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Mental health practitioners continually struggle to find a simple framework for describing the characteristics of the psychologically healthy individual. Hillel's often quoted saying provides relevant insight into the healthy personality and a convenient framework against which to examine psychological health.

Circadian variation in hemostatic factors may contribute to a higher frequency of cardiac events observed in the morning and with activity. Diurnal changes in these factors were investigated by measuring in vitro platelet aggregability in response to epinephrine and adenosine diphosphate together with beta-thromboglobulin and platelet factor 4 as indexes of in vivo platelet activation. Activation of coagulation was measured by thrombin-antithrombin III complexes and D-Dimers. Tests were performed in 9 normal healthy subjects. Circadian changes occurred in beta-thromboglobulin (p less than 0.05) and platelet factor 4 (p less than 0.06). Plasma levels of beta-thromboglobulin and platelet factor 4 were lowest with patients supine and resting at 7 and 8 A.M., and increased with activity, with peak levels achieved at 3 P.M. (p less than 0.01). Thrombin-antithrombin III complexes (p = 0.44), D-Dimer (p = 0.36) and in vitro platelet aggregability to adenosine diphosphate (p = 0.20) did not show diurnal variation. There was a trend toward circadian variation in vitro platelet aggregability to epinephrine, but these changes did not achieve statistical significance (p = 0.16). Circadian changes of in vivo release of beta-thromboglobulin and platelet factor 4 correlated to patient activity and not to the morning peaks in ischemic events. These data indicate that changes in platelet function and not in coagulation have a diurnal occurrence.

A 12-week, multicenter, double-blind, randomized, placebo-controlled trial of imazodan, a type III phosphodiesterase inhibitor, was conducted in 147 patients with congestive heart failure to determine clinical efficacy and safety. Patients were randomized to placebo or 2, 5 or 10 mg of imazodan administered twice daily. Patients were maintained on their standard therapy including diuretics, digoxin and an angiotensin-converting enzyme inhibitor. The mean ejection fraction was 23 +/- 10%. Exercise time increased from baseline in all 4 groups. There was no significant difference observed between the placebo group and any of the treated groups with regard to exercise time, ejection fraction, frequency of ventricular premature complexes or ventricular tachycardia. When analyzed by intent to treat, the placebo mortality was 7% (3 of 44) and the imazodan mortality was 8% (8 of 103) (p = not significant). This study failed to demonstrate that imazodan provided any benefit in exercise performance when compared with placebo.

Peak III phosphodiesterase (PDE) inhibitors have combined positive inotropic and vasodilator effects. We studied 10 patients with chronic heart failure during and after infusion of intravenous (i.v.) ICI 153,110, an investigational peak III PDE inhibitor. Maximum hemodynamic response for the group occurred after cessation of infusion at a lower plasma drug concentration. At maximum hemodynamic response, cardiac index (CI) increased (2.4 +/- 0.5 vs. 3.2 +/- 0.37 L/min/m2, p less than 0.05) with a decrease in mean arterial pressure (MAP 91 +/- 5 vs. 80 +/- 3 mm Hg, p less than 0.05), pulmonary capillary wedge pressure (PCWP 25 +/- 2 vs. 17 +/- 3.1 mm Hg, p less than 0.01), systemic vascular resistance (SVR 1,422 +/- 106 vs. 983 +/- 97 dynes.s.cm-5, p less than 0.05) and pulmonary vascular resistance (PVR 227 +/- 39 vs. 16 +/- 31 dynes.s.cm-5, p less than 0.05). During the infusion, plasma renin activity (PRA) decreased from 6.34 +/- 2.53 to 3.6 +/- 3 ng/ml/h (NS). The five patients with high baseline PRA had a significant decrease (11.2 +/- 2.5 vs. 5.4 +/- 1.67 ng/ml/h, p less than 0.01) that preceded changes in CI and SVR by 1-2 h. These data suggest that reduction in PRA may have contributed to the hemodynamic effects of this peak III PDE inhibitor.

