Sleep parameters in patients using pacemakers with sleep rate function on.

INTRODUCTION: The cardiovascular system (CVS) is heavily influenced by the autonomic nervous system. Additionally, there is a functional alteration during the various stages of sleep. In nonrapid eye movement (NREM), a state of cardiovascular relaxation occurs during stages three and four. A large amount of rapid ocular movements is concentrated in rapid eye movement (REM) sleep. During this phase, fluctuations in arterial pressure (AP) and heart rate (HR) can be readily noted. Sleep disordered breathing (SDB) has been associated with cardiac rhythm disorders. Recently, cardiac rhythm disorder treatment with pacemaker (PM) highlighted a reduction in abnormal respiratory events during sleep. OBJECTIVE: Comparison of sleep parameters of patients using PM with a sleep rate (SR) algorithm based on its rate-modulated capability during physical activity (Integrity PM with SR function on and off). METHODS: Twenty-two patients (14 women, 8 men), implanted with an Integrity PM (St. Jude Medical Cardiac Rhythm Management Division, Sylmar, CA) with SR function for standard clinical indications, were evaluated utilizing a double-blind protocol. The indication for pacing included sinus node disease (SND), atrium ventricular blockage (AVB), and atrial fibrillation (AF). Following randomization, half of our patients had SR function switched to "on" mode while the other half were on "off" mode. During the first stage of the protocol, all patients underwent two consecutive nights of polysomnographic sleep recordings (PSG). During the first night patients slept in the sleep lab only for adaptation purpose. PSG full recording was carried out in the subsequent night. At a later stage, the programing of SR functions was shifted to "on" or "off" modes. One week later, a third assessment was undertaken. RESULTS: Twelve patients (54%) showed sleep efficiency improvement (total sleeping time/recording time) with PM SR on. This group had the least effective sleep efficiency with PM off, if compared with the others who highlighted no change in this sleep parameter (72 +/- 12 vs 81 +/- 7%, P = 0.01, respectively). This first group displayed a lower latency for REM sleep than the last one (89 +/- 55 vs 174 +/- 107 minutes, P = 0.01, respectively). In 11 (50%) patients, the number per sleep hour of microarousals was reduced when PM SR was switched on. When we compared such findings to the group whose parameters had not changed, we noted that the first set of patients were sleepier (ESE: 9 +/- 4 vs 5 +/- 5, P = 0.04, respectively), and showed more microarousals with PM SR off (20 +/- 14 vs 7 +/- 5 microarousal/hour, P = 0.007). CONCLUSION: In PM patients with sleep-related issues, the SR function activation improved sleep both from a qualitative and quantitative perspective.

Obese children should be screened for hypercholesterolemia.

Screening only those with a positive family history misses many children with hypercholesterolemia. This study investigated whether sensitivity improved by adding obesity as a criterion when screening children for cholesterol. During a two-year period screenings were conducted on 506 inner-city subjects aged 5-19. Demographic, clinical, and dietary information was also recorded. Mean age of participants was 11 +/- 4 years; 52 percent were female, 53 percent black, 39 percent Hispanic, and 8 percent other. Mean cholesterol level was 4.14 mmol/l (160 mg/dl). In multivariate analysis obesity was an independent risk factor for hypercholesterolemia, F = 13.14, p < 0.001. The sensitivity of obesity as a screening tool for hypercholesterolemia was better than that for positive family history (42 vs. 24 percent, respectively). Combining the two improved the sensitivity to 49 percent. The authors recommend expanding the indications for screening children to include obesity, in addition to positive family history of hypercholesterolemia or premature cardiovascular disease.

A multi-center analysis of the use of enalapril and lisinopril in elderly hypertensive patients.

OBJECTIVE: To evaluate the clinical use and adverse effects of enalapril and lisinopril in elderly hypertensive subjects. DESIGN: A multi-center, retrospective, drug use evaluation survey. SETTING: Ambulatory care clinics at 14 VA and 14 academic medical centers. PATIENTS: 422 elderly (> 60 years of age) patients with hypertension and no clinical evidence of congestive heart failure. INTERVENTION: At least 3 consecutive months of anti-hypertensive therapy with either enalapril or lisinopril. MEASUREMENTS: Blood pressure, serum creatinine, serum potassium, concomitant disease states, concurrent medications, and documentation of any adverse event that might be related to ACE inhibitor therapy. RESULTS: There were no significant differences in systolic and diastolic blood pressures, serum creatinine, or serum potassium between enalapril- and lisinopril-treated patients at baseline and after 3 months of therapy. Both treatments resulted in a significant reduction in diastolic blood pressure. There was no significant difference in the incidence of adverse effects between the two treatments. Significantly more patients were dosed on a twice daily regimen of enalapril than lisinopril. CONCLUSION: The data from this retrospective study confirm the safe and effective use of enalapril and lisinopril, two long-acting ACE inhibitors, in elderly hypertensive patients.

Semisynthetic fluorohydrolases prepared by chemical modification of ribonuclease.

