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Biomedical subjects

G Ryan

Publications and source records attributed to G Ryan.

At least 73 records · Page 4Linked to original sources

Radiation myelopathy following transplantation and radiotherapy for non-Hodgkin's lymphoma.

BACKGROUND: Combined modality therapy with chemotherapy and radiotherapy has become increasingly popular in the management of solid malignancies. However, unexpected toxicities may arise from their interactions. METHODS AND MATERIALS: We report the case of a young woman with a large mediastinal non-Hodgkin's lymphoma who underwent high-dose chemotherapy with autologous bone marrow transplantation and involved field radiotherapy, and who developed radiation myelopathy after a latent period of only 3 months. The spinal cord dose did not exceed 40.3 Gy in 22 fractions over 4.5 weeks, which is well within accepted tolerance limits. She had no other identifiable risk factors for radiation myelopathy, suggesting an adverse drug-radiation interaction as the most likely cause of her injury. RESULTS AND CONCLUSIONS: This represents the first report of radiation myelopathy at accepted safe radiation doses following high-dose chemotherapy with autologous bone marrow transplantation, and we recommend caution in the choice of radiotherapeutic dose in this setting.

Adult↗

Umbilical artery blood flow velocity in pregnancies complicated by systemic lupus erythematosus.

PURPOSE: We evaluated the role of umbilical artery Doppler velocimetry in the surveillance of pregnancies complicated by systemic lupus erythematosus (SLE). METHODS: We retrospectively studied 56 women with SLE whose pregnancies were managed at our perinatal center between 1988 and 1995. RESULTS: Absent or reversed end-diastolic flow velocity was detected in 6 (11%) of 56 patients. This sub-group of patients had an increased risk of pre-eclampsia, intrauterine growth restriction, cesarean section, and preterm delivery. CONCLUSIONS: A high incidence (11%) of abnormal umbilical artery waveforms was detected. This finding was associated with an increased risk of maternal and fetal complications.

Adult↗

Epithelial cell damage is induced by neutrophil-derived, not pseudomonas-derived, proteases in cystic fibrosis sputum.

Airway histopathological changes in cystic fibrosis (CF) include damage to the epithelial tissue and accumulation of polymorphonuclear leukocytes (PMN). Airways of CF patients are usually colonized with bacteria such as mucoid Pseudomonas aeruginosa (PA). Bacteria and PMN can both release proteolytic enzymes capable of causing tissue damage. This study aims to clarify and compare the roles of these agents in epithelium damage. Epithelial cell (EC) damage and detachment induced by sputum samples from CF or non-CF patients, with and without lung infection, were assessed on amnionic EC in an in vitro model of airway epithelium. Protease activity was determined using inhibitor profiles, and compared to the proteolytic activity of isolated neutrophils and bacteria. Sputa from CF patients and infected non-CF patients induced high levels of detachment. PA also induced high levels of EC detachment but Staphylococcus aureus and Haemophilus influenzae, two other bacteria commonly isolated from CF sputa, induced no detachment. Antiprotease inhibition profiles were similar for PMN and sputa-induced EC detachment, but different for PA-induced detachment. These results suggest that PMN proteolytic enzymes, probably elastase and cathepsin G, are more likely to be the inducers of tissue damage in the airways of CF patients than PA proteolytic enzymes.

Adult↗

The Platelet Function Analyzer (PFA-100): a novel in-vitro system for evaluation of primary haemostasis in children.

The PFA-100 system provides an in-vitro method of assessing primary platelet-related haemostasis by measuring the time (the closure time, or CT) taken for a platelet plug to occlude a microscopic aperture cut into a membrane coated with collagen and either epinephrine or ADP. We used the system to establish normal ranges for CTs in healthy children, adults and neonates. Mean CTs of healthy children were independent of the needle gauge used (21G or 23CG) for blood sampling; they were very similar to the mean CTs of healthy adults, but longer than mean CTs of healthy neonates. Although children with haemophilia had normal CTs, the PFA-100 system was found to be potentially useful in screening for von Willebrand disease in children.

