The changes in plasma arginine-vasopressin in patients with essential hypertension and the correlation with patient's condition

The levels of plasma arginine-vasopressin (AVP) in 80 patients with essential hypertension were measured, and its impact on the disease and its clinical significance were studied. The results showed that: (1) The levels of plasma AVP in patients with essential hypertension were significantly higher than that in normotensive subjects (P < 0.001). It dropped to normal level after antihypertensive drugs. (2) The concentrations of plasma AVP in both hypertensive subjects and normotensive subjects were not correlated with age and sex (P < 0.05). (3) The concentration of plasma AVP in patients with essential hypertension was the highest in stage III, the lowest in stage I, and middle in stage II. (4) The levels of plasma AVP in patients with malignant hypertension were significantly higher than that in patients with benign hypertension (P < 0.05). A positive correlation was found between the levels of plasma AVP and blood pressure (r = 0.3398, P < 0.01). (5) The concentrations of plasma AVP in hypertensive subjects with ventricular hypertrophy were higher than that in hypertensive subjects with out ventricular hypertrophy (P < 0.05). (6) The concentrations of plasma AVP in hypertensive subjects with heart failure were significantly higher than that in hypertensive subjects with out heart failure (P < 0.001). The results suggest that AVP has a role in the pathogenesis of hypertension, hypertension complicated with ventricular hypertrophy and hypertension complicated with heart failure. The levels of plasma AVP may be viewed as an index of the patient's condition in hypertensive subjects.     

Modern trends in the treatment of hypertension

The main problem of treatment of hypertension in this country as well as abroad is the fact that only less than one quarter of hypertensive patients are treated effectively and have thus normal blood pressure readings. More effective treatment of hypertension is thus one of the main tasks of health care systems in different countries. The objective of treatment of hypertension is to achieve a normal blood pressure. Evidence has been provided that diuretics and beta-blockers markedly reduce cerebrovascular and cardiovascular mortality, in particular in the elderly. ACE inhibitors are the drugs of choice in patients with heart failure or asymptomatic left ventricular dysfunction and in patients with diabetic nephropathy. Unsuitable for treatment of hypertension are short acting calcium channel blockers, in particular nifedipine. On the other hand, long-acting calcium channel blockers reduce the cerebrovascular mortality in elderly hypertensive patients. A number of questions still remain the subject of research: a) should diastolic pressure be reduced to values lower than 90 mm Hg; so far it is necessary only in hypertensive subjects with diabetes mellitus and in juvenile hypertensives; b) is the influence of new groups of antihypertensive drugs, in particular calcium channel blockers, similar, better or worse than that of diuretics and beta-blockers in the prevention of cardiovascular and cerebrovascular morbidity and mortality?; c) is it wise to recommend acetylsalicylic acid also to hypertensive patients without clinical signs of IHD or atherosclerotic affection of other vessels?; d) what is the value of combined antihypertensive and hypolipidaemic pharmacological treatment? Will this combination be not much more valuable in the prevention of IHD?; e) is the prognosis of hypertensive subjects with left ventricular hypertrophy better when ACE inhibitors are used as compared with other antihypertensive drugs?; f) do ACE inhibitors influence the prognosis of diabetic patients more favourably than beta-blockers?     