A process for conformational modification of protein, which we have previously reported, was investigated as a means of generating fluorohydrolase activity in bovine ribonuclease (RNase). The resulting modified RNase had catalytic activity that depended upon the chosen modifier. Bovine pancreatic ribonuclease, modified by addition of hexamethylphosphoramide (HMPA) at pH 3, was derivatized with diimidates of chain lengths from C1 to C8. The derivative with the highest activity was obtained when RNase was crosslinked with dimethyl pimelimidate (C5). This derivative, which was active over a pH range of 6.5 to 8.0 with an optimum pH of 7.4, hydrolyzed phenylmethylsulfonylfluoride (PMSF) and the potent acetylcholinesterase inhibitor, diisopropyl phosphorofluoridate (DFP). The mean fluorohydrolase activity for four preparations using dimethyl pimelimidate was 0.8 +/- 0.2 U mg-1. Gel filtration on G-75 Sephadex and SDS-polyacrylamide gel electrophoresis showed components having a molecular weight of 13,000 and 27,000, with activity restricted to the 27,000 molecular weight fraction. After gel filtration, the specific activity was 9.1 +/- 2.4 U mg-1, resulting in a molecular activity of 125 min-1. The mechanism of this unique transformation of RNase into a fluorohydrolase is not known, nor has the location of the active site been determined.

NaCN inhibits the stereospecific depletion of LTB4 by guinea pig polymorphonuclear leukocytes.

Caseinate elicited suspension of guinea pig peritoneal PMNs synthesized LTB4, 6t-LTB4, 12-epi-6t-LTB4 and 5HETE after incubations with A23187 and arachidonic acid. Concentrations of LTB4 peaked in 3 minutes and were then rapidly depleted. 6t-LTB4 and 12-epi-6t-LTB4 also peaked in concentrations in 3 min but were depleted slower than LTB4. NaCN inhibited the depletion of LTB4 in a dose dependent fashion without dramatically affecting biosynthesis.

Automated extraction and HPLC resolution of lipoxygenase and cyclooxygenase products utilizing high pressure column switching.

An automatable column switching technique for extraction of cyclooxygenase and lipoxygenase products has been developed. The extraction column is a 0.4 cm X 3 cm stainless steel column slurry packed with Polygosil (C18, 25-40 mu particle diameter). Supernatants of incubations terminated by the addition of 1 volume MeOH, bath sonicated and centrifuged were pumped onto the extraction column. The non-adherent polar material was eluted to waste with up to five times the sample volume with a high polarity mobile phase. Following this, the extraction column was then eluted to an analytical column with a mobile phase of decreased polarity.

Blood pressure, plasma volume, and catecholamine levels during enalapril therapy in blacks with hypertension.

The effect of enalapril, an antihypertensive inhibitor of angiotensin-converting enzyme, on plasma catecholamine levels and plasma volume (PV) has not been well established. In a randomized, double-blind study, 29 subjects (28 blacks and one white) received one of the following dosing regimens: hydrochlorothiazide (HCTZ), 25 mg twice a day (group 1; n = 12); enalapril, 10 mg twice a day (group 2; n = 12); or enalapril, 10 mg twice a day, with HCTZ, 25 mg twice a day (group 3; n = 5). Dosages were doubled after 4 wk if diastolic blood pressure was greater than or equal to 90 mm Hg. After 8 wk of therapy, supine blood pressure decreased by 24.1/16.0 mm Hg (systolic/diastolic) in group 1, by 10.8/4.0 mm Hg in group 2, and by 48.0/27.8 mm Hg in group 3. Mean values of supine plasma levels of norepinephrine, epinephrine, and dopamine did not change with therapy. PV fell 7.9% in group 1, 1.3% in group 2, and 5.0% in group 3. There were no correlations between changes in PV and blood pressure, but a decrease in PV correlated with an increase in plasma norepinephrine levels in the group treated with HCTZ alone (r = -0.65) and in all 29 subjects combined (r = -0.45). Enalapril alone was not very effective in lowering blood pressure in these subjects, but the combination of enalapril with HCTZ was very effective. There was no evidence of a direct effect of enalapril on the sympathetic nervous system or on PV.

Time course of regression of left ventricular hypertrophy in treated hypertensive patients.

In a prospective study, 32 hypertensive patients with echocardiographic evidence of left ventricular hypertrophy were treated with methyldopa, hydrochlorothiazide, or methyldopa and hydrochlorothiazide combined. Echocardiograms and electrocardiograms were obtained in each of the 32 patients before treatment, at the point of initial blood pressure control, and then one, three, and six months thereafter; in 27 patients these studies were also obtained after 12 and 18 months. Left ventricular end-diastolic posterior wall thickness decreased in seven patients whose blood pressure was controlled with methyldopa alone (p less than 0.01) and in 17 patients whose blood pressure was controlled with methyldopa and hydrochlorothiazide combined (p less than 0.01); in both groups, the reduction in left ventricular posterior wall thickness at end-diastole was apparent one month after blood pressure control was established (p less than 0.05). In contrast, no significant reduction in left ventricular posterior wall thickness at end-diastole was observed in eight patients who had equivalent control of blood pressure with hydrochlorothiazide alone (p = 0.34). During the 18-month follow-up period, ventricular septal thickness at end-diastole decreased in the group treated with methyldopa and hydrochlorothiazide combined (p = 0.03); whereas, ventricular septal thickness at end-diastole appeared to increase in the group treated with hydrochlorothiazide alone (p less than 0.01). These results suggest that evidence of regression of left ventricular hypertrophy may be detected as early as one month after blood pressure is controlled with methyldopa or methyldopa and hydrochlorothiazide combined; whereas, long-term control of hypertension with hydrochlorothiazide alone was not associated with evidence of regression of left ventricular hypertrophy. Although the patient number are small, these data suggest that there are differences in the long-term effects of diuretics and sympatholytic drugs on left ventricular anatomy, which may, in part, relate to divergent effects on the sympathetic nervous system.

