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Biomedical subjects

M C McCormick

Publications and source records attributed to M C McCormick.

At least 37 records · Page 2Linked to original sources

The bacteriophage T4 DNA packaging apparatus targets the unexpanded prohead.

During the morphogenesis of the bacteriophage T4 capsid, a conformational change of the major head shell protein, gene product (gp) 23, causes a 50% increase in capsid volume. This expansion is required to accept the full length chromosome and, therefore, must precede the completion of packaging. The expanded shell is thinner and more stable than its precursor, and can bind accessory proteins which further stabilize it. In phages lambda, T3, T7 and P22, expansion occurs during DNA packaging. However, in T4, expanded capsids can package DNA in vitro and expansion occurs in cells infected with packaging-defective mutants, raising the possibility that expansion and packaging are not coupled. Proteolytically mature gp23 (gp23*) in unexpanded proheads is sensitive to chymotrypsin cleavage at Phe154-Ser155, creating a 38 kDa peptide, while gp23* in expanded capsids is refractory to the protease. We used an expansion assay based on this protease sensitivity to determine the expansion status of capsids isolated from various packaging-defective mutants with the goal of determining whether packaging and expansion are normally linked. In infections at 20 degrees C, mutants in the packaging enzymes gp16 and gp17 fail to expand. However, in gene 49(-) mutants, which initiate packaging but fail to complete it, expansion is complete. Thus, packaging drives expansion, and the unexpanded prohead is the substrate for the packaging reaction. We also show that expansion observed in 16(-) and 17(-) infections at 37 degrees C is linked to aberrant packaging. Capsids produced at 15 minutes, when no packaging can be detected, never expand. However, by 35 minutes when aberrant packaging begins, so does expansion of freshly made capsids. Thus in all cases now examined, expansion is only observed in vivo when DNA packaging is also occurring, indicating that these two processes are coupled.

Bacteriophage T4↗

Health care use of 3-year-old low birth weight premature children: effects of family and neighborhood poverty.

OBJECTIVE: The objective of this study was to examine the effect of family and neighborhood income on health care use of young children born prematurely and of low birth weight (N = 619). DESIGN: A birth cohort was enrolled in a clinical randomized trial of early childhood educational and family services. SETTINGS/PARTICIPANTS: Infant Health and Development Program provided a sample of low birth weight premature infants stratified by clinical site, birth weight, and treatment group. Maternal reports of health care use, family income, and heath insurance were obtained at 12, 24, and 36 months of corrected age. Neighborhood income was based on census tract residence at birth. MAIN OUTCOME MEASURES: Maternal reports of hospitalizations, doctor visits, and emergency department visits were used; data were averaged over the child's first 3 years of life. RESULTS: Children from poorer families were more likely to be hospitalized and to have more emergency department visits than were children from more affluent families. Residence in poor and middle-income neighborhoods was associated with more emergency department visits than residence in affluent neighborhoods. Families in middle-income neighborhoods reported more doctor visits than families in poor or affluent neighborhoods. CONCLUSION: Neighborhood residence influences health care use by poor and nonpoor families and by insured and uninsured families. The use of the emergency department for low birth weight premature children in middle-income and poor neighborhoods is discussed.

Child, Preschool↗

Restricting access to neonatal intensive care: effect on mortality and economic savings.

OBJECTIVE: Neonatal intensive care for very low birth weight (VLBW) infants is expensive, and cost-containment policies have been proposed that would restrict care according to birth weight. We examined the potential reduction in neonatal intensive care unit (NICU) VLBW charges and the impact on survivors if care were not offered to infants of extremely low birth weights or gestational ages. DESIGN: We reviewed hospital charges for a retrospective cohort of VLBW infants born during the 5-year period from 1988 to 1992. Local charges and survival statistics were applied to national VLBW birth statistics to estimate the national effects of a birth weight-based rationing program. SETTING: A high-risk perinatal referral center. PATIENTS: A consecutive sample of 1361 VLBW infants was tracked from birth to discharge home, transfer to a level II nursery, or death. MAIN OUTCOME MEASURES: Hospital charges and survival. RESULTS: Mean charges per survivor ranged from $250 654 for infants weighing <500 g to $74 101 for those weighing 1000 to 1500 g. Policies denying care to infants born at <500, 600, or 700 g would lead to total NICU care savings of 0.8%, 3.2%, and 10.3%, respectively. Applying the local birth weight-specific survival rates, such policies applied nationally would not have offered care to 136, 575, and 2689 potential survivors annually. Birth weight-based rationing schemes also are shown to increase further the racial disparity of NICU deaths. CONCLUSIONS: To attain significant reduction in NICU charges, policies offering care to the larger or more mature VLBW infants only will result in denying care to many infants who would otherwise survive.

