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Biomedical subjects

M C Allen

Publications and source records attributed to M C Allen.

At least 55 records · Page 3Linked to original sources
PubMed1993

The limit of viability--neonatal outcome of infants born at 22 to 25 weeks' gestation.

BACKGROUND: With improved survival of preterm infants, questions have been raised about the limit of viability. To provide better information and counseling for parents of infants about to be delivered after 22 to 25 weeks' gestation, we evaluated the mortality and neonatal morbidity of preterm infants born at these gestational ages. METHODS: We studied retrospectively all 142 infants born at 22 to 25 weeks' gestation (as judged by best obstetrical estimate) from May 1988 through September 1991 in a single hospital. Mortality in the first six months, including stillbirths, and neonatal morbidity (i.e., the presence of intracranial pathologic conditions, chronic lung disease, and retinopathy of prematurity) were analyzed. RESULTS: Fifty-six infants (39 percent) survived for six months. Survival improved with increasing gestational age; none of 29 infants born at 22 weeks' gestation survived, as compared with 6 of 40 (15 percent) born at 23 weeks, 19 of 34 (56 percent) born at 24 weeks, and 31 of 39 (79 percent) born at 25 weeks. There were seven stillbirths at 22 weeks' gestation and four stillbirths at 23 weeks. The more immature the infant, the higher the incidence of neonatal complications as determined by the number of days of mechanical ventilation, the length of the hospital stay, and the presence of retinopathy of prematurity, periventricular or intraventricular hemorrhage, or periventricular leukomalacia. Only 2 percent of infants born at 23 weeks' gestation survived without severe abnormalities on cranial ultrasonography, as compared with 21 percent of those born at 24 weeks and 69 percent of those born at 25 weeks. CONCLUSIONS: We believe that aggressive resuscitation of infants born at 25 weeks' gestation is indicated, but not of those born at 22 weeks. Whether the occasional child who is born at 23 or 24 weeks' gestation and does well justifies the considerable mortality and morbidity of the majority is a question that should be discussed by parents, health care providers, and society.

Female↗
PubMed1993

The high-risk infant.

A large number of infants are born each year with biologic or environmental risk factors that put them at increased risk for developmental disability, although most do not go on to have major disabilities. Some risk factors, for example, intraparenchymal hemorrhage, periventricular cysts, encephalomalacia, and abnormal neurodevelopmental examination, carry a much higher risk of developmental disability than others. There is much overlap among risk factors, and infants with multiple risk factors generally have a greater risk of disability than infants with just a single risk factor. All high-risk infants should receive careful pediatric follow-up that includes developmental screening, but efficient use of so far quite limited resources argues for selection of the highest risk infants for comprehensive developmental follow-up or early intervention programs. A system of tracking and monitoring high-risk infants during infancy and childhood would allow for early identification of developmental delay and appropriate referral for community resources.

Child, Preschool↗
PubMed1993

Effect of hyperbaric and normobaric oxygen on pulmonary endothelial cell function.

The effect of prior exposure to raised partial pressures of oxygen on pulmonary endothelial cell function was assessed in the isolated perfused rat lung preparation. Prolonged exposure to both 1 bar (48 h) and 2.5 bar (11 h) of oxygen caused pulmonary edema and dyspnea. Exposure to 1 bar oxygen for 48 h (approximately 0.66 lethal duration) caused a decrease in pulmonary 5-hydroxytryptamine (5-HT) clearance, suggesting compromised endothelial cell integrity. No change in 5-hydroxy-indole acetic acid (5-HIAA) efflux was noted. However, exposure to 2.5 bar of oxygen for up to 11 h (approximately 0.85 lethal duration) did not decrease pulmonary 5-HT clearance, implying that endothelial cell integrity was not compromised after this oxygen exposure. Exposure to 2.5 bar oxygen resulted in a reduction in 5-HIAA efflux, possibly indicating a decrease in metabolism of cleared 5-HT. The absence of a demonstrable impairment of 5-HT clearance during the development of pulmonary toxicity on exposure to 2.5 bar of oxygen suggests that there may be important differences in pathologic mechanisms in response to oxygen exposure at partial pressures 1 and 2.5 bar.

