Biomedical subjects

Kenneth Caidahl

Publications and source records attributed to Kenneth Caidahl.

At least 19 recordsLinked to original sources

PubMed2006

Platelet-derived growth factor B retention is essential for development of normal structure and function of conduit vessels and capillaries.

OBJECTIVE: Extracellular retention of PDGF-B has been proposed to play an important role in PDGF-B signalling. We used the PDGF-B retention motif knockout mouse (RetKO) to study the effects of retention motif deletion on development of micro- and macrovascular structure and function. METHODS: Passive and active properties of conduit vessels were studied using myograph techniques and histological examination. Capillary structure and function was studied using measurements of capillary density in skeletal muscle and by assessing aerobic physical performance in a treadmill setup. Cardiac function was assessed using echocardiography. RESULTS: Myograph experiments revealed an increased diameter and stiffness of the aorta in RetKO. Histological examination showed increased media collagen content and a decreased number of aortic wall layers, however with a similar number of vascular smooth muscle cells. This outward eutrophic remodelling of the aorta was accompanied by endothelial dysfunction. RetKO showed decreased capillary density in skeletal muscle and signs of a defective delivery of capillary oxygen to skeletal muscle, as shown by a decreased physical performance. In RetKO mice, echocardiography revealed an adaptive eccentric cardiac hypertrophy. CONCLUSION: We conclude that retention of PDGF-B during development is essential for a normal conduit vessel function in the adult mouse. Furthermore, PDGF-B retention is also necessary for the development of an adequate capillary density, and thereby for a normal oxygen delivery to skeletal muscle. The lack of primary effects on cardiac function supports the redundant role of PDGF-B in cardiac development.

Animals↗

PubMed2006

Can the left ventricular early diastolic tissue-to-blood time interval be used to identify a normal pulmonary capillary wedge pressure?

The pulsed Doppler early diastolic left ventricular (LV) tissue (e)-blood (E) onset temporal relationship (e-E) is suggested to predict pulmonary capillary wedge pressure (PCWP), through the formulas: tau = 32 + 0.7(e-E) and PCWP = LV end-systolic pressure x e(-IVRT/tau). Small changes/errors in E could influence the quotient IVRT/tau by oppositely affecting IVRT and e-E. At rest in 50 healthy individuals we noted: e-E: 2 +/- 14 ms; IVRT: 89 +/- 17 ms; calculated tau: 33 +/- 10 ms; and PCWP: 9 +/- 9 mmHg (> 12 mmHg in 28%). Non-pharmacological preload alterations in 14 individuals rendered an intraindividual 'PCWP'-fluctuation of up to 40 mmHg. This application may therefore not be clinically robust.

Aged↗

PubMed2006

CRP, interleukin-6, secretory phospholipase A2 group IIA, and intercellular adhesion molecule-1 during the early phase of acute coronary syndromes and long-term follow-up.

OBJECTIVES: The objectives of this study were to examine the time course of the inflammatory response in acute coronary syndromes (ACS) and to assess the markers of inflammation and their relation to disease severity. METHODS: We prospectively studied 134 patients with ACS who survived for at least 30 months. The patients were divided into four groups: acute myocardial infarction (MI) with (n=54) or without (n=46) ST-segment elevation and unstable angina with (n=14) or without (n=20) increased risk. Plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6), secretory phospholipase A2 group IIA (sPLA2-IIA), and intercellular adhesion molecule-1 (ICAM-1) were measured on days 1 and 4 and after 3 and 30 months. RESULTS: The highest levels of CRP and sPLA2-IIA were seen on day 4 but for IL-6 on day 1. These three markers, but not ICAM-1, were significantly related to disease severity, CKMB, and ejection fraction. Patients in Killip class II-IV had higher levels than those in Killip class I. The individual acute-phase responses correlated with marker levels at 3 and 30 months. ICAM-1 correlated with the development of congestive heart failure. CONCLUSIONS: In ACS there seems to be an individual predisposition to inflammatory response. Plasma IL-6 is the first marker to rise, while sPLA2-IIA and CRP peak later. All three markers, especially CRP, may discriminate between MI and non-MI. ICAM-1 seems to reflect other aspects of the inflammatory processes than the other markers. The results emphasize the complexity of the inflammatory response in ACS and stress the need for further studies involving multiple markers.

