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Biomedical subjects

F D Johnstone

Publications and source records attributed to F D Johnstone.

At least 37 records · Page 2Linked to original sources

Does early growth delay occur in diabetic pregnancy?

OBJECTIVE: To identify the date of ovulation in pregnant women with Type 1 diabetes in order to assess the validity of the concept of early growth delay. DESIGN: Identification of ovulation by measurement of urinary luteinising hormone and assessment of fetal growth using ultrasound scan. SETTING: Diabetic pre-pregnancy and antenatal clinic in a teaching hospital. SUBJECTS: Twenty women with Type 1 diabetes who had attended a pre-pregnancy clinic. MEASURES: Urinary LH, by laboratory and kit methods, during conception cycles. Human chorionic gonadotrophin measured in early pregnancy. Early ultrasound scans by a single observer blind to menstrual and ovulation dates. OUTCOME: Gestation calculated from ovulation date and gestation estimated from menstrual dates, compared with gestation at age indicated by early ultrasound scan. RESULTS: When the date of ovulation was identified in 20 women with Type 1 diabetes there was no evidence of growth delay in any pregnancy. When gestation was estimated from menstrual dates there was apparent early growth delay in six pregnancies. CONCLUSION: This study, together with others discussed, indicates that early growth delay is probably an artefact of incorrectly estimated ovulation date.

Diabetes Mellitus, Type 1↗

Maternal HIV infection, drug use, and growth of uninfected children in their first 3 years.

OBJECTIVE: To determine the separate effects of maternal HIV infection and drug use during pregnancy on growth of uninfected children in their first 3 years. DESIGN: Retrospective analysis of measurements from health visitor records made during routine child health surveillance at 6 weeks, 10 months, and 3 years of age. Multilevel analysis allowed for between-infant variation in fitted growth lines, and adjustment for other factors. Growth was described in terms of an intercept (z score at term) and growth slopes (change in z score per year) up to, and from, 4 months. SUBJECTS: 290 case babies delivered in Edinburgh hospitals to women who reported injection drug use by either themselves or their HIV infected partner, and 186 community controls. A total of 131 (45%) of the case babies were born to women who used drugs, predominantly opiates, during pregnancy and 93 (32%) to HIV infected women. The eight infected children were excluded from analysis. MAIN OUTCOME MEASURES: Age and sex standardised z scores for height, weight, and body mass index. RESULTS: 459 (96%) of the 476 records for cases and controls were traced, yielding 1432 weight and 939 height measurements. Maternal HIV infection was not found to affect growth; at 3 years the estimated effect on weight z score was 0.16 with 95% confidence interval (-0.25 to 0.57) and for height 0.18 (-0.19 to 0.55). Drug use during pregnancy was associated with lighter babies at 40 weeks followed by depressed growth in the first four months, these infants remaining just slightly smaller at 3 years with an estimated effect on z scores of -0.5 for weight with 95% confidence interval (-0.89 to -0.11) and -0.37 (-0.72 to -0.02) for height. CONCLUSIONS: Maternal HIV infection does not adversely affect growth in uninfected infants, and the effect of drug use during pregnancy is limited to small decrease in size at 3 years.

Body Height↗

Spread of maternal HIV infection in Scotland from 1990 to 1992.

In Scotland since January 1990, unlinked anonymous testing of Guthrie cards has documented maternal HIV-1 antibody in neonatal blood. District postcode and quarter year of birth determined prevalence and spread of infection. The Fujirebio particle agglutination assay screened for HIV-1 antibody, with confirmation by ELISA and full western blotting. Births to known HIV infected women were reported to the Royal College of Obstetricians and Gynaecologists. 0.3/1000 childbearing women were infected with HIV-1 with no significant increase from 1990 to 1992. Spread of infection from 11 to 26 districts has occurred. In 1990, 74%(14/19) of HIV positive deliveries were known to obstetricians falling to 33%(7/21) in 1992. Spread of HIV-1 infection has occurred to mothers who live outside closely defined areas and who do not belong to recognised high risk groups. In Scotland, two thirds of mothers and their infants will not receive early prophylactic care for their HIV disease.

AIDS Serodiagnosis↗

Immunohistochemical characterization of endometrial lymphoid cell populations in women infected with human immunodeficiency virus.

