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Biomedical subjects

R McConnell

Publications and source records attributed to R McConnell.

At least 19 recordsLinked to original sources

Iodine excretion in regions of Ukraine affected by the Chornobyl Accident: experience of the Ukrainian-American cohort study of thyroid cancer and other thyroid diseases.

Urinary iodine concentrations were measured in 11,926 subjects who are participants in the Ukrainian-American Cohort Study of Thyroid Cancer and Other Thyroid Diseases Following the Chornobyl Accident. Measurements were made in two time periods corresponding to the first and second thyroid screening cycles (1998-2000, 2001-2003). These time periods fall before and after initiation of a government program to increase iodine sufficiency. Median urinary iodine concentrations did increase in the later time period compared to the earlier [47.5 microg/L, 95% confidence interval (CI) 46.5-48.9 microg/L versus 41.7 microg/L, 95% CI 40.4-42.5 microg/L], but levels remained in the mild-to-moderate iodine deficiency range as defined by the World Health Organization (WHO), indicating the need for further efforts at iodination. In both time periods, urinary iodine levels were found to vary by place of residence and were lower in rural compared to urban areas. Iodine status needs to be considered when evaluating risk of thyroid cancer and other thyroid diseases.

Adolescent↗

Educational intervention to control cockroach allergen exposure in the homes of hispanic children in Los Angeles: results of the La Casa study.

BACKGROUND: Cockroach allergy is common among inner city children with asthma, and exposure to cockroach allergen is associated with more severe disease. However, there has been little evaluation of educational approaches for controlling cockroach infestations and reducing allergen exposure. OBJECTIVE: An educational intervention to reduce cockroach allergen exposure in the homes of Hispanic children in Los Angeles was implemented and evaluated. METHODS: Caretakers of 150 children with asthma were randomly assigned to an in-home intervention or comparison group. In the intervention group, peer health educators trained the caretaker to control cockroaches by reducing harbourage and access to food and by applying boric acid, and to reduce allergen exposure by cleaning. Allergen impermeable covers were placed on the child's mattress and pillows. Knowledge, reported and observed behaviour, cockroach counts, and cockroach allergen (Bla g 1) in dust samples from the kitchen and the child's bedding were assessed at study entry and at follow-up 4 months later. RESULTS: There was improvement in knowledge and in observed and reported behaviour hypothesized to be associated with cockroach control. The geometric mean cockroach number in the intervention homes at the follow-up visit was 60% lower than in the non-intervention homes (95% confidence interval (CI) 14%, 81%). Geometric mean total cockroach allergen collected from the child's bedding was 64% lower in the intervention group (95% CI 12%, 85%). In homes with heavier initial cockroach infestation, there was a larger reduction in total kitchen dust allergen and concentration associated with the intervention than in homes with fewer initial cockroaches. CONCLUSIONS: We conclude that reduction in number of cockroaches and in total allergen in bedding dust can be achieved by caretakers of asthmatic children following a single home educational intervention by peer educators.

Adolescent↗

Muscular strength and vibration thresholds during two years after acute poisoning with organophosphate insecticides.

AIMS: To evaluate the association of acute organophosphate (OP) poisoning with chronic sensory and motor neurological impairment. METHODS: This study concerns the third of a series of three examinations of hand strength and vibration thresholds in a two year period after acute OP poisoning among 48 Nicaraguan men. The first two examinations were performed at hospital discharge and seven weeks after poisoning, and the present examination two years later. Twenty eight cattle ranchers and fishermen who had never experienced pesticide poisoning were examined as controls, also three times over the two year period. The poisonings were categorised as caused by "non-neuropathic" OPs and "neuropathic" OPs, each subdivided in moderate and severe poisonings. RESULTS: Men poisoned with OP insecticides had persistent reduced hand strength. We previously reported weakness at hospital discharge for OP poisoned in all categories that worsened seven weeks later for those severely poisoned with neuropathic OPs. Strength improved over time, but the poisoned were still weaker than controls two years after the poisoning, most noticeably among the subjects most severely poisoned with neuropathic OPs. Also, index finger and toe vibration thresholds were slightly increased at the end of the two year period, among men with OP poisonings in all categories, but patterns of onset and evolvement of impairment of vibration sensitivity were less clear than with grip and pinch strength. CONCLUSIONS: Persistent, mainly motor, impairment of the peripheral nervous system was found in men two years after OP poisoning, in particular in severe occupational and intentional poisonings with neuropathic OPs. This finding is possibly due to remaining organophosphate induced delayed polyneuropathy.

