Leukocyte Interferon-alpha in the Treatment of Chronic Hepatitis C in Finland

Background: Food intake, accompanied by systemic and splanchnic haemodynamic changes, has only been studied in males. The extent to which splanchnic postprandial hyperaemia shows gender differences is unknown. Methods: We tested 1) the splanchnic hyperaemic response to food in females and 2) whether postprandial haemodynamic changes show gender differences. Twenty-four healthy women (aged 20-35 years) and 20 healthy men (aged 21-34 years) participated in the study. A liquid test meal (Ensure plus, 1.5 kcal/ml) was perfused intraduodenally for 75 min through an enteral feeding tube at a rate of 3 ml/min after a 45-min basal period. Blood flow parameters were measured using Echo-Doppler technology. Results: Basal diastolic arterial blood pressure was significantly (P     

Infantile chronic idiopathic intestinal pseudo-obstruction: the role of small intestinal manometry as a diagnostic tool and prognostic indicator.

BACKGROUND: Chronic idiopathic intestinal pseudo-obstruction (CIIP) presenting in infancy is a rare but serious condition of heterogeneous aetiology often with an uncertain outcome. AIM: To assess whether intestinal manometry in the first two years of life can help define a neuropathic or myopathic aetiology or clinical outcome, or both, in cases of infantile CIIP. SUBJECTS AND METHODS: 14 consecutive children who presented in the first year of life with CIIP were studied histologically and by small intestinal manometry. RESULTS: Five had a myopathic disorder, four were neuropathic, and five unclassified following histological investigation of full thickness intestinal biopsy specimens. Analysis of fasting phase III activity showed four patterns: (1) (n = 4) no detectable motor activity, (2) (n = 5) low amplitude phase III activity, (3) (n = 3) poorly formed phase III complexes of short duration, (4) (n = 2) well formed cyclical phase III activity with abnormal propagation. The seven children with low amplitude phase III: motility index (MI) < 10 KPa/min, all had a poor outcome (death or dependence on parenteral nutrition) after 1-10 years follow up, compared with two of seven of those with a MI > 10 KPa/min. Of the five with myopathic histology, four had a MI < 10 KPa/min. CONCLUSION: These results show that small intestinal manometry is useful not only as an aid in diagnosing the aetiology of CIIP presenting in infancy, but also in predicting outcome.     

Small intestinal absorption of amino acids and a dipeptide in pancreatic insufficiency.

In this study a perfusion technique has been used to investigate in vivo jejunal absorption and transmural potential difference evoked by the neutral amino acids phenylalanine (56 or 20 mmol/l) and glycine (20 mmol/l), the dibasic amino acid lysine (56 or 5 mmol/l), and a dipeptide glycyl-l-phenylalanine (20 mmol/l) in 11 children with pancreatic insufficiency due to cystic fibrosis and in three children with other causes of exocrine pancreatic insufficiency. Net absorption and potential difference evoked by phenylalanine in both cystic fibrosis and pancreatic insufficiency, and net absorption of glycine in cystic fibrosis were significantly reduced; but the absorption of lysine and glycyl-l-phenylalanine was normal. Absorption of the constituent amino acids from the dipeptide was normal or increased in cystic fibrosis. Thus, these studies show a defect in active absorption of neutral amino acids in cystic fibrosis with pancreatic insufficiency and exocrine pancreatic insufficiency. We speculate that pancreatic factors participate in neutral amino acid absorption.     

Disordered small intestinal motility: a rational basis for toddlers'' diarrhoea

Toddler diarrhoea is the commonest cause of chronic diarrhoea without failure to thrive in childhood, but its pathogenesis remains obscure. We have studied upper small intestinal motility in three groups of children (control group 1 - children with no intestinal pathology undergoing duodenal intubation, n = 6; control group 2 - children with gastrointestinal pathology other than toddler diarrhoea, n = 11; control group 3 - children with toddler diarrhoea, n = 8). We studied fasting motor patterns and the response of the migrating motor complex to intravenous cholecystokinin and an intraduodenal bolus of 5% dextrose. The characteristics of the migrating motor complex in the three groups did not differ but their response to dextrose did. Intraduodenal dextrose disrupted the migrating motor complex in four out of four children in group 1; seven out of nine children in group 2; and nil of eight children with toddler diarrhoea in group 3. We suggest that this failure of intestinal motor response may play a major role in the pathogenesis of the diarrhoea in this condition.     

