Subcortical ischaemic changes in young hypertensive patients: frequency, effect on cognitive performance and relationship with markers of endothelial and haemostatic activation.

Information on subcortical ischaemic changes (SIC) in young hypertensive patients is scarce. We evaluated the frequency of SIC at magnetic resonance imaging (MRI), the possible effect on cognition of these patients, and the role of plasma markers known as indicators of endothelial and haemostatic activation. Inclusion criteria were age

Effects of losartan and chlorthalidone on blood pressure and renal vascular resistance index in non-diabetic patients with essential hypertension and normal renal function.

Antihypertensive drugs can differ in target organ protection despite similar blood pressure (BP) control. We compared the effects of losartan (L) and chlorthalidone (C) on renal vascular resistance index (RVRI) in 194 grade I to II, non-diabetic hypertensive patients with increased RVRI (>0.68 m/s by echo-Doppler) but normal renal function. Patients were randomly allocated to C 25 mg/d or L 50 mg/d according to a single blind, PROBE study design. After 4 weeks of treatment, 92 patients (48 L/44 C) with BP <140/90 mm Hg were enrolled in the long-term phase of the study. After 12 months a normalization of RVRI was observed in 47 of 48 patients treated with L (97.5%) and only in 14 of 44 of those treated with C (25.8%) despite no differences in BP control. Patients whose RVRI remained elevated during C therapy underwent a 2-week washout period and then were treated with L 50 mg/d for 12 additional months. After that period 28 of 30 (95%) of patients who were nonresponders to C showed a normalization of RVRI despite no differences in BP control. In conclusion, our data suggest that treatment with L can improve renal hemodynamic and exert a protective renal effect beyond BP control in patients with hypertension.

Pemphigus vulgaris: environmental factors. Occupational, behavioral, medical, and qualitative food frequency questionnaire.

BACKGROUND: There have been reports suggesting the involvement of environmental factors in the disease process of pemphigus. Factors suggested include exposure to pesticides or certain drugs. OBJECTIVE: To analyze the association of pemphigus with environmental exposure to various agents, including smoking, recreational and occupational insults, drugs, and food. DESIGN AND SETTING: In-person interviews of pemphigus patients and control subjects were conducted by trained medical investigators using a structured questionnaire. Questions included occupational, behavioral, medical, and qualitative food frequency details. The multicenter study was conducted at outpatient services of teaching hospitals in Bulgaria, Brazil, India, Israel, Italy, Spain, and the USA. PARTICIPANTS: A total of 126 pemphigus patients (55 men, 71 women; age, 54 +/- 17 years) and 173 healthy controls (87 men, 86 women; age 50 +/- 19 years) were interviewed in the period between October 1, 1999 and March 31, 2000. The diagnosis of pemphigus was based on clinical, histologic, immunohistologic, and immunohistochemical criteria. The disease duration was 2-27 years (8.4 +/- 7.2 years). Individuals with skin diseases other than pemphigus were selected as control subjects. MAIN OUTCOME MEASURE: Information on drugs, foods, and occupational, environmental, constitutional, and other possible risk factors was analyzed by t-tests and chi-squared tests as applicable. A multivariate logistic regression model was applied to the data to study simultaneously the independent relationship between each risk factor and pemphigus vulgaris. RESULTS: The risk for pemphigus vulgaris was lower for ex-smokers and current smokers than for patients who had never smoked. Exposure to pesticides and occupational exposure to metal vapor were associated with an increased risk of pemphigus. Pemphigus patients had more pregnancies than controls. There were differences in environmental factors between countries, with exposure to gardening materials and pesticides being highest among patients from Bulgaria, followed by Israel. Disease characteristics also exhibited differences between countries. Bulgarian patients less frequently had oral mucous membrane lesions: 66% compared to 92% for Israeli patients and 83% for Italians. The distribution of the disease in skin and mucous membranes was similar among patients from all countries. Exclusive skin involvement was seen in 50% of patients, mucous membranes alone in 23% of patients, and both skin and mucous membranes in 27% of patients. CONCLUSIONS: The beneficial effect of smoking on pemphigus might be explained by its effect on the immune system. In addition, smoking has an antiestrogenic effect, while pesticides have an estrogenic effect. The lower numbers of smokers among patients, the higher exposure rates to pesticides, and the higher number of female patients who had been pregnant may point to the contribution of estrogens to the disease process. It remains to be determined whether measures, such as avoiding exposure to pesticides or metal vapor, may be beneficial in the clinical context. As the present study was a survey, more definitive studies should be conducted to validate the results.

