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Biomedical subjects

G Ryan

Publications and source records attributed to G Ryan.

At least 109 records · Page 6Linked to original sources

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↗

Should unpublished data be included in meta-analyses?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OBJECTIVE: To identify the extent to which meta-analyses currently include unpublished data and whether editors, meta-analysts, and methodologists believe unpublished material should be included.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identified all articles indexed by the key word meta-analysis from January 1989 to February 1991 and determined whether unpublished material had been searched for, obtained, and included in the meta-analyses.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 INTERVENTION: We asked the respondents about their attitudes concerning inclusion of unpublished data and publication of articles from which data had previously been included in a scientific overview. MAIN OUTCOME MEASURES: Inclusion of unpublished data and opinions about whether unpublished material should be included in overviews and whether prior inclusion of data in an overview should bear on publication.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↗

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↗

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↗

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↗

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↗

Fetal urine analysis for the assessment of renal function in obstructive uropathy.

OBJECTIVES: The assessment of fetal renal function plays a key role in the evaluation of posterior urethral valve obstruction cases. The aim of our study was to determine the value of several urinary compounds, including beta 2-microglobulin, N-acetyl-beta-D-glucosaminidase, and microalbumin in the assessment of prenatal renal function in cases of posterior urethral valve and their potential role in the selection of such cases for in utero shunting. STUDY DESIGN: A range of urinary compounds was measured, including beta 2-microglobulin, N-acetyl-beta-D-glucosaminidase, and microalbumin in 25 cases of posterior urethral valve obstruction. These cases were divided into four groups based on outcome. The Mann-Whitney test and analysis of covariance were used. RESULTS: Sodium, calcium, and beta 2-microglobulin were the best predictors for fetal survival. beta 2-Microglobulin values > 13 mg/L were almost invariably associated with fatal outcome. CONCLUSION: The estimation of beta 2-microglobulin may help in counseling parents and in selecting cases for in utero shunting.

Acetylglucosaminidase↗

Variability of the plateau response to methacholine in subjects without respiratory symptoms.

BACKGROUND: Interpretation of measurements of limited maximal airway narrowing, or plateau response, requires knowledge of its variability within subjects and between methods. METHODS: The repeatability of the plateau response to inhaled methacholine with a dosimeter (D) method (maximal dose 210 mumol) and a tidal breathing (T) method (730 mumol), and the agreement of the two methods, were measured in 16 subjects with mild or no asthma. Two tests by each method (D1,D2,T1,T2) were performed in random order over four consecutive days, with a third dosimeter (D3) test one week later. The dose producing a decrease in forced expiratory volume in one second (FEV1) of 10% (PD10) and the plateau were calculated from each dose-response curve. RESULTS: A plateau was reached in all five tests in 12 subjects and in all tests except D3 in 14 subjects. PD10 was inversely related to the plateau (r = -0.95 for D, r = -0.77 for T). The 95% ranges for differences between two determinations of the plateau in a subject were +/- 11.9% (change in FEV1), +/- 19.2%, and +/- 20.3%, estimated from D1-2 and 1-3, and T1-2 tests, respectively. From the same tests the 95% ranges for the difference of a single determination from an individual's true mean value were +/- 8.3%, +/- 13.6%, and +/- 14.3%. The limits of agreement between methods indicated that 95% of the measurements of the plateau by tidal breathing ranged from 15.2% below to 13.3% above those obtained by dosimeter. There was no significant bias between methods. Tachyphylaxis over 24 hours occurred with PD10 but not with the plateau response. CONCLUSIONS: The plateau response is a subject characteristic which is independent of the method of inhalation challenge testing. Repeatability of the plateau is low in this group of subjects with low airway responsiveness.

Adult↗

Metanephric transforming growth factor-beta 1 regulates nephrogenesis in vitro.

Development of the metanephric kidney during embryogenesis is regulated by a number of polypeptide growth factors of renal origin. We have defined previously a role for insulin-like growth factors (IGF) I and II and for transforming growth factor (TGF)-alpha. To delineate the effect of TGF-beta 1, on renal organogenesis, we cultured metanephroi surgically dissected from 13-day-old rat embryos in serum-free chemically defined media. TGF-beta 1 mRNA was present in kidneys from 13-day-old rat embryos, and positive immunostaining for TGF-beta 1 could be demonstrated in cultured metanephroi. However, TGF-beta bioactivity could not be detected in media obtained from the metanephroi. Addition of 10(-9) M TGF-beta 1 to cultures inhibited tubulogenesis, but had no effect on synthesis of IGF-I or -II. Addition of anti-TGF-beta 1 antibodies to cultures accelerated tubulogenesis within the metanephric blastema. These findings establish the potential for TGF-beta 1 production within the rat metanephros during development in vivo. It is possible that this peptide exerts a negative control on the process of tubulogenesis within metanephric blastema and in this manner acts to shape the architecture of mature kidney.

Animals↗

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↗