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Biomedical subjects

J Bosch

Publications and source records attributed to J Bosch.

At least 19 recordsLinked to original sources
PubMed2006

Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial.

BACKGROUND: Rosiglitazone is a thiazolidinedione that reduces insulin resistance and might preserve insulin secretion. The aim of this study was to assess prospectively the drug's ability to prevent type 2 diabetes in individuals at high risk of developing the condition. METHODS: 5269 adults aged 30 years or more with impaired fasting glucose or impaired glucose tolerance, or both, and no previous cardiovascular disease were recruited from 191 sites in 21 countries and randomly assigned to receive rosiglitazone (8 mg daily; n=2365) or placebo (2634) and followed for a median of 3 years. The primary outcome was a composite of incident diabetes or death. Analyses were done by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT00095654. FINDINGS: At the end of study, 59 individuals had dropped out from the rosiglitazone group and 46 from the placebo group. 306 (11.6%) individuals given rosiglitazone and 686 (26.0%) given placebo developed the composite primary outcome (hazard ratio 0.40, 95% CI 0.35-0.46; p<0.0001); 1330 (50.5%) individuals in the rosiglitazone group and 798 (30.3%) in the placebo group became normoglycaemic (1.71, 1.57-1.87; p<0.0001). Cardiovascular event rates were much the same in both groups, although 14 (0.5%) participants in the rosiglitazone group and two (0.1%) in the placebo group developed heart failure (p=0.01). INTERPRETATION: Rosiglitazone at 8 mg daily for 3 years substantially reduces incident type 2 diabetes and increases the likelihood of regression to normoglycaemia in adults with impaired fasting glucose or impaired glucose tolerance, or both.

Adult↗
PubMed2006

Thermal history influences diapause development in the solitary bee Megachile rotundata.

Respiration rate, time to pupation and the expression patterns of selected genes were examined during the diapause to post-diapause transition in the alfalfa leafcutting bee, Megachile rotundata held at constant 4 degrees C in winter storage. Respiration quotients were at or below 0.7 from December to May and then increased to over 0.8 in June and July. The time required for prepupae to reach the pupal stage following transfer to 29 degrees C decreased from 23 days in December to 10 days in July. HSP70 was expressed at a consistently high level in all the diapausing prepupae stored at 4 degrees C. In contrast, we demonstrated previously that HSP70 expression in diapausing prepupae maintained under field conditions began decreasing after December and was expressed at trace levels in the June samples. Transferring prepupae stored at 4 to 25 degrees C at monthly intervals from December to July induced a significant decrease in HSP70. Levels of HSC70 showed no changes during the transition to post-diapause development in prepupae maintained at 4 degrees C. Transferring the prepupae to 25 degrees C during the April-June time interval elicited an increase in HSC70 expression. HSP90 was expressed at a consistent level in prepupae stored at 4 degrees C but decreased to very low levels after being transferred to 25 degrees C in December-February prepupae: no decrease was noted in the April-July prepupae. Actin was expressed at trace levels in the diapausing prepupae maintained at 4 degrees C and increased slightly in the post-diapausing pupae. Transferring prepupae stored at 4 to 25 degrees C at monthly intervals from December to July induced an increase in actin expression. These results indicate that the level of gene expression for selected genes in diapausing and post-diapause bees is highly influenced by their thermal history.

Actins↗
PubMed2006

Abdominal aortic aneurysm screening using non-imaging hand-held ultrasound volume scanner--a pilot study.