Adolescent↗

Congenital chylothorax in siblings.

We describe two cases of congenital chylothorax in siblings with important differences from previously described familial cases. Our findings support the likelihood of an autosomal recessive inheritance in some cases of this condition, rather than X-linked recessive inheritance, which has also been suggested. Autopsy findings from one of these cases and others previously described suggest that the pathophysiological mechanisms involved may be variable.

Chylothorax↗

Increased perception of airway narrowing in patients with mild asthma.

To compare the perception of airway narrowing of nonasthmatic subjects with those having wheeze or mild asthma (doctor-diagnosed), the relationship between FEV1 and breathlessness was examined in 123 subjects from a general population sample. Scores for breathlessness, using the Borg scale, were recorded before and after inhaling incremental doses of methacholine to a maximal dose of 196 mcmol or a maximum change in FEV1 of 50%. A history of asthma symptoms, including wheeze in the previous 12 months, and doctor-diagnosed asthma was obtained by questionnaire. At any given level of FEV1 there was wide variation in Borg scores between subjects, however median Borg scores and the mean slope of Borg score on FEVI was greater in the asthmatic subjects or those with wheeze compared with nonasthmatic subjects or those without wheeze. In both nonasthmatic and asthmatic subjects, those with airway hyperresponsiveness had increased maximum symptom scores and maximum changes in FEVI, but similar Borg scores relative to change in FEVI, compared with those without hyperresponsiveness. We conclude that the perception of mild and moderate degrees of airway narrowing varies widely between individuals but is increased in subjects with a history of mild asthma or wheeze in the last 12 months, independently of airway responsiveness.

Adult↗

Childhood drownings and fencing of outdoor pools in the United States, 1994.

OBJECTIVES: To determine the prevalence of proper fencing around outdoor swimming pools among US households and to describe this fencing in relation to demographic and other household factors. To estimate the number of drownings among children <5 years of age that might be prevented by having proper fencing around all residential pools in the United States. METHODS: A 1994, randomly dialed national telephone survey contacted 5238 adults who reported demographic information and household characteristics including whether the household had an outdoor swimming pool and the fencing around the pool. Data were weighted to obtain national estimates and percentages. The number of preventable drownings was estimated with a population-attributable risk equation. RESULTS: Approximately 18.5 million American households owned or had access to an outdoor swimming pool in 1994, and 76% (13.9 million) of them appeared to have had adequate fencing. Adequate fencing was associated with household income and type of home. We estimate that 19% of pool-related drownings among children <5 years of age in 1994 (88 drownings) might have been prevented if all residential pools in the United States were properly fenced. CONCLUSIONS: Adequate pool fencing prevents a child from having access to a swimming pool if a responsible adult is not present and has been promoted as a method to prevent drowning. Our research suggests that even if all residential pools in the United States were properly fenced, most drownings among children <5 years of age would not be prevented. Thus, additional strategies to prevent drowning will be needed.

Accident Prevention↗

Familial ileal perforation: prenatal diagnosis and postnatal follow-up.

We report sibs (a brother and a sister) who presented prenatally with ultrasound findings of meconium peritonitis and postnatally were found to have perforation of the terminal ileum. The sister presented with fetal ultrasound findings of severe ascites and peritoneal calcifications. She had no prenatal intervention and was born at 38 weeks' gestation. Laparatomy revealed perforation of the terminal ileum with meconium peritonitis. Her post-surgical course was uncomplicated and at 30 months of age her growth and development are normal. Her brother presented prenatally with signs of meconium peritonitis including severe ascites and peritoneal calcifications. Prenatal aspiration of the ascitic fluid was performed and unlike his sister he was born prematurely, was operated on at 8 days, and developed bronchopulmonary dysplasia. He is currently 1 year old and has normal growth and development. The aetiology of the ileal perforation is not known. There were no findings suggesting connective tissue disorder and the aetiology of the intestinal perforation is not known. The occurrence of the same rare abnormality in sibs of different sexes points towards an autosomal recessive disorder.

