Long-term trends in childhood diabetes mortality: 1968-1998.

OBJECTIVE: In the context of recent improvements in type 1 diabetes therapy, to describe longitudinal trends in mortality attributable to childhood diabetes and to investigate socioeconomic and health services correlates of mortality. RESEARCH DESIGN AND METHODS: We extracted mortality data for 1968-1998 from National Center for Health Statistics files and covariates from the Bureau of Health Professions Area Resource File. Analytical techniques included linear and Poisson regression and standard descriptive statistics. RESULTS: Childhood (defined as 0-19 years of age) age-adjusted mortality from diabetes declined from 9.5 (1968) to 3.0 (1984) deaths per 10 million but remained relatively constant subsequently. All-cause childhood mortality, however, continued to decline. Older children experienced higher mortality rates, as did those living in counties with higher levels of unemployment. CONCLUSIONS: Despite recent improvements in therapy, diabetes-related mortality among children has not declined for 14 years. This finding may be partially attributable to sociodemographic factors influencing access to care, but the remaining mortality may defy available treatment methods. Reducing childhood diabetes mortality rates below the current apparent plateau may require new prevention and/or treatment strategies.

The relationship between social stratification and all-cause mortality among children in the United States: 1968-1992.

BACKGROUND: US childhood poverty rates have increased for most of the past 2 decades. Although overall mortality among children has apparently fallen during this interval, these aggregate mortality rates may hide a disproportionate burden imposed on the least advantaged. This study assessed the impact of social stratification on long-term US childhood mortality rates and examined the temporal relationship between mortality attributable to social stratification and childhood poverty rates. METHODS: Using US childhood mortality data obtained from the Compressed Mortality File (National Center for Health Statistics) and a county-level measure of social stratification (residential telephone availability), I evaluated the impact of social stratification on long-term trends (1968-1992) in age-adjusted mortality and compared the resulting attributable proportions to trends in childhood poverty rates. RESULTS: Between 1968 and 1987 the proportion of US childhood deaths attributable to social stratification decreased from.22 to.17. Subsequently, it increased to.24 in 1992, despite continuous declines in overall childhood mortality rates. These proportions correlated strongly with earlier childhood poverty rates, taking into account an apparent 9-year lag. Among black children comparable trends were not observed, although throughout this time period their mortality rates were far higher than among the rest of the population and declined more slowly. CONCLUSIONS: Despite declining childhood mortality rates between 1968 and 1992, children living in the least advantaged counties continued to die at higher rates than those living in the most advantaged counties. This differential worsened considerably after 1987, and by 1992 had a substantive impact on US life expectancy at birth, resulting in perhaps the most significant (in terms of years of life lost) reversal in the health of the US public in the 20th century.

Long-term trends in childhood infectious disease mortality rates.

OBJECTIVES: This study assessed long-term trends in US childhood infectious disease mortality rates (CIDMR). METHODS: We calculated age-adjusted and age group-specific US CIDMR (1968-1996) by using data from the Compressed Mortality File (1968-1992, 1996) and Multiple Cause of Death Files (1993-1995) of the National Center for Health Statistics and English data for historical comparison (1861-1964). RESULTS: US CIDMR declined continuously from 1968 to 1996, although the rate of decline slowed after 1974. Respiratory and central nervous system categories declined most; HIV-related deaths offset these declines somewhat. CONCLUSIONS: CIDMR declined nearly 200-fold between 1861 and 1996, but no substantive improvement occurred after 1986.

Inherited macrocephaly-hamartoma syndromes.

Recent discoveries in the molecular biology of the phosphatase and tensin homolog (PTEN) locus in the q22-23 region of chromosome 10 prove and/or suggest that several syndromes previously considered to be clinically and genetically distinct entities should actually be unified into a single entity. This conclusion is most secure for the Cowden and "Bannayan-Zonana" phenotypes, but almost certainly should also include the "Riley-Ruvalcaba" and Lhermitte-Duclos phenotypes as well benign familial macrocephaly and external hydrocephalus. The clinical and molecular data supporting this unification are presented along with a proposal for new nomenclature-the PTEN MATCHS (macrocephaly, autosomal dominant, thyroid disease, cancer, hamartomata, skin abnormalities) syndrome-based on the observed clinical abnormalities.

