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Biomedical subjects

G Ryan

Publications and source records attributed to G Ryan.

At least 19 recordsLinked to original sources

Fc epsilon RI-beta polymorphism and risk of atopy in a general population sample.

OBJECTIVE: To establish the prevalence of Fc epsilon RI-beta polymorphisms Leu181 and Leu181/Leu183 on chromosome 11q13 in the general population and to examine whether when maternally inherited they confer a risk of atopy. DESIGN: A population based survey for measures of atopy (skin prick test reactions, specific IgE titres, total serum IgE concentration), bronchial hyperresponsiveness, and carriage of Fc epsilon RI-beta Leu181 and Leu181/Leu183. SETTING: The rural coastal town of Busselton, Western Australia. SUBJECTS: 1004 members of 230 two generation families identified through adults aged under 55. RESULTS: Fc epsilon RI-beta Leu181/Leu183 was identified in 45 subjects (4.5%). All 13 children who had inherited the variant maternally were atopic. Six had asthma and nine rhinitis. The odds ratio of a positive skin prick test reaction to house dust mite or grass pollen in these children compared with the other 523 children was 7.37 (95% confidence interval 1.62 to 33.60). The 95% confidence interval for the odds ratio of a positive specific IgE response (radio-allergosorbent test) was 3.00 to infinity, and the odds ratio for bronchial hyperresponsiveness was 3.70 (1.21 to 11.60). By contrast, the eight children who had derived the variant paternally had negative skin prick and radioallergosorbent test results and did not have increased bronchial responsiveness. CONCLUSION: Fc epsilon RI"' beta Leu181/Leu183 when inherited maternally identifies a genetic risk factor for atopy and bronchial hyperresponsiveness.

Adolescent

Spontaneous cessation of umbilical blood flow in the acardiac fetus of a twin pregnancy.

The acardiac fetus is a rare entity found only in monozygotic multiple pregnancy. Although the acardiac fetus is non-viable, the perinatal mortality rate for the normal fetus may be as high as 50 per cent, and is usually associated with fetal heart failure and hydrops fetalis, or as the result of prematurity. In this communication, we describe a case of spontaneous cessation of blood flow to an acardiac fetus and discuss the management of this condition with special reference to optimizing the outcome for the normal fetus.

Abnormalities, Severe Teratoid

Neonatal alloimmune thrombocytopenia due to anti-P1A1 (anti-HPA-1a): importance of paternal and fetal platelet typing for assessment of fetal risk.

Neonatal alloimmune thrombocytopenia (NAIT), which usually involves sensitization to P1A1 (HPA-1a), may have devastating complications for the fetus. These may be prevented by antenatal treatment of severe cases with either maternally administered high-dose gamma-globulin and/or repeated intrauterine platelet transfusions. Determination of the paternal platelet phenotype is useful for counseling parents who have had one or more affected pregnancies. This report of an unaffected pregnancy in a woman with a history of previous pregnancies complicated by NAIT illustrates the role of paternal and fetal platelet phenotyping in managing existing pregnancies at risk of NAIT.

Adult

Prepregnancy counselling: experience from 1,075 cases.

OBJECTIVE: To assess the activity of a prepregnancy counselling clinic in terms of investigations, counselling, treatment and subsequent pregnancy outcome. DESIGN: Review of 1,075 couples attending over a nine year period. SETTING: University Hospital offering a tertiary referral service for fetal medicine. SUBJECTS: Couples referred to the clinic from a variety of sources. MAIN OUTCOME MEASURES: Categories of referral, value of diagnostic tests, and subsequent pregnancy outcome. RESULTS: The main categories of referral were: previous miscarriage (44.4%); previous fetal abnormality (19.6%); chronic maternal disease (22.3%); and others (13.7%). Routine investigations produced a low yield of abnormality (1%), in contrast to investigations selected for specific reasons (12%). Subsequent pregnancy outcome, which was unaltered in either the previous miscarriage or fetal abnormality groups, did improve in the chronic maternal disease group. CONCLUSIONS: This study does not prove the value of prepregnancy counselling. However, it does illustrate the importance of making an accurate assessment of previous problems and current health as a means of determining both maternal and fetal risks in a subsequent pregnancy, a process which seems to lead to an improved outcome within selected groups. The importance of continuity of care in all couples, especially when there has been a previous adverse pregnancy outcome is emphasized.

Abortion, Spontaneous

The importance of serial biophysical assessment of fetal wellbeing in gastroschisis.

