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Biomedical subjects

M C Allen

Publications and source records attributed to M C Allen.

85 records · Page 5Linked to original sources
PubMed1982

Tritiated peptides. 12. Synthesis and biological activity of [4-3H-Phe8]substance P.

Substance P has been prepared 3H labeled at Phe8 by catalytic deiodination of a protected precursor. Synthesis of the precursor was by solid-phase methodology on polydimethylacrylamide resin and by condensation in solution of fragments covering sequences 1-4, 5-7, and 8-11. Free peptide made by each route analyzed satisfactorily and had the same chromatographic characteristics as unlabeled substance P. It was indistinguishable from the latter by radioimmunoassay when N and C terminally directed antisera were used and in the ability to cause contractions of isolated guinea pig ileum. Specific radioactivity was 23 Ci/mmol.

Amino Acids↗
PubMed1982

Single-dose comparison of buprenorphine 0.3 and 0.6 mg i.v. given after operation: clinical effects and plasma concentration.

The plasma concentrations and clinical effects of a single i.v. dose of buprenorphine 0.3 or 0.6 mg were studied in patients recovering from surgery. Analgesic and hormonal effects were greater with the greater dose without a parallel increase in respiratory depression. A comparison with previous work suggests that increased efficacy results either from the use of the larger dose or equivalently if the first required postoperative dose of 0.3 mg has been preceded by a similar loading dose.

Aged↗
PubMed1982

Dural permeability to narcotics: in vitro determination and application to extradural administration.

The permeability of cranial and lumbar dura to various substances including a number of narcotic analgesics was measured in vitro. Preliminary data On human postmortem material is reported. Permeability had a linear relation to the inverse of the square root of molecular weight. This is the expected relationship for a diffusion process dependent upon molecular weight. The differential mass selectivity coefficients for lumbar and cranial dura were calculated; they were similar at 0.8 and 0.9. This was greater than for diffusion in simple liquids, but much less than that for biological lipid membranes. This suggests that the low rates of diffusion are a property of the thickness of the dura rather than any inherent impermeability. A simple model for the dural transfer of drugs is described, and applied to narcotics. Its purposes were to suggest: the factors involved in the dural transfer of drugs; the physicochemical properties of drugs relevant to their dural transfer; worthwhile measurements in future studies. The model indicates that drug molecular weight and rate of absorption are important determinants of the efficiency of dural transfer. Low molecular weight and slow absorption produce high dural transfers. When applied to narcotics, these factors could produce a difference of up to an order of magnitude in the amount transferred directly across the dura.

Absorption↗
PubMed1982

Acute i.v. Methadone Kinetics in Man: relationship to chronic studies.

Twenty-six patients were given methadone 10 mg i.v. to obtain acute human kinetics. Plasma methadone concentrations from separate 3- and 6-h studies were measured by radioimmunoassay. Kinetic parameters derived from triexponential NONLIN analysis showed that T1/2 alpha and T1/2 beta were 2 and 30 min respectively; no reliable estimate for T1/2 gamma could be obtained. The clearance was estimated as 149 /+- 62 and 163 /+- 49 ml min-1 in the 3- and 6-h studies respectively. These values are compared with those published for chronic administration. The difficulties in determining accurate terminal half-life and clearance values from short duration studies are discussed; these difficulties are accentuated by the long terminal half-life of methadone. Appropriate estimates of clearance may be derived from an acute short duration study provided that the average of triexponential fits to individual patients data is used, even when data extend from only 3h. As might be anticipated, no analysis produced appropriate terminal half-life values for this drug.

Adult↗
PubMed1982

Sublingual buprenorphine used postoperatively: ten hour plasma drug concentration analysis.

