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Biomedical subjects

J E McLaughlin

Publications and source records attributed to J E McLaughlin.

At least 19 recordsLinked to original sources
PubMed2005

Ortner syndrome and haemophilia.

Compression and paralysis of the left recurrent laryngeal nerve by a dilated pulmonary artery is a rare complication of pulmonary hypertension. We here report the case of a patient with severe haemophilia A and HIV infection who presented with a persistent hoarseness of voice and a left vocal cord palsy caused by HIV-associated pulmonary hypertension. This case suggests that HIV-associated pulmonary hypertension should be suspected in any HIV patient presenting with unexplained left vocal cord palsy.

Adult↗
PubMed2001

Relationship of leisure-time physical activity and occupational activity to the prevalence of obesity.

OBJECTIVE: To assess the interaction between leisure-time physical activity (LTPA) and occupational activity (OA) on the prevalence of obesity. DESIGN: Secondary data analysis of a population based cross-sectional US national sample (NHANES III). SUBJECTS: A total of 4889 disease-free, currently employed adults over age 20 y. MEASUREMENTS: Subjects body mass index (BMI) was categorized as (1) obese (BMI> or =30 kg/m(2)), or (2) non-obese (BMI<30 kg/m(2)). LTPA was divided into four categories: (1) no LTPA; (2) irregular LTPA; (3) regular moderate intensity LTPA; and (4) regular vigorous intensity LTPA. OA was grouped as (1) high OA and (2) low OA. Age, gender, race-ethnicity, smoking status, urbanization classification, alcohol consumption and income were statistically controlled. RESULTS: In all, 16.8% (s.e. 0.7) of the total subject population were obese (15.1% (s.e. 1.1) of men and 19.1% (s.e. 1.1) of women). Logistic regression revealed that compared to those who engage in no LTPA and have low levels of OA, the likelihood of being obese is 42% (95% CI 0.35, 0.96) lower for those who engage in no LTPA and have high OA, 48% (95% CI 0.32, 0.83) lower for those who have irregular LTPA and have high levels of OA, and about 50% lower for all those who have regular LTPA through moderate or vigorous activity levels regardless of OA level. CONCLUSION: When considering disease free adults above 20 y of age employed in high and low activity occupations, a high level of occupational activity is associated with a decreased likelihood of being obese.

Adult↗
PubMed2001

Validation of the COSMED K4 b2 portable metabolic system.

The purpose of this investigation was to assess the accuracy of the COSMED K4 b2 portable metabolic measurement system against the criterion Douglas bag (DB) method. During cycle ergometry on consecutive days, oxygen consumption (VO2), carbon dioxide production (VCO2), minute ventilation (VE), and respiratory exchange ratio (R) were measured at rest and during power outputs of 50, 100, 150, 200, and 250W. No significant differences (P > 0.05) were observed in VO2 between the K4 b2 and DB at rest and at 250W. Though the K4 b2 values were significantly higher (P<0.05) than DB values at 50, 100, 150, and 200 W, the magnitude of these differences was small (0.088, 0.092, 0.096, and 0.088 L x min(-1), respectively). VCO2 and VE values from the K4 b2 were significantly lower than the DB at 200 and 250 W, while no significant differences were observed from rest through 150W. The slight overestimation of VO2 (50-200 W) combined with the underestimation of VCO2 (200 and 250W) by the K4 b2 resulted in significantly lower R values at every stage. These findings suggest the COSMED K4 b2 portable metabolic measurement system is acceptable for measuring oxygen uptake over a fairly wide range of exercise intensities.

Analysis of Variance↗
PubMed2001

Validity of inspiratory and expiratory methods of measuring gas exchange with a computerized system.

