Retroperitoneal abscess and omphalitis in young infants.

AIM: To evaluate the aetiopathogenetic factors in cases of retroperitoneal abscess in young infants, particularly the correlation with omphalitis. METHODS: We describe the cases of two infants, aged 8 and 3 wk, respectively, with a history of omphalitis during the first weeks of life and subsequent development of a retroperitoneal abscess. Both infants underwent surgical drainage of the abscess. RESULTS: In case 1, Staphylococcus aureus was found in cultures from abscess pus, and in case 2 from umbilical pus, abscess purulent material and blood. Both infants are in good health after a follow-up of 6 mo and 8 y, respectively. CONCLUSION: Retroperitoneal abscesses in young infants are usually considered to be idiopathic. A correlation with omphalitis was found in both of the reported cases and it is thought that this could have been due to an aetiopathogenetic factor. Furthermore, we stress the importance of suspicion of retroperitoneal abscesses for early diagnosis and treatment, and discuss the therapeutic strategies.

Impact of arterial stiffening on left ventricular structure.

Aging of the vasculature results in arterial stiffening and an increase in systolic and pulse pressures. Although pressure load is a stimulus for left ventricular hypertrophy, the extent to which vascular stiffening per se, independent of blood pressure, influences left ventricular structure is uncertain. Two hundred seventy-six subjects (79 normotensive and 197 otherwise healthy hypertensive individuals) underwent echocardiography to assess left ventricular structure. Arterial stiffness was estimated by the pressure-independent stiffness index, beta, and the pressure-dependent elastic modulus derived from simultaneous carotid ultrasound and applanation tonometry. Systemic arterial compliance (the inverse of stiffness) was estimated by the arterial compliance index. In multivariate analysis, beta was related to age (P<0.001) and smoking history (P<0.01) but not mean pressure, whereas elastic modulus was related to age and mean pressure (both P<0.001). The arterial compliance index was only related to age. Whereas systolic and diastolic pressures and the elastic modulus were positively associated with left ventricular mass (all P<0.001), primarily because of increases in wall thicknesses, beta and the arterial compliance index bore no relation to left ventricular mass. beta was inversely related to chamber diameter and directly related to left ventricular relative wall thickness, the ratio of wall thickness to chamber radius. Younger and older hypertensive subjects had comparable left ventricular mass, despite higher systolic and pulse pressures in the older group, whereas older hypertensives had higher mean relative wall thickness, associated with a significant increase in arterial stiffness (beta, 7.06 versus 5.17; elastic modulus, 595 versus 437 dyne/cm(2) x10(-6)) and reduction in the arterial compliance index (0.87 versus 1.05 mL/mm Hg per square meter) (all P<0.001). Thus, the extent to which arterial stiffness relates to left ventricular hypertrophy is dependent on the method by which arterial stiffness is estimated. Pressure-dependent methods show an association with left ventricular hypertrophy, whereas the pressure-independent stiffness index, beta, and the arterial compliance index are most strongly associated with aging and left ventricular concentric remodeling but not hypertrophy.

Carotid intimal-medial thickness and stiffness are not affected by hypercholesterolemia in uncomplicated essential hypertension.

The combined effects of hypertension and hypercholesterolemia on carotid anatomy and stiffness were studied in 62 normotensives, 141 uncomplicated essential hypertensives with a total cholesterol level <240 mg/dL, and 60 essential hypertensives with a total cholesterol level >/=240 mg/dL. Carotid ultrasonography was performed to evaluate intimal-medial thickness (IMT), relative wall thickness, and the presence of plaque. Carotid pressure waveforms were recorded by applanation tonometry to measure carotid stiffness (beta) and pressure wave reflection (ie, augmentation index). After adjusting for age, body mass index, and smoking habit by analysis of covariance, no significant differences were found between normocholesterolemic hypertensives and hypercholesterolemic hypertensives in terms of IMT (0.79+/-0.19 versus 0.81+/-0.19 mm), relative wall thickness (0.27+/-0.07 versus 0.28+/-0.07), carotid stiffness (6.1+/-3.2 versus 5.6+/-2.7), augmentation index (18. 7+/-12.9% versus 17.3+/-12.8%), and prevalence of plaque (30.8% versus 30.7%). In the whole population, carotid IMT was significantly related to age (r=0.43), systolic (r=0.35) and diastolic (r=0.35) blood pressures, body surface area (r=0.22), and cholesterol levels (r=0.22) (all P<0.05). Carotid stiffness was significantly related to age, blood pressure, body mass index, and body surface area but not to cholesterol levels. In multivariate analyses, age, body surface area, and systolic blood pressure, but not cholesterol, smoking habit, or sex, were independent correlates of IMT (multiple R=0.54, P<0.0001), whereas carotid stiffness was independently associated with age, body surface area, and sex (R=0. 38, P<0.0001). In conclusion, hypertension is a potent stimulus of vascular hypertrophy. The superimposition of hypercholesterolemia does not substantially augment these changes or further increase arterial stiffness in uncomplicated hypertensive subjects.

