Quality of life in normotensives compared to hypertensive men treated with isradipine or methyldopa as monotherapy or in combination with captopril: the LOMIR-MCT-IL study.

Quality of life (QOL) measures were assessed in a multi-center, double-blind, case-controlled trial of 1 year's duration. A total of 368 hypertensive male patients were randomly assigned to monotherapies of either isradipine, methyldopa or placebo. If normotension was not achieved, captopril was added. QOL assessments in the hypertensives and in 155 normotensives included a self-structured scale to measure the subjective perception of QOL, the severity, desirability and controllability of recent critical life events, semantic memory, physical dysfunction, sleep disorders, sexual difficulties, depression and work-related stress. The overall withdrawal rate during the trial was 19%, mainly due to lack of efficacy and adverse experiences. At baseline, and at the end of the trial, the normotensives as compared to hypertensive patients, had significantly better scores in most QOL measures. Patients treated with the combination of isradipine and captopril reported more favorable changes in the subjective measure of QOL (P < 0.03) and in semantic memory (P < 0.001) than patients treated with any of the monotherapies or with methyldopa in combination with captopril. There were no statistically significant differences among treatments for changes of other indices of QOL. In most QOL measurements, normotensives rated better then hypertensives. Patients treated on long-term therapy with the combination of isradipine and captopril showed improvement in self-structured QOL measures and semantic memory, compared to patients treated either with methyldopa or placebo.

Complementary organ expression of IL-1 vs. IL-6 and CSF-1 activities in normal and LPS-injected mice.

The specific expression of pro-inflammatory cytokines may affect the functioning of organs in different ways. The results of specific cytokine bioassays used in this study show a distinct pattern of tissue expression of IL-1 IL-6 and CSF-1. Cytokine activity was assessed in conditioned media (CM) and lysates (LYS), obtained from different organs of control or lipopolysaccharides (LPS)-injected mice; LPS representing a potent inflammatory stimulus. Low constitutive levels of IL-1 could be demonstrated only in CM/LYS from organs with lymphoreticular function, such as the liver, spleen, intestine and lungs. On the other hand, IL-6 and CSF-1 were mainly detected in the CM (and not in lysates) of organs, such as the heart, kidneys, muscle and brain. LPS injection basically resulted in an accentuated form of the constitutive pattern. CSF-1 displays a similar pattern of expression to that of IL-6, best detected in CM after LPS stimulation. Thus, a mirror-image relationship emerges between the patterns of IL-1 and IL-6/CSF-1 expression in two groups of organs: those with lymphoreticular function, which manifest high IL-1 and low IL-6/CSF-1 activity, as compared to organs characterized by highly specialized and potentially vulnerable functions (such as the heart, brain, muscle and kidney), which exhibit high IL-6/CSF-1 and low IL-1 activity. Due to their defensive functions, lymphoreticular organs, which are in charge of the 'gates of entry' to the body, mount extensive IL-1-mediated inflammatory responses, even at the cost of possible tissue-damage. On the other hand, the more vulnerable internal organs mount IL-6/CSF-1-mediated responses which are milder and bear less potential for tissue damage. The distinct patterns of expression of pro-inflammatory cytokines in different organs, at steady state or under inflammatory conditions, may shed light on tissue characteristic homeostatic and defence mechanisms.

Long-term prognosis of low-risk, post-MI patients: the importance of subjective perception of disease.

In 1980, 87 male patients (age range 34-60 years), hospitalized after their first myocardial infarction (MI), were asked why they believed they got the infarct and what would help them cope with it. In a multiple regression analysis, their causal attributions accounted for 15% of the explained variance in their physical, sexual, social and work functioning after 6 and 18 months, their level of education accounted for 25% and the severity of their infarct for 10%. This result was replicated in a cross-cultural study. A follow-up study shows that 12 years after the MI, the patients' initial causal attributions still accounted for part of their rehabilitation and life expectancy. Of the original 87, 23 had died between 1980-1992 from cardiac causes and 50 male patients were located and re-interviewed at the Soroka ICCU, in 1992. This suggests a very low-risk post-MI sample. The only risk-factor, accounting for the difference between the surviving and the deceased patients, was the initial obesity of the latter. The functional capacity outcome of the survivors was accounted for by their age (24%) and initial causal attributions (26%). Also the initial causal attributions (5%) still accounted for the subjective perception of functioning among the survivors. These results suggest that the initial causal attributions may have created positive or negative self-fulfilling prophecies which had long-term consequences, especially in a low-risk, post-MI population, in which risk factors hardly effected long-term prognosis.