Adult↗

Ontario Maternal Serum Screening Program: practices, knowledge and opinions of health care providers.

OBJECTIVE: To determine the practices, knowledge and opinions of health care providers regarding a prenatal genetic screening program in Ontario. DESIGN: Cross-sectional self-reported survey. SETTING: Ontario. PARTICIPANTS: Random sample of 2000 family physicians, all 565 obstetricians and all 62 registered midwives in the province. Among subjects who were eligible (those providing antenatal care or attending births) the response rates were 91% (778/851), 76% (273/359) and 78% (46/59) respectively. MAIN OUTCOME MEASURES: Which patients were offered maternal serum screening (MSS), how results were being communicated, knowledge of the test's sensitivity, likes and dislikes about MSS and recommendations regarding the program. RESULTS: Most (97%) of respondents stated that they were offering MSS to the pregnant women in their practices; 88% were offering it routinely to all pregnant women (87% of the family physicians, 90% of the obstetricians and 100% of the midwives). Most (92%) of the respondents stated that they communicate positive results to their patients personally as soon as they are received; 23% did so for negative results. The respondents correctly identified the initial positive rate but underestimated the false-positive rate. About one-third did not respond to these knowledge questions. Of those who gave feedback on the screening program, 50% recommended that it not be changed, 29% suggested that it be changed, and 22% recommended that it be scrapped. CONCLUSIONS: Participation in the Ontario Maternal Serum Screening Program by health care providers has been good, although knowledge about MSS is far from ideal. Many providers have reservations about the program. In light of concerns raised about the high false-positive rate and the anxiety such results generate in pregnant women, there is a need for more education of providers and patients and a better understanding of women's experiences with genetic screening.

Abnormalities, Multiple↗

Prenatal diagnosis and management of neonatal alloimmune thrombocytopenia.

Neonatal alloimmune thrombocytopenia (NAIT) is an uncommon (1 in 2,000 livebirths) but serious disorder characterized by marked thrombocytopenia in the fetus and neonate. Platelet destruction is caused by a maternal antibody directed against a fetal platelet antigen inherited from the father and lacking in the mother's platelets. Intracranial hemorrhage (ICH) is the most devastating complication of NAIT, affecting approximately 20% of all proven cases, up to 50% of which occur antenatally. Because close to 100% of subsequent pregnancies will be equally or more severely affected, antenatal management directed at preventing ICH in utero has assumed great clinical importance. In recent years, considerable progress has been made in this regard, and although clinical uncertainties still exist, the natural history of this disease and its response to various antenatal interventions have become reasonably well understood. This review will focus on the diagnosis and current management of NAIT, including controversies surrounding current treatment modalities and future prospects for treatment and prevention.

Blood Platelets↗

A phase III study of radiotherapy with and without continuous-infusion fluorouracil as palliation for non-small-cell lung cancer.

This study assesses the effect of adding continuous-infusion fluorouracil to palliative thoracic radiation therapy (RT) on the rate and duration of symptom relief in patients with advanced non-small-cell lung cancer (NSCLC). Two hundred eligible patients with NSCLC were randomized to receive either 20 Gy in five daily fractions as palliation for intrathoracic disease or the same RT with concurrent continuous infusion of 1 g m(-2) day(-1) fluorouracil for 5 days. Survival, response and rates of symptom relief in the two groups were compared according to treatment intent, and toxicities were compared according to treatment received. The overall response rate was higher in patients randomized to the combination (29%) than in patients randomized to RT alone (16%) (P = 0.035). However, there were no significant differences between the treatment arms in terms of overall or progression-free survival or in palliation of symptoms. Patients treated with RT plus fluorouracil had significantly more acute toxicity, including nausea and vomiting (P = 0.01), oesophagitis (P = 0.0003), stomatitis (P = 0.0005) and skin reaction (P = 0.003). This study suggests for the first time an interaction between RT and infusional fluorouracil in NSCLC. Although RT plus fluorouracil resulted in a significantly higher response rate than achieved with RT alone, this did not translate into more effective palliation. Because the combination produced significantly more toxicity than RT alone, it is not recommended for the palliative treatment of NSCLC. Nevertheless, these results suggest that opportunities may exist for exploitation of the observed enhancement of antitumour effect in the setting of high-dose radical RT for NSCLC.

