Metabolism of apolipoproteins AI and AII in subjects carrying similar apoAI mutations, apoAI Milano and apoAI Paris

ApoAI Milano (AI(M)) and apoAI Paris (AI(P)) are mutant forms of apoAI in which cysteine is substituted for arginine at residues 173 and 151 respectively leading to the formation of homodimers and heterodimers with apoAII. Heterozygous subjects with these mutants are characterized by low levels of plasma HDL cholesterol and apoAI. The present study analyzed the metabolism of the different complexes of apoAI in three subjects, two AI(M) and one AI(P), using a primed-constant infusion of trideuterated leucine. In AI(M) carriers, the mutant form was almost equally distributed in AI(M) dimer, AI(M):AII heterodimer and the monomer, whereas, in the AI(P) subject, the mutant apoAI was essentially in the apoAI(P):AII complex. Normal apoAI was low in the AI(M) subjects (20 and 16 mg/dl) but very low in the AI(P) subject (0.3 mg/dl). In the AI(M) subjects, the low levels of apoAI were due to a rapid catabolism with a normal synthetic rate. However, the apoAI kinetics were heterogeneous with a rapid catabolism of the AI(M):AII complex (FCR of 0.430 and 0.401 day(-1)) and the AI(M) monomer (FCR of 0.570 and 0.406 day(-1)) whereas the AI(M) dimer was catabolized slowly (FCR of 0.114 and 0. 118 day(-1)). In contrast, AI(P) was catabolized relatively slowly with a FCR of 0.263, 0.182 and 0.258 day(-1) for AI(P) homodimer, apoAI(P):AII heterodimer and AI(P) monomer. In the three subjects, normal apoAI was catabolized quickly, with an FCR of 0.805 and 0.601 day(-1) in AI(M) carriers and 0.526 day(-1) in the AI(P) carrier. Therefore, the low level of apoAI in the AI(P) carrier is caused by a low production rate of apoAI, particularly of normal apoAI. In conclusion, apoAI is kinetically heterogeneous in AI(M) and in AI(P) subjects. Moreover, the two mutations lead to significant differences in the kinetic behavior of mutant apoAI depending on its inclusion in its complexes.     

Influence of aortic insufficiency on the hemodynamic significance of a coronary artery narrowing.

The coronary hemodynamic effects of controlled aortic insufficiency (AI) were studied in 10 dogs. Coronary blood flow (CBF), before and during reactive hyperemia (RH) with graded coronary diameter narrowings (CN), aortic (Ao) and left ventricular (LV) pressures (P), and aortic blood flow (AoF) were recorded. Opening an adjustable basket catheter, positioned across the aortic valve, created reversible AI quantitated from phasic AoF. AI was regulated so that mean CBF was similar with or without AI. During AI, heart rate and systolic AoP were unchanged, but diastolic AoP declined 14 mm Hg (mean) and end-diastolic LVP increased 8 mm Hg, both p less than 0.05. With CN greater than or equal to 85%, mean CBF decreased with or without AI. Coronary resistance was similar with or without AI. During AI with no CN, peak RH CBF declined significantly and was similar to peak RH with 70% CN without AI. Furthermore, AI with 60% CN caused additional reduction in peak RH and was similar to peak RH with 80% CN without AI. These data suggest that CBF reserve, exposed during RH, is decreased during AI. With AI, a given CN has coronary hemodynamic properties similar to higher degrees of CN without AI. These results may relate to clinical findings of ischemia in patients with AI and no or moderate CN.     

Is augmentation index a good measure of vascular stiffness in the elderly?