Acute Disease↗

Environmental tobacco smoke and absenteeism related to respiratory illness in schoolchildren.

Household environmental tobacco smoke (ETS) exposure accounts for substantial morbidity among young children, but the ETS-associated morbidity burden among school-age children is less well defined. Illness-related school absenteeism is a measure of a broad spectrum of adverse effects of ETS exposure in school-age children. The authors investigated the relations between ETS exposure, asthma status, and illness-related school absenteeism in a cohort of 1,932 fourth-grade schoolchildren from 12 southern California communities during January-June 1996. Incidence rates and adjusted relative risks of illness-related absences were determined by using an active surveillance system. The effects of ETS exposure on absenteeism were assessed by using stratified incidence rates and Poisson regression to adjust for sociodemographic factors. ETS exposure was associated with an increased risk of respiratory-illness-related school absences (relative risk (RR) = 1.27, 95% confidence interval (CI): 1.04, 1.56). Children living in a household with two or more smokers were at increased risk of such absences (RR = 1.75, 95% CI: 1.33, 2.30). Children's asthma status affected their response to ETS. Compared with unexposed children without asthma, children with asthma were at increased risk of respiratory-illness-related school absences when exposed to one (RR = 2.35, 95% CI: 1.49, 3.71) or two or more (RR = 4.45, 95% CI: 2.80, 7.07) household smokers. Children without asthma also had an increased risk if exposed to two or more smokers (RR = 1.44, 95% CI: 1.04, 2.00). Therefore, ETS exposure is associated with increased respiratory-related school absenteeism among children, especially those with asthma.

Absenteeism↗

Growth hormone improves clinical status in prepubertal children with cystic fibrosis: results of a randomized controlled trial.

OBJECTIVES: We conducted a 1-year randomized controlled trial to test the hypothesis that growth hormone (GH) improves the clinical status of children with cystic fibrosis. STUDY DESIGN: Nineteen prepubertal children were randomized to control (NonTX, n = 9) or to daily injections of GH (0.3 mg/kg/wk) (GHTX, n = 10) for 1 year. Every 3 months height, weight, and lean tissue mass were measured. Caloric intake, resting energy expenditure, pulmonary function, and respiratory muscle strength were measured every 6 months, as were total number of hospitalizations and courses of outpatient intravenous antibiotics. RESULTS: The GHTX group had significantly greater height, height velocity (NonTX = 3.8 +/- 1.4 cm/y, GHTX = 8.1 +/- 2.4 cm/y; P =.002), weight, weight velocity (NonTX = 2.1 +/- 0.9 kg/y, GHTX = 4.5 +/- 1.1 kg/y; P =.004), and change in lean tissue mass (NonTX = 2.1 +/- 1.6 kg, GHTX = 4.7 +/- 1.7 kg; P =.01) analyzed by the Student t test. The GHTX group had significant improvement in delta forced vital capacity compared with the year before study, and respiratory muscle strength improved. The number of hospitalizations and outpatient intravenous antibiotic courses significantly decreased in the GHTX group but did not change in the NonTX group. No subject had development of cystic fibrosis-related diabetes. CONCLUSIONS: Results of the first randomized controlled trial of GH treatment in cystic fibrosis indicate that GH improves growth and clinical status.

Body Composition↗

The effects of ambient air pollution on school absenteeism due to respiratory illnesses.

