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Biomedical subjects

G Berry

Publications and source records attributed to G Berry.

At least 55 records · Page 3Linked to original sources

Mortality from all cancers of asbestos factory workers in east London 1933-80.

OBJECTIVE: To give the observed and expected deaths due to cancer at all separate sites in asbestos workers in east London, and to analyse these for overall effect and exposure-response trend. METHODS: The mortality experience of a cohort of over 5000 men and women followed up for over 30 years since first exposure to asbestos has been extracted. RESULTS: There was a large excess of deaths due to cancer (537 observed, 222 expected). Most of these were due to cancer of the lung (232 observed, 77 expected) and pleural (52) and peritoneal (48) mesothelioma. The exposure-response trend for all these three causes was highly significant. There was also an excess of cancer of the colon (27 observed, 15 expected) which was significantly related to exposure. There were significant excesses of cancer of the ovary, of the liver, and of the oesophagus but with no consistent relation to exposure. CONCLUSIONS: The excess risk of cancer after exposure to asbestos was mainly due to cancer of the lung and mesothelioma. An exposure related excess of cancer of the colon was also detected but the possibility that some of these deaths may have been peritoneal mesotheliomas could not be excluded. There was no consistent evidence of exposure related excesses at any other site.

Asbestos↗

Neonatal herpes prevention: a minor public health problem in some communities.

BACKGROUND: Neonatal herpes is a condition with high morbidity and mortality. The greatest risk occurs when the mother acquires herpes simplex virus (HSV) towards the end of pregnancy. A study from Seattle has suggested that the risk of acquisition of HSV during pregnancy was 3.7%. In Australia, HSV-2 infection is less common in pregnant women than in the United States. Consequently we conducted a study to establish HSV seroprevalence and the rate of HSV seroconversion in this population. METHODS: The study was conducted at Westmead Hospital, Sydney, between June 1995 and April 1998. Women completed a questionnaire covering risk factors for the acquisition of genital herpes. A serum sample during pregnancy and a specimen of cord blood were obtained and tested for antibodies to HSV-2 using a type specific indirect enzyme linked immunosorbent assay (ELISA). Equivocal results were resolved by western blot. A subset of the paired sera was tested for antibodies to HSV-1. The data were analysed using SPSS. RESULTS: 326 of the 2616 (12.5%) women were HSV-2 seropositive. Three women (0.15%) acquired HSV-2 infection during pregnancy. None of the three babies of these mothers developed neonatal herpes. 416 maternal cord pairs were tested for HSV-1 antibodies and 330 (79.3%) were positive. No HSV-1 seroconversions occurred. CONCLUSIONS: In this population, HSV acquisition was uncommon (0.34% per year) and neonatal herpes was rare. A cost effective analysis suggested that type specific serology to screen pregnant women and their partners in low prevalence communities was not cost effective.

Adult↗

Assessment of risk for pelvic inflammatory disease in an urban sexual health population.

OBJECTIVES: To determine the sexual and demographic risk factors for the acquisition of presumptive pelvic inflammatory disease (PID). METHODS: A retrospective, case-control study in women, who attended the Sydney Sexual Health Centre (SSHC), between April 1991 and December 1997. Logistic regression analysis was used to adjust for confounding variables. RESULTS: 741 women with PID and an equal number of controls were included. Cases were significantly younger than controls (p < 0.001). 42% of cases were born in north or South East Asia, compared with 12% of the controls (p < 0.001). The adjusted odds ratio for being born in north or South East Asia was 2.8 (95% CI 1.70-4.46), for not speaking English at home was 1.6 (95% CI 1.02-2.55), for having had previous PID was 5.9 (95% CI 3.59-9.73), and for being employed in the commercial sex industry and being born in north or South East Asia was 2.8 (95% CI 1.22-6.22). Women aged 15-19 were at considerable risk of developing PID (OR 5.3 (95% CI 2.76-10.11)). Women with previous human papillomavirus infection were significantly less likely to develop PID (OR 0.6 (95% CI 0.42-0.79)). The use of IUCDs (OR 4.5 (95% CI 2.14-9.39)), condoms (OR 1.4 (95% CI 1.03-1.87)), and not using contraception (OR 1.8 (95% CI 1.20-2.76)) was each associated with an increased risk. CONCLUSIONS: Several measures may help to reduce the burden of PID. Women should be encouraged to delay the onset of sexual activity and IUCDs should not be used in young women. Sexual health services for women whose home language is not English, and for commercial sex workers born in north or South East Asia should be improved.

