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Biomedical subjects

G J Knight

Publications and source records attributed to G J Knight.

At least 19 recordsLinked to original sources

Prenatal screening for Down's syndrome with use of maternal serum markers.

BACKGROUND: Approximately 35 percent of all cases of Down's syndrome in fetuses can be detected by measuring maternal serum alpha-fetoprotein during the second trimester in the general population of pregnant women. Recent case-control studies indicate that this detection rate could be approximately doubled by measuring serum levels of unconjugated estriol and chorionic gonadotropin, which are abnormally low and abnormally high, respectively, in women carrying fetuses affected by Down's syndrome. METHODS: We prospectively screened 25,207 women and adolescents in the second trimester of pregnancy and assigned each a risk of fetal Down's syndrome with an algorithm that took into account measurements of all three serum markers in combination with maternal age. On this basis, 1661 subjects (6.6 percent) were initially assigned a second-trimester risk of fetal Down's syndrome of at least 1 in 190, and 962 (3.8 percent) were offered amniocentesis for chromosomal analysis after verification of gestational age. Gestational age was determined on the basis of the first day of the last menstrual period or, when available, by ultrasonography. RESULTS: Among the 760 women and adolescents who chose amniocentesis, 20 cases of fetal Down's syndrome were detected, along with 7 other chromosomal disorders. There was 1 additional case of fetal Down's syndrome among the 202 women who chose not to have amniocentesis. The rate of detection of Down's syndrome was thus 58 percent (21 of 36 expected cases), and the frequency of identifying a fetus with Down's syndrome in women undergoing amniocentesis was 1 per 38 amniocenteses (95 percent confidence interval, 1 in 25 to 1 in 62). CONCLUSIONS: Measuring serum alpha-fetoprotein, chorionic gonadotropin, and estriol is more effective in screening for fetal Down's syndrome than measuring maternal serum alpha-fetoprotein alone. Such an expanded protocol can readily be incorporated into existing prenatal screening programs.

Adolescent

An unsuccessful cotinine-assisted intervention strategy to reduce environmental tobacco smoke exposure during infancy.

OBJECTIVE: To test a low-intensity physician's office-based intervention strategy using infant urine cotinine measurements, aimed at reducing infant exposure to environmental tobacco smoke. DESIGN: A randomized intervention trial. SETTING: Offices of 28 physicians (pediatricians and family practitioners) and two hospital-based clinics in the Greater Portland, Me, area. PARTICIPANTS: Infants brought to the physician by a parent (usually the mother) for an initial well-child visit. A total of 518 of these infants and their mothers consented to provide information about household smoking habits and to provide a sample of the infant's urine for biochemical analysis. SELECTION PROCEDURE: From among the consecutive sample of 518 enrolled mother/infant pairs, 103 mothers reported that they smoked 10 or more cigarettes per day, and these were randomized on an individual basis for intervention (52 pairs) or control (51 pairs). Randomization took place at the study center when the infant's urine sample and information about household smoking habits were received. INTERVENTION: The physician telephoned the mother to report the urine cotinine result and to explain its meaning. The physician then signed and sent an individualized form letter to the mother, providing specific recommendations for changing household smoking habits. RESULTS: Follow-up urine cotinine measurements were obtained in 27 (52%) of 52 infants from the intervention group and in 29 (57%) of the 51 controls 2 months later. The mean log ratio of the follow-up to initial urine cotinine measurements was 6% lower in the intervention group than in the control group. This difference was not statistically significant. CONCLUSION: The low-intensity intervention strategy did not significantly influence infant exposure to environmental tobacco smoke in the household.

Adult

Prospective intervention trial of a screening protocol to identify fetal trisomy 18 using maternal serum alpha-fetoprotein, unconjugated oestriol, and human chorionic gonadotropin.

