Current state of high-risk infant follow-up care in the United States: results of a national survey of academic follow-up programs.

OBJECTIVE: High-risk infant follow-up programs have the potential to act as multipurpose clinics by providing continuity of clinical care, education of health care trainees and facilitating outcome data research. Currently there are no nationally representative data on high-risk infant follow-up practices in the United States. The objective of this study is to collect information about the composition of high-risk infant follow-up programs associated with academic centers in the United States, with respect to their structure, function, funding resources and developmental assessment practices, and to identify the barriers to establishment of such programs. STUDY DESIGN: Staff neonatologists, follow-up program directors and division directors of 170 Neonatal Intensive Care Units (NICU) associated with pediatric residency programs were invited to participate in an anonymous online survey from October 2009 to January 2010. RESULT: The overall response rate was 84%. Ninety three percent of the respondents have a follow-up program associated with their NICU. Birth weight, gestational age and critical illness in the NICU were the major criteria for follow-up care. Management of nutrition and neurodevelopmental assessments was the most common service provided. Over 70% have health care trainees in the clinic. About 75% of the respondents have the neurodevelopmental outcome data available. Most of the respondents reported multiple funding sources. Lack of personnel and funding were the most common causes for not having a follow-up program. CONCLUSION: High-risk infant follow-up programs associated with academic centers in the United States are functioning as multidisciplinary programs providing clinical care, trainee education and facilitating outcomes research.

Hospital and neurodevelopmental outcomes of extremely low-birth-weight infants with necrotizing enterocolitis and spontaneous intestinal perforation.

OBJECTIVE: We sought to determine the incidence of necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) in surviving extremely low-birth-weight (ELBW, <1000 g birth weight) infants and to establish the impact of NEC on outcomes by hospital discharge and at 18 to 22 months adjusted age in a large, contemporary, population-based practice. STUDY DESIGN: Hospital outcome data for all ELBW infants born in the greater Cincinnati region from 1998 to 2009 were extracted from the National Institute of Child Health Neonatal Research Network Database. Neurodevelopmental outcome at 18 to 22 months was assessed using Bayley Scales of Infant Development-II scores for Mental Developmental Index and Psychomotor Developmental Index. Multivariable logistic regression was used and adjusted odds ratios reported to control for confounders. RESULT: From 1998 to 2009, ELBW infants accounted for 0.5% of the 352 176 live-born infants in greater Cincinnati. The incidence of NEC was 12%, with a 50% case-fatality rate. Death before discharge, morbid complications of prematurity and neurodevelopmental impairment were all increased among infants diagnosed with NEC. Infants with surgical NEC and SIP had a higher incidence of death, but long-term neurodevelopmental outcomes were not different comparing surviving ELBW infants with medical NEC, surgical NEC and SIP. CONCLUSION: Although ELBW infants comprise a very small proportion of live-born infants, those who develop NEC and SIP are at an increased risk for death, morbid complications of prematurity and neurodevelopmental impairment. No significant differences in neurodevelopmental outcomes were observed between the medical and surgical NEC and SIP groups.

Neurodevelopmental and functional outcomes of extremely low birth weight infants in the National Institute of Child Health and Human Development Neonatal Research Network, 1993-1994.