OBJECTIVES: we investigated the exact relationship between age and gender on augmentation pressure (AG) and augmentation index (AI) measured over the radial (muscular) and carotid (elastic) arteries. DESIGN AND METHODS: AG is the contribution that wave reflection makes to systolic arterial pressure. AI is an indirect measure of arterial stiffness and is calculated as AG divided by pulse pressure (PP) x100. AG and AI both increase with age. AG and AI were measured in 458 subjects using SphygmoCor. A total of 755 readings were obtained (302 carotid, 453 radial). The mean age was 57.5 +/- 13.7 years. Diabetic subjects were excluded. Among the subjects, 13.5% were hypertensive. RESULTS: statistically, women had mean values of AI significantly higher than men in both radial and carotid arteries. These differences were less marked with AG. Quadratic equations better described the relationship between AI and age but not AG and age. Thus, AI increased with age up to our median age of 55 years but plateaued thereafter, whereas the AG continued to increase steadily with age. A multiple regression analysis demonstrated that both AI and AG were negatively related to height and positively related to diastolic blood pressure (DBP). CONCLUSIONS: AG continues to increase in the elderly over the age of 55, but not AI. AI is higher in women and higher when measured over the carotid than the radial. AI is positively related to DBP and negatively to height. AG is proposed as a more suitable measure of arterial stiffness than AI.     

Accuracy of Intraoperative Transesophageal Echocardiography in the Prediction of Future Neo‐aortic Valve Function after the Ross Procedure in Children and Young Adults

Objective. Neo‐aortic insufficiency (neo‐AI) has been noted following the Ross procedure. The purpose of this study was to evaluate the ability of intraoperative transesophageal echocardiography (TEE) to predict future neo‐AI in pediatric patients undergoing the Ross from January 1995 to December 2003, who had an intraoperative TEE, and discharge and follow‐up transthoracic (TTE) echocardiograms. Design. Retrospective case series. Patients. All patients who underwent the Ross procedure at Children's Hospital of Philadephia between January 1995 and December 2003, and had an intraoperative TEE, discharge, and follow‐up (>6 months) transthoracic echocardiogram (TTE) (by July 1, 2004) were included. Outcome Measures. Grade of neo‐AI was assessed on intraoperative TEE, discharge, and follow‐up TTE echocardiogram reports. Results. Follow‐up was available in 99/115 (86%) survivors. Median age at Ross was 9.3 years (4 days?34 years). No patient had more than mild neo‐AI on intraoperative TEE. At discharge, 2 patients (2%) had moderate neo‐AI. At most recent follow‐up (median 4.2 years, 8 months?9.3 years), 21 patients (21%) had moderate or greater neo‐AI; 9 underwent neo‐aortic reintervention. The presence of any neo‐AI on intraoperative TEE had 100% sensitivity and negative predictive value for diagnosing moderate or greater neo‐AI at discharge. Patients who had mild neo‐AI on TEE were more likely to have moderate or greater neo‐AI at most recent follow‐up than those patients with no neo‐AI on TEE (9% vs. 30%, P = 0.01). Conclusion. Intraoperative TEE is an excellent screening tool for the presence of significant neo‐AI at the time of hospital discharge. Neo‐AI progresses over time after Ross procedure and is more likely to progress in those patients with neo‐AI on intraoperative TEE. However, predictive validity decreases over time as neo‐AI progresses.     

Comparison of augmentation index derived from multiple devices

One of the most commonly evaluated features of the arterial pressure waveforms is augmentation index (AI). Multiple devices have been developed and marketed that measure AI at peripheral arteries. Currently, it is not known if and how these measures of AI are related. Aortic and radial AI (using SphygmoCor), radial AI (Omron), and finger AI (Itamar) were measured in 40 apparently healthy subjects. All the AI values were correlated with each other with Pearson r-values ranging from 0.78 to 0.94. The coefficients of variation ranged from 3.4 to 20.0%. We concluded that even though the absolute values derived by each technique were different, there were high and significant correlations between AI values.     

Allatinhibin, a neurohormonal inhibitor of juvenile hormone biosynthesis in Manduca sexta

The corpora allata (CA) of Manduca sexta larvae become incapable of synthesizing juvenile hormone (JH) early in the wandering stage of the last larval stadium. They then switch to the synthesis and release of JH acids. This change in CA activity is induced by an inhibitory factor--allatinhibin (AI)--from the brain. AI activity is present in the fifth (Vth) instar hemolymph from about Day 4 (day of wandering) until Day 7 (early prepupa). CA of early fifth instar larvae (uninhibited) incubated in vitro with brain-corpora cardiaca-corpora allata (Br-CC-CA) complexes or brain alone from wandering larvae are inhibited as demonstrated by bioassay. On the basis of these observations, an in vitro-in vivo assay for AI was developed. Br-CC-CA or Br alone were first incubated in tissue culture medium overnight. Day 0 (0d) Vth instar CA incubated for 16 hr in such medium will lose the ability to induce a larval molt in allatectomized 0d IVth instar larvae if the medium contained AI activity. The highest AI activity was exhibited by the medium obtained from incubations of brain from wandering larvae whereas the medium from incubation of 0d Vth and 0d pupal brains showed no AI activity. Dose-response data show that AI is active at 0.03 brain equivalents/200 microliters medium. CA must be exposed to AI for 12-16 hr for manifestation of inhibition. AI causes a stable inhibition of CA. AI is heat-labile, protease sensitive, has a molecular size between 1.0 and 3.5 kDa, and is clearly distinct from the allatostatins described by others.     

