A randomised Phase II trial to evaluate the toxicity of high-dose rifampicin to treat pulmonary tuberculosis.

Setting: Randomised Phase IIB clinical trial.

Objectives: To assess whether increasing the dose of rifampicin (RMP) from 10 mg/kg to 15 or 20 mg/kg results in an increase in grade 3 or 4 hepatic adverse events and/or serious adverse events (SAE).

Methods: Three hundred human immunodeficiency virus negative patients with newly diagnosed microscopy-positive pulmonary tuberculosis (TB) were randomly assigned to one of three regimens: 1) the control regimen (R10), comprising daily ethambutol (EMB), isoniazid (INH), RMP and pyrazinamide for 8 weeks, followed by INH and RMP daily for 18 weeks; 2) Study Regimen 1 (R15), as above, with the RMP dose increased to 15 mg/kg body weight daily for the first 16 weeks; and 3) Study Regimen 2 (R20), as above, with RMP increased to 20 mg/kg.

Clinical usefulness, angiographic characteristics, and safety evaluation of intracoronary acetylcholine provocation testing among 921 consecutive white patients with unobstructed coronary arteries.

Background: Coronary spasm can cause myocardial ischemia and angina in patients with and those without obstructive coronary artery disease. However, provocation tests using intracoronary acetylcholine administration are rarely performed in clinical routine in the United States and Europe. Thus, we assessed the clinical usefulness, angiographic characteristics, and safety of intracoronary acetylcholine provocation testing in white patients with unobstructed coronary arteries.

A published pharmacogenetic algorithm was poorly predictive of tacrolimus clearance in an independent cohort of renal transplant recipients.

Aims: An algorithm based on the CYP3A5 genotype to predict tacrolimus clearance to inform the optimal initial dose was derived using data from the DeKAF study (Passey et al. Br J Clin Pharmacol 2011; 72: 948-57) but was not tested in an independent cohort of patients. Our aim was to test whether the DeKAF dosing algorithm could predict estimated tacrolimus clearance in renal transplant recipients at our centre.

High prevalence of a pathological response to acetylcholine testing in patients with stable angina pectoris and unobstructed coronary arteries. The ACOVA Study (Abnormal COronary VAsomotion in patients with stable angina and unobstructed coronary arteries).

Objectives: This study aimed at determining the prevalence of epicardial and microvascular coronary spasm in patients with anginal symptoms, despite angiographically normal coronary arteries.

Background: Despite a typical clinical presentation with exercise-related anginal symptoms (chest pain or dyspnea) with or without occasional attacks of resting chest pain suggestive of coronary artery disease, 40% of patients undergoing diagnostic angiography have normal or "near" normal coronary arteriograms. Many of these patients are given a diagnosis of noncardiac chest pain, and some are considered to have microvascular angina.

Vitamin C intake from diary recordings and risk of breast cancer in the UK Dietary Cohort Consortium.

Background/objectives: Vitamin C intake has been inversely associated with breast cancer risk in case-control studies, but not in meta-analyses of cohort studies using Food Frequency Questionnaires, which can over-report fruit and vegetable intake, the main source of vitamin C. This is the first study to investigate associations between vitamin C intake and breast cancer risk using food diaries.

Subjects/methods: Estimated dietary vitamin C intake was derived from 4-7 day food diaries pooled from five prospective studies in the UK Dietary Cohort Consortium.

Dietary fat and breast cancer: comparison of results from food diaries and food-frequency questionnaires in the UK Dietary Cohort Consortium.

Background: Epidemiologic studies of dietary fat and breast cancer risk are inconsistent, and it has been suggested that a true relation may have been obscured by the imprecise measurement of fat intake.

Objective: We examined associations of fat with breast cancer risk by using estimates of fat intake from food diaries and food-frequency questionnaires (FFQs) pooled from 4 prospective studies in the United Kingdom.

Design: A total of 657 cases of breast cancer in premenopausal and postmenopausal women were matched on study, age, and recruitment date with 1911 control subjects.

Validation of echocardiographic left atrial parameters in atrial fibrillation using the index beat of preceding cardiac cycles of equal duration.