OBJECTIVE: To review antenatal and intrapartum assessment of pregnancies complicated by gastroschisis. DESIGN: Retrospective descriptive study. SETTING: University College Hospital, London. SUBJECTS: 24 consecutive cases of gastroschisis between 1986 and 1991. RESULTS: The gestational age at sonographic diagnosis was 20.3 weeks (SD 6.77) and at birth was 36.5 weeks (SD 2.06). There were 21 live births, all with good surgical outcome. There were 16 vaginal deliveries and eight caesarean sections. The elective sections were for oligohydramnios and dilated bowel (1) and clinically suspected growth retardation (1); the intrapartum caesarean sections were for fetal distress (4) and premature breech presentation (2). There were six with dilated gut on ultrasound; one of these ended in a stillbirth. There was a significant association between gut dilatation and caesarean section for fetal distress (P = 0.004). There was also a significant association between meconium staining and fetal distress (P = 0.021). Of these babies, 46% were < or = third centile for corrected birth weight. CONCLUSIONS: While half of the babies with gastroschisis were small for gestational age at birth, reliable antenatal prediction of birth weight is difficult. Gut dilatation may be an indicator of either antenatal or intrapartum fetal distress, but does not correlate with poor neonatal surgical outcome. We suggest close antenatal surveillance of fetal wellbeing in all cases of gastroschisis because, in addition to growth retardation, many show some evidence of fetal distress and 12.5% end in stillbirth, even when appropriately grown.

Abdominal Muscles

Growth factors and metanephrogenesis.

The formation of all organs during embryogenesis, including kidney, is dependent on the timed and sequential expression of a number of polypeptide growth factors. Synthesis and actions of one or more members of the insulin-like growth factor, epidermal growth factor/transforming growth factor-alpha, transforming growth factor-beta, platelet-derived growth factor, fibroblast growth factor, and nerve growth factor families have been characterized in the developing metanephric kidney. Studies originating from a number of laboratories have defined the localization of growth factor mRNAs, receptors and peptides, have delineated patterns of growth factor synthesis, and have established the growth factor dependency of embryonic kidney development. The results of these investigations will be summarized in this editorial review and integrated within the broader context of growth factor cellular physiology and growth factor expression in nonrenal systems.

Animals

Metanephric transforming growth factor-alpha is required for renal organogenesis in vitro.

The role of transforming growth factor-alpha (TGF-alpha) in metanephric development was examined. Metanephroi were removed from 13-day-old rat embryos and grown in organ culture for up to 6 days using serum-free chemically defined media. During this time the metanephroi increased in size and morphological complexity. Messenger RNA for TGF-alpha was present in the renal anlage. Immunoreactive TGF-alpha was produced by metanephroi in vitro and released into culture media. TGF-alpha of metanephric origin coeluted with recombinant human 125I-TGF-alpha after high-performance liquid chromatography of media. In contrast, epidermal growth factor was not detectable. Levels of TGF-alpha were relatively constant during 4 days in culture and averaged approximately 10(-10) M. Growth of the metanephric anlage, arborization of the ureteric bud, and tubulogenesis within the metanephric blastema were inhibited by the addition of anti-TGF-alpha antibodies to organ cultures. These data demonstrate production of TGF-alpha by developing rat metanephroi in organ culture. The peptide is necessary for growth and development in vitro. Our findings suggest a necessary role for TGF-alpha of metanephric origin as a promoter of renal organogenesis in vivo.

Animals

Maximal airway narrowing in a general population.

To characterize airway responses in a population sample, respiratory symptoms, smoking habits, and changes in FEV1 (delta FEV1) to inhaled methacholine (maximal cumulative dose of 196 mumol or maximal decrease in FEV1 of 50%) were recorded in 201 subjects. From each dose-response curve the plateau (delta FEV1 less than or equal to 5% over two or more dose steps) response, the maximal response (average of responses on the plateau or maximal delta FEV1 when no plateau was present), slope, and PD20 (dose required to cause delta FEV1 greater than 20%) were derived. The pattern of dose-response curves was a continuous change from being flat (maximal delta FEV1 less than or equal to 5%), becoming steeper with a plateau that occurred at a greater change in FEV1 as the curves were shifted more to the left, to being the steepest without a plateau response. Maximal delta FEV1 was significantly related to the PD20 (r = -0.64, p less than 0.001) and the slope (r = 0.63, p less than 0.001). A history of doctor-diagnosed asthma or wheeze in the last 12 months was related to the level of the maximal delta FEV1 and to PD20. Likelihood ratios [LR = sensitivity/(1-specificity)] for asthma or wheeze were higher for a maximal delta FEV1 of 50% plus a PD20 of 4 mumol (LR = 6.5) or 1 mumol (LR = 7) than for either alone. Subjects without reported asthma or wheeze more often had a plateau on the dose-response curve (76%) than those with a positive history (49%, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Asthma

Expression of insulin-like growth factor in adult and embryonic kidney.