Physical activity reduces genetic susceptibility to increased central systolic pressure augmentation: a study of female twins

OBJECTIVES: We sought to examine associations between the augmentation index (AI) and metabolic, adiposity, and lifestyle factors, independent of genetic influences, and to determine whether gene-environment interactions modulate these relationships. BACKGROUND: Reported associations between AI, an index of systemic arterial stiffness, and metabolic, adiposity, and lifestyle factors remain contradictory. The modulating effect of genetic risk is unknown. METHODS: We studied 684 female twins (age 18 to 71 years); AI was derived from the pressure waveform measured at the radial artery by applanation tonometry. Percentage of total body fat (TBF) and percentage of central abdominal fat (CAF) were assessed by dual-energy X-ray absorptiometry. RESULTS: In univariate analysis, age-adjusted AI was significantly associated with fasting triglyceride levels (r = 0.1, P = 0.03), apolipoprotein-B/A1 (r = 0.1, P = 0.04), percentage of TBF (r = 0.11, P = 0.006), and percentage of CAF (r = 0.11, P = 0.004). In co-twin case-control (monozygotic twin) analysis, a 3.1% absolute within-pair difference in percentage of CAF accounted for a 6% within-pair difference in AI, independent of genetic effects. Smokers and subjects with alcohol intakes >15 U/week had higher AI than nonsmokers (p = 0.01) and nondrinkers (p = 0.02), respectively. Forty percent of the variance in AI was explained by age, central mean arterial pressure, heart rate, height, percentage of CAF, and smoking. In gene-environment interaction analysis, subjects at high genetic risk of increased AI participating in regular leisure-time physical activity had AI values similar to low genetic risk subjects. CONCLUSIONS: Central abdominal adiposity is a significant determinant of AI in female twins, independent of hemodynamic, lifestyle, and, importantly, genetic effects. Smoking is associated with increased AI, even after controlling for abdominal obesity and other AI determinants. Physical activity reduces genetic predisposition to increased AI.     

Diastolic stiffness and myocardial structure in aortic valve disease before and after valve replacement

Passive diastolic properties were determined in 10 control patients and 21 patients with aortic valve disease before and 17.5 months after successful valve replacement. Ten patients had severe aortic stenoses (AS), five had combined aortic valve lesions (AS + aortic insufficiency [AI]), and six patients had severe AI. Left ventricular endomyocardial biopsies were obtained before and after surgery in patients with AS, AS + AI, and AI. Simultaneous echocardiographic and high-fidelity pressure measurements were made in all patients, and left ventricular chamber stiffness was calculated from a viscoelastic pressure-circumference relationship and left ventricular myocardial stiffness from a viscoelastic stress-strain relationship. The constant of chamber stiffness, beta', was slightly although not significantly increased in patients with AS (0.27 before and 0.24 after surgery), but was normal in those with AS + AI (0.22 before and 0.17 after surgery) and slightly decreased in those with AI (0.18 before and 0.16 after surgery) when compared with in control subjects (0.21). The constant of myocardial stiffness beta was normal in patients with AS (13.2), AS + AI (11.5), and AI (11.7) before surgery compared with in the control group (12.5). beta increased, however, significantly in those with AS (25.2; p less than .02), but not in those with AS + AI (16.3; NS) and AI (12.8; NS) after surgery. Myocardial morphologic characteristics showed a significant decrease in muscle fiber diameter in patients with AS, AS + AI, and AI, as well as a significant increase in interstitial fibrosis from 15% to 26% (p less than .05) in those with AS and a slight increase from 15% to 22% (NS) in those with AS + AI and from 19% to 24% (NS) in those with AI. Left ventricular fibrous content (left ventricular muscle mass index multiplied by interstitial fibrosis) remained, however, unchanged in all three groups after aortic valve replacement. In conclusion, left ventricular chamber stiffness is increased in AS but decreased in AI, whereas LV myocardial stiffness is normal in patients with aortic valve disease before surgery. After surgery, left ventricular myocardial stiffness increased significantly in AS patients but remained unchanged in those with AI. Postoperative changes in myocardial structure were characterized by a decrease in muscle fiber diameter and a relative increase in interstitial fibrosis, whereas fibrous content remained unchanged. Thus, regression of myocardial hypertrophy in aortic valve disease is accompanied by an increase of myocardial stiffness in concentric hypertrophy that is not seen in eccentric hypertrophy.     

