Effect of maternal and infant covariates on sibship correlation in birth weight

Birth weight on 12,644 singleton infants from 6,196 sibships born in Maryland between 1980 and 1984 were used to estimate the effects of nine maternal and infant covariates on the sibship correlation in birth weight. Assuming a homogeneous correlation across all families, the estimated intraclass correlation was 0.4664 (+/- 0.0099). This high sibship correlation makes it possible to predict, with reasonable accuracy, the birth weight of a child given information on previous sibs, as well as covariates on the mother and/or infant pertinent to a given pregnancy. The reduction in variance associated with incorporating information on the nine covariates used here was approximately equal to that obtained by conditioning on a single previous sib. Testing for heterogeneity in correlation among different groups of families showed that a crude measure of parity (first live birth vs. other), time between births, mother's marital status, and maternal age at the birth of the last child significantly influenced the sibship correlation in birth weight.     

Gestational age and intrauterine growth retardation among white and black very low birthweight infants: a population-based cohort study

Summary. Very low birthweight (VLBW) is a commonly used endpoint in perinatal epidemiology, but the population of VLBW infants comprises a wide range of gestational ages and rates of fetal growth. We used data from a population-based study of all 1072 black and white VLBW liveborn infants born in 29 counties in Georgia between April 1986 and March 1988. Less than 1% of the VLBW infants were ≥ 37 weeks gestation; most were 29–32 weeks (26%) or 25 to 28 weeks (40%); 12% were 22 weeks or less. All infants 33 weeks gestation or greater were growth retarded. The population of VLBW infants seems to comprise three groups: approximately 11% very immature infants of 22 weeks or less; the majority of infants, born between 23 and 30 weeks, 90% of which are of normal weight for their gestational age; and a group of less premature, growth-retarded infants from 31 to 36 weeks. We found little or no difference in the distribution of gestational age or the percentage of intrauterine growth rates (IUGR) between black and white infants. In the USA the VLBW rate among black infants is over three times greater than that among white infants and consequently the rates of the three types of VLBW among black infants are likely to be triple those among white infants.     

Randomised comparison of CHOEP versus alternating hCHOP/IVEP for high-grade non-Hodgkin's lymphomas: Treatment results and prognostic factor analysis in a multi-centre trial

Background: With CHOP, the standard protocol of recent decades,about 30% of long-term survival has been reported. A numberof studies using more aggressive multidrug regimens or alternatingchemotherapies have recently suggested higher CR rates and increasedsurvival. In 1989 we reported similar results with a combined-modalitytreatment administering 6 cycles of CHOP supplemented with etoposideand an involved field irradiation for patients in PR or CR. Patients and methods: To confirm the efficacy of this approach,we initiated a prospective randomised trial comparing 4 cyclesof CHOP-VP 16 (CHOEP) with 4 cycles of two alternating regimens,‘hCHOP and IVEP’. One hundred seventy-five patientswith high-grade non-Hodgkin's lymphomas stages II-IV were stratifiedfor age, stage and LDH and randomised to receive either fourcycles of cyclophosphamide, doxorubicin, vincristine, etoposide,prednisolone (CHOEP) in arm A or four cycles of chemotherapywith a dose-intensified CHOP (hCHOP) alternating with ifosfamide,etoposide, vindesine, prednisolone (IVEP) in arm B. After fourcycles of chemotherapy an involved field irradiation with atotal dose of 35 Gy was given to all patients demonstrated tobe in complete or partial remission. Results: Of the 185 randomised patients, 175 were eligible and171 evaluable for response and survival. One hundred forty-sixof the 171 patients (85%) achieved complete remission (CR) with87% and 84% CRs in arms A and B, respectively. With a medianfollow-up of 36 months the estimated overall survival at 2 yearsis 66% and 73% for arms A and B. The percentage of all patientsin first CR is estimated to be 59% and 55% at 2 years for armsA and B, respectively. None of the differences in CR rate, survival,or relapse-free survival are statistically significant. Multivariateanalysis of subgroups incorporating the factors of sex, age,performance status, stage, B symptoms, bulky disease, LDH andhistology revealed that only stage and LDH were factors whichindependently affected outcome. The estimated 2-year survivalrate of patients with stages II, III and IV is predicted tobe 84%, 62% and 52%, respectively. Patients with LDH >250U/I have an estimated survival of 52% at 2 years versus 84%for patients with LDH     

Nucleic acid spot hybridization with nonradioactive labeled probes in screening for human papillomavirus DNA sequences

We examined 161 human tissue samples using the spot hybridization technique with nonradioactive labeled DNA probes of human papillomavirus (HPV). Whole cells were spotted on nitrocellulose filters; DNA of the cells was denatured and fixed to the filter. Then the DNA spots were hybridized to nonradioactive labeled DNA and monitored by a sandwich immunoenzymatic reaction. This technique is simple, sensitive, specific, requires no special equipment, and can be used in clinical settings. HPV DNA was found in 92% of samples in which, on the basis of histologic and colposcopic criteria, its presence was suspected, as well as in 31 samples where it was not suspected.     