Aged↗

PubMed2006

Endothelial dysfunction in growth hormone transgenic mice.

Acromegaly [overproduction of GH (growth hormone)] is associated with cardiovascular disease. Transgenic mice overexpressing bGH (bovine GH) develop hypertension and hypercholesterolaemia and could be a model for cardiovascular disease in acromegaly. The aims of the present study were to investigate the effects of excess GH on vascular function and to test whether oxidative stress affects endothelial function in bGH transgenic mice. We studied the ACh (acetylcholine)-induced relaxation response in aortic and carotid rings of young (9-11 weeks) and aged (22-24 weeks) female bGH transgenic mice and littermate control mice, without and with the addition of a free radical scavenger {MnTBAP [Mn(III)tetrakis(4-benzoic acid)porphyrin chloride]}. We also measured mRNA levels of eNOS (endothelial nitric oxide synthase) and EC-SOD (extracellular superoxide dismutase). Intracellular superoxide anion production in the vascular wall was estimated using a dihydroethidium probe. Carotid arteries from bGH transgenic mice had an impaired ACh-induced relaxation response (young, 46 +/- 7% compared with 69 +/- 8%; aged, 52 +/- 5% compared with 80 +/- 3%; P < 0.05), whereas endothelial function in aorta was intact in young but impaired in aged bGH transgenic mice. Endothelial dysfunction was corrected by addition of MnTBAP in carotid arteries from young mice and in aortas from aged mice; however, MnTBAP did not correct endothelial dysfunction in carotid arteries from aged bGH transgenic mice. There was no difference in intracellular superoxide anion production between bGH transgenic mice and control mice, whereas mRNA expression of EC-SOD and eNOS was increased in aortas from young bGH transgenic mice compared with control mice (P < 0.05). We interpret these data to suggest that bGH overexpression is associated with a time- and vessel-specific deterioration in endothelial function, initially caused by increased oxidative stress and later by other alterations in vascular function.

Acetylcholine↗

PubMed2006

Low risk is associated with poorer quality of life than high risk following acute coronary syndrome.

BACKGROUND: Morbidity after acute coronary syndromes includes both physical and mental disorders affecting quality of life. The aim of this investigation was to study quality of life at a 3-month follow-up in patients with acute coronary syndrome, with the main objective of exploring whether unstable angina pectoris and myocardial infarction (MI) patients differ in this respect. METHODS: This investigation was part of a prospective risk stratification study of consecutive patients with acute coronary syndrome of whom 814 below the age of 75 years (278 diagnosed with unstable angina pectoris and 536 with myocardial infarction) accepted an invitation to a follow-up visit 3 months after discharge. At follow-up, the patients completed the Cardiac Health Profile, a disease-specific quality of life questionnaire, designed to evaluate perceived cognitive, emotional, social and physical function. RESULTS: Quality of life was mainly influenced by patient characteristics and previous history. The Cardiac Health Profile scores in unstable angina pectoris patients were significantly higher (i.e. poorer quality of life) than myocardial infarction patients at the 3-month visit (34, 22, 50; median, 25th, 75th percentile and 30, 19, 44; median, 25th, 75th percentile, respectively, P=0.006). The adjusted odds ratio for a poorer quality of life in unstable angina pectoris patients in relation to myocardial infarction patients was 1.39 (95% confidence interval 1.03, 1.87; P=0.03). The highest Cardiac Health Profile scores were seen in the unstable angina pectoris patients without electrocardiogram signs of ongoing ischemia and/or elevated markers of myocardial necrosis. CONCLUSION: Patients with unstable angina pectoris, especially of the low-risk type, and therefore treated accordingly, are more likely to experience poorer quality of life following an acute hospitalization than patients with other types of acute coronary syndrome. Once myocardial infarction or high-risk unstable angina pectoris has been ruled out, these patients still require a careful and systematic follow-up.