Effect of influenza immunization on immunologic and virologic characteristics of pediatric patients infected with human immunodeficiency virus.

OBJECTIVES: We evaluated the responses of HIV-infected children to a single dose of split-virus influenza vaccine and the relationship to viral load and other characteristics. METHODS: Fifty-three HIV-infected children ages 1.8 to 13.2 years were given influenza vaccine for the 1994 to 1995 influenza season (Wyeth-Ayerst: A/Texas H1N1, A/Shangdong H3N2 and B/Panama). Immunologic and virologic factors were assessed at the time of and 2 to 10 weeks after immunization. RESULTS: The differences between pre- and postimmunization CD4+ counts, CD4+:CD8+ ratios and viral load were not significant. Thirty-one of 53 children (58.4%) had a > 2-fold increase and 16 of 53 (30%) had a 4-fold rise in their postimmunization antibody titers for at least one component of the vaccine. Influenza immunization in the 1993 to 1994 flu season and administration of intravenous immunoglobulin around the time of immunization was not associated with immune response to the vaccine. Factors that were negatively associated with antibody response included increased time between samples (P = 0.004) and decreased preimmunization CD4+:CD8+ ratio (P = 0.02). CONCLUSIONS: Influenza immunization in this population is safe, and a positive antibody response to influenza immunization is not associated with significant clinical events or change in HIV-1 plasma viral burden.

Prenatal diagnosis.

The enormous progress witnessed in the field of prenatal diagnosis during the past two decades is likely to continue into the future. Improved imaging techniques are likely to enhance the resolution of noninvasively obtained fetal images considerably over their current excellent quality. Although this undoubtedly will be true for ultrasonography, the increased speed of magnetic resonance equipment may offer a new realm of imaging possibilities. Computerized image processing, analysis, and three-dimensional reconstructions all should make interpretation of fetal images easier and more understandable to the nonspecialist. Advances in molecular genetics will continue to accelerate, greatly expanding the range and accuracy of prenatal diagnosis. The alert pediatrician who is sensitive to genetic issues may, by early detection of pediatric disorders and careful family history assessment, be in a position to identify families at risk for serious genetic conditions and provide the opportunity to make informed decisions on reproductive options that avert a major tragedy. The pediatrician, working with obstetric colleagues, should be part of a team effort to support families going through prenatal testing. Familiarity with these rapidly changing technologies will make it far easier to support the family needing additional explanation about prenatal diagnosis issues.

Correlation of skeletal muscle biopsy with phenotype in the familial macrocephaly syndromes.

The muscle biopsy results from 14 children with macrocephaly and hypotonia/weakness were correlated with clinical findings compatible with any of the autosomal dominant macrocephaly syndromes. Thirteen of the 14 had evidence of lipid storage myopathy, either generalised or focal. All 13 had examinations consistent with either benign familial macrocephaly, Ruvalcaba-Myhre-Smith syndrome, or Bannayan-Zonana syndrome. These results suggest that all three of these disorders may represent phenotypic variability at a single genetic locus.

Application of D'Arcy Thompson's coordinate transformation approach to clinical genetics photographs using image processing techniques.

The coordinate transformation approach outlined by D'Arcy Thompson for analysing biological shape was extended using modern computerised image processing techniques so that it could be applied to photographs for the study of patients with syndromes of altered facial morphogenesis. Photographs digitised at a resolution of 512 by 480 pixels were subjected to 'rubbersheeting' transformations using a fast microcomputer. Starting with a photograph of a normal child, a single application of the rubbersheeting algorithm produced features such as an upturned nose quite simply. Other facial anomalies may also be recreated with multiple applications. Preliminary results suggest that this technique may be a useful tool in attempts to understand and analyse the changes in facial configuration in a variety of syndromes with facial anomalies.