AKEntAnnos. The Sardinia Study of Extreme Longevity.

This paper describes an epidemiological study performed in all centenarians living in Sardinia, a large island located in the Mediterranean sea, 120 Km from the Italian coast. Due to its long-standing isolation, low immigration rate, high endogamy and rather uniform lifestyle, Sardinia offers an ideal setting in which to study the genetic traits associated with extreme longevity and successful aging. A total of 233 potentially eligible centenarians were traced in the entire territory. Of these, 66 died prior to being interviewed, 11 were not found and unknown, and 15 refused to be interviewed. A multidimensional home interview was administered to 141 centenarians, and an equivalent number of 60-year-old controls matched for gender and area of residence. Furthermore, 41 living siblings of the centenarians, and 41 age- and sex-matched controls for these siblings were also studied. The prevalence of centenarians was 13.56 per 100,000, and the female/male ratio was approximately 2. Prevalence and female/male ratio were consistent across the four Sardinian municipalities and are, respectively, higher and lower than those reported in other population-based surveys. A number of methodological problems confronted in doing the field work, and plans for future analysis of this rich dataset are discussed.

Impact of arterial elastance as a measure of vascular load on left ventricular geometry in hypertension.

OBJECTIVE: Effective arterial elastance (Ea), integrating the pulsatile component of left ventricular (LV) afterload, is an estimate of aortic input impedance. We evaluated relationships of Ea with left ventricular anatomy and function in essential hypertension. DESIGN: A cross-sectional analysis in 81 normotensive and 174 untreated hypertensive individuals enrolled in a referral hypertension centre. METHODS: Using echocardiography we determined left ventricular mass index (LVMI), relative wall thickness (RWT), stroke volume (SV), endocardial (FSe) and midwall (FSm) fractional shortening and total peripheral resistance (TPR). Carotid pressure waveforms were obtained by arterial tonometry, and end-systolic pressure (Pes) was measured at the dicrotic notch. Ea index (EaI) was calculated as Pes/(SV index); LV elastance (Ees) was estimated as Pes/LV end-systolic volume, and ventriculo-arterial coupling was evaluated by the Ea/Ees ratio. RESULTS: EaI was higher in hypertensives than in normotensives (3.02 +/- 0.63 versus 2.40 +/- 0.52 mmHg/l per m2; P< 0.0001). Using the 95% upper confidence limit in normotensives, hypertensives were divided in two groups with normal or elevated EaI. The 38 hypertensives with elevated EaI had higher RWT (0.41 +/- 0.06 versus 0.37 +/- 0.05), lower LVMI (87.5 +/- 18.5 versus 96.8 +/- 19.3 g/m2), higher TPR (2247 +/- 408 versus 1658 +/- 371 dynes/cm s(-5)) and lower FSe and FSm (35 +/- 5 versus 39 +/- 5 and 16 +/- 2 versus 18 +/- 2%; all P< 0.05) than patients with normal EaI. Ea/Ees ratio was increased and cardiac output was reduced in hypertensives with elevated EaI. CONCLUSIONS: High values of EaI identify a minority of hypertensive patients characterized by elevated TPR, left ventricular concentric remodelling, depressed left ventricular systolic function and impaired ventriculo-arterial coupling.

Stroke volume/pulse pressure ratio and cardiovascular risk in arterial hypertension.