1 A 10 h study of plasma drug concentrations of the opiate buprenorphine after use was designed because a previous 3 h study had shown that peak plasma drug concentrations in some patients had not occurred by 3 h after the sublingual dose. 2 Fifteen postoperative patients were studied: at 3 h after a 0.3 mg intravenous dose five patients received a sublingual preparation of 0.4 mg of buprenorphine, five 0.8 mg of buprenorphine and five placebo. Plasma drug concentrations of buprenorphine were measured by specific radioimmuno-assay. 3 Plasma drug concentrations after sublingual buprenorphine were significantly higher than those in the placebo group by 1 h. They remained significantly higher over the succeeding nine hours. The mean time to peak plasma drug concentration was about 200 min in both the 0.4 mg and 0.8 mg groups (range 90-360 min). The plasma drug concentrations in the 0.8 mg group were approximately twice those in the 0.4 mg group; the ratio of the relative systemic availabilities was similarly 1.8:1. The absolute systemic availability was estimated at about 55% for both groups. Uptake of buprenorphine from the sublingual site was essentially complete by 5 h after the dose was given. 4 The implications for the timing of sublingual doses in clinical use are discussed.

Aged↗
PubMed1982

A controlled comparison of the effects of extradural diamorphine and bupivacaine on plasma glucose and plasma cortisol in postoperative patients.

The effects of an extradural narcotic, diamorphine, and of an extradural local anesthetic, bupivacaine, on postoperative responses of plasma glucose and cortisol levels following surgery were investigated in 20 fit women undergoing major gynecologic operations. The operations were conducted with morphine premedication and extradural local anesthetic with nitrous oxide, oxygen, and halothane. After surgery the patients were given either further extradural local anesthetic or 5 mg of extradural diamorphine. After surgery plasma glucose and plasma cortisol concentrations decreased in patients given extradural diamorphine, but increased in those given extradural local anesthetic. The differences between the groups were statistically highly significant (p less than 0.05) for both glucose and cortisol. The effects on metabolic responses to surgery produced by a small (5 mg) dose of diamorphine injected into the extradural space suggest a local action of the narcotic at the level of the spinal cord. Only very large intravenous doses of narcotics have previously been shown to suppress these responses.

Adult↗
PubMed1981

Sublingual buprenorphine used postoperatively: clinical observations and preliminary pharmacokinetic analysis.

1 Buprenorphine is a long-acting opiate analgesic. This study was designed to investigate the pharmacokinetics of this drug when given by the sublingual route to ten postoperative patients. Plasma levels of buprenorphine were measured by a specific radioimmunoassay. 2 Plasma levels of the drug following sublingual administration of 0.4 mg showed an apparent delay in absorption and then rose slowly to reach low but significant levels by 3 h. There was considerable variation in the time at which peak levels were achieved. The average systemic availability of the drug by this route was estimated to be 30% by 3 h. 3 Analgesic efficacy and duration of sublingual buprenorphine were assessed using demand analgesia. The analgesia was of about 9 h duration, similar to that achieved by parenteral administration of 0.3 mg of the drug to an equivalent group of patients. The sublingual dose caused a significant fall in the postoperatively elevated group of patients. The sublingual dose caused a significant fall in the postoperatively elevated plasma glucose, and prevented any further rise in plasma cortisol. 4 Reasons for the efficacy of the sublingual route are discussed and it is suggested that this route may be particularly appropriate for highly lipophilic drugs like buprenorphine.

Analgesia↗
PubMedDate not supplied

Screening for cerebral palsy in preterm infants: delay criteria for motor milestone attainment.

We evaluated the efficacy of various delay criteria (12.5%, 25%, 37.5%, 5%, 50% delay) for motor milestone attainment to screen a sample of 173 high-risk preterm infants with gestational age < 32 weeks who had been sequentially followed for 18 to 24 months. Sensitivities were best with 12.5% and 25% delays, but specificities and positive predictive values were relatively lower. Since societal resources for evaluation and treatment of cerebral palsy are limited, the excellent specificities (81% to 95%) and positive predictive values (48% to 85%) with 50% delay are more important than the somewhat lower sensitivities, especially since milestones involve a multistep screening process. Screening preterm infants by obtaining a history of motor milestone attainment with each child care visit, correcting for degree of prematurity, and using a 50% delay criteria is a practical, inexpensive method of identifying infants at highest risk of cerebral palsy.

