Jacqueline Sulkes

Serum protein N-glycans profiling for the discovery of potential biomarkers for nonalcoholic steatohepatitis.

The hepatic histology in nonalcoholic fatty liver disease can vary from isolated hepatic steatosis to steatohepatitis can progress to cirrhosis and liver-related death. The aim was to evaluate the use of blood serum N-glycan fingerprinting as a tool for differential diagnosis of nonalcoholic steatohepatitis from steatosis. A group of 47 patients with NAFLD was diagnosed by clinical laboratory analysis and ultrasonography, and was studied histologically using the Brunts scoring system. The control group included 13 healthy individuals. N-glycan profiles of serum proteins were determined by DNA sequencer-based carbohydrate analytical profiling. We have found that the concentrations of two glycans (NGA2F and NA2) and their logarithm ratio of NGA2F versus NA2 (named GlycoNashTest) were associated with the degree of NASH-related fibrosis, but had no correlation with the grade of inflammation nor steatosis severity. When used to screen NAFLD patients, GlycoNashTest could identify advanced NASH-related fibrosis (F3-F4) with the diagnosis sensitivity of 89.5% and specificity of 71.4%. The serum N-glycan profile is a promising noninvasive method for detecting NASH or NASH-related fibrosis in NAFLD patients, which could be a valuable supplement to other markers currently used in diagnosis of NASH.

Thromboxane Production in Human Lung During Cardiopulmonary Bypass: Beneficial Effect of Aspirin?

BACKGROUND Increased systemic levels of thromboxane (Tx) during cardiopulmonary bypass (CPB) in humans have been reported. It is not known whether this reflects a general systemic response to the surgical procedure or an increased pulmonary production of Tx in response to ischemia and reperfusion. METHODS Thromboxane B2 levels were measured in the right atrium and left atrium of 14 patients undergoing coronary artery bypass grafting for angina. Eight patients (group 1) were without aspirin for at least 15 days before operation, and 6 patients (group 2) were treated with aspirin (100 mg/day) for at least 1 month before operation. Levels of TxB2 were determined by enzyme immunoassay after lipid extraction and separation. RESULTS Thromboxane B2 levels were elevated throughout CPB. In group 1, left atrial TxB2 levels were significantly higher (p < 0.05) than right atrial levels at all study points during CPB. After pulmonary reperfusion, TxB2 levels in both atria increased significantly (p < 0.02) compared with the levels before cross-clamping of the aorta, and there was an increasing gradient between the two atria (p < 0.05). Mean plasma TxB2 levels during CPB in group 2 were significantly reduced (p < 0.0001) in the right atrium (by 73%) and in the left atrium (by 69%) compared with levels in group 1. CONCLUSIONS The rise in TxB2 levels in the left atrium after CPB in humans reflects production of Tx mainly in the lungs, most probably by ischemic pulmonary tissue and intravascular hematologic components. Aspirin markedly reduces Tx production during CPB, and it might play a major role in preventing pulmonary injury after operations with CPB in humans.

Papaverine Hydrochloride for the Treatment of Renal Colic: An Old Drug Revisited. A Prospective, Randomized Study

PURPOSE We assessed the efficacy of papaverine hydrochloride, a commonly used smooth muscle relaxant, for the treatment of renal colic as a single agent and in combination with sodium diclofenac. MATERIALS AND METHODS A prospective, single-blind clinical study was performed at 2 centers. A total of 86 patients with acute renal colic were randomized to 3 treatment groups of 120 mg intravenous papaverine hydrochloride (29), 75 mg intramuscular sodium diclofenac (30), and papaverine hydrochloride plus sodium diclofenac (27). Pain intensity was assessed with the Visual Analog Scale at 0, 20 and 40 minutes after treatment. Further analgesia given at patient request consisted of 1 mg/kg intramuscular meperidine. Urinalysis, complete blood evaluation and imaging were performed in all patients. All adverse effects were recorded. RESULTS Baseline characteristics were similar in the 3 groups. Pain intensity decreased significantly (p <0.01) after 20 and 40 minutes in all groups. Papaverine hydrochloride was as effective as sodium diclofenac in alleviating pain and the combined treatment group showed a slight trend of more rapid relief. Significantly more patients in the papaverine group required further analgesia and 4 patients (14.8%) reported minor adverse effects (dizziness in 3, sleepiness in 1). CONCLUSIONS Papaverine hydrochloride is as effective as sodium diclofenac for the short-term relief of acute renal colic pain and may be advantageous in patients with contraindications for nonsteroidal anti-inflammatory drugs. However, sodium diclofenac appears to provide a longer effective analgesia.

Clinical cosmobiology: The Lithuanian study 1990-1992

The numbers of deaths from ischaemic heart disease (IHD), stroke (CVA), all accidents except vehicular, vehicular accidents and suicide (overall total, totals for men and women) per month for 36 months (1990–1992) in Lithuania were analysed in relation to: (1) month of the year (1–12); (2) geomagnetic activity; and (3) solar activity. A total of 122227 deaths (64490 men and 57737 women) was studied, and the results compared with those obtained in an earlier study in Israel, differing geographically and climatically from Lithuania. It was shown that the time of year, solar activity, and geomagnetic activity were related to the monthly death distribution, especially regarding death from IHD and suicide. Age and gender differences were apparent in the relationship between death distribution and physical environmental factors. At age >70 years, many of these relationships change. The monthly distribution of deaths from IHD and suicide are adversely correlated with solar activity and with each other. Differences are presumed in serotoninergic effects as caused by environmental influences.

