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Biomedical subjects

W Gorman

Publications and source records attributed to W Gorman.

At least 19 recordsLinked to original sources

Haemoglobinopathy screening in an maternity hospital.

Recent changes in population movement mean that an increasing number of mothers who deliver in Ireland and their infants are at risk of haemoglobinopathies, in particular sickle cell anaemia. Early detection of sickle cell anaemia improves outcome. For this reason, many hospitals have established antenatal and neonatal screening programmes targeting high-risk ethnic groups. We audited the provision rate of one such programme operated in the National Maternity Hospital in 2003. Using the hospital's databases, we estimated the number of mothers from high-risk ethnic groups, and how many were appropriately screened. We then calculated the neonatal screening provision rate to those infants at risk of homozygous haemoglobinopathies. In 2003, 1231 (14.9%) women from high-risk ethnic groups delivered in the National Maternity Hospital. Nine hundred and ninety one (80.5%) were screened appropriately. One hundred and thirty of these women had abnormal antenatal screens, resulting in 131 infants delivered at risk of homozygous haemoglobinopathy. Fifty eight of these infants (45%) were screened in the neonatal period. The screening programme audited did not achieve a satisfactory provision rate either antenatally or neonatally.

Ethnicity↗

Predicting the rate of cognitive decline in aging and early Alzheimer disease.

OBJECTIVES: To determine prognostic factors affecting the course of Alzheimer disease (AD) and to determine the role of region-specific brain volumes as predictors of cognitive decline. METHODS: Longitudinal data from 166 normal elderly individuals and 59 early AD patients were analyzed. Brain volumes were extracted from MRI scans using semiautomated recursive segmentation methods. Prognostic factors were considered significant if they had a significant effect on the rate of cognitive decline. RESULTS: In multivariate analysis, higher Clinical Dementia Rating Scale (CDR) score at entry was a significant prognostic factor for an increased rate of cognitive decline. Significant prognostic factors within the baseline CDR = 0 group were base rate of progression and percent total high signal intensity (HSI), percent ventricular, and percent CSF volumes. Base rate of progression, family history, and percent ventricular volume were significant prognostic factors within the CDR = 0.5 group and APOE had a marginally significant effect on the rate of cognitive decline in the CDR = 1 group. CONCLUSIONS: Percent total HSI, ventricular, and total CSF volume measures can independently predict the rate of cognitive decline and improve the predictive power of statistical models that use only clinical data. Brain volumetric measures from MRI can be used to estimate the rate of cognitive decline even among normal elderly individuals and thus may aid in the prediction of time of onset of disease.

Age of Onset↗

The use of silver-stained "comets" to visualize DNA damage and repair in normal and Xeroderma pigmentosum fibroblasts after exposure to simulated solar radiation.

The alkaline and neutral comet assays have been widely used to assess DNA damage and repair in individual cells after in vivo or in vitro exposure to chemical or physical genotoxins. Cells processed under neutral conditions generate comets primarily from DNA double strand breaks, whereas under alkaline conditions, comets arise from DNA single and double strand breaks and alkali-labile lesions. A modified version of the alkaline comet assay, as described here, used silver stain to visualize the comets and a Gelbond base to facilitate the manipulation and processing of samples. To demonstrate how these modifications improve the assay, fibroblasts derived from both normal and Xeroderma pigmentosum (Xp) individuals were exposed to simulated solar radiation and the resulting DNA damage and repair evaluated and compared with results from the relevant literature. Comets from normal fibroblasts reached their maximum length at about an hour after irradiation. Dose-dependent increases in comet length were observed up to at least 360 mJ/cm2. In contrast, comet lengths from repair deficient Xp fibroblasts were shorter than normal cells reflecting their reduced capacity to generate single strand breaks by the excision of DNA dimers. For incubation times of more than 1 h, comet lengths from normal fibroblasts underwent a time-dependent decrease, supporting the contention that this change was related to the ligation step in the DNA repair process. These changes were compatible with the model of DNA damage and repair established by others for ultraviolet radiation.

Cell Line↗

Quantifying aggregation of IgE-FcepsilonRI by multivalent antigen.