Adolescent↗

Lung function growth and its relation to airway hyperresponsiveness and recent wheeze. Results from a longitudinal population study.

To evaluate the association between growth in height and growth in lung function, and to identify the potential temporal relationships between airway hyperresponsiveness (AHR), respiratory symptoms, and lung function growth during adolescence and young adulthood, we analyzed data collected from the Belmont cohort. Among the 718 schoolchildren initially studied at 1982 (aged 8-10 yr), 557 were studied between two times and six times at 2-yr intervals until 1992. Baseline lung function, AHR by histamine inhalation test, and recent wheeze by questionnaires, were measured at each visit. We found that between 17 and 19 yr of age, when growth in height had stopped, growth in FEV(1) was approximately 200 ml/yr in boys and 100 ml/yr in girls. Peak growth velocity of height occurred at age 13 both in boys and in girls, whereas peak growth velocity of FEV(1) occurred at the same age only in girls and 1 yr later in boys. Having AHR and recent wheeze at the previous study time were both associated with lower subsequent growth in FEV(1), but not with subsequent growth in FVC. We conclude that lung function continues to grow after the cessation of height growth and that growth in FEV(1) is reduced in subjects with AHR and/or recent wheeze.

Body Height↗

CD4(+) T helper cells engineered to produce latent TGF-beta1 reverse allergen-induced airway hyperreactivity and inflammation.

T helper 2 (Th2) cells play a critical role in the pathogenesis of asthma, but the precise immunological mechanisms that inhibit Th2 cell function in vivo are not well understood. Using gene therapy, we demonstrated that ovalbumin-specific (OVA-specific) Th cells engineered to express latent TGF-beta abolished airway hyperreactivity and airway inflammation induced by OVA-specific Th2 effector cells in SCID and BALB/c mice. These effects correlated with increased concentrations of active TGF-beta in the bronchoalveolar lavage (BAL) fluid, demonstrating that latent TGF-beta was activated in the inflammatory environment. In contrast, OVA-specific Th1 cells failed to inhibit airway hyperreactivity and inflammation in this system. The inhibitory effect of TGF-beta-secreting Th cells was antigen-specific and was reversed by neutralization of TGF-beta. Our results demonstrate that T cells secreting TGF-beta in the respiratory mucosa can indeed regulate Th2-induced airway hyperreactivity and inflammation and suggest that TGF-beta-producing T cells play an important regulatory role in asthma.

Allergens↗

Economic impact of increased clinical intervention rates in community pharmacy. A randomised trial of the effect of education and a professional allowance.

OBJECTIVE: To determine the economic impact of an interventional programme aimed to increase the rate of clinical interventions undertaken in community pharmacy. STUDY DESIGN AND PERSPECTIVE: A randomised controlled trial of 4 parallel groups of pharmacies, conducted from a government perspective. Economic evaluations were based on savings/costs attributable to healthcare costs avoided, healthcare costs incurred by the pharmacists' actions, change in medication costs, pharmacy time and telephone calls made by the pharmacist. The study was conducted during November and December 1996 and costings were based on 1997 figures. INTERVENTIONS: A professional fee-for-service [10 Australian dollars ($A; $A1 = 6.50 US dollars) per intervention] and education (an intensive 1-week course or advanced education) were implemented in an attempt to increase clinical interventions by the pharmacists. Group A pharmacies (n = 10) served as a control group and received neither education nor remuneration; group B received education and professional remuneration (n = 9); group C had received prior continued education and now received advanced education and professional remuneration (n = 11); and group D received professional remuneration with no education. MAIN OUTCOME MEASURES AND RESULTS: The proactive clinical interventions in group C saved a mean of $A85.35 per 1000 prescriptions [95% confidence interval (CI)-$A157.11 to $A24.95). This was 4 times greater than savings generated by pharmacies in group B (mean savings of $A25.65 per 1000 prescriptions) and 6 times greater than control pharmacies. A sensitivity analysis which extrapolated results to Australian prescription figures showed that the control group was capable of generating savings in the order of $A2.4 million per year while pharmacists in group C would save the healthcare system $A15 million per year. CONCLUSIONS: These results provide the first economic estimates for the provision of clinical interventions in Australian community pharmacies. It is believed that they illustrate the value of pharmaceutical services to the healthcare system and to the Australian community in terms of both quality of care and savings.