Relation between aerobic capacity and extent of myocardial ischemia in patients with normal cardiac function

BACKGROUND The relation between aerobic capacity and extent of exercise-induced myocardial ischemia has not been investigated. Fifty patients with coronary artery disease (>/=50% stenosis) without myocardial infarction underwent cardiopulmonary exercise testing followed by quantitative thallium perfusion imaging. Results were compared with those of age- and sex-matched healthy controls with a low likelihood of coronary artery disease. Patients with Q-wave infarction, pulmonary disease, and peripheral vascular disease were excluded. Cardiopulmonary exercise testing and thallium perfusion imaging parameters were correlated for extent of global ischemia, occurrence of increased pulmonary thallium uptake, and transient ventricular dilatation during exercise. RESULTS Patients with global ischemia <20% (group 1, n = 25) had normal cardiopulmonary exercise testing results, similar to the control group, except for workload and maximal predicted heart rate, which were reduced. However, patients with ischemia >/=20% (group 2, n = 25) had poor cardiopulmonary exercise testing results compared with the controls. The ventilatory anaerobic threshold showed the most significant decrease of all cardiopulmonary exercise testing parameters (48% +/- 6% vs 57% +/- 6%, P <.0001), and it was the only parameter to correlate with extent of ischemia (r = -0.5; P <.003) as well as frequency of increased pulmonary uptake and transient ventricular dilatation (r = -0.33, P =.03). CONCLUSIONS Ventilatory anaerobic threshold is significantly related to extent of myocardial ischemia and signs of heart failure during exercise. However, patients with mild to moderate exercise-induced ischemia may have normal cardiopulmonary exercise testing performance.

Basal and Post-Methionine Serum Homocysteine and Lipoprotein Abnormalities in Patients With Chronic Liver Disease

Background Lipoprotein abnormalities are commonly found in chronic liver diseases (CLDs), particularly hypercholesterolemia in primary biliary cirrhosis (PBC). However, affected patients may not be at increased risk of coronary heart disease. Cirrhotic patients display impaired methionine clearance, and an increased level of homocysteine, a methionine metabolite, is an independent risk factor for coronary heart disease. Thus, we hypothesized that the low risk of coronary heart disease in patients with CLD may be related to low serum levels of homocysteine. The aim of this study was to test this hypothesis after methionine load and to describe the serum lipoprotein profile in patients with PBC and in patients with hepatocellular liver disease. Methods Fifteen female patients (mean age, 58.2±11.7 years) with PBC, 15 female patients (mean age, 54.5 ± 9.6 years) with other causes of CLD, and 15 healthy sex- and age-matched controls were given L-methionine (50 mg/kg of ideal body weight). Basal fasting serum homocysteine level and 2, 4, and 6 hours of post-methionine load were determined using high-performance liquid chromatography with a fluorometric detector. Levels of fasting serum cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), lipoprotein (a) (Lp(a)), and apoprotein B were also determined. Results Results showed that mean basal and post-methionine load (6 hours) serum homocysteine levels were statistically significantly higher in the patients with PBC and with CLD than in the control group (P=0.04) and that levels of serum cholesterol, LDL, HDL, and apoprotein B were significantly higher in the PBC patients than in the other two groups (P≤0.05). There was no correlation between any of these parameters and the severity of liver disease. Serum HDL was significantly lower in the CLD group (P≤0.05) and correlated with severity of liver disease. There was no significant difference in serum cholesterol, LDL, or apoprotein B between the CLD group and the controls. Serum triglyceride and Lp(a) levels were similar for all three groups. Conclusions In contrast to previous reports, the site of the methionine metabolic impairment was found to be below the homocysteine synthesis level. For most patients with CLD, factors other than serum homocysteine or Lp(a) are responsible for the reduction in the risk of coronary heart disease. Further studies with larger samples are needed.

Traffic accidents and environmental physical activity

Environmental physical activity (EPA) is considered as one of main regulators of human homeostasis. Evidence is growing that components of this activity through the “human factor” (i.e., changing human physiological and psychological status) can affect the dynamics of traffic accidents (TA)—the modern life epidemic. This paper presents results of studies conducted in order to reveal the potential influence of EPA [solar (SA), geomagnetic (GMA) and cosmic ray (CRA) activities] on the number of TA and related casualties in the years of the maximum and declining phase of SA cycle 23 (2000–2005). We selected the 7,160 most severe TA and their related 7,558 deaths and 1,647 severe injuries, registered in the Grand Baku Area (Azerbaijan, middle latitudes), for analysis. A significant increase of TA and victims was observed during the whole year and also during the last months of the year. The monthly numbers of TA and victims were inversely related to SA (probability p = 0.0002), and non-significantly to background GMA, but were significantly affected by major geomagnetic disturbances and storms. A strong correlation between CRA variations (cosmic ray intensity measured by ground-based neutron monitors on the Earth’s surface) and the number of TA (p = 0.001) has been observed. It was found that the number of TA which occur within a month depends significantly on the particular month of the year, the CRA, and the SA levels (inverse correlation). The increase of the number of TA is also significantly linked to geomagnetic storms, but not to steady GMA. These effects can be related to changes in human functional and behavioral markers provoked by EPA influences.

Relationship Between Autonomic Control of Heart Rate and QT Dispersion in Patients with Acute Anterior Wall Myocardial Infarction

Heart rate variability (HRV) and QT dispersion are new and promising noninvasive indices for postinfarction risk stratification. The relationship between measures in patients with acute myocardial infarction (AMI) is unknown.