Animals↗
PubMed1992

Using gross motor milestones to identify very preterm infants at risk for cerebral palsy.

The authors evaluated the efficacy of 10 gross motor milestones to screen for cerebral palsy in 173 high-risk, very preterm infants (less than or equal to 32 weeks gestation) followed for 18 to 24 months. Correcting for preterm birth and using population norms led to a better improvement in specificity and positive predictive values; race-specific norms did not contribute significantly. Incorporating a history of milestone attainment into the routine during sequential office visits will help health-care providers to monitor the development of high-risk infants.

Cerebral Palsy↗
PubMed1991

Estimation of gestational age: implications for developmental research.

Recent research in neonatology and obstetrics has challenged the validity of standard gestational age assessment methods. Length of gestation is a central component of research on the development of at-risk infants, yet issues concerning accuracy of this information are rarely addressed by developmental researchers. This article reviews prenatal and postnatal methods of gestational age estimation and evaluates implementation of this information in research. Recommendations concerning the assignment of gestational age in the perinatal period and the use of age correction for preterm infants are offered.

Female↗
PubMed1990

Gross motor milestones in preterm infants: correction for degree of prematurity.

The age of gross motor milestone attainment and how it is affected by degree of prematurity at delivery were studied in 100 high-risk, preterm (less than 32 weeks) infants with normal motor outcome. We calculated the mean age of attainment for each milestone on the basis of chronologic age from the date of delivery and term age equivalent, correcting for degree of preterm delivery. Half of these preterm infants were male; 70% were black. The infants were compared with a population of normal infants born at term. In this very preterm population, there were no consistent sex differences, but black infants generally attained motor milestones before white infants. For each motor milestone, regardless of gender or race, the mean term age equivalents of attainment for very preterm infants closely approximated the mean ages of milestone attainment for term infants, whereas the mean chronologic ages were delayed 2 or 3 months. We conclude that very preterm infants can be expected to demonstrate sequential gross motor development at a rate expected for degree of prematurity. Chronologic age is not a valid measurement scale to use in determining motor delay in very preterm infants.

Aging↗
PubMed1990

Estradiol-induced increase in number of gonadotropin-releasing hormone receptors in cultured ovine pituitary cells.

Primary cultures of ovine pituitary cells were used to characterize the effects of estradiol on number of GnRH receptors. Number of GnRH receptors was determined by the specific binding of a saturating dose of a radioiodinated GnRH analog. Estradiol stimulated an increase in number of GnRH receptors that was dose-dependent and had a time course similar to that observed in vivo. Estradiol at concentrations from 0.4 to 40 nM increased (p less than 0.05) the number of GnRH receptors relative to controls. Numbers of GnRH receptors were increased (p less than 0.05) from 8 to 24 h after addition of estradiol, with a maximum occurring at 12 h. Actinomycin D (10 micrograms/ml) and cycloheximide (25 micrograms/ml) prevented the estradiol-induced increase in number of GnRH receptors at 12 h, suggesting that both mRNA transcription and protein synthesis are required for this action of estradiol. Cortisol, progesterone, and tamoxifen had no direct effect on number of GnRH receptors. However, tamoxifen blocked the estradiol-induced increase in number of GnRH receptors. There appeared to be some synergism between estradiol and progesterone since the number of receptors in cells treated with both steroids tended (p less than 0.1) to be greater than after treatment with estradiol alone. Thus, estradiol elicits an increase in the number of pituitary receptors for GnRH that is time- and dose-dependent, specific, and requires both mRNA transcription and protein synthesis. This effect of estradiol probably plays a role in increasing the sensitivity of the pituitary to GnRH prior to the preovulatory surge of LH.

