Atherosclerotic vascular disease is more prevalent among black ESKD patients on long-term CAPD in South Africa.

BACKGROUND: Occurrence of cardiovascular disease (CVD) in the setting of chronic kidney disease (CKD) can be described as a "cruel alliance", with CVD responsible for about half of all deaths among CKD patients. Chronic kidney disease patients are more likely to die from CVD than progress to end stage kidney disease (ESKD). Dyslipidaemia, a known traditional risk factor for CVD, is highly prevalent among CKD patients and with an even higher frequency among ESKD patients on dialytic therapies. Prolonged exposure of continuous ambulatory peritoneal dialysis (CAPD) patients to high glucose concentrations in CAPD fluid have been associated with increased risk of cardiovascular events. In this study, we investigated the relationship of atherosclerotic vascular disease (AsVD) to clinical and echocardiographic parameters among black South Africans with CKD (stage 3) and ESKD on CAPD and haemodialysis (HD). METHODS: This was a cross-sectional study of 40 adult (18-65 years) non-diabetic CKD patients (kidney disease outcome quality initiative [KDOQI] stage 3), 40 ESKD patients on CAPD, 40 ESKD patients on HD and 41 age and sex-matched healthy controls. An interviewer-administered questionnaire was used to obtain information on participants' sociodemographic and cardiovascular risk factors. Anthropometric parameters were measured. Serum blood samples were analysed for creatinine, albumin and lipid profile; lipoprotein ratios, Framingham's risk score and the 10-year risk of developing coronary heart disease (CHD) were calculated. Echocardiography was performed on all patients and carotid intima media thickness (CIMT) was measured in both right and left carotid arteries at 1 cm proximal to the carotid bulb. Spearman's rank correlation and binary logistic regression were conducted to determine the relationship of AsVD to clinical and echocardiographic parameters. RESULTS: Atherosclerotic vascular disease was most prevalent among ESKD patients on CAPD (70%, n = 28/40). Chronic kidney disease and HD patients exhibited a similar prevalence (47.5%, n = 19/40), while the prevalence in controls was 17.1% (n = 7/41). Presence of AsVD was associated with significantly older age, higher waist hip ratio (WHR), left ventricular mass index (LVMI) and Framingham's 10-year risk of developing CHD. Significant differences in clinical and echocardiographic parameters were observed when the study groups were compared. Age and LVH independently predicted AsVD. CONCLUSION: Atherosclerotic vascular disease was more prevalent among CAPD patients compared to pre-dialysis CKD and HD patients. Among all lipoprotein ratios assessed, non-HDL-C showed the most consistent significant difference between the groups. Age (> 40 years) and presence of LVH were independent predictors of AsVD.

First description of Mycobacterium tuberculosis and M. canettii concomitant infection: report of two cases.

We report the first two cases of tuberculous coinfection with Mycobacterium tuberculosis and M. canettii. Both patients were young Djiboutian females with pulmonary tuberculosis (TB). One had a miliary pattern with concomitant human immunodeficiency virus infection. Both recovered completely with a standard four-drug anti-tuberculosis treatment regimen. Due to the different natural reservoirs and routes of infection of these two strains, our study supports the common belief that multiple strains of infection in TB are related to superinfection rather than concomitant infection.

Identification of patients with preeclampsia from normal subjects using wavelet-based spectral analysis of heart rate variability.