The accuracy of a computerized metabolic system, using inspiratory and expiratory methods of measuring ventilation, was assessed in eight male subjects. Gas exchange was measured at rest and during five stages on a cycle ergometer. Pneumotachometers were placed on the inspired and expired side to measure inspired (VI) and expired ventilation (VE). The devices were connected to two systems sampling expired O(2) and CO(2) from a single mixing chamber. Simultaneously, the criterion (Douglas bag, or DB) method assessed VE and fractions of O(2) and CO(2) in expired gas (FE(O(2)) and FE(CO(2))) for subsequent calculation of O(2) uptake (VO(2)), CO(2) production (VCO(2)), and respiratory exchange ratio. Both systems accurately measured metabolic variables over a wide range of intensities. Though differences were found between the DB and computerized systems for FE(O(2)) (both inspired and expired systems), FE(CO(2)) (expired system only), and VO(2) (inspired system only), the differences were extremely small (FE(O(2)) = 0.0004, FE(CO(2)) = -0.0003, VO(2) = -0.018 l/min). Thus a computerized system, using inspiratory or expiratory configurations, permits extremely precise measurements to be made in a less time-consuming manner than the DB technique.

Adult↗
PubMed2000

Determination of selected fate and aquatic toxicity characteristics of acrylic acid and a series of acrylic esters.

Acrylic acid, methyl acrylate, ethyl acrylate, and butyl acrylate are commercially important and widely used materials. This paper reports the results of a series of fate and aquatic toxicity studies. The mobility in soil of acrylic acid and its esters ranged from 'medium' to 'very high'. Calculated bioconcentration factors ranged from 1 to 37, suggesting a low bioconcentration potential. Acrylic acid and methyl acrylate showed limited biodegradability in the five day biochemical oxygen demand (BOD5) test, while ethyl acrylate and butyl acrylate were degraded easily (77% and 56%, respectively). Using the OECD method 301D 28-d closed bottle test, degradability for acrylic acid was 81% at 28 days, while the acrylic esters ranged from 57% to 60%. Acrylic acid degraded rapidly to carbon dioxide in soil (t1/2 < 1 day). Toxicity tests were conducted using freshwater and marine fish, invertebrates, and algae. Acrylic acid effect concentrations for fish and invertebrates ranged from 27 to 236 mg/l. Effect concentrations (LC50 or EC50) for fish and invertebrates using methyl acrylate, ethyl acrylate, and butyl acrylate ranged from 1.1 to 8.2 mg/l. The chronic MATC for acrylic acid with Daphnia magna was 27 mg/l based on length and young produced per adult reproduction day and for ethyl acrylate was 0.29 mg/l based on both the reproductive and growth endpoints. Overall these studies show that acrylic acid and the acrylic esters studied can rapidly biodegrade, have a low potential for persistence or bioaccumulation in the environment, and have low to moderate toxicity.

Acrylates↗
PubMed2000

Histopathological detection of owl's eye inclusions is still specific for cytomegalovirus in the era of human herpesviruses 6 and 7.

BACKGROUND: Cytomegalovirus (CMV) is the prototype member of the beta-herpesvirinae, which can cause multiple organ dysfunction in the immunocompromised host. Human herpesvirus 6 (HHV-6) and HHV-7 are newer members of the beta-herpesvirinae that can cause febrile illness in young children and are also possible pathogens in the immunocompromised patient. AIM: CMV is detected in histopathological sections by visualisation of owl's eye inclusion bodies. The aim of this study was to quantify the relation between CMV, HHV-6, and HHV-7 viral loads and the presence of owl's eye inclusions in histological sections. METHODS: Histopathological examination of postmortem material and recording of owl's eye inclusion bodies were performed. CMV, HHV-6, and HHV-7 were detected by qualitative and quantitative polymerase chain reaction (PCR) from the same postmortem samples. Statistical analysis of the histopathological and PCR results was performed. RESULTS: There was a significant association between the detection of owl's eye inclusion bodies and positive CMV PCR (p < 0.001); the median CMV viral load was significantly higher in samples that were positive for owl's eye inclusions (p < 0.001). No association was found between the presence of owl's eye inclusions and HHV-6 or HHV-7 positivity. CONCLUSION: Histological detection of owl's eye inclusion bodies is an insensitive but highly specific method for detecting CMV organ involvement. Owl's eye inclusion bodies are not associated with HHV-6 or HHV-7 infection.

Cytomegalovirus↗
PubMed1999

Interactions between beta-herpesviruses and human immunodeficiency virus in vivo: evidence for increased human immunodeficiency viral load in the presence of human herpesvirus 6.

