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Biomedical subjects

A Ungar

Publications and source records attributed to A Ungar.

At least 19 recordsLinked to original sources

Isolated ambulatory hypertension is common in outpatients referred to a hypertension centre.

The present investigation was aimed at determining the prevalence and the blood pressure (BP) profile of isolated ambulatory hypertension, defined as an elevated ambulatory BP with normal office blood pressure, in a series of 1488 consecutive outpatients referred for routine clinical evaluation of suspected or established arterial hypertension. All patients underwent both office BP (OBP) measurement by a physician and 24-h ambulatory blood pressure monitoring (ABPM). Using OBP values (cutoff for diagnosis of hypertension >/=140/90 mmHg) and daytime ABPM (cutoff for diagnosis of hypertension >/=135/85 mmHg), patients were classified into eight subgroups. In the whole series we found that, independent of treatment status, the prevalence of isolated ambulatory hypertension exceeded 10%. More importantly, 45.3% of individuals who presented with normal OBP values, showed elevated BP at ABPM. Night-time BP, 24-h pulse pressure, and BP variability were significantly higher in isolated ambulatory hypertensives than in normotensive or in white-coat hypertensive individuals. Therefore, isolated ambulatory hypertension is characterized by a blood pressure profile that is similar to that observed in sustained hypertension. These findings suggest that isolated ambulatory hypertension is very common and probably the indications for ABPM should be more extensive in outpatients referred to hypertensive centre.

Academic Medical Centers↗

Methodology of head-up tilt testing potentiated with sublingual nitroglycerin in unexplained syncope.

Shortened head-up tilt testing (HUT) potentiated with sublingual nitroglycerin (60 degrees passive standing for 20 minutes followed, if negative, by 400 microg of sublingual nitroglycerin spray with the test continuing for another 20 minutes) differs from conventional nitroglycerin HUT for a shorter drug-free phase (20 vs 45 minutes). To compare the positivity rate of the 2 protocols, both tests were performed in a randomized sequence in 10 patients with unexplained syncope (study 1), and another 42 patients were randomly assigned either to conventional or to shortened nitroglycerin HUT (study 2). To evaluate the reproducibility of the shortened nitroglycerin HUT, another 38 patients with unexplained syncope underwent 2 consecutive tests within a 7+/-8 day interval (study 3). Finally, to evaluate the specificity of the test, 47 control subjects underwent shortened nitroglycerin HUT (study 4). Seven positive responses were observed during shortened nitroglycerin HUT, and there were 8 positive responses during conventional nitroglycerin HUT (p = NS) in the study 1 group. Fifteen positive (71%) responses, 5 negative responses, and 1 exaggerated response were observed during shortened nitroglycerin HUT; 16 positive (76%, p = NS vs. shortened nitroglycerin HUT), 3 negative, and 2 exaggerated responses were observed during conventional nitroglycerin HUT in the study 2 group. During the first test, 21 patients (55%) had a positive, 15 patients had a negative, and 2 patients had an exaggerated response in study group 3. During the second test, 15 positive (39%), 19 negative, and 4 exaggerated responses were observed. Thus, the reproducibility was 67% for a positive and 94% for a negative test. In control subjects, 2 positive (4%) responses, 38 negative, and 7 exaggerated responses were observed with a specificity of 96% in study group 4. In patients with unexplained syncope, shortened nitroglycerin HUT allowed a positivity rate similar to that of the conventional test. Moreover, the shortened test provided a high specificity and adequate reproducibility for both the positive and the negative responses.

Administration, Sublingual↗

Changes in renal autacoids and hemodynamics associated with aging and isolated systolic hypertension.

