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Biomedical subjects

R A Primhak

Publications and source records attributed to R A Primhak.

At least 37 records · Page 2Linked to original sources

Diuretics acting on the distal renal tubule for preterm infants with (or developing) chronic lung disease.

OBJECTIVES: The aim of this review is to assess the risks and benefits of diuretics acting on distal segments of the renal tubule (distal diuretics) in preterm infants with or developing chronic lung disease (CLD). Primary objectives are to assess changes in need for oxygen or ventilatory support and effects on long-term outcome, and secondary objectives are to assess changes in pulmonary mechanics and potential complications of therapy. SEARCH STRATEGY: We used the standard method of the Cochrane Neonatal Review Group. We used the following keywords: ¿ or ¿ and , limited to and limited to or . We searched Medline (1966-1998), Embase (1974-1998) and the Cochrane Controlled Trials Register (CCTR) from the Cochrane Library (1999, issue 2). In addition, we hand searched several abstract books of national and international American and European Societies. SELECTION CRITERIA: We included in this analysis trials in which preterm infants with or developing CLD and at least five days of age were all randomly allocated to receive a distal diuretic (i.e., a diuretic acting on the distal renal tubule). Eligible studies needed to assess at least one of the outcome variables defined a priori for this systematic review. Primary outcome variables included changes in need for respiratory support and oxygen supplementation, mortality, bronchopulmonary dysplasia (BPD), death or BPD, chronic lung disease at 36 weeks of postconceptional age (gestational age + postnatal age), length of stay, and number of rehospitalizations during the first year of life. Secondary outcome variables included pulmonary mechanics and potential complications of therapy. DATA COLLECTION AND ANALYSIS: We used the standard method for the Cochrane Collaboration which is described in the Cochrane Collaboration Handbook. Two investigators extracted, assessed and coded separately all data for each study, using a form that was designed specifically for this review. Any disagreement was resolved by discussion. We combined parallel and cross-over trials and, whenever possible, transformed baseline and final outcome data measured on a continuous scale into change scores using Follmann's formula. MAIN RESULTS: Of six studies fulfilling entry criteria, most focused on pathophysiological parameters and did not assess effects on important clinical outcomes defined in this review, or the potential complications of diuretic therapy. In preterm infants > 3 weeks of age with CLD, a four-week treatment with thiazide and spironolactone improved lung compliance and reduced the need for furosemide. Thiazide and spironolactone decreased the risk of death and tended to decrease the risk for lack of extubation after 8 weeks in intubated infants. There is no evidence to support the hypothesis that adding spironolactone to thiazide or that adding metolazone to furosemide improves the outcome of preterm infants with CLD. REVIEWER'S CONCLUSIONS: In preterm infants > 3 weeks of age with CLD, acute and chronic administration of distal diuretics improve pulmonary mechanics. Chronic administration of diuretics (thiazide with spironolactone) reduces mortality in intubated patients. Large studies are needed to assess (1) whether chronic diuretic administration improves mortality, duration of oxygen dependency, ventilator dependency, length of hospital stay and long-term outcome in patients without long-term toxicity and (2) whether adding spironolactone to thiazides or adding metolazone to furosemide has any beneficial effect.

Chronic Disease↗

Use of diclofenac in children with asthma.

This study investigated the effect of diclofenac on the lung function of 70 children aged 6-15 years with a diagnosis of asthma, recruited from a hospital respiratory clinic. Peak flow and a forced expiratory flow-volume loop were measured and the patients were then given 1-1.5 mg.kg-1 effervescent diclofenac orally. Spirometry was repeated at 10, 20 and 30 min, a 15% decrease in results being considered a significant reduction in lung function. No patient demonstrated a consistent reduction in lung function of > 15% during the study and there were no reports of wheezing or increased bronchodilator use after completion of the spirometry. In conclusion, we studied a group of genuine asthmatics and found no clinically significant incidence of bronchospasm with the use of a single therapeutic dose of diclofenac.

Adolescent↗

A comparison of neonatal and adult lung impedances derived from EIT images.