BACKGROUND: The spectral analysis of the heart rate variability (HRV) shows a decrease in the power of the high frequency (HF) component in preeclamptic pregnancy compared with normal pregnancy; such a decrease is associated with an increase in the low frequency (LF) and the very low frequency (VLF) power. The physiological interpretation is that preeclamptic pregnancy is associated with a facilitation of sympathetic regulation and an attenuation of parasympathetic influence of HR compared with non-pregnancy and normal pregnancy. OBJECTIVE: To use an efficient nased on spectral analysis non-invasive technique to identify preeclamptic pregnant subjects from normal pregnant in Oman. METHODS: The soft-decision wavelet-based technique is implemented to find the power of the HRV bands in high resolution manner compared to the classical fast Fourier Transform method. Data was obtained from 20 preeclamptic pregnant subjects and 20 normal pregnant controls of the same pregnancy duration, obtained from Nizwa and Sultan Qaboos University hospitals in Oman. RESULTS: The soft-decision wavelet method succeeds to identify patients from normal pregnant with specificity, sensitivity and accuracy of 90%, 80% and 85%, respectively, compared to the FFT which results in 75% specificity, sensitivity and accuracy. CONCLUSION: The LF power obtained by Soft-decision wavelet decomposition is shown to be a successful feature for identification of preeclampsia.

Classification of sleep apnea using wavelet-based spectral analysis of heart rate variability.

BACKGROUND: Obstructive Sleep Apnea (OSA) is the cessation of breathing during sleep due to the collapse of upper airway. Polysomnographic recording is a conventional method for detection of OSA. Although it provides reliable results, it is expensive and cumbersome. Thus, an advanced non-invasive signal processing based technique is needed. OBJECTIVE: The main purpose of this work is to predict the severity of sleep apnea using an efficient wavelet-based spectral analysis method of the heart rate variability (HRV) to classify sleep apnea into three different levels (mild, moderate, and severe) according to its severity and to distinguish them from normal subjects. METHODS: The standard FFT spectrum analysis method and the soft-decision wavelet-based technique are to be used in this work in order to rank patients to full polysomnography. Data of 20 normal subjects and 20 patients with mild apnea and 20 patients with moderate apnea and 20 patients of severe apnea are used in this study. The data is obtained from the sleep laboratory of Sultan Qaboos University hospital in Oman. Four different classification versions have been used in this work. RESULTS: Accuracy result of 90% was obtained between severe and normal subjects and 85% between mild and normal and 75% between severe and moderate and 83.75% between normal and patients. CONCLUSIONS: The VLF/LF power spectral ratio of the wavelet-based soft-decision analysis of the RRI data after a high-pass filter resulted in the best accuracy of classification in all versions.

Association of adiponectin promoter variants with traits and clusters of metabolic syndrome in Arabs: family-based study.

Plasma levels of adiponectin are decreased in type 2 diabetes, obesity and hypertension. Our aim was to use a family-based analysis to identify the genetic variants of the adiponectin (ADIPOQ) gene that are associated with obesity, insulin resistance, dyslipidemia and hypertension, among Arabs. We screened 328 Arabs in one large extended family for single nucleotide polymorphisms (SNPs) in the promoter region of the ADIPOQ gene. Two common SNPs were detected: rs17300539 and rs266729. Evidences of association between traits related to the metabolic syndrome and the SNPs were studied by implementing quantitative genetic association analysis. Results showed that SNP rs266729 was significantly associated with body weight (p-value=0.001), waist circumference (p-value=0.037), BMI (p-value=0.015) and percentage of total body fat (p-value=0.003). Up to 4.1% of heritability of obesity traits was explained by the rs266729 locus. Further cross-sectional analysis showed that carriers of the G allele had significantly higher values of waist circumference, BMI and percentage of total body fat (p-values 0.014, 0.004 and 0.032, respectively). No association was detected between SNP rs266729 and other clusters of metabolic syndrome or their traits except for HOMA-IR and fasting plasma insulin levels, p-values 0.035 and 0.004, respectively. In contrast, both measured genotype and cross-sectional analysis failed to detect an association between the SNP rs17300539 with traits and clusters of metabolic syndrome. In conclusion, we showed family-based evidence of association of SNP rs266729 at ADIPOQ gene with traits defining obesity in Arab population. This is important for future prediction and prevention of obesity in population where obesity is in an increasing trend.

Calciphylaxis causing digital, gangrene in end stage renal disease: a case report and review.