The aging kidney is characterized by a decrease in renal blood flow and glomerular filtration rate mainly due to glomerulosclerosis. Nevertheless, even in the presence of these changes, the kidney maintains its functionality until advanced age. However, there is a tendency towards greater renal vasoconstriction in the elderly as compared with young individuals. This occurs either in physiological circumstances such as physical exercise, or in disease manifestations, such as the effective circulatory volume depletion that develops, for example, in heart failure. This tendency may be secondary to the reduction of renal autacoid modulatory capacity, particularly at the vasodilating prostaglandin level. In an acute experimental model we could demonstrate that, in the healthy elderly, the renal response to adrenergic activation by mental stress is characterized by a prolonged and pronounced vasoconstriction. In addition to this, in elderly patients affected by isolated systolic hypertension, we demonstrated an impairment of renal hemodynamic and humoral adaptation capacity in response to adrenergic activation and blood pressure increase. In the presence of sudden blood pressure increase, the kidney of these patients responds with a passive vasodilation and a glomerular filtration rate increase without any activation of humoral modulatory substances. The impairment in renal adaptation capacity may predispose these patients to renal injury, particularly in the presence of the many hypertensive peaks which characterize everyday life of elderly individuals. In conclusion, these results show that renal adaptation capacity of elderly patients with isolated systolic hypertension is completely lost. Further studies will elucidate whether antihypertensive treatment per se, or specific classes of antihypertensive drugs, are able to revert this impairment.

Aged↗

Cardiopulmonary resuscitation of older, inhospital patients: immediate efficacy and long-term outcome.

OBJECTIVE: To determine the independent effect of advancing age on prognosis after cardiopulmonary resuscitation (CPR). DESIGN AND SETTING: Retrospective analysis of clinical records of patients who received CPR in a geriatric department equipped with an intensive care unit. PATIENTS: A total of 245 patients (146 men, 99 women; mean age, 70+/-11 yrs) received CPR. Of these, 221 had a cardiocirculatory arrest (CA) in the intensive care unit and 24 had a CA in the general ward of the department. Acute myocardial infarction was the most frequent admission diagnosis. INTERVENTIONS: CPR according to standard guidelines in all cases. MEASUREMENTS AND MAIN RESULTS: Immediate, short-term (hospital discharge), and long-term (median follow-up, 31.5 months; range, <1-124 months) survival. Older patients had a lower immediate survival (<70 yrs [72/137] 52.6% vs. > or =70 yrs [43/108] 39.4%; p < .05) and, less frequently, ventricular tachycardia/ fibrillation (VT/VF) as a cause of CA. VT/VF bore the lowest immediate mortality rate (19/104; 18.3%) as compared with asystole/complete heart block (66/102; 64.7%) or pulseless electrical activity (40/49; 81.6%; p < .001). Acute myocardial infarction, acute heart failure, hypotension, and occurrence of CA in the intensive care unit were also univariate predictors of unfavorable, immediate prognosis. However, in a multiple logistic analysis model, the mechanism of CA (asystole/complete heart block or pulseless electrical activity vs. VT/VF), acute myocardial infarction, heart failure, and hypotension were independent predictors of unfavorable immediate prognosis, whereas advancing age was not. Similarly, after initially successful CPR, short-term survival was independently associated with acute myocardial infarction, hypotension before CA, initial rhythm at CA, and need for mechanical ventilatory support after CPR, but not with age. Longterm survival (42 patients; 17.2% of the original cohort; median survival, 32 months) was also independent of age, whereas it was negatively associated with heart failure. CONCLUSION: Immediate, short- and long-term prognosis after in hospital CPR is independent of age, at least when possible confounders are simultaneously taken into account.

Aged↗

Movicol in treatment of constipation and faecal impaction.

To resolve severe constipation or faecal impaction requires the induction of a large increase in faecal water content that hitherto has only been achieved with enemas. A novel iso-osmotic laxative has been shown to achieve a similar effect from oral dosing.

Cathartics↗

Changes in renal autacoids in aged human hypertensives.