An objective method of extracting respiratory data from lung images is presented, together with a technique for automatically generating regions of interest delineating the anterior and posterior regions of the lungs. The method is used to extract data on the change in lung impedance with frequency, and on calculated Cole parameters, from 19 normal neonates (gestational age 32 to 42 weeks) and 8 normal adults (age 21 to 82 years). A comparison of the impedance properties of neonatal and adult lungs was made. The variation of lung impedance with frequency in neonates, as derived from EIT images, is significantly different from that found for adults. The implications for a model of the electrical impedance of lung tissue are discussed.

Adult↗

The bronchoprotective effect of inhaled salmeterol in preschool children: a dose-ranging study.

The optimal dose of salmeterol in infants and preschool children is not known. The aim of this study was to assess the bronchoprotective effect of different doses of salmeterol using methacholine-induced wheeze in children aged <4 yrs. Children <4 yrs old with a history of recurrent wheeze underwent two methacholine challenges within 7 days. One hour before each challenge they were pretreated in double-blind fashion using a metered-dose inhaler and Babyhaler spacer. Placebo was given before one challenge, and either 25, 50 or 100 microg of salmeterol before the other. Both the dose and treatment order were random. The provocative concentration of methacholine causing wheeze (PCwheeze) was measured on each occasion. Studies were terminated when wheeze occurred or arterial oxygen saturation (Sa,o2) fell below 91%. Of the 42 children enrolled, 33 completed the study. Two subjects refused the challenge test, two failed to return and five developed upper respiratory tract infections or wheeze between the two tests. The mean (range) age of the population was 27 (8-46) months. Ratios of PCwheeze between treatment and placebo challenges were calculated for each dosage group. The treatment/placebo ratios (95% confidence intervals) were 1.2 (0.6-2.4) for 25 microg, 2.5 (1.4-4.6) for 50 microg (p<0.01), and 4.0 (2.1-7.4) (p<0.001) for 100 microg doses. In recurrently wheezy children aged <4 yrs a single dose of salmeterol between 25 and 100 microg has a dose-dependent effect on methacholine-induced wheeze, and this is significantly different from placebo at 50 and 100 microg. This study suggests that the Babyhaler effectively delivers salmeterol to children <4 yrs of age and that doses between 50-100 microg are efficacious.

Administration, Inhalation↗

Methacholine challenge in preschool children: methacholine-induced wheeze versus transcutaneous oximetry.

Tracheal/chest auscultation for wheeze and transcutaneous oximetry have both been suggested as measures of outcome in bronchial provocation tests in young children. This study aimed to compare the sensitivity and safety of these two techniques as end-points for methacholine challenge in children aged <4 yrs. Seventy-two methacholine challenges were performed in 39 children aged <4 yrs with recurrent wheeze. Arterial oxygen saturation (Sa,O2) and transcutaneous oxygen pressure tcPO2 continuously, and the test was terminated when wheeze was heard or at Sa,O2 <91%. tcPO2 was not used as an end-point. Wheeze or desaturation occurred at < or =8 mg x mL(-1) methacholine in every test. One child had transient clinical cyanosis, but no other ill-effects were seen. Fifty-six tests (78%) were terminated for wheeze, seven (10%) for fall in Sa,O2 and nine (12%) showed simultaneous responses in both parameters. Twenty-eight tests (39%) contained a fall in tcPO2 >3 kPa but six of these also showed a significant rise. Fifty-three tests (75%) contained a fall in tcPO2 >15%, but 20 of these also showed a significant rise. Tracheal/chest auscultation with Sa,O2 monitoring is a sensitive and relatively safe end-point for bronchial challenges in preschool children. The erratic pattern of transcutaneous oxygen pressure response in some children casts doubt on its reliability as a proxy measure of bronchial obstruction.

Auscultation↗

Variable phenotype in Kaufman-McKusick syndrome: report of an inbred Muslim family and review of the literature.

Multiple congenital anomalies (MCA) in two siblings and digit abnormalities in four related individuals from a large highly inbred Muslim family are described. The pattern of MCA is consistent with the autosomal recessive Kaufman-McKusick syndrome [MIM 236700]. The present report reviews the previously published reports on this uncommon MCA dysmorphic syndrome and draws attention to the marked variation in the phenotype.