Calcific uraemic arteriolopathy (CUA), a potentially life-threatening vasculopathy of the skin and subcutaneous tissues is rarely associated with advanced chronic kidney disease (CKD) particularly in patients on haemodialysis. It is more frequently reported in whites than in blacks and commonly accompanies hyperphosphataemia, elevated calcium-phosphate product and marked secondary hyperparathyroidism. We report a rare case of CUA that complicated end stage renal disease secondary to obstructive uropathy in a 68 year old Nigerian. The risk factors for CUA, diagnosis, management and our peculiar limitations were reviewed and discussed.

An appraisal of kidney dysfunction and its risk factors in patients with sickle cell disease.

Sickle cell disease (SCD), a genetically inherited disease of blacks, often presents with disabling acute complications which can occasionally be fatal. Its renal manifestations are increasingly being recognized as affected patients now survive to middle and rarely old age. We set out to determine the magnitude of kidney dysfunction in our SCD patient population and evaluate its predictive factors. We reviewed the available case records of SCD patients managed in our hospital. Information on socio-demographic, clinical and laboratory data were retrieved and collated. A total of 374 (99.46%) were reviewed with complete data; the median age was 23 years (range 7-62), while median age at diagnosis of SCD was 4 years (range 0.25-31). 235 patients (68.2%) had no kidney disease while the remaining 139 (37.2%) had proteinuria, hematuria or reduced glomerular filtration rate (GFR) <60 ml/min. The age of patients was a significant predictor of kidney disease (p = 0.002) and correlated with the level of serum creatinine (r = 0.188, p < 0.001), GFR (r = 0.245, p < 0.0001) and the degree of proteinuria (r = 0.174, p = 0.006). Patients with kidney disease had a significantly higher number of crises/hospitalizations (p < 0.001). Seven patients died in all and 4 (57%) of them had end-stage renal disease. We concluded that kidney disease is a common complication of SCD and significantly contributes to mortality. The age of the patients, duration of SCD and frequency of crises/hospitalizations are strong predictors of development of kidney disease.

The pattern, clinical characteristics and outcome of ESRD in Ile-Ife, Nigeria: is there a change in trend?

BACKGROUND: The prevalence of chronic renal failure and End Stage Renal Disease (ESRD) has remained high worldwide and the epidemiology has changed significantly in the last decade in industrialised countries. While there have been significant improvements in these patient's outcomes in developed countries, their state and survival is still appalling in developing countries. OBJECTIVE: To determine the clinical pattern, presentation and management outcomes in our ESRD population over a 19-year period (1989-2007). METHODS: Seven hundred and sixty patients' records were reviewed. Data on major causes, clinical presentation, management and survival were retrieved and collated. Data was analysed using SPSS package version 16. RESULTS: Their ages ranged between 15-90 years (mean ± SD; 39.9±1.67years) with male preponderance (70.3%). Major presenting complaints were body swelling and uraemic symptoms in most studied patients. The predisposing conditions included chronic glomerulonephritis, hypertension, obstructive uropathy and diabetes mellitus. Renal replacement therapy offered included HD in 556(73.2%), Continous Ambulatory Peritoneal Dialysis (CAPD) in only 9(1.2%) patients and renal transplantation in only 7(0.9%). Only 38(6.8%) survived on HD for longer than three months while 7(77.8%) CAPD patients and all transplanted patients survived for between six months and four years (p<0.00001). Median duration of survival after diagnosis for all the patients was 2 weeks (range 0-50 months). CONCLUSION: End stage renal disease is still prevalent with chronic glomerulonephritis and hypertension being the common causes. Prognosis is still grave hence subsidized renal replacement therapy and preventive nephrology should be targeted in such underserved populations.

Dynamic properties of eye movements in mitochondrial chronic progressive external ophthalmoplegia.