Aggregation of cell surface receptors by multivalent ligand can trigger a variety of cellular responses. A well-studied receptor that responds to aggregation is the high affinity receptor for IgE (FcepsilonRI), which is responsible for initiating allergic reactions. To quantify antigen-induced aggregation of IgE-FcepsilonRI complexes, we have developed a method based on multiparameter flow cytometry to monitor both occupancy of surface IgE combining sites and association of antigen with the cell surface. The number of bound IgE combining sites in excess of the number of bound antigens, the number of bridges between receptors, provides a quantitative measure of IgE-FcepsilonRI aggregation. We demonstrate our method by using it to study the equilibrium binding of a haptenated fluorescent protein, 2,4-dinitrophenol-coupled B-phycoerythrin (DNP25-PE), to fluorescein isothiocyanate-labeled anti-DNP IgE on the surface of rat basophilic leukemia cells. The results, which we analyze with the aid of a mathematical model, indicate how IgE-FcepsilonRI aggregation depends on the total concentrations of DNP25-PE and surface IgE. As expected, we find that maximal aggregation occurs at an optimal antigen concentration. We also find that aggregation varies qualitatively with the total concentration of surface IgE as predicted by an earlier theoretical analysis.

2,4-Dinitrophenol↗

The echogenic thalamus in hypoxic ischaemic encephalopathy.

This paper reports 16 term infants in whom an echogenic thalamus was identified on cranial ultrasonography. Fourteen of the patients suffered severe birth asphyxia. The prognostic significance of this finding and the underlying pathogenesis is assessed.

Asphyxia Neonatorum↗

Clinico-pathological findings in non-immune hydrops fetalis.

Non-immune hydrops fetalis is becoming a relatively more important cause of hydrops as the incidence of rhesus-related hydrops falls. We describe a series of 33 cases, occurring over a 7 year period covering most of the 1980's. We found a very wide range of aetiological factors, but cardiac conditions, both structural and dysrhythmic, formed the largest subgroup (12 cases, 36%). Seven cases (22%) remained idiopathic. Prognosis was very poor, with only 4 infants surviving. Outcome was best in the cases due to intra-uterine supraventricular tachycardia. Nineteen cases were detected antenatally, but except in the cases of fetal tachyarrhythmias, this had little effect on outcome.

Female↗

Bronchopulmonary dysplasia: a radiographic and clinical review of 20 patients.

This paper reviews the radiological features of 20 infants with bronchopulmonary dysplasia, with particular emphasis on the early radiological findings in these infants, the clinical findings and radiological progression. Of 20 infants, eight had idiopathic respiratory distress in the first week of life, two infants had early radiological abnormalities other than idiopathic respiratory distress and 10 infants had normal initial chest radiographs. The complicating features included lower respiratory infections (88%), patent ductus arteriosus (40%) and areas of atelectasis (40%). Areas of atelectasis were more common in infants with an initially normal chest radiograph than in those with idiopathic respiratory distress syndrome (p = 0.015). Mortality from severe bronchopulmonary dysplasia was 70% in this series.

Bronchopulmonary Dysplasia↗

Neonatal seizures: the Dublin Collaborative Study.

Asphyxial seizures occurred in 89 of 101,829 infants born alive at term (0.87/1000) in three large maternity hospitals from January 1980 to December 1984. These seizures were significantly associated with antenatal complications, primiparity, and prolonged pregnancy. Meconium staining of the amniotic fluid was also associated with asphyxial seizures, but there were high false positive (11%) and false negative (50%) rates. Fifteen of the infants who had seizures died (18%) and 21 (25%) were handicapped at 1 year. Outcome was most successfully predicted by the way the infant was feeding at 1-2 weeks. All infants taking more than half their estimated requirements by mouth at 1 week were normal, and those still being fed by tube at 2 weeks were handicapped.

Asphyxia Neonatorum↗

Age-related differences in memory for lateral orientation of pictures.

Two experiments examined memory for the lateral orientation of scenic pictures by young and elderly adults. In Experiment 1, an input list of pictures was followed by a test demanding discrimination between (a) targets versus reversed copies of input items, or (b) targets versus new pictures which verbally resembled input items. The age-related difference was reliably larger in the former task than in the latter. Experiment 2 compared incidental versus intentional acquisition of orientation under conditions of short (1 second) and long (5 second) presentation of pictures at input. With short presentation, though not with long presentation, intentional instructions reliably impaired orientation memory. With both presentation times, robust age-related differences were obtained. The results suggest an age-related deficit in truly non-intentional encoding of orientation, and pose a challenge for capacity theories of memory across the lifespan.

Adult↗

Transcutaneous bilirubinometry: an evaluation.