Abnormalities, Multiple↗

Pulmonary function, exercise performance, and growth in survivors of congenital diaphragmatic hernia.

A cohort of survivors of congenital diaphragmatic hernia (CDH), with matched controls, was studied to assess growth, respiratory function, and exercise performance. Nineteen of 24 survivors from an 11 year period (79%) were compared with 19 matched controls. Subjects had detailed auxology, performed spirometry and cycle ergometry, and completed questionnaires about respiratory symptoms and exercise. There were no significant differences between the groups for height, weight, sitting height, head circumference, or body mass index expressed as SD scores. The mean (95% confidence interval) percentage predicted forced vital capacity (FVC) was 84.7% (79.1 to 90.3) in index cases and 96.5% (91.4 to 101.6) in controls (p < 0.01). There was no significant difference in total lung capacity. Expiratory flow rates corrected for FVC were also similar between groups, suggesting normal airway function relative to lung size. Mean maximum oxygen consumption in ml/kg/min was 40.1 (36.8 to 43.4) and 42.2 (38.5 to 45.8) in index and control cases. These differences were not significant. Index cases achieved a similar minute ventilation to controls by more rapid and shallower breathing. Index cases had lower perception of their own fitness and lower enjoyment of exercise, although habitual activity levels were similar. Survivors of CDH repair have reduced functional lung volumes, but normal airway function compared with matched controls. They have no growth impairment nor significant impairment of exercise performance, although they have more negative perceptions of their own fitness. They should be encouraged and expected to participate fully in sport and exercise.

Child↗

Arterial oxygen saturation profiles in healthy preterm infants.

AIM: To construct a reference range of SpO2 values in healthy preterm infants using a simple data logging device. METHODS: Thirty three healthy preterm infants were monitored for a continuous period of 4 hours at rest using an Ohmeda Biox 3700 E Pulse Oximeter and an electronic data logger (Rustrack Ranger). Stored data were downloaded and saved as individual files on a personal computer. RESULTS: The study group median and 5th and 95th percentiles were used to construct a cumulative frequency curve of time against SpO2 value, representing the normal reference range of SpO2 profiles in healthy preterm infants. CONCLUSION: Comparison of an infant's SpO2 profile against this curve may be more helpful in guiding supplemental oxygen treatment in that individual than a figure for a mean SPO2 and its standard deviation.

Arteries↗

Neonatal respiratory distress in near-term infants--consider surfactant protein B deficiency.

Two infants presenting with respiratory distress in the first 24 h of life are described. Both patients underwent extensive investigation before the diagnosis of surfactant protein B-deficiency was reached. Both children died within 2 months of birth. Parental consanguinity was known to be a feature in the first case, who proved to have a previously unrecognized mutation of the surfactant protein B gene. In the second case, a history of parental consanguinity was not sought from the Caucasian family, but was later volunteered by the parents themselves. Case 2 proved to have the "common" surfactant protein B-deficient genotype. The key to diagnosis is having a high index of suspicion in any term or near-term newborn with severe respiratory distress; parental consanguinity must be excluded. Surfactant protein B-deficiency can be readily diagnosed from bronchoalveolar lavage specimens; a simple, inexpensive procedure which is well tolerated in newborns.

Bronchoalveolar Lavage Fluid↗

Reproducibility of electrical impedance tomographic spectroscopy (EITS) parametric images of neonatal lungs.