OBJECTIVES: The purposes of this study were to report the neurodevelopmental, neurosensory, and functional outcomes of 1151 extremely low birth weight (401-1000 g) survivors cared for in the 12 participating centers of the National Institute of Child Health and Human Development Neonatal Research Network, and to identify medical, social, and environmental factors associated with these outcomes. STUDY DESIGN: A multicenter cohort study in which surviving extremely low birth weight infants born in 1993 and 1994 underwent neurodevelopmental, neurosensory, and functional assessment at 18 to 22 months' corrected age. Data regarding pregnancy and neonatal outcome were collected prospectively. Socioeconomic status and a detailed interim medical history were obtained at the time of the assessment. Logistic regression models were used to identify maternal and neonatal risk factors for poor neurodevelopmental outcome. RESULTS: Of the 1480 infants alive at 18 months of age, 1151 (78%) were evaluated. Study characteristics included a mean birth weight of 796 +/- 135 g, mean gestation (best obstetric dates) 26 +/- 2 weeks, and 47% male. Birth weight distributions of infants included 15 infants at 401 to 500 g; 94 at 501 to 600 g; 208 at 601 to 700 g; 237 at 701 to 800 g; 290 at 801 to 900 g; and 307 at 901 to 1000 g. Twenty-five percent of the children had an abnormal neurologic examination, 37% had a Bayley II Mental Developmental Index <70, 29% had a Psychomotor Developmental Index <70, 9% had vision impairment, and 11% had hearing impairment. Neurologic, developmental, neurosensory, and functional morbidities increased with decreasing birth weight. Factors significantly associated with increased neurodevelopmental morbidity included chronic lung disease, grades 3 to 4 intraventricular hemorrhage/periventricular leukomalacia, steroids for chronic lung disease, necrotizing enterocolitis, and male gender. Factors significantly associated with decreased morbidity included increased birth weight, female gender, higher maternal education, and white race. CONCLUSION: ELBW infants are at significant risk of neurologic abnormalities, developmental delays, and functional delays at 18 to 22 months' corrected age.

Safety and pharmacokinetics of an intramuscular humanized monoclonal antibody to respiratory syncytial virus in premature infants and infants with bronchopulmonary dysplasia. The MEDI-493 Study Group.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory disease in infants and children. MEDI-493 (palivizumab, Synagis) is a humanized monoclonal IgG1 antibody to the fusion protein of RSV, and it is highly active in vitro against RSV A and B strains. OBJECTIVE: To describe the safety, tolerance, immunogenicity and pharmacokinetics of monthly intramuscular injections of MEDI-493 among premature infants and children with bronchopulmonary dysplasia and to compare these data with information previously obtained with intravenous dosing. DESIGN: A Phase I/II multicenter, open label, escalating dose clinical trial. PATIENT POPULATION AND DOSING REGIMEN: Children (n=65) born prematurely at < or =35 weeks of gestation who were < or =6 months of age (n=41) and children with bronchopulmonary dysplasia who were < or =24 months of age (n=24) were enrolled. From 1 to 5 monthly injections were given at doses of 5 mg/kg (n=11), 10 mg/kg (n=6) and 15 mg/kg (n=48). Serum was collected before administration of each dose, 30 days after the last dose, and 2, 7 and 14 days after the first and second doses for measurement of MEDI-493 concentrations by enzyme-linked immunosorbent assay. RESULTS: The pharmacokinetics of MEDI-493 were similar to those of other human IgG1 antibodies. Mean serum MEDI-493 concentrations were 91.1 microg/ml (range, 52.3 to 174.0) 2 days after the initial dose of 15 mg/kg and 49.2 microg/ml (range, 13.5 to 132.0) at 30 days. Monthly dosing of 15 mg/kg maintained mean trough concentrations of approximately 70 microg/ml. These concentrations were similar to previously published trough concentrations after i.v. administration. MEDI-493 injections were well-tolerated. Only three children had adverse events judged to be possibly related to MEDI-493. Ten children had transient, low titer anti-MEDI-493 binding titers (1:10 to 1:40) which were not associated with a pattern of specific adverse events or alterations of MEDI-493 concentrations. Two patients in the 5-mg/kg dose group were hospitalized for RSV; no RSV hospitalizations were found in the higher dose groups. CONCLUSIONS: MEDI-493 was safe and well-tolerated. Monthly intramuscular doses of 15 mg/kg maintained mean trough serum concentrations that were above 40 microg/ml (the value associated with 99% reduction of pulmonary RSV in the cotton rat model). These concentrations were similar to those previously reported with i.v. administration of MEDI-493.

