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Biomedical subjects

M C Allen

Publications and source records attributed to M C Allen.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The evolution of primitive reflexes in extremely premature infants.

A longitudinal study describes the pattern of appearance of eight primitive reflexes in a population of 47 viable extremely premature infants, beginning as early as 25 wk postconceptional age (PCA). Infants were examined weekly, from 1 wk of age until discharge from the neonatal intensive care unit. Primitive reflexes were graded as to completeness and intensity of response. Three patterns emerged: the upper and lower extremity grasp reflexes were present in all premature infants, from 25 wk and beyond, the Moro, asymmetric tonic neck reflex and Galant (lateral trunk incurvature reflex) were present in some premature infants as early as 25 wk PCA, and in the majority by 30 wk PCA, and the lower extremity placing, positive support, and stepping were occasionally present prior to 30 wk PCA, yet were not uniformly present and/or complete even at term. In each case, the primitive reflex became stronger, more complete, more consistently elicited and more prevalent with increasing postconceptional age. The pattern of primitive reflexes in the premature infant at term (40 wk PCA) is similar to that of full-term newborns. Sequential assessment of the primitive reflexes may be a useful method of evaluating extremely premature infants prior to term.

Birth Weight

Medical complications of prematurity.

The improved survival of extremely premature infants has generated intense interest in the quality of life of the survivors. This review focuses on the major long-term complications of prematurity (developmental disability, retinopathy of prematurity, chronic lung disease) and concludes with an overview of the broader spectrum of morbidity. Severe impairment (cerebral palsy, mental retardation, retrolental fibroplasia, severe chronic lung disease) fortunately occurs in a small proportion of survivors. However, the prevalence of the lesser morbidities (minimal cerebral dysfunction/learning disability, poor growth, postneonatal illnesses, rehospitalization) is less clearly defined. These problems all have an impact on families, and on medical and educational services.

Attention Deficit Disorder with Hyperactivity

Renal failure and the use of morphine in intensive care.

Intravenous morphine infusions were given to 20 patients in the intensive-care unit to provide sedation and analgesia. In 10 of the patients renal impairment was already present or developed during intensive care. Plasma morphine concentrations for a given dose of morphine and morphine clearance depended on renal function; dose-related plasma morphine concentrations rose as renal function deteriorated. Reduced morphine clearance leads to increased elimination half-life of the drug, and neurological impairment caused by unrecognised high concentrations of morphine could result in an incorrect diagnosis of cerebral damage in patients in intensive care.

Adult