Background: The clinical assessment of left atrial function during atrial fibrillation is challenging and often inaccurate because of the beat-to-beat variability in the cycle length. The aim of this study was to validate the use of an index beat, the beat following two preceding cardiac cycles of equal duration, for the measurement of left atrial functional indices, including area, volume, and expansion index. The index beat was compared with the conventional but time-consuming method of averaging multiple consecutive cardiac cycles.

Usefulness of pericardial effusion as new diagnostic criterion for noninvasive detection of myocarditis.

Cardiovascular magnetic resonance (CMR) imaging holds promise for diagnosing myocarditis in vivo. The CMR diagnosis of myocarditis is determined by the ventricular morphology/function, late gadolinium enhancement, and T(2)-weighted imaging for myocardial edema. However, in routine clinical practice, we encounter patients with suspected myocarditis in the absence of left ventricular dysfunction, myocardial edema, or late gadolinium enhancement.

3-year follow-up of patients with coronary artery spasm as cause of acute coronary syndrome: the CASPAR (coronary artery spasm in patients with acute coronary syndrome) study follow-up.

Objectives: We sought to determine the prognosis of patients with acute coronary syndrome without culprit lesion and proof of coronary spasm during 3 years of follow-up.

Background: Coronary artery spasm has been identified as an alternative cause for acute coronary syndrome (ACS) in patients without culprit lesion. In the CASPAR (Coronary Artery Spasm as a Frequent Cause for Acute Coronary Syndrome) study, we recently showed that ∼50% of ACS patients without culprit lesion, in whom intracoronary acetylcholine provocation was performed, had coronary spasm.

Red cell distribution width in heart failure: prediction of clinical events and relationship with markers of ineffective erythropoiesis, inflammation, renal function, and nutritional state.

Objectives: The goal of this study was to independently validate the recent observations on the predictive role of red cell distribution width (RDW) for outcomes in chronic heart failure and to provide epidemiologic data on the biological correlates of RDW in heart failure (HF). Understanding the mechanism underlying this observation is unclear, largely hampered by the lack of epidemiologic studies demonstrating factors that are associated with anisocytosis in cardiovascular diseases.

Methods: One hundred ninety-five patients (145 men, 50 women) with systolic HF were enrolled and followed up for a median of 14.

Central corneal thickness measurements with optical coherence tomography and ultrasound pachymetry in healthy subjects and in patients after photorefractive keratectomy.

Purpose: To compare central corneal thickness measurements made using two different methods, optical coherence tomography (OCT) and ultrasound pachymetry, applied both in normal eyes and in eyes on which photorefractive keratectomy (PRK) had been performed. A second objective was to assess the intrasession variability of OCT measurements.

Methods: In this prospective study, central corneal thickness was measured in 20 normal subjects (normal group) and in 20 PRK patients using the StratusOCT instrument model 3000 (Carl Zeiss Meditec), and also with an ultrasound pachymeter.

Acute rejection modulates gene expression in the collecting duct.

Kidney transplantation, especially when associated with acute rejection, leads to changes in the expression of many genes, including those encoding solute transporters and water channels. In a rat model of acute rejection after allogeneic renal transplantation, impaired renal function, increased urine volume, and increased fractional excretion of sodium were observed. Gene array analysis revealed that these findings were associated with significant downregulation of water channels (aquaporin-1, -2, -3, and -4) and transporters of sodium, glucose, urea, and other solutes.

Gene expression profiling in Paget's disease of bone: upregulation of interferon signaling pathways in pagetic monocytes and lymphocytes.

Unlabelled: We examined the gene expression profile of genes involved in bone metabolism in 23 patients with PD compared with 23 healthy controls. We found a significant overexpression of the genes of the IFN pathway along with a downregulation of tnf-alpha. Our result suggest that IFN-mediated signaling may play important roles in aberrant osteoclastogenesis of PD.

Overrepresentation of the N363S variant of the glucocorticoid receptor gene in patients with bilateral adrenal incidentalomas.

Context: Some variants of the glucocorticoid receptor (GR) gene have been found to alter glucocorticoid sensitivity and have been associated with altered metabolic profiles.

Objective: The objective of the study was to examine whether N363S and ER22/23K variants of the GR gene may be associated with the development of adrenal incidentalomas and whether these variants may contribute to metabolic abnormalities frequently present in these patients.