Repeated adeno-associated virus serotype 2 aerosol-mediated cystic fibrosis transmembrane regulator gene transfer to the lungs of patients with cystic fibrosis: a multicenter, double-blind, placebo-controlled trial

STUDY OBJECTIVES: The primary objective was to determine the safety and tolerability of repeated doses of aerosolized adeno-associated serotype 2 vector containing cystic fibrosis transmembrane conductance regulator (CFTR) complementary DNA (cDNA) [tgAAVCF], an adeno-associated virus (AAV) vector encoding the complete human CFTR cDNA. Secondary objectives included evaluation of pulmonary function assessed by spirometry, lung abnormalities by high-resolution CT (HRCT), airway cytokines, vector shedding, serum neutralizing antibody to AAV serotype 2 (AAV2), and gene transfer and expression in a subset of subjects undergoing bronchoscopy with bronchial brushings. DESIGN: Randomized, double-blind, placebo-controlled, phase II trial. SETTING: Eight cystic fibrosis (CF) centers in the United States. SUBJECTS: CF patients with mild lung disease, defined as FEV(1) > or =60% predicted. INTERVENTIONS: Subjects were randomized to inhale three aerosolized doses of 1 x 10(13) deoxyribonuclease-resistant particles of tgAAVCF or matching placebo at 30-day intervals using the Pari LC Plus nebulizer (PARI; Richmond, VA). Measurements and results: Of 42 subjects randomized, 20 subjects received at least one dose of tgAAVCF and 17 subjects received placebo. No difference in the pattern of adverse events or laboratory abnormalities was noted between the two treatment groups. Improvements in induced-sputum interleukin-8 (p = 0.03) and FEV(1) (p = 0.04) were observed at day 14 and day 30, respectively, in the group receiving tgAAVCF when compared to those receiving placebo. No significant differences in HRCT scans were noted. Vector shedding in sputum was observed at low levels up to 90 days after the third dose of vector. All subjects receiving tgAAVCF exhibited an increase (by at least fourfold) in serum AAV2-neutralizing antibodies and detectable levels in BAL fluid from five of six treated subjects undergoing BAL. Gene transfer but not gene expression was detected in a subset of six tgAAVCF subjects who underwent bronchoscopy. CONCLUSIONS: Repeat doses of aerosolized tgAAVCF were safe and well tolerated, and resulted in encouraging trends in improvement in pulmonary function in patients with CF and mild lung disease.     

Gene delivery of human apolipoprotein E alters brain Abeta burden in a mouse model of Alzheimer's disease

Apolipoprotein E (apoE) alleles are important genetic risk factors for Alzheimer's disease (AD), with the epsilon4 allele increasing and the epsilon2 allele decreasing risk for developing AD. ApoE has been shown to influence brain amyloid-beta peptide (Abeta) and amyloid burden, both in humans and in transgenic mice. Here we show that direct intracerebral administration of lentiviral vectors expressing the three common human apoE isoforms differentially alters hippocampal Abeta and amyloid burden in the PDAPP mouse model of AD. Expression of apoE4 in the absence of mouse apoE increases hippocampal Abeta(1-42) levels and amyloid burden. By contrast, expression of apoE2, even in the presence of mouse apoE, markedly reduces hippocampal Abeta burden. Our data demonstrate rapid apoE isoform-dependent effects on brain Abeta burden in a mouse model of AD. Gene delivery of apoE2 may prevent or reduce brain Abeta burden and the subsequent development of neuritic plaques.     

Endothelial nitric oxide synthase gene Glu298Asp polymorphism and blood pressure, left ventricular mass and carotid artery atherosclerosis in a population-based cohort

OBJECTIVE: Decreased production of endothelial nitric oxide (NO) is associated with different cardiovascular pathology. We studied the association between the Glu298Asp polymorphism of the NO producing gene, endothelial nitric oxide synthase (eNOS), and hypertension, left ventricular mass (LVM) and carotid artery intima-media thickness (IMT) in a population-based cohort of hypertensive and control subjects. DESIGN: Cross-sectional case-control study. SETTING: District around Oulu University Hospital, Northern Finland. SUBJECTS AND METHODS: The study population consisted of 600 middle-aged hypertensive subjects (300 men and 300 women) and 600 controls (300 men and 300 women) living in the City of Oulu. The hypertensive subjects were randomly selected by age stratification from the Social Insurance Institute register for reimbursement of antihypertensive medication. For each hypertensive subject, an age- and sex-matched control was randomly selected from the national health register. The overall participation rate was 87.8%. In the present study a total of 1024 subjects were screened. Echocardiographic examinations were performed by a trained cardiologist and carotid ultrasonographic examinations by a trained radiologist. RESULTS: The genotype distributions and allele frequencies between the hypertensive and control subjects and the relationship between the Glu298Asp variant and blood pressure, LVM and carotid artery IMT were determined. No differences in genotype distribution or allele frequencies were found between the hypertensive and control groups (the frequency of the Asp allele 0.299 vs. 0.288, respectively). Also, we could not find any association between the eNOS genotype and the measured cardiovascular complications. CONCLUSIONS: The Glu298Asp variant of the eNOS gene does not seem to be a major risk factor for cardiovascular alterations in the general population.     

Feasibility of mobile mental wellness training for older adults

Mobile technology has been increasingly adopted in promotion of mental health among older people. This study assessed the feasibility of a mobile mental wellness training application for individual use and for group work from the perspectives of older adults and social care professionals. The older individuals recruited for the study were participants in a Circle of Friends group and family caregivers' peer support group offered by the communal senior services. The qualitative and quantitative results of interviews, questionnaires, observation, and application usage were reported. Seven older adults started using the application independently at home in parallel with the group activity. This study revealed new information regarding the barriers to the older adults' full adoption of such mobile technologies. The results indicated that there may be potential in the incorporation of mobile technologies in promotion of mental health of older people at group settings.