OBJECTIVE: To determine whether lymphocytic infiltration of the endometrium accompanies human immunodeficiency virus (HIV) infection. METHODS: Endometrial samples from 12 HIV-infected women and from rigorously matched controls were examined. The following markers were used: common leukocyte antigen (CD45), T lymphocytes (CD3), monocytes-macrophages (CD68), and CD4 and CD8 lymphocytes. Cell counts were performed without knowledge of HIV status. Factors considered in relation to these markers were menstrual symptoms, pelvic pain, peripheral blood CD4+ count, and time since seroconversion. RESULTS: Histology showed conventional features of chronic endometritis in only one case. In the remainder, the endometrium of HIV-infected women, compared with controls, showed an increase in CD45 cells (P < .02) and an increase in CD3 staining cells (P < .05). This appeared to be restricted to those with menstrual symptoms, and this group also had lower peripheral blood CD4 counts. There was no difference in cells of the monocyte-macrophage series (CD68). In contrast to control samples, CD4 lymphocytes were infrequent or absent in the endometrium of HIV-infected women, regardless of peripheral blood CD4 count or presence of menstrual symptoms; however, this was not universal, as one sample showed an area of dense CD4 cell infiltration. The ratio of CD4 to CD8 was reduced in HIV-seropositive samples compared with controls (P < .02). CONCLUSION: We hypothesize that chronic endometritis of a nonclassical form may be common in advancing HIV disease, possibly directed against HIV-infected cells or self-determined antigens. This could be associated with morbidity and may represent a reservoir of infection. Endometrial depletion of CD4 cells is a common, but not universal, feature and may be independent of immune compromise.

Adult↗

Lymphocyte subpopulations in early human pregnancy.

OBJECTIVE: To examine changes in lymphocyte subpopulations in early pregnancy using a methodologically appropriate study design that addresses previous sources of bias. METHODS: Thirty-seven healthy women without risk factors for human immunodeficiency virus (HIV) were reviewed when less than 9 weeks pregnant (median 51 days, range 44-61) and again at least 4 weeks following termination of pregnancy. No woman took the oral contraceptive pill. Blood was taken on each occasion at the same time of day under the same conditions of rest and food intake, transported immediately to the laboratory, and directly prepared for analysis. Lymphocyte surface markers were determined by staining with dual-colored, isotype-matched monoclonal antibody fluorescent conjugates, followed by whole blood lysis and subsequent flow cytometric analysis. RESULTS: Pregnancy was associated with a significant reduction in total lymphocytes (P < .0001) and also in CD4+ cells, whether expressed as a percentage of lymphocytes (P = .004), an absolute count (P = .0006), or a ratio (P = .01). Change was independent of the basal level except for lymphocytes, and almost all indices had significant correlations between pregnant and nonpregnant values. CONCLUSIONS: In this study design, each woman served as her own control and all factors remained constant except the pregnancy state. Early pregnancy causes a reduction in total lymphocytes of about 6% expressed as a percentage of total white cell count, and in CD4+ cells by 3% as a percentage of lymphocytes, or 100/mm3. We believe this fall can be accepted as definitive.

Adolescent↗

A population-based, controlled study of the relation between HIV infection and cervical neoplasia.

OBJECTIVE: To study a geographically defined population of women exposed to a drug-related risk for human immunodeficiency virus (HIV), together with carefully matched neighbourhood controls, in order to examine (1) the proportion of different groups having cervical cytopathology screening; (2) the association between HIV infection and cervical intraepithelial neoplasia; (3) the independent effect of CD4+ lymphocyte count and duration of HIV infection; and (4) the correspondence between cervical cytopathology and colposcopically directed biopsy. DESIGN: A population-based study. SUBJECTS: All women domiciled in Lothians with the following characteristics: between 1983 and 1987 they had a history of injection drug use or a seropositive partner with a history of injection drug use; they had a pregnancy after that exposure where their serostatus was known. In addition, neighbourhood controls were identified by computer matching for the following criteria--post-code sector, housing deprivation score, age, parity, pregnancy outcome, ethnic group, year of pregnancy, smoking. MAIN OUTCOME MEASURES: Search was carried out for the cervical smear nearest in time to the index pregnancy end date, providing serostatus was known at that time. All identified smears were assessed by a cytopathologist without knowledge of clinical information, study group or serostatus. RESULTS: Of 376 women, appropriate cervical smears were identified for 336. The proportions screened in the different groups were similar. There were more abnormal smears in the seropositive group than in the drug-related seronegative (P < 0.01) or the neighbourhood control groups (P < 0.001). HIV-infected women with abnormal smears had lower CD4+ lymphocyte counts (P < 0.0005). There was a reasonable correspondence between cytopathological classification and histological grading, and this was of similar strength in cases and controls (weighted kappa 0.72, 0.74). CONCLUSIONS: There is a definite relation between HIV infection and cervical intraepithelial neoplasia. This is related to immune depletion but whether this is the sole mechanism for the association is unclear.

