Biomedical subjects

G Ryan

Publications and source records attributed to G Ryan.

At least 37 records · Page 2Linked to original sources

PubMed1996

Platelet-surface glycoproteins in healthy and preeclamptic mothers and their newborn infants.

Preeclampsia, a common complication of pregnancy, contributes significantly to maternal and fetal morbidity and mortality. It may lead to both quantitative and qualitative defects of maternal and neonatal platelets. In this prospective study, flow cytometry has been used to study expression of platelet-surface glycoproteins (GPs) on maternal and neonatal platelets of both healthy and preeclamptic subjects. We studied 15 preeclamptic women, 20-44 y of age, and their newborns (median gestational age, 32 wk; range, 26-38) and seven healthy women (aged 26-41 y) and their healthy newborns (median gestational age, 38 wk; range, 38-42). Compared with their healthy and preeclamptic mothers, resting platelets from neonates expressed significantly less CD41 and CD9. Thrombin activation resulted in significant increases in platelet-surface expression of CD62P, CD63, CD41, CD9, and CD36 in neonates and their healthy mothers. Compared with neonates of healthy mothers, platelets from neonates of preeclamptic mothers expressed lower levels of CD62P, CD63, CD9, and CD36 on activated platelets. These findings suggest that preeclampsia influences the expression of platelet-surface GPs on neonatal and maternal platelets, which may affect platelet function, leading to an additional risk for bleeding in thrombocytopenic neonates of mothers with preeclampsia.

Adult↗

PubMed1995

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↗

PubMed1995

A phase III study of accelerated radiotherapy with and without carboplatin in nonsmall cell lung cancer: an interim toxicity analysis of the first 100 patients.

PURPOSE: In 1989 we initiated a multicenter randomized trial to determine if accelerated radiotherapy with or without concurrent carboplatin improves local control and survival in patients with limited nonsmall cell lung cancer. This interim analysis was performed on the first 100 patients to determine whether the toxicity of the four treatment arms is acceptable. METHODS AND MATERIALS: One hundred patients with limited nonsmall cell lung cancer have been randomized to receive one of four treatments: arm I, radiotherapy 60 Gray (Gy) in 30 fractions in 6 weeks; arm II, accelerated radiotherapy 60 Gy in 30 fractions in 3 weeks; arm III, radiotherapy as in arm I plus carboplatin 350 mg/m2 during weeks 1 and 5 of radiotherapy; arm IV, radiotherapy as in arm II plus carboplatin 350 mg/m2 during week 1. Survival was measured for the group as a whole and treatment-related toxicities in the four arms were compared. RESULTS: The estimated median survival for all 100 patients was 17.1 months with 33% estimated survival at 2 years. The major toxicities were hematologic and esophageal. Patients receiving carboplatin had more neutropenia (p < 0.0001) and thrombocytopenia (p = 0.002) than patients receiving radiotherapy alone, and this was most marked in patients on arm III. Both carboplatin and accelerated radiotherapy separately caused more severe esophagitis when compared to conventional radiotherapy alone (p = 0.011 and p = 0.0017, respectively). Esophagitis was more prolonged in patients having accelerated radiotherapy (p < 0.0001, median duration 3.2 months compared with 1.4 months for patients receiving conventional fractionation). Six patients (23%) treated on arm II have required dilatation of esophageal stricture, one dying with a laryngo-esophageal fistula. CONCLUSION: In patients receiving radiotherapy for unresectable lung cancer, overall treatment time can be halved and carboplatin administered concurrently with increased but acceptable esophageal and hematologic toxicity.

Adult↗

PubMed1995

Mutation analysis of Western Australian families affected by cystic fibrosis.