Effects of lithium carbonate (Li2CO3) on in-vitro-cultured normal human skin explants.

The early morphological changes induced by lithium carbonate, a well-known psoriasis-provoking drug, were studied on cultured skin. Normal human skin from patients undergoing mastectomy was cultured in the presence of 3 mM, 6 mM and 10 mM of Li2CO3 for 4 days. The morphological changes were then evaluated by three observers in a blind manner and their reports were matched and collated. The cultured skin in the presence of Li2CO3 showed cell crowding of keratinocytes in the lower part of the epidermis, indicating epidermal hyperplasia. Another striking finding was intercellular oedema and vacuolar alteration with formation of small cavities in the upper dermis. There was no evidence of parakeratosis or any other histological characteristic of psoriasis, except hyperproliferation of the epidermis. Based on our knowledge of mechanisms of lithium action, we proposed two competitive explanations for its action on the epidermis: i) that lithium acts directly on dividing cells of the epidermis; and ii) that it acts indirectly by altering epidermal barrier function. Although we lack definite proof, we suggest that the observed morphological changes, in particular the non-specific stimulus to epidermal proliferation, are the primary events which initiate the process that will ultimately lead to the development of psoriasis in a predisposed patient.

Progressive impairment of left ventricular diastolic filling with advancing age: a Doppler echocardiographic study.

OBJECTIVE: To identify the sequence and significance of left ventricular filling abnormalities associated with progressive aging in humans. DESIGN: Cross-sectional study comparing three age groups. SETTING: Department of Geriatrics at University of Naples. PARTICIPANTS: Seventy-five healthy subjects in three age groups: 25 subjects from 25 to 45 years (Group I), 25 subjects from 46 to 65 years (Group II), and 25 subjects from 66 to 85 years (Group III). INTERVENTION: None. MAIN OUTCOME MEASURES: All underwent pulsed-doppler echocardiography under color guide to measure the following parameters: peak velocity flow for early (E wave) and late (A wave) mitral flow; A/E wave ratio; deceleration time of mitral flow (MDt); isovolumic relaxation time (IRT); ratio of velocity time integrals of the A wave to the velocity time integrals of the entire mitral spectrum (VTIA/VTIM). RESULTS: Peak velocity of the E wave was slightly lower in Group II and III compared to Group I; in contrast, peak velocity of the A wave was greater (P less than 0.005) in aged individuals. Also A/E wave ratio, MDt, and IRT were significantly greater with advancing age (P less than 0.01; P less than 0.05 and P less than 0.001, respectively). Finally, VTIA/VTIM tended to be greater in the oldest group, but not significantly so. CONCLUSIONS: Left ventricular relaxation is progressively impaired in late middle age and old age, presumably an early marker of cardiac aging. Increased left atrial pressure is compromised only in the oldest group, presumably representing a compensation for impaired left ventricular relaxation.

Effectiveness of glibenclamide on myocardial ischemic ventricular arrhythmias in non-insulin-dependent diabetes mellitus.

Glibenclamide, a hypoglycemic sulfonylurea, is a blocker of the adenosine triphosphatase-modulated potassium ion channels. The opening of these channels in the myocardial cells, induced by acute myocardial hypoxia, can be responsible for ischemic ventricular arrhythmias. To evaluate the antiarrhythmic effects of this drug 19 non-insulin-dependent diabetic patients were selected. They had coronary artery disease and evidence on Holter monitoring of ventricular premature complexes or nonsustained ventricular tachycardia, or both, induced by transient myocardial ischemia. In all patients, 24-hour electrocardiographic monitoring was performed to evaluate the number and duration of myocardial ischemic events, the frequency of ventricular premature complexes and nonsustained ventricular tachycardia per minute of ischemia and the percentage of ventricular premature complexes versus total ischemic beats. Selected patients were classified in 2 groups: group A (9 patients) received metformin (placebo) and group B (10 patients) was treated with glibenclamide. On the fourteenth day patients underwent 24-hour control monitoring. Then a crossover between the 2 groups was made and a new Holter monitoring sequence was performed at the end of the second phase. Results indicate that glibenclamide significantly (p less than 0.001) reduced both the frequency of ventricular premature complexes and the episodes of nonsustained ventricular tachycardia during transient myocardial ischemia, but did not change the number and duration of acute myocardial ischemic attacks and did not reduce the spontaneous ventricular arrhythmias. Thus, glibenclamide appears to have an antiarrhythmic effect in preventing ventricular arrhythmias induced by transient myocardial ischemia.