Fixed combination verapamil SR/trandolapril

Urapidil is a peripheral postsynaptic alpha 1-adrenoceptor antagonist with central agonistic action at serotonin 5-HT1A receptors. It reduces blood pressure by decreasing peripheral vascular resistance. Oral urapidil decreases blood pressure in patients with mild to moderate essential hypertension and associated risk factors such as hyperlipidaemia or type 2 (non-insulin-dependent) diabetes mellitus with no effect on heart rate. The antihypertensive efficacy of urapidil is similar to that of most comparators in patients with mild to moderate essential or secondary hypertension and no concomitant risk factors. However, the antihypertensive efficacy of urapidil was lower than that of hydrochlorothiazide in a well designed trial. Lipid levels and glucose metabolism are not adversely affected and may improve with urapidil in patients with lipid or glucose abnormalities. Urapidil can be safely combined with other antihypertensive agents such as hydrochlorothiazide and nifedipine and improves blood pressure control in previous nonresponders to monotherapy. Intravenous urapidil reduces blood pressure in patients with pre-eclampsia or hypertension in pregnancy and in patients with hypertensive crises or peri- or postoperative hypertension. The decrease in blood pressure is similar to that observed after nifedipine, enalaprilat, sodium nitroprusside and dihydralazine, greater than that of ketanserin according to 1 larger study, and greater than that of sublingual nitroglycerin in 1 trial in patients with nonsurgical hypertensive crises and pulmonary oedema. However, more patients responded to treatment with urapidil than with enalaprilat or nifedipine. Heart rate is less likely to be altered by urapidil than with some comparator drugs. Urapidil appears to be well tolerated, with most adverse events being mild and transient. The incidence of adverse events with urapidil is similar to that with prazosin, metoprolol, atenolol, sodium nitroprusside and hydrochlorothiazide and less than that with nifedipine and clonidine. Urapidil may not be as well tolerated as captopril and, in 1 study, more urapidil than nitrendipine recipients discontinued treatment because of adverse events. Conclusions: urapidil reduces blood pressure without altering heart rate. The oral formulation is an effective choice in patients with hypertension and concomitant dyslipidaemia or type 2 diabetes mellitus, in whom the drug does not adversely affect and may improve lipid profiles and glucose metabolism. The intravenous formulation is effective in controlling various hypertensive crises and hypertension associated with pregnancy or surgery and is similar to or better than other first-line agents used in these conditions. Thus, urapidil may be a useful alternative to currently available antihypertensive agents.     

Sex differences in the pharmacological treatment of hypertension: a review of population-based studies

OBJECTIVE: To summarize all available literature on sex differences in the pharmacological treatment of hypertension with respect to the percentage of hypertensive patients treated pharmacologically and the selection of antihypertensive drugs. The influences of the calendar period, age, definition of hypertension, prevalence of hypertension and country on these sex differences were examined. DATA IDENTIFICATION: A secondary analysis of data from 46 population-based studies in 22 countries on the prevalence of pharmacologically treated hypertension was conducted to estimate sex ratios for the prevalence of drug treatment for hypertension. RESULT: Overall, women with hypertension were 1.33-fold [95% confidence interval (CI) 1.32-1.34] more likely to be treated pharmacologically for hypertension than were hypertensive men. With increasing age, the female: male ratio for pharmacological treatment of hypertension decreased from 2.26 (95% CI 1.56-3.27) at ages 20-29 years to 1.22 (95% CI 1.11-1.34) at ages 60-69 years. In all countries more women than men were treated for hypertension, with the biggest difference observed in the USSR (1983-1986), where about twice as many women as men were treated for hypertension. Women more frequently used diuretics, whereas men more often used beta-blockers, angiotensin converting enzyme inhibitors and calcium antagonists. CONCLUSIONS: Hypertensive women are more often treated for hypertension than hypertensive men and their pattern of use of antihypertensive drugs differs from that of men. Further research is required in order to explain sex differences in the treatment of hypertension with respect to the prevalence of pharmacological treatment of hypertension and choice of antihypertensive drugs, and to investigate the consequences of this difference for long-term outcomes.     

Comparative antihypertensive effectiveness of once-daily mibefradil and diltiazem CD. Mibefradil Hypertension Study Group

This multicenter, double-masked, randomized, forced-titration, parallel-group trial was designed to determine whether we could confirm the results of a previous trial that demonstrated a significantly greater antihypertensive effect for mibefradil compared with diltiazem CD. Two hundred thirty-nine patients with uncomplicated mild-to-moderate essential hypertension and a baseline sitting diastolic blood pressure (SDBP) between 95 and 114 mm Hg were randomized to receive once-daily treatment with mibefradil 50 mg (n = 119) or diltiazem CD 180 mg (n = 120). After 4 weeks of treatment, all patients underwent forced titration to mibefradil 100 mg or diltiazem CD 360 mg for an additional 8 weeks. After 12 weeks of active treatment, the mean reduction from baseline in trough SDBP was significantly greater with mibefradil than with diltiazem CD (-14.3 +/- 6.6 mm Hg vs -11.7 +/- 7.4 mm Hg, respectively). In addition, significantly more patients receiving mibefradil had a decrease in SDBP > or = 10 mm Hg or a decrease to < or = 90 mm Hg by week 12 than did patients receiving diltiazem CD (82% vs 72%, respectively). The tolerability of mibefradil and diltiazem CD were comparable, with similar percentages of patients in both groups reporting at least one adverse event (21% vs 22%, respectively) that was considered to be at least remotely related to the study drug. The results of this study confirm those of the previous trial. Once-daily treatment with mibefradil 100 mg is significantly more effective than diltiazem CD 360 mg in lowering both diastolic and systolic blood pressure. Both drugs are well tolerated.     

