equally effective in patients with and without diabetes. METHODS: Systematic review and meta-analysis by indirect comparison of randomised controlled trials comparing stents eluting sirolimus or paclitaxel with conventional bare metal stents. The overall study population and patients with and without diabetes were analysed separately by using the ratio of incidence rate ratios (RIRR). RESULTS: The analysis was based on 10 trials (six with sirolimus, four with paclitaxel), 4513 patients (1146 patients with diabetes), 5755 years of follow up, and 2464 events. In patients without diabetes sirolimus eluting stents were superior to paclitaxel eluting stents with respect to in-stent (RIRR 0.21, 95% confidence interval (CI) 0.10 to 0.48, p < 0.001) and in-segment restenosis (RIRR 0.47, 95% CI 0.24 to 0.92, p = 0.027), target lesion revascularisation (RIRR 0.54, 95% CI 0.30 to 0.99, p = 0.045), and major adverse cardiac events (RIRR 0.46, 95% CI 0.26 to 0.83, p = 0.010). In patients with diabetes the two drug eluting stents did not differ significantly in any of these end points. Meta-regression analysis showed a significant difference between patients with and without diabetes (tests for interaction for in-stent and in-segment restenosis, p = 0.036 and p = 0.016). CONCLUSION: Indirect evidence indicates that sirolimus eluting stents are superior to paclitaxel eluting stents in patients without diabetes but not in patients with diabetes.

[Endogenous hypercortisolism and immunologically-mediated disease: three cases]. / Endogener Hypercortisolismus und immunologisch vermittelte Erkrankungen: drei Fälle.

HISTORY AND CLINICAL FINDINGS: We report three women with hypercortisolism presenting with symptoms and signs of Cushing's syndrome. In two of the patients, initial symptoms of hypercortisolism were associated with spontaneous amelioration of previously known atopic dermatitis and psoriasis, respectively. DIAGNOSTIC PROCEDURES: Diagnosis was established by demonstrating both lack of responsiveness to dexamethasone (1mg) suppression test and increased 24-hour urine cortisol secretion. One patient had a low serum ACTH level indicating Cushing's syndrome of adrenal origin. In the other two patients hypercortisolism proved to be ACTH-dependent, the source being the pituitary, as demonstrated by CRH stimulation test (elevation of ACTH and cortisol by 35 % and 20 %, respectively) and sampling of the petrosus sinus. In both patients imaging confirmed the presence of a pituitary adenoma. TREATMENT AND COURSE: All three patients underwent successful surgery: the first patient had an adrenalectomy, the other two transseptal transsphenoidal hypophysectomy. As symptoms and signs of hypercortisolism improved, the previously quiescent signs of atopic dermatitis and psoriasis recurred and one patient developed Graves' disease. CONCLUSIONS: Following successful treatment of endogenous hypercortisolism, symptoms of unrelated immunologically mediated conditions, especially autoimmune thyroiditis, may occasionally appear. Furthermore, the clinical course of coexisting immunologically mediated diseases may help to diagnose Cushing's syndrome and to monitor the patients after surgical treatment.

Sitosterolaemia in Switzerland: molecular genetics links the US Amish-Mennonites to their European roots.

Sitosterolaemia is a rare autosomal recessive disease characterized by increased intestinal absorption of plant sterols, decreased hepatic excretion into bile and elevated concentrations in plasma phytosterols. Homozygous or compound heterozygous loss of function mutations in either of the ATP-binding cassette (ABC) proteins ABCG5 and ABCG8 explain the increased absorption of plant sterols. Here we report a Swiss index patient with sitosterolaemia, who presented with the classical symptoms of xanthomas, but also had mitral and aortic valvular heart disease. Her management over the last 20 years included a novel therapeutic approach of high-dose cholesterol feeding that was semi-effective. Mutational and extended haplotype analyses showed that our patient shared this haplotype with that of the Amish-Mennonite sitosterolaemia patients, indicating they are related ancestrally.

Treatment outcomes and mortality of 94 patients with acromegaly.

BACKGROUND: Due to new therapeutic modalities and modified therapeutic goals outcome of patients with acromegaly may change over time and differ by centre. We analysed treatment outcomes and mortality of our patients with acromegaly seen between 1971 and 2003. METHOD: The cohort consisted of 94 patients who had been followed for 0.3-31 years (mean 10.6 years). Remission criteria were a normalized IGF-I concentration, a nadir GH level during oral glucose load of <1.0 microg/l and a random GH value of <2.5 microg/l. FINDINGS: Transsphenoidal surgery achieved remission in 80% of patients with micro-adenomas (<1 cm), 65% with meso-adenomas (> or = 1 cm to <2 cm) and 27% with macro-adenomas (> or = 2 cm). Patients with meso-adenomas operated on after 1995 tended to have a better outcome compared to those operated on before 1995 (Remission in 83% vs. 38%). Radiotherapy resulted in disease control in 22 of 47 patients (47%). Intramuscular depot formulation of octreotide (Sandostatin LAR) led to disease control in 17 of 26 patients (65%). After multimodal therapy persistent acromegalic activity remained in 18% of the patients; only one of them had an adenoma of <2 cm. The standardized mortality ratio was 1.30 (95% CI 0.52-2.67) for patients in remission and 1.38 (95% CI 0.51-3.00) for patients with persistent acromegalic activity. CONCLUSIONS. Most patients with adenomas of <2 cm can be expected to achieve remission by transsphenoidal surgery alone. Furthermore, virtually all patients with adenomas of <2 cm and more than 80% of patients with adenomas of > or = 2 cm can be expected to achieve remission by adjuvant treatment. Aggressive multimodal therapy is critical in the management of acromegaly reducing mortality risk close to that of the general population.

Quality of life and coping behaviour in Type 1 diabetes mellitus: relationship with metabolic control.

Uncovering factors possibly leading to insufficient metabolic control in Type 1 diabetes, both on the part of the patient or the treating physician, is of considerable relevance. The present long-term study investigated the relevance of patient-related vs education-related factors for the success in achieving acceptable glycaemic control. Adolescents or young adults with Type 1 diabetes mellitus (n= 26, mean age= 22+/-2 yr, diabetes duration= 11+/-5 yr) were followed during 36+/-5 months. All patients were treated by the same diabetologist. At the beginning of the study coping behaviour, quality of life and evaluation of emotional status were assessed. Changes in HbA1c were used as a parameter of glycaemic control. At follow-up there was a significant decrease in HbA1c of 0.4% (p<0.01). However, this was not in statistically significant correlation with age, gender, aspects of quality of life or coping behaviour. Therefore, glycaemic control and/or improvement of glycaemic control in adolescents or young adults with Type 1 diabetes mellitus seems to be primarily related to other factors, eg continuous education provided in a stable setting.