Alexander Dzien

Changes of serum antibodies to heat-shock protein 65 in coronary heart disease and acute myocardial infarction

Accumulating evidence indicates the involvement of heat shock proteins (hsp), a family of stress-inducible proteins, in atherosclerosis. For carotid atherosclerosis an association with an increase in hsp65 antibodies has been demonstrated. To investigate whether such antibodies are also associated with coronary heart disease (CHD) and acute myocardial infarction (MI), an age- and sex-matched study with patients suffering from CHD (n = 114) and MI (n = 89) and healthy controls (n = 76) was performed. All study participants (n = 279) were consecutively recruited according to typical diagnostic criteria. Determination of antibody titres to hsp65 was performed by an enzyme-linked immunosorbent assay (ELISA). Hsp65 antibody titres in CHD showed a significant increase compared to the healthy control group (P = 0.029), however, hsp65 antibody titres were found to be significantly lower in acute MI, compared to CHD (P = 0.005). Alteration in hsp65 antibody titres showed no correlation to established cardiovascular risk factors, e.g. serum total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, blood pressure, smoking, alcohol intake and body weight. In conclusion, serum concentrations of hsp65 antibodies were elevated independently in coronary heart diseases and declined in patients with acute myocardial infarction, indicating a possible involvement of the antibodies in the pathogenesis of this disease.

Compounds enhanced in a mass spectrometric profile of smokers' exhaled breath versus non-smokers as determined in a pilot study using PTR-MS

A pilot study has been carried out to define typical characteristics of the trace gas compounds in exhaled breath of non-smokers and smokers to assist interpretation of breath analysis data from patients who smoke with respiratory diseases and lung cancer. Exhaled breath was analyzed using proton transfer reaction-mass spectrometry (PTR-MS) for 370 volunteers (81 smokers, 210 non-smokers, 79 ex-smokers). Volatile organic compounds corresponding to product ions at seven mass-to-charge ratios (m/z 28, 42, 69, 79, 93, 97, 123) in the PTR-MS spectra differentiated between smokers and non-smokers. The Youden index (= maximum of sensitivity + specificity - 1, YI) as a measure for differentiation between smokers and non-smokers was YI = 0.43 for ions at the m/z values 28 (tentatively identified as HCN), YI = 0.75 for m/z = 42 (tentatively identified as acetonitrile) and YI = 0.53 for m/z = 79 (tentatively identified as benzene). No statistically significant difference between smokers and non-smokers was observed for the product ions at m/z = 31 and 33 (compounds tentatively identified as formaldehyde and methanol). When interpreting the exhaled breath of lung cancer or COPD patients, who often smoke, compounds appearing at the above-mentioned seven mass-to-charge ratios should be considered with appropriate care to avoid misdiagnosis. Validation studies in larger numbers of patients with more precise delineation of their smoking behavior and using additional analytical techniques such as GC/MS and SIFT-MS should be carried out.

The analysis of healthy volunteers' exhaled breath by the use of solid-phase microextraction and GC-MS

We analysed breath and inhaled room air samples from 39 healthy volunteers (28 non-smokers, 8 smokers and 3 ex-smokers) by SPME-GC-MS. Mixed expiratory and indoor air samples were collected in freshly cleaned Tedlar bags. Eighteen millilitres of each sample were transferred into sealed, evacuated glass vials, preconcentrated by solid-phase microextraction (SPME, carboxen/polydimethylsiloxane) and investigated by gas chromatography with mass spectrometric detection (GC-MS). For the unequivocal identification of potential marker compounds, pure calibration mixtures of reference compounds (depending on commercial availability) were prepared to determine the retention time and mass spectra with respect to our analytical setting. Applying the adapted SPME-GC/MS method with limit of detection in the high ppb range (0.05-15.00 ppb), we succeeded in identifying altogether 38 compounds with concentrations in exhaled breath being at least 50% higher than concentration in inhaled air. From these 38 compounds, 31 were identified not only by the spectral library match but also by retention time of standards. A comparison of retention times and spectrum obtained for standards and determined compounds was performed. We found hydrocarbons (isoprene, 2-pentene, 2-methyl-1-pentene, benzene, toluene, p-cymene, limonene, 2,4-dimethylheptane, n-butane), ketones (acetone, hydroxypropanone, methylvinyl ketone), ethers (dimethyl ether, 1,3-dioxolane), esters (ethyl acetate), aldehydes (propanal, hexanal, heptanal, acrolein) and alcohols (ethanol, 2-metoxyethanol, isopropyl alcohol, 2,2,3,3- tetramethylcyclopropanemethanol, 3,4-dimethylcyclohexanol). Proper identification of compounds in different cohorts of patients and volunteers is the base for further investigation of origin, biochemical background and distribution of potential breath biomarkers.