BACKGROUND: Screening for abdominal aortic aneurysms (AAA) is cost-effective and timely repair improves outcome. Using standard ultrasound (US) an AAA can be accurately diagnosed or ruled-out. However, this requires training and bulk equipment. AIM: To evaluate the diagnostic potential of a new hand-held ultrasound bladder volume indicator (BVI) in the setting of AAA screening. METHODS: In total, 94 patients (66 +/- 14 years, 67 men) referred for atherosclerotic disease were screened for the presence of AAA (diameter > 30 mm using US). All patients underwent both examinations, with US and BVI. Using the BVI, aortic volume was measured at 6 pre-defined points. Maximal diameters (US) and volumes (BVI) were used for analyses. RESULTS: In 54 (57%) patients an AAA was diagnosed using US. The aortic diameter by US correlated closely with aortic volume by BVI (r = 0.87, p < 0.0001). Using a cut-off value of > or = 50 ml for the presence of AAA by BVI, sensitivity, specificity, positive and negative predictive value of BVI in detection of AAA were 94%, 82%, 88% and 92%, respectively. The agreement between the two methods was 89%, kappa 0.78. CONCLUSION: The bladder volume indicator is a promising tool in screening patients for AAA.

Aged↗
PubMed2006

Structure of a ribulose 5-phosphate 3-epimerase from Plasmodium falciparum.

The crystal structure of Pfal009167AAA, a putative ribulose 5-phosphate 3-epimerase (PfalRPE) from Plasmodium falciparum, has been determined to 2 A resolution. RPE represents an exciting potential drug target for developing antimalarials because it is involved in the shikimate and the pentose phosphate pathways. The structure is a classic TIM-barrel fold. A coordinated Zn ion and a bound sulfate ion in the active site of the enzyme allow for a greater understanding of the mechanism of action of this enzyme. This structure is solved in the framework of the Structural Genomics of Pathogenic Protozoa (SGPP) consortium.

Animals↗
PubMed2006

Rationale, design and baseline characteristics of a large, simple, randomized trial of combined folic acid and vitamins B6 and B12 in high-risk patients: the Heart Outcomes Prevention Evaluation (HOPE)-2 trial.

BACKGROUND: Epidemiological studies suggest that mild to moderate elevation in plasma homocysteine concentration is associated with increased risk of atherothrombotic cardiovascular (CV) disease. Simple, inexpensive and nontoxic therapy with folic acid and vitamins B6 and B12 reduces plasma homocysteine levels by approximately 25% to 30% and may reduce CV events. Therefore, a large, randomized clinical trial--the Heart Outcomes Prevention Evaluation (HOPE)-2 study--is being conducted to evaluate this therapy in patients at high risk for CV events. OBJECTIVES: To evaluate whether long-term therapy with folic acid and vitamins B6 and B12 reduces the risk of major CV events in a high-risk population. The primary study outcome is the composite of death from CV causes, myocardial infarction and stroke. METHODS: A total of 5522 patients aged 55 years or older with pre-existing CV disease or with diabetes and additional risk factor(s) at 145 centres in 13 countries were randomly assigned to daily therapy with combined folic acid 2.5 mg, vitamin B6 50 mg and vitamin B12 1 mg, or to placebo. Follow-up will average five years, to be completed by the end of 2005. RESULTS: The patients' baseline characteristics confirmed their high-risk status. Baseline homocysteine levels varied between countries and regions. HOPE-2 is one of the largest trials of folate and vitamins B6 and B12 and is expected to significantly contribute to the evaluation of the role of homocysteine lowering in CV prevention.

Aged↗
PubMed2005

Pathophysiology of portal hypertension in HCV-related cirrhosis. Putative role of assessment of portal pressure gradient in Peginterferon-treated patients.

Chronic HCV infection is the leading aetiologic factor for cirrhosis, end-stage liver disease, hepatocellular carcinoma and liver transplantation worldwide. Pegylation of alfa interferons has improved the management of this disease. Interferon treatment has antifibrotic and immunomodulatory activities. Recent evidence supports the contention that Hepatitis C virus-related cirrhosis of the liver should no more be considered an irreversible disease; fibrosis is a potentially reversible process. Fibrosis and even cirrhosis reversal have been previously demonstrated either in experimental or clinical studies of other liver diseases. Development of portal hypertension is the main drive to the complications of advanced liver diseases: prognosis worsens significantly when portal hypertension becomes clinically significant. It is thus conceivable that within therapeutic trials involving patients with advanced fibrosis of the liver, measurement of the hepatic venous pressure gradient, the gold standard in the clinical assessment of portal hypertension and its management, could provide information on the portal pressure-lowering effects of interferon treatment affecting the fibrosis score. This can be accomplished by either sustained virological response either by fibrosis reduction achieved by chronic low-dose Peginterferon administration. If the introduction of drug therapy with non-selective beta blockers in the treatment of portal hypertension represents a milestone in the treatment of patients with cirrhosis and high-degree portal hypertension, the next step must then be prophylactic reversal of initial portal hypertension prompted by either HCV eradication and pharmacological inhibition of fibrosis progression by long-term Peginterferon before higher degrees of portal hypertension ensue.