Patterns of alcohol consumption and alcohol-impaired driving in the United States

Background:  Alcohol-related motor vehicle crashes kill approximately 17,000 Americans annually and were associated with more than $51 billion in total costs in 2000. Relatively little is known about the drinking patterns of alcohol-impaired (AI) drivers in the United States.
Methods:  2006 Behavioral Risk Factor Surveillance System (BRFSS) was analyzed for alcohol consumption and self-reported AI driving among U.S. adults aged ≥18 years for all states. Alcohol consumption was divided into 4 categories: binge/heavy, binge/nonheavy, nonbinge/heavy, and nonbinge/nonheavy. Binge drinking was defined as ≥5 drinks for men or ≥4 drinks for women on one or more occasions in the past month, and heavy drinking was defined as average daily consumption of >2 drinks/day (men) or >1 drink/day (women). The prevalence of AI driving was examined by drinking pattern and by demographic characteristics. Logistic regression analysis was used to assess the association between drinking patterns and AI driving.
Results:  Five percent of drinkers were engaged in AI driving during the past 30 days. Overall, 84% of AI drivers were binge drinkers and 88% of AI driving episodes involved binge drinkers. By drinking category, binge/nonheavy drinkers accounted for the largest percentage of AI drivers (49.4%), while binge/heavy drinkers accounted for the most episodes of AI driving (51.3%). The adjusted odds of AI driving were 20.1 (95% CI: 16.7, 24.3) for binge/heavy, 8.2 (6.9, 9.7) for binge/nonheavy, and 3.9 (2.4, 6.3) for nonbinge/heavy drinkers, respectively.
Conclusions:  There is a strong association between binge drinking and AI driving. Most AI drivers and almost half of all AI driving episodes involve persons who are not heavy drinkers (based on average daily consumption). Implementing effective interventions to prevent binge drinking could substantially reduce AI driving.     

Cyclosporin A inhibits apolipoprotein AI gene expression

Cyclosporin A (CsA), a calcineurin inhibitor, has been widely used as an immunosuppressant, and is known to induce hyperlipidemia and dyslipoproteinemia with low levels of high-density lipoprotein (HDL). Since apolipoprotein AI (apo AI) is a major protein component of HDL particles and reduction of apo AI results in low levels of HDL, we hypothesized that CsA inhibits apo AI gene expression contributing to its lipid effects. Therefore, we first measured the serum apo AI protein levels in rats with or without CsA treatment, and found that both serum apo AI protein and liver apo AI mRNA levels were significantly reduced in response to CsA treatment. In stably transfected Hep G2 cells harboring an apo AI-474-CAT reporter gene, we found that intracellular calcium mobilization by A23187 a calcium ionophore stimulated apo AI gene expression and the calcineurin inhibitors, CsA and FK605, selectively inhibited this stimulation. Therefore, we conclude that activation of the calcineurin pathway by intracellular calcium mobilization stimulates apo AI gene expression and calcineurin inhibition by CsA results in reduced apo AI gene expression.     

An updated model of clinical asthma.