Design, Setting, And Patients: The study included 99 patients with unilateral and 44 patients with bilateral adrenal incidentalomas, 102 population-matched control subjects, and 100 patients with type 2 diabetes mellitus.

Childhood leukaemia incidence in Hungary, 1973-2002. Interpolation model for analysing the possible effects of the Chernobyl accident.

The incidence of childhood leukaemia in Hungary has yet to be reported, although data are available since the early 70s. The Hungarian data therefore cover the time before and after the Chernobyl nuclear accident (1986). The aim of this study was to assess the effects of the Chernobyl accident on childhood leukaemia incidence in Hungary.

Fermented Wheat Germ Extract Reduces Chemotherapy-Induced Febrile Neutropenia in Pediatric Cancer Patients.

Purpose: An open-label, matched-pair (by diagnosis, stage of disease, age, and gender) pilot clinical trial was conducted to test whether the combined administration of the medical nutriment MSC (Avemar) with cytotoxic drugs and the continued administration of MSC on its own help to reduce the incidence of treatment-related febrile neutropenia in children with solid cancers compared with the same treatments without MSC.

Methods: Between December 1998 and May 2002, 22 patients (11 pairs) were enrolled in this study. At baseline, the staging of the tumors was the same in each pair (mostly pTNM = T2N0M0), with the exception of two cases in which patients in the MSC group had worse prognoses (metastasis at baseline).

Fermented wheat germ extract reduces chemotherapy-induced febrile neutropenia in pediatric cancer patients.

Purpose: An open-label, matched-pair (by diagnosis, stage of disease, age, and gender) pilot clinical trial was conducted to test whether the combined administration of the medical nutriment MSC (Avemar) with cytotoxic drugs and the continued administration of MSC on its own help to reduce the incidence of treatment-related febrile neutropenia in children with solid cancers compared with the same treatments without MSC.

Methods: Between December 1998 and May 2002, 22 patients (11 pairs) were enrolled in this study. At baseline, the staging of the tumors was the same in each pair (mostly pTNM = T2N0M0), with the exception of two cases in which patients in the MSC group had worse prognoses (metastasis at baseline).

Exclusion and inclusion of alpha and beta T cell receptor alleles.

Exclusion and inclusion of T cell receptor (TCR) genes were analyzed in alpha beta TCR transgenic mice. Both transgenes are expressed unusually early on the surface of CD4-8-, HSA+, IL-2R- thymocytes. These progenitor cells give rise to progeny, which at the single-cell level contains endogenous alpha but not beta TCR-RNA as well as protein, in addition to products encoded by the transgenes.

Development of the CD4 and CD8 lineage of T cells: instruction versus selection.

T cells bearing the alpha beta T cell receptor (TCR) can be divided into CD4+8- and CD4-8+ subsets which develop in the thymus from CD4+8+ precursors. The commitment to the CD4 and CD8 lineage depends on the binding of the alpha beta TCR to thymic major histocompatibility complex (MHC) coded class II and class I molecules, respectively. In an instructive model of lineage commitment, the binding of the alpha beta TCR, for instance to class I MHC molecules, would generate a specific signal instructing the CD4+8+ precursors to switch off the expression of the CD4 gene.

Surface expression of the beta T cell receptor (TCR) chain in the absence of other TCR or CD3 proteins on immature T cells.

T cell receptor (TCR) beta genes are rearranged prior to TCR alpha genes. A productively rearranged TCR beta gene suppresses further V beta gene rearrangement. Here we show that in beta TCR transgenic mice the TCR beta-chain can be expressed on the surface of immature CD4-8- thymocytes, but not on mature T cells, in the absence of any other known TCR chain and proteins of the CD3 complex.

In transgenic mice the introduced functional T cell receptor beta gene prevents expression of endogenous beta genes.

Transgenic mice were constructed with a functional T cell receptor beta gene. Transcription of the introduced gene is largely confined to T cells, but low levels of transcripts are also seen in B cells and in other tissues. Serological analyses show that most, if not all, of the T lymphocytes express the transgenic beta chain on the cell surface and lack beta chains encoded by endogenous beta genes.