We investigated the relations between ozone (O3), nitrogen dioxide (NO2), and respirable particles less than 10 microm in diameter (PM10) and school absenteeism in a cohort of 4th-grade school children who resided in 12 southern California communities. An active surveillance system ascertained the numbers and types of absences during the first 6 months of 1996. Pollutants were measured hourly at central-site monitors in each of the 12 communities. To examine acute effects of air pollution on absence rates, we fitted a two-stage time-series model to the absence count data that included distributed lag effects of exposure adjusted for long-term pollutant levels. Short-term change in O3, but not NO2 or PM10, was associated with a substantial increase in school absences from both upper and lower respiratory illness. An increase of 20 ppb of O3 was associated with an increase of 62.9% [95% confidence interval (95% CI) = 18.4-124.1%] for illness-related absence rates, 82.9% (95% CI = 3.9-222.0%) for respiratory illnesses, 45.1% (95% CI = 21.3-73.7%) for upper respiratory illnesses, and 173.9% (95% CI = 91.3-292.3%) for lower respiratory illnesses with wet cough. The short-term effects of a 20-ppb change of O3 on illness-related absenteeism were larger in communities with lower long-term average PM10 [223.5% (95% CI = 90.4-449.7)] compared with communities with high average levels [38.1% (95% CI = 8.5-75.8)]. Increased school absenteeism from O3 exposure in children is an important adverse effect of ambient air pollution worthy of public policy consideration.

Absenteeism↗

Growth hormone decreases protein catabolism in children with cystic fibrosis.

Despite aggressive nutritional therapy, low body weight and protein catabolism are common problems in children with cystic fibrosis. Previous studies by our group and others have demonstrated improvement in both height and weight in children with cystic fibrosis who were treated with human recombinant GH, and our group has recently documented improved clinical status and lean tissue mass as well. The purpose of this report is to summarize our findings of the effect of GH on whole body protein kinetics in cystic fibrosis and to relate these findings to changes in TNF-alpha levels. We conducted a 1-yr study of 19 prepubertal children with cystic fibrosis (age 7-12 yr, all <94% of ideal body weight). Ten children were randomly assigned to take daily injections of GH (0.3 mg/kg.wk), and nine were randomly assigned to be controls. Baseline results from the subjects with cystic fibrosis were compared with results obtained from nine age- and gender-matched healthy children. Whole body protein turnover was measured at baseline and every 6 months using the stable isotope [1-(13)C]leucine and mass spectrometric analysis. Leucine rate of appearance, a measure of protein catabolism, was similar in both cystic fibrosis subgroups at baseline and was significantly higher than in the control children without cystic fibrosis. Treatment with GH resulted in a significantly lower leucine rate of appearance, as well as significantly lower leucine oxidation. The rate of protein synthesis, as calculated from these numbers, actually decreased in the cystic fibrosis subgroup. TNF-alpha levels were higher in both cystic fibrosis subgroups than in controls and correlated with leucine rate of appearance. The results of this study suggest that one reason GH improves body weight and lean tissue mass is due to improved whole body protein catabolism and improved efficiency of whole body protein kinetics.

Algorithms↗

Tracheal gas insufflation.

Tracheal gas insufflation (TGI) is an adjunct to mechanical ventilation that reduces CO (2) present in the anatomic deadspace. This is accomplished by flowing fresh gas (typically 6-10 lpm) directly into the trachea via a catheter placed into the endotracheal tube positioned at the distal end or by an embedded catheter in the wall of a specially designed endotracheal tube. This is thought to improve gas mixing because of the turbulent flow created at the tip of the catheter. There are two methods of gas flow delivery and cycling. Gas flow may be delivered directly toward the carina or in a reverse flow fashion. Cycling of TGI flow may be just during exhalation or during both inhalation and exhalation. A system integrated into the monitoring and controls of a mechanical ventilator could eventually prove the safest and most effective. However, currently there are no FDA-approved devices for TGI administration. It is critical to monitor the adverse effects (triggering, auto-PEEP [positive end expiratory pressure], air trapping, and patient comfort) created by the additional flow introduced into the ventilator circuit, while balancing the CO (2) clearance. There are limited data, mostly from animal studies. However, the trials done in both animal and humans are promising with regard to effective CO (2) elimination and avoidance of unacceptably high peak airway pressures. Available equipment has limited studies with infants. Even within the adult population, much work needs to be done to determine the optimal catheter position, the most appropriate TGI flow characteristics, and improve the safety of TGI.