The aging process determines several modifications of the kidney, that, however, do not provoke any dysfunction in normal conditions. But in the elderly--in the presence of stressful situations and particularly when adrenergic activation is present--the kidney is more vulnerable than in the young, and renal failure may arise. Variations typical of the aging kidney are accelerated when hypertension overlaps the physiological renal process, because both senescence and hypertension weight on the same structures, i.e. glomeruli. We studied renal hemodynamic adaptation capacity both in the healthy elderly and in patients affected by isolated systolic hypertension, in an acute experiment which requires the application of a mental stress-induced adrenergic activation. In hypertensive patients we have already demonstrated a total lack of renal adaptation capacity. In fact, while the elderly normotensives react with a prolonged and pronounced vasoconstriction, in those with isolated systolic hypertension, adrenergic activation induces a passive renal vasodilation and glomerular hyperfiltration. The anomalous adaptation capacity of renal hemodynamics is probably due to an impairment in the paracrine response of renal vasculature. Indeed in the hypertensive elderly, unlike in the normotensive one, no variations of autacoid production occur during the adrenergic activation. Following on from this, pattients affected by isolated systolic hypertension passively suffer the many hypertensive peaks which characterize their every day life. The altered renal autoregulation of the elderly with isolated systolic hypertension may explain the accelerated glomerulosclerosis and the greater incidence of renal damage and end-stage renal disease which characterize this condition. These aspects underline the primary role of the antihypertensive treatment of isolated systolic hypertension, not only for the prevention of cardiovascular mortality but also of renal damage and/or end-stage renal disease.

Aging↗

Undertreatment of hypertension in community-dwelling older adults: a drug-utilization study in Dicomano, Italy.

OBJECTIVE: To define: (1) the prevalence of and (2) factors associated with undertreatment of hypertension in older persons; and (3) the prevalence of specific drug regimens and reasons for their selection. PARTICIPANTS: Cross-sectional survey of persons aged > or =65 years living in Dicomano, Italy. MAIN OUTCOME MEASURES: Prevalence of untreated and uncontrolled hypertension, both defined on the basis of two blood pressure (BP) cut-off points (> or =140/90 and > or =160/90 mm Hg) and of the presence of pharmacological treatment Predictors of undertreatment were analysed for the higher BP cut-off only. RESULTS: Five hundred of 692 (72.3%) and 380/692 (54.9%) participants met the 140/90 and the 160/90 mm Hg BP criterion, respectively. Of the latter, 162 (42.6%) were untreated, 119 (31.3%) had uncontrolled and 99 (26.1%) controlled hypertension. Women [odds ratio (OR), 0.4; 95% confidence interval (CI), 0.2-0.7], participants with coronary artery disease (CAD) (OR, 0.2; 95% CI, 0.1-0.6), stroke (OR, 0.3; 95% CI, 0.1-0.7), and preserved cognitive status (Mini Mental State Examination score >21: 0.3; 95% CI, 0.2-0.7) were more frequently treated. Uncontrolled hypertension was less likely in women (OR, 0.5; 95% CI, 0.3-1.0) and CAD patients (OR, 0.3; 95% CI, 0.1-0.7). Angiotensin converting enzyme (ACE)-inhibitors (55%), calcium (Ca)-antagonists (31%) and diuretics (20%) were the drugs most commonly prescribed. ACE-inhibitors were preferred, and diuretics rarely used, in diabetic subjects. Ca-antagonists were used mostly in CAD participants. CONCLUSIONS: Hypertension is undertreated in the majority of noninstitutionalized older adults, especially in men with impaired cognition and no vascular disease. Drug regimens are mostly based on ACE-inhibitors and Ca-antagonists, as a result of associated clinical conditions, requiring individualized treatment.

Adrenergic beta-Antagonists↗

Impaired renal adaptation to stress in the elderly with isolated systolic hypertension.

