Biomedical subjects
Publications and source records attributed to Iddo Z Ben-Dov.
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BACKGROUND: Lanthanum (La) carbonate is an effective phosphate-binder, used to reverse hyperphosphataemia due to chronic kidney disease. Some recent studies in rodents have cast safety uncertainties. The aims of this study were to examine the effects of La on parathyroid hormone (PTH) gene expression and hepatic toxicity. METHODS: Uraemia was induced in rats by a 0.3% adenine-containing diet for 2 weeks. Thereafter, rats were maintained for 4 weeks on an adenine diet with 1.5 or 3% La. Normal, uraemic, and uraemic rats fed a low-phosphorus (P) diet served as controls. RESULTS: Azotaemia developed in all adenine-fed rats. La of 3%, but not 1.5% La, decreased serum P to normal in uraemic rats. Both La 1.5 and 3% decreased urine P excretion. Plasma PTH was tripled in uraemic compared with normal rats. Both the 3.0% La and the low-P diet decreased PTH to normal. PTH mRNA content was increased 2-fold in uraemic compared with normal rats. The 3% La or the low-P diet decreased PTH mRNA levels to normal in uraemic rats. Liver enzymes were normal in all groups. Adenine-induced uraemia decreased liver weight with no additional effect of La. Liver weights corrected for body-weights were the same in all study groups, including the La group. Therefore, La had no effect upon absolute or corrected liver weight. Liver magnetic resonance imaging and microscopy did not reveal toxic changes due to La. CONCLUSIONS: These findings confirm that in rats with adenine-induced uraemia, the P-binder La reverses the hyperphosphataemia and hyperparathyroidism. They are the first demonstration that La decreases PTH gene expression. Importantly, we found no evidence of drug-induced liver toxicity.
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BACKGROUND: White-coat hypertension and masked hypertension have clinical and prognostic consequences. However, reproducibility of these phenomena is unknown. We examined the reproducibility of the white-coat and masking effects with real-life ambulatory blood pressure monitoring (ABPM). METHODS: In a retrospective analysis of a prospectively assembled ABPM database there were 196 subjects (age 58+/-16 years, 59% female, 73% treated for hypertension) who underwent repeat ABPM for standard clinical indications. White-coat hypertension (or isolated manual uncontrolled hypertension) was defined as normal (<135/85 mmHg) awake blood pressure (BP) and abnormal (>or=140/90 mmHg) manual BP. Masked hypertension (or isolated ambulatory uncontrolled hypertension) was defined as abnormal awake BP with normal manual BP. RESULTS: Treated and untreated subjects had similar distribution among hypertension subgroups; 16% white-coat hypertension (in treated subjects, isolated manual uncontrolled hypertension), 13% masked hypertension (in treated subjects, isolated ambulatory uncontrolled hypertension), 59% uncontrolled hypertension, 12% normal blood pressure (or controlled hypertension). In the second session the prevalence of white-coat and masked hypertension increased. Of 31 subjects with white-coat hypertension in the first session 19 (61%) remained ambulatory normotensive in the second session, while 18 of 25 (72%) masked hypertensive subjects remained ambulatory hypertensive. The reproducibility of the systolic manual-awake blood pressure difference was not inferior to that of other ambulatory variables. In untreated subjects the reproducibility of white-coat hypertension, masked hypertension and the white-coat effect was even better. CONCLUSION: In a real-life ABPM database, we found white-coat hypertension and the masking phenomenon to be reasonably reproducible, as compared to other BP variables.
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PURPOSE: The American Heart Association Council on High Blood Pressure Research recently issued recommendations for blood pressure measurement in humans. According to these recommendations, normal 24-hour ambulatory blood pressure is defined as less than 130/80 mm Hg. Concurrently, normal daytime and nighttime blood pressure levels are defined as less than 135/85 mm Hg and less than 120/70 mm Hg, respectively. Our aim was to investigate the intrinsic compatibility of these blood pressure cutoffs in clinical practice. SUBJECTS AND METHODS: We analyzed 4121 consecutive ambulatory blood pressure measurement sessions. Age was 57 +/- 7 years, 53% were female, and 64% and 9% were treated for hypertension and diabetes, respectively. Body mass index was 27 +/- 4 kg/m2, and manual blood pressure was 148 +/- 22/85 +/- 12 mm Hg. Subjects were classified as having normal 24-hour blood pressure if the corresponding value was less than 130/80 mm Hg. Normal awake-sleep blood pressure was diagnosed if awake blood pressure was less than 135/85 mm Hg and sleep blood pressure was less than 120/70 mm Hg. RESULTS: Concordance between the cutoffs was found in 92% of the subjects (kappa = 0.77). Among the 8% of discordant subjects, only 1% were hypertensive applying the 24-hour (but not awake-sleep) blood pressure values, whereas 7% were hypertensive according to awake-sleep but not 24-hour blood pressure values (P <.0001). CONCLUSIONS: In real-life ambulatory blood pressure measurement, a generally good agreement was found between the recently issued ambulatory blood pressure normality suggestions. However, some subjects are classified as hypertensive only according to one of these methods, more often by the awake-sleep cutoff of 135/85 and 120/70 mm Hg. This discordance may be significant in large-scale clinical blood pressure monitoring.
