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Biomedical subjects

J Simpson

Publications and source records attributed to J Simpson.

At least 91 records · Page 5Linked to original sources

Women's occupation and cancer: preliminary analysis of cancer registrations in England and Wales, 1971-1990.

BACKGROUND: In recent years increasing attention has been paid to examining the relation between women's health and their own occupation. The findings presented here relate to an analysis of 381,915 cancers in women registered in England and Wales over the 20-year period 1971-1990. METHODS: To explore the value of the data for epidemiological research, five sites (pleura, bladder, stomach, lung, and breast) and two occupations (agriculture and textile) were selected. Associations between cancer and occupation were evaluated using age and social class adjusted proportional registration ratios (PRRs) and 95% confidence intervals (CI). RESULTS: Pleural cancer risk was increased in a range of occupations with a potential for asbestos exposure (e.g., PRR 608, 95% CI 381-921 for craft and other production process workers), and the well-established link between bladder cancer and employment in the rubber industry was confirmed (PRR 303, 95% CI 188-464). Associations between "dusty" occupations and stomach cancer were noted (e.g., PRR 198, 95% CI 126-298 for ceramic decorators and finishers), and possible links with lung cancer and smoke in the work environment were highlighted (e.g., PRR 167, 95% CI 147-189 for publicans). As a group, agricultural workers were found to be at increased risk of non-Hodgkin's lymphoma (PRR 164, 95% CI 126-211), and textile workers at increased risk of pleural cancer (PRR 145, 95% CI 111-185). No evidence for an occupational aetiology for breast cancer was found within these data. CONCLUSIONS: Occupational information collected at cancer registration in the United Kingdom can be reliably used to identify groups that may be at increased risk of disease.

Adult↗

Fine-needle aspiration cytology of adenoid cystic carcinoma of the breast.

Adenoid cystic carcinoma (ACC) of the breast is a rare variant of breast malignancy and has a better prognosis than its counterpart in the salivary glands. In this communication, our experience with seven cases of ACC of the breast is presented in which the diagnosis was established on fine-needle aspiration cytology (FNAC). The cytologic samples in all cases were cellular and featured three-dimensional clusters of uniform ductal epithelial cells with cystic spaces, bland nuclei, fine chromatin, and scanty cytoplasm arranged around spheres or cores of homogenous material. The cytodiagnosis of ACC in all cases correlated with subsequent examination of cell blocks of the aspirate and tissue. The cytodiagnostic criteria for ACC of the breast which are useful in a correct FNAC diagnosis are discussed.

Adult↗

Pattern of airway inflammation and its determinants in children with acute severe asthma.

The aim of this study was to examine the relationship between sputum cell counts and clinical variables in children with an acute exacerbation of asthma. Sputum was successfully obtained from 37 of 42 children presenting to the Emergency Department with acute asthma, using ultrasonically nebulized normal saline (n = 19) or spontaneous expectoration (n = 18). Sputum portions were selected and dispersed, and total and differential cell counts were performed. Sputum supernatant was assessed for eosinophil cationic protein (ECP), interleukin (IL)-5, and IL-8. The exacerbations were of 3 inflammatory cell patterns: eosinophilic (n = 16 or 43% of total), combined eosinophilic/neutrophilic (E/N; n = 13.3 or 35% of total), or noneosinophilic (n = 8 or 22% of total). IL-5 was highest in eosinophilic exacerbations. Combined E/N exacerbations had increased mast cells (77%) and higher sputum ECP levels than eosinophilic exacerbations: 2,146 ng/mL vs. 666 ng/mL (P = 0.04). The speed of onset of the exacerbation was not related to the inflammatory cell profile. Logistic regression identified maintenance asthma treatment (odds ratio (OR), 5.9; 95% confidence interval (CI), 1.3-26.8) and lung function during the acute episode (OR, 4.0; 95% CI, 1.7-93) as significantly associated with the intensity of sputum eosinophilia. Eosinophils were lowest in children who received maintenance treatment with oral corticosteroids compared to those with no background asthma preventer therapy (P = 0.001). In conclusion, we identified three distinct patterns of airway inflammation in children with acute asthma; they included increased eosinophils, combined eosinophilic-neutrophilic infiltration, and a noneosinophilic pattern. Eosinophil degranulation was greatest with the combined eosinophilic/neutrophilic pattern of airway inflammation. Sputum eosinophils were associated with clinical severity, and background asthma therapy, but not with outcome, nor with speed of onset of exacerbations. These different inflammatory cell profiles imply different etiological agents and may require differing treatment strategies.