Breath isoprene - aspects of normal physiology related to age, gender and cholesterol profile as determined in a proton transfer reaction mass spectrometry study

Abstract Background: This study was performed to clarify variations in breath isoprene concentrations with age, gender, body mass index (BMI) and total serum cholesterol. Our cohort consisted of 205 adult volunteers of different smoking background without health complaints. Total cholesterol in blood serum was measured in 79 of these volunteers. Methods: Mixed expiratory exhaled breath was sampled using Tedlar bags. Concentrations of isoprene were then determined using proton transfer reaction-mass spectrometry. Results: Isoprene concentrations ranged from 5.8 to 274.9 ppb, with an overall geometric mean (GM) of 99.3 ppb. There was no statistically significant difference in mean isoprene in breath between males and females (GM 105.4 and 95.5 ppb, respectively). Ageing led to a decrease in concentration in men, with an estimated slope of the regression line for log-transformed isoprene concentrations of –0.0049, but did not influence isoprene levels in women. We did not observe any significant correlation between isoprene breath content and cholesterol level in blood, even after adjusting for the possible influence of age. Similarly, no correlation was found between isoprene levels and BMI. Conclusions: Isoprene concentrations in exhaled breath showed gender-specific correlations with respect to age. Further investigations are necessary to clarify the relation between isoprene concentrations in exhaled breath and cholesterol levels and synthesis rates in blood. Clin Chem Lab Med 2008;46:1011–8.

Treatment of severe cancer pain by low-dose continuous subcutaneous morphine

&NA; In a prospective and intraindividually controlled trial, we have compared the efficacy and safety of a continuous subcutaneous morphine infusion with conventional intermittent oral or subcutaneous morphine application. Twenty‐eight in‐patients with cancer pain received a short‐term infusion lasting 2–42 days, and 8 out‐patients underwent long‐term infusion from 49 to 197 days during the terminal stage of their disease. Continuous subcutaneous morphine infusion significantly (P < 0.001) improved both pain and quality of life when compared to conventional morphine application. With continuous infusion, 5–48 mg (median 19 mg) of morphine was required daily, significantly (P < 0.001) less than the 10–90 mg (median 50 mg) necessary with conventional use. As a result of lower dosage, side effects under continuous infusion were infrequent and mild. Constipation occurred in 3 of the 36 patients and was always controlled by the addition of laxatives; no nausea, sedation or respiratory depression were observed. Signs of tolerance developed in 2 patients on long‐term infusion, but the use of continuous subcutaneous methadone for 2 weeks reversed the tolerance. The study presented indicates that low‐dose continuous subcutaneous morphine provides a valuable treatment modality for severe terminal cancer pain exhibiting a high degree of both efficacy and safety.

Prognostic value of antibody titre to heat-shock protein 65 on cardiovascular events.

Accumulating evidence suggests that the immune system is involved in atherogenesis, such as the correlation of the antibody titre to heat shock protein (hsp) with atherosclerotic lesions in the carotid and coronary arteries. Because the prognostic value of the hsp antibody titre for future cardiovascular events has not been evaluated until now, we performed a follow-up study on 195 subjects without a history of established cardiovascular risk factors (e.g. hypercholesterolaemia, diabetes, smoking), recruited for hsp antibody titre determination in 1995. Cardiovascular events were defined as unstable angina with the need for hospitalisation, myocardial infarction, re-vascularisation (PTCA, bypass), stroke and cardiovascular death. Among 79 men with coronary artery disease defined by coronary angiography, hsp antibody titres were signficantly higher in those with future cardiovascular events (467.0 ± 56.3) than in patients without further events (351.0 ± 23.3; p < 0.049). Because anti-hsp-antibody titres might be of prognostic value for coronary artery disease, patients with an increased hsp antibody titre should obtain intensive management of classical risk factors.