Hemodynamic changes in left ventricular function during acute coronary insufficiency: a Doppler echocardiographic study.

To define the availability of Doppler echocardiography in evaluating left ventricular hemodynamic changes induced by some clinical findings of acute coronary insufficiency, we selected 12 patients with angina and 32 affected by acute myocardial infarction. Doppler echocardiography was performed at hospital admittance and during recovery time. Left ventricular contractility was defined on the systolic aortic flow spectrum by measuring the aortic velocity maximum, the time to peak/left ventricular ejection time ratio, and the cardiac output. During the first examination, left ventricular contractility significantly decreased in patients with angina and in those with acute myocardial infarction. After the acute phase, these parameters slightly improved. Left ventricular diastolic filling was evaluated in the transmitral flow. A decreased E-wave velocity and an increased late component (A wave) with inversion of the E/A wave ratio were found in patients with acute myocardial infarction during the first examination. This morphology inverts when the patients stabilize. On the contrary, this ratio stayed above one during and after angina. In this study, we also defined the usefulness of the color Doppler method in setting up criteria to identify some early morphological complications of acute myocardial infarction in 12 patients with acute infarction and a new systolic murmur. This technique showed an ischemic rupture of the ventricular septum in five cases and mitral regurgitation in seven. The color Doppler method has allowed us to obtain a semi-quantitative assessment of the mitral regurgitation and the location of the ventricular septal defect.

Hypertension in the elderly is associated with impaired glucose metabolism independently of obesity and glucose intolerance.

We evaluated insulin secretion, insulin sensitivity and blood pressure changes after oral administration of glucose in hypertensive and normotensive elderly subjects. The hypertensive group consisted of 12 subjects (aged 72.5 +/- 1.9 years, mean +/- s.e.m.) who had a history of hypertension lasting 10-25 years and were not more than 20% above ideal body weight. The normotensive group consisted of 12 subjects matched to the hypertensive group for age, sex and weight. All subjects underwent an oral glucose tolerance test (75 g glucose dissolved in 300 ml water), an intravenous glucose tolerance test (0.33 g/kg of a 50% glucose solution) and a euglycaemic, moderately hyperinsulinaemic glucose clamp. In both groups, oral glucose tolerance was normal according to the criteria of the National Diabetes Data Group; the hypertensive group showed significantly higher plasma glucose and insulin responses to oral glucose than the normotensive group, suggesting insulin resistance. The results of the euglycaemic clamp confirmed the state of reduced insulin sensitivity. Our data demonstrate that oral but not intravenous glucose produces a fall in blood pressure in hypertensive but not in normotensive patients, probably because activation of the sympathetic nervous system is impaired in hypertensive subjects; moreover, hypertension in the elderly seems associated with a state of reduced sensitivity to insulin.

Effects of the angiotensin converting enzyme inhibitor enalapril compared with diuretic therapy in elderly hypertensive patients.

The aim of this study was to evaluate the usefulness of the angiotensin converting enzyme (ACE) inhibitor enalapril in a group of 30 patients (mean age 73.3 years) with moderate hypertension and normal haematological and chemical parameters (170 +/- 8.1 mmHg systolic and 104 +/- 5.8 mmHg diastolic blood pressure), who were receiving diuretic therapy with chlorthalidone (12.5 mg/day). This therapy caused a significant decrease in systolic and diastolic blood pressure (to 165 +/- 6.7 and 98 +/- 4.7 mmHg, respectively; P less than 0.001) but it also induced hypokalaemia (3.04 +/- 0.7 mmol/l; P less than 0.001) and multiple (greater than 10/h) and complex premature ventricular depolarizations (2nd, 3rd and 4th Lown grade). Enalapril treatment (5 mg/day for 5 days and 10 mg thereafter) was added to the diuretic therapy and after 2 months a further decrease in blood pressure was observed (to 158 +/- 5.6 mmHg systolic, P less than 0.001; 87.2 +/- 5.0 mmHg diastolic, P less than 0.001). Moreover, there was a significant reduction in the mean heart rate (from 79 to 72 beats/min, P less than 0.005) and an increase in serum potassium (to 4.19 +/- 0.2 mmol/l; P less than 0.001). In 80% of patients a 24-h dynamic electrocardiogram showed a significant reduction in both the number and complexity of premature ventricular depolarizations. Our findings suggest that ACE inhibitors can be useful in patients developing hypokalaemia during therapy. However, we are not yet able to explain the beneficial effects of enalapril in decreasing the frequency of premature ventricular depolarizations.