Acute Disease↗

Cloning and characterization of a trypsin inhibitor cDNA from amaranth (Amaranthus hypochondriacus) seeds.

We previously isolated and sequenced the major trypsin inhibitor from Amaranthus hypochonidriacus seeds. This amaranth trypsin inhibitor (AmTI) is a 69 amino acid protein with high homology to members of the potato-1 inhibitor family. This paper describes the cloning and expression of a cDNA encoding this trypsin inhibitor in various vegetative tissues of the amaranth plant during seed development and imbibition, and investigates the possible induction of AmTI expression by wounding. We obtained a 393 bp cDNA sequence with an open reading frame corresponding to a polypeptide with 76 amino acid residues. With the exception of one residue (Ser-41), the polypeptide agrees with the amino acid sequence previously reported, plus 7 more residues at the N-terminus. These N-terminal residues are thought to be part of the signal used for intracellular sorting. The organ specificity of AmTI gene expression was investigated by northern analysis, showing that mRNA corresponding to AmTI genes was present in stems of plants growing under normal conditions. The kinetics of accumulation of the AmTI-mRNA, protein, and inhibitory activity during seed development and imbibition was determined. AmTI-mRNA accumulation reached a maximum at 14 days after anthesis (daa) and then gradually decreased, being barely detectable 36 daa. The AmTI protein accumulation followed the same profile as the inhibitory activity, both were delayed with respect to the mRNA. The maximum level was observed 22 daa, and then gradually decreased until a steady state was reached as seed maturation proceeded. Upon imbibition, a gradual decrease in AmTI protein and inhibitory activity was shown; however, an AmTI transcript was detected 24 h after imbibition. In contrast to representative members of the potato I family, this inhibitor was not inducible by wounding of leaves.

Amino Acid Sequence↗

The effects of mefloquine treatment in pregnancy.

We investigated the relationship between mefloquine antimalarial treatment and the outcome of pregnancy in Karen women living in an area along the western border of Thailand where multidrug-resistant Plasmodium falciparum infections are common. Of 3,587 pregnancies investigated, 208 (5.8%) were exposed to mefloquine, 656 (18.3%) to quinine only, and 909 (25.3%) to other antimalarials, and 2,470 (68.9%) had no documented malaria. There were 61 stillbirths and 313 abortions. Women who received mefloquine treatment during but not before pregnancy had a significantly greater risk of stillbirth than did women treated with quinine alone (odds ratio [OR], 4.72; 95% confidence interval [CI], 1.7-12.7), women exposed to other treatments (OR, 5.10; 95% CI, 2-13.1), and women who had no malaria (OR, 3.50; 95% CI, 1.6-7.6) (P < .01). This association remained after adjustment for all identified confounding factors. Mefloquine was not associated with abortion, low birth weight, neurological retardation, or congenital malformations. Mefloquine treatment during pregnancy was associated with an increased risk of stillbirth.

Abnormalities, Drug-Induced↗

CYP2D6 status of extensive metabolizers after multiple-dose fluoxetine, fluvoxamine, paroxetine, or sertraline.

The aim of this study was to evaluate the CYP2D6 inhibitory effects of four selective rerotonin re-uptake inhibitors (SSRIs). Thirty-one healthy subjects were phenotyped as extensive metabolizers using the dextromethorphan/dextrorphan (DM/DX) urinary ratio as a marker for CYP2D6 activity before and after 8 days of administration of fluoxetine 60 mg (loading dose strategy), fluvoxamine 100 mg, paroxetine 20 mg, or sertraline 100 mg in a parallel-group design. Statistical analysis was performed on log-transformed DM/DX ratios because of variability within and between treatment groups. DM/DX ratios before (DM/DX(BL)) and after (DM/DX(SSRI)) were compared within and between the four SSRI groups. DM/DX(BL) ratios were not significantly different between the four SSRI treatment groups. Comparing within groups, significant differences between DM/DX(BL) and DM/DX(SSRI) were found for the fluoxetine (p < 0.001; ratio values, 0.020 vs. 0.364) and paroxetine (p = 0.0005, ratio values 0.029 vs. 1.085) but not for the fluvoxamine or sertraline groups. Comparing between groups, significant differences in DM/DX(SSRI) ratios were found for fluoxetine versus sertraline (p = 0.0019, DM/DX = 0.364 vs. 0.057), fluoxetine versus fluvoxamine (p < 0.0001, DM/DX = 0.364 vs. 0.019), paroxetine versus sertraline (p = 0.0026, DM/DX = 1.085 vs. 0.057), and paroxetine versus fluvoxamine (p < 0.0001, DM/DX = 1.085 vs. 0.019). No significant differences were noted between the two potent CYP2D6 inhibitors, fluoxetine and paroxetine, or the two weakest inhibitors, fluvoxamine and sertraline. Five subjects in the fluoxetine and four subjects in the paroxetine groups changed to poor metabolizer phenotype (DM/DX > or = 0.3) after treatment. Although CYP2D6 inhibitory effects of fluvoxamine and sertraline did not yield significant differences from baseline, some subjects exhibited DM/DX ratio increases of 150 to 200%. One paroxetine-treated subject did not exhibit any CYP2D6 inhibition. SSRI dose and plasma concentration may be correlated with the extent of CYP2D6 inhibition and should be further investigated.

