William Henry, Duke of Gloucester (1689-1700), son of Queen Anne (1665-1714), could have ruled Great Britain.

Hope for continuation of the Stuart dynasty in Britain ended with the death, from pneumonia in 1700, of the 11-year-old son of Princess Anne and Prince George, William Henry Duke of Gloucester. Considered by some to have been physically and mentally unfit to reign, careful examination of primary source materials shows him to have been a bright and interesting boy with mild hydrocephalus. Had he lived, he could have ruled.

Identification and evaluation of mental retardation.

Mental retardation in young children is often missed by clinicians. The condition is present in 2 to 3 percent of the population, either as an isolated finding or as part of a syndrome or broader disorder. Causes of mental retardation are numerous and include genetic and environmental factors. In at least 30 to 50 percent of cases, physicians are unable to determine etiology despite thorough evaluation. Diagnosis is highly dependent on a comprehensive personal and family medical history, a complete physical examination and a careful developmental assessment of the child. These will guide appropriate evaluations and referrals to provide genetic counseling, resources for the family and early intervention programs for the child. The family physician is encouraged to continue regular follow-up visits with the child to facilitate a smooth transition to adolescence and young adulthood.

Very long survival in pediatric cancer between 1944 and 1993.

OBJECTIVE: To identify factors associated with very long survival among all cancer cases diagnosed at age 19 years or younger registered by the Cancer Data Service at the University of Kansas Medical Center in Kansas City, Kansas, U.S.A. in the 40-year period between 1944 and 1983, with follow-up to 1993. METHODS: There were 2720 pediatric patients with 2750 cancers who were studied. Forty-four types of cancer were grouped into 11 diagnostic categories. Diagnosis years spanned four eras: 1944-1953, 1954-1963, 1964-1973, and 1974-1983. Cases were compared using specific characteristics and were divided into short-term and long-term survivors with the division generously set at seven years. The proportions of the long-term survivors were compared by specific characteristics. RESULTS: Among the diagnostic categories, leukemias were the most common (29.8%), followed by CNS tumors (15.2%), and Hodgkin's disease (9.0%). Male to female ratio was 4:3; average age at diagnosis was 8.83 +/- 6.08 years. Long-term survivors totaled 1148 (41.7%). Prognosis was better in cases diagnosed in earlier stages and in later eras. Proportion of long-term survivors increased from 18.7% in era I to 52.6% in era IV. Improvement of survival was statistically significant in most diagnostic categories. CONCLUSIONS: This study shows continuing improvement of survival during four consecutive eras for childhood and adolescent cancer. Early diagnosis was associated with better survival. Unstaged cases decreased over time reflecting progress in diagnostic techniques. Many patients died before seven years after diagnosis. Those who survived more than seven years had excellent survival. Pediatricians can expect to participate in the care of these patients long after the original dianosis and treatment.

Toward a caring culture in professional nursing.

Nursing is a profession founded on the traditional value of caring. Faced with rapid and tumultuous change in the health care system, nurses are finding the environment of practice more stressful and less supportive. The ideal of nursing as a caring community is at risk because of economic and political forces. The authors review the impact of managed care and reaffirm the notion of the caring community in the nursing profession. Specific assessment guidelines and recommendations for the caring community are set forth for practitioners working in a variety of organizational settings. Organizational culture is emphasized as the context for caring practice.

Genetic disease in offspring of long-term survivors of childhood and adolescent cancer.

Numerous case series have addressed the concern that cancer therapy may damage germ cells, leading to clinical disease in offspring of survivors. None has documented an increased risk. However, the methodological problems of small series make it difficult to draw firm conclusions regarding the potential of cancer treatments to damage the health of future offspring. We conducted a large interview study of adult survivors of childhood cancer treated before 1976. Genetic disease occurred in 3.4% of 2,198 offspring of survivors, compared with 3.1% of 4,544 offspring of controls (P=.33; not significant); there were no statistically significant differences in the proportion of offspring with cytogenetic syndromes, single-gene defects, or simple malformations. A comparison of survivors treated with potentially mutagenic therapy with survivors not so treated showed no association with sporadic genetic disease (P=.49). The present study provides reassurance that cancer treatment using older protocols does not carry a large risk for genetic disease in offspring conceived many years after treatment. With 80% power to detect an increase as small as 40% in the rate of genetic disease in offspring, this study did not do so. However, we cannot rule out the possibility that new therapeutic agents or specific combinations of agents at high doses may damage germ cells.