Screening for renovascular hypertension in a population with relatively low prevalence

OBJECTIVE: To evaluate the accuracy and cost-efficacy of the diagnostic procedure and treatment for renovascular hypertension. SETTING AND PATIENTS: A total of 519 patients referred to the university clinic for hypertension were screened for renovascular hypertension with 405 captopril challenge tests (CCT) and 450 captopril renographies (CRG). INTERVENTIONS: Abdominal angiography was performed on 84 patients for positive screening. Fifteen patients underwent angiography for a sole suspicious clinical presentation. The angiography revealed 17 renal artery stenoses and five occlusions in 20 patients. Fifteen technically successful angioplasties and three nephrectomies were performed. RESULTS: In the patients who underwent angiography, CCT had a specificity of 39% and a sensitivity of 67% for renovascular hypertension. CRG had a sensitivity of 100% and a specificity of 68%. In the whole study population, the estimated specificity of CCT was 88% and that of CRG 95%. Invasive treatment reduced systolic/diastolic blood pressure from 157/99 to 140/87 mmHg and the number of antihypertensive drugs used from 2.6 to 1.4 in 16 patients (mean age 49 years). Angiotensin converting enzyme (ACE) inhibition was effective in four elderly patients. Cost-efficacy analysis Screening with CRG and invasive treatment cost US$15400 per successful invasive treatment Equally effective pharmacological treatment would have cost US$10400. Limiting the screening with CRG to the 173 patients with no obvious renal parenchymal disease and with hypertension at a younger age (< or =30 years) or unresponsive to two antihypertensive drugs (diastolic blood pressure > 90 mmHg) would have yielded a prevalence of 12% and missed only one elderly patient who responded to ACE inhibition. The limited screening, along with invasive treatment, would have cost US$7300 per patient CONCLUSIONS: CRG is superior to CCT for screening of renovascular hypertension. Screening with CRG is cost-effective when limited to patients with no obvious renal parenchymal disease and with hypertension that does not respond to two antihypertensive drugs or is detected in patients no older than 30 years.     

Hypertension in diseases of the kidney. Pathogenesis and therapy

Renal disease is the cause of hypertension in about 5% of all hypertonics. Patients with renal hypertension are threatened by cardiovascular complications of hypertension even more frequently than patients with essential hypertension. Hypertension is moreover an important factor in the progression of renal insufficiency. In the pathogenesis of renal hypertension an important role is played by sodium and fluid retention and activation of the renin-angiotensin system. Progression of rental insufficiency can be retarded only by more strict control of hypertension than in patients with normal renal function. Optimal treatment is administration of angiotensin converting enzyme inhibitor which moreover in the majority of patients retards the progression of renal insufficiency more markedly than other antihypertensive drugs.     

Compliance with antihypertensive treatment in consultation rooms for hypertensive patients

Compliance with antihypertensive therapy was examined by a questionnaire in 124 essential hypertension patients in an outpatient hypertension clinic. It was found that antihypertensive drugs were used regularly by only 62% of patients, with forgetting and feeling of well-being without therapy the principal reasons given for irregular drug taking. Treatment of hypertension is reported to have a deleterious effect on physical and mental activity, routine activities, sexual activity, memory, athletics and family life in only 2% of patients. Patients who were aware that increased BP reduces life span used the prescribed drugs more regularly and came regularly for checkups compared with patients lacking the relevant information. Patients over 60 years of age and smokers exhibited the worst compliance. No significant differences were found for sex or duration of treatment. With regard to nonpharmacological measures, most patients were willing to begin a programme of regular physical exercise, reduce weight, learn relaxation techniques and reduce alcohol intake: smokers, however were unable to stop the habit.     