Safety, tolerance and pharmacokinetics of a humanized monoclonal antibody to respiratory syncytial virus in premature infants and infants with bronchopulmonary dysplasia. MEDI-493 Study Group.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants. MEDI-493 (palivizumab) is a humanized monoclonal antibody to the fusion protein of RSV and is active in animal models for prevention of pulmonary RSV replication. OBJECTIVE: To describe the safety, tolerance, immunogenicity and pharmacokinetics of repeat intravenous doses of MEDI-493 in premature infants or infants with bronchopulmonary dysplasia. DESIGN: Phase I/II multicenter, randomized, double blind, placebo-controlled, dose escalation trial. PATIENT POPULATION: Infants born prematurely (< or = 35 weeks of gestation) who were < or = 6 months of age and infants with bronchopulmonary dysplasia who were < or = 24 months of age were eligible for study participation. STUDY AGENTS: Participants received 3, 10 or 15 mg/kg MEDI-493 or 0.9% saline intravenously every 30 days for up to five doses. RESULTS: MEDI-493 was safe and well-tolerated and did not induce a specific anti-MEDI-493 response. The mean half-life of 20 days was comparable with that of other immunoglobulin G preparations. Mean trough serum concentrations 30 days after Infusion 1 were 6.8, 36.1 and 60.6 microg/ml for the 3-, 10- and 15-mg/kg dose groups, respectively. After Infusion 2 the trough concentrations were 11.9, 45.2 and 70.7 microg/ml. After subsequent doses the mean trough values ranged from 14 to 18 microg/ml in those given 3 mg/kg and were > 40 microg/ml for patients who received 10 or 15 mg/kg MEDI-493 (46 to 72 microg/ml and 88 to 96 microg/ml, respectively). CONCLUSIONS: MEDI-493 was safe and well-tolerated in this high risk pediatric population. Mean serum concentrations of MEDI-493 that have been shown to produce a 2-log reduction in pulmonary RSV titer in cotton rats were maintained when 10 or 15 mg/kg MEDI-493 was given every 30 days to pediatric patients at high risk for serious RSV disease. Monthly doses of 15 mg/kg maintained concentrations of > 40 microg/ml for the majority of patients.

Compressive neuropathies and tendinopathies in the athletic elbow and wrist.

Overuse syndromes of the upper extremity in the athletic population are a common and often difficult problem for physician and patient alike. Optimal function of the upper extremity is tied intimately to success in many sporting activities. Correct diagnosis and proper care require a thorough knowledge of the pertinent anatomy, pathophysiology, and pathomechanics involved in each disorder. Conservative care with rest, activity modification, and medication is adequate for most athletic injuries. Surgical intervention may be indicated for continuing pain, decreased performance, or to prevent chronic changes. Surgery must be followed by thoughtfully prepared training and rehabilitation programs to optimize the chances of a successful outcome.

Magnetic resonance imaging for diagnosis of digital flexor tendon rupture after primary repair.

Because the clinical diagnosis of rupture of a digital flexor tendon was uncertain 10 days after primary repair, magnetic resonance imaging was used for evaluation, correlating precisely with the surgical pathology. This non-invasive tool can be very helpful in the early post-operative period when active flexion is not possible to aid in the clinical diagnosis of tendon rupture.

Two concurrent spinal dural arteriovenous fistulae in a patient with rapidly progressive myelopathy. A case report.

A rare case of two separate spinal dural arteriovenous fistulae (DAVFs) occurring concurrently in a patient with a rapidly progressive myelopathy is reported. Although concurrent spinal DAVFs may be "well known," their occurrence has been only anecdotally reported. To the authors' knowledge, this well documented case of a presumably rare variant of spinal DAVFs is the first to appear in the literature and is instructive for reconsidering approaches to optimal diagnosis and evaluation of posttherapeutic efficacy of these lesions.

Complications in phalangeal and metacarpal fracture management. Results of extensor tenolysis.