Two prenatal centres in New England, routinely using a screening protocol for fetal Down syndrome that included maternal serum alpha-fetoprotein (AFP), unconjugated oestriol (uE3), and human chorionic gonadotropin (hCG) measurements in combination with maternal age, adopted a separate screening protocol for trisomy 18. That protocol identified a pregnancy as being at high risk when AFP, uE3, and hCG measurements all fell at or below specified cut-offs (0.75, 0.60, and 0.55 multiples of the median, respectively), regardless of maternal age. Among the first 19,491 women screened, 98 (0.5 per cent) were found to have values which placed them in the high-risk category. Four of these women were subsequently found not to be pregnant. In two others, samples from non-pregnant individuals were found to have been incorrectly submitted for analysis in place of the samples from the pregnant women. All of the remaining 92 women were counselled and offered amniocentesis and fetal karyotyping. Eighty-eight (96 per cent) accepted. Karyotypes or birth outcomes were available on all 92 pregnancies. Six cases of trisomy 18 and one case of Turner syndrome were identified by karyotype. One case of trisomy 18 was identified for every 14 unaffected pregnancies offered amniocentesis. In the present prospective study, an estimated 85 per cent of the cases of trisomy 18 were identified. However, given the small number of cases (six), the 95 per cent confidence interval for the detection rate is broad (40-95 per cent).

Adult

Single daily dose ceftriaxone therapy in epiglottitis.

Ceftriaxone as a single daily intravenous dose for 5 days was used to treat seven patients with proven Haemophilus influenzae epiglottitis. All children responded favourably. The serum levels achieved exceeded the MIC by up to 1500 times at the trough level during and for up to 24 h after the completion of the treatment. Side effects were mild and transient and did not disrupt the continuity of the treatment. Ceftriaxone potentially offers a number of clinical and economic advantages in the management of epiglottitis.

Ceftriaxone

Primary staphylococcal pneumonia in childhood: a review of 69 cases.

Primary staphylococcal pneumonia is a rapidly progressive illness with well-described clinical and radiological features and a significant mortality rate. This retrospective study of cases diagnosed over a 20 year period at a tertiary paediatric hospital was undertaken to document the epidemiology and assess the management and mortality of the disease. The survey demonstrated that far fewer patients are being seen than formerly and confirmed that this is a disease primarily affecting infants and Aboriginal children. The initial radiological features were not diagnostic in the majority of cases but typical changes appeared in most at some time during the illness. The use of surgical drainage was not associated with a decrease in the duration of fever or length of hospital stay. The mortality rate has improved but remains significant.

Child

Lack of an association between late fetal death and antiphospholipid antibody measurements in the second trimester.

To examine the relationship between elevated antiphospholipid antibody levels in the maternal circulation and late fetal death, we carried out a case-control study in which levels of anticardiolipin and antiphosphatidylserine antibodies were measured in banked second-trimester sera from 309 pregnancies ending in fetal death and from 618 viable control pregnancies. The sera were obtained from a population base of approximately 22,000 pregnancies enrolled for maternal alpha-fetoprotein screening between 15 and 20 weeks' gestation. The anticardiolipin immunoglobulin G level was markedly elevated (15.6 SD) in one serum sample associated with a fetal death. Otherwise, the anticardiolipin and antiphosphatidylserine measurements were similar in the two populations. Several other factors known to be associated with fetal death were also examined, and these all demonstrated the expected relationship. Antiphospholipid antibody measurements obtained at 15 weeks' gestation or later in the general pregnancy population are not helpful in identifying pregnancies at risk for fetal death.

Adult

Cotinine-assisted intervention in pregnancy to reduce smoking and low birthweight delivery.