Ratio of stroke volume (SV, M-mode echocardiography) to pulse pressure (PP) has been proposed as an estimate of total arterial compliance and has been shown to be related to body size, age, and heart rate in normal adults. SV/PP was estimated in 294 hypertensive patients (98 women) as a raw value by use of SV/body surface area (SVi) and by the ratio of SV/PP to the value predicted by a previously developed equation (%SV/PP). At baseline, the 50 patients who had cardiovascular events over the following 10 years exhibited higher PP and lower SV/PP, SVi/PP, and %SV/PP (all P<0.008) than patients without events. Crude risk of follow-up total and fatal cardiovascular events increased with increasing level of PP and decreasing SV/PP, SVi/PP, and %SV/PP (all P<0.002). In multivariate logistic regression models with continuous covariates, the risk of total cardiovascular events was independently related to increasing age (P<0.0001) and left ventricular (LV) mass index (P<0.003) and decreasing values of %SV/PP (P<0.006) but not to increasing systolic, pulse, or mean blood pressure or gender. Similar although less strong results were obtained with the use of SVi/PP (P<0.02), whereas SV/PP did not enter the model as an independent predictor. Risk of cardiovascular death was only predicted by age and LV mass index. The %SV/PP was also an independent predictor of total cardiovascular events in Cox proportional hazards analysis (exp[b]: 2.49, P<0.001) independent of age (exp[b]: 1.05, P<0.003) and LV mass index (exp[b]: 1.02, P<0.0003), whereas no effect was detected for height. Thus, in patients with arterial hypertension, a reduced ratio of M-mode echocardiographic SV/PP as a percentage of the value predicted by demographic variables is a predictor of cardiovascular morbid events independent of age and LV mass index.

Reliability and limitations of echocardiographic measurement of left ventricular mass for risk stratification and follow-up in single patients: the RES trial. Working Group on Heart and Hypertension of the Italian Society of Hypertension. Reliability of M-mode Echocardiographic Studies.

OBJECTIVE: To investigate the clinical reliability of repeated measurements of left ventricular mass in a single patient. DESIGN: We used test-retest reliability analysis, within-class correlation and interval of agreement measures. METHODS: Two M-mode tracings (three consecutive cycles) were recorded in the same session and 3-10 days apart (5+/-2 days; mean +/- SD) in 261 participants (age 45+/-13 years, body mass index 24.7+/-3.6 kg/m2; 131 hypertensive and 130 normotensive; 50% of each group women) in 16 centres in Italy. The two tracings were read by two observers in each centre, after classification by a three-order quality score (1 = poor, 2 = sufficient, 3 = optimal). RESULTS: The average quality score was 2.11+/-0.71 (21% poor, 50% sufficient, 29% optimal). Left ventricular mass values ranged from 56 to 419 g (170+/-61 g). On the same day, within-observer 90% interval of agreement between tracing 1 and tracing 2 was -28 to +22 g (-17 to +11% of tracing 1). For day-to-day test-retest within-observer variability (average three cycles), the 90% interval of agreement was -30 to +35 g (-18 to +18%). This variability decreased to -13 to +12% at the 80% interval of agreement and -12 to +11% at the 75% interval of agreement. The 90% interval of agreement of test- retest between-observer variability was -26 to 30 g (-19 to +15%). A negligible regression toward the mean was identified. Categorical consistency of retest in the identification of hypertensive patients with left ventricular hypertrophy, classified in the first study, was 87% (k = 0.87). CONCLUSIONS: Measurement of left ventricular mass in single patients allows reliable risk stratification on the basis of the presence of left ventricular hypertrophy. The probability of a true change in left ventricular mass over time is maximized for a single-reader difference greater than 18% of the initial value, although differences of 10-13% might also have clinical relevance.

Relation of age to left ventricular function in clinically normal adults.