Acute Disease↗

PubMed2005

Short-term administration of growth hormone (GH) lowers blood pressure by activating eNOS/nitric oxide (NO)-pathway in male hypophysectomized (Hx) rats.

BACKGROUND: The aim of the study was to evaluate the acute and continuous (up to 14 days of treatment) effect of growth hormone (GH) on blood pressure (BP) regulation and to investigate the interplay between GH, nitric oxide (NO) and BP. In un-supplemented and GH supplemented hypophysectomized (Hx) male rats as well as intact rats, continuous resting mean arterial blood pressure (MAP) was measured using telemetry. Baroreceptor activity and the influences of NO on BP control were assessed during telemetric measurement. Furthermore, basal plasma and urine nitrate levels and aortic endothelial nitric oxide synthase (eNOS) expression were analysed. Endothelial function as well as vascular structure in the hindquarter vascular bed was estimated using an in vivo constant-flow preparation. RESULTS: Hypophysectomy was associated with decreased MAP (Hx: 83 +/- 3 vs Intact: 98 +/- 6 mmHg, p < 0.05) and heart rate (HR) (Hx: 291 +/- 4 vs Intact: 351 +/- 7 beat/min, p < 0.05). Endothelial dysfunction and reduced vasculature mass in the hindquarter vascular bed was found in Hx rats. GH substitution caused a further transient decrease in MAP and a transient increase in HR (14% and 16% respectively, p < 0.05). The reduction in MAP appeared to be NO dependent. Aortic eNOS expression was unchanged. GH substitution resulted in an impaired baroreceptor function. Two weeks of GH treatment did not normalise the BP, vascular structure and the endothelial function in the resistance vessels. CONCLUSION: GH substitution seems to have a short lasting effect on lowering blood pressure via activation of the NO-system. An interaction between GH, NO-system and BP regulation can be demonstrated.

Animals↗

PubMed2005

Left ventricular diastolic dysfunction late after aortic valve replacement in patients with aortic stenosis.

Patients with severe aortic stenosis (AS) are known to have increased left ventricular (LV) mass and diastolic dysfunction. It has been suggested that LV mass and diastolic function normalize after aortic valve replacement (AVR). In the present study, change in LV mass index and diastolic function 10 years after AVR for AS was evaluated. Patients who underwent AVR from 1991 to 1993 (n = 57; mean age 67 +/- 8.6 years at AVR, 58% men) were investigated with Doppler echocardiography preoperatively and 2 and 10 years postoperatively. Diastolic function was evaluated by integrating mitral and pulmonary venous flow data. Expected values for each patient, taking age into consideration, were defined using a control group (n = 71; age range 18 to 83 years). Patients were classified into 4 types: normal diastolic function (type A), mild diastolic dysfunction (type B), moderate diastolic dysfunction (type C), and severe diastolic dysfunction (type D). There was a reduction in LV mass index between the preoperative (161 +/- 39 g/m2) and 2-year follow-up (114 +/- 28 g/m2) examinations (p <0.0001), but no further reduction was seen at 10 years (119 +/- 49 g/m2). The percentage of patients with increased LV mass index decreased from 83% preoperatively to 29% at 2-year follow-up (p <0.001). The percentage of patients with moderate to severe LV diastolic dysfunction (types C and D) was unchanged between the preoperative (7%) and 2-year follow-up (13%) examinations (p = 0.27). The percentage of patients increased at 10-year follow-up to 61% (p <0.0001). In conclusion, this reveals the development of moderate to severe diastolic dysfunction 10 years after AVR, despite a reduction in the LV mass index.

