Canine RPGRIP1 mutation establishes cone-rod dystrophy in miniature longhaired dachshunds as a homologue of human Leber congenital amaurosis.

Cone-rod dystrophy 1 (cord1) is a recessive condition that occurs naturally in miniature longhaired dachshunds (MLHDs). We mapped the cord1 locus to a region of canine chromosome CFA15 that is syntenic with a region of human chromosome 14 (HSA14q11.2) containing the retinitis pigmentosa GTPase regulator-interacting protein 1 (RPGRIP1) gene. Mutations in RPGRIP1 have been shown to cause Leber congenital amaurosis, a group of retinal dystrophies that represent the most common genetic causes of congenital visual impairment in infants and children. Using the newly available canine genome sequence we sequenced RPGRIP1 in affected and carrier MLHDs and identified a 44-nucleotide insertion in exon 2 that alters the reading frame and introduces a premature stop codon. All affected and carrier dogs within an extended inbred pedigree were homozygous and heterozygous, respectively, for the mutation. We conclude the mutation is responsible for cord1 and demonstrate that this canine disease is a valuable model for exploring disease mechanisms and potential therapies for human Leber congenital amaurosis.

Long-term effects of nurse home visitation on children's criminal and antisocial behavior: 15-year follow-up of a randomized controlled trial.

CONTEXT: A program of home visitation by nurses has been shown to affect the rates of maternal welfare dependence, criminality, problems due to use of substances, and child abuse and neglect. However, the long-term effects of this program on children's antisocial behavior have not been examined. OBJECTIVE: To examine the long-term effects of a program of prenatal and early childhood home visitation by nurses on children's antisocial behavior. DESIGN: Fifteen-year follow-up of a randomized trial. Interviews were conducted with the adolescents and their biological mothers or custodial parents. SETTING: Semirural community in New York. PARTICIPANTS: Between April 1978 and September 1980, 500 consecutive pregnant women with no previous live births were recruited, and 400 were enrolled. A total of 315 adolescent offspring participated in a follow-up study when they were 15 years old; 280 (89%) were born to white mothers, 195 (62%) to unmarried mothers, 151 (48%) to mothers younger than 19 years, and 186 (59%) to mothers from households of low socioeconomic status at the time of registration during pregnancy. INTERVENTION: Families in the groups that received home visits had an average of 9 (range, 0-16) home visits during pregnancy and 23 (range, 0-59) home visits from birth through the child's second birthday. The control groups received standard prenatal and well-child care in a clinic. MAIN OUTCOME MEASURES: Children's self-reports of running away, arrests, convictions, being sentenced to youth corrections, initiation of sexual intercourse, number of sex partners, and use of illegal substances; school records of suspensions; teachers' reports of children's disruptive behavior in school; and parents' reports of the children's arrests and behavioral problems related to the children's use of alcohol and other drugs. RESULTS: Adolescents born to women who received nurse visits during pregnancy and postnatally and who were unmarried and from households of low socioeconomic status (risk factors for antisocial behavior), in contrast with those in the comparison groups, reported fewer instances (incidence) of running away (0.24 vs 0.60; P = .003), fewer arrests (0.20 vs 0.45; P = .03), fewer convictions and violations of probation (0.09 vs 0.47; P<.001), fewer lifetime sex partners (0.92 vs 2.48; P= .003), fewer cigarettes smoked per day (1.50 vs 2.50; P= .10), and fewer days having consumed alcohol in the last 6 months (1.09 vs 2.49; P = .03). Parents of nurse-visited children reported that their children had fewer behavioral problems related to use of alcohol and other drugs (0.15 vs 0.34; P = .08). There were no program effects on other behavioral problems. CONCLUSIONS: This program of prenatal and early childhood home visitation by nurses can reduce reported serious antisocial behavior and emergent use of substances on the part of adolescents born into high-risk families.

Long-term effects of home visitation on maternal life course and child abuse and neglect. Fifteen-year follow-up of a randomized trial.

CONTEXT: Home-visitation services have been promoted as a means of improving maternal and child health and functioning. However, long-term effects have not been examined. OBJECTIVE: To examine the long-term effects of a program of prenatal and early childhood home visitation by nurses on women's life course and child abuse and neglect. DESIGN: Randomized trial. SETTING: Semirural community in New York. PARTICIPANTS: Of 400 consecutive pregnant women with no previous live births enrolled, 324 participated in a follow-up study when their children were 15 years old. INTERVENTION: Families received a mean of 9 home visits during pregnancy and 23 home visits from the child's birth through the second birthday. DATA SOURCES AND MEASURES: Women's use of welfare and number of subsequent children were based on self-report; their arrests and convictions were based on self-report and archived data from New York State. Verified reports of child abuse and neglect were abstracted from state records. MAIN RESULTS: During the 15-year period after the birth of their first child, in contrast to women in the comparison group, women who were visited by nurses during pregnancy and infancy were identified as perpetrators of child abuse and neglect in 0.29 vs 0.54 verified reports (P<.001). Among women who were unmarried and from households of low socioeconomic status at initial enrollment, in contrast to those in the comparison group, nurse-visited women had 1.3 vs 1.6 subsequent births (P=.02), 65 vs 37 months between the birth of the first and a second child (P=.001), 60 vs 90 months' receiving Aid to Families With Dependent Children (P=.005), 0.41 vs 0.73 behavioral impairments due to use of alcohol and other drugs (P=.03), 0.18 vs 0.58 arrests by self-report (P<.001), and 0.16 vs 0.90 arrests disclosed by New York State records (P<.001). CONCLUSIONS: This program of prenatal and early childhood home visitation by nurses can reduce the number of subsequent pregnancies, the use of welfare, child abuse and neglect, and criminal behavior on the part of low-income, unmarried mothers for up to 15 years after the birth of the first child.