Animals↗
PubMed1990

Tone and reflex development before term.

The evolution of tone and reflexes from 25 weeks postmenstrual age (gestational age plus chronologic age) to term in a population of 42 surviving infants is described. The infants were born in 1983 at the Johns Hopkins Hospital, had birth weights less than 1300 g, were examined weekly until neonatal intensive care unit discharge, and did not develop cerebral palsy. Lower-extremity flexor tone was first detectable at 29 weeks post-menstrual age by the popliteal angle and heel to ear maneuvers. Flexor tone, recoil, and hyperreflexia were all noted 2 to 3 weeks earlier in the lower extremities (33 to 35 weeks) than in the upper extremities (35 to 37 weeks). Hip tone (35 to 37 weeks) followed knee flexor tone, but preceded shoulder tone (37 to 38 weeks). Trunk tone on ventral suspension emerged closer to term (36 to 40 weeks), and more than half of infants evaluated at term continued to demonstrate head lag when pulled to sitting position. The emergence of the primitive and pathologic reflexes reflects (both in timing and pattern) the evolution of tone: development of the reflexes in the lower extremities precedes that of those in the upper extremities, and development of the distal reflexes precedes that of the proximal. Maturation of tone, deep tendon reflexes, pathologic reflexes, and primitive reflexes occurs in an orderly, sequential manner, with a well-defined pattern: caudocephalad (lower extremities to upper extremities) and centripetal (distal to proximal).

Child Development↗
PubMed1990

Infant stimulation curriculum for infants with cerebral palsy: effects on infant temperament, parent-infant interaction, and home environment.

To assess the effects of intervention in cerebral palsy, 48 infants 12 to 19 months of age, with mild to severe spastic diplegia, were randomly assigned to receive either 6 months of infant stimulation followed by 6 months of physical therapy (test group) or 12 months of neurodevelopmental physical therapy (contrast group). The infant stimulation protocol consisted of cognitive, motor, sensory, and language activities. Outcome was assessed after 12 months by using Carey Infant Temperament Questionnaire subscores (activity, rhythmicity, adaptability, approach, threshold, intensity, mood, distractibility, and persistence); Roth Mother-Child Relationship Evaluation subscores (acceptance, overprotection, overindulgence, rejection); and Home Observation for Measurement of the Environment subscores (maternal responsiveness, avoidance of restriction and punishment, organization of environment, play materials, maternal involvement, and variety of daily stimulation). Motor and cognitive outcomes suggesting advantage for the test group have been reported previously. After 12 months of intervention, mothers with infants in the contrast group showed a greater improvement in emotional and verbal responsiveness as measured by the Home Observation for Measurement of the Environment (mean score change in control group = 1.2, test group = 0.3 P less than .04). None of the 19 other measures differed significantly between treatment groups in change from baseline. This study demonstrates no short-term systematic effect on temperament, maternal-infant interaction, or home environment attributable to the inclusion of an infant stimulation curriculum in an intervention program for infants with spastic diplegia. It suggests that motor and cognitive advantages associated with infant stimulation are not mediated by measurable changes in the psychosocial variables studied.

Cerebral Palsy↗
PubMed1989

Home oxygen therapy for chronic lung disease in extremely low-birth-weight infants.

Chronic lung disease that requires prolonged oxygen therapy commonly complicates the recovery of extremely low-birth-weight infants (less than 1000 g). We report follow-up data through 18.5 +/- 0.9 (mean +/- SEM) months of age in 30 extremely low-birth-weight infants (birth weight, 783 +/- 24 g; gestational age, 26.0 +/- 0.3 weeks) who were discharged home receiving supplemental oxygen. Oxygen was prescribed to maintain arterial oxygen saturation at 95% or greater. At discharge, postconceptional age was 40.5 +/- 0.6 weeks, and weight was 2220 +/- 50 g. Duration of home oxygen therapy was 4.5 +/- 0.5 months. The mean weight percentile increased from less than 5 to 23 between discharge and the last follow-up. All infants survived; only 6 required hospitalization for acute medical illnesses. We conclude that carefully supervised home oxygen therapy permits the safe early discharge of selected extremely low-birth-weight infants with chronic lung disease.