Extensor tendon adherence and joint contracture after phalangeal and metacarpal fracture are common complications that affect finger motion and hand function. The results obtained by extensor tenolysis and dorsal capsulotomy are discussed in this article. Surgical outcome was evaluated as it related to extensor tenolysis and capsulotomy relative to the final total active motion, total passive motion, and active extensor lag. This information will be useful in discussing the expected results of surgery with the patient and in guiding postoperative rehabilitation.

A point mutation in a Drosophila GABA receptor confers insecticide resistance.

Vertebrates and invertebrates both have GABA (gamma-aminobutyric acid) as a major inhibitory neurotransmitter. GABAA receptors in vertebrates assemble as heteromultimers to form an integral chloride ion channel. These receptors are targets for drugs and pesticides and are also implicated in seizure-related diseases. Picrotoxinin (PTX) and cyclodiene insecticides are GABAA receptor antagonists which competitively displace each other from the same binding site. Insects and vertebrates showing resistance to cyclodienes also show cross-resistance to PTX. Previously, we used a field-isolated Drosophila mutant Rdl (Resistant to dieldrin) insensitive to PTX and cyclodienes to clone a putative GABA receptor. Here we report the functional expression and novel pharmacology of this GABA receptor and examine the functionality of a resistance-associated point mutation (alanine to serine) within the second membrane-spanning domain, the region thought to line the chloride ion channel pore. This substitution is found globally in Drosophila populations. This mutation not only identifies a single amino acid conferring high levels of resistance to the important GABA receptor antagonist PTX but also, by conferring resistance to cyclodienes, may account for over 60% of reported cases of insecticide resistance.

A single-amino acid substitution in a gamma-aminobutyric acid subtype A receptor locus is associated with cyclodiene insecticide resistance in Drosophila populations.

Resistance to cyclodiene insecticides, documented in at least 277 species, is perhaps the most common kind of resistance to any pesticide. By using cyclodiene resistance to localize the responsible gene, a gamma-aminobutyric acid type A receptor/chloride ion-channel gene was previously cloned and sequenced from an insecticide-susceptible Drosophila melanogaster strain. We now describe the molecular genetics of the resistance allele. A single-base-pair mutation, causing a single-amino acid substitution (Ala-->Ser) within the second membrane-spanning region of the channel, was found to be the only consistent difference between resistant and susceptible strains of D. melanogaster. Some resistant strains of Drosophila simulans show the same mutation, whereas others show an alternative single-base-pair mutation in the same codon, resulting in the substitution of a different amino acid (glycine). These constitute single-box-pair mutations in insects that confer high levels of resistance to insecticides. The presence of the resistance mutations was then tested in a much larger set of strains by the PCR and subsequent digestion with a diagnostic restriction endonuclease. Both resistance-associated mutations cause the loss of a Hae II site. This site was invariably present in 122 susceptible strains but absent in 58 resistant lines of the two species sampled from five continents. PCR/restriction endonuclease treatment was also used to examine linkage of an EcoRI polymorphism in a neighboring intron in D. melanogaster, which was found associated with resistance in all but 3 of 48 strains examined. These PCR-based techniques are widely applicable to examination of the uniqueness of different resistance alleles in widespread populations, the identification of resistance mechanisms in different species, and the determination of resistance frequencies in monitoring.

Conservation of cyclodiene insecticide resistance-associated mutations in insects.

Cyclodiene insecticide resistance has accounted for over 60% of reported cases of insecticide resistance. In Drosophila melanogaster resistance is associated with a single base pair substitution in the GABA receptor/chloride ion channel gene Rdl. This substitution predicts the replacement of an alanine with a serine in the second membrane spanning domain, the region thought to line the chloride ion channel pore. Here we report, via the use of degenerate primers in the polymerase chain reaction, that precisely the same substitution is present in three pests from three different insect orders: the house fly (Diptera), red flour beetle (Coleoptera) and American cockroach (Dictyoptera). This finding suggests that there are a limited number of mutations that can confer resistance to cyclodienes, putative channel blockers, while still maintaining adequate chloride ion channel function. The conservation of the resistance-associated mutation between Drosophila and pest insects directly validates the approach of using this insect as a model system for isolating and studying resistance genes. The importance of single base pair substitutions in the evolution of pesticide resistance and in the design of molecular monitoring techniques is discussed.