Birth Weight↗

Declining severity adjusted mortality: evidence of improving neonatal intensive care.

OBJECTIVES: Declines in neonatal mortality have been attributed to neonatal intensive care. An alternative to the "better care" hypothesis is the "better babies" hypothesis; ie, very low birth weight infants are delivered less ill and therefore have better survival. DESIGN: We ascertained outcomes of all live births <1500 g in two prospective inception cohorts. We estimated mortality risk from birth weight and illness severity on admission and measured therapeutic intensity. We calculated logistic regression models to estimate the changing odds of mortality between cohorts. PATIENTS AND SETTING: Two cohorts in the same two hospitals, 5 years apart (1989-1990 and 1994-1995) (total n = 739). RESULTS: Neonatal intensive care unit mortality declined from 17.1% to 9.5%, and total mortality declined from 31.6% to 18.4%. Cohort 2 had lower risk (higher birth weight, gestational age, and Apgar scores and lower admission illness severity for newborns >/=750 g). Risk-adjusted mortality declined (odds ratio, 0.52; confidence interval, 0.29-0. 96). One third of the decline was attributable to "better babies" and two thirds to "better care." Use of surfactant, mechanical ventilation, and pressors became more aggressive, but decreases in monitoring, procedures, and transfusions resulted in little change in therapeutic intensity. CONCLUSIONS: Mortality decreased nearly 50% for infants <1500 g in 5 years. One third of this decline is attributable to improved condition on admission that reflects improving obstetric and delivery room care. Two thirds of the decline is attributable to more effective newborn intensive care, which was associated with greater aggressiveness of respiratory and cardiovascular treatments. Attribution of improved birth weight specific mortality solely to neonatal intensive care may underestimate the contribution of high-risk obstetric care in providing "better babies."

Hospital Mortality↗

The contribution of neighborhood and family income to developmental test scores over the first three years of life.

The effects of neighborhood and family income and family risk factors on developmental test scores at ages 1 through 3 are examined using a subsample (N = 347) from the Infant Health and Development Program. Beneficial effects of low numbers of risks were found for scores at ages 1 through 3. Family poverty was associated with lower scores at ages 2 and 3. Neighborhood affluence was associated with higher scores at age 3. The family risks-test score association at ages 1 through 3 and family income-test score association at ages 2 and 3 were mediated by home environment. Mediated effects were stronger for family income-test score associations at age 3 than for neighborhood income. Moderating effects of family risk on family and neighborhood income effects revealed an interaction between family poverty and risks for scores at age 3. Explanations for the early links between family risks and test scores and the later links between income and test scores are discussed.

Child Development↗

Failure to screen newborns for inborn disorders: a potential consequence of changes in newborn care.

OBJECTIVES: To determine how changes in the structure of the hospital care of infants, such as shortened post-natal stays, affect the completeness of newborn screening. DESIGN: Cohort. SETTING: Two large maternity hospitals. PARTICIPANTS: 8751 consecutive births at the study hospitals during 1993. MAIN OUTCOME MEASURE: The completeness of initial specimen collection and processing as determined by matching of birth and screening records. RESULTS: At least one specimen was received by the screening program for 8675 (99.1%) of the births. Most non-screened patients (71/76, 93%) had been admitted to the neonatal intensive care unit (NICU). Of these, 53/71 (75%) were low birth weight infants who died within 48 h of birth. Even after excluding these non-survivors, NICU patients were 37 times more likely to be unscreened than their healthy counterparts (22 vs. 0.6 per 1000 infants, 95% C.I. 12.8, 92.8 P < 0.01). A common characteristic of non-screened NICU survivors, (12/18) was interhospital transfer for sub-specialty care. Among patients in the healthy-baby nursery, early discharge (i.e. < 24 h of age) accounted for 2/5 (40%) of the cases of non-screening. The non-screening rate among patients discharged early was 25 times higher than for those discharged after 24 h (9.8 vs. 0.4 per 1000 infants, 95% C.I. 4.2, 149 P < 0.01). CONCLUSIONS: Although the overall rate of screening was high, NICU patients, especially those requiring transfer, are disproportionately at risk for non-screening. Early discharge of healthy newborns was also significantly associated with non-screening. This latter finding is of special importance given the current trend toward shorter hospital stays for newborns. Increased attention to ensuring the collection of specimens from these two high-risk populations is warranted.