Hemorheologic effects of vasodilation in essential hypertension

Arterial hypertension is often associated with plasma volume contraction and hemoconcentration, which negatively affect the vascular flow resistance and microcirculation. Since some antihypertensive drugs can affect blood rheology, the purpose of this study was to evaluate whether acute and long-term arterial vasodilation with cadralazine influences rheologic parameters in essential hypertension. Twelve patients with unsatisfactorily controlled essential hypertension were studied. In the acute double-blind phase of the study the patients were allocated to treatment with either cadralazine or placebo. Intraarterial blood pressure, cardiac output (dye dilution), and blood rheology (viscosity, hematocrit) were registered before and after the first dose of cadralazine. Then 9 patients (3 dropouts) were treated with cadralazine and placebo during two four-week crossover periods and continued with cadralazine medication during the eight-week open phase of the study. Blood pressure and blood hemoglobin were followed during long-term treatment. A single oral dose of cadralazine caused vasodilation (total peripheral resistance index decreased from 45 to 33 U x m2, P < 0.05), which was accompanied by hemodilution (hematocrit declined from 46.9% to 42.5%, P < 0.05) and a blood viscosity reduction of more than 10%. Viscosity of 45% suspension of erythrocytes in plasma was also reduced, suggesting a possible modification of the microrheologic factors. The changes in total peripheral resistance correlated negatively with the changes in hematocrit. An antihypertensive effect of cadralazine was still observed during the chronic phase of the study, which was not accompanied by hemodilution. It is concluded that arterial vasodilation with cadralazine reduces flow resistance in the circulatory system in hypertension and has acute rheologic effects that disappear during chronic medication.     

Influence of risk factors and pharmacological treatment on mortality in patients with essential hypertension

BACKGROUND: The V JNC consensus stated that although new antihypertensive agents, such as angiotensin converting enzyme inhibitors and calcium channel blockers, are considered safer drugs, there is no firm evidence from large controlled trials that these drugs are associated with a lower cardiovascular mortality. AIM: To study the association between cardiovascular risk factors, blood pressure levels, pharmacological treatment and mortality in a group of hypertensive patients followed at an hypertension outpatient clinic. PATIENTS AND METHODS: Patients with essential hypertension were treated with different antihypertensive medications, according to physicians criteria, and controlled until death or loss from follow up. Causes of death were obtained from hospital records and death certificates. Survival was analyzed using life tables, comparisons between groups of patients were done using chi square or a Cox's proportional hazards model. RESULTS: Three hundred thirty-nine hypertensive patients aged 33 to 80 years old were followed for a mean period of 9.8 +/- 4.9 years. Eighty-six were treated with beta blockers, 64 with diuretics, 133 with calcium antagonists and 56 with ACE inhibitors. Blood pressure dropped similarly with all medications. During follow up, 79 patients died. Life table analysis showed that patients with a history of angina, diabetes or myocardial infarction had higher mortality rates. Similarly, patients treated with beta blockers and diuretics had higher mortality than patients treated with calcium antagonists or angiotensin converting enzyme inhibitors. The proportional hazards model showed that the effect of treatment modality persisted after correction for the other risk factors for mortality. CONCLUSIONS: In this series of hypertensive patients, those treated with beta blockers or diuretics had higher mortality rates than those receiving calcium channel antagonists or angiotensin converting enzyme inhibitors.     

Outcome of hypertension management in Asian Americans

BACKGROUND: Ethnic and/or racial differences in drug response to antihypertensive agents have been recognized, yet the prescribing practices and the information on efficacy of various agents rely mainly on the response of whites to drugs. OBJECTIVES: To assess the management of hypertension in Asian Americans and to compare it with an age- and sex-matched group of white patients with hypertension. METHODS: The patients' medical records were used as the primary source of information for the data collection. The observational period was a 12-month window and included 200 patients of Asian origin with hypertension and 196 white patients with hypertension whose medical records were randomly selected. RESULTS: The study describes the pattern of use of antihypertensive agents and the differences in response to antihypertensive agents between Asian Americans and whites. The preferred antihypertensive agents in both Asian and white patients included monotherapy with either calcium channel blockers or angiotensin-converting enzyme inhibitors. However, medication changes, dose reduction, and the experience of side effects were all significantly more frequently recorded in Asian patients than in white patients (P < .001, P < .008, and P < .002, respectively). CONCLUSIONS: These findings are supportive of some previous reports on ethnic differences in drug response to antihypertensive agents. The findings also point to the need for further prospective studies on the outcome of hypertension management in Asian American patients.     

