Observations on the specificity of the urinary 5-hydroxyindoleacetic acid determination with 1-nitroso-2-naphtol

Cardiac function during acute hyperglycaemia was investigated by means of echocardiography in eight insulin-dependent (type 1) diabetic patients without microvascular or cardiac disease. Blood glucose was raised from 5.1±0.8 to 13.0±0.9 mmol/l for 1 h and then to 20.1 + 1.2 mmol/l for 1 h. A saline control study was performed to obtain an equal amount of plasma volume expansion. The left ventricular end-diastolic diameter increased significantly in both studies, however, significantly more following glucose infusion (3.3% at blood glucose of 13.0 mmol/l, 5.4% at blood glucose of 20.1 mmol/l versus 2.7% after both saline infusions). At the blood glucose level of 20.1 mmol/l, fractional shortening of the left ventricle and cardiac output were increased as compared with the baseline level and the level during moderate hyperglycaemia, and also increased compared with values of non-diabetics. In conclusion acute hyperglycaemia is followed by increased myocardial performance, probably as a consequence of increased peripheral blood flow.     

Enzyme replacement therapy for alpha-mannosidosis: 12 months follow-up of a single centre, randomised, multiple dose study

Background

Alpha-mannosidosis (OMIM 248500) is a rare lysosomal storage disease (LSD) caused by alpha-mannosidase deficiency. Manifestations include intellectual disabilities, facial characteristics and hearing impairment. A recombinant human alpha-mannosidase (rhLAMAN) has been developed for weekly intravenous enzyme replacement therapy (ERT). We present the preliminary data after 12 months of treatment.

Methods

This is a phase I-II study to evaluate safety and efficacy of rhLAMAN. Ten patients (7–17 y) were treated. We investigated efficacy by testing motor function (6-minutes-Walk-Test (6-MWT), 3-min-Stair-Climb-Test (3-MSCT), The Bruininks-Oseretsky Test of Motor Proficiency (BOT2), cognitive function (Leiter-R), oligosaccharides in serum, urine and CSF and Tau- and GFA-protein in CSF.

Results

Oligosaccharides: S-, U- and CSF-oligosaccharides decreased 88.6 % (CI ?92.0 ?85.2, p?<?0.001), 54.1 % (CI ?69.5- ?38.7, p?<?0,001), and 25.7 % (CI ?44.3- ?7.1, p?<?0.05), respectively. Biomarkers: CSF-Tau- and GFA-protein decreased 15 %, p?<?0.009) and 32.5, p?<?0.001 respectively. Motor function: Improvements in 3MSCT (31 steps (CI 6.8-40.5, p?<?0.01) and in 6MWT (60.4 m (CI ?8.9 ?51.1, NS) were achieved. Cognitive function: Improvement in the total Equivalence Age of 4 months (0.34) was achieved in the Leiter R test (CI ?0.2-0.8, NS).

Conclusions

These data suggest that rhLAMAN may be an encouraging new treatment for patients with alpha-mannosidosis.The study is designed to continue for a total of 18 months. Longer-term follow-up of patients in this study and the future placebo-controlled phase 3 trial are needed to provide greater support for the findings in this study.     

The relationship of serum triglycerides,serum HDL,and obesity to the risk of wheezing in 85,555 adults

BackgroundAsthma has been linked to obesity and the presence of the metabolic syndrome.Objective: To explore which components of the metabolic syndrome that were associated with wheezing, a main symptom of asthma. Further, to explore whether these associations were different in individuals with and without rhinitis symptoms.MethodsWe used data from the Ibermutuamur Cardiovascular Risk Assessment Plan (ICARIA) including 85,555 Spanish workers (median age = 34, range = 16–75 years) with assessments of self reported wheezing and rhinitis symptoms. Fasting blood samples were analysed for serum triglyceride (s-TG), HDL (s-HDL) and glucose; blood pressure, waist circumference (WC) and body mass index (BMI) were measured.ResultsIn mutually adjusted analyses including all components of the metabolic syndrome and possible confounders, elevated WC (or BMI), elevated s-TG and low s-HDL were significantly associated with wheezing. Odds ratio (OR) with confidence interval (CI) were: elevated WC = 1.54 (1.46–1.62), elevated s-TG = 1.24 (1.18–1.30), low s-HDL = 1.17 (1.12–1.22). These associations were stronger in individuals without than in those with rhinitis symptoms, OR's (CI's) were WC = without rhinitis 1.70 (1.57–1.85) vs. with rhinitis 1.47 (1.37–1.58). Elevated s-TG = without rhinitis 1.36 (1.26–1.46) vs. with rhinitis 1.21 (1.13–1.29). Low s-HDL = without rhinitis 1.24 (1.15–1.34) vs. with rhinitis 1.11 (1.04–1.18).ConclusionsHigh s-TG and low s-HDL were associated with wheezing after adjustment for adiposity. This may substantiate elevated s-TG and lowered s-HDL as markers or inducers of inflammation associated disease. The study supports the notion that these biochemical markers have differential effects on different types of wheezing.     