Adult↗

Isolated ductal closure in utero diagnosed by fetal echocardiography.

In utero isolated ductal closure is uncommon and can lead to fetal hydrops and death if not recognized. Five fetuses were diagnosed prenatally by echocardiography. The reasons for referral were hydrops (2), cardiomegaly (1), polyhydramnios and choroid plexus cyst (1), and polyhydramnios and teratoma of the neck (1). Gestational age was median 32, range 18-41 weeks. Two mothers received indomethacin for polyhydramnios, with the echocardiogram performed 5 and 3 days after the last dose. Three had a negative history of drug ingestion. Fetal echocardiograms showed absent flow in the ductus arteriosus, dilated right ventricle with decreased function, and mild or moderate tricuspid and pulmonary insufficiency in all. The left ventricle was hypercontractile, with significantly increased left ventricular stroke output when compared to the right. Four fetuses were delivered by cesarean section and had an uneventful course. One fetus died shortly after birth due to airway obstruction from a large teratoma. Autopsy showed ductal constriction. Postnatal echocardiograms showed absent ductal flow and dilated right ventricle. On follow-up, survivors remained asymptomatic with cardiac size returning to normal. Premature closure of the ductus arteriosus should be considered in hydrops of unknown etiology, right ventricular dysfunction, and following indomethacin therapy. Urgent delivery results in an excellent prognosis.

Adult↗

Patients' perceptions of outcomes of a Canadian hospitalization.

Notes that with health care reform moving at tremendous speed throughout Canada, a great deal of interest in outcomes research has been generated. States that the research team consisted of 17 professional practice leaders from eight disciplines. Proposes, through the research, to identify from the perspective of former patients what results they hoped to achieve prior to discharge from hospital and what facilitated and hindered them in achieving these results. Reports that a representative sample was selected for the study. Forty-one former patients each participated in up to two focus groups, with a total of 16 focus groups conducted. Hierarchical analysis revealed themes that fell within the framework of structure, process and outcomes. The findings will assist in ensuring that more appropriate and effective care is offered to patients by a variety of disciplines.

Adult↗

Testing airway responsiveness using inhaled methacholine or histamine.

Airway responsiveness assessed using histamine and methacholine is safe, reproducible and relatively easily undertaken in adults and children. Results are similar for methacholine and histamine although methacholine is better tolerated. Responsiveness is increased in children and the elderly, and in women compared to men, possibly due to body size effects. Baseline lung function confounds the interpretation of airway responsiveness and may explain the effect of smoking in most studies. Results are most usefully expressed as the provocative dose producing a 20% fall in FEV1 (PD20FEV1) or the dose-response slope (DRS). When technical factors are controlled the reproducibility of the test is from one to two doubling doses. Measurements of airway responsiveness have been widely used in clinical and research practice. However, assessing their value in diagnosing asthma is limited by the lack of a gold standard for the definition of asthma. Using a cut-off value of 8 mg/mL or 8 mumol for PD20, the tests will discriminate asthmatic from non-asthmatic subjects (based on questionnaire definitions of asthma) with a sensitivity of around 60% and a specificity of around 90%. These properties of the test result in positive and negative predictive values of 86% and 69% when the prevalence of asthma is high (50%-as in the clinical setting) and 40% and 95% when the prevalence of asthma is low (10%, as in general population studies). In the usual clinical setting, assessing the significance of atypical or non-specific symptoms, the tests are of intermediate value in predicting the presence of asthma and less useful in excluding asthma. The additional benefit of testing airway responsiveness to measuring peak flows or to a trial of therapy has yet to be fully assessed. Testing of airway responsiveness may be of value in assessing occupational asthma, asthma severity and the effects of potential sensitizers or treatments. In research, tests of airway responsiveness are more useful for excluding cases of asthma. In population studies, they serve as an objective marker of abnormal airway function which may be genetically determined and, like allergy, are strongly associated with asthma. The predictive value of airway hyperresponsiveness for the development of airway disease is yet to be clearly established. In epidemiology the benefits of measuring airway responses must be weighed against the added inconvenience and cost that is incurred.