Comparison of isradipine and enalapril effects on regional carotid circulation in patients with hypertension with unilateral internal carotid artery stenosis

This randomized, double-blind, placebo-controlled study was aimed at detecting cerebrovascular effects of isradipine and enalapril in patients with moderate hypertension depending on the presence and grade on unilateral stenosis of internal carotid artery (ICA). We evaluated carotid vascular resistance by using Doppler analysis and regional cerebral blood flow (rCBF) by using 133Xe-clearance technique before and after a single 5-mg oral dose of isradipine, enalapril, or placebo. Their effects were randomly and consecutively tested in 73 patients with essential hypertension subdivided into three groups: without carotid occlusive lesions, with moderate (50-75%), and with severe (76-99%) unilateral asymptomatic ICA stenosis. There were no differences in age, gender, and antihypertensive effects of the drugs between these three subgroups. Three major variants of cerebrovascular drug effects were observed: absence of changes (variant I), decrease in carotid vascular resistance with increase in rCBF and elimination of side-to-side asymmetry (variant II), and increase in carotid vascular resistance with further reduction of rCBF ipsilaterally ICA stenosis, and increased side-to-side asymmetry (variant III). Frequency of variant III was significantly higher in patients with severe ICA stenosis. Enalapril produced variant I of cerebrovascular effects in most patients examined; variant III was observed only in 13% of patients with severe ICA stenosis. Isradipine produced variant I of cerebrovascular effects much less frequently than did enalapril. For this drug, variant II was most typical in patients without ICA stenosis and with moderate ICA stenosis. In 43.5% of patients with severe ICA stenosis, however, isradipine produced reduction of cerebral perfusion. Presumably the presence of ICA stenosis, especially >75%, increases the risk of cerebrovascular disorders in antihypertensive therapy. In patients with severe ICA stenosis, treatment with enalapril appears to be safer than that with isradipine.     

Effect of antihypertensive treatment on urinary albumin excretion, glomerular filtration rate, and renal plasma flow in patients with essential hypertension

In 20 patients with essential hypertension the urinary albumin execretion, glomerular filtration rate (GFR),and renal plasma flow (RPF) were examined before and after antihypertensive treatment. Albumin excretion measured by radioimmunoassay was increased before treatment, and there was a significant fall during treatment. In patients responding well to therapy (diastolic pressure below 100 mm Hg), albumin excretion was significantly lower than in patients responding poorly to therapy. There was a positive correlation between albumin excretion before treatment and diastolic pressure during treatment, indicating that the albumin excretion rate may be used to predict the result of antihypertensive treatment. Patients with excretion rates below 25 mug/min generally respond well to the treatment used. No definite changes in GFR and RPF were found during treatment, and there was no correlation between albumin excretion and GFR and RPF. It is suggested that the increased albumin excretion in essential hypertension is due both to functional and morphological alterations in the glomerulus, namely increased glomerular filtration pressure and vascular damage.     

Biotransformation of 2,4,6-trinitrotoluene (TNT) by a Methanococcus sp. (strain B) isolated from a lake sediment

The newly developed antihypertensive drugs, the long-acting beta-blocker propranolol and the sustained release calcium antagonist verapamil, are compared in their antihypertensive, platelet function, rheological properties and metabolic effects. The trial was a double-blind, randomised, placebo-controlled cross-over study. Thirty patients with mild to moderate hypertension received propranolol (40-120 mg) or verapamil (80-200 mg) once daily in two separate ten week courses. After ten weeks treatment both drugs had significantly reduced both SBP and DBP. Beta-thromboglobulin (beta-TG) concentration, reflecting the status of platelet activation in vivo, was significantly decreased after propranolol (129.6 +/- 13.5 vs. 77.9 +/- 8.6 ng/ml) and verapamil (129.6 +/- 13.5 vs. 90.7 +/- 10.1 ng/ml) treatments while platelet aggregation induced by ADP, collagen, arachidonic acid or adrenaline and the production of thromboxane B2 (TXB2), 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) and platelet cyclic 3'-5' adenosine monophosphate (C-AMP) concentration were not affected. Significant alterations in rheological parameters such as plasma and whole blood viscosity, fibrinogen level and red cell deformability were not found. Higher cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels were observed after propranolol treatment but not in verapamil treatment. Side-effects were mild, tolerated and no patient had to be withdrawn from the study. In conclusion, propranolol and verapamil are generally effective antihypertensive as well as rheologically safe drugs. Compared with the metabolic effect on serum lipid, verapamil may be a better choice. Both drugs possess the tendency to inhibit platelet properties which is desirable in hypertension treatment.     