In vitro, beta-herpesviruses can stimulate or inhibit HIV replication under particular circumstances. In order to investigate the effects of beta-herpesvirus infection on HIV replication and vice versa at an organ level, we determined the quantitative relationships between cytomegalovirus (CMV), human herpesviruses (HHV) 6 and 7, and HIV-1 proviral DNA using quantitative competitive PCR methods in 141 organs collected at autopsy from 11 AIDS patients. The presence of HHV-6 DNA in an organ was significantly associated with elevated HIV-1 proviral DNA (difference in HIV median loads, 1.3 log10 genomes; P = 0.004). Consistent with this, there was a trend for the presence of HIV-1 proviral DNA to be associated with an elevated HHV-6 load (0.44 log10 difference; P = 0.07). In contrast, there were no significant differences between viral loads in the combinations of either CMV or HHV-7 with HIV-1 proviral DNA load. Pairwise combinations of the beta-herpesviruses revealed that the quantity of HHV-7 was increased in the presence of HHV-6 (difference in median loads, 1.3 log10; P = 0.001) and the quantity of HHV-6 was increased in the presence of HHV-7 (difference in median loads, 0.7 log10; P=0.002). These results demonstrate that the presence of HHV-6 in an organ is significantly associated with an elevated HIV-1 proviral load and have implications for understanding HIV pathogenesis in the human host and the role that beta-herpesviruses, especially HHV-6, might play as cofactors in the HIV disease process.

AIDS-Related Opportunistic Infections↗
PubMed1999

Shorter survival in HIV-positive patients with diarrhoea who excrete adenovirus from the GI tract.

Adenoviruses have been described as a cause of diarrhoea in patients infected with the human immunodeficiency virus (HIV). The prevalence of adenoviruses was studied in all HIV-positive patients presenting with diarrhoea at the Royal Free Hospital in London between 1991 and 1995. In addition, all postmortems carried out in HIV-positive individuals registered at the same centre between 1990 and 1997 were reviewed for evidence of adenovirus infection. Adenovirus was detected in 16.1% of patients presenting with diarrhoea. These individuals had a significantly lower CD4 count and were more likely to have had a diagnosis of acquired immunodeficiency syndrome (AIDS) than patients with diarrhoea in whom adenovirus was not detected. The median survival was 1 year compared with 2.4 years for those without adenoviruses; this difference remained significant (P = .008) after controlling for differences in CD4 counts between the groups. Gastrointestinal adenovirus excretion occurs at an advanced stage of HIV disease, and is associated with a poor prognosis. We suggest that adenoviruses may contribute to mortality in this population.

Adenoviridae↗
PubMed1999

Validation of Aerosport KB1-C portable metabolic system.

The purpose of this study was to test the validity of the Aerosport KB1-C portable metabolic measurement system against the criterion Douglas bag method. During cycle ergometry, simultaneous measurements of minute ventilation (VE), oxygen consumption (VO2), and carbon dioxide production (VCO2) were made at rest and at power outputs of 50, 100, 150, 200, and 250 W. No significant differences (P > 0.05) were observed for VE, VO2, and VCO2 between the KB1-C and Douglas bag at 100, 150, and 250 W, while the KB1-C was significantly different (P < 0.05) from Douglas bag values at rest, 50, and 200 W. R values were found to be significantly different (P < 0.05) at 100, 150, and 200 W, while no significant differences were observed at rest, 50, and 250 W. The fractional concentrations of oxygen (FEO2) and carbon dioxide (FECO2) were not significantly different at 50, 100, 200, and 250 W while values at rest and 150 W were significantly different (P < 0.05). These findings show that the Aerosport KB1-C portable metabolic system is acceptable for measuring oxygen uptake in the range of 1.5 and 3.5 L x min(-1), using the medium flow pneumotach setting. At lower intensities, the low-flow pneumotach setting provides acceptable results.

Adult↗
PubMed1998

Quantitative differences in the distribution of zidovudine resistance mutations in multiple post-mortem tissues from AIDS patients.