AIMS: To relate dynamic properties of eye movements to visual disability in a patient with chronic progressive external ophthalmoplegia (CPEO) due to mitochondrial DNA deletion. METHODS: Visual function was evaluated by neuro-ophthalmological examination and visual function index (VF-14). Eye movements were measured using the magnetic search coil technique. RESULTS: The patient denied diplopia or oscillopsia at rest or during locomotion. His range of eye movements was limited to <12 degrees horizontally, and <19 degrees vertically with smaller movements of the left eye. All classes of movements were impaired, but the eyes accelerated to over 1000 degrees /s/s at the onset of saccades and in response to brisk head rotations. CONCLUSIONS: Diplopia and oscillopsia were suppressed, probably due to visual system adaptation during the slow disease progression. We postulate that relative sparing of pale global extraocular fibres accounted for preserved acceleration of saccades and vestibular eye movements.

Insertion-deletion polymorphism in the angiotensin-converting enzyme (ACE) gene among Sudanese, Somalis, Emiratis, and Omanis.

The angiotensin-converting enzyme (ACE) gene in humans contains an insertion-deletion polymorphism in its intron 16. Because of its involvement with the renin-angiotensin system, the insertion-deletion polymorphism of the ACE gene has been widely investigated in different populations and in case-control studies. However, similar studies for Arab populations are limited in number. Therefore we have investigated the frequencies of the *I and *D alleles of the ACE gene among Sudanese, Somalis, and Arab nationals of the United Arab Emirates and Oman using previously described methods. Our data indicate a preponderance of the *D allele among the Arab and African populations studied (Sudanese, 0.64; Somalis, 0.73; Emiratis, 0.61; and Omanis, 0.71).

Left Ventricle Myocardium Volume Densities in Spontaneously Hypertensive Rats (SHR) Following Combination of Exercise and ACE Inhibitor Treatment: A Stereological Study / Densidad de Volumen del Miocardio del Ventrículo Izquierdo en Ratas Espontáneamente Hipertensas (REH) Posterior a la Combinación de Ejercicios y Tratamiento Inhibidor de la ACE: Estudio Estereológico

This study was designed to test the possible effects of a combination of physical and pharmacological therapy intervention on myocardial structure of the left ventricle in spontaneously hypertensive rats (SHR). Twelve weeks old spontaneously hypertensive rats (n = 40) were divided into four groups of sedentary, (Sed) as controls, exercise only (Exer), lisinopril only 20mg/kg/day (Lis), and exercise + lisinopril (LisExer). Exercise training was performed on a treadmill (5m/min.) for 60 minutes/day, 5 days/week for 10 weeks. At the end of 10 weeks, all the rats were terminally anaesthetised, the heart was arrested in diastole by intravenous procaine and whole animal perfusion fixation through the abdominal aorta was carried out using Karnovsky's fixative (pH 7.24). The heart was removed and left ventricle plus the interventricular septum was serially sectioned at a thickness of 3 mm. One piece was randomly chosen, and embedded in JB4 resin. Six sections were obtained from each block, stained with toluidine blue:acid fucin. Measurement of volume fraction (Vf), of myocardium, capillaries and interstitium were carried out using a stereology software (Histometrix MIL6 Kinetic imaging Ltd.). Mean Vf of capillaries in Sed group was 0.114 ± 0.01 (SEM). This was significantly increased in LisExer group. The Vf of muscle in Sed group was 0.795 ± 0.02 (SEM). This was significantly decreased in Lis but unchanged in Exer group. Capillaries Vf was significantly higher in LisExer as compared to Lis or Exer groups (p<0.05). Muscle Vf was not different betweenLisExer and Lis groups. The outcome of these changes could well be a better enhancement of cardiac performance in hypertension by combined exercise and ACE inhibitor treatment than either of the interventions alone.