OBJECTIVE: To investigate the feasibility and impact of integrating a cotinine-assisted smoking intervention programme with an existing antenatal maternal serum alpha-fetoprotein (AFP) screening service for open neural tube defects. DESIGN: A multisite randomized controlled trial. SETTING: 139 physician offices and clinic sites in Maine providing antenatal care. SUBJECTS: 2848 pregnant women who smoked 10 or more cigarettes daily, enrolled at between 15 and 20 weeks gestation, from a population base of approximately 18,000 pregnancies. INTERVENTIONS: The women were individually allocated at random to intervention or control groups within each centre at the time the serum sample was received for AFP measurement. The intervention group received an interpreted measurement of the serum cotinine, reported through the physician to the woman, along with a self-help smoking cessation booklet and a repeat serum cotinine measurement one month later, again interpreted and reported through the physician to the woman. Women in the control group received the usual anti-smoking advice provided by the antenatal care site and were not told of the study. MAIN OUTCOME MEASURES: Birthweight, physician cooperation with study protocol (as measured by effectiveness in obtaining repeat serum samples for cotinine measurements). RESULTS: Pregnancy outcome data were available for 97% of the study population, including birthweight for 2700 singleton viable pregnancies. The smoking intervention programme led to a significant 66 g increase in mean birthweight (P = 0.03; 95% CI+9 to +123 g) and to a 30% reduction in the rate of low birthweight in pregnancies managed by the 70 physicians who secured the highest rate of obtaining repeat serum samples for cotinine measurements in their intervention group. Among the remaining 69 physicians, intervention had no detectable effect on birthweight. CONCLUSION: A cotinine-assisted smoking intervention programme managed from a central location as an adjunct to a maternal serum AFP screening service can, with the cooperation of physicians responsible for antenatal care, lead to a significant and cost-effective reduction in the number of low birthweight babies. This programme is inexpensive, requires little extra effort, and does not need specially trained personnel.

Adult

Self-rated physical activity level during the second trimester and pregnancy outcome.

To examine the relationship between level of physical activity during pregnancy and subsequent pregnancy outcome, we asked women enrolling for maternal serum alpha-fetoprotein (MSAFP) screening in Maine during the years 1984-1988 to rate their usual physical activity level as light, moderate, or vigorous. Overall, 23,091 women were approached and 21,342 (92%) responded. Ten percent rated their physical activity level as light, 84% as moderate, and 6% as vigorous. Those who identified their physical activity level as vigorous were, on average, slightly older and more educated, and weighted less than women in the other two categories. However, there were no significant differences in the rates of low birth weight or fetal or neonatal death.

Adult

Second-trimester levels of maternal serum unconjugated oestriol and human chorionic gonadotropin in pregnancies affected by fetal anencephaly and open spina bifida.

Unconjugated oestriol (uE3) and human chorionic gonadotropin (hCG) levels were determined in second-trimester maternal serum (MS) samples from 21 pregnancies associated with fetal anencephaly and 15 pregnancies associated with fetal open spina bifida. Each measurement was expressed as a multiple of the median (MoM) for unaffected pregnancies for each completed week of gestation. In pregnancies associated with anencephaly, the median value for MSuE3 was very low (0.17 MoM, range less than 0.12-0.33 MoM), suggesting a functional defect in the fetal adrenal prior to 20 weeks' gestation; the median value for MShCG was also low (0.73 MoM), although not to the same extent as for MSuE3. A biological explanation for the hCG result is not apparent. In pregnancies associated with open spina bifida, the MSuE3 and MShCG values were unremarkable, consistent with a lack of involvement of these open fetal defects in the synthesis and secretion of uE3 and hCG.

Anencephaly

Maternal serum alpha-fetoprotein screening for fetal Down syndrome in the United States: results of a survey.

To determine the status of maternal serum alpha-fetoprotein screening for fetal Down syndrome in the United States, we surveyed member laboratories in the External Quality Assessment Scheme for Pregnancy alpha-Fetoprotein in the spring of 1988. Of the 123 member laboratories that provide screening services, 109 responded. The 109 laboratories screened 586,000 pregnancies annually, and 96 provided interpretations for risk of fetal Down syndrome, accounting for 534,000 pregnancies. Numbers of women screened annually per laboratory ranged from less than 200 to greater than 27,000 (median 3000). A total of 85 of the 96 laboratories used a combination of the maternal serum alpha-fetoprotein cut-off. Ultrasonographic gestational dating was used for the initial interpretation in 25% of the screened pregnancies. The median initial positive rate (the number of women initially classified as being at increased risk) was 3.7% overall, and smaller laboratories were more likely either to have outlying initial positive rates or to be unable to provide such rates. Median initial positive rates were lower for enzyme immunoassay kits than for radioimmunoassay kits (3.0% versus 4.8%). These results indicate that, whereas most laboratories appear to perform satisfactorily in screening for fetal Down syndrome, some laboratories appear to perform satisfactorily in screening for fetal Down syndrome, some laboratories need to refine their methods of assigning risk and others need to develop mechanisms to document initial positive rates and, when appropriate, to analyze the cause of outlying initial positive rates. This survey, combined with information from nonsurveyed laboratories known to screen for fetal Down syndrome, allows an estimation that 1 million pregnancies annually were provided with fetal Down syndrome interpretations in the United States in mid-1988.