Adult↗

PubMed2005

Treatment and short-term outcome in women and men with acute coronary syndromes.

OBJECTIVE: To study differences in treatment and early morbidity and mortality in relation to gender, type of acute coronary syndrome (ACS) and age in patients under 80 years of age. METHODS: We studied 1744 consecutive patients with ACS with assumed decreasing order of severity [ST-elevation myocardial infarction (MI), non-ST-elevation MI and unstable angina of high- and low-risk types] admitted to the coronary care unit at Sahlgrenska University Hospital. RESULTS: The use of thrombolysis and percutaneous coronary interventions (PCI) did not differ significantly between gender groups and women did not suffer from more severe complications than men. Treatment with beta-blockers, ACE inhibitors and aspirin was used on a similar scale among women and men. In-hospital complications and use of intravenous drugs were strongly associated with severity of disease in a similar way among women and men. The mortality rates at 30 days were 12.4% and 7.4% in MI with and without ST-segment elevation, but only 1.3% and 1.0% in unstable angina of high- and low-risk types. The use of primary PCI decreased with age, as did coronary angiography and PCI in the subacute phase, irrespective of gender. CONCLUSION: Among patients <80 years with ACS admitted to a coronary care unit, the suspicion that women are treated less aggressively than men could not be verified. Nor did women suffer from more complications or have a significantly higher 30-day mortality than men. Elderly patients were significantly less likely to undergo invasive procedures than those of a younger age, irrespective of gender.

Acute Disease↗

PubMed2005

Usefulness of atrial size inequality as an indicator of abnormal left ventricular filling.

Although pulsed Doppler echocardiography estimates current left ventricular (LV) filling, left atrial (LA) size reflects LV filling and pressure over time. However, the wide normal LA size range may blunt this diagnostic tool. Our objective was to compare the intraindividual atrial area difference (LA--right atrial [RA] area) and absolute LA area in their detection of a LA enlargement with respect to the degree of current LV filling impairment. We examined patients with acute coronary syndromes in sinus rhythm and without valvular disease (n = 154), and age- and gender-matched healthy controls (n=50) with echocardiography, applying pulsed Doppler international recommendations to group the patients according to the LV filling pattern: 0, normal; 1, delayed relaxation; 2, an isolated abnormal mitral pulmonary venous A-wave duration difference; 3, pseudonormal; and 4, restrictive. The LA and RA areas were measured in the 4-chamber view. Control values defined the normal range of: absolute LA area, LA area adjusted for body height, and LA-RA area. These areas indicated a LA enlargement in: (1) controls, 2%, 2%, and 4%, respectively; (2) patients with LV filling graded as normal/mildly impaired (groups 0 and 1), 15%, 17%, and 46%, respectively; moderately impaired (group 2), 26%, 29%, and 52%, respectively; and severely impaired (group 3 and 4), 42%, 38%, and 54%, respectively. Unequally sized atria appear to detect LA enlargement sensitively, especially when Doppler evidence of LV filling pathology is sparse. Clinically, with no obvious current cause for LA enlargement, a diagnosed "atrial size inequality" may still indicate a history of such causes.

Aged↗

PubMed2005

The E/e filling index and right ventricular pressure in relation to applied international Doppler recommendations of left ventricular filling assessment.