Replication of HIV introduces errors into the genome which are responsible for conferring a growth advantage over wildtype virus when drugs such as zidovudine (ZDV) exert a selective pressure. The molecular basis for HIV-1 resistance to ZDV has been mapped to codons 41, 67, 70, 215 and 219 of the reverse transcriptase gene both in vitro and in clinical samples of blood. This study has investigated the relationship between the quantitative prevalence of ZDV resistance in multiple organs of the same individual. Proviral HIV-1 load was measured by quantitative-competitive PCR in 90 samples from organs of 11 patients dying with AIDS. Nine of these patients had been prescribed zidovudine. The distribution of wildtype and mutant sequences at the positions 41, 67, 70, 215 and 219 of the reverse transcriptase was assessed using a point mutation assay. The results showed that the highest proviral loads were predominately found in lymph node, spleen and lung and there was a significant association between viral load and resistance to ZDV (P=0.008). Inter-organ distribution of wildtype and mutant sequences at codons 41, 67, 70, 215 and 219 was frequently not uniform and in some patients differed markedly between the lymphoreticular system and other organs. These results demonstrate that treatment of HIV-1 infection with zidovudine does not exert uniform selective pressures in multiple organs. These findings have implications for the interpretation of resistance data and design of treatment strategies for HIV, arguing in particular that alterations in therapeutic regimens should consider the likelihood of different resistance patterns being present in multiple sites within the same individual.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Changes in lung lymphocyte populations reflect those seen in peripheral blood in HIV-1 positive individuals.

We have investigated the level of lymphocytosis present in the lung of human immunodeficiency virus (HIV)-1+ infected patients with and without pulmonary disease and how changes in natural killer (NK), B and T-cells seen in peripheral blood (PB) compare with those seen in bronchoalveolar lavage fluid (BALF). Lymphocyte subpopulations and their expression of activation, cytotoxic markers and memory status were characterized by triple immunofluorescence. Macrophages accounted for over 80% of the BAL cells. Only three out of 72 patients had a lymphocyte percentage >30%. No statistically significant differences in the relative proportions of NK, CD4 and CD8 populations were seen in BALF when compared to PB, except for a twofold increase in the percentage of activated CD8 cells in BALF. The only differences in BALF populations between the HIV-1+ groups were a lower percentage of CD4+ cells, and a higher percentage of activated CD8+ cells in the patients with pneumonitis. In the present cohort of patients there was little evidence for an overall lymphocytosis in bronchoalveolar lavage fluid of HIV-1+ subjects. Changes observed in lymphocyte subsets of bronchoalveolar lavage fluid populations reflected those in peripheral blood, and were similar for patients with and without pneumonitis. Evidence of increased CD8 subset activity in bronchoalveolar lavage fluid did, however, emerge.

AIDS-Related Opportunistic Infections↗
PubMed1998

Retrospective neuropathological review of prion disease in UK haemophilic patients.

In 1996, the CJD surveillance unit in Edinburgh, UK described nvCJD which was thought to be the human equivalent of bovine spongiform encephalopathy (BSE). The identification of prion protein in the tonsil of an affected individual has raised the question of transmission of nvCJD via blood products. This study examines the post mortem brains of 33 patients who were treated with clotting factor concentrate of predominately UK donor source during the years 1962-1995. The brains were examined by conventional histological methods and also for the prion protein using monoclonal antibodies KG9 and 3F4. No evidence of spongiform encephalopathy was found and the immunocytochemistry was negative for PrP in all cases. It is concluded that, at present, there is no evidence for the transmission of nvCJD via clotting factor concentrate to patients with haemophilia.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Cerebral nocardia abscesses in a patient with AIDS: correlation of magnetic resonance and white cell scanning images with neuropathological findings.

We present a case of cerebral nocardiosis in a patient with AIDS. Space-occupying lesions were identified using magnetic resonance imaging (MRI) and white cell scanning. Nocardia asteroides was isolated from blood cultures. The patient's response to treatment with amikacin, imipenem and ceftriaxone was followed clinically and radiologically. When he died 6 months later, N. asteroides was isolated at post-mortem from a cerebral abscess. Although cerebral infections associated with the infiltration of neutrophils are rare in patients with AIDS, this case demonstrates that indium-labelled neutrophils can be used to identify a brain abscess and monitor its response to antimicrobial therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Quantification of human herpesvirus 6 in immunocompetent persons and post-mortem tissues from AIDS patients by PCR.

