Intravenous nitroglycerin for rapid uterine relaxation.

BACKGROUND: To investigate the effect of nitroglycerin in vitro and in vivo on human uterine contractile activity. METHODS: In vitro myometrial strips were obtained from six pregnant women at term who underwent elective cesarean section. The biopsies were mounted in tissue baths. After spontaneous or oxytocin-induced activity had been accomplished, nitroglycerin in various concentrations was added to the baths and the effects were continuously registered. In vivo, in an open study nitroglycerin was administered as a bolus injection of 100-200 micrograms intravenously to 32 women at cesarean section when uterine relaxation was urgently needed; to 22 other women after vaginal delivery for facilitation of manual removal of retained placentas, and to one patient at vaginal delivery of premature twins. RESULTS: In vitro nitroglycerin induced a dose-dependent inhibition of spontaneous as well as oxytocin-induced myometrial contractile activity. Complete muscular relaxation was obtained at a concentration of 25-50 micrograms/ml. In vivo all patients had rapid effective uterine relaxation after intravenous injection of 100-200 micrograms nitroglycerin. CONCLUSION: Nitroglycerin administered intravenously seems to be a rapid and effective uterine muscle relaxant agent without overt adverse effects on mother or fetus.

A positron emission tomography study of cerebral blood flow and oxygen metabolism in healthy male volunteers anaesthetized with eltanolone.

BACKGROUND: The effects of eltanolone anaesthesia in humans on regional cerebral blood flow, regional cerebral metabolic rate of oxygen and oxygen extraction ratio were to be evaluated using positron emission tomography (PET). METHODS: Six healthy male volunteers were studied. Series of PET-measurements with 15O and H2(15)O were carried out in the awake state (baseline)(n = 6), during eltanolone anaesthesia (n = 5) and during early recovery (n = 5), when the subjects were oriented with respect to person, place and time. Eltanolone was given as a programmed infusion. RESULTS: Cerebral blood flow (rCBF) was reduced in almost all cortex regions studied by 31 +/- 16% (mean +/- SD, P < 0.01). During recovery rCBF increased to 109 +/- 26% of pre-anaesthetic baseline levels (P < 0.01). Eltanolone in the doses administered lowered oxygen metabolism (rCMRO2) by 52 +/- 8% (P < 0.01) in cortex regions. During recovery rCMRO2 increased to 90 +/- 13% of baseline (P < 0.01). The oxygen extraction (OER) in cortical regions decreased by 32 +/- 23% (P < 0.01) during anaesthesia and returned to 82 +/- 10% of baseline (P < 0.01) during recovery. Less reduction in cortical blood flow during eltanolone anaesthesia was seen in the uncus (P < 0.01), though no differences in the depression of oxygen metabolism were seen. Oxygen extraction remained homogeneous throughout the brain. CONCLUSION: Eltanolone anaesthesia was shown to reduce cerebral oxygen metabolism and cerebral blood flow in healthy volunteers. There were no signs of ischaemic effects.

Pharmacokinetics of eltanolone following bolus injection and constant rate infusion.

Disposition of intravenous anaesthetic eltanolone was studied when administered as a bolus injection (B) of 0.75 mg/kg and constant rate intravenous infusion at 2 mg/kg/hr (12) and 3.5 mg/ kg/hr (13.5) for 2 hr in healthy male volunteers. Venous blood samples were collected for 12 hr and 20 hr following bolus injection and intravenous infusion, respectively. Serum eltanolone concentrations were determined by a specific gas chromatographic mass spectrometric assay. Using a nonlinear regression analysis, the individual data sets were best fitted by a three-compartment mamillary model with central elimination. Derived pharmacokinetic parameters expressed as median and 95% confidence intervals indicated an initial fast distribution with a half-life of 1.80 (0.23-5.47) min (B), 1.44 (0.97-2.06) min (12) and 1.44 (0.95-2.39) min (13.5), an intermediate phase with a half-life of 35.4 (28.7-45.2) min (B), 39.6 (31.0-47.9) min (12) and 35.4 (33.3-44.9) min (13.5) and a moderately short terminal phase with a half-life of 3.8 (2.7-5.9) hr (B), 5.0 (4.2-6.1) hr (12) and 4.6.(4.0-4.8) hr (13.5). The serum clearance after bolus injection was 1.37 (1.23-1.67) L/hr/kg and after infusion was 1.36 (1.25-1.52) L/hr/kg (12) and 1.17 (1.11-1.31) L/hr/kg (13.5). The pharmacokinetics of eltanolone appear to be linear over the dosage range studied. Pharmacokinetic parameters obtained after bolus injection were very much similar to the parameters obtained after infusion with the exception of t1/2 beta which was longer after the infusion (significant) and the volume of central compartment which was lower after infusion (not significant). Context sensitive times were estimated for a 30%, 50% and 80% drop in the concentration of eltanolone after different infusion times. A 30% drop in concentration is estimated to take about 2 to 3 min. A 50% drop in concentration is estimated to take about 8 min when duration of infusion is 3 hr and reaches a value of about 10 min by a duration of infusion of 10 hr. A 80% drop in concentration is estimated to take about 55 min following an infusion of 1 hr and it reaches a value of 70-80 min following an infusion of 10 hr.