Does the combination of ACE inhibitor and calcium antagonist control hypertension and improve quality of life? The LOMIR-MCT-IL study experience.

The LOMIR-MCT-IL study was designed to investigate the effects of different antihypertensive drugs on the quality of life (QoL) of men with mild-to-moderate hypertension. This report focuses on the subgroup of patients treated with the combination of the angiotensin converting enzyme (ACE) inhibitor captopril and the calcium antagonist isradipine. The LOMIR-MCT-IL was a double-blind multicenter, placebo-controlled, one-year follow-up study in which 368 hypertensive men, aged 40-65 years, were randomly allocated to receive either isradipine, methyldopa or placebo at three titration levels. If diastolic blood pressure (DBP) remained > 90 mmHg, captopril was added openly. The QoL evaluation introduced a qualitative self-structured subjective measure in addition to prestructured quantitative measures. The quality of life was assessed at baseline, after 6 months and at the end of the study. Methyldopa normalized DBP in 50% of patients when given as monotherapy and an additional 34% with the addition of captopril (84% total). With placebo, 36% normalized DBP and another 39% on addition of captopril (75% total) and, with isradipine, 64% normalized DBP and an additional 26% with added captopril (90% total). Assessment of QoL showed that both the placebo and the isradipine+captopril groups showed significant improvement in semantic memory after antihypertensive treatment. The isradipine+captopril group showed a clear tendency towards lower depression scores, better quality of sleep, better subjective evaluation of QoL and a more positive evaluation of personal life events in comparison to the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of the electrocardiogram in hypertensive patients: the LOMIR-MCT-IL study experience.

Electrocardiograms (ECGs) of hypertensive men enrolled into the LOMIR-MCT-IL study were evaluated at entry and after 1 year of follow-up. The sensitivity of a modified version of the Minnesota Code (MC) to detect ECG abnormalities was compared with the diagnosis of the treating physician. Changes in the ECG were related to blood pressure and heart rate. A total of 368 patients with mild-to-moderate hypertension were included in a double-blind multicentre study to evaluate the quality of life with different treatments (isradipine, methyldopa or placebo). ECGs of 335 patients at entry and 232 patients who completed the study were available for evaluation by the treating physician, and a central cardiology unit using the modified MC. The most frequent abnormality recognized by the MC was an abnormal P wave (n = 77, 23%). Abnormal repolarization (10%), increased voltage of the QRS (5.4%) and abnormal intraventricular conduction (10%) were the other most frequent abnormalities. No correlation was detected between the abnormal P wave and other ECG abnormalities. Patients with an abnormal P wave showed significantly higher systolic blood pressure (SBP) (p < 0.001) and heart rate (p < 0.05). At the end of follow-up, abnormal P waves were still present in 58 (25%) of the patients. In 21 patients, the abnormal P wave did not change from entry and, in 37, the abnormality developed in spite of a normalized blood pressure. In 56 patients, the abnormal P wave was no longer present. Correlation between diagnosis by the MC and the physician was poor.(ABSTRACT TRUNCATED AT 250 WORDS)

A multicenter, double-blind, randomized, placebo-controlled study of isradipine and methyldopa as monotherapy or in combination with captopril in the treatment of hypertension. The LOMIR-MCT-IH Research Group.

This multicenter, double-blind, randomized trial of 1 year's duration compared the safety and efficacy of isradipine, methyldopa, and placebo in 368 men, aged 40 to 65 years, with mild-to-moderate essential hypertension. Initial treatment with isradipine (1.25 mg twice daily), methyldopa (250 mg twice daily), or placebo was started after a wash-out and single-blind placebo period. If normotension [diastolic blood pressure (DBP) < 95 mm Hg] was not achieved, doses were doubled. If the maximum dose as monotherapy did not result in normotension, captopril (25 mg or, if necessary, 50 mg, once daily) was added to the treatments of the three patient groups. Despite the marked placebo effect during the first 2 weeks of treatment, monotherapy with isradipine resulted in a higher rate of normalization (more than 64%) compared with 50% in the methyldopa group and 36% in the placebo group. Adding captopril to the treatments of non-responders increased the rate of normalization to 90% in the isradipine group, 84% in the methyldopa group, and 75% in the placebo group. Twenty-one patients dropped-out and 70 patients discontinued the study, the majority because of a lack of efficacy and adverse reactions. The most common adverse reactions reported were cardiovascular and gastrointestinal complaints, headaches, and sleep and sexual disorders, mostly by patients taking methyldopa. Isradipine was well tolerated and the side-effects were minimal. These results indicate that isradipine is superior to methyldopa and, whether as monotherapy or in combination with captopril, highly effective and well tolerated in the treatment of mild-to-moderate hypertension.