Autonomic dysfunction associated with locked-in syndrome in a child.

This is a report of a young boy with the unusual combination of autonomic dysfunction with locked-in syndrome following multiple shunt revisions for hydrocephalus. A review of the literature on autonomic dysfunction syndrome and the complex clinical picture of the combined syndromes in a pediatric patient are discussed. The marked effectiveness of treatment with carbidopa/levodopa over bromocriptine for both syndromes is noted.

High-risk children referred to an early-intervention developmental program.

Early-intervention programs for infants with developmental disabilities or with high-risk factors for such problems were first established in the United States more than 20 years ago. The benefits of such programs are generally recognized. This study describes the presenting problems of 698 children referred to an early-intervention program over a 15-year period (1975-1989). Medical condition groups rather than specific diagnoses are considered. The developmental progress of 464 children who attended the program for at least 6 months was determined by comparing their admission and discharge developmental quotients (DQ). Admission trends over time are noted and the value of intervention programs for young children with disabilities is discussed.

Oxidative and other DNA damages as the basis of aging: a review.

DNA damages occur continuously in cells of living organisms. While most of these damages are repaired, some accumulate. In particular, there is evidence for DNA damage accumulation in non-dividing cells of mammals. These accumulated DNA damages probably interfere with RNA transcription. We consider that the decline in the ability of DNA to serve as a template for gene expression is the primary cause of aging. Oxidative DNA damages are among the best documented and prevalent DNA damages and are likely to be a prominent cause of aging.

Childhood cancer survivors: attained adult heights. Compared with sibling controls.

As part of a large collaborative study, the authors administered a pretested questionnaire to 62 childhood and adolescent cancer survivors and 62 same-sex sibling controls. The authors requested information regarding attained adult height on the questionnaire. Mean adult height of survivors (172.2 cm) was less than that of controls (174.1 cm), at a borderline significant difference of p = 0.0757. Multivariate analysis examined four potential, independent variables as possible predictors of this difference. The presence of brain tumor (vs. nonbrain tumor) (p less than .0001) and diagnosis at an early age (less than or equal to 8 years vs. 9-15 years) (p = .05) were factors significantly related to the differential; sex of patient and type of therapy were not. Our findings thus identify malignancy site and age at diagnosis as important predictors of adult height in childhood and adolescent cancer survivors.

Unknown syndrome in sibs: microcephaly, seizures, mental retardation, congenital heart disease, and skeletal abnormalities.

We present two male sibs with a series of malformations including microcephaly, mental retardation, congenital heart disease, skeletal abnormalities, micropenis, and mild hypothyroidism. Both have had seizures. While the pattern of abnormalities is similar to that previously reported in this journal as an unknown syndrome, the facies is clearly distinct, the hypothyroidism is mild, micropenis is present, and there are additional minor skeletal abnormalities.

Significance of minor abnormalities in children.

Minor abnormalities reflect problems in prenatal development and can provide useful clues to the presence of major anomalies or developmental problems. In a comparative study, children with Down's syndrome, as expected, had significantly more minor abnormalities than those with other syndromes or major anomalies and those with developmental delay and/or cerebral palsy of unknown etiology. These two groups were not significantly different from each other in the number of minor abnormalities, but both had significantly more abnormalities than the group of normal children.

Reproductive problems and birth defects in survivors of Wilms' tumor and their relatives.