Antiviral Agents↗
PubMed2005

Subtyping obsessive-compulsive disorder: clinical and immunological findings in child and adult onset.

It has been suggested that certain kinds of childhood OCD with specific clinical, biological and immunological characteristics may form a subgroup of OCD. We study the presence of these characteristics in child onset OCD and propose that the disorder be considered as a subtype of adult OCD. Forty adult patients with OCD were divided in two groups according to time of disease onset: 18 early onset and 21 late. Both sets were compared with a control group of 14 psychiatric patients. Child onset OCD was associated with higher mean ASLO titers, higher frequencies of history of tic disorders and tonsillitis in childhood and compulsive symptoms. No differences were found in D8/17 antibody titers or in other autoimmune parameters. The findings suggest that child onset OCD can be considered as a subgroup of adult OCD, although more specific biological markers are needed to identify it.

Adolescent↗
PubMed2005

Temporal variation in overwintering gene expression and respiration in the solitary bee Megachile rotundata.

Partial clones of Megachile rotundata HSP90, HSP70, HSC70 and actin were developed by RT-PCR. These clones were used to generate probes to screen for the expression of their respective transcripts in heat-shocked pupae and in diapausing prepupae through post-diapausing pupae. Northern blot analysis revealed transcript sizes for MrHSP90, MrHSP70, MrHSC70, and Mractin of 3.6, 2.3, 2.5, and 1.4kb, respectively. MrHSP90 and MrHSP70 were highly upregulated in post-diapausing pupae exposed to 40 degrees C for 1h, while MrHSC70 was only slightly induced by heat shock. Levels of MrHSC70 and MrHSP90 showed little change between field collected diapausing prepupae and post-diapausing pupae. In contrast, MrHSP70 was highly upregulated in diapausing prepupae and Mractin was at or below the level of detection in diapausing prepupae. Transferring field reared overwintering prepupae in February to 25 degrees C for 3 days induced an expression pattern of MrHSP70 and Mractin more typical of post-diapausing bees, indicating the likelihood that the transition to post-diapause development had occurred prior to February. However, measurements revealed possible cyclic respiration patterns, including low respiratory quotient (RQ) values during February and March and a transition during April to more continuous respiration with elevated RQ values.

Animals↗
PubMed2005

The HOPE (Heart Outcomes Prevention Evaluation) Study and its consequences.

The HOPE study was a 19 country, prospective randomized trial in which the ACE-inhibitor Ramipril but not Vitamin E significantly reduced the risk of future cardiovascular events in a high-risk population of men and women, including many with diabetes. The benefits were present in all sub-groups, independent of the presence or absence of diabetes, hypertension, evidence of cardiovascular disease, microalbuminuria, blood pressure lowering, the use of aspirin, lipid-lowering or antihypertensive medication. It provided clear evidence that Ramipril should safely and cost-effectively be used in individuals not known to have low ventricular ejection fraction or heart failure but at high-risk of cardiovascular events. It was also beneficial in patients with renal insufficiency, reducing progression of proteinuria and development of new microalbuminuria. It provided micro- and macrovascular benefits in people with diabetes, reduced the development of new cases of diabetes and showed a positive and graded association between the waist-to-hip ratio and the risk of developing diabetes. Sub-studies completed and on-going into the predictive role of natriuretic peptides, infectious and inflammatory markers, provide insight into possible mechanisms of action of Ramipril.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2005

Effect of temperature on Osmia lignaria (Hymenoptera: Megachilidae) prepupa-adult development, survival, and emergence.