Photogrammetric evaluation in clinical genetics: theoretical considerations and experimental results.

As newer mathematical approaches are applied to the field of clinical genetics accurate methods of craniofacial measurement are increasingly necessary. If photogrammetric techniques are to be used certain theoretical and practical issues must be taken into account. Errors due to projection are particularly important, but systematic and random errors must also be considered. We discuss theoretical aspects of projection errors along with experimental measurements. Systematic errors in excess of 20% were found during simulations of typical clinical conditions, although smaller errors were obtained using techniques practical in a clinical setting. Photogrammetric measurements are potentially valuable in the field of clinical genetics but must be used cautiously.

Myotonic dystrophy and hyperparathyroidism: association with neurofibromatosis and multiple endocrine adenomatosis type 2A.

Four patients with hyperparathyroidism associated with myotonic dystrophy have been identified. All were females aged between 2 and 45 years. They were from three separate families, with two related patients being mother and daughter. In addition, one patient had medullary carcinoma of the thyroid and was diagnosed as having multiple endocrine adenomatosis, type 2A; another had an unspecified thyroid carcinoma; a third patient had neurofibromatosis. Our data suggest that myotonic dystrophy may somehow be associated with one or more of these disorders of neural crest origin.

Use of computers in dysmorphology.

As a consequence of the increasing power and decreasing cost of digital computers, dysmorphologists have begun to explore a wide variety of computerised applications in clinical genetics. Of considerable interest are developments in the areas of syndrome databases, expert systems, literature searches, image processing, and pattern recognition. Each of these areas is reviewed from the perspective of the underlying computer principles, existing applications, and the potential for future developments. Particular emphasis is placed on the analysis of the tasks performed by the dysmorphologist and the design of appropriate tools to facilitate these tasks. In this context the computer and associated software are considered paradigmatically as tools for the dysmorphologist and should be designed accordingly. Continuing improvements in the ability of computers to manipulate vast amounts of data rapidly makes the development of increasingly powerful tools for the dysmorphologist highly probable.

Recurrent seizures following mucosal application of TAC.

A 5-year-old 20-kg boy developed grand mal seizures following application of 2 mL of tetracaine-adrenalin-cocaine to an oral mucosa laceration. Diazepam 6 mg IV followed by 195 mg phenobarbital was required to terminate the seizures. The patient was transferred to a pediatric intensive care unit for further evaluation and treatment. A toxicology screen obtained after transfer was positive only for diazepam and phenobarbital. The child remained lethargic for several hours but otherwise had a normal neurological examination. Brain computed tomography was normal. Anticonvulsant medication was discontinued prior to discharge and the child had no subsequent seizures.

Ruvalcaba-Myhre-Smith syndrome.

In 1980 a syndrome was first described in two adult males, consisting of macrocephaly, pigmented macules on the glans and shaft of the penis, and hamartomatous intestinal polyps. Since then, 10 additional cases have been identified. Herein, we present two new cases and review the cutaneous manifestations as well as additional features in patients with the Ruvalcaba-Myhre-Smith syndrome.

A population-based study of hemolytic-uremic syndrome in Oregon, 1979-1982.

The authors conducted a retrospective hospital-based chart review of cases of hemolytic-uremic syndrome among children less than or equal to 18 years of age, hospitalized in Oregon during the four-year period from January 1979 to December 1982. Thirty children with hemolytic-uremic syndrome living in Oregon were hospitalized during this period, for an average annual incidence of 0.97 cases per 100,000 children. Seventy per cent of cases occurred in children under five years of age, for an incidence of 2.65 cases per 100,000 children. Twenty-seven (90%) of the 30 children were white, and 17 (57%) were female. Twenty-four (80%) had a diarrheal prodromal illness including 20 who had bloody diarrhea. Twelve children (40%) acutely required peritoneal dialysis, and two (7%) developed chronic renal failure. Three children died, for a case fatality ratio of 10%. Sixty per cent of the 30 cases occurred during the summer and early fall months. Geographic clustering was also evident. Hemolytic-uremic syndrome is a rare but endemic disease in Oregon and may occur in small clusters. Although descriptions of several large series of patients have been published, this study describes the first statewide population-based study of this syndrome.