BACKGROUND & AIMS: Hepatitis A virus (HAV) infection is the most common cause of acute hepatitis but is rarely reported during pregnancy. Our aim was to evaluate the impact of acute HAV infection on pregnancy outcome. METHODS: Consecutive admissions of 79,458 pregnant females during a 25-year period were retrospectively reviewed. RESULTS: Thirteen cases of second and third trimester HAV infection were found and evaluated. Nine of the 13 patients (69%) developed gestational complications, including premature contractions (n = 4), placental separation (n = 2), premature rupture of membranes (n = 2), and vaginal bleeding (n = 1). In 8 of these patients, complications led to preterm labor, at a median of 34 gestational weeks (range, 31-37 weeks). Delivery was vaginal in 12 of the 13 cases; fetal distress was noted in a single case, and meconium in amniotic fluid in 2 cases. Median birth weight was 1778 grams and 3040 grams in preterm and term deliveries, respectively (P < .05). Child outcome was favorable in all cases. In 4 cases, neonatal serum HAV RNA levels were measured and found negative. The presence of fever and hypoalbuminemia were associated with delivery at an earlier gestational week. There was a positive relation between gestational week at diagnosis of HAV infection and birth week (r = 0.68, P = .02), suggesting a causality relationship. All mothers featured full recovery from HAV infection. CONCLUSIONS: Acute HAV infection during pregnancy is associated with high risk of maternal complications and preterm labor. HAV serology and maternal vaccination during prepregnancy evaluation should be considered in areas of the world in which susceptible adult populations exist.
OBJECTIVE: Adrenergic alpha-antagonists have been suggested to confer lesser protection, compared to diuretics, when used as first agents for hypertension. While differences in clinic blood pressure may be partly responsible, this inferiority is unexpected in light of the metabolic advantages of alpha-blockade. The aim of this study was to evaluate the relationship between use of alpha-blockers and blood pressure dipping. METHODS: A database of a 24-h ambulatory monitoring service was cross-sectionally evaluated for associations between antihypertensives and dipping. There were 681 treated subjects during a 3-year period (age 63 +/- 14, 57% female). RESULTS: Overall, 78 of 681 treated hypertensive subjects used alpha-blockers (11%). Nine per cent of dippers and 16% of nondippers were treated with alpha-blockade, odds ratio 2.0. Whereas clinic, 24-h, and awake blood pressures were similar in alpha-blocker users and nonusers, sleep blood pressure was significantly higher in the former group. Furthermore, significantly fewer subjects given alpha-blockers had a controlled sleep blood pressure. Among alpha-blocker nonusers sleep blood pressure was the best controlled category, whereas in alpha-blocker users manual blood pressure had the highest rate of control. Generally, accounting for covariates of alpha-blockade (age, gender, diabetes, total number of medications) did not influence the above-mentioned trends. Finally, a limited negative dose-response relationship between alpha-blockade and dipping magnitude was also noticed. CONCLUSIONS: We found a significant negative association between adrenergic alpha-blockade and the magnitude of sleep-related blood pressure decline. Awaiting results from interventional studies, this may suggest a need to perform ambulatory monitoring in patients given alpha-blocking agents (or at least supine and standing measurements), and may partially clarify the inferiority of doxazosin in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).
OBJECTIVES: To find possible association between liver enzymes and mortality in older people. DESIGN: A prospective cohort study. SETTING: Jerusalem. PARTICIPANTS: A systematically selected representative sample of 455 70-year-old ambulatory individuals was prospectively followed for 12 years. MEASUREMENTS: An extensive social and medical profile was developed at age 70 using a detailed interview and physical and ancillary examination. Information on mortality was obtained annually. Differences in survival between subjects stratified according to liver enzyme levels were assessed using the Kaplan-Meier method. Multivariable survival analyses using a Cox proportional hazards model were performed to determine the association between liver enzyme levels at age 70 and mortality over 12 years. RESULTS: Median alanine aminotransferase (ALT) activity of the study population was 11.00 U/L for women and 13.00 U/L for men. Twelve-year survival rates for women with ALT below and above the median levels were similar (78%). For men, these rates were 54% and 65%, respectively (P < .001). Proportional hazards models demonstrated that this greater mortality risk was independent of numerous common risk factors for mortality (hazard ratio (HR) = 1.5, 95% confidence interval (CI) = 1.08-2.19). Adding an interaction between sex and low ALT to the model demonstrated a higher risk of mortality for men with low ALT levels (HR = 2.42, 95% CI = 1.15-5.08). No such risk was demonstrated for the other liver enzymes. CONCLUSION: ALT activity represents a strong and independent surrogate marker for mortality in community-dwelling elderly men.