In a retrospective cohort study of 47 Wilms' tumor survivors and their 77 sibling controls, female survivors had a fourfold excess risk (risk ratio, 4.1; 95% confidence interval, 1.7-10.1) for any adverse livebirth outcome, including birth defects, compared with their sibling controls. Wives of male survivors had no apparent excess risk for problem pregnancies. The families had a number of severe reproductive problems and major birth defects, such as primary amenorrhea in two survivors, bicornuate uterus in two survivors and one control, and mental retardation in one male survivor and a male control. The son of a female survivor died after bilateral Wilms' tumors. Birth defects in the offspring of female survivors are compatible either with intrauterine constraint, possibly due to radiation-induced fibrosis or with the complex of malformations associated with Wilms' tumor. Female survivors of Wilms' tumor appear to be at increased risk for a variety of reproductive problems, from sterility to fetal loss, early delivery, and birth defects in offspring. Furthermore, relatives of survivors of Wilms' tumor may be at risk of having associated birth defects, with clinically significant consequences.

Hepatoblastoma in families with polyposis coli.

We observed hepatoblastoma in four unrelated children who have a family history of polyposis coli and found this association in ten other kindreds in the literature. The one child in our series who has survived hepatoblastoma showed multiple colonic adenomas at 7 years of age. She and eight affected maternal relatives also had congenital hypertrophy of the retinal pigment epithelium, a new marker of gene carriers in some polyposis coli families. These findings suggest that childhood hepatoblastoma is an associated feature of familial polyposis coli.

A strategy to improve developmental screening during well baby visits.

There is evidence that the developmental exam is frequently neglected during the well baby exam because of time constraints. We placed a simple, standardized developmental screening instrument on the medical record of children under two years of age and then monitored physician use of the chart for the next 18 months. Developmental screening increased from 15.7% during the 12 months prior to our intervention to 41.9% during the 12 months after our intervention. Use of the screening instrument by faculty appeared to have an important influence on resident physician use of the instrument during the well baby exam.

Accumulation of DNA damages in aging Paramecium tetraurelia.

Paramecium tetraurelia cells of ages 4, 15, and 27 days were labeled with [14C]-thymidine. In addition, cells were grown clonally for 27 days (108 generations) and labeled with [14C]-thymidine in the presence of 0.5 or 7.5 micrograms/ml of mitomycin-C (MMC) or no MMC. These cells were gently deposited on a filter membrane, which impedes the passage of DNA strands. The cells were then lysed with detergents and the cellular components washed through the filters, leaving double-stranded DNA intact on the surface. Proteinase K was used to remove histone or DNA-bound proteins. The DNA was then eluted under alkaline conditions, which denatures double-stranded DNA and converts apurinic/apyrimidinic sites into single-strand breaks. The results obtained with the cells of ages 4, 15, and 27 days (16, 60, and 108 generations, respectively) indicate that as Paramecium tetraurelia ages during asexual reproduction, apurinic/apyrimidinic lesions, strand breaks or single-strand gaps accumulate. This accumulation may be the basic mechanism of aging in such cells. In the MMC-treated cells of 27 days (108 generations), the MMC reduced elution of DNA fragments more at the higher than at the lower pH's used; random MMC cross-links should occur more often in longer strands than in shorter strands. The reductions in elution preferentially at higher pH, at which longer single strands would be eluted, confirmed the pH-versus-length relationship for Paramecium DNA eluted under our conditions.

Accumulation of DNA fragments in aging Paramecium tetraurelia in axenic and nonaxenic media.

The accumulation of DNA fragments in aging Paramecium tetraurelia after 15 days (or approximately 60 generations) of clonal growth in both axenic and nonaxenic media was assayed by alkaline elution assay. This sensitive technique permits measurement of single-strand breaks in double-stranded DNA. The results obtained indicate that P. tetraurelia aged in axenic medium accumulate more apurinic/apyrimidinic lesions, strand breaks, or single-strand gaps than do P. tetraurelia aged in nonaxenic medium. This implies that cells grown in axenic medium have a shorter lifespan than do cells grown in nonaxenic medium. The accumulation of DNA fragments may be the basic mechanism of aging in P. tetraurelia.