Adult↗

Maternity care and maternal serum screening. Do male and female family physicians care for women differently?

OBJECTIVE: To examine whether male and female family physicians practise maternity care differently, particularly regarding the maternal serum screening (MSS) program. DESIGN: Mailed survey fielded between October 1994 and March 1995. SETTING: Ontario family practices. PARTICIPANTS: Random sample of 2000 members of the College of Family Physicians of Canada who care for pregnant women. More than 90% of eligible physicians responded. MAIN OUTCOME MEASURES: Attitudes toward, knowledge about, and behaviour toward MSS. RESULTS: Women physicians were more likely than men to practise part time, in groups, and in larger communities. Men physicians were more likely to perform deliveries; women were more likely to do shared care. Despite a shorter work week, on average, female physicians cared for more pregnant women than male physicians did. Among those providing intrapartum care, women performed more deliveries, on average, than men. Women physicians were more likely than men to offer MSS to all pregnant patients. Although average time spent discussing MSS before the test was similar, women physicians had better knowledge of when best to do the test and its true-positive rate. All differences reported were statistically significant (P < or = 0.001). CONCLUSIONS: Among family physicians caring for pregnant women, women physicians cared for more pregnant women than men did. Both spent similar time discussing MSS with their patients before offering screening, but more women physicians offered MSS to all their patients and were more knowledgeable about MSS than men physicians.

Delivery, Obstetric↗

The role of a single formin isoform in the limb and renal phenotypes of limb deformity.

BACKGROUND: Mutations of the murine limb deformity (ld) locus are responsible for a pleiotropic phenotype of completely penetrant limb malformations and incompletely penetrant renal agenesis and/or dysgenesis. The ld locus encodes a complex family of mRNA and protein isoforms. MATERIALS AND METHODS: To examine the role of one of the more prominent of these isoforms, isoform IV, we specifically eliminated it by gene targeting. RESULTS: Unlike other mutant ld mice, homozygous mice bearing this isoform IV disruption display incompletely penetrant renal agenesis, but have perfectly normal limbs. Whole mount in situ hybridization demonstrated that this targeted disruption was specific for isoform IV and did not interfere with the expression of other ld isoforms. The isoform IV-disrupted allele of ld does not complement the renal agenesis phenotype of other ld alleles, in a manner consistent with its penetrance, and like the isoform IV-deficient mice, these compound heterozygotes have normal limbs. Sequence analysis of formin isoform IV in other ld mutant alleles did not detect any amino acid changes relative to the strain of origin of the mutant allele. CONCLUSIONS: Thus, the disruption of isoform IV is sufficient for the renal agenesis phenotype, but not the limb phenotype of ld mutant mice. Structural mutations in this isoform are only one of several genetic mechanisms leading to the renal phenotype, since amino acid changes in this isoform were not detected. These results demonstrate that this gene is limb deformity, and that variable isoform expression may play a role in generating the pleiotropic ld phenotype.

Abnormalities, Multiple↗