AIM: A ratio>15 between the early diastolic pulsed Doppler velocities of the mitral inflow (E) and the basal left ventricular (LV) tissue (e) has been demonstrated to predict an elevated LV filling pressure (FP). An elevated LVFP implies an elevated right ventricular pressure (RVp). In order to investigate the sensitivity of the E/e filling index, we compared E/e and RVp, in their ability to identify a Doppler-assumed elevation of LVFP. METHODS AND RESULTS: Application of pulsed Doppler international recommendations grouped 134 patients with acute coronary syndromes (ACS) and 50 age- and sex-matched controls, according to LV filling: normal; delayed relaxation; an isolated pathological mitral-pulmonary venous-A-wave-duration difference; pseudo normal; or a restrictive filling pattern. An E/e>15 and an RVp>30 mmHg showed the following (%) sensitivity (32/94), specificity (95/76), positive (68/59), and negative (80/97) predictive values of a Doppler-assumed elevation of LVFP, in terms of either a pseudo normal or a restrictive filling pattern. CONCLUSION: The low sensitivity of E/e to detect a Doppler-assumed elevation of LVFP could limit its clinical usefulness as a single variable, in ACS. The high sensitivity and negative predictive value of RVp support its use as an additional LV filling variable in these patients.

Aged↗

PubMed2005

Short-term administration of supraphysiological recombinant human growth hormone (GH) does not increase maximum endurance exercise capacity in healthy, active young men and women with normal GH-insulin-like growth factor I axes.

CONTEXT: Despite the fact that the use of GH as a doping agent in sports is widespread, little is known about its short-term effects. OBJECTIVE: The objective was to study the effects of GH on exercise capacity. DESIGN: A double-blind, placebo-controlled study was used, with a treatment period of 28 d. SETTING: Subjects from general community studied ambulatory at a university hospital. PARTICIPANTS: Thirty healthy active young normal volunteers (15 women and 15 men) were recruited by local announcement, and all completed the study. INTERVENTION: All subjects were randomized to receive a low GH dose (0.033 mg/kg.d or 0.1 IU/kg.d), a high GH dose (0.067 mg/kg.d or 0.2 IU/kg.d), or placebo. MAIN OUTCOME MEASURES: Power output and oxygen uptake on bicycle exercise were the main outcome measures. RESULTS: We found no effect of the low or high dosages of GH on maximum oxygen uptake during exercise (mean +/- se for placebo, 45.2 +/- 1.6 to 45.2 +/- 2.1 ml/kg.min; GH low dose, 42.8 +/- 1.6 to 42.8 +/- 1.6 ml/kg.min; GH high dose, 44.8 +/- 3.4 to 44.8 +/- 2.2 ml/kg.min; not significant by two-way ANOVA). Neither was there any effect on maximum achieved power output during exercise or on blood pressure, heart rate, or the electrocardiographic ST level at rest or during exercise. GH significantly increased total body weight (P = 0.028), an effect predominantly ascribed to fluid retention (increased extracellular water volume), whereas muscle mass (as indicated by intracellular water volume) did not change. However, changes in the latter correlated to changes in physical performance, possibly due to different training efforts. CONCLUSION: Administration of supraphysiological recombinant human GH during a period of 4 wk does not improve power output or oxygen uptake.

Blood Pressure↗

PubMed2005

Determinants for an impaired quality of life 10 years after coronary artery bypass surgery.

OBJECTIVE: To identify determinants of an inferior quality of life (QoL) 10 years after coronary artery bypass grafting (CABG). SETTING: Sahlgrenska University Hospital, Göteborg, Sweden. PARTICIPANTS: All patients from Western Sweden who underwent CABG between 1988 and 1991 without simultaneous valve surgery and no previous CABG. MAIN OUTCOME MEASURES: Questionnaires for evaluating QoL 10 years after the operation. Three different instruments were used: The Nottingham health profile (NHP), the psychological general wellbeing index (PGWI), and the Physical Activity Score (PAS). RESULTS: 2000 patients underwent CABG, of whom 633 died during 10 years of follow-up. Information on QoL at 10 years was available in 976 patients (71% of survivors). A history of diabetes and chronic obstructive pulmonary disease were the two independent predictors for an inferior QoL with all three instruments. Furthermore, there were three predictors of an inferior QoL with two of the instruments: high age, female sex and a history of hypertension. A number of factors predicted an inferior QoL with one of the instruments. These were the duration of angina pectoris and functional class prior to CABG, renal dysfunction, a history of cerebrovascular disease, obesity, height, duration of respirator treatment and requirement of inotropic drugs postoperatively. In addition, when introducing preoperative QoL into the model a low QoL before surgery was a strong independent predictor also of an inferior QoL 10 years after CABG. CONCLUSION: Variables independently predictive of an impaired QoL 10 years after CABG, irrespective of the instrument used, were an impaired QoL prior to surgery, chronic obstructive pulmonary disease and a history of diabetes. However, other factors reflecting gender, the previous history as well as postoperative complications were also associated with the QoL 10 years later in at least one of these instruments.