Using a randomized crossover design, 1-g intravenous doses of cephalothin and cefoxitin, a cephalosporinase-resistant cephamycin, were infused into 12 normal adult males over periods of 120, 30, and 3 min, the last with and without prior intravenous infusions of probenecid (1 g). Mean peak serum concentrations of antibiotic activity after cephalothin infusions were 23, 56, 103, and 102 mug/ml, respectively, and after cefoxitin infusions they were 27, 74, 115, and 125 mug/ml, respectively. Probenecid treatment prolonged the terminal serum half-life of cephalothin-like activity from 0.52 to 1.0 h, and of cefoxitin from 0.68 to 1.4 h. In contrast to cephalothin, which was found to be metabolized about 25% to the less active desacetyl form, cefoxitin was metabolized less than 2% to the virtually inactive descarbamyl form, as judged from urinary recoveries. Neither antibiotic displayed detectable organ toxicity. Of 300 recent clinical isolates of gram-negative bacilli other than Pseudomonas spp., 83% were susceptible to cephalothin but 95% were susceptible to cefoxitin. Organisms resistant to cephalothin but susceptible to cefoxitin included strains of Escherichia coli, Proteus vulgaris, Klebsiella spp., Serratia marcescens, Enterobacter spp., and Bacteroides spp.

Myocardial blood flow was measured by the 133Xe clearance technique in 21 patients 6 to 31 months after saphenous vein grafting for coronary arterial disease. Preoperative measurements were made in 16. All patients had improved symptomatically, and 20 had returned to work. Thirty of 39 grafts were entered and selective injections of 133Xe performed. Flow in the left coronary artery (LCA) was unchanged postoperatively in 9, increased in 5, and decreased in 1 (preoperative mean = 54 ml/100 g/min, SD +/- 16; postoperative mean = 65 ml/100 g/min, SD +/- 20). Flow in the right coronary artery (RCA) was unchanged postoperatively in 3, decreased in 9, and increased in 2 (preoperative mean = 46 ml/100 g/min, SD +/- 18; postoperative mean = 33 ml/100 g/min, SD +/- 12). Nine of 14 grafts to the left anterior descending coronary artery showed flow rates significantly greater than those in the corresponding LCA. Two of the 3 circumflex grafts showed flow rates significantly lower than those in the LCA. Four of 8 right grafts showed significantly higher flow rates than those in the corresponding RCA. These findings correlated well with the angiographic appearances. We conclude that saphenous vein grafting increases total myocardial blood flow. The data suggest that the coronary arteries and the grafts are supplying different regions of the myocardium, and that the graft regions were previously underperfused. There would appear to be little mixing of blood between artery and graft regions.

CI-930, a new type III phosphodiesterase inhibitor, was evaluated for treatment of refractory congestive heart failure. The hemodynamic, pharmacokinetic and clinical response to the drug was determined in 10 patients. At the peak plasma concentration after intravenous CI-930, cardiac index increased from 2.0 to 2.7 liters/min/m2 (p less than 0.002), pulmonary artery wedge pressure decreased from 26 to 17 mm Hg (p less than 0.001) and systemic vascular resistance decreased from 1,999 to 1,471 dynes cm-5 (p less than 0.05). Heart rate and blood pressure did not change significantly. Similar changes were observed with oral CI-930. Peak CI-930 plasma concentration occurred 1.2 +/- 0.8 hours after oral administration. Beneficial hemodynamic effects were sustained 12 to 18 hours after the oral dose. The sustained hemodynamic effects observed after oral administration appear to be related to an active metabolite of CI-930 that has prolonged duration of action and slow washout. The drug was well tolerated and has potential for treatment of congestive heart failure.

Jewish tradition established the Sabbath as a special day. Its observance was both part of a religious tradition and an example of psychological health. This article explores the values and attitudes that underlie Sabbath observance, identifies some of the themes and behaviors most characteristic of these observances, and relates these to current mental health practices.

Continuous recording of intra-arterial blood pressure and electrocardiograms has been performed in 41 ambulant untreated essential hypertensive subjects for periods up to 48 hours. Statistical analysis of the results has revealed: (1) A group of patients who developed a persistent tachycardia during the day. This response was not observed in a control population free of overt cardiovascular disease. (2) Three different haemodynamic responses to day-time activities suggesting different mechanisms for the production of high blood pressures. No normal controls are available for these changes. (3) No differences in responses between patients defined as 'labile' and 'fixed' hypertensives.