Fat-Free Mass and Fasting Glucose Values in Patients with and without Statin Therapy Assigned to Age Groups between 75 Years

Objective: The aging-associated changes in body composition result in an increased cardiometabolic risk. A tremendous reduction of cardiovascular morbidity and mortality can be obtained by statin therapy. Statins are well tolerated, with myopathy as the most serious negative side effect. Some recently published studies indicate that the incidence of type 2 diabetes might be increased during intensified statin therapy. The aim of our study was to investigate whether statin therapy has an influence on the aging-associated changes in fat-free mass (FFM). Methods: A total of 3,280 persons attending a medical outdoor center between January 2005 and July 2011 were assigned to 3 age groups from <60 to >75 years. Clinical data, body mass index (BMI), and body composition were evaluated in the different age groups in patients with and without statin therapy. To analyze the impact of statin use on FFM, we regressed a patients FFM on an interaction term between statin use and age and other control variables. Results: Aging was associated with a decrease in BMI and FFM, while fat mass continuously increased up to the age of >75 years. This was paralleled by a continuous increase in fasting glucose levels in patients with and without statin therapy. The loss of FFM between the age group <60 years and >75 years was more pronounced in statin-treated patients (10.88%) than in non-statin users (8.47%). Creatine phosphokinase values revealed a decrease of 7.77 U/l between the age groups <60 and >75 years in non-statin users and of 14.75 U/l in statin users. Statistical analysis indicated that the effect of statin therapy on FFM is more pronounced in younger than in older patients. Conclusions: Patients under statin therapy seem to be more vulnerable to the aging-associated lowering of FFM. Diagnostic procedures and interventions to prevent a loss of muscle mass might be of particular advantage in elderly patients under statin therapy.

Uneventful self poisoning with a very high dose of captopril

A 43-year-old patient with mild heart failure attempted suicide by ingesting between 5000 and 7500 mg of captopril. Blood pressure oscillated around 100-120/50-75 mmHg and pulse rate showed no tendency to accelerate (75-100/min). The psychiatric examination showed no drug induced psychopathological symptoms. The calculated half-life of captopril was 4.4 h. Seven hours after ingestion of approximately 50 times the maximal therapeutic daily dose of captopril the serum concentration reached 20 micrograms/ml. The calculated amount of absorbed captopril was approximately 5400 mg. Atrial natriuretic factor (ANF) plasma levels were slightly elevated and showed no tendency to increase or to fall.

Stimulating effect of intermediate-density lipoproteins (IDL) from hyperlipemic plasma on hepatic lipase.

SummaryThe main lipoprotein density classes, namely very-low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), low-density lipoproteins (LDL), high-density lipoproteins2 (HDL2) and HDL3 were investigated with respect to their influence on hepatic lipase (HTGL) activity in vitro.Lipoproteins from pooled normal plasma (NP) and from pooled hyperlipemic plasma (HP) were prepared by means of sequential ultracentrifugation. Hepatic lipase was determined radioenzymatically after preincubation with protamine sulfate. It could be demonstrated that IDL from HP were able to stimulate HTGL activity by approximately 100% above the baseline value. HDL3 from both NP and HP revealed an inhibiting effect on HTGL activity. VLDL, LDL, and HDL2 exhibited no significant effect on HTGL activity.It is speculated that HTGL could possibly represent a second pathophysiological pathway for the catabolism of IDL in hyperlipemia but this presumption is supported by only a few investigations in vivo.

Pronounced diastolic blood pressure day- and nighttime difference: an indicator for longevity?

Accessible online at: http://BioMedNet.com/karger Dear Sir, Recently published intervention trials for antihypertensive therapy could clearly demonstrate that intensive blood pressure lowering is of advantage in reducing cardiovascular events, especially for diabetic patients [1, 2]. Beside an overall increased risk for hypertension, diabetes mellitus type 2 is associated with a reduced diastolic dayand nighttime difference (non-dipping) in 24hour blood pressure profile, where nighttime blood pressure values are normally 10–20% lower than daytime measurements [3]. Nondippers experience more cardiovascular events than nocturnal dippers, with female non-dippers having the greatest risk [4]. With respect to the circadian blood pressure rhythm and adequate antihypertensive treatment regimens, we were interested in the age dependence of the diastolic dayand nighttime difference and in the possible correlation with cardiovascular risk factors. For this purpose we evaluated the 24-hour blood pressure profiles of 511 outpatients (263 women, 248 men), consecutively recruited in our medical center. 24-Hour ambulatory blood pressure controls were performed as diagnostic procedures for hypotensive or hypertensive episodes, and measurements took place every 20 min from 06.00 to 24.00 h and hourly during the night with a portable device (Schiller BR 102, Basel, Switzerland). Our study population comprised 259 patients (51%) with antihypertensive medication, and 62 patients with diabetes mellitus type 2 (12%). The correlation between the diastolic dayand nighttime difference and other variables was computed with the Spearman correlation coefficient. The mean values of the diastolic dayand nighttime difference revealed a continuous decline with increasing age from 15.7 B 7.1 mm Hg in the group between 20 and 30 years to 10.0 B 9.3 mm Hg in patients between 70 and 80 years. This could be observed in women as well as in men (table 1), and in patients without and with antihypertensive medication, and could thus not only be ex-