OBJECTIVE: To document the results of mutation analysis on 160 individuals with cystic fibrosis and 31 obligate carriers of the cystic fibrosis gene in 191 Western Australian families to facilitate accurate genetic counselling. METHODS: We tested for 17 mutations of the cystic fibrosis gene by either a variation of the polymerase chain reaction amplification refractory mutation system (PCR-ARMS) or with a series of restriction enzyme cuts and dot blots using chemiluminescent probes. RESULTS: At least one of the two intragenic mutations causing cystic fibrosis was identified in 98% of affected individuals and both were detected in 68%. The delta F508 deletion occurred in 89.8% of patients: 51% were homozygous for this defect. In carriers, 85% of the mutations were detected with a panel of 16 probes, identifying 17 intragenic defects: the delta F508 deletion occurred in 72.4%. Both cystic fibrosis mutations were detected in 68% of cystic fibrosis families. CONCLUSIONS: By analysis with 16 intragenic cystic fibrosis genomic probes, we have documented the frequencies of various mutations in the Western Australian population. These data will be useful in accurate genetic counselling for affected families and carrier screening for the general population.

Adult↗

PubMed1995

Detection of a recessive major gene for high IgE levels acting independently of specific response to allergens.

The genetic control of the total IgE, the immunoglobulins E involved in allergy, remains still unclear. Although high IgE levels were found to be determined by a recessive major gene in several studies, other modes of inheritance were also reported. Moreover, at least two different genetic mechanisms controlling the IgE regulation have been suggested: one involved in the specific IgE response and the other one in the nonspecific response. To better understand the genetic mechanisms controlling IgE variation, we performed segregation analysis of IgE levels by ignoring or taking into account the specific response to allergens (SRA). Analyses were conducted using the class D regressive model, in a sample of 234 Australian nuclear families randomly selected during the winter months, when IgE levels are the lowest (basal). SRA, when included as a covariate in the model, was defined by one of the three following criteria: (1) raised specific IgE level for one or more allergens, (2) positive skin test for one or more allergens, and (3) at least one of the (1) or (2) criteria. When the presence of SRA is ignored, the familial transmission of total IgE level is compatible with the segregation of a recessive major gene and residual familial correlations. When the presence of SRA is accounted for in the analysis, whether defined by criteria (1), (2), or (3), there is still evidence for a recessive major gene controlling IgE levels but residual familial correlations are no longer significant. In addition, no interaction between this major gene and SRA is shown here. Our results suggest that this gene, which accounts for 28% of the variation of the trait, may be involved in the control of basal IgE production, independently of specific response to allergens.

Adolescent↗

PubMed1995

The prognostic factors in the prenatal diagnosis of the echogenic fetal lung.

The prenatal diagnosis of an echogenic fetal lung (EFL) is now often made in the early second trimester using high-resolution ultrasound. This ultrasound appearance is usually caused by a congenital cystic adenomatoid lung malformation (CCAM), an intrapulmonary lung sequestration or obstruction of a major airway. In order to provide prognostic guidelines to parents who may be considering termination of a fetus with these findings, we have analysed a series of 11 cases diagnosed in our centre over the past 2 years in conjunction with 60 cases from major published series. The data suggest that in the absence of non-immune hydrops fetalis (NIHF) or other anomalies, the outcome for the fetuses is excellent, with over 90 per cent survival. Neither early diagnosis (24 weeks) nor the presence of mediastinal shift is a poor prognostic indicator. In addition, it appears that if NIHF is absent at diagnosis, the chance that it will develop as the pregnancy continues is small (6 per cent). Furthermore, there is a significant (up to 30 per cent) chance that this ultrasound finding will resolve in utero. The development of in utero fetal surgical techniques may be the only hope for those hydropic fetuses who appear to have a dismal prognosis.

Bronchopulmonary Sequestration↗

PubMed1995

Repression of Pax-2 by WT1 during normal kidney development.

The developmental, regulatory gene Pax-2 is activated during early kidney morphogenesis and repressed in mature renal epithelium. Persistent Pax-2 expression is also observed in a variety of kidney tumors. Yet, little is known about the signals regulating this transient expression pattern in the developing kidney. We have examined the spatial and temporal expression patterns of Pax-2 and the Wilm's tumor suppresser protein WT1 with specific antibodies in developing mouse kidneys. A marked increase in WT1 protein levels coincided precisely with down-regulation of the Pax-2 gene in the individual precursor cells of the visceral glomerular epithelium, suggesting a direct effect of the WT1 repressor protein on Pax-2 regulatory elements. To examine whether WT1 could directly repress Pax-2 transcription, binding of WT1 to three high affinity sites in the 5' untranslated Pax-2 leader sequence was demonstrated by DNAseI footprinting analysis. Furthermore, co-transfection assays using CAT reporter constructs under the control of Pax-2 regulatory sequences demonstrated WT1-dependent transcriptional repression. These three WT1 binding sites were also able to repress transcription, in a WT1-dependent manner, when inserted between a heterologous promoter and the reporter gene. The data indicate that Pax-2 is a likely target gene for WT1 and suggest a direct link, at the level of transcriptional regulation, between a developmental control gene, active in undifferentiated and proliferating cells, and a known tumor suppressor gene.