Concentration-effect relationships of eltanolone given as a bolus dose or constant rate intravenous infusion to healthy male volunteers.

BACKGROUND: The primary purpose of this study was to evaluate concentration-effect relationships of the new steroid anesthetic eltanolone during recovery from a bolus dose and constant rate intravenous infusion in healthy male volunteers. METHODS: Ten subjects received a bolus dose of 0.75 mg/kg eltanolone over 20 s. A 2-h constant rate intravenous infusion of eltanolone was given to five subjects at a rate of 2 mg.kg-1.h-1 and to another five subjects at a rate of 3.5 mg.kg-1.h-1. Recovery performance was assessed as the time required to reach different end-points and by means of three different psychomotor tests. RESULTS: A low interindividual variability was found in the serum concentration of eltanolone at the pharmacodynamic end-points during recovery. The Cp50 value for "eye opening" was 382 micrograms/L (95% confidence interval, 285-489) after a bolus dose corresponding to a median time of 16 min (range 8-25). After eltanolone infusion, the Cp50 value for "eye opening" was 507 micrograms/L (95% confidence interval, 425-605) and the corresponding median time was 21 min (range 8-25) in the low-dose group and 49 min (range 31-66) in the high-dose group. The Cp50 values at the same effect end-points in the bolus group were less than those in the infusion groups, probably because of insufficient equilibration time between serum and the effect compartment. CONCLUSIONS: Recovery characteristics of eltanolone were predictable because of a relatively low interindividual variability in serum concentrations but with a slow blood:effect compartment equilibration.

The use of intravenous nitroglycerin for emergency cervico-uterine relaxation.

A patient with a twin pregnancy was in preterm labour after 25 gestational weeks when, during vaginal delivery of the second twin, severe spasm of the cervix and fetal bradycardia ensued. Induction of general anesthesia did not relax the cervix. After bolus doses of nitroglycerin 100 + 50 micrograms i.v., prompt cervico-uterine relaxation was obtained allowing manual extraction of the baby. A short review of the literature and a summary of our experience in the administration of nitroglycerin i.v. in obstetrics are presented.

Clinical pharmacokinetics of propofol given as a constant-rate infusion and in combination with epidural blockade.

STUDY OBJECTIVES: To investigate the pharmacokinetics of propofol in combination with epidural anesthesia or with intravenous (i.v.) alfentanil infusion, and to investigate the clinical feasibility of this anesthetic technique in lower abdominal surgery. DESIGN: Randomized, open clinical study. SETTING: Operating theaters and postanesthesia recovery unit at the department of gynecology of a university medical center. PATIENTS: 20 healthy, consenting ASA physical status I and II adult female patients undergoing lower abdominal surgery. INTERVENTIONS: A total i.v. anesthetic technique was used in all patients. In Group 1, a continuous infusion of propofol was combined with an epidural block with bupivacaine. Group 2 patients received a combination of propofol and alfentanil infusions. MEASUREMENTS AND MAIN RESULTS: The pharmacokinetics of propofol are best fitted to a two-compartment open model and were similar in both patient groups. Propofol blood clearance was 29.8 +/- 6.51 ml/min/kg, and volume of distribution was 3.60 +/- 1.34 L/kg, resulting in a blood elimination half-life of 144 +/- 46 minutes. The entire period of anesthesia was stable in the alfentanil group. In the epidural group, the initial period of anesthesia was too light as judged by the autonomic response to tracheal intubation, which also correlated in time to a lower propofol blood concentration than was seen in the alfentanil group. No evidence was found that an epidural block induced a change in propofol kinetics, apart from the lower blood concentration during the initial period of anesthesia. CONCLUSIONS: We could not show any statistically significant influence of an epidural blockade on the pharmacokinetic parameters of propofol. Nevertheless, the concentration-time profile changed during infusion, rendering the described infusion regimen, in combination with epidural anesthesia, unsatisfactory for adequate hypnosis. The propofol infusion regimen combined with alfentanil provided immediate and stable blood concentrations that were adequate for surgery.

Concentration-effect relationships of propofol after total intravenous anesthesia.

To evaluate the concentration-effect relationships of propofol during recovery after total intravenous anesthesia, 20 female patients undergoing lower abdominal surgery were studied. In 10 patients (Group B) the propofol infusion was supplemented with an epidural block with bupivacaine to evaluate the relation between the blood concentration of propofol and various pharmacodynamic end-points. The remaining 10 patients (Group A) received an alfentanil infusion intravenously instead of the epidural block to assess the dynamic interactions of alfentanil and propofol. Postoperative performances (drowsiness, amnesia, cooperation, and orientation) were evaluated by means of scoring scales. Critical flicker fusion threshold (CFF) also was used to assess the level of postoperative alertness. A propofol blood concentration of 2.5 micrograms/mL was required for satisfactory hypnosis during surgery and at 0.8 +/- 0.4 microgram/mL, the patients were considered fully awake. A concomitant alfentanil infusion reduced the propofol concentration required by 0.2-0.4 microgram/mL for the same degree of effect. Rapid recovery was seen in all patients, but in the group receiving alfentanil infusion there was a shift to the left of the concentration-effect curve in regard to drowsiness and a statistically significant prolongation of recovery by CFF-measurement which suggests a possible dynamic interaction with alfentanil. We conclude that there is a good correlation between the blood concentration of propofol and the pharmacodynamic responses during recovery.