Journal Article↗

Maternal smoking during pregnancy, environmental tobacco smoke exposure and childhood lung function.

BACKGROUND: Exposure to environmental tobacco smoke (ETS) during childhood and in utero exposure to maternal smoking are associated with adverse effects on lung growth and development. METHODS: A study was undertaken of the associations between maternal smoking during pregnancy, exposure to ETS, and pulmonary function in 3357 school children residing in 12 Southern California communities. Current and past exposure to household ETS and exposure to maternal smoking in utero were assessed by a self-administered questionnaire completed by parents of 4th, 7th, and 10th grade students in 1993. Standard linear regression techniques were used to estimate the effects of in utero and ETS exposure on lung function, adjusting for age, sex, race, Hispanic ethnicity, height, weight, asthma, personal smoking, and selected household characteristics. RESULTS: In utero exposure to maternal smoking was associated with reduced peak expiratory flow rate (PEFR) (-3.0%, 95% CI -4.4 to -1.4), mean mid expiratory flow (MMEF) (-4.6%, 95% CI -7.0 to -2.3), and forced expiratory flow (FEF(75)) (-6.2%, 95% CI -9.1 to -3.1), but not forced expiratory volume in one second (FEV(1)). Adjusting for household ETS exposure did not substantially change these estimates. The reductions in flows associated with in utero exposure did not significantly vary with sex, race, grade, income, parental education, or personal smoking. Exposure to two or more current household smokers was associated with reduced MMEF (-4.1%, 95% CI -7.6 to -0. 4) and FEF(75) (-4.4%, 95% CI -9.0 to 0.4). Current or past maternal smoking was associated with reductions in PEFR and MMEF; however, after adjustment for in utero exposure, deficits in MMEF and FEF(75) associated with all measurements of ETS were substantially reduced and were not statistically significant. CONCLUSIONS: In utero exposure to maternal smoking is independently associated with decreased lung function in children of school age, especially for small airway flows.

Adolescent↗

Association between air pollution and lung function growth in southern California children.

Average growth of lung function over a 4-yr period, in three cohorts of southern California children who were in the fourth, seventh, or tenth grade in 1993, was modeled as a function of average exposure to ambient air pollutants. In the fourth-grade cohort, significant deficits in growth of lung function (FEV(1), FVC, maximal midexpiratory flow [MMEF], and FEF(75)) were associated with exposure to particles with aerodynamic diameter less than 10 micrometer (PM(10)), PM(2.5), PM(10)-PM(2.5), NO(2), and inorganic acid vapor (p < 0.05). No significant associations were observed with ozone. The estimated growth rate for children in the most polluted of the communities as compared with the least polluted was predicted to result in a cumulative reduction of 3.4% in FEV(1) and 5.0% in MMEF over the 4-yr study period. The estimated deficits were generally larger for children spending more time outdoors. In the seventh- and tenth-grade cohorts, the estimated pollutant effects were also negative for most lung function measures, but sample sizes were lower in these groups and none achieved statistical significance. The results suggest that significant negative effects on lung function growth in children occur at current ambient concentrations of particles, NO(2), and inorganic acid vapor.

Adolescent↗

Sex-specific effects of asthma on pulmonary function in children.