A quantitative competitive PCR assay for human herpesvirus 6 (HHV-6) was developed. Firstly, viral burden was determined in the blood of 25 healthy persons. Using 1 microgram of DNA, the prevalence of HHV-6 was 36% (9/25). Eight persons had viral loads of < or = 32 HHV-6 genomes/microgram DNA. The viral burden in the ninth individual was 1.2 x 10(6) HHV-6 genome copies/microgram DNA, which remained constant over a period of 10 months. This demonstrates the persistence of a high HHV-6 load in the absence of apparent disease. Secondly, HHV-6 burden was determined in 100 post-mortem tissues from seven AIDS patients and three controls. For all tissues combined, there was a statistically significant higher median viral load in AIDS patients (56 copies/microgram DNA, range 0-43321) compared to controls (10 copies/microgram DNA, range 0-423) (P = 0.04). The precision and reproducibility of this assay will allow hypotheses concerning the pathogenic potential of HHV-6 to be tested quantitatively.

AIDS-Related Opportunistic Infections↗
PubMed1995

Use of the polymerase chain reaction to detect genomes of human immunodeficiency virus and cytomegalovirus in post-mortem tissues.

The polymerase chain reaction (PCR) was used to amplify a 149 base-pair region of the cytomegalovirus (CMV) genome and a 551 base-pair region of the HIV-1 proviral long terminal repeat (LTR) present in DNA extracted from post-mortem tissue. Multiple tissues (n = 116) obtained from 16 patients which were subjected to PCR were also subjected to cell culture and histopathological analyses. One hundred and seven samples (92%) contained CMV DNA and 66/116 (57%) contained HIV proviral DNA at a level of > or = 10 genomes. Both viruses were detected in 60/116 (51.7%) of samples, with co-infection most frequent in the lung (69%). Cell culture for CMV detected 9.3% of the PCR-positive samples, whilst histology identified CMV inclusions in 15.9% of samples, all of which were CMV PCR-positive. CMV was most frequently detected in adrenal and lung tissues by histology. These results show that co-infection with CMV and HIV is a common occurrence in organs from AIDS patients and provide further evidence for a role of cytomegalovirus in the pathogenesis of AIDS.

AIDS-Related Opportunistic Infections↗
PubMed1995

Comparison of the maximum tolerated dose (MTD) dermal response in three strains of mice following repeated exposure to acrylic acid.

The dermal response of three strains of mice (ICR, C3H and B6C3F1) exposed to repeated doses of 0, 1 or 4% acrylic acid was examined over 13 wk. Microscopic and gross changes to the skin were classified as being indicative of exceeding the maximum tolerated dose (MTD), reaching the MTD, or tolerating the dose based on proposed MTD guidelines established in US Environmental Protection Agency (EPA) Workshops on dermal carcinogenesis bioassays. A significant number of animals in all three strains with repeated exposure to 4% acrylic acid experienced skin irritation that was classified as having reached or exceeded the MTD compared with animals exposed to either 1% acrylic acid or the 0% acrylic acid acetone control. These results were observed within the first 3 wk of exposure, but there was some accommodation to irritation by 8 wk of exposure. Microscopic findings provided a more sensitive index for exceeding MTD than gross observations taken only at autopsy, but generally correlated well for MTD if gross observations were taken at regular intervals during treatment. That is, to set MTD, gross observations could be used if taken over the entire course of the exposure, but using microscopic findings was generally a more reliable or sensitive measure. EPA guidelines suggest that it is inappropriate to conduct a dermal bioassay at concentrations that exceed the MTD. Acrylic acid at 4% in acetone clearly exceeded the MTD based on microscopic or gross observation criteria. At 4%, strain differences were evident by gross observation only, with the ICR strain being less susceptible to irritation than C3H or B6C3F1 strains. These strain differences were not apparent with microscopic examination. Acrylic acid at 1% in acetone, although demonstrating signs of minimal irritation, was fairly well tolerated by all mice in all strains. Thus, acrylic acid at 1% in acetone, one-quarter of the concentration that was in clear excess of the MTD, would be the appropriate dose concentration for lifetime skin studies based on MTD criteria.

Acrylates↗