The reproducibility of electrical impedance tomographic spectroscopy (EITS) images of neonatal lungs have been investigated in 11 clinically stable babies. We have used the Sheffield Mark IIIa EITS system. An average inspiration frame was generated from the data frames associated with maximum inspiration. Frequency images were reconstructed from these frames. The frequency images were analysed to locate the pixel with the maximum change in the right lung field. The change was defined as the 614 kHz measurement relative to 9.6 kHz. A 3 x 3 pixel region of interest was centred at this point. The changes in impedance with frequency for this region of interest show good overall reproducibility between electrode applications for eight frequencies (95% limits of agreement +/- 28%). This reproducibility is improved (95% limits of agreement +/- 13%) by omitting the highest frequency (1.2 MHz) which is most subject to system noise. The parameters for the Cole model derived from data with the highest frequency omitted are less reproducible between electrode applications (95% limits of agreement, R/S +/- 0.83, fc +/- 81.6, RC +/- 0.52, SC +/- 0.39). We suspect that the parametric model used may have an effect on this. The signals recorded at the highest frequency (1.2 MHz) are a major source of variability. The reproducibility results are improved by omitting this frequency from the analysis.

Body Water↗

Longitudinal study of free running exercise challenge: reproducibility.

The reproducibility of free running exercise challenge has been examined in an unselected population of 8-10 year olds. Using a standardised protocol, monthly exercise tests were performed on 143 children over one year. A positive test was defined using both a 15% and 20% fall in peak expiratory flow after exercise. The mean (95% confidence interval, CI) population frequency for a positive test at 15% fall was 14.9% (6.5 to 23.3) and coefficient of variation 24.6%. For a 20% fall, the mean (95% CI) population frequency was 7.9% (2.9 to 12.9) and coefficient of variation 27.8%. Seventy two (50.3%) of the children gave at least one positive response at 15% fall. Exercise testing is not reproducible in the community setting and should not be used as a screening test. Exercise data from epidemiological studies of asthma should be interpreted with caution.

Asthma↗

Stability of respiratory symptoms in unlabelled wheezy illness and nocturnal cough.

OBJECTIVE: To assess the natural history of respiratory symptoms not labelled as asthma in primary schoolchildren. DESIGN: Repeat questionnaire survey of subgroups identified from a previous questionnaire survey after a two year delay. SUBJECTS: The original population of 5321 Sheffield children aged 8-9 years yielded 4406 completed questionnaires in 1991(82.8%). After excluding children with a label of asthma, there were 370 children with current wheeze, 129 children with frequent nocturnal cough, and a random sample of 222 children with minor cough symptoms and 124 asymptomatic children. RESULTS: Response rates in the four groups were 233 (63.0%), 77 (59.7%), 160 (72.1%), and 90 (72.6%) respectively. Of those who initially wheezed, 114 (48.9%) had stopped wheezing and 42 (18.0%) had been labelled as having asthma. Those with more frequent wheezing episodes (p < 0.02) and a personal history of hay fever (p < 0.01) in 1991 were more likely to retain their wheezy symptoms. In the children with frequent nocturnal cough in 1991, 20.1% had developed wheezing, 42.9% had a reduced frequency of nocturnal coughing, and 14.2% had stopped coughing altogether two years later. One sixth had been labelled as having asthma. Children with nocturnal cough were more likely to develop wheezing if they had a family history of atopy (p = 0.02). Only 3.8% and 3.3% of those with minimal cough and no symptoms respectively in 1991 had developed wheeze by 1993 (1.9% and 1.0% labelled as asthma). CONCLUSIONS: Most unlabelled recurrent respiratory symptoms in 8-10 year olds tend to improve. Unlabelled children who have persistent symptoms have other features such as frequent wheezing attacks and a family or personal history of atopy. If a screening questionnaire were to be used to identify such children, a combination of questions should be employed.

Asthma↗

Multifrequency and parametric EIT images of neonatal lungs.

The aims of the study were to investigate the problems involved in making multifrequency EIT measurements on neonates and to compare the images obtained with the results from a group of normal adults. The Sheffield electrical impedance tomographic spectroscopy (EITS) system acquires multifrequency data using a set of eight drive and eight receive electrodes. EITS measurements were made on an inhomogeneous group of 10 neonates admitted to the special care baby unit for observation and feeding. R/S, characteristic frequency, RC and SC parameters were generated using the Cole equation. Comparisons of the parameters were made with data collected from normal adults in another study. We have shown that it is possible to obtain EITS parametric images of neonatal lungs and that there are some differences in Cole parameters between the adult and neonatal groups.