Australia↗

Meta-analysis on the association between environmental tobacco smoke (ETS) exposure and the prevalence of lower respiratory tract infection in early childhood.

The aim of this study was to obtain quantitative information from published data on the association between environmental tobacco smoke (ETS) exposure and the prevalence of serious lower respiratory tract infections (LRTI) in infancy and early childhood. We identified 21 relevant publications on the relation between ETS and the prevalence of serious LRTI by reviewing reference lists in relevant reports and by conducting manual and computer searches (Medline database; Dissertation abstracts index of Xerox University Microfilms) of published reports between 1966 and 1995. Thirteen studies were included in a quantitative overview using random effects modeling to derive pooled odds ratios. Sensitivity analyses were conducted to test the decision rules used in extracting odds ratio data. The results of community and hospital studies are broadly consistent and show that the child of a parent who smokes is at approximately twice the risk of having a serious respiratory tract infection in early life that requires hospitalization. This association was pronounced in children younger than age two and diminished after the age of two. The combined odds ratio for hospitalization for lower respiratory tract infections in infancy or early childhood is 1.93 (95% CI 1.66-2.25); the combined odds ratio of prevalence of serious LRTI at age less than 2 years, between 0 and 6 years, and between 3 and 6 years were 1.71 (95% CI 1.33-2.20); 1.57 (1.28-1.91), and 1.25 (0.88-1.78), respectively. There was no evidence of heterogeneity across the studies in these combined odds ratios. We conclude that this meta-analysis provides strong evidence that exposure to ETS causes adverse respiratory health outcomes such as either a serious LRTI or hospitalization for LRTI. New public health campaigns are urgently needed to discourage smoking in the presence of young children.

Age Distribution↗

Underground coal miners' foot and boot problems.

The New South Wales (NSW) Joint Coal Board Health and Safety Trust funded an investigation into foot problems reported by 400 randomly selected underground coal miners from 15 mines in NSW. Miners were interviewed and their responses were entered directly into laptop computers. Digital cameras were also used to take pictures of skin conditions and miners' posture. Observations of the skin results indicate that miners find gumboots to be hot, sweaty and uncomfortable. Skin breakdown and tinea, is frequent and disabling and responsible for absences from the workforce that are costly for both miner and employer. A more comfortable and better designed boot is needed, fabricated in waterproof leather together with socks that 'wick' the moisture away from the foot. Socks worn were of varying components and washed at irregular intervals, indicating a need for regular changes of socks and improved hygiene.

Coal↗

Models for mesothelioma incidence following exposure to fibers in terms of timing and duration of exposure and the biopersistence of the fibers.