The transcutaneous bilirubinometer was evaluated in 60 term and 10 preterm infants. A significant correlation was found between the transcutaneous index and the total serum bilirubin concentration for both term and preterm infants. The reliability of the transcutaneous bilirubinometer as a screening method was confirmed, and index criteria for serum bilirubin analysis have been suggested for term babies. The instrument was precise and accurate and the method both noninvasive and atraumatic. Since individual serum bilirubin levels and the transcutaneous index may correlate poorly the transcutaneous method cannot replace traditional serum bilirubin estimation.

Bilirubin↗

Energy metabolism in Capnocytophaga ochracea.

Among the microflora of the gingival sulcus are members of the genus Capnocytophaga which have been implicated as possible etiological agents of juvenile periodontitis and systemic infectious diseases. In this study, the pathway used by C. ochracea strain 25 for generating energy from glucose was investigated. When grown in a complex medium supplemented with glucose and NaHCO(3), the major end products formed were acetate (4.6 mmol), succinate (11.0 mmol), pyruvate (4.3 mmol), and oxalacetate (3.6 mmol), and the molar growth yield was 58. Addition of yeast extract to the growth medium caused (i) an increase in acetate (9.2 mmol) and succinate (14.3 mmol), (ii) a decrease in pyruvate (0 mmol) and oxalacetate (1.1 mmol), and (iii) the molar growth yield increased to 75. Glucose was transported by a phosphoenolpyruvate:phosphotransferase system and then catabolized to phosphoenolpyruvate by enzymes of the Embden-Meyerhof-Parnas pathway. No activities were detected for the key enzymes of the Warburg-Dickens, Entner-Douderoff, or hexose phosphoketolase pathways. During growth in the yeast extract-supplemented medium, approximately 37% of the phosphoenolpyruvate carbon was converted to acetate by pyruvate kinase, a pyruvate-decarboxylating enzyme activity, and acetate kinase; the remaining 63% was converted to succinate via phosphoenolpyruvate carboxykinase, malate dehydrogenase, fumarate hydratase, and fumarate reductase.

Adenosine Triphosphate↗

Pharmacokinetic profile of caffeine in the premature newborn infant with apnea.

The pharmacokinetic profile of caffeine was studied in 32 premature newborn infants with apnea: 12 following a single intravenous dose; 3 after a single oral dose; 7 during treatment with an initial empirical (high) maintenance dose schedule; and 10 during treatment with a revised (lower) dose schedule. Mean (+/- SE) AV d, t 1/2, ke1, and clearance following a single intravenous dose were 0.916 +/- 0.070 1/kg, 102.9 +/- 17.9 hours, 0.009 +/- 0.001/hours and 8.9 +/- 1.5 ml/kg/hour, respectively. Rapid absorption was noted with plasma concentrations of 6 to 10 mg/l achieved within 30 minutes to two hours following an oral dose of 10 mg/kg. Cpss of caffeine in infants given a high empirical dose (11.2 +/- 1.5 mg/kg/day) ranged from 22.5 to 84.2 mg/l (mean = 45.3) whereas a dose schedule based on kinetic data (2.5 mg/kg/day) yielded plasma concentrations ranging from 7.4 to 19.4 mg/l (mean = 13.7). We suggest a loading dose of 10 mg/kg intravenously or orally followed by a daily maintenance dose of 2.5 mg/kg/day administered as a single dose for the treatment and prevention of neonatal apnea.

Administration, Oral↗

Efficacy of caffeine in treatment of apnea in the low-birth-weight infant.

The efficacy of caffeine citrate in the management of apnea in the newborn infant was evaluated. Caffeine citrate was given to 18 preterm neonates with recurrent apneic spells. Mean (+/- SE) birth weight and gestational age were 1,065.0 +/- 71.9 gm and 27.5 +/- 0.6 weeks, respectively. Mean age at onset of apnea and at initiation of caffeine treatment was 6.5 +/- 3.7 days and 18.2 +/- 4.9 days, respectively. Caffeine citrate was administered with a loading dose of 20 mg/kg intravenously followed within two to three days by 5 to 10 mg/kg once or twice daily. All infants except one showed a significant decrease in the frequency of apneic episodes associated with caffeine therapy. Mean frequencies of apneic spells were 13.6 +/- 2.5 and 2.1 +/- 0.6 apnea per day before and after initiation of caffeine treatment, respectively. Respiratory rate was increased, and blood [h]+ion concentration and Pco2 were decreased. The data suggest that caffeine is an effective pharmacologic respirogenic agent in the preterm infant with apnea.

Apnea↗