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Biomedical subjects

R McConnell

Publications and source records attributed to R McConnell.

At least 37 records · Page 2Linked to original sources
PubMed1999

Cortical lesions in multiple sclerosis.

Although previous studies have shown that the lesions of multiple sclerosis may involve the cerebral cortex, there is little published research on the prevalence and distribution of such lesions. Using neuropathological techniques and MRI, a series of studies has been undertaken in order to assess this, in particular to identify their relationship to cortical veins. A serial MRI study showed that the use of gadolinium proffered an increase in cortical lesion detection of 140% and showed that 26% of active lesions arose within or adjacent to the cortex. In a post-mortem study, MRI under-reported lesions subsequently analysed neuropathologically, particularly those arising within the cortex. In a further 12 cases examined, 478 cortical lesions were identified, of which 372 also involved the subcortical white matter. Seven different lesion types were identified; the majority arose within the territory of the principal cortical veins, whilst the remaining quarter arose within the territory of the small branch or superficial veins. Small cortical lesions are common in multiple sclerosis and are under-reported by MRI. Investigation of the cortical venous supply shows how such lesions may arise, and why the majority also involve the underlying white matter.

Adult↗
PubMed1999

Air pollution and bronchitic symptoms in Southern California children with asthma.

The association of air pollution with the prevalence of chronic lower respiratory tract symptoms among children with a history of asthma or related symptoms was examined in a cross-sectional study. Parents of a total of 3,676 fourth, seventh, and tenth graders from classrooms in 12 communities in Southern California completed questionnaires that characterized the children's histories of respiratory illness and associated risk factors. The prevalences of bronchitis, chronic phlegm, and chronic cough were investigated among children with a history of asthma, wheeze without diagnosed asthma, and neither wheeze nor asthma. Average ambient annual exposure to ozone, particulate matter (PM(10) and PM(2.5); [less than/equal to] 10 microm and < 2.5 microm in aerodynamic diameter, respectively), acid vapor, and nitrogen dioxide (NO(2)) was estimated from monitoring stations in each community. Positive associations between air pollution and bronchitis and phlegm were observed only among children with asthma. As PM(10) increased across communities, there was a corresponding increase in the risk per interquartile range of bronchitis [odds ratio (OR) 1.4/19 microg/m(3); 95% confidence interval (CI), 1.1-1.8). Increased prevalence of phlegm was significantly associated with increasing exposure to all ambient pollutants except ozone. The strongest association was for NO(2), based on relative risk per interquartile range in the 12 communities (OR 2.7/24 ppb; CI, 1.4-5.3). The results suggest that children with a prior diagnosis of asthma are more likely to develop persistent lower respiratory tract symptoms when exposed to air pollution in Southern California.

Adolescent↗
PubMed1999

A theoretical basis for investigating ambient air pollution and children's respiratory health.

Acute respiratory health effects in children from exposure at current ambient levels of ozone are well documented; however, evidence for acute effects from other criteria pollutants such as nitrogen dioxide and respirable particles is inconsistent. Whether chronic effects result from long-term exposure to any of these pollutants during childhood is an important unresolved question. Establishing whether acute or chronic effects result from childhood exposure and identifying sensitive subgroups may require integration of biologic mechanisms of lung defenses, injury, and response into the study design and statistical models used in analyses. This review explores the theoretical basis for explaining such adverse effects in light of our contemporary understanding of mechanisms of lung injury and response at the cellular and molecular levels. The rapidly evolving understanding of the effects of air pollution on cellular and molecular levels presents an opportunity to develop and refine innovative biologically based hypotheses about the effects of childhood exposure. We hypothesize that children with low fruit and vegetable intake, low antioxidant levels, high polyunsaturated fat intake, or who have inherited certain alleles for genes involved in lung defenses and immune response regulation may be at increased risk for adverse effects. Because responses to air pollutants of interest are complex and involve a number of pathophysiologic processes, the magnitude of main effects of dietary factors, genes, and gene-environment interactions may be modest for individuals; however, each may make an important contribution to the population burden of preventable respiratory diseases.

Air Pollution↗
PubMed1997

The El Paso smelter 20 years later: residual impact on Mexican children.