Intra-arterial blood pressure recordings were studied in 10 ambulant subjects with essential hypertension to evaluate the effect of a single daily dose of acebutolol. Blood pressures and heart rates, measured on a beat-to-beat basis were averaged over every hour, for the daytime, night-time, and for the total 24 hours. Acebutolol significantly lowered the average daytime systolic pressure (160 to 142 mmHg, p = less than 0.01), diastolic pressure (78 to 66 mmHg, p = less than 0.01), and the heart rate (92 to 77 beats/min, p = less than 0.001). Significantly lower pressures were demonstrated up to 11 hours after the last dose of acebutolol. The effect on heart rate lasted up to 13 hours. The observed lowering of pressures and heart rate during the remaining 11 hours did not reach statistical significance.

Severe hypertension, for which no cause could be found, developed in an adolescent female. The patient's blood pressure was refractory to intensive pharmacologic intervention. After 11/2 years of medical management, the patient's intra-arterial blood pressures were found to be in the normotensive range. Individuals with labile hypertension may be refractory to pharmacologic control and may require continuous pressure monitoring in order to establish a proper diagnosis.

Fifty patients on a regimen of procainamide were studied in regard to the association between antinuclear antibodies (ANA) and the development of drug-induced systemic lupus erythematosus (SLE)-like syndrome. Four groups were identified: Group 1 was ANA-positive, with clinical manifestations (serologic and clinical findings); Group 2 was ANA-positive, without clinical manifestations (serologic findings only); Group 3 was ANA negative (no patients with clinical manifestations); and Group 4 had SLE persisting after discontinuance of procainamide. The leukocyte-specific ANA (LSANA) patterns were predominant, with peripheral LSANA confined to Groups 1 and 4. Furthermore, the titer of the homogeneous LSANA, to which peripheral LSANA converts on dilution, was clinically significant. A homogeneous LSANA titer of 160 or greater was seen essentially only in patients with clinical manifestations of the SLE-like syndrome. Serial ANA determinations are therefore necessary to monitor patients receiving procainamide.

Twenty-four-hour recordings of intra-arterial blood pressure, heart rate, and calculation of the index of peripheral vascular resistance were obtained in 20 untreated ambulant hypertensive patients during their routine activities outside the hospital. Blood pressures and heart rates were higher during the day, with a mean night-to-day increase of 22%, 34%, and 26%, for systolic, diastolic, and mean pressures, respectively. The average increase in the heart rate was 32%. Overall, the index of resistance was lower (12%) during the day. However, eight patients (40%) demonstrated no change or an increase in the peripheral vascular resistance. Six of these eight patients had an average daytime mean pressure above 120 mm Hg. There was a significant decrease in the index of resistance during exercise in all but one of the 16 subjects. Hemodynamic parameters of 1 hour before and 1 hour after awakening were similar to the values obtained during the entire night and the rest of the day, respectively. Our data suggest that in patients with "progressive" hypertension, the ability to decrease vascular resistance from night to day is compromised.

Hemodynamic response after intravenous and oral administration of a new phosphodiesterase inhibitor, CI-914, was studied in 13 patients with severe congestive heart failure. Comparable significant increases in cardiac index of 26% (p less than 0.01) and 19% (p less than 0.02) after intravenous and oral administration were observed. Systemic vascular resistance, right atrial and pulmonary artery wedge pressure decreased significantly after intravenous drug administration. Although similar changes occurred after oral administration, they were not statistically significant. Peak CI-914 plasma concentration occurred 2.3 +/- 2.2 hours after oral drug administration and exhibited measurable hemodynamic effects for up to 10 to 12 hours. Seven of the 13 patients received long-term oral CI-914 for as long as 12 weeks and exhibited an improvement in New York Heart Association functional class and exercise capacity. Five patients died with progressive heart failure, 1 patient died suddenly and 1 died of sepsis. The drug was well tolerated and appears to have potential as a cardiotonic agent.

Sequential changes in radionuclide angiographic measurement of left and right ventricular performance and quantitative thallium-201 scintigraphy were studied in 20 patients sustaining their first acute myocardial infarction (AMI). The studies were performed on the average 29.4 hours and 9.4 days after hospital admission. Anterior infarction had greater impairment of left ventricular (LV) performance in terms of ejection fraction and percentage of abnormal contraction area in addition to larger thallium-201 perfusion defects. At the time of the late study evidence of thallium-201 perfusion of infarcted area was seen in 14 of 20 patients, five of whom demonstrated improvement of regional wall motion. The remaining patients in the reperfused group and all of the patients in the nonperfused group failed to show evidence of LV functional improvement. This study indicates that reperfusion as measured by thallium-201 scintigraphy does occur spontaneously in 70% of patients with AMI and only in those patients with established reperfusion is there any potential for improvement in LV performance.