A model of asthma, based on the Expert Panel Report but updated to allow for the independence of bronchial hyperresponsiveness from airway inflammation, is presented. The updated model of asthma can be summarized: (1) AI = f1(Allergen)-f2(AI); (2) BHR = f3(Allergen)-f4(BHR); (3) PR = f5(AI); (4) Asthma = f6(AI + BHR + PR); where AI is airway inflammation, Allergen is sensitization by allergen, BHR is bronchial hyperreactivity, and PR is pulmonary remodeling. The updated model demonstrates that preventing bronchial hyperreactivity will not prevent the lung destruction associated with asthmatic pulmonary remodeling. The updated model of clinical asthma presented here helps to provide a basis for computer simulation of chronic asthma.     

Relationship between augmentation index obtained from carotid and radial artery pressure waveforms

OBJECTIVE: Increased aortic and carotid arterial augmentation index (AI) has been directly linked with cardiovascular disease risk, mortality and morbidity. The aim of this study was to examine whether AI obtained directly from radial artery pressure waveforms (radial AI) can provide information comparable with carotid arterial AI measurements. METHODS: In a cross-sectional study of 204 apparently healthy subjects (88 men and 116 women) aged 19-76 years (51 +/- 15 years, mean +/- SD), carotid AI [(second peak carotid systolic pressure - first peak carotid systolic pressure)/carotid pulse pressure*100] and radial AI [(second peak radial systolic pressure - diastolic pressure)/(first peak radial systolic pressure - diastolic pressure)*100] were measured using applanation tonometry. RESULTS: Radial AI was strongly correlated with carotid AI (r = 0.86, P < 0.0001, SD of difference 10.0%), although radial AI was consistently approximately 66% higher than carotid AI. In 16 apparently healthy young adults (11 men and five women, aged 23 +/- 3 years) handgrip exercise was immediately followed by post-exercise muscle ischaemia (PEMI) to compare changes in carotid and radial AI during increased sympathetic nervous activity. PEMI caused parallel increases in carotid and radial AI (26 and 19%). Accordingly, changes in radial AI with PEMI were strongly correlated with corresponding changes in carotid AI (r = 0.86, P < 0.0001, SD of difference 7.3%). CONCLUSION: These results suggest that AI obtained directly from radial arterial pressure waveforms could provide equivalent information to carotid arterial AI, and has potential as a surrogate marker of cardiovascular disease.     

Prevalence and distribution of autoimmune diseases in 368 rheumatoid arthritis families

OBJECTIVE: To investigate whether frequency of rheumatoid arthritis (RA) and/or other autoimmune (AI) disorders was increased in RA French Caucasian families among the first- (FDR) and second-degree relatives (SDR), and to test whether the presence of AI disease family history identified a specific RA subset. METHODS: We conducted telephone interviews to obtain histories of AI diseases among the FDR and SDR of 368 RA probands, belonging either to trio or affected sib-pair (ASP) families. All the AI diagnoses were confirmed by the physician of the affected relative. RESULTS: Probands of the ASP families were characterized by older age at RA onset, longer disease duration, and larger family size versus trio families. In the trio families, the prevalence of AI diseases was 6.05% (4.76%-7.57%) in FDR and 2.40% (1.85%-3.06%) in SDR. In ASP families, the prevalence of AI diseases was, respectively, 10.24% (8.68%-11.97%) and 1.79% (1.41%-2.25%). The most frequent AI diseases among relatives were RA, thyroid AI diseases, and vitiligo. In trio families, a proband with a mean age of RA onset < 30 years was associated with AI disease prevalence in the relatives, and male gender was associated with prevalence of RA among the FDR. CONCLUSION: The prevalence of AI diseases is increased, particularly among FDR, in French RA families, and some characteristics of the RA proband seem to be associated with prevalence of AI diseases in families.     

Childhood onset analgesic intolerance: A marker for bronchial asthma in adulthood?

Analgesic intolerance (AI) which is classically known as a disease of the middle-aged adults, not uncommonly starts in childhood. In this study we sought to identify the characteristics of childhood onset AI and evaluated its association with the development of asthma. Among 729 analgesic intolerant patients followed in our institution between January 1991 and July 2004, 50 (16 male, 34 female, 6.8% of the total AI population) had history of AI starting before the age of 18. The prevalence of asthma was 24% in childhood and increased to 40% during adulthood. Atopy was more common in patients with bronchial asthma (p<0.05). The mean (+/-SD) age of onset for asthma (18.6+/-9.7years) was significantly greater than the onset of both rhinitis and AI (13.0+/-6.5 and 13.2+/-4.0 years, respectively). This finding is different than the chronology of events reported in the literature for adult onset AI patients, in which rhinitis and asthma usually precede the development of AI. The presence of such a difference in the sequence of disease patterns may be a clue for the pathophysiologic differences underlying childhood and adult onset AI. The role of childhood onset AI as a risk factor for developing for asthma in adulthood should be further assessed in prospective patient cohorts.     