The aim of this study was to evaluate the renal response in the elderly with isolated systolic hypertension (ISH) when an adrenergic activation, as induced by mental stress, is applied. Renal hemodynamics and kidney neurohumoral response to mental stress were studied in 8 elderly patients with ISH (aged 63 to 82 years) along with 8 elderly normotensive subjects. The study encompassed four 30-minute experimental periods (baseline, mental stress, and recovery I and II). In these patients, the mental stress-induced blood pressure rise was associated with a significant increase in both effective renal plasma flow ((131)I-labeled hippurate clearance) and glomerular filtration rate ((125)I-labeled iothalamate clearance) (+42% and +29%, respectively; P<0.01 for both), without variations in filtration fraction, while elderly normotensives reacted to adrenergic stimulation with renal vasoconstriction but with the glomerular filtration rate constant. Variations in renal vasoactive substances, which paralleled hemodynamics of the kidney, differed in the 2 groups. In normotensives, excretion (radioimmunoassay) of endothelin-1, prostaglandin E(2), and cGMP increased during the stimulus (+50%, +54%, and +59%, respectively; P<0.05). In ISH patients the release of these autacoids did not vary in any of the experimental periods. In conclusion, in patients with ISH the renal adaptive capacity to sympathetic activation is impaired, and the data may suggest that the glomerulus passively suffers the blood pressure increase, probably because of the insufficiency of the neurohumoral response, particularly in regard to the increase of endothelin-1. This hemodynamic pattern may predispose ISH patients to a higher risk of renal injury.

Adaptation, Physiological↗

Excessive vasoconstriction after stress by the aging kidney: inadequate prostaglandin modulation of increased endothelin activity.

The adaptive capacity of the aging kidney to stimulation of the sympathetic nervous system, as induced by a 30-minute mental stress (MS), was assessed in 8 elderly healthy women (68 to 82 years of age) and compared with that of 8 younger women (24 to 40 years of age). The study encompassed 4 consecutive 30-minute periods (baseline, mental stress, recovery 1, and recovery 2). In the elderly subjects, baseline effective renal plasma flow (ERPF)(iodine 131-labeled hippurate clearance) was lower and glomerular filtration rate (GFR)(iodine 125-labeled iothalamate clearance) was proportionally less reduced than in the younger group; the filtration fraction (FF) was higher. The elderly group excreted more endothelin 1 (ET-1) (P < .05), prostaglandin E2 (PGE2), and 6-keto-prostaglandin F1alpha (6-keto PGF1alpha)(P < .001 for both)(radioimmunoassay). Mental stress induced similar increases in blood pressure, heart rate, and plasma catecholamines in the 2 age groups, limited to the stimulation period. In the elderly group, mental stress caused a prolonged decrease in ERPF that reached its maximum 60 minutes after mental stress (-33%, P < .05), while GFR remained constant during the whole experiment, so that FF increased. In the younger subjects, renal hemodynamic changes were limited to the mental stress period. ET-1 increased during mental stress and the first recovery period in the elderly group (+50% and +25%, P < .05) as it did in the younger group, but the elderly group differed from the younger in that vasodilating prostaglandins increased only during mental stress. In conclusion, the aging kidney reacts to adrenergic stimulation with more-pronounced and -prolonged vasoconstriction that is probably caused by a defect in prostaglandin modulation of endothelin activity. Autoregulation of GFR is maintained at the expense of increased intraglomerular pressure.

6-Ketoprostaglandin F1 alpha↗

Increased renal formation of thromboxane A2 and prostaglandin F2 alpha in heart failure.

Renal formation of the vasoconstrictor prostaglandins thromboxane A2 (TXA2) and prostaglandin F2 alpha (PGF2 alpha) was investigated in 25 patients with cardiac failure, divided into New York Heart Association functional classes I to IV, and in eight healthy control subjects. Plasma renin activity (PRA) and hemodynamic parameters were also investigated. Renal vasoconstrictor eicosanoid formation, measured in urinary daily excretion, was not different between patients in class I and control subjects. Class II to IV patients showed progressively increasing production of PGF2 alpha (F = 49.8, p < 0.001, analysis of variance) and TXA2 (F = 37.8, p < 0.002). PGF2 alpha excretion peaked in class IV (+ 1266% vs class I, p < 0.001). Compared with class I, urinary excretion of thromboxane B2 was + 816% in class III and + 1561% in class IV (both p < 0.001). PRA was significantly increased only in class IV (+ 1558%, p < 0.001). The current results indicate a progressive increase in renal production of vasoconstrictor eicosanoids directly related to New York Heart Association class and suggest that these prostanoids may have a role in deterioration of renal function.