Animals↗

PubMed1994

Genetic linkage of T-cell receptor alpha/delta complex to specific IgE responses.

IgE responses to inhaled proteins underlie the clinical syndrome of allergic (atopic) asthma and rhinitis. We have investigated genetic linkage between specific IgE reactions to highly purified major allergens and the T-cell receptor (TCR) alpha and beta gene complexes on chromosome 14 and 7, respectively. Antigens tested included highly purified proteins from the housedust mite Dermatophagoides pteronyssinus, the domestic cat and dog, grass pollen, and the mould Alternaria alternata. Affected sibling-pair methods were used in two independent sets of families, one in the UK and one in Australia. No linkage of IgE serotypes to TCR-beta was detected, but significant linkage to TCR-alpha was seen in both family groups. For several of the IgE phenotypes investigated (positive responses to whole allergen sources or purified antigens or serum IgE above the 70th percentile in the population) the affected sibling-pairs showed significant sharing of TCR-alpha microsatellite alleles from both parents. The results show that a gene (or genes) in the TCR-alpha region modifies specific IgE responses.

Alleles↗

PubMed1994

Fetal vascular atrial natriuretic peptide receptors in human placenta: alteration in intrauterine growth retardation and preeclampsia.

OBJECTIVE: Our purpose was to quantify fetoplacental vascular atrial natriuretic peptide receptor subtypes in human pregnancies complicated by intrauterine growth retardation or preeclampsia and to relate these parameters to the fetoplacental vascular impedance as assessed by Doppler velocimetry. STUDY DESIGN: Guanylate cyclase-coupled and uncoupled receptors were quantified by radioligand-binding methods in membrane fractions prepared from primary and secondary stem villous vessels. Data for 16 abnormal pregnancies delivered preterm were compared with that for six gestationally matched preterm controls. RESULTS: The number of guanylate cyclase-coupled receptors was significantly (p < 0.001) greater in pregnancies complicated by intrauterine growth retardation or preeclampsia irrespective of normal or abnormal umbilical artery Doppler blood flow velocity pattern. The number of guanylate cyclase-uncoupled receptors was unaltered. CONCLUSIONS: Because fetal plasma atrial natriuretic peptide concentration is normal or elevated in intrauterine growth retardation and preeclampsia, these data suggest that atrial natriuretic peptide-mediated fetoplacental vasodilation is augmented in these disorders even in the presence of increased vascular resistance within the fetoplacental unit.

Atrial Natriuretic Factor↗

PubMed1994

The expression of IgG Fc receptors on circulating leucocytes in the fetus and new-born.

The expression of Fc-gamma-R (FcR) classes on circulating leucocyte lineages (lymphocytes, monocytes, granulocytes) was determined by flow cytometry in 46 fetuses at 18-35 weeks of gestation and in 11 full-term neonates, and compared to that in 20 adults. Classes of FcR present on adult leucocytes could be detected on the corresponding fetal cells as early as 18 weeks of pregnancy. Generally, in the fetus, FcR expression was lower than in the adult while in the neonate it approached values found later in life. However, percentages of Fc-gamma-RIII-positive fetal/new-born monocytes, and those of FcR-positive new-born granulocytes were considerably raised above adult levels. The modified pattern of FcR expression on fetal/new-born leucocytes is likely to influence their IgG-mediated effector activities towards targets such as red cells and platelets.

Adult↗

PubMed1994

The effect of neuromuscular blockade on human fetal heart rate and its variation.