Aged↗

PubMed2005

Low adipocyte IRS-1 protein expression is associated with an increased arterial stiffness in non-diabetic males.

OBJECTIVE: Low adipocyte IRS-1 protein expression is a biomarker for insulin resistance and early atherosclerosis. However, whether IRS-1 protein expression is related to systemic arterial stiffness, is unknown. METHODS AND RESULTS: Ten non-diabetic male subjects with low adipocyte IRS-1 protein expression (LIRS) were matched with 10 non-diabetic males with normal IRS-1 protein expression (NIRS). Augmentation index (AIx) and time for reflection of pulse wave (Tr) were studied with pulse wave analysis, both in the fasting state and during a euglycemic hyperinsulinemic clamp. The LIRS-group showed an increased fasting insulin concentration (fP-insulin 71+/-4 pmol/L versus 58+/-5 pmol/L; p=0.02 (mean+/-S.E.)), whereas glucose disposal rate during the clamp (8.7+/-0.8 mg/kg LBM/min versus 10.3+/-1.3 mg/kg LBM/min; n.s.) did not differ significantly. Blood pressure, lipid parameters, adiponectin, endothelin-1 and CRP concentrations were similar. However, in the basal state, AIx was increased (129+/-4% versus 116+/-2%; p<0.02) and Tr was decreased (150+/-3 ms versus 171+/-5 ms; p<0.01), suggesting stiffer vessels in the LIRS-group. The LIRS-group exhibited an attenuated AIx response to hyperinsulinemia compared to the NIRS-group. CONCLUSIONS: The data suggest that non-obese non-diabetic men with a low adipocyte IRS-1 protein expression have an increased systemic arterial stiffness.

Adipocytes↗

PubMed2005

Recent methodological advances in the mass spectrometric analysis of free and protein-associated 3-nitrotyrosine in human plasma.

L-Tyrosine and L-tyrosine residues in proteins are attacked by various reactive-nitrogen species (RNS) including peroxynitrite to form 3-nitrotyrosine (NO(2)Tyr) and protein-associated 3-nitrotyrosine (NO(2)TyrProt). Circulating NO(2)Tyr and NO(2)TyrProt have been suggested and are widely used as biomarkers of oxidative stress in humans. In this article the mass spectrometry (MS)-based analytical methods recently reported for the quantification of circulating levels of NO(2)Tyr and NO(2)TyrProt are discussed. These methodologies differ in sensitivity, selectivity, specificity and accessibility to interferences with the latter mainly arising from artifactual formation of NO(2)Tyr and NO(2)TyrProt during sample treatment such as acidification and chemical derivatization. Application of these methodologies to healthy normal humans revealed basal circulating levels for NO(2)Tyr which range between 0.7 and 64 nM, i.e. by two orders of magnitude. Application of gas chromatography-tandem mass spectrometry (GC-tandem MS) methods by two independent research groups by using two different protocols to avoid artifactual nitration of L-tyrosine revealed almost identical mean plasma levels of the order of 1.0 nM in healthy humans. The lower limits of quantitation (LOQ) of these methods were 0.125 and 0.3n M, respectively. This order of magnitude for basal NO(2)Tyr is supported by two liquid chromatography-tandem mass spectrometry (LC-tandem MS) methods with LOQ values of 4.4 and 1.4 nM. On the basis of the data provided by GC-tandem MS and LC-tandem MS the use of a range of 0.5-3 nM for NO(2)Tyr and of 0.6 pmol/mg plasma protein or a molar ratio of 3-nitrotyrosine to tyrosine in plasma proteins of the order of 1:10(6) for NO(2)TyrProt in plasma of healthy humans as reference values appear reasonably justified. Recently reported clinical studies involving 3-nitrotyrosine as a biomarker of oxidative stress are discussed in particular from the analytical point of view.