Adolescent↗

Renal adaptation to stress: a possible role of endothelin release and prostaglandin modulation in the human subject.

The aim of this study was to define the neurohumoral response associated with the renal hemodynamic perturbations induced by mental stress acting as an adrenergic stimulus. In 8 healthy women, the effects of mental stress were studied during four consecutive 30-minute periods (baseline, mental stress, recovery I, recovery II). Mental stress induced sympathetic activation as evidenced by increases in blood pressure, heart rate, and plasma norepinephrine level. Effective renal plasma flow (iodine 131-labeled hippurate clearance) decreased only during mental stress (-22%, p < 0.05 vs baseline); glomerular filtration rate (iodine 125-labeled iotalamate clearance) remained constant during the entire experiment; the filtration fraction increased significantly during mental stress and recovery I (+30% and +22%, respectively, p < 0.02 for both). Complex neuroendocrine responses were associated with the hemodynamic changes. Urinary excretion of endothelin-1 and 6-keto-PGF(1alpha) increased during mental stress (+53%, p < 0.01, and +20%, p < 0.01, respectively) and recovery I (+49% and +29%, respectively, p < 0.01 for both). Urinary cyclic guanosine monophosphate rose only during mental stress (+77%, p < 0.05), whereas excretion of PGE2 showed a stepwise increase throughout recovery I and II (+292%, p < 0.01, and +360%, p < 0.001, respectively). In conclusion, the present experiments demonstrate that renal hemodynamic response induced by mental stress is a complex reaction in which endothelin-1, prostaglandins, and presumably nitric oxide take part.

Adaptation, Physiological↗

Ectopic expression of either the Drosophila gooseberry-distal or proximal gene causes alterations of cell fate in the epidermis and central nervous system.

Previous studies have shown that the segment polarity locus gooseberry, which contains two closely related transcripts gooseberry-proximal and gooseberry-distal, is required for proper development in both the epidermis and the central nervous system of Drosophila. In this study, the roles of the gooseberry proteins in the process of cell fate specification have been examined by generating two fly lines in which either gooseberry-distal or gooseberry-proximal expression is under the control of an hsp70 promoter. We have found that ectopic expression of either gooseberry protein causes cell fate transformations that are reciprocal to those of a gooseberry deletion mutant. Our results suggest that the gooseberry-distal protein is required for the specification of naked cuticle in the epidermis and specific neuroblasts in the central nervous system. These roles may reflect independent functions in neuroblasts and epidermal cells or a single function in the common ectodermal precursor cells. The gooseberry-proximal protein is also found in the same neuroblasts as gooseberry-distal and in the descendants of these cells.

Animals↗

Inhibitory regulation by co-released peptides of catecholamine secretion by the canine adrenal medulla.

1. We have stimulated the peripheral end of the cut left splanchnic nerve in anaesthetized dogs while collecting the venous effluent of the left adrenal gland for catecholamine estimation. 2. With low frequency stimulation the resting output of catecholamines was inhibited but at high frequencies it was augmented. 3. The inhibition of catecholamine output by low frequency stimulation was reversed by opiate antagonists (naloxone and nalmefene) but enhanced by angiotensin converting enzyme inhibitors (captopril and enalapril).

Adrenal Medulla↗

Metabolic requirements for release of endogenous noradrenaline during myocardial ischaemia and anoxia.