The extent to which age, independent of cardiovascular diseases, influences left ventricular (LV) function in adults is uncertain. Echocardiograms and simultaneous arterial pressure in 464 clinically normal adults aged 16 to 88 years were used to measure LV dimensions, endocardial and midwall LV fractional shortening, stroke volume, cardiac output, and circumferential end-systolic stress. The ratios of observed endocardial and midwall shortening to values predicted for observed end-systolic stress were used as measures of chamber and myocardial function. LV endocardial shortening increased slightly with age, as did an index of LV chamber performance, the end-systolic stress/volume index ratio (r = 0.11, p = 0.019, and r = 0.20, p <0.001). However, when age-related increases in LV wall thickness and blood pressure were controlled for by examining afterload-corrected endocardial shortening, no age relation was detected. Weak age-related declines were observed in midwall shortening (r = -0.09, p = 0.043) and afterload-corrected midwall shortening (r = -0.12, p <0.01). Cardiac index decreased slightly with advancing age (r = -0.14, mean -6.7 ml/min/m2/ year, p = 0.003). Total peripheral resistance and the pulse pressure/stroke volume ratio, a measure of arterial stiffness, increased more strongly with age (r = 0.27 and 0.38, both p <0.001). Thus, LV pump performance at rest measured by cardiac index is slightly lower in older than in younger clinically normal adults. Endocardial fractional shortening was slightly higher in older subjects, but the physiologically more appropriate midwall measures of myocardial function decreased slightly. The observed change in LV pump performance was related to smaller LV chamber size and higher total peripheral resistance in older subjects.

Relation of left ventricular longitudinal and circumferential shortening to ejection fraction in the presence or in the absence of mild hypertension.

OBJECTIVES: To study left ventricular longitudinal shortening in arterial hypertension and the relative contribution of longitudinal and circumferential fiber shortening to ventricular ejection. METHODS: Two-dimensional and M-mode echocardiograms were obtained for 50 normotensive subjects (aged 49 +/- 12 years) and 50 never-treated mild hypertensive patients (aged 49 +/- 11 years), to measure the minor-axis endocardial and midwall shortening, long-axis shortening and ejection fraction. RESULTS: The midwall shortening was lower in hypertensive than it was in normotensive subjects (P < 0.001) and was related inversely to the circumferential wall stress for both groups (P < 0.04 and 0.0001, respectively). The long-axis shortening in hypertensive patients (22.2 +/- 4.2%) and in normotensives (23.6 +/- 5.4%) was not statistically different, and was not related either to the meridional or to the circumferential wall stress. The ejection fraction was also similar for the two groups (68.2 +/- 6.3 versus 68.6 +/- 5.6%). Both for normotensive and for hypertensive subjects, the ejection fraction was influenced mainly by the midwall shortening (61 and 40% of the variance for normal and hypertensive individuals, respectively), with a minor contribution from the long-axis shortening, which was 7% for normotensive subjects and 18% for hypertensive patients, a statistically significant difference (P < 0.001). The combined effect of midwall and longitudinal shortenings on the ejection fraction was regulated by the relative wall thickness, and was maximal for hypertensive patients with an ejection fraction greater than that predicted by the midwall shortening. CONCLUSIONS: Left ventricular ejection is produced principally by circumferential shortening and is related independently to the relative wall thickness. In the presence of arterial hypertension and an altered cardiac load, longitudinal shortening becomes an important mechanism by which to augment ejection, thereby offsetting the reduction in midwall shortening.

Estimation of left ventricular chamber and stroke volume by limited M-mode echocardiography and validation by two-dimensional and Doppler echocardiography.

This study has been designed to improve estimation of stroke volume from linear left ventricular (LV) dimensions measured by M-mode echocardiography, in symmetrically contracting ventricles. In experimental studies, the ratio of LV epicardial long/short axes "Z" is about 1.3. We measured systolic and diastolic epicardial long and short axes by 2-dimensional echocardiography in 115 adults with widely varying LV short-axis dimensions (LV end-diastolic dimension = 3.95 to 8.3 cm). In a learning series of 23 normotensive and 27 hypertensive subjects, Z(diastole) was 1.3 +/- 0.1 and Z(systole) = 1.2 +/- 0.1, similar to findings in experimental animals. Regression equations were developed by comparing LV volumes by M-mode and 2-dimensional echocardiography. In a test series (65 subjects), LV volumes were calculated using separate regression equations for end-diastolic volume ([LV end-diastolic dimension] 4.765 - 0.288 x posterior wall thickness]) and for end-systolic volume ([LV end-systolic dimension] [4.136 - 0.288 x posterior wall thickness]). Because the term 0.288 x wall thickness was only about 8% of the first term between brackets, the average wall thickness in the learning series was substituted in the Z-volume formulas applied to the test series: end-diastolic volume = (4.5 x [LV end-diastolic dimensions]2) and end-systolic volume = (3.72 x [LV end-diastolic dimension]2). The mean relative error produced with this simplified method was 0.9%. in diastole and 1.4% in systole. Compared with Teichholz' M-mode volume method, Z-derived end-diastolic volume in the test series was equally well related to 2-dimensional volumes (both r = 0.88), with a better intercept (1.5 vs -23 ml, p <0.001) and a slope closer to the identity line (1.1 vs 1.4). Similar results were found for systolic volumes. In a second test series of 1,721 American Indian participants in the Strong Heart Study without mitral regurgitation or segmental LV wall motion abnormalities, Doppler-derived LV stroke volume (70 +/- 14 ml/beat) was similarly predicted by the Z-derived method (r = 0.65, 70 +/- 11 ml/beat) and Teichholz formulas (r = 0.64, 72 +/- 13 ml/beat), but Z-derived volumes had a regression line significantly closer to the identity line (p <0.005). Thus, LV chamber and stroke volumes can be determined from M-mode LV diameters over a wide range of LV sizes and in epidemiologic as well as clinical populations. The performance of this new method appears better than that obtained using the Teichholz formula, with a formula that is easy to handle and makes calculation of LV volumes by pocket calculator possible, even from limited echocardiographic studies.