The solitary bee Osmia lignaria Say continues to be developed as an orchard pollinator in the United States and southern Canada. Female bees are active during the early spring and construct nests consisting of a linear series of unlined cells delimited by mud partitions. Cells are provisioned with a pollen/nectar mass on which an egg is deposited, and nests are sealed with a mud plug. In 1997, we initiated two experiments on the development, mortality, and emergence of O. lignaria at selected laboratory temperature regimes and outdoors. In the first experiment (published previously), we compared temperature treatments for their adequacy in maintaining healthy O. lignaria populations. In a second experiment (reported here), we determined the relationship between rearing temperatures and prepupa-adult development rates as well as emergence time and longevity after wintering and incubation the following spring. We observed important differences in O. lignaria prepupa versus pupa responses to selected temperature treatments. The relationship between temperature and days to pupa was U-shaped, with additional time to transit the prepupa-pupa interval at temperatures above and below 26 degrees C. The negative relationship between temperature and the length of the pupa to adult interval contrasts with the U-shaped thermal response observed for prepupae. Thus, with each increase in thermal heat units over the range of temperature treatments tested, we observed an additional reduction in the pupa-adult interval. Individuals reared at constant 18 degrees C required 2.4 times as many days to transit the pupa-adult interval compared with those at constant 32 degrees C. Our results suggest that there is a need for the development of regionally adapted, latitude-specific breeding populations of this outstanding orchard crop pollinator.

Animals↗
PubMed2005

Serum potassium, cardiovascular risk, and effects of an ACE inhibitor: results of the HOPE study.

BACKGROUND: Both hyper- and hypokalemia increase cardiovascular risk. Modest hyperkalemia is common with angiotensin-converting enzyme inhibition. We studied post-hoc the association of an initial, on-treatment serum potassium measurement with subsequent cardiovascular outcomes over 4.5 years in 9297 individuals at high cardiovascular risk, randomized to an ACE inhibitor or to placebo. METHODS: Post-hoc analysis of cardiovascular outcomes, as related to serum potassium levels, in the HOPE (Heart Outcomes and Prevention Evaluation) study which compared ramipril to placebo, and included 692 patients with a serum potassium level >5.0 mM and 137 with a serum potassium level <3.5 mM, defined as hyper- and hypokalemia, respectively. Serum potassium was measured 1 month after start of randomized treatment. RESULTS: With hyperkalemia, the primary event rate was unchanged compared to normokalemia (15.5 vs 15.7%, p > 0.4, respectively), with hypokalemia, the primary event rate was higher (22.6% vs 15.5%, respectively, p = 0.023). The hazard ratio for the primary outcome associated with this initial hypokalemia was 1.44 (1.00-2.06) on multivariate analysis. The combined primary outcome (myocardial infarction, cardiovascular death, stroke) was not different throughout deciles of serum potassium but the lowest and highest deciles included many with normokalemia. Randomized treatment was withheld because of hyperkalemia in 8 and 6 people allocated to ramipril and placebo, respectively. The benefit of ramipril on cardiovascular outcomes was independent of serum potassium, but ramipril reduced hypokalemia in the entire cohort (1.15 vs 1.86% with placebo, p = 0.005), particularly in those participants on diuretics (3.8% vs 6.5%, p = 0.07). CONCLUSIONS: In patients at high cardiovascular risk, modest hypokalemia predicts a less favorable outcome while modest hyperkalemia does not. Ramipril reduces hypokalemia and decreases risk.

Aged↗
PubMed2004

Rationale, design and recruitment characteristics of a large, simple international trial of diabetes prevention: the DREAM trial.