Most patients with chronic kidney disease develop secondary hyperparathyroidism with disabling systemic complications. Calcimimetic agents are effective tools in the management of secondary hyperparathyroidism, acting through allosteric modification of the calcium-sensing receptor (CaR) on the parathyroid gland (PT) to decrease parathyroid hormone (PTH) secretion and PT cell proliferation. This study showed that rats that were fed an adenine high-phosphorus diet had increased serum PTH and PTH mRNA levels at 7 and 21 d. For studying the effect of activation of the CaR by the calcimimetics R-568 on PTH gene expression, R-568 was given by gavage to uremic rats for the last 4 d of a 7-d adenine high-phosphorus diet. R-568 decreased both PTH mRNA and serum PTH levels. The effect of the calcimimetic on PTH gene expression was posttranscriptional and correlated with differences in protein-RNA binding and posttranslational modifications of the trans acting factor AUF1 in the PT. The AUF1 modifications as a result of uremia were reversed by treatment with R-568 to those of normal rats. Therefore, uremia and activation of the CaR mediated by calcimimetics modify AUF1 posttranslationally. These modifications in AUF1 correlate with changes in protein-PTH mRNA binding and PTH mRNA levels.
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BACKGROUND: The prevalence and implications of masked hypertension are under investigation. The aim of this study was to investigate the clinical characteristics associated with masked hypertension in subjects referred for ambulatory blood pressure (BP) monitoring. METHODS: We analyzed 1494 BP monitoring sessions. A subject was considered to have isolated clinic hypertension if clinic BP was > or =140/90 mmHg and awake BP was <135/85 mmHg. Masked hypertension was diagnosed when clinic BP was <140/90 mmHg and awake BP was > or =135/85 mmHg. RESULTS: Of 1494 individuals, 16% had normal BP, 11% had isolated clinic hypertension, 61% had hypertension, and 11% had masked hypertension. Subjects with masked hypertension were younger and more likely to be male than subjects with isolated clinic hypertension, and their awake heart rate was significantly higher. A negative correlation was found between the awake-clinic systolic BP difference and clinic systolic BP (r = -0.7, P < .0001). The reproducibility of the masking phenomenon was comparable to that of other variables. CONCLUSIONS: In a group of consecutive subjects referred for ambulatory BP monitoring, masked hypertension was found to be as common as isolated clinic hypertension. Masking was correlated with male sex, young age, and higher awake heart rate, thus suggesting a causal relationship with greater daytime physical activity. The linear association of the masking and the white-coat effects to clinic BP suggests that regression toward the mean may partially explain these phenomena.
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OBJECTIVE: Blood pressure dipping pattern has clinical and prognostic consequences. However, reproducibility of night-time blood pressure fall during 24-h ambulatory blood pressure monitoring is considered limited. This limited reproducibility is possibly a result of inadequate day-night definitions. We retrospectively examined the reproducibility of blood pressure dipping in clinical practice, applying a method that accounts for sleep-awake states and does not rely on arbitrary day-night definitions. We also examined dipping repeatability in subjects with changing blood pressure. METHODS: Of 962 consecutive ambulatory measurements performed in our unit during a 3-year period, 100 patients (age 60+/-15) had a prior session, and were the subjects of this study. Based on patients' report we defined 'awake blood pressure' as the average of pressure recordings while the subject was awake, including night-time arousals, and 'sleep blood pressure' as the average of pressure recordings while the subject was sleeping, including afternoon naps. RESULTS: We found systolic blood pressure dipping not less reproducible than 24-h, awake- and sleep systolic blood pressure, as evaluated by both Pearson correlations (r=0.52 versus 0.5, 0.5, 0.49, respectively, P < or =0.0002 in all), and Bland-Altman repeatability. In a subgroup of 35 subjects (age 63+/-15) with at least 10 mmHg change in systolic blood pressure between the two sessions, systolic blood pressure dipping remained reproducible (r=0.45, P<0.007). CONCLUSIONS: When interpreted in a way that accounts for sleep-awake pattern, sleep-induced systolic blood pressure dipping in clinical practice is a very reproducible feature of ambulatory blood pressure monitoring, in accordance with its vital prognostic implications.