To evaluate the effects on lung function of asthma, time since diagnosis of asthma, and age at diagnosis of asthma, we examined school children in a cohort of 2,277 fourth- and seventh-graders at least twice during a 4-yr follow-up period. Sex-specific models for each lung function were fitted through mixed-effects models that used regression splines and captured age-dependent trends in the effect of asthma on lung function. In males, a history of asthma was associated with large and statistically significant deficits in maximum midexpiratory flow (MMEF) (-4.89%) and forced expiratory flow at 75% of expired FVC (FEF(75)) (-6.62%), whereas in females these deficits were smaller (-1.93% and -2.45%, respectively) and were not statistically significant. However, larger deficits were seen in both males and females with longer time since diagnosis. In males with more than 6 yr since diagnosis, there were significant deficits in FEV(1) (-3.91%), MMEF (-7.39%), FEF(75) (-8.12%), and peak expiratory flow rate (PEFR) (-4.65%) as compared with children with less than 3 yr since diagnosis. There were fewer females with more than 6 yr since diagnosis, but deficits were similar to those of males for FEV(1) (-2.52%), MMEF (-9.26%), and FEF(75) (-14.28%). Large deficits in flow rates in both large and small airways were observed in males and females for whom asthma was reported to have been diagnosed before age 3 yr. There was little evidence that lung growth in children with asthma "catches up" at older ages. Therefore, because a constant percent deficit in lung function implies an increasingly large absolute deficit in older children with larger lungs, these results are consistent with prior evidence that lung function deficits in children with asthma persist into adulthood. We also suggest that in children, commonly observed differences between sexes in the impact of asthma on lung function may reflect differences in the duration and age of onset of asthma in males and females.

Age of Onset↗

Effects of in utero and environmental tobacco smoke exposure on lung function in boys and girls with and without asthma.

To investigate whether the effects of in utero exposure to maternal smoking and environmental tobacco smoke (ETS) exposure on lung function vary by sex or asthma status, we examined medical history and tobacco smoke exposure data for 5,263 participants in the Children's Health Study. At study enrollment, parents or guardians of each subject completed a questionnaire, and lung function was measured spirometrically with maximum forced expiratory flow-volume maneuvers. To assess the in utero effects of maternal smoking and ETS exposure on lung function, we used regression splines that accounted for the nonlinear relationship between pulmonary function, height, and age. In utero exposure to maternal smoking was independently associated with deficits in lung function that were larger for children with asthma. Boys and girls with a history of in utero exposure to maternal smoking showed deficits in maximum midexpiratory flow (MMEF) and a decrease in the FEV(1)/FVC ratio. As compared with children without asthma, boys with asthma had significantly larger deficits from in utero exposure in FVC, MMEF, and FEV(1)/FVC, and girls with asthma had larger decreases in FEV(1)/FVC. The effect of ETS exposure varied by children's gender and asthma status. Deficits in flows associated with current ETS exposure were present in children with and without asthma but were significant only among children without asthma. Past ETS exposure was associated with reduced FEV(1), MMEF, and FEV(1)/FVC among boys with asthma. In contrast, past ETS exposure was associated with decreased flow rates in girls without asthma. In summary, both in utero exposure to maternal smoking and ETS exposure were associated with persistent deficits in lung function. The effects of in utero exposure were greatest among children with asthma.

Adolescent↗

Effects of arsenic exposure on the frequency of HPRT-mutant lymphocytes in a population of copper roasters in Antofagasta, Chile: a pilot study.

A pilot biomarker study was conducted to investigate the feasibility of using the hypoxanthine guanine phosphoribosyltransferase (HPRT) gene in peripheral blood lymphocytes as a biomarker for detecting genetic effects of arsenic exposure. Blood and urine samples were obtained from workers highly exposed to arsenic in a copper roasting plant in Antofagasta, Chile. Individuals were classified according to their job titles into three potential exposure groups: high, medium, and low. To confirm exposure, arsenic concentration was determined in urine samples. The HPRT mutant frequencies were measured in lymphocytes from 15 individuals ranging in age from 24 to 66 years. The mean mutant frequencies for the three exposure groups were: low (9 x 10(-6)), medium (11 x 10(-6)), and high (24 x 10(-6)). An increased mutant frequency was observed in the highly exposed group, but the response was so slight that it is not likely that this assay will be capable of providing dose-response information across a range of lower, more typical environmental arsenic levels.