AIMS/HYPOTHESIS: Diabetes is a rapidly rising independent risk factor for atherosclerosis and serious illness. This risk can be reduced by lifestyle changes and/or various drugs. Novel therapies to prevent diabetes, as well as new risk factors for diabetes, atherosclerosis and obesity require testing and identification. METHODS: People with impaired fasting glucose or impaired glucose tolerance were randomised to ramipril (15 mg/day) or placebo and rosiglitazone (8 mg/day) or placebo with a 2x2 factorial design. They are assessed semi-annually for the primary outcome (diabetes or death). Diabetes is diagnosed if two consecutive plasma glucose levels exceed diagnostic thresholds (i.e. fasting >/=7.0 mmol/l or 2-h >/=11.1 mmol/l) within a 3-month period. Assuming an annual primary outcome incidence of 5%, there is more than 90% power to detect a 22% reduction. Approximately 20% of participants are having annual carotid ultrasounds to assess the effects on atherosclerosis. Patients screened but not randomised are being followed prospectively to identify determinants of obesity, diabetes and related disorders. RESULTS: A total of 24,872 individuals in 21 countries were screened over 2 years and are eligible for follow-up. Of these, 5269 were randomised: 1835 (35%) had isolated impaired glucose tolerance, 739 (14%) had isolated impaired fasting glucose, and 2692 (51%) had both disorders. Annual carotid ultrasounds are currently being performed in 1406 randomised individuals. CONCLUSIONS/INTERPRETATION: The DREAM trial and related studies will determine if ramipril or rosiglitazone reduces the number of cases of diabetes and atherosclerosis, and will identify novel risk factors for diabetes.

Adult↗
PubMed2004

Impact of ramipril in patients with evidence of clinical or subclinical peripheral arterial disease.

AIMS: The aim of this study was to assess the prognostic importance of peripheral arterial disease (PAD) as evaluated by ankle blood pressure index (ABI), and the impact of ramipril on the prevention of major cardiovascular events in PAD patients included in the Heart Outcomes Prevention Evaluation (HOPE) study. METHODS AND RESULTS: Patients were randomized to treatment with ramipril or placebo and followed for 4.5 years. Ankle brachial blood pressure index was measured, mainly by digital palpation of the foot pulse, at baseline in 8986 patients. The ABI was subnormal (< or =0.9) in 3099 patients and normal in 5887 patients. A low ABI was a strong predictor of morbidity and mortality during the follow-up even in patients with no clinical symptoms of PAD (n=6769). This was so for the primary outcome of the study; ABI>0.9:13.1%, 0.6-0.9: 18.2% and <0.6: 18.0% (P<0.0001) and for mortality from all causes: in those with a normal ABI it was 8.5%, in those with ABI >0.6-0.9, 12.4% and 14.2% in those with an ABI lower than 0.6 (P<0.0001). Ramipril reduced the risk of clinical outcomes in those with a clinical history of PAD as well as in the patients with subclinical PAD. CONCLUSIONS: The ABI even if measured simply by palpation of the foot arteries is a strong predictor for future cardiovascular events and for all-cause mortality. Ramipril prevented major cardiovascular events in patients with clinical as well as subclinical PAD.

Aged↗
PubMed2004

fMRI activation maps based on the NN-ARx model.

The most significant progresses in the understanding of human brain functions have been possible due to the use of functional magnetic resonance imaging (fMRI), which when used in combination with other standard neuroimaging techniques (i.e., EEG) provides researchers with a potential tool to elucidate many biophysical principles, established previously by animal comparative studies. However, to date, most of the methods proposed in the literature seeking fMRI signs have been limited to the use of a top-down data analysis approach, thus ignoring a pool of physiological facts. In spite of the important contributions achieved by applying these methods to actual data, there is a disproportionate gap between theoretical models and data-analysis strategies while trying to focus on several new prospects, like for example fMRI/EEG data fusion, causality/connectivity patterns, and nonlinear BOLD signal dynamics. In this paper, we propose a new approach which will allow many of the abovementioned hot topics to be addressed in the near future with an underlying interpretability based on bottom-up modeling. In particular, the theta-MAP presented in the paper to test brain activation corresponds very well with the standardized t test of the SPM99 toolbox. Additionally, a new Impulse Response Function (IRF) has been formulated, directly related to the well-established concept of the hemodynamics response function (HRF). The model uses not only the information contained in the signal but also that in the structure of the background noise to simultaneously estimate the IRF and the autocorrelation function (ACF) by using an autoregressive (AR) model with a filtered Poisson process driving the dynamics. The short-range contributions of voxels within the near-neighborhood are also included, and the potential drift was characterized by a polynomial series. Since our model originated from an immediate extension of the hemodynamics approach [Friston, K.J., Mechelli, A., Turner, R., Price C.J. (2000a). Nonlinear responses in fMRI: the balloon model, volterra kernels, and other hemodynamics. NeuroImage 12, 466-477.], a natural interpretability of the results is feasible.