Although there has been considerable concern regarding cross-border industrial contamination between Mexico and the United States, there are remarkably few data. One notable case study is the smelter in El Paso, Texas. In 1974 blood lead levels higher than 40 micrograms/dl were detected in 52% of children studied near the smelter, in the adjacent Mexican community of Anapra in Ciudad Juarez, Chihuahua. Lead smelting at this plant was halted in 1985, and as a result, lead levels in air decreased sharply; consequently, children's exposure to lead and other metals should have diminished accordingly. In order to assess the effect of removal of lead emissions from the area, three geographical locations in Anapra, varying in distance from the smelter source, were evaluated for lead, arsenic, and cadmium levels in soil and for lead in blood of children. It was found that lead levels in soil were inversely correlated with distance from the smelter. Arsenic and cadmium levels in soil were constant among the three sectors. However, at residential sites closer to the smelter, a higher percentage of children was found with blood lead levels exceeding the Centers for Disease Control's action level of 10.0 micrograms/dl. In the sector closest to the border 43% of children had blood lead levels greater than 10.0 micrograms/dl. Although blood lead levels in children living in Anapra have dropped approximately fourfold in 20 years, our results indicate a moderate continued risk of lead exposure. This study demonstrates the persistent impact that may result from cross-border contamination and raises provocative questions regarding appropriate action and the responsibility for financing such action.

Air Pollutants↗
PubMed1997

Patient-ventilator flow dyssynchrony: flow-limited versus pressure-limited breaths.

OBJECTIVES: Patient-ventilator flow dyssynchrony occurs when ventilator flow delivery is insufficient to meet patient demands. If sufficiently severe, flow dyssynchrony can produce significant imposed loads on ventilatory muscles. Flow dyssynchrony can be improved by increasing ventilator flow delivery. We hypothesized that the variable flow pressure-limited breath would be a better approach for matching patient flow demands than adjusting a set flow on a conventional volume-cycled breath. DESIGN: Clinical interventional study. SETTING: Medical intensive care unit. PATIENTS: Sixteen stable, mechanically ventilated patients receiving volume-cycled assist-control ventilation. INTERVENTIONS: Flow dyssynchrony was produced by reducing the set flow by 50%. Dyssynchrony was quantified by measuring the esophageal pressure time product during the assisted breath. Two strategies were then employed in an attempt to reduce the dyssynchrony. One strategy was to increase flow back to the initial set flow and then further increase flow by an additional 25% (VI strategy). The other strategy was to use a pressure-limited breath feature coupled to a volume assist breath (the P strategy). With the P strategy, the pressure limit was set at 75% and 100% of the static elastic recoil pressure at end-inspiration. MEASUREMENTS AND MAIN RESULTS: Pressure time product, intrinsic positive end-expiratory pressure, and the ventilatory pattern were measured with each strategy and were analyzed by analysis of variance. Induced baseline flow dyssynchrony, as measured by the pressure time product, was > 5 cm H2O/sec in ten of 16 patients. This dyssynchrony was significantly reduced by both the VI strategy and the P strategy, although the P strategy appeared to be more effective in those patients with the greatest baseline dyssynchrony. Baseline inspiratory time was also shortened by both the VI strategy and the P strategy; the VI strategy shortened baseline inspiratory time more than the P strategy. Baseline tidal volume, frequency, and intrinsic positive end-expiratory pressure were only minimally affected by either strategy. CONCLUSION: The pressure-limited, variable-flow approach to ventilator gas delivery appears to be more responsive to a vigorous patient effort than a fixed-flow approach.

Adult↗
PubMed1997

Lead exposure in Latin America and the Caribbean. Lead Research Group of the Pan-American Health Organization.

As a result of the rapid industrialization of Latin America and the Caribbean during the second half of this century, exposure to lead has become an increasingly important problem. To obtain an estimate of the magnitude of lead exposure in the region, we carried out a survey and a literature search on potential sources of lead exposure and on blood lead concentrations. Sixteen out of 18 Latin American and 2 out of 10 Caribbean countries responded to the survey. Lead in gasoline remains a major problem, although the lead content has decreased in many countries in the last few years. The impact of leaded fuel is more important in urban settings, given their high vehicular density. Seventy-five percent of the population of the region lives in urban areas, and children younger than 15 years of age, the most susceptible group, comprise 30% of the population. Other sources of lead exposure identified in the region included industrial emissions, battery recycling, paint and varnishes, and contaminated food and water. Lead is recognized as a priority problem by national authorities in 72% of the countries that responded to the survey, and in 50% of the countries some legislation exists to regulate the lead content in certain products. However, compliance is low. There is an urgent need for a broad-based coalition between policy makers, industry, workers, unions, health care providers, and the community to take actions to reduce environmental and occupational lead exposures in all the Latin American and Caribbean countries.