Body Weight↗
PubMed1989

Renin inhibitors. Synthesis of transition-state analogue inhibitors containing phosphorus acid derivatives at the scissile bond.

The synthesis of five amino phosphorus derivatives, 1a-e, is described. The derivatives were incorporated into a series (18) of analogues of the 5-14 portion of angiotensinogen, in most cases at the scissile Leu-Val bond. The resultant compounds were tested in vitro for their ability to inhibit human plasma renin. Replacement of the scissile bond with the phosphinic analogue of Leu10-Val11 (1b) gave the most potent inhibitors, having IC50 = 7.5 x 10(-8) M for H-Pro-His-Pro-Phe-His-(1b)-Ile-His-Lys-OH and IC50 = 1.0 x 10(-7) M for Z-Arg-Arg-Pro-Phe-His-(1b)-Ile-His-NH2. The shorter phosphonic acid sequence Z-Pro-Phe-His-(1d) retained biological activity with an IC50 = 6.4 x 10(-6) M.

Amino Acids↗
PubMed1989

Neonatal neurodevelopmental examination as a predictor of neuromotor outcome in premature infants.

There was a marked correlation (P less than .000001) between neonatal neurodevelopmental examination results and neuromotor outcome at 1 year of age or older in 210 high-risk premature infants (mean birth weight 1,107 g, mean gestational age 28.4 weeks). This neonatal examination consisted of assessment of posture, extremity and axial tone, deep tendon reflexes, pathologic reflexes, primitive reflexes, symmetry, oromotor function, cranial nerve function, auditory and visual responses, and behavior. Premature infants whose neonatal neurodevelopmental examination results were abnormal had significantly higher incidences of both cerebral palsy (38% v 6%, P less than .000001) and minor neuromotor dysfunction (27% v 13%, p less than .05) than did premature infants whose examination results were normal. This correlation continued to be highly significant even with the analysis of subgroups (infants born at or before 27 weeks' gestation, infants with chronic lung disease discharged with oxygen supplementation, infants with periventricular hemorrhage) and when a variety of individual perinatal, demographic, and social variables were used as controls. Normal or nearly normal neonatal neurodevelopmental examination results can be used to reassure parents of high-risk premature infants. Although abnormal neonatal neurodevelopmental examination results cannot be used to diagnose handicap in premature infants, they can be used to select a group of high-risk infants who should be carefully monitored during infancy and childhood.

Cerebral Palsy↗
PubMed1988

The effects of physical therapy on cerebral palsy. A controlled trial in infants with spastic diplegia.

Legislatively mandated programs for early intervention on behalf of handicapped infants often stipulate the inclusion of physical therapy as a major component of treatment for cerebral palsy. To evaluate the effects of physical therapy, we randomly assigned 48 infants (12 to 19 months of age) with mild to severe spastic diplegia to receive either 12 months of physical therapy (Group A) or 6 months of physical therapy preceded by 6 months of infant stimulation (Group B). The infant-stimulation program included motor, sensory, language, and cognitive activities of increasing complexity. Masked outcome assessment was performed after both 6 and 12 months of therapy to evaluate motor quotient, motor ability, and mental quotient. After six months, the infants in Group A had a lower mean motor quotient than those in Group B (49.1 vs. 58.1, P = 0.02) and were less likely to walk (12 vs. 35 percent, P = 0.07). These differences persisted after 12 months of therapy (47.9 vs. 63.3, P less than 0.01, and 36 vs. 73 percent, P = 0.01, respectively). We noted no significant differences between the groups in the incidence of contractures or the need for bracing or orthopedic surgery. Group A also had a lower mean mental quotient than Group B after six months of therapy (65.6 vs. 75.5, P = 0.05). The routine use of physical therapy in infants with spastic diplegia offered no short-term advantage over infant stimulation. Because of the limited scope of the trial, our conclusions favoring infant stimulation are preliminary. The results suggest that further study of the effects of both physical therapy and infant stimulation is indicated.