Assessment of left ventricular function by meridional and circumferential end-systolic stress/minor-axis shortening relations in dilated cardiomyopathy.

Echocardiographic meridional wall stress-endocardial shortening relations provide estimates of left ventricular (LV) contractility that do not uniformly detect myocardial dysfunction despite severe symptoms in dilated cardiomyopathy. To improve detection of myocardial dysfunction in patients with congestive heart failure (CHF) due to dilated cardiomyopathy, echocardiographic meridional and circumferential end-systolic stress were related to endocardial and midwall shortening in 42 patients (95% dead within a mean of 22 months) with dilated cardiomyopathy and 140 normal subjects. A method to estimate LV long-axis dimension from M-mode minor-axis epicardial measurements was developed in a separate series of 115 subjects. Endocardial shortening to meridional wall stress relation identified 31 of 42 CHF patients falling below the 95% normal confidence interval of the reference population; use of midwall shortening decreased this number to 26 (p = NS). The use of circumferential wall stress identified 39 of 42 patients with subnormal endocardial LV shortening and 41 of 42 patients with depressed midwall performance (p < 0.01 vs use of meridional stress). The circumferential/meridional wall stress ratio was 2.6 +/- 0.5 in normal subjects and 1.3 +/- 0.2 in CHF patients (p < 0.0001). Thus, use of circumferential end-systolic stress as the measure of afterload improves the detection of myocardial dysfunction by stress/shortening relations in patients with CHF. The ratio between the 2 stresses decreases with more spherical LV shape. Midwall and endocardial shortening measurements are equivalent in the setting of thin LV walls as occurs in dilated cardiomyopathy.

Influence of obesity on left ventricular midwall mechanics in arterial hypertension.

The evaluation of the effect of obesity on left ventricular systolic performance may differ in relation to the method used to measure left ventricular function and to the type of study population. Whether obesity worsens left ventricular midwall mechanics in arterial hypertension has never been investigated. Accordingly, we assessed echocardiographic left ventricular midwall shortening-circumferential end-systolic stress relations in 156 normotensive and normal-weight (reference) adults, 94 normotensive and overweight (1985 National Institutes of Health partition values) to obese (body mass index > 30 kg/m2) adults, 263 hypertensive and normal-weight adults, and 224 hypertensive and overweight-to-obese adults. There was an inverse relation of midwall shortening to circumferential end-systolic stress in all groups (all P < .005). Left ventricular performance as a ratio of observed to predicted midwall shortening fell below the fifth percentile in 4 of 94 (4%) of overweight-to-obese normotensive individuals. Eighty-eight of 487 hypertensive subjects (18.1%) exhibited depressed midwall shortening as a percentage of the value predicted from wall stress, with no difference between normal-weight (50 of 263 [19%]) and overweight (38 of 224 [17%]) subjects. Sixty-one normotensive and 131 hypertensive subjects were frankly obese. After adjustment for sex and age, midwall shortening, as either absolute values or a percentage of predicted, was not statistically different among obese, overweight, and normal-weight subjects in both normotensive and hypertensive groups. For each quartile of observed-to-predicted midwall shortening ratio, obese subjects had greater left ventricular end-diastolic volume than normal-weight subjects among both normotensive and, more evidently, hypertensive subjects. A predicted midwall shortening was generated from both wall stress and left ventricular volume with the use of multiple regression analysis. High body mass index, mean blood pressure, aging, and male sex independently predicted low afterload and left ventricular volume-independent midwall left ventricular performance (multiple R = .31, P < .0001). Thus, (1) midwall left ventricular systolic performance in asymptomatic overweight or frankly obese individuals is comparable to that in normal-weight individuals in both the presence and absence of arterial hypertension; (2) however, maintenance of normal life ventricular performance in obese individuals is associated with the use of Starling reserve; and (3) this compensatory mechanism is especially evident when arterial hypertension and obesity coexist.

