Factor analysis of bowel symptoms in US and Italian populations

BACKGROUND AND AIMS: Functional gastrointestinal disorders are diagnosed by the presence of a characteristic set of symptoms. Aims of this study were to validate the Rome symptom criteria by factor analysis and to determine whether symptoms cluster in the same way in different cultures. METHODS: One thousand forty-one gastroenterology clinic patients in the US (response rate 53%) and 228 family members accompanying clinic patients in Italy (84%) completed a previously validated symptom questionnaire. Factor analysis identified clusters of symptoms which are highly correlated with each other, and these were compared to the Rome diagnostic criteria. RESULTS: In the US, 13 factors were identified. The irritable bowel factor was composed of three core symptoms corresponding to the Rome II classification system. Two dyspepsia factors were identified which correspond to the ulcer- and motility-like subtypes proposed in the Rome I classification system. All symptoms of constipation formed a single cluster as proposed in the Rome II classification system. Symptom clusters in the US agreed well with symptom clusters identified in Italian subjects. CONCLUSIONS: Empirically derived symptom clusters agree in most respects with the Rome II classification system and support their validity. These symptom clusters are independent of cultural differences in diet and behaviour.     

Genome-scale reconstruction of the Saccharomyces cerevisiae metabolic network

The metabolic network in the yeast Saccharomyces cerevisiae was reconstructed using currently available genomic, biochemical, and physiological information. The metabolic reactions were compartmentalized between the cytosol and the mitochondria, and transport steps between the compartments and the environment were included. A total of 708 structural open reading frames (ORFs) were accounted for in the reconstructed network, corresponding to 1035 metabolic reactions. Further, 140 reactions were included on the basis of biochemical evidence resulting in a genome-scale reconstructed metabolic network containing 1175 metabolic reactions and 584 metabolites. The number of gene functions included in the reconstructed network corresponds to approximately 16% of all characterized ORFs in S. cerevisiae. Using the reconstructed network, the metabolic capabilities of S. cerevisiae were calculated and compared with Escherichia coli. The reconstructed metabolic network is the first comprehensive network for a eukaryotic organism, and it may be used as the basis for in silico analysis of phenotypic functions.     

In silico model-driven assessment of the effects of single nucleotide polymorphisms (SNPs) on human red blood cell metabolism

The completion of the human genome project and the construction of single nucleotide polymorphism (SNP) maps have lead to significant efforts to find SNPs that can be linked to pathophysiology. In silico models of complete biochemical reaction networks relate a cell's individual reactions to the function of the entire network. Sequence variations can in turn be related to kinetic properties of individual enzymes, thus allowing an in silico model-driven assessment of the effects of defined SNPs on overall cellular functions. This process is applied to defined SNPs in two key enzymes of human red blood cell metabolism: glucose-6-phosphate dehydrogenase and pyruvate kinase. The results demonstrate the utility of in silico models in providing insight into differences between red cell function in patients with chronic and nonchronic anemia. In silico models of complex cellular processes are thus likely to aid in defining and understanding key SNPs in human pathophysiology.     

Determination of specific oxygen uptake rates in human hematopoietic cultures and implications for bioreactor design

Oxygen plays an important role in the cultivation of primary cellsex vivo. In this study, we used hermetically sealed tissue culture well inserts equipped with oxygen electrodes to measure the oxygen utilization of cultured human bone marrow mononuclear cells (BM MNCs). The oxygen uptake rate (OUR) of BM MNCs was determined during a 14-day culture in which both adherent and nonadherent cells were present. Early in the culture, the cells exhibited very low OURs. The specific OURs (uptake rate per cell) were at approximately 0.005 μmol/10⁶ cells/hr shortly after the initiation of culture. The OUR then increased as the cultures developed. After about 8 to 10 days of cultivation the specific OURs had increased to 0.038±0.006 and 0.025±0.005 μmol/10⁶ cells/hr for adherent and nonadherent cells, respectively, after which no further increase was observed. Based on these oxygen uptake rate data, a mathematical model of oxygen diffusion was formulated and use to investigate issues associated with hematopoietic bioreactor design, including initial cell density, medium depth, reactor configuration, and oxygen partial pressure.In situ OUR measurements confirmed predicted oxygen limitations based on the mathematical model and the experimentally determined OURs. High-density hematopoietic cultures present design challenges in terms of sufficient and uniform delivery of oxygen to an active hematopoietic culture. These challenges can be met by using parallelplate bioreactors with thin liquid layers.     