Este estudio fue diseñado para probar los posibles efectos de una combinación de ejercicios y una intervención de terapia farmacológica en las estructuras del miocardio del ventrículo izquierdo, en ratas espontaneamente hipertensivas (SHR). Ratas de 20 semanas espontáneamente hipertensas (n = 40) fueron divididas en cuatro grupos: sedentarias (Sed) y controles, solamente con ejercicio (Ejer), solamente con lisinopril con 20mg/kg/día (Lis), y ejercicios + lisinopril (LisEjer). Los ejercicios fueron ejecutados en una máquina de entrenamiento (5m/min.) por 60 minutos/día, 5 días/semana por 10 semanas. Al término de las 10 semanas, las ratas fueron sacrificadas bajo anestesia, el corazón fue detenido en diástole usando procaina intravenosa. Los animales fueron perfundidos a través de la parte abdominal de la aorta, usando solución de Karnovsky (pH 7.24). El corazón fue removido y tanto al ventrículo izquierdo como al septo interventricular se les realizaron cortes seriados de 3 µm. Una pieza fue seleccionados al azar, y sumergida en resina JB4. Fueron obtenidas 6 secciones de cada bloque y luego teñidas con azul de toluidina:fucsina ácida. Las mediciones de fracción volumétrica (Vf) del miocardio, capilares, e intersticio fueron obtenidas usando un software de estereología (Histometrix MIL6 Kinetic imaging Ltd.). El promedio Vf de capilares en el grupo Sed, fue 0.114 ± 0.01 (SEM). Éste fue significativamente mayor en el grupo LisExer. El Vf de músculo en Sed fue 0.795 ± 0.02 (SEM). Éste fue significativamente menor en Lis pero no varió en el grupo Ejer. Vf capilares fue significativamente alto en LisExjr, si es comparado con los grupos Lis o Ejer (p<0.05). En Vf músculo no hubo diferencias entre los grupos LisEjer y Lis. El resultado de estos cambios pudo deberse a un mejor funcionamiento cardiaco en ratas hipertensa,s producto de ejercicios combinados y tratamiento con inhibidor ACE, que en aquellos en que se efectó un solo procedimiento.

A family study in Oman: large, consanguineous, polygamous Omani Arab pedigrees.

OBJECTIVE: To establish a suitable human model for the study of the genetics of complex diseases. METHODS: We have selected an Omani Arab population to provide the statistical power required to study the genetics of complex diseases with confidence. This model consists of five multigenerational highly inbred pedigrees, descending from a small number of founders just a few generations ago with environmental homogeneity, restricted geographical distribution, detailed records and well-ascertained and -validated pedigrees. Stringent criteria were adopted for defining the phenotypes of hypertension, diabetes mellitus, dyslipidemias and obesity. The SOLAR genetic software package was used to draw the pedigree structure. RESULTS: Outstanding statistical power to detect susceptibility loci was obtained. CONCLUSIONS: This model represents a large homogeneous human family-based population for the study of genetic and environmental factors contributing to complex diseases.

Ischemic injury to mitochondrial electron transport in the aging heart: damage to the iron-sulfur protein subunit of electron transport complex III.

The aging heart sustains greater injury during ischemia and reperfusion compared to adult hearts. Aging decreases oxidative function in interfibrillar mitochondria (IFM) that reside among the myofibers, while subsarcolemmal mitochondria (SSM), located beneath the plasma membrane, remain unaltered. Aging decreases complex III activity selectively in IFM via alteration of the cytochrome c binding site. With 25 min of global ischemia, complex III activity decreases in SSM and further decreases in IFM in the aging heart. Ischemia leads to a marked decrease in the electron paramagnetic resonance signal of the iron-sulfur protein (ISP) in both SSM and IFM, despite a preserved content of ISP peptide. Thus, ischemia results in a functional decrease in the iron-sulfur center in ISP without subunit peptide loss. In the aging heart, at the onset of reperfusion, IFM contain two tandem defects in the path of electron flow through complex III, providing a likely mechanism for enhanced oxidant production and reperfusion damage.

Blood pressure and its reactivity in the offspring of first cousin hypertensive and first cousin normotensive parents: a preliminary report.