Insulin-like growth factors (IGFs) I and II are proinsulin-like peptides. IGF I is produced in adult and embryonic kidney. It is likely that IGF I produced locally in adult kidney regulates processes of renal transport, metabolism and growth. Renal IGF I production is stimulated by growth hormone (GH) and by epidermal growth factor (EGF). The identity of additional factors that regulate IGF I gene expression in settings such as compensatory hypertrophy and diabetes mellitus is unknown. IGF I and IGF II produced in embryonic kidney promote the metanephrogenic process. The identity of factors that regulate metanephric IGF gene expression is yet to be determined.

Autoradiography

Atrial natriuretic peptide: a vasodilator of the fetoplacental circulation?

Paired maternal and fetal atrial natriuretic peptide concentrations were measured in 62 percutaneous umbilical blood samplings performed principally for the assessment and treatment of rhesus isoimmunization. Pretransfusion fetal atrial natriuretic peptide levels were significantly higher than maternal atrial natriuretic peptide levels (median 117 pg/ml vs median 32 pg/ml; p less than 0.001); paired pretransfusion fetal and maternal atrial natriuretic peptide samples showed a weak correlation with each other (R2 = 17%; p = 0.002). Fetal atrial natriuretic peptide levels correlated inversely with hematocrit (R2 = 14%; p = 0.003), but not with albumin or gestational age. Paired pretransfusion and posttransfusion (median = 134 pg/ml) fetal atrial natriuretic peptide levels (n = 38) showed a significant rise after transfusion (p less than 0.001); this rise was related to the percentage of fetoplacental blood volume transfused (R2 = 33%; p = 0.035). In a subgroup of 26 procedures, change in fetal atrial natriuretic peptide levels was weakly correlated with transient reductions in the Doppler systolic/diastolic ratio of the umbilical artery (R2 = 14%; p = 0.07). These data support work in animals that indicate a role for atrial natriuretic peptide in the human fetus, but these data do not confirm that atrial natriuretic peptide modulates fetoplacental vascular impedance in the human fetus.

Atrial Natriuretic Factor

Insulin-like growth factors I and II are produced in the metanephros and are required for growth and development in vitro.

The role(s) of one family of polypeptide growth factors in a developing organ system was examined. Renal anlagen (metanephroi) were surgically removed from 13-d-old rat embryos and grown in organ culture for up to 6 d. Over this period of time when placed in serum-free defined media, the metanephroi increased in size and morphologic complexity. Messenger RNAs for both insulin-like growth factors (IGFs), IGF I and IGF II, were present in the metanephroi. Immunoreactive IGF I and IGF II were produced by the renal anlagen and released into culture media. Levels were relatively constant during the 6 d in culture and averaged 3.5 X 10(-9) M IGF I and 8.3 X 10(-9) M IGF II in media removed from metanephroi after contact for 24 h. IGF binding protein activity was not detected in culture media. Growth and development of metanephroi in vitro was prevented by the addition of anti-IGF I or anti-IGF II antibodies to organ cultures. IGF II produced by metanephroi was active in an IGF II biological assay system and addition of anti-IGF II receptor antibodies to organ cultures prevented growth and development, consistent with the action of IGF II in metanephroi being mediated via the IGF II receptor. The data demonstrate production of both IGF I and IGF II by developing rat metanephroi in organ culture. Each of these peptides is necessary for growth and development of the renal anlage to take place in vitro. Our findings suggest that both IGF I and IGF II are produced within the developing metanephros in vivo and promote renal organogenesis.

Animals

Evaluation of two rapid group B streptococcal antigen tests in labor and delivery patients.

Two rapid group B streptococcal antigen tests were compared with nonselective blood agar culture in 1062 unselected patients admitted to labor and delivery. Vaginal specimens taken from each patient on admission were used to perform each of two rapid tests and corresponding cultures. The rapid tests were the Streptex latex agglutination assay and the Equate Strep B test, which uses a solid-phase immunoassay. Overall, 105 patients (9.9%) had at least one positive culture. The sensitivities for the rapid tests were 15.1% for Streptex and 21.5% for Equate. Specificities were 99.3 and 98.7%, respectively. Sensitivity was minimally increased in the setting of ruptured membranes for both tests. Likewise, use of separate swabs for streaking the culture plate and performing the rapid test increased the sensitivity, but this was not significant for either test. In control experiments, the limit of sensitivity of both rapid tests was 5 x 10(6) colony-forming units. We conclude that at present, these tests are not sensitive enough for routine use in this type of clinical setting.