Ageing induces left ventricular concentric remodelling in normotensive subjects.

OBJECTIVE: To assess whether age affects left ventricular anatomy independently of age-related hypertension or concomitant heart diseases. DESIGN AND METHODS: In 430 consecutive normotensive and clinically healthy subjects aged 16-85 years we obtained echocardiographic measurements of left ventricular posterior wall thickness, internal diameter, relative wall thickness, Penn mass index and systemic haemodynamics. The pulse pressure : stroke volume ratio was calculated as an estimate of systemic arterial stiffness. The subjects were divided into three age groups: < or = 40 (group 1, n = 137), 41-64 (group 2, n = 261) and > or = 65 years (group 3, n = 32). RESULTS: Systolic blood pressure increased from group 1 to group 3, as did the pulse pressure : stroke volume ratio and posterior wall thickness, whereas the left ventricular internal diameter was less in group 3 than in groups 1 and 2. The relative wall thickness increased from group 1 to groups 2 and 3, whereas the left ventricular mass index did not differ among age groups. Age was related positively to the systolic blood pressure, pulse pressure : stroke volume ratio, posterior wall thickness index and relative wall thickness, and negatively to the left ventricular internal diameter but not to the left ventricular mass index. CONCLUSIONS: In healthy adults, relative wall thickness increases with age whereas left ventricular mass does not change. The concentric remodelling of left ventricular geometry parallels age-related stiffening of the arterial tree, elevation of systolic blood pressure and decrease in left ventricular volume. Thus partition values of relative wall thickness should be adjusted for age.

Relationship of effective arterial elastance to demographic and arterial characteristics in normotensive and hypertensive adults.

OBJECTIVE: To evaluate demographic and vascular correlates of the effective arterial elastance noninvasively in normotensive and hypertensive adults. METHODS: In 202 subjects carotid ultrasonography and external arterial tonometry were simultaneously performed; carotid cross-sectional area, absolute and relative wall thicknesses, Peterson's and Young's elastic moduli and beta', a pressure-dependent index of arterial stiffness, were calculated. The impact of reflected waves on central pressure waveforms was evaluated by the 'augmentation index' (the relative increment in systolic pressure caused by the late-systolic peak). Left ventricular mass and relative wall thickness were assessed echocardiographically. The effective arterial elastance was estimated by dividing the pressure at the dicrotic notch by the Doppler-determined stroke index. RESULTS: The effective arterial elastance was higher in women among normotensives but similar between sexes among hypertensive subjects. It was correlated to age, mean blood pressure, body mass index and measures of arterial function, including Peterson's and Young's elastic moduli and beta', and to the augmentation index. It was also related to absolute and relative carotid wall thicknesses, lumen diameter and indexed cross-sectional area. Age, beta' and carotid cross-sectional area independently predicted effective arterial elastance in multiple regression analysis. CONCLUSIONS: Effective arterial elastance is related to demographic and arterial structural and functional characteristics. Increases in effective arterial elastance resulting from altered arterial structure and function may play a role in inducing left ventricular adaptative modifications.

A mutation in the dystrophin gene selectively affecting dystrophin expression in the heart.