Adult↗

Asthma treatment, perceived respiratory disability, and morbidity.

An entire school year of 8-9 year old schoolchildren in Sheffield were surveyed using the core questions of the international study of asthma and allergies in childhood in order to assess the morbidity associated with diagnosed asthma. Of 5321 children surveyed, replies were obtained from 4539 (85.3%). A current diagnosis of asthma was reported in 466 (10.3%), and a further 6.4% reported symptoms compatible with significant undiagnosed asthma. A validated questionnaire was used to assess symptoms and perceived disability in 336 (72.1%) of the children with diagnosed asthma. One third reported symptoms every day or most days, while 15.3% reported frequent nocturnal symptoms. There was no significant difference in reported symptoms between those receiving inhaled steroids, sodium cromoglycate, or no prophylaxis. Despite this, parents of children receiving inhaled steroids perceived more disability, and worried more about their children's health. It is concluded that perceived symptoms and morbidity are high in children with diagnosed asthma, and speculate that level of treatment is determined by parental tolerance of symptoms as much as by the symptoms themselves.

Administration, Inhalation↗

Antioxidant status in asthma.

Reduced levels of glutathione peroxidase (GSH-Px) have been observed in adults with asthma. This study examines the antioxidant status in children with asthma compared with a control group in a cross-sectional analysis. Red blood cell GSH-Px, superoxide dismutase (SOD), and plasma concentrations of retinol, vitamin C, alpha tocopherol, and cholesterol were measured in 37 subjects (26 males) with stable controlled asthma. Thirty-five subjects (20 males) without eczema, hayfever, or recurrent respiratory symptoms were used as a control group. Children with asthma had significantly reduced red blood cell GSH-Px activity compared with controls [median (inter-quartile range) for asthma group, 10.25 (9.25-11.91); for control group, 11.75 (10.34-12.26) IU/g Hb; P = 0.006]. There were no significant differences in activity of SOD or vitamin C, retinol, or alpha tocopherol/cholesterol ratio. The reduction in GSH-Px activity may have therapeutic and etiological implications for asthma. The effects of disease activity and treatment on antioxidant status needs for further study.

Adolescent↗

Early changes in lung function and response to surfactant replacement therapy.

Dynamic respiratory system compliance (Cdyn) was measured in 44 preterm babies before, immediately after, and for 96 h following administration of artificial surfactant (Exosurf). There was no significant change in Cdyn for the whole group over the entire study period. Subdivision into three groups on the basis of Cdyn prior to surfactant revealed a significant and sustained deterioration in lung function in those babies with the highest starting compliance and a significant and sustained improvement in those with the lowest compliance. Inspired oxygen and alveolar/arterial oxygen gradient also exhibited significant differences with least improvement in the babies with the best initial lung function and most improvement in the babies with worst initial lung function and most improvement in the babies with worst initial lung function. Despite clear initial differences in clinical status, neither long-term oxygen requirements nor the incidence of chronic lung disease differed significantly between the three groups. We conclude that the response of an individual baby to the administration of surfactant is, in part, determined by the lung function before surfactant is administered. Babies with higher initial lung compliance are more likely to deteriorate after administration and caution should be used before selection of such babies for surfactant treatment.

Humans↗

Does vitamin C intake influence the rate of tyrosine catabolism in premature babies?

A study was conducted to investigate the relationship between vitamin C intake and the rate of tyrosine catabolism in premature babies. A 13C tyrosine breath test was developed for the measurement of tyrosine catabolism. Premature babies were randomly allocated to receive a daily intake of vitamin C which ranged from 8 to 100 mg/kg body weight, for 5 days. Tyrosine catabolism was measured at the beginning and the end of this period. Daily intakes of vitamin C of 20 mg/kg or more elicited a greater increase in tyrosine catabolism over 5 days than 8 mg/kg/day. The magnitude of the difference, in terms of percentage of tyrosine metabolised, was, however, small and of doubtful biological significance. Vitamin C intakes above 20 mg/kg/day had no further measurable effect on the catabolism of tyrosine.

Ascorbic Acid↗