Mineral nutrition and bone mineralization in full-term infants.

Bone mineralization is an intricate and tightly regulated process. Calcium, magnesium and phosphorus are the main minerals and play a principal role in skeletal mineralization. The following conclusions can be derived from different clinical studies. The large differences in Ca/P ratio between different formulas and between formulas and human milk suggest that most healthy full-term infants can adjust to a wide range of Ca/P ratio in their diet. The differences in serum levels of mineral and of mineral-regulating hormones are rarely clinically significant and most probably reflect continued compensatory mechanisms activated in response to dietary differences to maintain these levels within clinically normal ranges. Thus in most cases, these compensatory mechanisms are sufficient to reverse both short-term and long-term consequences and to prevent clinical disease. In the case of neonatal tetany, the compensatory mechanisms are overwhelmed, resulting in clinical signs and disease. Vitamin D is known to play an essential role in bone mineralization. Our studies have shown significant differences in vitamin D status in breast-fed infants with and without vitamin D supplementation and in infants fed various "humanized" formulas, whether cow milk-based or soy protein-based. The major variables affecting bone mineralization are Ca/P ratio and mineral-regulating hormones. However, factors such as season, geography (i.e. sun exposure), race and sex may have a significant long-term influence on bone mineralization and mineral metabolism. Some biological differences such as differences in serum vitamin D metabolite level may directly effect Ca/P absorption and retention and thus bone mineralization and growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Complications of replantation surgery.

Potential complications after replantation surgery are numerous and varied in their nature. The average replantation patient can expect somewhere between two to three subsequent operations to maximize function. Many surgical complications and unsatisfactory functional outcomes can be avoided through careful assessment of patients and their injuries.

Reconstruction of traumatic absence of the thumb by microvascular free tissue transfer from the foot.

The development of microvascular surgical techniques during the last quarter century has advanced the ability of the hand surgeon to reconstruct the traumatically amputated thumb. The use of tissue from the foot has become the mainstay of therapy for this previously exceedingly difficult reconstructive problem. Although numerous minor variations of thumb reconstruction with use of the toes from the foot are available, three main techniques--the complete great toe transfer, wraparound flap, and second toe transfer--provide a predictable outcome. With multiple donor sites available, the surgeon can choose a procedure based on the needs of the patient as well as the particular preferences of the individual surgeon involved. The uniform goal in thumb reconstruction is to provide a cosmetically acceptable, stable, mobile, and sensible thumb that can be used in opposition and pinch maneuvers. Transfer of the great toe can provide excellent reconstruction in the selected patient. This transfer may be the procedure of choice in the child who requires continued epiphyseal growth of the transferred digit. The esthetic appeal of this transfer is somewhat dependent on individual patient variation and the appearance of the toe relative to that of the contralateral uninjured thumb. In patients with a narrow great toe, the transfer can provide an ideal esthetic result. Disadvantages of this transfer are that it is less esthetic when the toe is very bulbous in appearance and that the resultant defect and morbidity in the donor foot may be significant, possibly affecting activities of daily living. The wraparound flap provides the unique ability to customize the thumb reconstruction. The final esthetic outcome of the thumb can be altered in nail size, circumference, and length. Use of the wraparound flap permits a greater portion of the great toe to be left with the foot in an attempt to preserve more normal gait and function postoperatively. This type of transfer does not permit interphalangeal joint motion and may not permit metacarpophalangeal joint motion. Therefore, the requirements of a normal carpometacarpal joint with excellent thenar musculature so that the postoperative thumb can be put through a functional arc of motion are essential. Transferring a portion of the distal phalanx in the wraparound flap permits the intercalary iliac crest graft to have viable bone on both the distal and proximal aspects, thereby reducing postoperative osteopenia of the iliac crest graft itself.(ABSTRACT TRUNCATED AT 400 WORDS)

Reconstruction of traumatic absence of the thumb by alternative microsurgical methods of reconstruction.

