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Biomedical subjects

H Simpson

Publications and source records attributed to H Simpson.

At least 73 records · Page 4Linked to original sources

Epidemiological study of wheeze, doctor diagnosed asthma, and cough in preschool children in Leicestershire.

OBJECTIVE: To determine the cumulative prevalences of wheeze and doctor diagnosed asthma and the point prevalences of recurrent cough and wheeze in children aged 5 years and under. DESIGN: Questionnaire survey of population based random sample of children registered on regional authority's child health index for immunisation; questionnaire completed by parents. SETTING: Leicestershire. SUBJECTS: 1650 white children born in 1985-9 who were surveyed in 1990. MAIN OUTCOME MEASURES: Cumulative prevalences of wheeze and doctor diagnosed asthma and point prevalences of recurrent cough and wheeze by age and sex. RESULTS: There were 1422 replies (86.2%; 726 for boys, 696 for girls). Overall, 11.0% (95% confidence interval 9.4% to 12.6%) of children had formally been diagnosed as having asthma, the cumulative prevalence in boys (12.7%) being somewhat higher than in girls (9.2%) (age adjusted odds ratio 1.47, p = 0.03). As expected, the cumulative prevalence of asthma increased significantly with age (7.5% (13/173) in children under 1 year, 15.9% (61/383) in children of 4 years and over; p < 0.001). The cumulative prevalence of wheeze overall was 15.6% (13.7% to 17.5%), being higher in boys (17.6%) than in girls (13.5%) (odds ratio 1.38, p = 0.03). The overall prevalence of recurrent cough without colds was 21.8% (19.6% to 23.9%), with a non-significant excess in boys (23.1% v 20.4%). The overall prevalence of wheezing attacks during the previous 12 months was 13.0% (11.3% to 14.8%) with a non-significant excess in boys (14.5% v 11.5%). CONCLUSIONS: These findings are baseline results and emphasise the importance of studying the age group of interest rather than relying on the recall of parents of school age children.

Age Factors↗

Modulation of mdr-1 expression by a H-ras oncogene in a human colon carcinoma cell line.

In an established colon differentiation model, introduction of a c-H-ras-1 oncogene into a poorly differentiated human colon carcinoma cell line (Clone A) results in changes associated with the acquisition of a more differentiated phenotype. Down-regulation of mdr-1 mRNA was shown to accompany ras-related differentiation events resulting in decreased Pgp synthesis and a significant reduction in membrane Pgp as detected by immunoprecipitation, Western-blot and FACS analysis. Consistent with these observations was a reduction in Pgp-mediated drug resistance associated with Clone-A ras transfectants, with no alteration in drug sensitivity being observed with non-MDR drugs in these cells. An alternative differentiation model involves exposure of Clone-A cells to sodium butyrate. Under these conditions, differentiation-related changes resulted in up-regulation of mdr-1 mRNA and Pgp synthesis, although no alteration in drug sensitivity was recorded. In agreement with this observation, the levels of membrane-associated Pgp remained unchanged throughout the period of exposure to sodium butyrate. This study shows that modulation of Pgp expression in colon differentiation is dependent upon the differentiation induction agent used.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Immortalization and neoplastic transformation of normal rat colon epithelium: an in vitro model of colonic neoplastic progression.

BACKGROUND: Because of the refractory nature of colon epithelium to growth and maintenance in vitro, the cell lines currently available for study are derived from tumors. Unlike most epithelial model systems, there exist no preneoplastic, nontumorigenic colon cell lines for manipulation and study. METHODS: Intact fetal rat colon was cultured in the presence of a feeder layer of cells producing a retrovirus that harbors the SV40 LT gene resulting in the establishment of immortalized colon cell lines. RESULTS: The epithelial and intestinal origin of cell lines was established from the constitutive expression of keratin and villin, respectively. All cell lines displayed an absence of anchorage independent growth and failed to produce tumors in vivo. Neoplastic transformation of immortalized rat colon epithelial cell lines was achieved following introduction of individual oncogenic ras gene members or the v-src oncogene. Probing of cell lysates with phosphotyrosine antibodies revealed altered phosphotyrosyl protein profiles associated with different stages of colonic neoplastic progression. CONCLUSIONS: The establishment of immortalized nontumorigenic colon epithelial cell lines facilitates the biochemical analysis of events associated with different stages of colonic neoplastic progression. In addition, this simple culture technique lends itself to studies involving alternative genetic elements implicated in the genesis of colon tumors.

Animals↗

Comparison of peripheral chemoreceptor responses in monozygotic and dizygotic twin infants.