The aim of this preliminary study was to determine whether young offspring of first cousin hypertensive parent(s), have higher blood pressure (BP) reactivity in response to their first BP measurement, as compared to the offspring of first cousin normotensive parents. The BP of 135 boys aged 9-10 years was measured, for the first time ever, after a 10-min supine rest, and subsequently, twice at 10-min intervals. The offspring of first cousin hypertensive parent(s) reacted with significantly higher systolic and diastolic BP than the offspring of normotensive first cousin parents in all three measurements. This study indicates that at an early age, the offspring of first cousin hypertensive parents, react with exaggerated BP response at their first casual BP measurement. We hypothesise that familial aggregation of BP may show more expression amongst the offspring of consanguineous marriage of hypertensive parent(s).

Exaggerated blood pressure reactivity in the offspring of first-cousin hypertensive parents.

OBJECTIVE: To study blood pressure and blood pressure reactivity in young offspring of normotensive or hypertensive parents who are consanguineous (first cousins) or are not blood-related. METHOD: Blood pressure, heart rate and body mass index (BMI) were measured in 9-10 year-old male offspring of 19 pairs of first-cousins normotensive, 16 pairs of first-cousin hypertensive and 12 pairs of non-blood-related hypertensive parents. RESULTS: The offspring of first-cousin hypertensive parents exhibited the greatest systolic and diastolic blood pressure reactivity to their first casual blood pressure measurement, while the offspring of first-cousin normotensive parents showed the least reactivity. The offspring of the hypertensive parents who were not blood-related showed an intermediate reactivity. Basal systolic blood pressure (SBP) was also highest in the offspring of first-cousin hypertensive parents, and their basal diastolic blood pressure (DBP) was higher than that in offspring of first-cousin normotensive parents. CONCLUSION: The augmented blood pressure response in the offspring of hypertensive parents may have prognostic implications and serve as an important and significant indicator of predisposition to hypertension later in life.

Assessment of aerobic fitness and its correlates in Omani adolescents using the 20-metre shuttle run test: A pilot study.

OBJECTIVE: To assess aerobic fitness in male and female adolescents using the multistage 20-metre shuttle run test and correlate it with selected fitness variables. METHOD: The subjects comprised 83 girls and 64 boys aged 15-16 years, randomly selected from two segregated government schools in Muscat. After the pupils filled in a short questionnaire on their personal leisure time activities of the preceding week, their heights and weights were measured. Aerobic fitness was assessed by estimating each pupil's minimal oxygen uptake levels (VO2max) using the multistage 20-metre shuttle running test (20-MST). RESULTS: Boys spent more time than girls on leisure physical activities, television, computer and video games and the Internet. The estimated VO2max in both boys and girls showed high correlation with their weekly physical activities. The time spent on television and computer negatively correlated with VO2max in girls but not in boys. Girls had higher body mass index (BMI) and less VO2max compared to boys; BMI showed a negative correlation with VO2max in girls but not in boys. CONCLUSION: Aerobic fitness in this sample was higher in boys than in girls and was strongly influenced by weekly physical activities in both genders. The 20-MST has proved a simple and inexpensive field test for aerobic fitness that could be implemented on a wide scale.

Physical fitness and fatness among Omani schoolboys: a pilot study.

OBJECTIVE: To study the applicability of simple field measurements of physical fitness in a sample of Omani boys and their relationships to selected variables. METHOD: Two field measures of physical fitness-the time to complete 1.6-km run/walk and the sum of 5 skinfold thicknesses-were correlated with personal and family physical activity-related and other variables in a sample of 109 Omani boys aged 9-11 years. RESULTS: Obesity in parents, especially in the mother, showed significant correlation with both fitness measures. The waist/buttocks ratio showed no significant correlation with the 1.6-km time. The number of siblings and siblings sharing a room, number of T.V-watching hours and the number of servants in the family showed no correlation with the chosen fitness indices. CONCLUSION: The results of this pilot study indicate that simple field fitness tests can be used in children and they can yield valuable information related to physical fitness. The same protocol used in this study could be applied to a national study in Oman.

Aging selectively decreases oxidative capacity in rat heart interfibrillar mitochondria.