Humans↗

PubMed2005

Preoperative moderate to severe diastolic dysfunction: a novel Doppler echocardiographic long-term prognostic factor in patients with severe aortic stenosis.

OBJECTIVE: We studied long-term outcomes in severe aortic stenosis and the importance of prosthesis type (mechanical vs biologic) and size, preoperative left ventricular ejection fraction, diastolic function, and left ventricular mass. METHODS: Patients undergoing valve replacement from 1991 to 1993 (n = 399, 45% women) were included. The diastolic function was evaluated by integrating mitral and pulmonary venous flow data with Doppler echocardiography. The patients were classified as having either normal diastolic function to mild diastolic dysfunction or moderate to severe diastolic dysfunction. Left ventricular ejection fraction and the diastolic function category were incorporated together with age, sex, and time since operation into a Poisson regression model with death as the end point. Prosthesis type and size and left ventricular mass were also investigated. RESULTS: The age (mean +/- SD) was 71 +/- 9 years, and the overall survival after 12 years was 50%. Although markedly reduced during the initial 6-month period, mortality risk subsequently increased more than could be explained by age (hazard ratio of 1-year difference = 1.12, P = .0005). The moderate to severe diastolic dysfunction pattern independently predicted late mortality (hazard ratio = 1.72, P = .0038), whereas left ventricular ejection fraction did not (hazard ratio = 0.99, P = .18). The prognostic importance of moderate to severe diastolic dysfunction did not diminish with time; on the contrary, it tended to increase. Mortality after 12 years was not predicted by left ventricular mass (P = .66), prosthesis type (P = .57), or prosthesis size (P = .58). CONCLUSION: This study reveals that moderate to severe diastolic dysfunction in patients with aortic stenosis is an independent predictor of late mortality after valve replacement and that its importance does not decrease with time. Our findings may suggest that moderate to severe diastolic dysfunction implies nonreversible myocardial changes that negatively affect survival.

Age Factors↗

PubMed2005

Selective quantification of free 3-nitrotyrosine in exhaled breath condensate in asthma using gas chromatography/tandem mass spectrometry.

Reactive nitrogen species can cause oxidative modifications of certain amino acid residues in proteins, notably the modification of tyrosine to 3-nitrotyrosine (3-NT), which is a potentially useful marker of oxidative stress. Since lung diseases are associated with airway inflammation and oxidative stress, quantification of 3-NT in exhaled breath condensate (EBC) may provide a non-invasive means for monitoring ongoing inflammatory processes. 3-NT-like immunoreactivity has previously been detected in EBC, but no definitive evidence for the presence of 3-NT in EBC is available. Here, a method based on gas chromatography/negative ion chemical ionization/tandem mass spectrometry was established for the quantification of free 3-NT in EBC. The detection limit was 0.56 pM (corresponding to 3.0 amol microl(-1) sample injected) and the method was found to give linear results (r2 > 0.999) in the concentration range of 0-5.0 nM. The coefficient of variation (CV) for within-day and between-day precision were 11 and 12%, respectively. No artifactual nitration was observed during sample processing. The method was applied to study subjects with asthma (n = 8), and healthy subjects (n = 10), but only a slight non-significant increase in 3-NT levels was found in the former group (median [interquartile ranges]; 99 [50-547] amol s(-1) vs. 75 [35-147] amol s(-1)). No correlation with exhaled nitric oxide (NO), pulmonary function or EBC levels of total protein was observed. The 3-NT levels were much lower compared to previously reported levels, based on immunochemical measurements. The method does not allow the simultaneous quantification of tyrosine in samples.