Adult

Cotinine analytical workshop report: consideration of analytical methods for determining cotinine in human body fluids as a measure of passive exposure to tobacco smoke.

A two-day technical workshop was convened November 10-11, 1986, to discuss analytical approaches for determining trace amounts of cotinine in human body fluids resulting from passive exposure to environmental tobacco smoke (ETS). The workshop, jointly sponsored by the U.S. Environmental Protection Agency and Centers for Disease Control, was attended by scientists with expertise in cotinine analytical methodology and/or conduct of human monitoring studies related to ETS. The workshop format included technical presentations, separate panel discussions on chromatography and immunoassay analytical approaches, and group discussions related to the quality assurance/quality control aspects of future monitoring programs. This report presents a consensus of opinion on general issues before the workshop panel participants and also a detailed comparison of several analytical approaches being used by the various represented laboratories. The salient features of the chromatography and immunoassay analytical methods are discussed separately.

Animals

Environmental tobacco smoke exposure during infancy.

We collected information about household smoking habits from 518 mothers when they made their first well child visit with a 6 to 8-week old infant. A urine sample was also collected from the infant, the cotinine concentration measured, and the measurement correlated with data provided by the mother. Eight percent of the infant urine cotinine values fell at or above 10 micrograms/L in the 305 households where no smoking was reported. Corresponding rates were 44 percent in the 96 households where a member other than the mother smoked, 91 percent in the 43 households where only the mother smoked, and 96 percent in the 74 households where both the mother and another household member smoked. In households where the mother smoked, infant urine cotinine levels were lower in the summer, and higher when the infant was breast-fed. A screening question about family smoking habits in conjunction with well child care could effectively define a group of infants exposed to environmental tobacco smoke and thus be at greater risk for respiratory diseases.

Adult

Amniotic fluid alpha-fetoprotein and acetylcholinesterase measurements in pregnancies associated with gastroschisis.

In this study we define for the first time the distribution of alpha-fetoprotein levels and acetylcholinesterase ratios in amniotic fluid samples associated with fetal gastroschisis. Elevated alpha-fetoprotein levels and positive acetylcholinesterase measurements are found in virtually all cases, indicating that these combined measurements are highly reliable in detecting this lesion.

Abdominal Muscles

Maternal serum screening for Down's syndrome in early pregnancy.

The possibility of improving the effectiveness of antenatal screening for Down's syndrome by measuring human chorionic gonadotrophin concentrations in maternal serum during the second trimester to select women for diagnostic amniocentesis was examined. The median maternal serum human chorionic gonadotrophin concentration in 77 pregnancies associated with Down's syndrome was twice the median concentration in 385 unaffected pregnancies matched for maternal age, gestational age, and duration of storage of the serum sample. Measuring human chorionic gonadotrophin in maternal serum was an effective screening test, giving a lower false positive rate (3%) at a 30% detection rate than that for maternal age (5%) and the two existing serum screening tests, unconjugated oestriol (7%) and alpha fetoprotein (11%). The most effective screening results were obtained with all four variables combined; at the same 30% detection rate the false positive rate declined to 0.5%. The new screening method would detect over 60% of affected pregnancies, more than double that achievable with the same amniocentesis rate in existing programmes (5%), and could reduce the number of children born with Down's syndrome in the United Kingdom from about 900 a year to about 350 a year.

Chorionic Gonadotropin