Improvement of superoxide production in monocytes from patients with chronic granulomatous disease by recombinant cytokines

Cytokines have been shown to modulate the respiratory burst of polymorphonuclear leukocytes and monocytes from normal controls. We have examined whether monocytes from children with chronic granulomatous disease (CGD) can be primed by cytokines other than interferon-gamma (IFN gamma), which has been demonstrated to improve the production of reactive oxygen species in vivo and in vitro. Monocytes isolated from peripheral blood were cultured without and with IFN gamma (500 U/mL), tumor necrosis factor-alpha (500 U/mL), interleukin-1 beta (IL-1 beta) (100 U/mL), and IL-3 (100 U/mL). After 3 days of culture, the phorbolmyristate acetate (2 ng/mL) and the formyl- methionyl-leucyl-phenylalanine (0.1 mumol/L)-stimulated superoxide- production was determined in a microtiter system. In nearly all of the 14 patients examined (5 autosomal, 5 X-chromosomal, and 4 of unknown inheritance), an improvement of superoxide production could be demonstrated. The most impressive effect with the cytokines newly tested was seen with monocytes from autosomal CGD patients treated with IL-3 and stimulated by phorbolmyristate acetate. In single patients cultivation of monocytes with IL-6 and granulocyte-macrophage colony- stimulating factor resulted in only slight improvement of superoxide production. Our findings indicate that cytokines other than IFN gamma can positively modulate the defective respiratory burst in CGD and that each patient reacts with an individual pattern to different cytokines.     

动脉血压监测及其影响因素

动脉血压 (ABP)是一项重要的血流动力学指标 ,正确监测很重要。重点介绍ABP的生理及影响 ABP的生理及病理生理学因素 ,ABP的监测原则 ,ABP波形及其临床解释。     

4－甲基－5－取代苯氧基－伯氨喹类似物的合成及抗疟活性的初步评价

以２－硝基－４－甲氧基－５－溴乙酰苯胺为原料，经６步反应，合成了７个４－甲基－５－取代苯氧基伯氨喹类似物（ＩＩ２～８）。抗疟活性的初步评价结果表明，这类化合物对鼠疟Ｐｌａｓｍｏｄｉｕｍｙｏｅｌｉｉ的病因性预防作用明显优于伯氨喹，可达伯氨喹的４～８倍；同时，ＩＩ２～８还有较强的杀血液裂殖体作用，ＩＩ２．５．６．８在０．７８１ｍｇ·ｋｇ－１的剂量对原虫的抑制率为１００％。     

Myocardial glutamate and alanine exchanges related to carbohydrate metabolism in patients with normal and stenotic coronary arteries

Summary. Myocardial exchanges of glutamate, alanine, glucose, lactate, free fatty acids (FFA) and oxygen in resting state were determined in nine subjects (controls) without and in 28 patients with coronary artery disease (CAD). Patients with CAD showed increased myocardial glutamate uptake (2·51±0·60 μmol/min) and alanine release (1·25±0·60μmol/min) compared to controls (glutamate uptake: 1·66±0·79 μmol/min; alanine release: 0·63±0·41 μmol/min). Myocardial glucose and lactate uptake was augmented in CAD patients, whereas FFA arterio-venous differences were decreased in patients with three-vessel-disease. The amount of glutamate taken up by the heart correlated positively to lactate uptake in all subjects (r= 0·84) and to external glucose utilization in patients with CAD (r= 0·72). Myocardial alanine release was positively related to glucose and lactate uptake in controls and in patients with only moderate CAD (one-vessel-disease). Glucose and FFA uptake correlated inversely in controls (r=0·84), but not in CAD patients. A tight relation between exchanges of glutamate/alanine and carbohydrate metabolism in human heart is demonstrated. The data suggest altered myocardial substrate exchange towards augmented carbohydrate utilization in CAD patients in resting state. The results agree with in vitro and animal studies suggesting extraction of glutamate from the circulation to be of importance for maintaining carbohydrate consumption in chronic ischaemic heart disease.