The peripheral chemoresponses of infant twin pairs were determined using a single-breath hyperoxic stimulus. A total of 43 twin pairs of comparable gestation and birth weight were studied during sleep at a mean (SD) age of 8 wk (1.4) while alternately breathing either air or 16% oxygen in nitrogen. Infants responded to a single breath of 100% oxygen by a reduction in ventilation; the mean (SEM) reduction in air was 273 ml/min (10.6) and in 16% oxygen 560 ml/min (18.4). Within-pair variances were compared in 14 monozygotic and 28 dizygotic pairs utilizing combined responses (air + 16% oxygen) computed for measurements made in behavioral quiet sleep and in 9 monozygotic and 20 dizygotic pairs for whom data were complete in polygraphically confirmed quiet sleep. The variance of responses within dizygotic twin pairs was greater than in monozygotic pairs when expressed in ml/min: F ratio 4.11 (p = 0.005) for all data and F ratio 7.67 (p = 0.003) in quiet sleep. Expressed in ml/min/kg the difference was less significant: F ratio 1.83 (p = 0.126) for all data and F ratio 3.46 (p = 0.039) in quiet sleep. Gender, birth weight, and birth order had no effect on these findings. This closer similarity of response in monozygotic twin pairs is explained by proposing a high degree of heritability for the response.

Chemoreceptor Cells↗

Serum sialic acid enzymatic assay based on microtitre plates: application for measuring capillary serum sialic acid concentrations.

We have adapted a commercially-available kit for the enzymatic determination of sialic acid so that the reaction can be carried out in microtitre wells and the coloured end product quantitated on an ELISA plate reader. The small volume of serum used allows sialic acid to be measured in capillary blood samples. The assay was based on release of sialic acid from glycoconjugates by neuraminidase, cleavage of sialic acid by N-acetyl neuraminic acid aldolase to pyruvate, and then oxidation of pyruvate to hydrogen peroxide by pyruvate oxidase. Hydrogen peroxide was determined by the red product formed in the presence of peroxidase, 4-aminoantipyrine and N-ethyl-N-2-hydroxyethyl-3-toluidine. The assay was linear to at least 10 mmol/l and unaffected by haemolysis, and by the addition of glucose, 3-hydroxybutyrate, bilirubin and pyruvate. Capillary serum sialic acid concentrations were not significantly different from simultaneously measured venous serum sialic acid levels. Self-collected capillary blood samples were obtained from healthy subjects over 6 h during the day. No variations in serum sialic acid concentrations were found in response to a meal. We conclude that this micro-adaptation of a specific sialic acid assay will be suitable for epidemiological surveys of serum sialic acid collected by patients and normal subjects.

Biomarkers↗

Prevention of hand injuries in cycle accidents.

More than one fifth of patients in a group involved in cycle crashes sustained hand injuries. The average time off work as a result of the hand injury in our study was 17.6 days. The number and severity of hand injuries would be reduced by the wearing of proper gloves and this is recommended. The gloves currently sold as "cycling" gloves are not adequate.

Abbreviated Injury Scale↗

Gaviscon and Carobel compared with cisapride in gastro-oesophageal reflux.

We compared the efficacy of the prokinetic agent cisapride with that of Gaviscon (an alginate/alkaline compound) plus Carobel (carob seed flour) in the treatment of gastrooesophageal reflux (GOR). Fifty infants with confirmed GOR received either oral cisapride (0.8 mg/kg/day) or Gaviscon plus Carobel for one month in a randomised, parallel group study. Parental evaluations, diary scores, and 24 hour lower oesophageal pH recordings before and at the end of each treatment were compared. In the cisapride group 14/26 (53%) were considered better by their parents compared with 19/24 (79%) of those who received Gaviscon plus Carobel. Diary scores, range (0.00-1.00), improved in both groups with the median change being greater in the Gaviscon plus Carobel group (-0.21) than the cisapride group (-0.15). Five of 17 pH variables had significantly improved from baseline in infants who had received cisapride compared with 11/17 in those receiving Gaviscon plus Carobel. However, unpaired analysis of diary and pH data showed no significant differences between the two groups. We conclude that first line treatment of GOR with cisapride is no more effective than conventional treatment with Gaviscon plus Carobel.

Alginates↗

Asthma severity at night during recovery from an acute asthmatic attack.

This study was undertaken to investigate the severity of night time asthma in children in hospital recovering from an acute attack of asthma. Twenty two children aged 5-14 years were studied. Coughing 'epochs' overnight varied from one to 156 (median 39.5) and mean overnight arterial oxygen saturation (Sao2) from 82 to 98% (mean 91.3). Log values for cough showed a correlation with Sao2. An Sao2 of less than 90% was invariably associated with coughing but Sao2 above 95% did not preclude cough. Peak flow measured in the morning or evening correlated with Sao2 but not with log cough, and clinical examination scores showed no correlation with overnight measurements. Night time Sao2 correlated better with daytime tests of lung function than log cough. In general, night time indices of severity reflected daytime pulmonary function status but night cough was sometimes prominent in less severely affected cases. At the time of discharge, clinical indices of severity underestimated the degree of functional impairment at night.

Acute Disease↗

Effect of controlled release salbutamol on nocturnal cough in asthma.

Sixteen asthmatic children completed a double blind placebo controlled crossover study of controlled release salbutamol (CRS) to assess its efficacy in controlling night time cough. Children with asthma were enrolled into the study on the basis of a history of persistent cough confirmed by two overnight tape recordings at home. Outcome was measured by two overnight tapes on each medication. Other treatment was unaffected. There was no significant fall in cough counts on CRS. Median scores were 14.5 and 12.0 coughing episodes per night for CRS and placebo respectively. Mean overnight oxygen saturation was identical in both treatment periods but morning peak flow showed a trend towards improvement on CRS. Treatment with CRS does not have a significant effect in control of night cough although it may improve objective measurements of lung function.