The health effects of inhaled fibers are related to the intensity and duration of exposure and occur many years after the exposure. In particular, the incidence of mesothelioma after exposure to asbestos is proportional to the intensity of exposure (fibers per milliliter of air) and the duration of exposure, and to the time that has elapsed since the exposure. The incidence increases with time since exposure to a power of between 3 and 4. The disease process resulting from exposure to fibers in the air is presumably related to the dose of fibers in the lungs, which depends on the exposure level and duration, and also on the size characteristics of the fibers influencing their inhalation and retention in the lungs. Models incorporating these characteristics have been found to be satisfactory in explaining the incidence of mesothelioma over time after exposure to asbestos. Most of the epidemiological modeling has been for occupational exposure to one of the amphibole asbestos types (crocidolite or amosite), for which heavy exposure produces a high incidence of mesothelioma. Occupational exposure to chrysotile asbestos has resulted in a much lower incidence of mesothelioma. Crocidolite asbestos is much more biopersistent than chrysotile asbestos in the sense that after retention in the lungs it is eliminated only slowly (half-time of several years). If fibers are eliminated then the dose in the lungs declines following exposure, and this may influence the disease process. This concept is more important for synthetic mineral fibers, such as glass wool, which are used as a substitute for asbestos. These fibers are much less biopersistent than asbestos, with half-times of weeks or even days. Biopersistence is related to the dissolution of fibers. This is a physical-chemical process that may be expected to proceed at about the same rate in rats and humans. The predicted effect of biopersistence of fibers has been explored using the basic mesothelioma incidence model generalized to include a term representing exponential elimination over time. The influence of solubility of fibers on the mesothelioma rate is 17 times higher in humans than in rats. This is because rats are aging and developing cancer at a much quicker rate than humans, and hence the influence of dissolution is less. Thus, the predicted mesothelioma incidence in humans is highly dependent on the rate of elimination across the range covering asbestos and the more durable synthetic fibers, but in rats a similar dependence occurs at a 17 times higher rate of elimination corresponding to the less durable synthetic fibers. The possible carcinogenic effects of fibers are often determined from animal experiments, but these results suggest that the extrapolation from rats to humans is highly dependent on the biopersistence of fibers, in the situation where the elimination is through dissolution of fibers at a rate independent of species and the speed of the cancer process is species dependent. This implies that relatively soluble fibers that do not produce disease in rat experiments are even less likely to produce disease in humans.

Algorithms↗

Allergen-specific Th1 cells fail to counterbalance Th2 cell-induced airway hyperreactivity but cause severe airway inflammation.

Allergic asthma, which is present in as many as 10% of individuals in industrialized nations, is characterized by chronic airway inflammation and hyperreactivity induced by allergen-specific Th2 cells secreting interleukin-4 (IL-4) and IL-5. Because Th1 cells antagonize Th2 cell functions, it has been proposed that immune deviation toward Th1 can protect against asthma and allergies. Using an adoptive transfer system, we assessed the roles of Th1, Th2, and Th0 cells in a mouse model of asthma and examined the capacity of Th1 cells to counterbalance the proasthmatic effects of Th2 cells. Th1, Th2, and Th0 lines were generated from ovalbumin (OVA)-specific T-cell receptor (TCR) transgenic mice and transferred into lymphocyte-deficient, OVA-treated severe combined immunodeficiency (SCID) mice. OVA-specific Th2 and Th0 cells induced significant airway hyperreactivity and inflammation. Surprisingly, Th1 cells did not attenuate Th2 cell-induced airway hyperreactivity and inflammation in either SCID mice or in OVA-immunized immunocompetent BALB/c mice, but rather caused severe airway inflammation. These results indicate that antigen-specific Th1 cells may not protect or prevent Th2-mediated allergic disease, but rather may cause acute lung pathology. These findings have significant implications with regard to current therapeutic goals in asthma and allergy and suggest that conversion of Th2-dominated allergic inflammatory responses into Th1-dominated responses may lead to further problems.

Allergens↗

Retinopathy in older persons without diabetes and its relationship to hypertension.

OBJECTIVE: To assess the prevalence and relationship of retinopathy lesions in older subjects without diabetes to systemic hypertension. METHODS: Three thousand six hundred fifty-four people aged 49 years or older attending the Blue Mountains Eye Study underwent a detailed eye examination, including medical history, blood pressure measurement, and fasting blood collection. Retinopathy lesions (hemorrhages and microaneurysms) were assessed from masked grading of stereoretinal photographs. Subjects with a history of diabetes or an elevated blood glucose level were excluded. Hypertension was defined as the current use of antihypertensive medications or an elevated blood pressure measurement on examination. RESULTS: Retinopathy was present in 325 subjects without diabetes, a prevalence of 9.8% (95% confidence interval [CI], 8.9%-10.9%), which increased with age. An increased age-adjusted relative risk (RR) for retinopathy was found for women (RR, 1.67; 95% CI, 1.26-2.21) and men (RR, 1.47; 95% CI, 1.07-2.00) with hypertension. In people using antihypertensive medications, retinopathy prevalence was higher for uncontrolled compared with controlled blood pressure but was not related to hypertension duration. Significant (P=.02 to P=.001) trends were found between increasing blood pressure quartiles and age-adjusted retinopathy prevalence, a relationship that was maintained after adjusting for fasting plasma glucose level at 3 diagnostic cut points for diabetes. CONCLUSIONS: This study supports the Beaver Dam Eye Study findings that retinal hemorrhages and microaneurysms are relatively frequent lesions in older people without diabetes and are significantly related to the presence and severity of hypertension.