Because of the improved predictability, relative lack of donor morbidity, and excellent cosmetic appearance associated with the various forms of toe-to-hand transfers, these operations have become the procedure of choice in the reconstruction of a traumatically amputated thumb. However, a transfer from the foot may not always be available. If severe injuries, such as burns, have occurred to the feet, although a transfer may be technically feasible, it should be avoided. Occasionally, a patient will refuse to sacrifice a portion of his or her foot for either cosmetic or cultural reasons. If the presence of significant peripheral vascular disease is documented in the patient, the anatomy and suitability of the vessels supplying the toes becomes entirely unpredictable, and alternative methods for thumb reconstruction should be considered. In the acute trauma setting, first consideration as a source of donor tissue for thumb reconstruction should be given to any other digits, either ipsilateral or contralateral. Any digit amputated or severely injured at or proximal to the proximal interphalangeal joint may be considered as a possible donor digit. Careful examination of the neurovascular structures in this situation is essential to demonstrate that the zone of injury does not prohibit an appropriate repair at the recipient thumb bed. In the nonacute setting, occasionally, digits on the same or opposite hand are a valuable donor source for thumb reconstruction. Any digit found to be nonfunctional for reasons related to its location may be available for amputation and transfer to the thumb.(ABSTRACT TRUNCATED AT 250 WORDS)

Mutations in a newly identified Drosophila melanogaster gene, mago nashi, disrupt germ cell formation and result in the formation of mirror-image symmetrical double abdomen embryos.

The mago nashi (mago) locus is a newly identified strict maternal effect, grandchildless-like, gene in Drosophila melanogaster. In homozygous mutant mago females reared at 17 degrees C, mago+ function is reduced, the inviable embryos lack abdominal segments and 84-98% of the embryos die. In contrast, at 25 degrees C, some mago alleles produce a novel gene product capable of inducing the formation of symmetrical double abdomen embryos. Reciprocal temperature-shift experiments indicate that the temperature-sensitive period is during oogenetic stages 7-14. Furthermore, embryos collected from mago1 homozygous females contain no apparent functional posterior determinants in the posterior pole. In viable F1 progeny from mago mutant females, regardless of genotype and temperature, polar granules are reduced or absent and germ cells fail to form (the grandchildless-like phenotype). Thus, we propose that the mago+ product is a component of the posterior determinative system, required during oogenesis, both for germ cell determination and delineation of the longitudinal axis of the embryo.

Long-term evaluation of Silastic trapezial arthroplasty in patients with osteoarthritis.

This study of 151 Silastic trapezial arthroplasties evaluates the long-term radiographic and clinical results in patients with osteoarthritis. A radiographic grading system was developed to objectively evaluate and quantify changes seen at the implant-bone contact areas, within the metacarpal medullary canal and distal pole of the scaphoid. Trapezial arthroplasties studied on average of 51 months after implantation revealed that in 56% (85 of 151) of scaphoids cysts had developed, and 74% (111 of 151) of the metacarpals had intramedullary radiolucency and/or cysts. Histopathologic evaluation of the areas of radiographic changes demonstrated silicone synovitis. Statistical analysis revealed that the radiographic changes in the scaphoid and medullary canal of the metacarpal were not directly related to time. Patient satisfaction, found to be 84% (127 of 151) of the study population, did not correlate with the grade of scaphoid or metacarpal radiographic change. This systematic radiographic grading system has been found useful in the long-term durability evaluation of Silastic trapezial arthroplasties.