Adult↗

PubMed2005

Disturbed right ventricular diastolic function in patients with systemic sclerosis: a Doppler tissue imaging study.

BACKGROUND: Cardiopulmonary involvement in patients with systemic sclerosis (SSc) carries a poor prognosis, mainly due to pulmonary hypertension and right-heart failure. To date, right ventricular (RV) involvement has not been studied in detail. We therefore assessed RV function in patients with SSc and related the findings to the clinical features of the disease. METHOD: Twenty-six consecutive patients (21 women) with SSc (mean age, 56 +/- 15 years [+/- SD]) and 25 healthy, age-matched control subjects (21 women) were studied. Doppler echocardiography including Doppler tissue imaging was used to evaluate cardiac function. Pulmonary function was also studied. RESULTS: Compared with control subjects, RV free wall thickness (5.8 +/- 1.7 mm vs 3.7 +/- 1.1 mm, p < 0.001) and right atrial (RA) systolic area (15.9 +/- 3.7 cm2 vs 13.0 +/- 2.3 cm2, p < 0.01) were increased in patients with SSc, while the global early diastolic/atrial component velocity ratio was reduced (1.2 +/- 0.4 vs 1.7 +/- 0.6, p < 0.01). The global isovolumic relaxation time (IVRT) [64 +/- 23 ms vs 39 +/- 13 ms, p < 0.001] and regional IVRT (83 +/- 40 ms vs 46 +/- 24 ms, p < 0.001) were prolonged in patients vs control subjects, whereas the RV global filling time was reduced (454 +/- 122 ms vs 548 +/- 104 ms, p < 0.01). RV systolic function and pulmonary pressures at rest were similar in the two groups, but the pulmonary artery acceleration time was reduced (119 +/- 34 ms vs 141 +/- 29 ms, p < 0.05) in patients compared to control subjects. Left ventricular function did not differ between the two groups. CONCLUSION: Patients with SSc exhibit altered RV diastolic function together with an increase in RV wall thickness and RA area. These findings appear to be early markers of RV disturbance, probably in response to intermittent pulmonary arterial hypertension.

Adult↗

PubMed2004

Spectrum of acute coronary syndromes: history and clinical presentation in relation to sex and age.

OBJECTIVES: To study sex-based differences in the clinical presentation in relation to age and type of acute coronary syndrome (ACS) in patients under 80 years of age. METHODS: The study includes 1,744 consecutive patients with the full spectrum of ACS (ST elevation myocardial infarction (MI), non-ST elevation MI, and unstable angina of high- and low-risk types) admitted to the coronary care unit in a university hospital. RESULTS: The women were older than the men and were as likely to present with ST elevation MI. They had lower rates of prior MI and prior coronary artery bypass surgery than men but similar rates of percutaneous coronary interventions. Further, women were less likely to have a short delay before admission to hospital and they were attended to less rapidly in the emergency department. The prevalence of risk factors, prior cardiovascular disease and ongoing treatment with cardiovascular drugs were strongly associated with less severe type of ACS with no significant sex interaction. Presentation with non-ST elevation MI was significantly associated with older age while the opposite was true for unstable low-risk angina. ECG signs of acute ischemia were not associated with age. Significant interactions between age and sex were observed for the prevalence of treatment with diuretics as well as hypotension at presentation, both more prevalent among women than men below 65 years of age. CONCLUSIONS: Women are struck by ACS at a higher age than men, are less likely to present early for hospital care, and at younger age women are more likely to present with hypotension. There is a striking difference in risk factors and previous history depending on type of ACS in both sexes.

Age Factors↗