Antigens, Bacterial

Risk factors for death in patients admitted to hospital with asthma: a follow-up study.

Hospital records of patients with asthma admitted to teaching hospitals in Perth, Western Australia between 1976 and 1980 were examined retrospectively to identify characteristics of the illness which were associated with subsequent death. From 5722 admissions there were 195 deaths to December 1982, 186 of whom had records available (cases); 452 of the surviving subjects were used for comparison (controls). There was no difference in age of onset of asthma or cigarette smoking habits between the two groups, but ischaemic heart disease as an associated condition was significantly more frequent in cases. On admission to hospital an arterial PCO2 less than 45 mmHg was more frequent in those who died, but there were no differences in arterial PO2, lowest pH, highest or lowest FEV1 and FVC. Cases more frequently used home nebulisers and were more frequently prescribed corticosteroids, antibiotics and sedatives or tranquilizers prior to admission, corticosteroids and sedatives or tranquilisers during admission and sedatives or tranquilisers on discharge. These results suggest that cases had more severe asthma in that they were more often treated with home nebulisers, corticosteroids and antibiotics, but with the exception of PaCO2 the commonly used measurements of severity of asthma did not identify those at risk of death. The prescription of sedatives or tranquillisers appears to be associated with an increased risk of death in subjects with asthma.

Adolescent

The effects of nedocromil sodium on the response to grain dust in West Australian grain workers.

Seasonal grain workers in Western Australia who develop respiratory symptoms after exposure to grain dust develop concomitant changes in lung function and bronchial responsiveness to methacholine. The mechanisms underlying these changes are not known. A detailed study was undertaken of seasonal grain workers in Western Australia to evaluate the effect of nedocromil sodium (Fisons, United Kingdom) on these changes to see if they could be prevented by this drug. Forty seven subjects participated. Symptoms and forced expiratory volume in one second (FEV1) were recorded before the study and before, during, and after each working shift, and bronchial responsiveness to methacholine was measured at the beginning and end of the study. Twenty three subjects received nedocromil and 22 received a placebo in a double blind design; there was no difference in baseline characteristics between the two groups. At the end of the study, no differences were found between the nedocromil and placebo groups in the prevalence of symptoms or development of new symptoms during the study. The drug had no effect on changes in methacholine PD20 or FEV1. As in previous studies, new symptoms developing during the season were more common in atopic subjects and were associated with a fall in methacholine PD20. It is concluded that nedocromil has no effect on the development of new symptoms in grain workers. The mechanisms underlying these symptoms require further study.

Adolescent

Exposure to grain dust and changes in lung function.

Respiratory symptoms and lung function were assessed in 41 seasonal grain handlers and related to duration of employment and level of exposure to grain dust. Ten public works department employees, not exposed to grain dust, were examined during the same period. Respiratory symptoms, forced expired volume in one second (FEV1), and bronchial responsiveness (dose of methacholine provoking a 20% fall in FEV1-PD20) were assessed before starting work and at weekly intervals during a period of employment lasting up to four weeks. Two atopic grainhandlers with pronounced bronchial hyperresponsiveness (PD20 less than 1 mumol) and a history of asthma withdrew from the study within two weeks because they developed severe asthma. Respiratory symptoms were more frequent and more often attributed to work in the grainhandlers than in the non-exposed subjects. In the grainhandlers the FEV1 decreased by a mean (95% confidence intervals) of 321 ml (198-444) (p less than 0.05) and the mean (95% confidence interval) PD20 decreased from 20.6 mumol (10.3-41.2) to 6.0 mumol (2.8-12.5) (p less than 0.05) after one week of work. Over the next three weeks the mean FEV1 returned towards the prestudy values. The mean PD20, however, remained significantly lower than the initial value. The mean FEV1 and PD20 did not change significantly in the non-exposed subjects. The frequency of symptoms and decreases in FEV1 were greater in grainhandlers when working in jobs where total exposure to dust was greater than 20 mg/m3 than when working in jobs where it was less than 10 mg/m3. The results indicate that occupational exposure to grain dust results in respiratory symptoms and changes in lung function, including increased airway responsiveness, within the first week of exposure to grain dust at work. These changes appear to be determined by the degree of dust exposure and suggest a direct effect of grain dust on the lung in these subjects.

Agricultural Workers' Diseases