Adolescent↗

Gastro-oesophageal reflux and respiratory function in infants with respiratory symptoms.

This study aimed to define the incidence and severity of gastro-oesophageal reflux (GOR), as measured using 24 hour oesophageal pH monitoring, in 38 infants with recurrent respiratory symptoms and to relate these findings to measures of respiratory function. Twenty one infants had a pH under 4 for more than 5% of the time (one definition of abnormal GOR) and nine had GOR exceeding age related normal values. Maximum expiratory flow at functional residual capacity was reduced in 37 infants, airways resistance was raised in 19 infants, and thoracic gas volume was abnormal in 11 infants. There was no association between indices of GOR and measures of lung function whether assessed by correlation or by chi 2 analysis for normal versus abnormal values. However, individual infants appeared to have respiratory symptoms produced by GOR. This suggests that host responsiveness to GOR may be of greater relevance than the amount of GOR.

Female↗

The effect of a single breath of 100% oxygen on breathing in infants at 1, 2, and 3 months of age.

Sequential measurements of the ventilatory response to a single breath of oxygen delivered during quiet sleep were made in 16 healthy infants between 1 and 3 months of age, alternately breathing air and 16% oxygen in nitrogen. At 1 month the response to a single breath of oxygen during normoxia was a decrease in minute ventilation of 264 +/- 34.2 (SEM) ml.min-1 during the 10-s period following the stimulus (p less than 0.001). During mild hypoxia the decrease in ventilation averaged 471 +/- 49.1 (SEM) ml.min-1 (p less than 0.001). The difference in response between measurements in air and mild hypoxia was significant (p less than 0.001). By the age of 3 months, the absolute ventilatory response to a single breath of oxygen increased significantly in normoxia by 118 +/- 35.2 ml.min-1 (p less than 0.01); the test response to breathing 16% oxygen paralleled the response to normoxia and was on average 254 +/- 26.6 ml.min-1 larger than the response when breathing air (p less than 0.001). When the three age groups were compared, calculating the response per killigram body weight showed that the response was similar at all three ages tested. These data provide a reference baseline for normal infants.

Chemoreceptor Cells↗

Gastro-oesophageal reflux and apnoeic pauses during sleep in infancy--no direct relation.

We studied the relation of gastro-oesophageal reflux with apnoea during sleep in 24 infants with antecedent respiratory abnormalities and/or proven gastrooesophageal reflux (GOR), by combined lower oesophageal pH and polygraphic monitoring. GOR, indicated by pH less than 4, was confirmed in 24 infants. There were no episodes of prolonged (greater than 20 s) central apnoea (CA). Fifty-six mixed or obstructive breathing episodes were identified in 12 infants (14 studies), of which 28 lasted between 3 and 6 s. Bradycardia (heart rate less than less than 80 beats/min for 10 s was not observed. There were 80 falls in transcutaneous oxygen (PtcO2 greater than 5 mmHg) but only 6 exceeded 10 mmHg and one 20 mmHg. There was no relationship between GOR and obstructive episodes in terms of frequency, duration or temporal occurrence, except in one infant. There were 1276 gross body movements, mainly during active or indeterminate sleep and, of these, 7% were associated with decreases in pH to less than 4. Movements occurred during the 60 s period preceding 83% of pH decreases greater than 1 pH unit compared to only 30% in the 60 s succeeding a pH drop. We conclude that, while GOR and obstructive episodes may co-exist in the patient groups studied, decreases in pH in the lower oesophagus do not usually induce either central or obstructive apnoea, and vice versa. Of the variables monitored, only gross body movements were temporally associated with pH drops, and usually preceded them.

Blood Gas Monitoring, Transcutaneous↗

Observations on gastro-oesophageal reflux, central apnoea and heart rate in infants.

Respiratory movements and heart rate were monitored continuously during the course of 2 h radionuclide studies to detect gastro-oesophageal reflux (GOR) in 22 infants following a milk feed. Twenty infants had GOR, to upper oesophageal/pharyngeal level in 19, and 17 had central apnoea between 3 and 15s. Prolonged central apnoea (greater than 20s) was not observed. Bradycardia, defined as a heart rate less than 80 beats/min for 10s or more, was observed in only 1 infant who did not have GOR. No correlation was found between the number or duration of reflux episodes and the frequency of respiratory pauses between 3 and 17s. When data from individual infants were examined a possible temporal relation between the occurrence of GOR and central apnoea was seen in only two infants; in each case, detailed examination suggested that apnoea was more closely associated with sleep than with GOR. Although the respiratory monitoring system did not include airflow sensors, the almost complete absence of bradycardia suggested that prolonged obstructive apnoeas did not occur. We conclude that any relation between GOR and central apnoeas less than 15 s is not of a direct cause/effect nature.

Bradycardia↗