Reliability of echocardiography in the detection of metastatic malignant pericardial masses.

Pericardial metastasis is a rare localization of a malignant neoplasm. We report a 28-year-old man with metastatic spread of an epithelial thymoma into the pericardium. This in turn compressed the heart with induction of exertional dyspnea, hepatomegaly, chest pain and increased jugular venous pressure. All these features occurred in the absence of significant hemodynamic impairment. Echocardiography revealed an intrapericardial mass at the level of the left ventricular free wall. Surgical removal of this pericardial neoplasm produced a rapid improvement in clinical status. Ultrasonography, therefore, is a reliable noninvasive method for the diagnosis of cardiac impairment due to a pericardial metastatic mass.

Noninvasive evaluation of left-to-right shunts by pulsed Doppler echocardiography.

The systemic and pulmonary blood flows and the ratio of pulmonary to systemic flow were noninvasively evaluated by pulsed Doppler echocardiography in 25 children with left-to-right shunts. Fourteen patients had atrial septal defect and 11 had ventricular septal defect. In patients with atrial septal defect, right ventricular stroke volume was obtained from the recordings of mean velocity flow and the diameter at the level of pulmonary valve in short-axis view. The left ventricular stroke volume was evaluated from the suprasternal approach by positioning the sample volume within the ascending aorta just above the valvar leaflets. In children with ventricular septal defect, the pulmonary blood flow was determined at the level of the mitral orifice, whereas the systemic blood flow was estimated from the ascending aorta. The systemic and pulmonary blood flows and their ratio determined by pulsed Doppler echocardiography in the 25 patients examined, were compared using simple linear regression analysis with the results obtained by cardiac catheterization. The ratio of pulmonary-to-systemic flow showed an excellent correlation in patients with atrial septal defect (r = 0.82) and in those with ventricular septal defect (r = 0.79). Our study validates the accuracy of cross-sectional Doppler echocardiography, especially for minimizing some possibility of errors in the presence of left-to-right shunts by employing new approaches.

[Post-necrotic endoventricular thrombosis. Comparative evaluation of the diagnostic reliability of 2-dimensional echocardiography and cineventriculography]. / Le trombosi endoventricolari post-necrotiche. Valutazione comparativa dell'affidabilità diagnostica dell'ecocardiografia bidimensionale e della cineventricolografia.

The purpose of this study was to assess the relative diagnostic value of two-dimensional echocardiography (2D-Echo) and biplane left ventricular cineangiography (CV) for detecting the presence of left ventricular mural thrombi (LVT) in selected patients (pts) with left ventricular aneurysm (LVA). The Echocardiographic and Angiographic data of 19 pts selected from a group of 58 pts with coronary artery disease who underwent surgery for aorto-coronary bypass and/or aneurismectomy, were retrospectively examined. The presence of LVA was shown at surgery in all patients, located near the cardiac apex in 10 pts, at the level of the antero-septal wall of left ventricle in 7 pts and of the antero-lateral wall in 2 pts. In 11 of the 19 pts (57.9%) a LVT was identified at surgery. The thrombus was large (greater than 2 cmq) in 6 pts and small (greater than 2 cmq) in 5 pts. In 10 of the 11 pts with LVT 2D-Echo showed the thrombus prior surgery (sensitivity = 91.6%) whereas CV identified the thrombus only in 7 pts (sensitivity = 73.3%). No false positive diagnosis of LVT was made by the two techniques (specificity = 100%). Six large and 4 small thrombi (1 false negative) were identified by 2D-Echo; 6 large and 1 small thrombi (4 false negative) were identified by CV. In conclusion, 2D-Echo showed a significantly higher sensitivity for LVT than CV in patients with prior Acute Myocardial infarction, especially for small thrombi.