The use of transdermal clonidine in the hypertensive patient with chronic renal failure.

The efficacy of transdermally administered clonidine was evaluated in twenty-four patients with mild-to-moderate hypertension (seated diastolic blood pressure 95-115 mmHg) and renal impairment. Patients were initially treated with oral clonidine; the dose was titrated until the seated diastolic pressure fell below 90 mmHg or a minimum 10% reduction in baseline was achieved. Oral clonidine produced a significant decrease in both systolic and diastolic blood pressure; mean seated diastolic blood pressure decreased 16.9 mmHg from baseline. When transdermal clonidine was substituted for twice daily dosage of oral clonidine, blood pressure decreases were fully maintained. Sixteen patients completed three months of stable-dose transdermal therapy. The results suggest that, in mild-to-moderate hypertensive patients with chronic renal impairment, blood pressure can be controlled with a once-weekly application of transdermal clonidine as effectively as with oral clonidine. Mean diastolic blood pressure was decreased approximately 17% during clonidine therapy independent of the severity of renal dysfunction or route of clonidine administration.

Shift from left to right axis deviation during ischemia.

A case report of a patient with persistent left anterior hemiblock admitted with acute ischemic heart disease is described. At effort during follow-up evaluation, the patient complained of retrosternal pain when the heart rate was 124 beats/min. No pathological ST-T changes were demonstrated at this time. At 133 beats/min, the precordial pain increased, the QRS axis displayed a marked shift to the right, and ischemic ST-T depression was recorded. In discussing this unreported phenomenon, it is pointed out that left anterior hemiblock does not necessarily represent an anatomical block of the atrioventricular bundle but may simply reflect a relative delay in conduction. In addition, acute ischemia may change the physiological behavior of the system resulting in slower conduction through the posterior rather than through the anterior atrioventricular bundle. The influence of left anterior and left posterior hemiblock on ischemic ST-T changes and on the coronary flow distribution is discussed.

Effects of mental and physical stress on plasma catecholamine levels before and after beta-adrenoceptor blocker treatment.

In a study in mild hypertensives, the impact of mental and physical stress on plasma epinephrine (E), norepinephrine (NE), and on their ratio (NE/E) was evaluated. The effect of two beta-adrenoceptor blocking drugs, atenolol and bopindolol, on plasma catecholamine levels was also examined. Each stressful stimulus significantly increased the NE and E levels compared to rest. The increase was progressive from mental stress, through the handgrip test to the treadmill test. A slight decrease in the NE/E ratio was observed following mental stress and the handgrip test, while this ratio increased during the treadmill test. No significant impact of beta blocking treatment on catecholamine levels was observed under any test condition.

Cardiovascular diseases, blood rheology, and dihydropyridine calcium antagonists.

Over the last 10 years, accumulating evidence has confirmed the ability of dihydropyridine calcium antagonists to improve red blood cell deformability. In this review of the literature, particular attention is paid to results obtained with isradipine, a second-generation derivative of the 1,4-dihydropyridine family. Isradipine appears to be more selective in various pharmacological properties, well tolerated, easy to administer, and effective in controlling blood pressure and reducing the frequency of ischemic events. While manifesting these desirable attributes, isradipine retains an unimpaired ability to improve red blood cell deformability. It is suggested that the therapeutic efficacy of dihydropyridine calcium antagonists is attributable, at least in part, to their ability to affect blood rheology by improving red blood cell deformability.

Response to mental and physical stress before and during adrenoreceptor blocker and angiotensin-converting enzyme inhibitor treatment in essential hypertension.

The effects of mental, static and dynamic stresses on physiologic parameters before and after beta-blocker (n = 24) and angiotensin-converting enzyme inhibitor (n = 29) treatment were examined. Mental stress induced similar elevation in systolic and diastolic blood pressures (BPs) with and without beta-blocker treatment. During angiotensin-converting enzyme inhibitor treatment, the change in systolic BP was significantly greater (p less than 0.05). Heart rate response was attenuated by beta blockers and unchanged by the angiotensin-converting enzyme inhibitor. Skin temperature and galvanic skin resistance significantly decreased (p less than 0.05) with mental stress. Beta blockers did not change the response pattern, whereas the angiotensin-converting enzyme inhibitor attenuated the stress-induced reduction of both skin temperature and galvanic skin response. After handgrip exercise, increases in systolic and diastolic BPs and heart rate were similar before and after beta-blocker treatment, whereas the angiotensin-converting enzyme inhibitor induced small but significantly fewer (p less than 0.05) changes in diastolic BP and heart rate. Treadmill exercise induced similar changes in systolic and diastolic BPs with both treatments compared with no treatment. The angiotensin-converting enzyme inhibitor appears to provide additional protection to that seen with beta blockers during mental and static stressors by blunted changes in skin temperature and galvanic skin resistance.