Prostacyclin accumulation during orthotopic liver transplantation in man.

Significant hypotension commonly occurs upon reperfusion of the donor liver. In this study we tried to determine if there is accumulation of prostacyclin in the portal system. Blood samples for prostacyclin in twelve patients undergoing orthotopic liver transplantation were studied. Samples were collected at the beginning and end of portal vein anastomosis. Hemodynamic measurements were determined 1 min before and 3 min after portal revascularization. The results show an increase of prostacyclin from 524 +/- 134 pg/ml (n less than 72 pg/ml) to 1132 +/- 264 pg/ml. Eight patients had a decrease in systolic blood pressure from 98 +/- 5 mmHg to 61 +/- mmHg with concomitant significant increase in cardiac output (6.0) from 6.9 +/- 0.7 to 9.9 +/- 1.05 L/mm and significant decrease in systemic vascular resistance (SVR) from 724 +/- 130 dynes/sec/cm to 309 +/- 98. In conclusion, 60% of patients undergoing OLT accumulate prostacyclin in the portal vein, which could be one of the causes of hypotension seen at reperfusion of the donor liver.     

Induction of HLA-DR expression on thyroid follicular cells by cytomegalovirus infection in vitro. Evidence for a dual mechanism of induction.

Cytomegalovirus (CMV) infection of primary cultures established from human thyroid nodular and normal (paranodular) tissues resulted in induction of human leukocyte antigen (HLA) DR expression on thyroid follicular cells (TFC), as detected by cell-surface immunofluorescence staining with monoclonal antibodies (MAb). Two distinct modalities of induction were observed. The first type occurred in cultures of normal tissue obtained from CMV-seropositive but not seronegative donors, was detected on 30% to 50% of the TFCs, even though the vast majority of these cells failed to show any morphologic or antigenic evidence of individual CMV infection, and was associated with production of gamma-interferon (gamma-IFN) in vitro. The induced molecules displayed the characteristic DR polypeptide profile on immunoprecipitation and electrophoretic analysis. These results demonstrate that CMV infection of normal thyroid cultures may induce DR expression on TFCs in the absence of pre-existing lymphoid infiltrates and suggest that the induction is the result of an in vitro response to CMV by previously sensitized immunocompetent cells present in these primary cultures. Such a response, associated with the release of gamma-IFN, would induce DR expression on neighboring uninfected cells. The second mode of induction occurred in all CMV-infected cultures, regardless of their tissue origin (nodular or normal) or the serologic status of the donors. Up to 50% of infected TFCs at a late stage of infection, having fully developed CMV antigen-positive intranuclear inclusions, also displayed the cell-surface DR-related determinant recognized by one of the four anti-DR MAbs used. This induction was restricted to TFCs, while CMV-infected fibroblastoid cells present in the monolayers were invariably negative. Induction by CMV of major histocompatibility class II antigens on human epithelial cells may have significant implications in the development of normal immune responses against local viral infection, the enhancement of alloimmune rejection of grafted organs, and the generation of organ-specific autoimmune responses.     

Penetrance in the presence of genetic susceptibility to environmental factors

Many single-gene disorders (especially dominant traits) are known to exhibit "incomplete penetrance," a term often criticized as reflecting our ignorance of genetic and environmental factors that may interact with the genotype to determine the ultimate phenotype of the individual. We explore the effects of an environmental factor on penetrance for a simple model of single gene-mediated susceptibility to environmental factors. We show that penetrance of the susceptible genotype increases with increasing frequency of exposure to the factor and the strength of interaction between the factor and the genotype (relative risk). For disorders with disease frequency of 0.001 or less (as seen with many congenital malformations), penetrance is generally low (less than 10%) if the exposure frequency is low (less than 10%) even in the face of strong gene-environment interaction. Such low penetrance can lead to low recurrence risks. Single-gene effects could easily be overlooked in genetic analysis unless specific environmental factors are considered.