Response of hypertension to conventional antihypertensive treatment and/or steroidogenesis inhibitors in Cushing's syndrome

OBJECTIVES: To evaluate the effect of conventional antihypertensive drugs and/or inhibitors of steroid production in the management of hypertension in Cushing's syndrome. DESIGN: A retrospective open clinical study with pre- and post-treatment assessment. SETTING: A university hospital, where patients were initially admitted and then followed-up in an ambulatory clinic over a period of 6 years. SUBJECTS: Forty consecutive hypertensive patients with Cushing's syndrome. INTERVENTIONS: Patients were divided into two groups according to the different management of hypertension. The first group (group 1) of 28 patients included those treated with antihypertensive drugs at full dose (diuretics, calcium antagonists, angiotensin converting enzyme [ACE] inhibitors, as single agents or in combination). The second group (group 2) of 12 patients received ketoconazole alone. MAIN OUTCOME MEASURES: Blood pressure variations compared to pre-treatment levels. RESULTS: Blood pressure normalization was obtained in four of the 28 patients of group 1. In 12 of the remaining patients, ketoconazole, an inhibitor of steroid production, was subsequently added and this normalized blood pressure in all but the one in whom cortisol was not decreased. In the 12 patients of group 2, ketoconazole alone lowered blood pressure within normal limits in all but one who had long-standing hypertension. CONCLUSIONS: In hypertensive patients with Cushing's syndrome, conventional antihypertensive therapy is mostly ineffective. Blood pressure response is satisfactory only after the restoration of normal cortisol levels, indicating the need for a specific treatment for hypertension in this disorder.     

Glucose and lipid metabolism during long-term antihypertensive treatment with indapamide in non-insulin-dependent diabetic patients

Thirty-nine patients with diabetes and hypertension were treated with indapamide for 24 weeks to study the effects of that drug on glucose and lipid metabolism. The drug was administered at a dose of 2 mg once per day in the morning as a single drug (26 patients) or in combination with other antihypertensive drugs (13 patients), including calcium antagonists, angiotensin-converting enzyme inhibitors, an alpha-blocker, or a beta-blocker. Blood pressure was reduced in both groups during treatment, and no alteration of glycemic control or lipid metabolism was observed. One patient complained of a mild headache, but treatment was continued. The results indicate that indapamide is useful for the long-term treatment of hypertension in diabetic patients, either alone or in combination with other antihypertensive agents.     

Apoptosis of lymphocytes induced by glucocorticoids and relationship to therapeutic efficacy in patients with systemic lupus erythematosus

OBJECTIVE: Glucocorticoids (GCs) are the drugs of first choice for treatment of systemic lupus erythematosus (SLE). However, the disease in some patients is resistant to these agents. This study evaluated the possibility of a relationship between response to GC treatment and the rate of apoptosis in vitro, and also analyzed Bcl-2 and Fas expression on peripheral blood mononuclear cells (PBMC) from patients with SLE in relation to GC-induced apoptosis. METHODS: Twenty-seven SLE patients and 13 normal controls were studied. Disease activity scores were determined before and after treatment and used to divide patients into 2 groups: GC-resistant and GC-responsive. Isolated PBMC were stimulated with anti-CD3 monoclonal antibodies, cultured with various concentrations of GC, and analyzed by alamar blue assay to determine the LC50, defined as the concentration of GC lethal to 50% of the cells. We measured the expression of CD4, CD8, Fas, and Bcl-2 by FACStar plus flow cytometry. RESULTS: Lymphocytes in the GC-resistant group of SLE patients showed a significantly lower percentage of GC-induced apoptotic cells than did lymphocytes from the responsive group or from normal controls. The LC50 in the resistant group was significantly higher than that in normal controls or the responsive group. The lymphocytes remaining in the resistant group after GC treatment were mainly CD8+, with a high expression of Bcl-2. There was no significant difference in Fas expression between the GC-responsive and GC-resistant groups. CONCLUSION: Determination of the LC50 may be useful in predicting the efficacy of GC treatment in SLE patients, and may be of use in considering other treatment options. CD8 and Bcl-2 double-positive lymphocytes that are insensitive to the apoptotic effect of GCs may play a role in the resistance to these agents in SLE patients.     