OBJECTIVE: To determine the effect of neuromuscular blockade on fetal heart rate and its variation. DESIGN: Case control study. SETTING: Tertiary referral fetal medicine unit in a London teaching hospital. SUBJECTS: Forty women with rhesus iso-immunisation requiring an intravascular fetal blood transfusion between 28 and 34 weeks gestation. INTERVENTION: Intravascular injection of pancuronium to the fetus prior to fetal blood transfusion in 20 cases. MAIN OUTCOME MEASURES: Comparison between the group receiving pancuronium and the control group with regard to differences in perceived fetal activity and computer derived numerical indices of fetal heart rate and fetal heart rate variation after fetal blood transfusion. RESULTS: After transfusion in the control group, there were fewer perceived fetal movements, a small reduction in fetal heart rate but no differences in number of fetal heart rate accelerations or measures of fetal heart rate variation. In the study group, pancuronium produced no change in fetal heart rate despite a virtual abolition of perceived fetal movements and fetal heart rate accelerations. Measures of fetal heart rate variation were reduced by 60%. Comparison of the pre- to post-transfusion changes between the two groups showed significant differences for all fetal heart rate indices. CONCLUSION: Fetal activity accounts for more than half the measured variation of the human fetal heart rate.

Blood Transfusion, Intrauterine↗

PubMed1994

Fetal blood transfusion.

The concept of transfusing the fetus in utero is simple, but its success demands an experienced, dedicated team, with excellent laboratory back-up. High-resolution ultrasound has enabled us to sample fetal blood. This allows immediate, precise assessment and rational treatment of the anemic fetus, with improved outcome for all such fetuses and, particularly, for the hydropic, moribund group. Fetal blood transfusion programs should be concentrated in regional perinatal centers.

Anemia↗

PubMed1994

Radiation and carboplatin combined-modality therapy in non-small cell lung cancer.

Previously untreated patients with stages I to IV, N0-3, M0 unresectable non-small cell lung cancer were randomized to arm I (conventional radiotherapy [RT], 60 Gy in 30 fractions over 6 weeks), arm II (accelerated RT, 60 Gy in 30 fractions over 3 weeks), arm III (conventional RT, as in arm I, plus carboplatin 70 mg/m2/d on days 1 to 5 during treatment weeks 1 and 5), or arm IV (accelerated RT, as in arm II, plus carboplatin 70 mg/m2/d on days 1 to 5 of week 1 only). An intensive analysis of toxicity in the first 92 patients entered revealed significantly more neutropenia (P < .0001) and thrombocytopenia (P = .004) in the combined-modality arms. Esophagitis was worse on arms II, III, and IV, but was more prolonged in the accelerated RT arms. Overall, however, the treatment on all study arms was well tolerated.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1993

Should unpublished data be included in meta-analyses? Current convictions and controversies.

OBJECTIVE: To identify the extent to which meta-analyses currently include unpublished data and whether editors, meta-analysts, and methodologists believe unpublished material should be included. DESIGN: This article describes two related studies: a literature review and a cross-sectional survey. SAMPLE SELECTION: For the literature review, we identified all articles indexed by the key word meta-analysis from January 1989 to February 1991 and determined whether unpublished material had been searched for, obtained, and included in the meta-analyses. For the cross-sectional survey, we surveyed authors of these meta-analyses, authors of articles addressing methodological issues in meta-analysis published during the same period, and editors of journals in which both types of articles were published. INTERVENTION: We asked the respondents about their attitudes concerning inclusion of unpublished data and publication of articles from which data had previously been included in a scientific overview. MAIN OUTCOME MEASURES: Inclusion of unpublished data and opinions about whether unpublished material should be included in overviews and whether prior inclusion of data in an overview should bear on publication. RESULTS: Of 150 meta-analyses, 46 (30.7%) included unpublished data in their primary analysis. Of authors surveyed, 85% responded. Of the meta-analysts and methodologists, 77.7% felt that unpublished material should definitely or probably be included in scientific overviews; this was true of 46.9% of the editors. A total of 86.4% of the meta-analysts and methodologists and 53.2% of the editors felt that inclusion of data in a prior overview should have no bearing on full publication of original research. CONCLUSION: While inclusion of unpublished data in scientific overviews remains controversial, most investigators directly involved in meta-analysis believe that unpublished data should not be systematically excluded. The most valid synthesis of available information will result when meta-analysts subject published and unpublished material to the same rigorous methodological evaluation and present results with and without unpublished sources of data.