Caribbean Region↗
PubMed1997

Applied PEEP during pressure support reduces the inspiratory threshold load of intrinsic PEEP.

OBJECTIVES: Mechanical ventilation in patients with obstructive airway disease (OAD) is associated with the development of dynamic hyperinflation and intrinsic positive end-expiratory pressure (PEEPi). One of the effects of this form of PEEPi is to act as an inspiratory threshold load that can produce ineffective breath triggering, dyspnea, and muscle fatigue. Recently it has been shown that applying PEEP in the ventilator circuit can reduce this imposed triggering load. We wished to investigate this further by studying patients with OAD being weaned with pressure support (PS) ventilation. Our first objective was to determine the prevalence and magnitude of this form of PEEPi in OAD patients who were clinically judged to be capable of triggering mechanical ventilatory breaths. Our second objective was to attempt to reduce the triggering load by applying circuit PEEP and then observe the response of patient-ventilator interactions during the patient-triggered, pressure-limited PS breath. DESIGN: Thirteen random patients with OAD who were receiving PS ventilation were studied by measuring airway pressures, airway gas flow, baseline esophageal pressure, esophageal pressure time products (PTP), and esophageal pressure changes before ventilator gas delivery began (delta Pes taken to represent PEEPi). Measurements were made at baseline and after stepwise increases in circuit PEEP up to the PEEPi. RESULTS: We found measurable PEEPi in all patients (average +/- SD of 9.54 +/- 4.3 cm H2O) and it was > 10 cm H2O in seven patients. As would be predicted, we observed progressive reductions in PEEPi as applied PEEP was given. We also observed that the component of patient effort (PTP) related to overcoming PEEPi also decreased, but the PTP related to tidal volume (VT) did not. The VT associated with the set PS thus did not change with application of PEEP, nor did the breathing frequency. CONCLUSION: PEEPi is common in OAD patients receiving mechanical ventilatory support. The imposed triggering load from PEEPi can be offset to large extent by circuit PEEP approaching the baseline PEEPi. Although total patient effort substantially falls with applied PEEP, the patient effort that combine with PS to effect VT does not.

Female↗
PubMed1997

Agricultural pesticide use in developing countries: health effects and research needs.

Large worker populations in the Third World are exposed to increasing amounts of pesticides, including pesticides severely restricted and banned in industrialized countries. Studies on knowledge, attitudes, and practices indicate that unsafe use of pesticides is the rule in Third World countries. Surveys of acute poisonings show high rates in these countries, despite underregistration. The scarce studies on chronic health outcomes demonstrate neurotoxic, reproductive, and dermatologic effects. Exposure assessment consists mainly of cholinesterase testing, and few studies have quantified dermal and respiratory exposure. The few intervention studies demonstrate the need for evaluation of the impact of preventive measures and policies. There is no evidence that widespread "safe-use" programs have greatly affected exposure and morbidity. It was concluded that research should focus on simple methods for surveillance of exposure and on surveillance of acute illness and its causes in order to develop and evaluate rapid local interventions. Studies on chronic effects should be carried out in selected countries, aiming at long-term and broader interventions. Policies that promote the use of pesticides should be critically evaluated. North-South and South-South research collaborations must be encouraged to address this global health problem.

Africa↗
PubMed1997

Respiratory symptoms, spirometry and chronic occupational paraquat exposure.