Aged↗

Subclinical health effects of environmental pesticide contamination in a developing country: cholinesterase depression in children.

The effect of exposure to pesticides among children in a Nicaraguan community in the path of rain water runoff from a large crop-dusting airport was evaluated by measuring plasma cholinesterase. Mean cholinesterase activity in 17 children in the path of runoff was 2.4 international units/ml blood/min, lower than the 2.9 IU/ml/min measured in a group of 43 children from an unexposed community (difference=0.49 IU/ml/min; 95% C.I. 0.24, 0.76). Six (35%) of the 17 exposed children had abnormally low cholinesterase levels. A possible explanation for this physiological effect of exposure to pesticides is the dermal absorption which may have occurred among children playing barefoot in puddles grossly contaminated by runoff from the airport. Drinking water from a well in the exposed community demonstrated low level residues of cholinesterase-inhibiting pesticides, although contamination with toxaphene (not a cholinesterase inhibitor) exceeded by over 8-fold the United States Environmental Protection Agency maximum permissible concentration in drinking water. The difficulty in measuring health effects resulting from environmental pesticide contamination, and in controlling exposure resulting from the rapidly increasing use of pesticides, is a growing problem for developing countries like Nicaragua.

Child↗

Organophosphate neuropathy due to methamidophos: biochemical and neurophysiological markers.

Neuropathy target esterase (NTE), the putative target enzyme for organophosphate induced delayed polyneuropathy (OPIDP), can be measured in lymphocytes but has rarely been assessed in acute human poisoning. Serum autoantibodies to nervous system proteins develop in hens poisoned with neuropathic insecticides and also have not been studied after human poisoning. Serial lymphocyte NTE (LNTE) was measured in a 16-year-old boy after acute poisoning with methamidophos for evaluation as a predictor of subsequent neuropathy. The profiles of serum autoantibodies to neurofilament triplet proteins, myelin basic protein, and glial fibrillary acidic protein were measured in order to characterize changes occurring as a result of OPIDP. Clinical neuropathy characterized by steppage gate and profound lower extremity weakness, decreased grip and pinch strength, and decreased ulnar and absent tibial compound muscle action potentials developed 2 weeks following poisoning. Sensory examination and nerve conduction studies were normal. On day 3 following poisoning LNTE was depressed (77% compared with subsequent baseline enzyme activity). Marked increases in serum immunoglobulin G (IgG) autoantibodies to glial fibrillary acidic protein and to neurofilament 200 were observed after the development of OPIDP. We conclude that inhibition of lymphocyte NTE is predictive of subsequent OPIDP. Serum autoantibody titers to nervous system proteins may be useful markers of neuropathy.

Adolescent↗

Identification of mutations in the repeated part of the autosomal dominant polycystic kidney disease type 1 gene, PKD1, by long-range PCR.

We have used long-range PCR to identify mutations in the duplicated part of the PKD1 gene. By means of a PKD1-specific primer in intron 1, an approximately 13.6-kb PCR product that includes exons 2-15 of the PKD1 gene has been used to search for mutations, by direct sequence analysis. This region contains the majority of the predicted extracellular domains of the PKD1-gene product, polycystin, including the 16 novel PKD domains that have similarity to immunoglobulin-like domains found in many cell-adhesion molecules and cell-surface receptors. Direct sequence analysis of exons encoding all the 16 PKD domains was performed on PCR products from a group of 24 unrelated patients with autosomal dominant polycystic kidney disease (ADPKD [MIM 173900]). Seven novel mutations were found in a screening of 42% of the PKD1-coding region in each patient, representing a 29% detection rate; these mutations included two deletions (one of 3 kb and the other of 28 bp), one single-base insertion, and four nucleotide substitutions (one splice site, one nonsense, and two missense). Five of these mutations would be predicted to cause a prematurely truncated protein. Two coding and 18 silent polymorphisms were also found. When, for the PKD1 gene, this method is coupled with existing mutation-detection methods, virtually the whole of this large, complex gene can now be screened for mutations.

Base Sequence↗