Adult↗

Lack of association between maternal phosphoglucomutase-1 phenotype and fetal macrosomia in diabetic pregnancy.

OBJECTIVE: To assess the reports that maternal phosphoglucomutase-1 (PGM1) phenotype is highly related to macrosomia in diabetic pregnancy. This could be either a direct metabolic phenomenon, or the PGM1 locus could be a marker for a tightly linked gene involved in the maternal control of fetal growth. DESIGN: A comparative biochemical genetic study. SETTING: A large diabetic pregnancy clinic. SUBJECTS: One hundred and fifty-two women who had diabetes during pregnancy, 136 being insulin dependent before pregnancy. Two hundred and thirty-six women without pre-existing medical or pregnancy complications who functioned as a control group. MEASURES: PGM1 phenotype was assessed by conventional electrophoresis and subgroups were examined using iso-electric focusing. OUTCOME: Standardised birthweight was corrected for sex, maternal parity and gestation confirmed in every case by early pregnancy ultrasound. Maternal diabetes control was assessed by glycosylated haemoglobin. RESULTS: No differences were found in the observed phenotype frequencies for diabetics and control pregnant women. No association between PGM1 phenotype and macrosomia in diabetic pregnancy was found. PGM1 did not make a significant contribution to birthweight, standardised birthweight, length or ponderal index of the baby as assessed by multiple regression. CONCLUSIONS: Our study of a larger number of insulin dependent diabetics in Scotland makes the claim that macrosomia in diabetic pregnancy is associated with PGM1 phenotype unlikely to be of general significance.

Analysis of Variance↗

Insulin requirements during pregnancy in women with type I diabetes.

OBJECTIVES: To document individual variations in the rise in insulin requirements during type I diabetic pregnancies, to relate the degree of increase to maternal characteristics and fetal outcome, and to examine these factors in a subgroup of patients experiencing a large fall in insulin requirement in the third trimester. METHODS: Insulin dose was documented in 237 pregnancies in women with type I diabetes. Multiple regression analysis was performed to identify significant associations with maternal and fetal characteristics. Eighteen pregnancies with a fall in insulin requirement of 30% or more in the third trimester were considered in detail. RESULTS: The mean absolute increase in insulin requirement was 52 units. The degree of rise was significantly related to maternal weight gain between 20-29 weeks and maternal weight at booking, and was inversely related to duration of diabetes. It was not related to the degree of diabetes control, complications of pregnancy, White class, or outcome of pregnancy. In the 18 women experiencing a large fall in insulin requirement, there was no relation with maternal characteristics or fetal outcome. CONCLUSION: There is a wide individual variation in the change in insulin requirements in type I diabetic pregnancy. The degree of increase is related only to maternal weight gain during weeks 20-29 and maternal weight at booking, and is inversely related to duration of diabetes. Large falls in insulin requirement remain unexplained and may not be associated with placental failure.

Diabetes Mellitus, Type 1↗

The effect of introduction of umbilical Doppler recordings to obstetric practice.

OBJECTIVE: To assess the effect on obstetric practice of clinician access to umbilical artery Doppler ultrasound results. DESIGN: Randomised controlled trial. SETTING: A large teaching hospital. SUBJECTS: Two thousand two hundred and eighty-nine pregnancies defined as being at risk by referral for Doppler or fetal monitoring. INTERVENTIONS: Continuous wave Doppler studies of umbilical artery. Results immediately available to clinicians. MAIN OUTCOME MEASURES: Fetal outcome: perinatal mortality, Apgar score and admission to the neonatal unit. Obstetric intervention: admission to hospital, induction of labour and caesarean section. Use of of fetal well being: cardiotocography, biophysical profile and ultrasound biometry. RESULTS: The treatment and control groups were comparable in age, parity, gestation at point of entry and risk features. There were no overall differences in perinatal outcome, obstetric intervention or use of fetal monitoring. Examination of a subset recruited only because of hypertension or suspected intrauterine growth retardation (n = 754) similarly showed no difference attributable to group randomisation. Comparison of only those pregnancies retrospectively defined as low risk and high risk showed more use of cardiotocography in the high risk group with access to Doppler (P = 0.007) but no difference in the low risk group. CONCLUSION: Doppler umbilical artery recording has been shown to perform well in prediction power of antenatal fetal compromise. What has been examined in this study is the response of clinicians to the test. The results suggest that obstetricians do not use the test to modify their risk assessment, and, therefore, the need for fetal monitoring in particular pregnancies. There is a real need for accumulation of information from very large data sets, particularly in the prediction power of Doppler for antenatal fetal compromise from apparently chronic utero-placental cause to guide use of monitoring resources. If simply added to existing fetal monitoring techniques in a hospital where these are widely used, then umbilical artery Doppler recordings may at present simply involve extra resources of staff and expenses, without benefit.