Acute and chronic hemodynamic effects at rest and during exercise of a new dihydropyridine calcium antagonist, nicardipine hydrochloride, were studied in 10 patients with chronic heart failure. Acute intravenous administration of nicardipine resulted in a significant decrease in arterial blood pressure, systemic vascular resistance, and pulmonary capillary wedge pressure. There was a significant increase in cardiac index, stroke volume index, and the left ventricular stroke work index. Cardiac index measured at peak exercise increased significantly when compared with the cardiac index obtained at peak exercise before the infusion. After 9 days of continuous therapy with nicardipine, 30 mg three times a day, a significant decrease in arterial blood pressure and systemic vascular resistance and a significant increase in the cardiac index, stroke volume index, and left ventricular stroke work index at rest were observed in response to a single oral dose of 30 mg nicardipine. Data at peak exercise were also obtained before and 2 hours after the oral administration of nicardipine. With this comparison there was a significant increase in cardiac index, stroke work index, and exercise duration. It is concluded that in this group of patients with severe chronic heart failure, nicardipine enhanced myocardial performance during rest and exercise and this enhancement is sustained after 9 days of oral therapy.

The immediate effects on heart rate and blood pressure of withdrawing antihypertensive drugs were studied over three-day periods in 26 patients. Four groups of drugs were studied. After withdrawal all patients taking clonidine showed a considerable increase in heart rate and blood pressure with intense ectopic activity. Patients taking postganglionic neurone-blocking drugs showed a similar but less pronounced reaction with increased ventricular ectopic activity. No alarming reactions were seen after withdrawal of methyldopa or beta-blocking drugs. Methyldopa and, especially, beta-blocking drugs are less likely to produce withdrawal reactions than clonidine or the postganglionic neurone-blocking drugs, and patients taking these drugs are therefore less likely to suffer violent reactions if they forget to take their tablets.

Pirmenol hydrochloride (CI-845), a new antiarrhythmic agent available for both oral and intravenous administration, was given to seven patients with chronic ventricular dysrhythmia in an open-label fashion. After intravenous infusion of 150 mg over 30 min, the mean (+/- SD) peak plasma concentration achieved was 2.14 +/- 0.75 microgram/ml. The terminal elimination half-life, the volume of the central compartment, and the total body clearance averaged 6.5 h, 0.70 +/- 0.36 L/kg, and 3.0 +/- 2.6 ml/min/kg, respectively. After a single 150-mg oral dose, the peak plasma concentration of 1.3 +/- 0.55 microgram/ml was achieved 1 to 3 h after dosing. The mean apparent elimination half-life was 7.6 h. An estimated absorption lag time ranging from 14 to 37 min was observed in all but one patient. The mean absolute bioavailability for the oral dose was 87%. Dysrhythmia data were available in six patients. Complete (100%) suppression of ventricular ectopic beats occurred in four patients for 1/2 to 15 h after intravenous infusion, and in three patients for 7 to 25 h after oral dose. This suppression occurred with a plasma pirmenol level as low as 0.4 microgram/ml. No significant side effects were observed.

1. Renal function has been studied in 312 hypertensive patients by quantitative renography with sodium o-[131I]iodohippurate (131I-labelled Hippuran) and estimation of overall effective renal plasma flow. In 59% of the patients the results were normal. 2. Severe hypertension was associated not only with reduced effective renal plasma flow but also a characteristic abnormality of Hippuran transport in 10% of the patients in which there was a wider than normal variation in transit times of Hippuran through the kidney, which may reflect non-uniformity of reabsorption of filtrate by different groups of nephrons. 3. Plasma renin activity was higher in a group of 14 patients with multimodal transit time spectra than in a matched hypertensive control group, with very substantial overlap between the two groups. 4. The renographic abnormality was usually reversed by treatment.

Comparisons with direct recordings show that the Physiometrics automatic blood-pressure recorder does not accurately reflect intra-arterial pressure and tends to over-read both systolic and diastolic pressures.