Adult↗

Population health environmental indicators: ecologic monitoring of environment-related health and disease trends.

BACKGROUND: Current State of the Environment (SoE) reporting focuses primarily on indicators directly related to the physical environment such as climate, and air, water and soil quality. As the environment has both direct and indirect effects on human health, an opportunity exists to include environment-related human disease indicators as an SoE indicator theme. OBJECTIVE: To develop a set of population health environmental indicators (PHEIs, phi s) that can illustrate environment-related disease (ERD) trends at the population level. METHODS: A literature review was conducted on environmental health monitoring and the current knowledge of environmental effects on human health. Key PHEIs were identified and routine health data collections accessed and analysed to illustrate temporal and geographic trends. RESULTS: Diseases with an environmental aetiology are tabulated and examples are given of the type and range of PHEIs that can be developed for an Australian geographic area. CONCLUSIONS: Illustrating environmental degradation in terms of resultant human diseases is a potent tool for promoting environmental protection measures. This paper examines a range of PHEIs that may be used as indicators of both environmental disease and environmental quality. IMPLICATIONS: PHEIs could be developed as a useful SoE indicator theme, and as a tool to help foster the convergence which is occurring between environmental health and public health fields.

Australia↗

Evaluation of a telepsychiatry pilot project.

We assessed a telepsychiatry pilot project in which a psychiatric hospital was linked with mental health clinics in five general hospitals. Information was collected through questionnaires administered to patients, service providers and psychiatric consultants, and by interviews. The technology was considered easy to use by participating health-care professionals and patients, and the quality of the sound and picture was adequate. Survey data suggested acceptance and satisfaction on the part of patients, service providers and psychiatric consultants. An economic analysis indicated that at 396 consultations per year the service cost the same as providing a travelling psychiatrist (C$610 per consultation); with more consultations, telepsychiatry was cheaper. Information gathered during the evaluation suggested that the use of videoconferencing for psychiatric consultations was a viable option for an integrated, community-based mental health service.

Canada↗

An assessment framework for telemedicine applications.

Pressures for the adoption of telemedicine place increased demands on purchasers to assess applications of the technique. Assessment principles are helpful in defining an evaluation framework for use at the local level. We suggest an assessment approach that includes five specific elements: specification; performance measures; outcomes; summary measures; and operational and other considerations. The approach described here was developed to assist with the needs of individual health authorities and institutions within the health-care system of Alberta. Aspects of the approach are illustrated using a telepsychiatry example under the assumptions made. Conventional psychiatry (where the patient visited the psychiatrist) was most expensive for the patient. The alternatives, telepsychiatry and outreach psychiatry (where the psychiatrist travelled to the patient), cost about the same from the service provider's perspective (and from that of society as a whole); they were both much cheaper for the patient. At higher volumes, telepsychiatry would be cheaper than outreach.

Evaluation Studies as Topic↗

Adverse effects in patients with acute falciparum malaria treated with artemisinin derivatives.

In prospective studies of acute uncomplicated, multidrug-resistant falciparum malaria on the western border of Thailand, the oral artemisinin derivatives were used alone in the treatment of 836 patients (artesunate 630, artemether 206), were combined with mefloquine (15-25 mg base/kg) in 2,826 patients, and mefloquine alone was used in 1,303 patients. The combined regimens of mefloquine plus an artemisinin derivative were associated with more side effects than those with an artemisinin derivative alone; acute nausea (31% versus 16%), vomiting (24% versus 11%), anorexia (51% versus 34%), and dizziness (47% versus 15%) (P < 0.001). Oral artesunate and artemether alone were very well tolerated. There was no difference in the incidence of possible adverse effects between the two drugs, and no evidence that either derivative caused allergic reactions, neurologic or psychiatric reactions, or cardiovascular or dermatologic toxicity. Blackwater fever occurred in three patients treated with mefloquine plus artesunate regimens. Oral artesunate and artemether are safe and well tolerated antimalarial drugs.