Cohort Studies↗

Results at age 8 years of early intervention for low-birth-weight premature infants. The Infant Health and Development Program.

OBJECTIVE: To reevaluate at age 8 years children who had participated during the first 3 years of life in a randomized clinical trial of special services for low-birthweight (LBW) premature infants. DESIGN: Follow-up of a randomized controlled trial of premature infants (< or = 37 weeks' gestation), stratified by 2 LBW groups (lighter [< or = 2000 g] and heavier [2001-2500 g]) and divided into intervention (n=377) and follow-up only (n=608) groups. SETTING: Eight sites serving diverse populations. PARTICIPANTS: At age 8 years, 874 children were assessed: 336 in the intervention group and 538 in the follow-up only group. INTERVENTION: The 3-year intervention consisted of home visits (birth to 3 years), child development center services (ages 1 to 3 years), and parent group meetings (ages 1 to 3 years). PRIMARY OUTCOME MEASURES: Cognitive functioning (Weschler Intelligence Scale for Children-III; Peabody Picture Vocabulary Test-Revised); academic achievement (Woodcock-Johnson Tests of Achievement-Revised); and parental reports of school performance, behavior (Child Behavior Checklist), and health (Child General Health Survey). RESULTS: At age 8 years, in the entire cohort and in the lighter LBW stratum, the intervention and follow-up only groups were similar on all primary outcome measures. Differences favoring the intervention group were found within the heavier LBW group: full-scale IQ score (4.4 points higher, P=.007), verbal IQ score (4.2 points higher, P=.01), performance IQ score (3.9 points higher, P=.02), mathematics achievement score (4.8 points higher, P=.04), and receptive vocabulary score (6.7 points higher, P=.001). On a physical functioning subscale, the whole intervention group received less favorable ratings, while the lighter LBW intervention group had lower maternal ratings assessing social limitations caused by behavior. CONCLUSION: Although at age 8 years there were modest intervention-related differences in the cognitive and academic skills of heavier LBW premature children, attenuation of the large favorable effects seen at 3 years was observed in both the heavier and lighter LBW groups. This indicates a need to develop additional intervention strategies for LBW premature children that can provide sustained benefits.

Child↗

Hospital use and health status of women during the 5 years following the birth of a premature, low-birthweight infant.

OBJECTIVE: This study examined the health status and hospital use of women after the birth of a premature, low-birthweight infant. METHODS: The subjects were women with infants who participated in a multisite, randomized trial of an early intervention program. The outcomes examined were (1) a maternal health rating of poor or fair (i.e., poorer health) 5 years following delivery and (2) hospital use for a non-pregnancy-related condition. RESULTS: By the fifth year after delivery, 29.7% of the women had been hospitalized for a non-pregnancy-related condition. Women who reported poorer health status (adjusted relative risk [RR] = 2.39; 95% confidence interval [CI] = 1.86, 3.07) or who had asthma (RR = 2.24; CI = 1.31, 3.80) were at greatest risk. After 5 years, 16.9% of the women said they were in poorer health. The number of intervening years in poorer health (1 year, RR = 3.17; CI = 2.04, 4.94; > 1 year, RR = 8.42; CI = 2.20, 12.88), more than 1 year of poverty (RR = 3.28; CI = 1.90, 5.66), obesity (RR = 3.30; CI = 1.44, 7.55), and more than 1 year of employment (RR = 0.55; CI = 0.36, 0.86) were all significantly associated with poorer health. CONCLUSIONS: The continued, substantial morbidity and hospital use of women with a premature, low-birthweight infant has not previously been reported. This observation needs to be verified.

Adult↗

Evaluating the Healthy Start program. Design development to evaluative assessment.

The national evaluation of the federally funded Healthy Start program involved translating a design for a process and outcomes evaluation and standard maternal and infant data set, both developed prior to the national evaluation contract award, into an evaluation design and client data collection protocol that could be used to evaluate 15 diverse grantees. This article discusses the experience of creating a process and outcomes evaluation design that was both substantively and methodologically appropriate given such issues as the diversity of grantees and their community-based intervention strategies; the process of accessing secondary data sources, including vital records; the quality of client level data submissions; and the need to incorporate both qualitative and quantitative approaches into the evaluation design. The relevance of this experience for the conduct of other field studies of public health interventions is discussed.