Deletions of the long arm of chromosome 10.

Patients with a partial deletion of the long arm of chromosome 10 are rare. We report eight new cases involving various segments of 10q: one terminal deletion (10q26), four (8;10) translocations resulting in terminal deletions (10q26) and duplications (8q24.3), a de novo interstitial deletion (10q23), an interstitial deletion due to a (10;13) translocation (10q11.2----10q22.1), and a ring (10p15----10q26).

The fetal valproate syndrome.

We evaluated seven children who had been exposed to sodium valproate (or valproic acid) in utero. A consistent facial phenotype was observed in all seven in addition to other birth defects in four. The facial changes consisted of epicanthal folds which continued inferiorly and laterally to form a crease or groove just under the orbit, flat nasal bridge, small upturned nose, long upper lip with a relatively shallow philtrum, a thin upper vermillion border, and downturned angles of the mouth. Hypospadias, strabismus, and psychomotor delay were found in two males; two children had nystagmus and two had low birth weight.

Hypercholesterolemia associated with alpha-1 antitrypsin deficiency and hepatitis: lipoprotein and apoprotein determinations, sterol balance and treatment.

Lipid metabolism was investigated in a 4-year-old boy with alpha-1 antitrypsin deficiency (ZZ phenotype) and liver disease. Plasma cholesterol and triglyceride levels were 604 mg/dl and 336 mg/dl respectively. Both parents had normal plasma lipids. Lipoprotein X was present at a concentration of 855 mg/dl and levels of apoproteins A-I, A-II, B and C-III were elevated. The plasma free fatty acid pattern was normal. Plasma cholesterol esterification was greatly depressed. Cholesterol absorption on two occasions was reduced about 13% compared with adult controls. Neutral and total steroid excretion was normal with increased excretion of bile acids. A low-cholesterol, low-fat diet reduced plasma cholesterol to 374 mg/dl and triglyceride to 236 mg/dl in two months. Cholesterol and lipoprotein X concentrations were elevated far out of proportion to the severity of the liver disease (total bilirubin 3.7 mg/dl, SGOT 280 IU/L). This suggests that lipoprotein metabolism in patients with this disorder is unusual and may differ from the derangements seen in other forms of liver disease.

A new lipid storage myopathy observed in individuals with the Ruvalcaba-Myhre-Smith syndrome.

Four patients with the Ruvalcaba-Myhre-Smith syndrome (primary macrocephaly with associated anomalies including pigmented macules on the penis in affected males, hamartomatous intestinal polyps, and lipomas) had evidence of delayed psychomotor development and/or hypotonia in childhood. Electromyography in 3 patients showed evidence of a myopathic process. Muscle biopsy in all four demonstrated a lipid storage myopathy with increased numbers of neutral lipid droplets--predominatly in type 1 fibers. The type 2 fibers were consistently smaller than expected. Electron microscopy was unremarkable except for evidence of lipid accumulation. Muscle carnitine and carnitine palmityl transferase levels were normal in one patient. This appears to be a previously unreported type of lipid storage myopathy characteristic of the Ruvalcaba-Myhre-Smith syndrome, a probable autosomal dominant trait.

Needle muscle biopsy in infants and children.

Percutaneous muscle biopsies were performed in 77 infants and children using the Bergstrom muscle biopsy needle and local anesthesia. Satisfactory specimens for histochemistry and electron microscopy were obtained in all but one case, and the procedure was well tolerated by all patients. No complications were observed. The percutaneous biopsy is a useful technique for the diagnosis of neuromuscular disorders in children.