The metabolic conditions required for noradrenaline (NA) release from ischaemic and anoxic perfused hearts of the rat were studied. Forty minutes of flow reduction to approximately 0.25 ml g-1 min-1 did not elicit enhanced noradrenaline overflow from the isolated heart perfused with normoxic perfusate even in the absence of added substrate. Enhanced overflow did occur when substrate-free ischaemia was induced after a 60 min period of substrate-free perfusion. Noradrenaline overflow was enhanced by perfusion at normal flow rates with an anoxic (Po2 less than or equal to 1 mmHg) perfusate containing no substrate. Such enhanced overflow occurred in the absence of calcium in the perfusate and was almost completely abolished by the addition of 11 mM glucose. Enhanced noradrenaline overflow occurring either during low flow ischaemia after substrate deprivation or during anoxic substrate-free perfusion at normal flow rates was markedly suppressed by desipramine. Exocytotic noradrenaline overflow induced by electrical stimulation of the left cervico-thoracic ganglion continued unchanged during 60 min of anoxia if the perfusate contained 11 mM glucose. In the absence of added substrate there was a decline in the overflow induced by such stimulation which was more rapid with anoxic than normoxic perfusate. Re-introduction of calcium, oxygen and substrate after 10, 20 or 30 min of calcium-free, substrate-free, anoxic perfusion was associated with a massive overflow of the intracellular enzyme lactate dehydrogenase. At 10 min there was an associated transient minor increase in NA overflow but at 20 and 30 min the overflow of NA, elevated as a result of anoxic perfusion, returned to pre-anoxic levels on the re-introduction of substrate and oxygen. 7 These studies demonstrate a central role for the metabolic status of the sympathetic nerve terminal in determining the magnitude ofexocytotic and nerve-impulse independent noradrenaline release from the heart. During the course of myocardial ischaemia in vivo nerve-impulse independent release would be expected to occur only in regions of severe flow reduction. This may produce heterogeneous stimulation of the myocardium.

Animals↗

Are protein synthesis inhibition and phase shifting of the circadian clock in Gonyaulax correlated?

We describe a method whereby the effect of protein synthesis inhibitors upon protein synthesis in Gonyaulax cultures may be reliably measured. Using this method, we found that protein synthesis inhibition and clock resetting were correlated, but that the correlation was not as close as has been reported in other systems. The effect of the inhibitors anisomycin and cycloheximide upon phase shifting of the circadian clock was a function of the illumination and temperature conditions to which the cells were subjected, but these factors did not appear to influence the inhibition of protein synthesis by these drugs. Cellular protein synthesis did not recover immediately from the inhibitors' effects; depending upon the previous concentration of the inhibitor, translational recovery from the drugs may require hours. This observation has important implications for the analysis of any phase response curve when the stimulus is a chemical.

Animals↗

Muscarinic and nicotinic mechanisms in the responses of the adrenal medulla of the dog and cat to reflex stimuli and to cholinomimetic drugs.

In isolated perfused adrenal glands of the cat, muscarinic and nicotinic agonists selectively released adrenaline and noradrenaline respectively. In isolated perfused adrenal glands of the dog, the output of adrenaline and noradrenaline remained in a fixed ratio at rest and when stimulated by muscarinic or by nicotinic agonists. In the anaesthetized dog, a combination of muscarinic and nicotinic antagonists was needed to block reflex responses of the adrenal medulla. A nicotinic antagonist was more effective in blocking the baroreceptor reflex response than the chemoreceptor reflex response.

Adrenal Medulla↗

Effects of the renin-angiotensin system on the reflex response of the adrenal medulla to hypotension in the dog.

We have studied the influence of the renin-angiotensin system on the control of catecholamine release from innervated and denervated adrenal glands of anaesthetized dogs. Captopril reduced the resting release of catecholamines and inhibited release evoked either by lowering carotid sinus pressure or by stimulating the peripheral end of the cut splanchnic nerve. Both responses were restored by exogenous angiotensin II, and the reflex response could also be restored by corticotrophin. Cycloheximide, in the presence of captopril, further reduced the resting release of catecholamines and prevented the restoration of the reflex response by angiotension II. Plasma renin activity did not rise during baroreceptor tests lasting 10 min, but catecholamine release was evoked from the first minute. We conclude that the response of the adrenal medulla to sympathetic activity requires a minimum circulating concentration of angiotensin II. It is severely impaired by inhibition of the renin-angiotensin system but function can be restored either by exogenous angiotensin II or by corticotrophin.

Adrenal Medulla↗