Comparison of Aneroid and Oscillometric Blood Pressure Measurements in Children

Limited data exist on the comparison of blood pressure (BP) measurements using aneroid and oscillometric devices. The purpose of the study was to investigate the difference in BP obtained using oscillometric and aneroid BP monitors in 9‐ to 10‐year‐old children. A total of 979 children were divided into group O, which underwent two oscillometric BP readings followed by two aneroid readings, and group A, which had BP measured in the reverse order. No significant difference was found between the mean (±standard deviation) of the two systolic BP readings obtained using the oscillometric and aneroid devices (111.5±8.6 vs 111.3±8.1 mm Hg; P=.39), whereas the mean diastolic BP was lower with the oscillometric monitor (61.5±8.0 vs 64.5±6.8 mm Hg; P<.001). A significant downward trend in BP was observed with each consecutive measurement, and agreement between the two monitors was limited. Multiple BP measurements are, therefore, recommended before the diagnosis of elevated BP or hypertension is made with either method.     

Experimental Referred Pain Extends Toward Previously Injured Location: An Explorative Study

Facilitated pain mechanisms have been demonstrated in musculoskeletal pain, but it is unclear whether a recent painful injury leaves the pain system sensitized. Pain characteristics were assessed in individuals who recently recovered from ankle pain (recovered pain group; n?=?25) and sex-matched control subjects (n?=?25) in response to tonic pressure pain and saline-induced pain applied at the shin muscle. Pain intensity and pain referral patterns were recorded bilaterally after the painful muscle stimulus. Pressure pain thresholds were measured at the lower legs and shoulder. Cuff pressure algometry on the lower leg was used to assess pain detection threshold, pressure evoking 6-cm pain score on a 10-cm visual analog scale, pain tolerance, temporal summation of pain, and conditioned pain modulation. Compared with in control subjects, saline-induced and pressure-induced pain in the shin muscle were more frequently felt as referred pain in the previously painful ankle (P < .05), and the pain area within the previously affected ankle was larger after saline-induced pain (P < .05). In the recovered pain group, conditioned pain modulation responses and the cuff pressure needed to reach a 6-cm pain score on a 10-cm visual analog scale was higher in the previously painful leg compared with in the contralateral leg (P < .05). No group differences were found in pressure pain threshold, pain detection threshold, pain tolerance, and temporal summation of pain.

A population-based study on motor performance and white matter lesions in older women

OBJECTIVE: To investigate the relationship between motor performance and white matter lesions (WMLs) on computed tomography (CT) of the brain in older women. DESIGN: Cross-sectional study. SETTING: Population-based study in G?teborg, Sweden. PARTICIPANTS: A total of 248 women aged 70, 74, and 78 years. MEASUREMENTS: Motor performance was measured by a Postural-Locomotion-Manual (PLM) test using an optoelectronic technique. WMLs on CT scans were rated as no, mild, moderate, or severe. RESULTS: White matter lesions were associated with impaired mobility of the lower extremities, that is, prolonged locomotion phase in the PLM test. This association was also present after controlling for age, hypertension, coronary heart disease, stroke, diabetes mellitus, chronic bronchitis, intermittent claudication, and smoking. CONCLUSIONS: Cerebral white matter lesions may contribute to motor impairments in older adults.     

Birth Weight and Childhood Blood Pressure

A large body of literature suggests an inverse relationship between birth weight and blood pressure in children, adolescents and adults. The most persistent findings have been observed in children with a history of low birth weight or intrauterine growth restriction, while a large number of studies carried out in populations with normally distributed birth weight have shown conflicting results. A recently reported strong direct association between high birth weight and blood pressure, and the significant positive effect of postnatal growth on blood pressure suggests that the fetal origins of adult disease hypothesis should be expanded to include the role of excessive fetal and postnatal growth. In this paper, we review recent studies on the relationship between birth weight and blood pressure in childhood, with a focus on confounding variables that may explain the conflicting results of published work in this field.