Aged↗

Quantitative fluorescence resonance energy transfer measurements using fluorescence microscopy.

Fluorescence resonance energy transfer (FRET) is a technique used for quantifying the distance between two molecules conjugated to different fluorophores. By combining optical microscopy with FRET it is possible to obtain quantitative temporal and spatial information about the binding and interaction of proteins, lipids, enzymes, DNA, and RNA in vivo. In conjunction with the recent development of a variety of mutant green fluorescent proteins (mtGFPs), FRET microscopy provides the potential to measure the interaction of intracellular molecular species in intact living cells where the donor and acceptor fluorophores are actually part of the molecules themselves. However, steady-state FRET microscopy measurements can suffer from several sources of distortion, which need to be corrected. These include direct excitation of the acceptor at the donor excitation wavelengths and the dependence of FRET on the concentration of acceptor. We present a simple method for the analysis of FRET data obtained with standard filter sets in a fluorescence microscope. This method is corrected for cross talk (any detection of donor fluorescence with the acceptor emission filter and any detection of acceptor fluorescence with the donor emission filter), and for the dependence of FRET on the concentrations of the donor and acceptor. Measurements of the interaction of the proteins Bcl-2 and Beclin (a recently identified Bcl-2 interacting protein located on chromosome 17q21), are shown to document the accuracy of this approach for correction of donor and acceptor concentrations, and cross talk between the different filter units.

Animals↗

Agreement between medical record data and patients' accounts of their medical history and treatment for dyspepsia.

We examined agreement between data abstracted from medical records and interview data for patients with dyspepsia admitted to hospital for endoscopy, to determine the extent to which health records could be used to validate self-reports of dyspepsia and the management of this condition. Results from the sample of 220 patients showed that there was poor agreement between data sources for information about duration of dyspepsia (k=0.34) and previous barium meal examination (k=0.34). Patients reported significantly longer dyspepsia histories (Wilcoxon sign test Z=4.13, p<0.0001) and significantly more barium meals (sign test Z=8.43, p<0.0001) than were documented in their records. There was also disagreement between data sources regarding the number of drugs taken before and after endoscopy (k=0.28 and k=0.31, respectively). Where there was disagreement for number of drugs there was no significant difference in the direction of the disagreement. There was moderate agreement regarding the name of pre-endoscopy medication (k=0.55) and substantial agreement for the name of medication used post-endoscopy (k=0.62). There was very poor agreement regarding diagnosis. The medical record was the gold standard for this information. Choice of data source, medical records or self-reports, will in many instances provide significantly different results and it is likely that this may also be true for other variables of interest to researchers. Thus in the case where no gold standards are available researchers need to consider carefully the implication of choice of data source on their results.

Dyspepsia↗

The use of cardiac biopsy to demonstrate reduced cardiotoxicity in AIDS Kaposi's sarcoma patients treated with pegylated liposomal doxorubicin.

BACKGROUND: Pegylated liposomal doxorubicin (PL-DOX) has been shown in preclinical models to induce less cardiotoxicity than non-liposomal doxorubicin. Endomyocardial biopsy is a highly sensitive and specific method for detecting anthracycline-induced cardiac damage. PATIENTS AND METHODS: Myocardial tissue from ten KS patients who had received cumulative PL-DOX (20 mg/m2/biweekly) of 440-840 mg/m2 was evaluated for evidence of anthracycline-induced cardiac damage. Controls were assembled from patients who had received cumulative doxorubicin doses of 174-671 mg/m2 in two earlier cardiac biopsy protocols. Two control groups were selected on the basis of both cumulative (+/- 10 mg/m2) and peak doxorubicin dose (60 or 20 mg/m2, control group 1), or peak dose alone (20 mg/m2, control group 2). RESULTS: PL-DOX patients had significantly lower biopsy scores compared with those of doxorubicin controls despite higher cumulative doses of anthracycline. The median biopsy scores for the PL-DOX and doxorubicin groups, respectively, were 0.3 vs. 3.0 (P = 0.002, Cochran-Mantel-Haenszel row mean difference test) for group 1 and 1.25 for group 2 (P < 0.001, Wilcoxon rank-sum test). CONCLUSIONS: Less severe cardiac changes were seen in patients given PL-DOX relative to historical control patients given comparable cumulative doses of doxorubicin.