Data Collection↗

PubMed1993

Unusual lymphangioma observed prenatally in a 45,X fetus.

We present a case of a large frontal lesion, suspected on antenatal ultrasound to be a cephalocele. The cardiac anatomy was abnormal and fetal blood sampling showed a 45,X chromosome constitution. Postmortem examination proved this to be a lymphangioma and confirmed the presence of a cardiac defect. We suggest that this lymphangioma represents an unusual manifestation of monosomy X and discuss the importance of doing chromosome analysis in the presence of such a lesion which is of similar appearance as a cephalocele.

Adult↗

PubMed1993

Growth factors and kidney development.

The formation of the metanephric kidney is dependent upon the timed and sequential expression of a number of polypeptide growth factors. To shed light on the participation of members of the insulin-like growth factor (IGF) and epidermal growth factor/transforming growth factor-alpha (EGF/TF-alpha) families, we measured the synthesis of IGF-I, IGF-II, EGF and TGF-alpha by developing rat metanephroi in organ culture and determined the effect of anti-growth factor antibodies on growth and development. IGF-I, IGF-II and TGF-alpha were produced by metanephroi and released into culture media. We could detect no EGF. Inclusion of anti-IGF-I, anti-IGF-II, anti-IGF-II receptor or anti-TGF-alpha antibodies in organ cultures inhibited growth and development of metanephroi. Our findings suggest that both members of the IGF family and TGF-alpha are produced within the developing metanephros and promote renal organogenesis.

Animals↗

PubMed1993

Absent end-diastolic flow velocity waveforms in the umbilical artery--the subsequent pregnancy.

OBJECTIVE: Our purpose was to assess the recurrence risk, course, and outcome of subsequent pregnancies in women with absent umbilical end-diastolic velocity. STUDY DESIGN: Absent umbilical end-diastolic velocity was detected in 88 women. Sixteen of them were prospectively followed up in their 19 subsequent pregnancies. These pregnancies were compared with their index pregnancies. RESULTS: The index pregnancy was invariably complicated with a perinatal mortality of 56%, growth restriction in 94% (15/16), and prematurity in 100% (75% < 32 weeks' gestation). In contrast, the outcome of the subsequent pregnancies was much better, and 74% (14/19) were uncomplicated. No perinatal deaths occurred, and none were delivered before 32 weeks' gestation. Absent umbilical end-diastolic velocity recurred in only two pregnancies, both of which were complicated. Six women had autoantibodies; these accounted for 80% (4/5) of subsequent complicated pregnancies. CONCLUSION: After an index pregnancy with absent umbilical end-diastolic velocity, subsequent pregnancies had favorable outcomes. Recurrence of absent umbilical end-diastolic velocity was low. The absence of autoantibodies and normal Doppler studies were associated with improved outcome.

Adult↗

PubMed1993

The use of saline solution as a contrast medium in suspected diaphragmatic hernia and renal agenesis.

OBJECTIVE: Our purpose was to determine the value of saline solution instillation as a contrast medium in suspected congenital diaphragmatic hernia and renal agenesis. STUDY DESIGN: Intrathoracic (n = 3) or intraperitoneal (n = 2) instillation was performed in five cases of suspected congenital diaphragmatic hernia. Amnioinfusion combined with intraperitoneal instillation was performed in five cases of suspected renal agenesis. RESULTS: Instillation clearly demonstrated the diaphragmatic defect in four of the five cases. In the cases with suspected renal agenesis, amnioinfusion led to recognition of a previously unsuspected sirenomelia, and intraperitoneal instillation demonstrated empty renal fossae in four cases. The final fetus with bilateral renal agenesis was thought antenatally to have a contralateral multicystic kidney. CONCLUSIONS: We suggest that intrathoracic or intraperitoneal saline solution instillation is a useful diagnostic procedure in carefully selected cases where confident ultrasonic diagnosis is often difficult and yet would significantly alter management. In cases of severe oligohydramnios amnioinfusion is a complementary procedure. In 80% of cases in this series there was significant improvement in visualization after the procedure.

Amnion↗