Acute Disease↗

A comprehensive breast and cervical cancer screening program for medically underserved women in Connecticut.

A comprehensive breast and cervical cancer early detection program supported by federal and state funds and administered by the Connecticut Department of Public Health, is actively recruiting and screening older, uninsured, low income women at contracted health-care facilities throughout the state. The program provides diagnostic testing, treatment referral, outreach, and educational activities. During the first 27 months of the program, 5,509 women were enrolled and screened. Women were recruited primarily through media sources and physician/nurse referrals. The majority of women served were non-Hispanic white, between ages 40 to 59, with annual incomes of less than $10,000, and a high school education or less. Some 62% of enrolled women either never had a mammogram or did not have a repeat mammogram within the time-frames recommended by ACS. Recruitment efforts continue to enroll medically underserved women for breast and cervical cancer screening services. Future efforts will focus on rescreening in order to achieve the program's overall mission of detecting breast and cervical cancers at earlier stages.

Adult↗

Automated identification of tubercle bacilli in sputum. A preliminary investigation.

OBJECTIVE: To use an automated method to detect tubercle bacilli in sputum specimens. STUDY DESIGN: Using fluorescence microscopy, tubercle bacilli were identified on auramine-stained sputum specimens. Images were then captured with a digital camera and enhanced through imaging processing techniques. The bacilli were recognized using neural network classifiers. RESULTS: This preliminary investigation demonstrated a sensitivity of 94.1% for the identification of individual bacilli. As there are usually fairly numerous tubercle bacilli in the sputum of patients with active pulmonary tuberculosis, the overall diagnostic accuracy of sputum smear-positive patients can be expected to be very high. CONCLUSION: Potential benefits of automated screening for TB bacilli are: rapid, accurate, inexpensive diagnosis; the ability to screen larger numbers of people; increased resources to monitor patients; and reduction in health risks to staff.

Evaluation Studies as Topic↗

Ca2+/calcineurin-inhibited adenylyl cyclase, highly abundant in forebrain regions, is important for learning and memory.

Activation of cAMP synthesis by intracellular Ca2+ is thought to be the main mode of cAMP generation in the brain. Accordingly, the Ca2+-activated adenylyl cyclases I and VIII are expressed prominently in forebrain neurons. The present study shows that the novel adenylyl cyclase type IX is inhibited by Ca2+ and that this effect is blocked selectively by inhibitors of calcineurin such as FK506 and cyclosporin A. Moreover, adenylyl cyclase IX is inhibited by the same range of intracellular free Ca2+ concentrations that stimulate adenylyl cyclase I. Adenylyl cyclase IX is expressed prominently in the forebrain. Substantial arrays of neurons positive for AC9 mRNA were found in the olfactory lobe, in limbic and neocortical areas, in the striatum, and in the cerebellar system. These data show that the initiation of the cAMP signal by adenylyl cyclase may be controlled by Ca2+/calcineurin and thus provide evidence for a novel mode of tuning the cAMP signal by protein phosphorylation/dephosphorylation cascades.

Adenylyl Cyclase Inhibitors↗

The primary function of a redundant Sp1 binding site in the mouse aprt gene promoter is to block epigenetic gene inactivation.

The promoter region of the mouse adenine phosphoribosyltransferase (aprt) gene contains one non-consensus Sp1 binding site at its 5' end followed by three consensus Sp1 binding sites. The two 3'-most binding sites are sufficient for maximal expression of aprt , suggesting that the non-consensus and consensus binding sites at the 5' end are redundant. However, the two 3' sites are not sufficient to block epigenetic inactivation, which led to the hypothesis that the redundant consensus and/or non-consensus 5' Sp1 binding sites are required to block inactivation events. To test this hypothesis, promoter region constructs were made in which the two 5' Sp1 binding sites were mutated alone or in tandem, and then each construct was tested for its ability to withstand epigenetic inactivation. A cis -acting methylation center that is normally located 1.2 kb upstream of the promoter was used to induce inactivation. The results demonstrate that the presence of the redundant consensus Sp1 binding site is required to block methylation-associated gene inactivation. Therefore, the Sp1 binding sites comprising the mouse aprt promoter have evolved two distinct functions, one to promote transcription and the other to block epigenetic inactivation.

Adenine↗