Blood pressure changes and oral contraceptive use: a study of 2676 black women in the southeastern United States.

Blood pressure (BP) and weight were measured on 2676 black women attending a large southeastern family planning clinic. Repeat measurements were made after a minimum of six and upt to 24 months on 673 women who continuously used nonhormonal contraceptive (OC) therapy, and 1390 women who continuously used OCs. The mean change in systolic blood pressure (SBP) adjusted for initial BP and change in per cent ideal body weight is +1.44 mmHg in the new users of OC. This slight increase in SBP is statistically significant (p = 0.04) relative to the +0.41 mmHg increase observed in the control group. However, the adjusted diastolic blood pressure (DBP) change (+0.46 mmHg in new OC users and +1.54 mmHg in the control group) fails to support the hypothesis of a greater increase in DBP in new OC users. The adjusted mean rise in mean arterial BP does not differ significantly between new OC users and the control group. The proportion of women developing a DBP greater than or equal to 90 mmHg during the average follow-up interval of one year is 2.4% in the control group, 1.0% in the new OC users and 0.2% in the continued OC users. These results provide evidence that OC use has no significant effect on the level of mean arterial BP in black women followed for 6-24 months; and fail to support the hypothesis of a causal relationship between OC use and elevated BP in black women.

PIP: (BP) Blood pressure and weight were measured in 2676 black women attending a large southeastern family planning clinic. Repeat measurements were made after a minimum of 6 and up to 24 months on 673 women who continuously used nonhormonal contraceptive methods (control group), 613 women who initiated (OC) oral contraceptive therapy, and 1390 who continuously used OCs. The mean change in (SBP) systolic blood pressure adjusted for initial BP and change in % ideal body weight is +1.44 mmHg in the new users of OCs. This slight increase in SBP is statistically significant (p=0.04) relative to the +0.41 mmHg increase observed in the control group. However, the adjusted (DBP) diastolic blood pressure change (+0.46 mmHg in new OC users and +1.54 mmHg in the control group) fails to support the hypothesis of a greater increase in DBP in new OC users. The adjust mean rise in mean arterial BP does not differ significantly between new Oc users and the controls. The proportion of women developing a DBP or = 90 mmHg during the average follow-up interval of 1 year is 2.4%. In the control group, 1.0% in the new OC users and 0.2% in the continued OC users. These results provide evidence that OC use has no significant effect on the level of mean arterial BP in black women followed for 6-24 months; they also fail to support the hypothesis of a causal relationship between OC use and elevated BP in black women.

Variation of ethinylestradiol blood levels among healthy women using oral contraceptives.

Data concerning ethinylestradiol (EE) blood levels among 93 healthy women using oral contraceptives are presented. Seventy-two per cent of the observed variation in EE blood levels was unexplainable on the basis of time since ingestion of the last oral contraceptive, day of menstrual cycle, race, age, weight, height, blood pressure, cigarette consumption, alcohol consumption, diurnal variation, or lifetime use of oral contraceptives.

PIP: This 2-fold investigation studied 1) the extent to which women vary in blood levels of ethinylestradiol (EE) after ingesting oral contraceptives (OCs) containing similar amounts of EE or mestranol (ME), which is metabolized to EE; and 2) whatever variations might be accountable on the basis of physical, behavioral, or other characteristics. 93 healthy OC users were given either OCs with 50 mcg of ME (84 subjects) of 50 mcg of EE (9 subjects). Linear regression was used to determine relevance of variation in EE blood levels based on hours since pill ingestion, day of menstrual cycle, or any other variables. Hours since OC showed the strongest relationship to log EE, accounting for 25% of the variation. Another 3% could be accounted for by day of menstrual cycle. The remaining 72% of observed variation in EE levels could not be explained in terms of time since ingestion of last OC, day of menstrual cycle, race, age, weight, height, or use-duration of OCs.

Blood pressure and oral progestational agents. A prospective study of 119 black women.

Blood pressure and body weight were carefully measured in 119 young black women before and after 6 to 24 months of contraceptive therapy with oral progestational agents (minipills). Results are compared with 673 women followed during continued use of nonhormonal contraceptive methods. Minipill therapy (0.35 mg of norethisterone) was associated with no significant (p greater than 0.05) increase in either systolic or diastolic blood pressure means. Minipill users did not develop diastolic blood pressures of 90 mm Hg or more during the study period. Substantial weight gain occurred as a side effect.