We have previously shown in a large X-linked pedigree that a deletion removing the dystrophin muscle promoter, the first muscle exon and part of intron 1 caused a severe dilated cardiomyopathy with no associated muscle weakness. Dystrophin expression was present in the muscle of affected males and transcription studies indicated that this dystrophin originated from the brain and Purkinje cell isoforms, upregulated in this skeletal muscle. We have now studied dystrophin transcription and expression in the heart of one member of this family. In contrast to the skeletal muscle, dystrophin transcription and expression were absent in the heart, with the exception of the distal Dp71 dystrophin isoform, normally present in the heart. The 43- and 50-kD dystrophin-associated proteins were severely reduced in the heart, despite the presence of Dp71, but not in skeletal muscle. The absence of dystrophin and the down-regulation of the dystrophin-associated proteins in the heart accounted for the severe cardiomyopathy in this family. The mutation present in these males selectively affects dystrophin expression in the heart; this could be secondary to the removal of cardiac-specific regulatory sequences. This family may represent the first example of a mutation specifically affecting the cardiac expression of a gene, present physiologically in both the skeletal and cardiac muscles.

Transcription of the dystrophin gene in normal tissues and in skeletal muscle of a family with X-linked dilated cardiomyopathy.

We recently described a family where a deletion of the dystrophin gene was associated with a severe dilated cardiomyopathy without skeletal muscle weakness. The deletion removed the muscle promoter region and the first muscle exon, but not the brain or Purkinje-cell promoters. Dystrophin was detected immunocytochemically in the skeletal muscle from this family, despite the fact that the deletion eliminated the transcriptional start site of the muscle isoform. In order to determine which promoter was driving dystrophin transcription in skeletal muscle of these individuals, we first evaluated the expression of the exon 1 of muscle, brain, and Purkinje-cell isoforms in normal human skeletal and cardiac muscles and in mouse brain and cerebellum. Our data indicate that, with the exception of minimal expression of the brain isoform, only the muscle isoform is significantly transcribed in skeletal muscle, whereas both the exon 1 muscle and brain isoforms are highly expressed in cardiac muscle. In contrast to what is observed in normal muscle, the skeletal muscle of our patients showed expression of both the brain and the Purkinje-cell isoforms. The overexpression, in skeletal muscle, of these two isoforms thus appears to be of crucial importance in preventing a myopathy in these affected males. The reason for the severe cardiomyopathy remains speculative, in the absence of dystrophin data on their heart. However, we have found in the 5' end of intron 1, a region deleted in our cases, regulatory sequences that might be of importance for dystrophin expression in various tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

The response of the ageing heart to regular physical exercise. An echo and Doppler study.

In upper middle age healthy subjects the functional cardiac reserve is known to be decreased (Port et al., 1980; Aubert et al., 1994). On the other hand regular physical exercise improves the cardiovascular function (Nishimura et al., 1980). The aim of this study was to establish whether regular physical exercise is associated with a significant change in the ageing process of the cardiovascular system.

Left ventricular hypertrophy and geometric remodeling in hypertension: stimuli, functional consequences and prognostic implications.

OBJECTIVE: To provide a coherent overview of the stimuli to development of abnormal left ventricular geometric patterns, their impact on cardiac function and their relationship to the prognosis of hypertension, studies performed by the authors and other investigators are reviewed. RESULTS: Clinical and experimental studies have shown that an elevated left ventricular mass reflects the additive effects on the heart of higher arterial pressure over time, increased cardiac volume load related to obesity, sodium intake or other stimuli, reduced contractile efficiency of the myocardium and altered arterial hemodynamics related to vascular hypertrophy and atherosclerosis. The heart may adapt to hypertension by developing concentric or eccentric left ventricular hypertrophy, or the newly described pattern of concentric left ventricular remodeling, or by retaining normal left ventricular geometry. Each geometric pattern is associated with a distinct combination of pressure and volume stimuli, contractile efficiency (reduced in those with concentric left ventricular hypertrophy or remodeling) and prognosis (worst with concentric hypertrophy and best with normal left ventricular geometry). An appraisal of left ventricular mechanics by a physiologically appropriate midwall-shortening/end-systolic stress relationship can identify impaired contractility in an appreciable proportion of hypertensive patients. Numerous studies have shown that increased left ventricular mass and abnormal geometry have a strong predictive value for cardiovascular death, myocardial infarction and stroke. CONCLUSIONS: Increasing evidence has demonstrated the central importance of left ventricular mass and geometry in the pathophysiology and prognosis of hypertension. These measures of preclinical disease can aid clinical decision-making by separating patients into those with a high or a relatively low risk, and hence a need for pharmacological treatment or its intensification, as well as providing useful bioassays for a spectrum of clinical and experimental research.