Continuous electrocardiographic (ECG) records were made over 24 hours in 130 ambulant outpatients complaining of syncope, dizzy turns, or palpitation. In all these patients resting ECGs had failed to show significant dysrhythmias. Exercise testing was performed on 64 patients and also failed to reveal any dysrhythmias. Analysis of the tape recordings, however, showed appreciable dysrhythmias in 74% of the group. In most cases the dysrhythmias were complex mixtures of rapid supraventricular and ventricular rhythms. bouts of ventricular tachycardia were seen in seven patients, all of whom were women. Episodic complete heart block was seen in only two patients, but prolonged ventricular gaps (greater than 1-5 s), not associated with ectopic beats, were found in 26. No episodes of ventricular fibrillation were recorded. We conclude that many patients with vague symptoms suggestive of transient cerebral ischaemia or irregular heart action have significant and often dangerous dysrhythmias which can be diagnosed only by long-term recording of the ECG under fully ambulant conditions.

We performed a randomized trial comparing intracoronary administration of streptokinase versus dextrose placebo within six hours after the onset of symptoms of acute myocardial infarction in 40 patients. The base-line clinical, hemodynamic, and angiographic findings were similar in the control and streptokinase-treated groups. Reestablishment of flow occurred in 12 of 20 patients treated with streptokinase and in 2 of 20 given placebo (P less than 0.05). Left ventricular function, angiographic ejection fraction, and regional wall motion, measured before and immediately after intervention, and serial radionuclide ejection fractions, measured at treatment, at 12 days, and at 5 months, were compared according to type of treatment (streptokinase vs. placebo) and outcome of therapy (reperfusion vs. no reperfusion). No statistically significant differences between groups were found. Thus, although streptokinase was more effective than placebo in achieving reperfusion, we detected no improvement of left ventricular function as a result of reestablished coronary flow.

Continuous recording of intra-arterial blood pressure in 11 ambulant patients taking postganglionic blocking drugs for the treatment of hypertension has shown an alternating pattern of high pressures at rest and very low pressures associated with exertion during normal daily activities. In 4 patients there was evidence of decreased cerebral or myocardial blood-flow during hypotensive episodes. It is suggested that these agents may predispose towards cerebral and myocardial infarction.

A comparison was made of the estimated size of the myocardial infarction occurring in 26 patients with a first infarction using creatine kinase (CK) enzyme release between radionuclide gated blood pool measurement of total and regional ventricular function and thallium-201 scintigraphic measurement of myocardial perfusion defects. Creatine kinase estimates of infarct size (enzymatic infarct size) correlated closely with the percent of abnormal contracting regions, left ventricular ejection fraction and thallium-201 estimates of percent of abnormal perfusion area (r = 0.78, 0.69 and 0.74, respectively, p less than 0.01). A close correlation also existed between percent abnormal perfusion area and percent of abnormal contracting regions (r = 0.81, p less than 0.01) and left ventricular ejection fraction (r = 0.69, p less than 0.01). Enzymatic infarct size was larger in anterior (116 +/- 37 CK-g-Eq) than inferior (52 +/- 29 CK-g-Eq) myocardial infarction (p less than 0.01) and was associated with significantly more left ventricular functional impairment as determined by left ventricular ejection fraction (33 +/- 7 versus 60 +/- 10%) (p less than 0.01) and percent abnormal perfusion area (58 +/- 14 versus 13 +/- 12) (p less than 0.01). No significant correlation was observed between enzymatic infarct size and right ventricular ejection fraction. These different methods of estimating infarct size correlated closely with each other in these patients with a first uncomplicated myocardial infarction.

An index of peripheral vascular resistance, derived from directly measured arterial pressure, has been developed and tested in an animal model. Assuming a mono-exponential character for diastole, the time constant for direct arterial pressure decay in the central aorta was obtained with high-fidelity recording techniques from six anaesthetized dogs. Changes in peripheral resistance were induced by infusion of phenylephrine or nitroprusside. The time constant correlated well with resistance determined from 1-min averages of pressure divided by integrated electromagnetic flow (r = 0.845). A portable system used for direct arterial pressure recording in ambulant outpatients yielded a mean correlation of 0.822 with resistance. In a study of patients undergoing cardiac catheterization, a time constant obtained from the brachial artery (the site of pressure recording in the ambulant subjects) correlated well with the aortic time constant (n = 6, r = 0.964). The results of the present work suggest that the time constant derived from direct arterial pressure waveform may be a useful index in the evaluation of the peripheral vascular resistance. Furthermore, with the help of the portable system it might be used for the continuous monitoring of resistance changes in ambulatory subjects.