OBJECTIVES: A cross-sectional study was conducted to evaluate the relationship between respiratory health and paraquat exposure. METHODS: The study population was selected from among workers at 15 Nicaraguan banana plantations which relied on paraquat for the control of weeds. All the workers were interviewed after they received their job assignment for the day of the survey, and all who reported never having applied paraquat and all who reported more than 2 years of cumulative exposure as applicators of paraquat with knapsack sprayers were invited for medical evaluation. One hundred and thirty-four exposed workers and 152 unexposed workers were administered a questionnaire interview asking about exposure and respiratory symptoms, and they underwent spirometric testing of forced expiratory volume in 1 s (FEV1.0) and forced vital capacity (FVC). RESULTS: In the exposed group 53% reported having experienced a skin rash or burn resulting from paraquat exposure, 25% reported epistaxis, 58% nail damage, and 42% paraquat splashed in the eyes. There was a consistent dose-response relationship between intensity of exposure (as indicated by a history of skin rash or burn) and the prevalence of dyspnea. This relationship was more marked for more severe dyspnea. There was a 3-fold increase in episodic wheezing accompanied by shortness of breath among the more intensely exposed workers. There was no relationship between exposure and FEV1.0 or FVC. CONCLUSIONS: The high prevalence of respiratory symptoms associated with exposure, in the absence of spirometric abnormalities associated with exposure, could be a result of unmeasured gas exchange abnormalities among workers with long-term exposure to paraquat.

Adult↗
PubMed1996

Estimating underreported pesticide poisonings in Nicaragua.

We undertook to estimate the degree of underreporting to a regional pesticide poisoning registry, and to estimate the true incidence of poisoning in an agricultural region of Nicaragua. We surveyed 633 workers at 25 of 33 agricultural cooperatives and any nearby private forms in a area geographically convenient to the regional health headquarters with a short structured interview about pesticide poisonings. Eighty-three percent of workers described current use of pesticides. Twenty-five percent described a pesticide poisoning in the preceding 12 months, and almost one-half (48%) described having been made ill by pesticides at some point in time. Sixty-nine (11%) described a poisoning in the preceding month, 23 of whom had received medical attention. The names of the medically treated were sought in the Regional Pesticide Poisoning Registry for the survey year of 1988. Only 8 of the 23 subjects were found reported to the registry when a total of 1,143 human pesticide poisonings were reported in the entire region. Using 65% as an estimate of underreporting to the registry, we calculate that 3,300 (95% CI 2100-7500) poisonings had received treatment in the region in 1988, of whom more than 2,100 remained unreported. Based on the ratio of total poisonings (treated and untreated) to registry-reported poisonings among our survey respondents, we estimate that 6,700 (95% CI 4100-18000) systemic poisonings, occurred in 1988 in the region. Underreporting of pesticide poisonings disguises the enormity of the problem in developing countries. Even in a region with a strong emphasis on illness reporting for targeted conditions, underreporting is substantial. This method for estimating underreporting is easily applied and provides a rough estimate of registry underreporting and actual incidence for conditions identifiable by a community-applied questionnaire.

Adolescent↗
PubMed1996

The significance of measles virus antigen and genome distribution in the CNS in SSPE for mechanisms of viral spread and demyelination.

The distribution of measles virus (MV) antigen and genomic RNA in the central nervous system (CNS) in 10 cases of subacute sclerosing panencephalitis (SSPE) was determined using optimized immunocytochemistry and in situ hybridization techniques. As in previous reports neurons and oligodendrocytes were found to be the most frequently infected cells. It was confirmed that MV infection in neuronal processes was predominantly dendritic but there was also some evidence suggestive of occasional axonal involvement, a finding confirmed by electron microscopy. In addition MV genomic RNA was detected in neuronal processes, in some cases in the absence of demonstrable MV antigen. The relationship between myelin destruction and oligodendrocytic infection suggested that the demyelination may be solely the result of virus infection. A possible correlation between viral distribution and form and the clinical duration of disease was examined. Viral antigen and genome were equally abundant in the cerebral cortex in most short duration cases (<6 months). However, in two of these cases viral RNA but not antigen was detected in the spinal cord. In long duration cases (>36 months) viral RNA was abundant in all areas of the CNS examined, frequently in the absence of demonstrable antigen. These findings may suggest viral spread in a cephalo-caudal direction, probably by transneuronal spread.

Child↗
PubMed1996

The expression of the endothelial cell antigen CD34 in demyelinating disease.