Child Health Services↗

The behavioral and emotional well-being of school-age children with different birth weights.

OBJECTIVE: To describe the mental and emotional well-being of children born at different birth weights assessed at school age and to identify neonatal, intervening health, and sociodemographic and environmental factors associated with mental and emotional well-being. METHODS: To address this issue, we used a prospective cohort study involving two previously studied cohorts, which were recontacted at 8 to 10 years of age to provide a multisite sample of 247 children weighing 1000 g or less at birth, 364 weighing 1001 to 1500 g, 724 weighing 1501 to 2500 g, and 533 weighing more than 2500 g. Maternal reports were obtained on three standardized measures of mental and emotional well-being (the Rand General Well-being Scale, the Behavior Problem Index, and the Harter Scale of Child Competence) and on intervening health, sociodemographic, and environmental variables. Neonatal variables were derived from records at birth. Statistical techniques included analysis of variance and ordinary least squares multiple regression. RESULTS: Lower birth weight children did not differ on the General Well-being Scale but were more likely to have behavior problems and to be considered less competent. Other important correlates of mental and emotional well-being included childhood illness, maternal mental health, home environment score, and exposure to household cigarette smoking. CONCLUSION: Although lower birth weight children have poorer mental and emotional well-being, a substantial portion of this adverse outcome reflects modifiable environmental factors.

Analysis of Variance↗

Normal birth weight intensive care unit survivors: outcome assessment.

UNLABELLED: RATIONALE/OBJECTIVE: Although the short- and long-term outcome of low birth weight neonatal intensive care unit (NICU) survivors has been extensively studied, much less information is available for normal birth weight (NBW) infants (greater than or equal to 2500 g) who require NICU care. METHODS: To address this issue, we retrospectively examined the neonatal hospitalizations and 6-month health status of 521 consecutive NBW admissions to a single NICU. Information on the neonatal hospitalization was obtained from a review of medical records. Postdischarge health status was collected by using telephone survey techniques. RESULTS: NBW infants comprised 88.1% of births in this hospital and 35.4% of NICU admissions during the study period. The in-hospital mortality rate for this group was 2%. The median length of stay was 7.7 days (range 1 to 110 days) with median hospital charges of $5222 (range $565 to $317,820). Only 59% of infants required active intensive care therapy; the remainder received only intensive monitoring. The need for intensive therapy on admission day along with the presence of prematurity and congenital anomalies were significant predictors of hospital charges (R2 = 0.31, P < .01). After initial discharge, 10.1% of these infants required rehospitalization in the first 6 to 8 months of life. The rate of readmission among infants with congenital anomalies was over 30%. In addition to its association with neonatal resource consumption, the presence of congenital anomalies along with low 5-minute Apgar scores was associated with higher postdischarge resource use, as measured by frequency of physician visits, need for special medical items, and rate of rehospitalization (P < .05). CONCLUSIONS: NBW infants represent a significant percentage of NICU admissions, but for many of these patients NICU admission could be avoided if alternative care settings that provided intensive monitoring were available. In addition, these infants also incur higher rates of postdischarge use of medical care.

Birth Weight↗

Late neuropsychological outcomes in preterm infants of normal IQ: selective vulnerability of the visual system.

Evaluated neuropsychological outcomes in 635 children, ages 7 to 10 years, in relation to birth weight group: < or = 1,000 g; 1,001-1,500 g; 1,501-2,500 g, and > 2,500 g. The prevalence of low IQ (< 85) was related to birth weight. Among children with IQ > 84 (N = 475): (a) Birth weight was unrelated to Verbal IQ, Performance IQ, Full-scale IQ, or reading achievement; (b) extremely low birth weight (ELBW) children achieved more poorly in mathematics than did other birth weight groups (p < .05); (c) ELBW and very low birth weight children performed more poorly on the Rey-Osterrieth Complex Figure, a complex visual processing task, than did heavier birth weight children (p < .05), but performance on the Beery Test of Visuomotor Integration was not related to birth weight. Results are consistent with heightened neurobehavioral vulnerability of visual processing to preterm birth.

Child↗