Adrenal insufficiency in patients with decompensated cirrhosis

Adrenal reserve depletion and overstimulation of the hypothalamus-pituitary-adrenal(HPA) axis are causes for adrenal insufficiency(AI) in critically ill individuals. Cirrhosis is a predisposing condition for AI in cirrhotics aswell. Both stable cirrhotics and liver transplant patients(early and later after transplantation) have been reported to present AI. The mechanisms leading to reduced cortisol production in cirrhotics are the combination of low cholesterol levels(the primary source of cortisol), the increased cytokines production that overstimulate and exhaust HPA axis and the destruction of adrenal glands due to coagulopathy. AI has been recorded in 10%-82% cirrhotics depending on the test used to evaluate adrenal function and in 9%-83% stable cirrhotics. The similarity of those proportions support the assumption that AI is an endogenous characteristic of liver disease. However, the lack of a gold standard method for AI assessment and the limitation of precise thresholds in cirrhotics make difficult the recording of the real prevalence of AI. This review aims to summarize the present data over AI in stable, critically ill cirrhotics and liver transplant recipients. Moreover, it provides information about the current knowledge in the used diagnostic tools and the possible effectiveness of corticosteroids administration in critically ill cirrhotics with AI.     

影响老年人反射波增强指数的诸因素

目的反射波增强指数(AI)是反映动脉反射波的一个指标。在老年人中,AI 是否是反映动脉硬化的一个较好指标,目前存在争议。为了更好地理解在老年人中运用 AI 的意义,我们在～老年人群中研究 AI 的影响因素。方法在上海青浦区赵巷镇选择70岁以上老年人,用 Omron 公司 HEM9000 AI 脉波检测仪进行左侧桡动脉脉搏波分析,心率取校正到75次/min 的 AI 进行统计分析。结果1286例受检者中包括761名(59%)女性,815例(63%)高血压病患者。平均年龄为76.3岁。女性的 AI 显著高于男性(90.3%vs 85.8%,P<0.01)。简单相关分析显示:不论男女,AI(P<0.05)都随着年龄的增加而升高,随身高和血糖水平的增加而降低。男性饮酒者的 AI 显著高于不饮酒者(87.3%vs 85.2%,P=0.03)。多元逐步回归分析显示:身高、平均动脉压和空腹血糖是女性 AI 的独立影响因素。在男性,AI 还受年龄和饮酒的影响。结论在70岁以上老年人中,年龄、性别、身高、平均动脉压和血糖水平是 AI 的独立影响因素。     

人血清载脂蛋白AI的大量分离、纯化及鉴定

采用正常人血清为原料，利用硫酸右旋糖酐浓缩血清、密度梯度区带离、脱脂和ＳｅｐｈａｄｅｘＧ－１５０柱层析技术，获得人血清载脂蛋白ＡＩ的纯品，经十二烷基磺酸钠－聚丙烯酰胺凝胶电泳、等电聚焦电泳、分子量测定等证明，所提取的载脂蛋白ＡＩ为纯品，分子量为２８１８０。本方法的优点是，通过浓缩血清，减少了离心次数，缩短了制备时间，且分离效果好，为大量制备纯净的载脂蛋白ＡＩ提供了一种新的方法。     

Gender influence on metabolic syndrome's effects on arterial stiffness and pressure wave reflections in treated hypertensive subjects