Disparate patterns of aldosterone response during diuretic treatment of hypertension

In 50 patients with essential hypertension treated with chlorthalidone, 100 mg daily for 6 weeks, treatment responders (fall in mean pressure, greater than or equal to 10%) and nonresponders experienced similar weight and electrolyte changes. Although induced increments and post-treatment values of plasma renin were higher in nonresponders than responders, there was a far more striking difference in aldosterone reactivity. Aldosterone excretion rose by less than 10% in the responders but almost doubled in the nonresponders. Again, within the normal renin subgroup alone (n = 28), nonresponders exhibited control renin values and treatment-induced changes in plasma renin closely similar to those in responders, but experienced a significantly greater increase in aldosterone excretion. Possibly this increase in aldosterone produced subtle volume retention or a direct pressor effect in nonresponding patients. Although changes in aldosterone and in renin correlated with each other in both responders and nonresponders, the slopes of the regression lines in the two groups differed significantly. Thus, cofactors governing sensitivity of the aldosterone response to renin stimulation ultimately may determine the antihypertensive effectiveness of diuretics.     

Effect of antihypertensive (pargyline hydrochloride-methyclothiazide) therapy in three types of hypertension: preliminary report after one year of observation

Fifty patients with elevated blood pressure were classified according to 3 sub-groups as follows: 11 with borderline hypertension, 8 with systolic hypertension, and 31 with diastolic hypertension. So far, they have been observed for one year while being treated with an antihypertensive preparation containing pargyline hydrochloride and methyclothiazide. Response to treatment depended in large measure upon the type of hypertension; the borderline type was virtually unchanged; in the systolic type there was some diminution in the systolic, but less in the diastolic pressure; and in the diastolic type there was a reduction in both systolic and diastolic pressures. Side effects (faintness, nervousness, mouth dryness, insomnia, genitourinary disturbances and elevated blood uric acid level), when they occurred, were usually relieved by appropriate alteration of the antihypertensive drug dosage, by a change in the time of administration, or by adding medication directed at treatment of the side effect. Evaluation of cardiac output before and after therapy showed no change in this parameter. The results suggest: (a) that the antihypertensive effect probably was achieved by diminishing the peripheral resistance rather than by reducing the cardiac output, and (b) that there was no deterioration of myocardial efficiency, as measured by cardiac output, during the one-year period of antihypertensive therapy. More knowledge of the natural history of hypertension in each of the 3 sub-groups is required for better assessment of the influence of antihypertensive therapy on the outcome of the disease. Judgment as to the desirability of initiating therapy can in some measure be based on the classification of patients into appropriate sub-groups.     

Laparoscopic repair of chronic traumatic diaphragmatic hernia: case report and review of the literature

This study compared the efficacy and tolerability of nisoldipine coat core (CC) 10-40 mg o.d. and hydrochlorothiazide (HCTZ) 25-50 mg o.d. Patients with mild-to-moderate essential hypertension received either nisoldipine CC 10 mg o.d. or HCTZ 25 mg o.d. Treatment was titrated at two-weekly intervals as necessary. The primary efficacy endpoint was a defined reduction in diastolic blood pressure (DBP). Response rates were similar for both the nisoldipine CC- and HCTZ-treated groups (74% and 70%, respectively). Secondary efficacy endpoints were reductions in both diastolic and systolic blood pressures (SBP). At treatment endpoint, the change from baseline in SBP was 16.2 mmHg for the nisoldipine CC group and 14.9 mmHg for the HCTZ group. Both drugs were well tolerated, and adverse events were generally minor and typical of these antihypertensive agents. Drug-related adverse events were greater in the nisoldipine CC- than the HCTZ-treated patients (50% and 37%, respectively). Nisoldipine CC was shown to demonstrate antihypertensive efficacy similar to HCTZ in the treatment of mild-to-moderate hypertension.