Immunization status of children of employees in a large corporation.

OBJECTIVE: To assess immunization levels for children of employees of a large corporation. DESIGN: A mail survey of a random sample of employees on the immunization history of one child per family. SETTING: US employees of Johnson & Johnson. PARTICIPANTS: 1500 employees with children born between 1984 and 1991. MAIN OUTCOME MEASURES: Coverage rates for recommended vaccines at different ages up to 6 years. MAIN RESULTS: Only 45.2% and 55.3% of the study children at ages 2 and 6 years were current for all recommended immunizations (65.1% and 70.3%, respectively, excluding the Haemophilus influenzae type b vaccine). Using the minimum standard required by many states for school entry, the coverage level at age 6 years was 90.4%. Factors associated with higher immunization rates at age 2 years were the corporate health plan (choices), higher pay level, greater parental formal education, white race, and knowing when to initiate immunization. Lower immunization rates at age 2 years were associated with delayed receipt of the first dose of diphtheria, tetanus, and pertussis vaccine, use of city or county clinics, employee-reported barriers of difficulty leaving work, and provider access problems, but not cost of services. After adjusting for the effects of other variables through logistic regression, race, pay level, and plan choice were no longer significant. Modeling with the remaining variables predicted rates of adequate immunization at age 2 years from 15% to 81%. CONCLUSION: Even in this relatively affluent group with good insurance (including immunizations), preschool immunization rates did not reach public health goals. Changing modifiable factors, such as knowing when to initiate immunization, enabling parents to leave work more easily, and improving provider access, might improve preschool immunization rates.

"Spontaneous" transfer of stimulus control from tact to mand contingencies.

An important issue in teaching verbal behavior to persons with severe handicaps is the transfer of stimulus control from tact (e.g., naming) to mand (e.g., requesting) relationships. Previous research has shown that topographies taught as tacts frequently fail to appear as mands unless transfer between these two response classes is explicitly programmed. Procedures promoting this transfer would provide a necessary instructional tool. Transfer from tact to mand contingencies was investigated in two adults with severe mental retardation. Correct pointing responses to line drawing symbols depicting the utensils required to access previously requested food (beverage) items were assessed prior to and following tact intervention. Mands for two of three utensils emerged following tact intervention. The results suggest transfer from tact variables to the conditioned establishing operation may be facilitated by the prior development of a minimal mand repertoire.

Cause of anaemia in malaria.

51Cr studies showed that after complete eradication of malarial parasites erythrocyte life-span is reduced for 4-5 weeks and that the reduction is associated with the presence of complement-containing immune complexes on the red-cell surface. The rate of erythrophagocytosis in the spleen is increased during this period. 59Fe studies of erythropoiesis indicated a mild degree of marrow depression. A very important factor causing anaemia in malaria appears to be a complement-mediated immune process.

Experimental Trypanosoma cruzi infection in rhesus monkeys 111. Electrocardiographic and histopathological findings.

In five rhesus monkeys surviving 'Peru strain' or 'strain 7' Trypanosoma cruzi infection for six to eight years, positive xenodiagnosis results and high indirect fluorescent antibody titres (4096 - 65536) persisted until the animals were killed. Abnormal electrocardiograph patterns in two monkeys (H and K) were possibly compatible with myocardial damage. Histopathological changes attributable to T. cruzi infection were minor in four monkeys but severe in one (R). In this animal, infected with what was judged previously to be the less virulent of the two T. cruzi stocks used ('strain 7'), there was severe myocarditis, with myofibre degeneration, and lesions of the oesophagus. Elevated serum levels of five enzymes were not detected in any of the chronically infected monkeys.

Experimental Trypanosoma cruzi infections in rhesus monkeys. II. The early chronic phase.

Information on the acute and early chronic phases of infection with Trypanosoma cruzi in eight rhesus monkeys is reported with particular reference to the pattern of subpatent parasitaemia and serology. Xenodiagnosis was superior to animal inoculation and blood culture in its capacity to detect subpatent parasitaemia. Each monkey showed an individual, relatively constant pattern of this not related to the nature of the inoculum. Levels of indirect fluorescent and indirect haemagglutinating antibodies remained elevated during a year of observations. One monkey died with a megaoesophagus. Another monkey after challenge with a heterologous strain by orbital inoculation failed to develop Romana's sign and showed no change in serum antibody levels or degree of xenopositivity.