Cerebral Palsy↗
PubMedDate not supplied

Perceptions of the limit of viability: neonatologists' attitudes toward extremely preterm infants.

Although recent technologic advances have dramatically improved the survival of preterm infants, little information exists regarding the attitudes of neonatologists toward their smallest patients, infants born at the "limit of viability." In this pilot study we sent a single mailing of a 25-question survey designed to provide information about the medical treatment of extremely preterm infants (< 22 to 27 weeks' gestational age) to 3056 neonatologists practicing in the United States in September 1992. The 1131 (37%) respondents were well distributed geographically and by nature of practice (i.e., academic, academic affiliate, and community hospitals). Most of the respondents counseled parents that all infants < or = 22 weeks' gestational age die and that at least 75% of infants born at 23 weeks' gestation die. Only for infants born at > or = 26 weeks' gestational age did most of the neonatologists counsel parents that mortality is < or = 50%. Nonintervention or compassionate care in the delivery room was believed to be appropriate for infants less than 23 weeks' gestational age by virtually all neonatologists, by 52% of respondents for infants 23 weeks' gestational age, and by only 1% of respondents for infants 25 weeks' gestational age. Approximately two thirds of neonatologists considered parental wishes regarding resuscitation, and one quarter considered parental parity/fertility history in their medical decision making for infants born at 23 to 24 weeks' gestation. If an infant who had been previously resuscitated decompensated in spite of maximal medical treatment, most of the neonatologists were not willing to provide full resuscitation for infants born at any gestation less than 27 weeks. However, the number of neonatologists who would actively encourage withdrawal of support in a decompensating infant decreased markedly for infants born at > or equal 25 weeks' gestation. Neonatologists who responded to this survey in 1992 considered 23 to 24 weeks of gestation the limit of viability and had great concerns regarding medical decision making for these infants.

Data Collection↗
PubMedDate not supplied

Conceptualization, measurement, and use of gestational age. I. Clinical and public health practice.

Despite its importance for both clinical and public health practice and the considerable effort spent during the past three decades to develop alternative estimation methods, the measurement of gestational age on both the individual and population level continues to be problematic. The availability of alternative approaches for the estimation of gestational age has to some extent obscured the basic differences in the conceptualization of these measures and influenced our current state of thinking about gestational age. As the evidence grows that these alternative gestational age estimation measures do not precisely correspond with one another, controversies have arisen regarding which method is most accurate. In the search for a single gestational age "gold standard," the potentially valuable information that these alternative measures may provide when used in combination should not be overlooked.

Female↗
PubMedDate not supplied

Impact of the perception of viability on resource allocation in the neonatal intensive care unit.

OBJECTIVE: To understand how neonatologists' perceptions of viability impact their willingness to recommend or provide medical interventions for infants born at 23 to 24 weeks' gestation. STUDY DESIGN: A 25-question survey mailed to 3056 neonatologists in the United States in 1992 yielded 1131 responses. Seven hundred seventy-five (775 of 1131, 69%) reported they believed that the lower limit of viability was 23 to 24 weeks' gestation. These respondents were asked if they were willing to recommend or provide a series of medical interventions for infants born at 23 and 24 weeks' gestation. RESULTS: Most respondents would provide ventilation (82% and 95%) and surfactant (62% and 78%) for infants born at 23 and 24 weeks' gestation, respectively. The respondent's prediction of <100% mortality, infant factors, and parental wishes were significant predictors of willingness to resuscitate infants born at 23 weeks' gestation. CONCLUSION: There is considerable variation among neonatologists in their willingness to recommend or provide medical interventions for infants born at 23 to 24 weeks' gestation.

Attitude of Health Personnel↗