Mitochondrial-derived oxidative injury contributes to cellular aging as well as to reperfusion-induced tissue damage. While the aging-heart suffers greater tissue damage following ischemia and reperfusion than the adult heart, the occurrence of aging-related alterations in mitochondrial oxidative metabolism in the elderly heart has remained uncertain. We determined if aging altered oxidative metabolism in either of the two populations of cardiac mitochondria, subsarcolemmal mitochondria (SSM) that reside beneath the plasma membrane or interfibrillar mitochondria (IFM) located between the myofibrils. SSM and IFM were isolated from 6-month adult and 24- and 28-month elderly Fischer 344 rat hearts. Aging-related alterations were limited to IFM, while SSM remained unaffected. Aging decreased the rate of oxidative phosphorylation in IFM, including when stimulated by electron donors specific for cytochrome oxidase. Cytochrome oxidase enzyme activity was decreased in IFM from aging hearts, while activity in SSM remained similar to adult controls. These findings allow future studies of aging-related decrements in oxidative function to focus upon IFM, while SSM provide an inherent control group of mitochondria that are free of aging-related alterations in oxidative function. The selective alteration of IFM during aging raises the possibility that the consequences of aging-induced mitochondrial dysfunction will be enhanced in specific subcellular regions of the senescent myocyte.

Baroreflex sensitivity and the blood pressure response to beta-blockade.

The objective of this analysis was to determine whether changes in baroreflex sensitivity (BRS) within 35 hypertensive patients (25 M, 10 F, mean age 47 years) treated with beta-blockade as monotherapy relate to reductions in ambulatory blood pressure (BP) or its variability. BP was recorded intra-arterially directly from the brachial artery before and during submaximal exercise. BRS was determined by the phenylephrine injection technique. MAP and its variability were determined for the awake period of 24-h BP monitoring. Subjects were randomised to one of atenolol, metoprolol, pindolol, or propranolol, and restudied after a mean of 5 months. Beta-blockade increased BRS in 24 patients and decreased BRS in 11. BRS increased from 6.53+/-4.94 to 9.40+/-8.62 ms/mm Hg (mean +/- s.d.) (P<0.01). Waking ambulatory MAP decreased from 125.8+/-15.8 to 106.4+/-16.2 mm Hg (P<0.0001), but its variability did not change. Higher BRS after chronic beta-blockade was associated with a decrease in waking ambulatory MAP (r = -0.55, P<0.001), but not with its variability (r = -0.08). Beta-blockade attenuated the pressor response to exercise, but there was a positive relationship between the effect of beta-blockade on BRS, and on the rise in systolic BP during bicycling (r = 0.63; P<0.001). Any dampening effect of beta-blockade on BP variability at rest in hypertensive patients with the greatest increase in BRS may be offset by increased pressor responses to physical activity such as exercise. Consequently, BP variability is unaffected, even though reductions in ambulatory BP during chronic beta-blockade are inversely related to changes in BRS. BP responses to beta-blockade may be a function of the action of this class of drugs on BRS. However, there is considerable variation, between subjects, in their effect on BRS. This may have implications for other conditions, such as dilated cardiomyopathy, or following myocardial infarction, in which improvement in BRS is one mechanism by which beta-adrenoceptor blockade could improve survival.

Effects of prolonged ACTH-stimulation on adrenocortical accumulation of lipofuscin granules in aged rats.

Subcellular deposition of lipofuscin granules is a marker of aging. Human and rodent adrenal cortices accumulate lipofuscin granules with age, but the mechanism that leads to the accumulation is not known. The ultrastructural appearance of lipofuscin granules resembles that of secondary lysosomes. Since adrenocortical subcellular events are predominantly influenced by ACTH action, we therefore studied the effect of prolonged ACTH-stimulation on adrenocortical accumulation of secondary lysosome-like granules, designated herein as lipofuscin granules. Using aged Fischer 344 male rats as a model, we found that a 7 day ACTH stimulation exerts a reducing effect on adrenocortical lipofuscin accumulation. Thus, adrenocortical accumulation of lipofuscin granules with age in vivo may not be an irreversible process.