In this study, the antigenic expression of CD34, a 110 kDa glycoprotein which is expressed on human haemopoietic progenitor cells and vascular endothelium, has been assessed in a variety of neuropathological conditions, including infectious and demyelinating disease. Using immunoperoxidase staining on paraffin sections, the immunohistochemical results show that CD34 antigen is expressed widely on human CNS endothelium in grey and white matter, in the eye including retina, and in the anterior and posterior lobes of the pituitary. In demyelinating disease CD34 antigen expression was not detected in acute lesions, whereas strong expression was observed in old lesions. CD34 endothelial positivity was observed in areas of gliosis, vasogenic oedema, vascular disease and in Alzheimer's and Parkinson's disease pathology. A general pattern emerged, with CD34 antigen reactivity predominantly negative in areas of inflammation with demyelination but positive in adjacent non-inflamed tissue, irrespective of myelin pathology. We conclude that perivascular inflammation is a key factor in the absence of immunoreactivity of CD34 in the CNS in demyelinating disease.

Antigens, CD34↗
PubMed1995

Microwave antigen retrieval for immunocytochemistry on formalin-fixed, paraffin-embedded post-mortem CNS tissue.

Microwave antigen retrieval methods were assessed for a panel of antibodies on formalin-fixed, paraffin-embedded sections from a range of human central nervous system (CNS) tissues taken at post-mortem. The immunoreactivity of a number of antigens (synaptophysin, PGP9.5, GFAP, carbonic anhydrase II, CD68, ferritin, HLA-DR, alpha beta-crystallin, measles and herpes viruses) was markedly enhanced by this procedure compared with other methods of antigen unmasking, such as trypsinization. Enhancement was noted both by an increased number of positive cells and by the intensity of reactions within individual cells and their processes. Furthermore, the microwave method produced uniform immunostaining over large surface area sections with no loss of morphological detail. Large cryostat sections of CNS tissue can be difficult to obtain with good morphology. The ability to retrieve a wide range of antigen in formalin-fixed, paraffin-embedded CNS tissue will greatly increase the range of investigations that can be carried out on this type of stored material.

Antigens↗
PubMed1994

Elevated quantitative vibrotactile threshold among workers previously poisoned with methamidophos and other organophosphate pesticides.

To evaluate chronic effects of acute organophosphate pesticide poisoning, quantitatively determined vibrotactile thresholds were measured as an index of peripheral neuropathy among agricultural workers in Nicaragua. Thirty-six male workers were evaluated between 10 and 34 months after hospitalization for acute organophosphate poisoning and compared to an age- and sex-matched community reference group. Vibrotactile thresholds were measured quantitatively in right and left index fingers and right and left great toes. Study subjects were stratified into three groups: 1) never poisoned; 2) poisoned with organophosphates other than methamidophos, agents which have not been reported to cause peripheral neuropathy; and 3) poisoned with methamidophos, a peripheral neurotoxin. For all digits, there was a statistically significant trend of increasing age- and height-adjusted thresholds across these three exposure categories. Over one fourth of patients previously poisoned with methamidophos we studied had abnormal vibrotactile thresholds. These results suggest that previously reported cases of organophosphate-induced delayed polyneuropathy may represent only the worst disease in a spectrum of impairment, a sequela of exposure that may be much more common than previously thought.

Acute Disease↗
PubMed1994

Screening for insecticide overexposure under field conditions: a reevaluation of the tintometric cholinesterase kit.

A semiquantitative tintometric field kit has been used in the developing world for almost 30 years to measure whole blood cholinesterase levels in persons exposed to organophosphate pesticides. The validity of this screening kit was evaluated among 79 workers heavily exposed to organophosphates by comparison with a reference assay for erythrocyte cholinesterase. Overall correlation between the two methods was good. However, either sensitivity or specificity of the tintometric kit was less than 75% for each of the three tintometric categories commonly used to define the limit of normal. Because baseline erythrocyte cholinesterase levels were not available for this population, the true sensitivity and specificity of the tintometric assay may be even lower.

Agriculture↗
PubMed1993

Angiosarcoma, porphyria cutanea tarda, and probable chloracne in a worker exposed to waste oil contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin.

A worker developed angiosarcoma, porphyria cutanea tarda, and skin lesions characteristic of mild chloracne. About 10 years earlier he had been employed at a truck terminal in Saint Louis, Missouri, at a time when it was sprayed with waste oil contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The occurrence of these three rare conditions in a single exposed worker supports the aetiological relation between environmental exposure to TCDD and the subsequent development of soft tissue sarcoma and porphyria cutanea tarda.

Acne Vulgaris↗