The risks and benefits of a low protein-essential amino acid-keto acid diet

Twelve patients with progressive renal failure were placed on a very low protein diet supplemented by an essential amino acid-keto acid mixture for six to twelve months. Total daily intake was 0.04 g nitrogen/kg and 50 kcal/kg. Eight subjects had a significant change in the slope of reciprocal plasma creatinine, becoming less steep and in two cases positive. GFR did not improve, but in four patients the decline over twelve months was less than 0.5 mliter/min. There were significant falls in blood and urinary urea, serum phosphate PTH and calcium X phosphate product. Body wt decreased during the first three months. Arm muscle circumference fell by 0.9 cm (P less than 0.005). Serum albumin and transferrin levels did not change significantly. Muscle mass and plasma creatinine fell simultaneously in several patients. Creatinine excretion per kg muscle mass, assessed anthropometrically, declined by 21% in the first three months. This diet may slow the decline in renal function in a proportion of patients. However, muscle mass can be lost. Serum protein levels do not accurately reflect nutritional changes. A fall in plasma creatinine may not be due to improved GFR but instead to altered creatinine metabolism.     

Lichen aureus and vascular fragility

Our observation concerns a patient aged 29 who has presented for the last two years a smooth lesion, non-infiltrated, golden yellow, and situated on the interior surface of the left knee. This lesion recalls the lichen aureus confirmed by standard histology nad Perls' coloration. There is capillary fragility without plaque anomaly. There is, however, no sign of subjacent venous incompetence.     

A pharmacokinetic interaction between carbamazepine and olanzapine: observations on possible mechanism

Objective: Olanzapine is a novel antipsychotic, which is effective against both the positive and negative symptoms of schizophrenia and causes fewer extrapyramidal adverse effects than conventional antipsychotics. The purpose of the present study was to assess the potential for a pharmacokinetic interaction between olanzapine and carbamazepine, since these agents are likely to be used concomitantly in the treatment of manic psychotic disorder. Method: The pharmacokinetics of two single therapeutic doses of olanzapine were determined in 11 healthy volunteers. The first dose of olanzapine (10 mg) was taken alone and the second dose (10 mg) after 2 weeks of treatment with carbamazepine (200 mg BID). Measurement of urinary 6-hydroxycortisol/cortisol excretion was used as an endogenous marker to confirm that induction of CYP3A4 by carbamazepine had occurred. Results: The dose of olanzapine given after a 2-week pre-treatment with carbamazepine was cleared more rapidly than olanzapine given alone. Olanzapine pharmacokinetic values for C_max and AUC were significantly lower after the second dose, the elimination half-life was significantly shorter, and the clearance and volume of distribution were significantly increased. Conclusion: Carbamazepine has been shown to induce several P450 cytochromes including CYP3A4 and CYP1A2. Since CYP1A2 plays a role in the metabolic clearance of olanzapine, the interaction may be attributed to induction of CYP1A2 by carbamazepine, leading to increased first-pass and systemic metabolism of olanzapine. The interaction is not considered to be of clinical significance because olanzapine has a wide therapeutic index, and the changes in plasma concentration of olanzapine are within the fourfold variation that occurs without concern for safety in a patient population. Received: 22 July 1997 / Accepted in revised form: 1 June 1998     

The future of radiological instrumentation

Future trends in the development of radiation protection instrumentation can be expected to be closely related to current trends in political and social activity that drive legislation, rule-making, and standard practice, with assistance provided by trends in material and electronic technology. Wide-range performance will be emphasized to arm the daily worker with instruments that routinely log background rates and, at the same time, are prepared to measure accident rates. Separate and simultaneous accumulation of data from several sensors to ensure complete coverage of the radiation types will be common. Mathematical manipulation of data will provide for summary data logging and, in some cases, solutions to integral equations to provide corrections to experimental data. Instruments will become more reliable by way of self-checking and correction. Miniaturization and large-scale integration of measuring instruments will provide some instrumentation for the people at large. To be effective, the instruments will necessarily cover a wide range and be very reliable. The net result of these several trends will provide for a widespread understanding of radiation protection and an implementation of "as low as reasonably achievable" among large segments of the population.     

GSK-3 dependent phosphoepitopes recognized by PHF-1 and AT-8 antibodies are present in different tau isoforms

It is widely known that the tau protein that forms the aggregates found in tauopathies like Alzheimer’s disease (AD) is hyperphosphorylated. Many of the sites that are hyperphosphorylated in AD can also be found phosphorylated in non-pathological control brains, although to a lesser extend. Among the different kinases that are able to phosphorylate tau in these sites, GSK-3 has emerged as a key effector of AD pathogenesis in view of its interaction with many of the proteins involved in the ethiology of AD. In this work, we have tested if control samples show only a decrease in the amount of phosphorylated tau molecules, or if the phosphorylation at different sites occurs in different tau isoforms, whereas in the pathological situation a single tau isoform is modified simultaneously at the different sites. Our results indicate that the second possibility takes place and that the differences in the phosphorylation of different tau isoforms could be due to a different subcellular distribution of these different tau isoforms in a neuron.     