Algorithms↗
PubMed2004

Review article: the relevance of portal pressure and other risk factors in acute gastro-oesophageal variceal bleeding.

Gastro-oesophageal variceal bleeding is the last step in a chain of events that starts with an increased portal pressure, and is followed by the formation and progressive dilatation of gastro-oesophageal varices. When the tension of the thin wall of the varices exceeds its elastic limit, the varices rupture and bleed. Wall tension is directly proportional to variceal pressure (which is a function of portal pressure) and variceal radius, and inversely related to the thickness of the variceal wall. The above facts explain why a high portal pressure (usually determined by the hepatic venous pressure gradient, or HVPG) and the presence at endoscopy of large varices with red wheals, red spots or diffuse redness on the varices (signalling a reduced wall thickness) correlate with the risk of bleeding.

Bacterial Infections↗
PubMed2003

Acute propranolol administration effectively decreases portal pressure in patients with TIPS dysfunction. Transjugular intrahepatic portosystemic shunt.

BACKGROUND AND AIMS: Up to 60% of patients treated with transjugular intrahepatic portosystemic shunt (TIPS) require angioplasty or restenting during the first year of follow up because of TIPS dysfunction (stenosis of the intrahepatic shunt increasing the portal pressure gradient above the 12 mm Hg threshold). We hypothesised that in patients with TIPS stenosis, propranolol administration, by decreasing portal inflow, would markedly decrease portal pressure. PATIENTS AND METHODS: Eighteen patients with TIPS dysfunction were investigated by measuring portal pressure gradient before and after acute propranolol administration (0.2 mg/kg intravenously; n=18). RESULTS: Propranolol markedly reduced the portal pressure gradient (from 16.6 (3.5) to 11.9 (4.8) mm Hg; p<0.0001), cardiac index (-26 (7)%), and heart rate (-18 (7)%) (p<0.0001). Portal pressure gradient decreased to less than 12 mm Hg in nine patients, more frequently in those with moderate dysfunction (portal pressure gradient 16 mm Hg) than in patients with severe dysfunction (portal pressure gradient >16 mm Hg) (8/10 v 1/8; p=0.015). CONCLUSIONS: Propranolol therapy may delay the increase in portal pressure and reduce the need for reintervention in patients with TIPS dysfunction.

Adult↗
PubMed2003

EEG and behavioral changes following neurofeedback treatment in learning disabled children.

Neurofeedback (NFB) is an operant conditioning procedure, by which the subject learns to control his/her EEG activity. On one hand, Learning Disabled (LD) children have higher values of theta EEG absolute and relative power than normal children, and on the other hand, it has been shown that minimum alpha absolute power is necessary for adequate performance. Ten LD children were selected with higher than normal ratios of theta to alpha absolute power (theta/alpha). The Test Of Variables of Attention (TOVA) was applied. Children were divided into two groups in order to maintain similar IQ values, TOVA values, socioeconomical status, and gender for each group. In the experimental group, NFB was applied in the region with highest ratio, triggering a sound each time the ratio fell below a threshold value. Noncontingent reinforcement was given to the other group. Twenty half-hour sessions were applied, at a rate of 2 per week. At the end of the 20 sessions, TOVA, WISC and EEG were obtained. There was significant improvement in WISC performance in the experimental group that was not observed in the control group. EEG absolute power decreased in delta, theta, alpha and beta bands in the experimental group. Control children only showed a decrease in relative power in the delta band. All changes observed in the experimental group and not observed in the control group indicate better cognitive performance and the presence of greater EEG maturation in the experimental group, which suggests that changes were due not only to development but also to NFB treatment.

Behavior↗