Acquired Immunodeficiency Syndrome↗

Bcl-2 and Bax interactions in mitochondria probed with green fluorescent protein and fluorescence resonance energy transfer.

It has been hypothesized that interaction of Bcl-2 and Bax may regulate apoptosis. The spatial and temporal interaction of Bcl-2 and Bax at the single cell level has not, however, been demonstrated. To achieve this goal, we have developed two-fusion FRET (fluorescence resonance energy transfer). Using green fluorescent protein (GFP)-Bax and blue fluorescent protein (BFP)-Bcl-2 fusion proteins coexpressed in the same cell, we demonstrate a direct interaction between Bcl-2 and Bax in individual mitochondria. Mitochondrially localized cytochrome c-GFP and BFP-Bcl-2 showed little or no FRET, while nuclear-localized GFP-human papillomavirus E6 and BFP-Bcl-2 did not interact when coexpressed in the same cell. These findings indicate that two-fusion FRET provides an opportunity to examine the interaction between two different proteins coexpressed in single intact mammalian cells.

3T3 Cells↗

Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein.

bcl-2, the prototypic cellular antiapoptotic gene, decreases Sindbis virus replication and Sindbis virus-induced apoptosis in mouse brains, resulting in protection against lethal encephalitis. To investigate potential mechanisms by which Bcl-2 protects against central nervous system Sindbis virus infection, we performed a yeast two-hybrid screen to identify Bcl-2-interacting gene products in an adult mouse brain library. We identified a novel 60-kDa coiled-coil protein, Beclin, which we confirmed interacts with Bcl-2 in mammalian cells, using fluorescence resonance energy transfer microscopy. To examine the role of Beclin in Sindbis virus pathogenesis, we constructed recombinant Sindbis virus chimeras that express full-length human Beclin (SIN/beclin), Beclin lacking the putative Bcl-2-binding domain (SIN/beclinDeltaBcl-2BD), or Beclin containing a premature stop codon near the 5' terminus (SIN/beclinstop). The survival of mice infected with SIN/beclin was significantly higher (71%) than the survival of mice infected with SIN/beclinDeltaBcl-2BD (9%) or SIN/beclinstop (7%) (P < 0.001). The brains of mice infected with SIN/beclin had fewer Sindbis virus RNA-positive cells, fewer apoptotic cells, and lower viral titers than the brains of mice infected with SIN/beclinDeltaBcl-2BD or SIN/beclinstop. These findings demonstrate that Beclin is a novel Bcl-2-interacting cellular protein that may play a role in antiviral host defense.

Alphavirus Infections↗

Questionnaire items that predict asthma and other respiratory conditions in adults.

The International Union Against Tuberculosis and Lung Disease questionnaire is widely used in epidemiologic studies of adult asthma. We examined whether the symptom questions could be classified into groups that represent different "syndromes," and whether some questions are better for predicting asthma than others. We analyzed questionnaire data from a population sample of 1,527 adults aged 18 to 55 years using factor analyses to classify the 17 respiratory symptom questions into four different groups that we termed asthma, cough, breathlessness, and urgent medical visit. The urgent medical visit was a subset of asthma. These four "syndromes" had good validity when measured against airway responsiveness to histamine, atopy to common allergens, lung function, smoking status, and body mass index. Questions that predicted asthma syndrome were those that asked about wheeze at rest or following exercise, asthma attack, chest tightness, and shortness of breath at rest. Questions about cough identified a different group of subjects who apparently did not have asthma. Questions of breathlessness did not aggregate with "asthma" or with "cough syndrome." The identification of particular questions that measure different respiratory conditions is important for epidemiologic studies when short questionnaires or more precise definitions are required.

Adolescent↗