The use of urine proteomic and metabonomic patterns for the diagnosis of interstitial cystitis and bacterial cystitis

The advent of systems biology approaches that have stemmed from the sequencing of the human genome has led to the search for new methods to diagnose diseases. While much effort has been focused on the identification of disease-specific biomarkers, recent efforts are underway toward the use of proteomic and metabonomic patterns to indicate disease. We have developed and contrasted the use of both proteomic and metabonomic patterns in urine for the detection of interstitial cystitis (IC). The methodology relies on advanced bioinformatics to scrutinize information contained within mass spectrometry (MS) and high-resolution proton nuclear magnetic resonance (1H-NMR) spectral patterns to distinguish IC-affected from non-affected individuals as well as those suffering from bacterial cystitis (BC). We have applied a novel pattern recognition tool that employs an unsupervised system (self-organizing-type cluster mapping) as a fitness test for a supervised system (a genetic algorithm). With this approach, a training set comprised of mass spectra and 1H-NMR spectra from urine derived from either unaffected individuals or patients with IC is employed so that the most fit combination of relative, normalized intensity features defined at precise m/z or chemical shift values plotted in n-space can reliably distinguish the cohorts used in training. Using this bioinformatic approach, we were able to discriminate spectral patterns associated with IC-affected, BC-affected, and unaffected patients with a success rate of approximately 84%.     

Molecular characterization of a coxsackievirus A24 variant that caused an outbreak of acute haemorrhagic conjunctivitis in Spain, 2004

BACKGROUND: Coxsackievirus A24 variant is one of the major etiological agents involved in acute haemorrhagic conjunctivitis. STUDY DESIGN: An outbreak of acute hemorrhagic conjunctivitis occurred in the Southeast of Spain between September and November 2004. Cellular and molecular methods were used to identify and characterize the viral agent associated with the epidemic. RESULTS: Enterovirus was detected in the conjunctival swabs of 35 patients. None of the viruses isolated could be typed by conventional neutralization assays; however, amplification and sequencing of the 3'-end VP1 region of 19 of the samples identified coxsackievirus A24 variant as the serotype causing the outbreak. Phylogenetic analysis of the 5'-half VP1 region of the genome revealed that Spanish sequences, like other strains isolated during outbreaks of hemorrhagic conjunctivitis in American and African countries in 2003 and 2004, were closely related to the isolates detected in Korea (2002), thus proving their worldwide spread. CONCLUSIONS: This is the first report of an epidemic of acute hemorrhagic conjunctivitis due to a coxsackievirus A24 variant in Spain. Molecular typing in combination with phylogenetic analysis is useful to study the enterovirus epidemiology associated with epidemics.     

Childcare as a stabilizing influence on HPA axis functioning: a reevaluation of maternal occupational patterns and familial relations

The influence of family relations, maternal occupational characteristics, and childcare1The UK terms "childcare," childcare centres' and "nurseries" are used throughout this paper to define group care for children prior to starting their first year of formal schooling at age 4 years and are used synonymously with the American terms "day-care" and "preschool." This form of group care is provided in a formal setting, outside the family home and excludes "childminding" (i.e., childcare that may be group based and offered at the home of the care provider/childminder). In the UK, this form of childcare is offered from zero to 4 years old. Children are separated according to their age into small groups usually consisting of 10-15 children. In the present study, all children were in the preschool-aged group (3-4 years old). Where childcare of a different or more generic form is referred to, then this has been made clear in the context or stated in the text. utilization on preschool children's cortisol production were investigated in 56 mother-child dyads. Family characteristics and maternal employment, childcare and child temperament were reported by mothers. Morning and evening levels of children's salivary cortisol were obtained. Children in highly expressive or reserved families exhibited higher cortisol levels compared to children in moderately expressive families. Elevated levels of cortisol were detected in children of mothers reporting low levels of job role quality or high levels of emotional exhaustion. Frequent childcare use was found to protect children against the physiological effects of low maternal job role quality and emotional exhaustion. Findings underscore the pervasive role of the family as set within an external support system and highlight the potential physiological impact of these interacting contexts for children. Further research is needed to fully understand current findings and to develop appropriate psycho-physiological interventions.     

Circulating neutrophil CD14 expression and the inverse association of ambient particulate matter on lung function in asthmatic children.

BACKGROUND: Identifying baseline inflammatory biomarkers that predict susceptibility to size-specific particulate matter (PM) independent of gaseous pollutants could help us better identify asthmatic subpopulations at increased risk for the adverse health effects of PM. OBJECTIVE: To evaluate whether the association between lung function and exposure to ambient levels of PM less than 2.5 microm in diameter (PM2.5) (fine) and 10 to 2.5 microm in diameter (PM(10-2.5)) (coarse) in children with persistent asthma differed across baseline measures of inflammation and innate immune activation. METHODS: We performed a panel study on a local population of 16 children with persistent asthma and evaluated daily pulmonary function (percentage of predicted peak expiratory flow and forced expiratory volume in 1 second) while concurrently measuring daily PM2.5 and PM(10-2.5) exposure from a central site in Chapel Hill, North Carolina. The children underwent a baseline medical evaluation that included assessment of several immunoinflammatory biomarkers in peripheral blood. RESULTS: Children without measurable CD14 expression on circulating neutrophils had significantly reduced pulmonary function (forced expiratory volume in 1 second and peak expiratory flow) with each interquartile range (IQR) increase in PM2.5 (IQR = 8.5 microg/m3) and PM(10-2.5) (IQR = 4.1 microg/m3) concentration, unlike children with measurable CD14 expression (P < .001 for interaction). CONCLUSIONS: Asthmatic children with muted surface expression of CD14 on circulating neutrophils may have a decreased capacity to respond to bacterial components of PM.