Adult↗

Fetal growth, gestation length and phosphoglucomutase-1 phenotype.

This study investigates reports that phosphoglucomutase-1 (PGM1) phenotype is associated with fetal growth and gestation length. A total of 350 women were studied, 234 having uncomplicated pregnancies and 114 with a baby weighing greater than 90th centile, corrected for parity, gestation and fetal sex. All women had gestation confirmed by early ultrasound. Conventional cellulose acetate electrophoresis was used to distinguish the three common PGM1 phenotypes and polyacrylamide gel isoelectric focusing to distinguish the ten PGM1 subtypes. Neither PGM1 phenotype nor subtype were found to be associated with gestation length or standardised birth weight. Logistic regression, where maternal age, parity, fetal sex, maternal weight, gestation and smoking were introduced as explanatory variables in addition to PGM1 phenotype testing against the dependent variables birth weight, standardised birth weight and gestation length, did not show differences related to PGM1 phenotype. Two possible reasons for the discrepancy with previously published data are discussed. We conclude that the study provides no support for the belief that PGM1 phenotype is related to fetal growth or gestation length and that the original observations could have arisen as a result of statistical artefact due to multiple testing.

Biomarkers↗

Survival time after AIDS in pregnancy.

OBJECTIVE: To examine the suggestion, based on theoretical considerations and case reports, that pregnancy decreases survival time after AIDS (acquired immunodeficiency syndrome). DESIGN: A total population study in Edinburgh. SETTING: A city with a moderately high prevalence of human immunodeficiency virus (HIV) infection in women. SUBJECTS: AIDS has been diagnosed in 22 women, five of whom had a pregnancy. MAIN OUTCOME MEASURES: Clinical characteristics, disease presentation, lymphocyte markers, pregnancy outcome, subsequent progress and survival time. RESULTS: Pregnancy was not obviously associated with a difference in clinical findings. The mean survival time for the three women with a pregnancy who died was 24 months and for the 11 women without a pregnancy it was 15 months. (P = 0.63 log rank test). CONCLUSIONS: The clinical presentation, severity of the illness and laboratory findings were not obviously different in pregnancy. All three women who had Pneumocystis carinii pneumonia for the first time in pregnancy survived this initial episode. Survival time was not obviously reduced by the conjunction of pregnancy with AIDS.

Acquired Immunodeficiency Syndrome↗

Doppler umbilical artery flow velocity waveforms in diabetic pregnancy.

OBJECTIVE: To assess the effect of uncomplicated diabetes on umbilical artery flow velocity waveforms (FVWs); to investigate the relation between glycaemic control and FVWs and the predictive value of umbilical artery FVWs for antenatal fetal compromise. DESIGN: Prospective descriptive study. SETTING: A large diabetic pregnancy clinic in a teaching hospital. SUBJECTS: 128 pregnancies complicated by diabetes mellitus. 170 non diabetic women with no pre-existing or pregnancy complications. INTERVENTIONS: In diabetic pregnancies, umbilical artery resistance index (RI) Doppler recordings and glycosylated haemoglobin were measured every 2 weeks from 28 weeks. MAIN OUTCOME MEASURES: Umbilical artery RI and antenatal fetal compromise defined as a non reactive, decelerative cardiotocograph and/or a biophysical profile score persistently less than 6 and leading to immediate caesarean section. RESULTS: Uncomplicated diabetic pregnancies had FVW values similar to those in the non-diabetic range. Glycaemic control was unrelated to umbilical artery FVW values. Abnormal umbilical artery RI was found in nine pregnancies, these were more likely to show evidence of fetal compromise and to be associated with birthweights of less than 50th centile. In seven pregnancies there was evidence of fetal compromise, but only three of these pregnancies had abnormal FVW values. CONCLUSIONS: The non-diabetic range of umbilical artery RI values is appropriate for diabetic pregnancies. Long-term glycaemic control, within the range in this study, does not seem to affect umbilical artery RI. Abnormal umbilical artery RI is a significant predictor of fetal compromise in diabetic pregnancy, but fetal compromise can occur in association with normal RI values. Undue reliance should not be placed on normal FVW values in diabetic pregnancies.

Apgar Score↗