The relationship between causal attribution and rehabilitation in patients after their first myocardial infarction. A cross cultural study.

Full rehabilitation of a patient following myocardial infarction (MI) involves resumption of work and the restoration of quality of life. Two groups of patients (87 Israeli and 98 Swedish) were admitted to the CCU and followed up after their first MI. To evaluate the patients' own perception of events ('causal attribution theory'), sequential interviews were scheduled. Physical risk factors correlated poorly with rehabilitation outcome at 6 months. However, two patient clusters were pinpointed according to the patients' subjective explanation of the factors contributing to their MI. These 'causal attribution scores' had a predictive value, independent of culture, age, education, disease severity and depression. It is therefore concluded that evaluation of patient perception may assist in planning intervention for high risk psychologically debilitated patients, and thus favourably enhance their rehabilitation outcome.

Effect of isradipine on factors affecting blood viscosity.

The objective of the study was to investigate the effect of isradipine on red blood cell filtrability in 20 men with mild-to-moderate hypertension. In this prospective, double-blind study, parallel groups of hypertensive male patients were randomized to receive either isradipine (n = 11) or placebo (n = 9). An additional group of nine normotensive age-matched volunteers served as controls. Tests were performed before and after patients were treated with either isradipine or placebo. The hypertensive patients differed from the normotensive controls in having a higher level of fibrinogen (P less than .04), a higher hematocrit (P less than .001), a higher filtration rate (P less than .05; impaired red blood cell deformability), and a higher mean corpuscular volume (MCV; P less than .005). Treatment with isradipine lowered blood pressure and improved red blood cell filterability (P less than .05) compared with placebo.

Energy expenditure in normal labor.

The energy expenditure in 23 healthy parturient women during spontaneous labor was assessed by continuous measurement of their O2 consumption and CO2 production. Due to the intermittent character of uterine contractions, normal labor and delivery did not impose high energy demands on the parturient, whereas a prolonged labor and delivery in which energy input was high led to maternal metabolic disturbances.

Isotonic and isometric responses of blood pressure and heart rate in mild to moderate hypertension with isradipine and propranolol.

The objectives of this study were (a) to evaluate the dose-response effect of isradipine, a dihydropyridine calcium antagonist, on the heart rate and blood pressure of males with mild to moderate hypertension; and (b) to compare these results with those obtained with propranolol, a beta-adrenoceptor blocker, on a matched patient population. Twenty-four patients entered a single-blind study, beginning with a 2-week washout placebo period followed by a forced-titration period. Treadmill and hand-grip tests were also performed. Two weeks were allocated to each stage of the therapy. The end point of the study was normalization of blood pressure with a minimum of side effects. Results and conclusions include the following: both drugs were effective in reducing systolic blood pressure (SBP) and diastolic blood pressure (DBP), but isradipine was more effective in reducing the DBP; isometric exercise can predict accurately the results of the isotonic exercise; the maximum therapeutic effect of propranolol was achieved during the second study-dose level; increases in the isradipine dose were reflected in a proportional reduction of SBP and DBP; and the incidence of side effects is lower among isradipine-treated patients compared to propranolol-treated patients.

Study of the factors affecting blood viscosity in patients with thromboangiitis obliterans. A preliminary report.

Hematocrit values, plasma fibrinogen levels, and erythrocyte deformability are well-recognized factors affecting blood viscosity. We studied the incidence of abnormalities in these factors among 17 patients suffering from thromboangiitis obliterans (Buerger's disease) compared with 14 normal age- and sex-matched control subjects. Hematocrit values and fibrinogen levels were higher, whereas the erythrocyte filterability index was lower among the patients with Buerger's disease (p less than 0.001). Incubation of washed erythrocytes from these patients with control plasma of blood type AB produced an improvement of the filterability index (p less than 0.005). Our findings suggest that patients suffering from Buerger's disease show, in addition to the well-recognized arterial lesions, an abnormality in the factors affecting blood viscosity. This may contribute to a worsening of the clinical manifestations. Evidence is presented suggesting that a plasmatic factor may be responsible for the impaired erythrocyte filterability.