BACKGROUND: In hypertensive subjects, aortic stiffness, an independent predictor of cardiovascular (CV) risk, measured from pulse wave velocity (PWV), contributes to enhance augmentation index (AI), a marker of the timing and amplitude of wave reflections. Whether PWV and AI are correlated and reflect CV risk in hypertensive men and women with metabolic syndrome (MS) remains unknown. METHODS: In a cohort of 613 (364 males) treated hypertensive subjects with and without MS (41% MS) pulse wave analysis was used to determine aortic PWV and carotid AI. CV risk was estimated from standard Framingham equations. RESULTS: In females, but not in males, aortic PWV was higher in subjects with MS, when compared with those without MS (12.7+/-0.3m/s versus 11.1+/-0.4m/s, p<0.001). This result was independent of age and blood pressure. Only in females AI was independently related to the presence of MS; AI did not differ between subjects with or without MS, both males and females. AI did not correlate with PWV, except in males without MS. The overall CV risk was strongly associated to PWV independently of MS and gender, but AI was associated to CV risk only in males. CONCLUSION: In treated hypertensive subjects, the effect of MS on PWV and AI is modulated by gender. The dissociation between PWV and AI observed in women with MS was due to "blunted" wave reflections. This finding is associated with the fact that PWV, but not AI, was a constant marker of CV risk in subjects with MS, whether men and women.     

Blood pressure is the main determinant of the reflection wave in patients with type 2 diabetes.

Augmentation index (AI), the ratio of augmented pressure by the reflection pressure wave to the pulse pressure (PP), is an index of arterial stiffness and central blood pressure (BP). Although type 2 diabetes mellitus (DM) is a major risk factor for atherosclerosis, there is controversy with respect to how DM affects AI. In the present study, we investigated possible determinants of AI in 194 type 2 DM patients (mean age 67+/-9 years). AI was measured in the left radial artery using an automated tonometric method. In a simple correlation analysis, AI showed a positive association with age, and a negative association with body height, body weight, waist circumference, heart rate (HR), plasma glucose, and HbA1c. Women had significantly higher AI than men. Stepwise regression analysis revealed that mean BP (MBP) (beta=0.260, p<0.001), HR (beta=-0.550, p<0.001) and body height (beta=-0.217, p<0.001) were independent determinants of radial AI. Similarly, the second peak of systolic BP (SBP2), an index of central aortic systolic BP (SBP), showed a positive association with age, BMI, waist circumference, MBP and AI, and a negative association with body height. In a separate analysis performed in diabetic patients with treated hypertension (n=123), again, only MBP, HR and body height were significant determinants of radial AI. There was no difference in radial AI and SBP2 among the classes of antihypertensive drugs used. These findings indicate that tight BP control would be effective in reducing the reflection wave and aortic BP, which could independently relate to cardiovascular disease in type 2 diabetic patients.     

Intramedullary apoptosis of hematopoietic cells in myelodysplastic syndrome patients can be massive: apoptotic cells recovered from high-density fraction of bone marrow aspirates

A higher percentage of apoptotic cells (apoptotic index or AI) is consistently found in bone marrow (BM) biopsies compared to BM aspirates of patients with myelodysplastic syndrome (MDS). Most studies have only investigated the low-density fraction (LDF) mononuclear cells from BM aspirates following density separation for AI determination. In the present study, both LDF and high-density fraction (HDF) cells for AI were examined by electron microscopy (EM) in 10 MDS patients and 4 healthy donors. Matched BM biopsies were subjected to AI detection by in situ end labeling (ISEL) of fragmented DNA. The results indicate that in LDF and HDF cells, AI is consistently higher in MDS patients (8.5% vs 1.5%, respectively; P =.039) compared to healthy donors (27% vs 4%, respectively; P =. 004). The BM biopsy AI was also higher in MDS patients than in healthy donors (3+ vs 0+, respectively; P =.036). In addition, in MDS patients, more apoptotic cells were found in HDF cells than in LDF cells (27% vs 8.5%, respectively;P =.0001). All stages of maturation, ranging from blasts to terminally mature cells belonging to all 3 lineages, were represented in the dying cells in both compartments. Using EM, typical Pelger-Huett-type cells appeared to be apoptotic granulocytes. Both LDF and HDF cells should be examined for an accurate estimation of apoptotic cells because AI would be underestimated if only the LDF cells were studied. Ultrastructural studies consistently show a higher AI in BM biopsies compared to BM aspirates despite the correction factor of HDF cells provided by AI. This may represent the actual extant state, which could conceivably be due to a higher concentration of proapoptotic signals in the biopsies. (Blood. 2000;96:1388-1392)