Cerebral Palsy↗
PubMed1988

Synthesis of somatostatin analogs resistant to the action of trypsin.

The synthesis of a series of octapeptides based on the somatostatin analog cyclo(-Asn-Phe-Phe-D-Trp-Lys-Thr-Phe-Gaba-) containing the substitutions [Aap9], [D-Lys9], [L-Trp8, D-Lys9], [L-Orn9] and [D-aThr10] is reported. The analogs were designed and have been shown to inhibit proteolysis at the proposed (1) primary cleavage site between Lys9-Thr10 and thereby increase their stability to enzymic attack.

Amino Acid Sequence↗
PubMed1987

Analysis of morphine and its major metabolites by differential radioimmunoassay.

The analysis of morphine, morphine-3-glucuronide (M-3-G) morphine-6-glucuronide (M-6-G) by differential radioimmunoassay using iodinated label and three different antisera is described. These methods were used to measure concentrations of morphine and its conjugated metabolites in human plasma, over a 3-h period, following a single 10 mg intravenous dose. In 13 patients peak concentrations of M-3-G (739 nmol/L +/- 73.7 SEM) were approximately 10 times greater than those of M-6-G (71.3 nmol/L +/- 8.6 SEM). Times to reach these peaks were similar for both metabolites. Decay of morphine from plasma followed a biexponential pattern with a mean terminal half-life of 59.3 min (+/- 8.1 SEM, n = 11). Accurate determination of the half-lives of the glucuronides was not possible due to the short sampling period, but M-6-G seemed to have a similar half-life to morphine, while M-3-G was eliminated more slowly.

Aged↗
PubMed1986

Assessment of early auditory and visual abilities of extremely premature infants.

The early auditory and visual abilities of 47 extremely premature infants (31 born less than or equal to 28 weeks gestation) were assessed with a bell, a light and an optokinetic nystagmus drum. All the infants altered to the bell and blinked to the light from 25 weeks postconceptional age (PCA) and beyond. A few infants at first had only a change in heart rate or respiratory rate in response to the bell, or required a high-intensity light to elicit a blink. The majority appeared to habituate to the bell and light during their first examination at one week of age. None of the infants blinked in response to a threatening gesture. Optokinetic nystagmus could be elicited as early as 30 weeks PCA, could be elicited in the majority by 36 weeks PCA, and universally by term (40 weeks PCA). The responses of 15 fullterm newborn infants were not significantly different from those of the preterm infants at term. Alerting to a bell, blinking to light and habituation to both are simple bedside maneuvers for assessing extremely premature infants less than 30 weeks PCA. Optokinetic nystagmus may be useful in assessing the visual abilities of premature infants closer to term.

Acoustic Stimulation↗
PubMed1986

Radioimmunoassay of buprenorphine with iodine label: analysis of buprenorphine and metabolites in human plasma.

Quantitative analysis of potent opiate drugs in plasma by radioimmunoassay is potentially inaccurate because of the occurrence of cross-reacting metabolites. This paper describes the chemical synthesis of buprenorphine-3-O-glucuronide, a metabolite of buprenorphine, and an extraction procedure coupled with radioimmunoassay which allows the sensitive and specific measurement of buprenorphine using an iodinated buprenorphine derivative. The measurement of extracted and unextracted samples using two different antisera allowed investigation of the metabolism of buprenorphine. In four patients who had taken sublingual buprenorphine for at least one month, N-dealkyl buprenorphine was present in similar concentrations to those of buprenorphine, while buprenorphine-3-O-glucuronide was present in two to three times those concentrations.

Administration, Oral↗