Blood pressure patterns and migration: a 14-year cohort study of adult Tokelauans.

The longitudinal relation between blood pressure changes and migration experience has been studied in a cohort of 654 adult Tokelauans through three survey periods between 1968 and 1982. Migration from a subsistence life-style on a Pacific atoll to an urbanized Western life-style in New Zealand is associated with increases in body mass in both men and women. Both the systolic and diastolic blood pressures of migrant men are significantly higher than would be expected in this cohort on the basis of age when compared with the nonmigrants. This is consistent with a rise around the time of migration to a level which is then maintained, with the diastolic pressures taking longer than the systolic pressures to respond to the migration stimuli. Most of this rise in blood pressure may be attributed to weight gain, but a significant part of the diastolic pressure excess remains unexplained. This pattern is not exhibited by the women, which may be a reflection of the sex roles in this Polynesian society. These findings indicate a need for new immigrants to be encouraged not to gain weight when confronted with new dietary choices.

Medical student's access to information and resources for the residency selection process.

In the study reported here, the authors analyzed senior medical students' attitudes regarding the availability of information and resources pertaining to the residency selection process. Results of a nationwide survey of students showed that when the students had access to information from medical professionals (that is, faculty members, deans, house staff physicians), they felt they had greater access to information than did students who made greater use of other sources (official directories, classmates and the "grapevine"). Furthermore, the findings suggest that greater availability of information from medical professionals was related to higher levels of overall satisfaction with the residency match. While no evidence is presented that demonstrates that medical school faculty members and administrators were unwilling to devote attention to any particular group of students, the data suggest that these professionals provided information regarding the residency selection process more often to medical students at high-prestige schools, students who chose high-prestige specialties, and students who perceived themselves as having high class rank than to other students. Also, students in publicly supported schools felt the cost of travel for interviews to be more burdensome than did the students in private schools.

An analysis of medical students' residency and specialty choices.

The contemporary geographic maldistribution of physicians and shortages in some specialty areas is a persistent problem facing United States federal and state wide health planners. This paper attempts to illustrate some of the formal and informal processes of the selection of specialties and residency programs based on a survey of senior students of 37 selected American medical schools at the time of the National Residency Matching Program in 1982. Results of a factor analysis on influences on specialty choice produced two major clusters of medical students; those predominantly influenced in specialty choice by the faculty and other senior physicians (sponsorship), and those predominantly influenced by the social dimension of the physicians' role (social responsibility). These medical specialty choice orientations were also systematically related to either choice of specialty vs primary care medicine, to a life-style or status related choice of residency program, and to students' perceptions regarding a program's evaluation of a candidate. The results of the survey suggested that students who chose primary care were more apt to be influenced by sources outside of the medical school. These findings raise questions regarding the efficacy of medical school curriculum in motivating career choices in primary care. This is particularly important in view of the stated need to increase the proportion of medical school graduates choosing primary care careers.

Longitudinal analysis of the relationship between blood pressure and migration: the Tokelau Island Migrant Study.

The Pacific atoll population of Tokelau has been followed since 1968 to assess the health consequences of migration to a western society. The blood pressure of a cohort of 532 adults who were still living in Tokelau in 1976 (nonmigrants) are compared with those of a cohort of 280 adults who had migrated to New Zealand (migrants). Significant differences between migrants and nonmigrants were detected in the rates of change of both systolic and diastolic pressures in men, and in the rates of change of diastolic pressures in women. The age-, body mass, and blood pressure-corrected rates of change were greater in migrants than in nonmigrants, and greater in men than in women. Blood pressures tend to rise 1 mmHg/year faster among male migrants than among male nonmigrants, and about 0.4 mmHg/year faster among female migrants than among female nonmigrants. These findings have clear implications for the health of migrants.

Correlations between appointment keeping and reorganization of hospital ambulatory pediatric services.

Over a period of 13 months before and after a university-affiliated hospital's daytime ambulatory pediatric facility was upgraded from an episodic care clinic to a primary care unit, 260 subjects were interviewed in an attempt to predict compliance with return appointment scheduling. The parents of patients more than 10 years of age were the least compliant, but most of the differences in compliance appeared due to the subject's evaluation of the diagnostic ability, thoroughness, and sympathy of the physician at the initial visit. Although no changes were noted in the subjects' demographic characteristics or in their general opinions of ambulatory health care delivery or of attitudes desired of physicians, their evaluations of recent visits improved and the missed appointment rate declined by 46% in the course of the study. Moreover, the pediatric house officers, who evaluated the patients, demonstrated an increased ability to assess the characteristics the subjects found important in physicians. Improvements are still needed, especially in the amount of communication between house officers, patients, and parents, but heeding clients' opinions about the provision of primary health care may help to make missed appointment rates negligible.