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Biomedical subjects

G Berry

Publications and source records attributed to G Berry.

At least 73 records · Page 4Linked to original sources
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

Sonographic screening for hepatocellular carcinoma in patients with chronic hepatitis or cirrhosis: an evaluation.

OBJECTIVE: The purposes of this study were to determine the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis or cirrhosis and to assess the cost and benefit of sonographic screening for HCC. MATERIALS AND METHODS: We reviewed 647 sonograms of 232 patients obtained over an 8-year period. One hundred fifty-two patients had at least two sonograms. One hundred fifty-four men and 78 women with a mean age of 51 years were included. Most patients (n = 207) had biopsy-proven cirrhosis. Ethnicity, age, gender, type of liver disease, and alpha-fetoprotein levels were analyzed to determine factors associated with HCC detection. The costs of sonography and other tests were calculated using the Australian government Medicare benefits schedule. RESULTS: Thirty-one patients (13%) had elevated alpha-fetoprotein levels. Liver masses were found in 25 (11%) patients. Six (2.6%) patients had HCC on biopsy (n = 3) or other tests. All cases of HCC were inoperable because of tumor multicentricity or metastases (n = 2) or both, or because of the relatively large size or poor physical condition of the patient (n = 4) or both. The only variable associated with detection of HCC was alcohol-related liver disease (p = .01). Of the six patients with HCC, one had an elevated alpha-fetoprotein level. The yearly incidence of HCC was 1.4%. Other masses shown by sonography included regenerating nodules (n = 5), hemangiomas (n = 5), focal fat sparing (n = 4), metastases (n = 2), and other lesions (n = 3). No patient underwent surgical resection, which precluded calculation of a survival benefit. The cost of our screening program was $8472 (United States dollars) per HCC. CONCLUSION. Sonographic screening is superior to alpha-fetoprotein assay for detection of HCC, but in this study, screening did not decrease mortality.

Adult↗
PubMed1997

Comparing dichotomous screening tests when individuals negative on both tests are not verified.

Two dichotomous screening tests are often compared by performing both tests in a sampled population, and submitting positive results on either test to verification by the reference standard. Unbiased estimates of the true positive and false positive rates of each test cannot be estimated directly. However, unbiased estimates of the relative true positive and relative false positive rates may be obtained. When one test has a higher true positive rate at the expense of a higher false positive rate, the trade-off is represented by the ratio of extra false positives detected to extra true positives detected. A 95% confidence interval for this ratio is derived. This ratio is prevalence dependent and only applies to the sampled population. For target populations of different prevalence, estimates of the ratio may be obtained if one of the following applies: (i) the test characteristics of one test are known; (ii) the relative prevalence is known; and (iii) certain assumptions are made.

Data Interpretation, Statistical↗
PubMed1997

The association between external weather conditions and pain and stiffness in women with rheumatoid arthritis.

OBJECTIVE: To determine the self-reported prevalence of weather sensitivity in a sample of female patients with rheumatoid arthritis (RA), and to determine if there is objective evidence of associations between weather and pain and stiffness in female patients with RA. METHODS: Fifty-three female patients residing in the Sydney metropolitan area participated in a study on the psychological determinants of disability from 1985 to 1987. During the study, subjects recorded pain on a visual analog scale and duration of morning stiffness for 14 day periods at 3-4 monthly intervals over 1-3 years (X = 15.7 months). After completion of the study, data on weather conditions were collected from the Bureau of Meteorology for the days that pain and stiffness records were made. Descriptive statistics and autoregression were used to analyze the data. RESULTS: Sixty percent of subjects reported that they were sensitive to weather. Six weather variables made a statistically significant contribution to daily pain score (p < 0.0001). However, they accounted for only 2.5% of the variance. Two weather variables contributed to duration of morning stiffness (p < 0.0001), but again these variables accounted for only a small portion of the variance (1.1%). A separate analysis for pain was carried out on the data from subjects who reported being weather sensitive. The results were consistent with those of the other analyses, with 2 variables accounting for only 1.7% of the variance (p < 0.0001). CONCLUSION: On the basis of these results it appears that weather makes only a minimal contribution to pain and stiffness in women with RA. The study may have been limited by its use of static measures of weather variables and pain. Further research using dynamic measures of pain and weather and a more extensive range of weather variables is needed.

Arthritis, Rheumatoid↗
PubMed1997

Treating grouped data as continuous in alcohol consumption measures.

In quantity-frequency methods used for self-report measurement of alcohol intake (or other exposures), respondents mark the appropriate ranges, e.g. '5 to 8 drinks', '5 or 6 times per week'. To calculate average consumption only single values, not ranges, can be multiplied, and midpoints are commonly used. This results in bias if the range lies in the tail of a distribution, as often happens with drinks per occasion. The same bias occurs when risk, for example, is plotted against consumption levels, which inevitable are grouped into ranges. Consequently, estimates of aggregate consumption can be exaggerated and curves of risk against exposure level can be misleading. A method is described to calculate a relatively unbiased representative value for a range, requiring only knowledge of the normal distribution table, the log-normal distribution, and basic arithmetic. Part of the procedure is also useful for estimating percentile points in data that have been grouped differently, such as income in dollar groups.

Alcohol Drinking↗
PubMed1996

Sexual health and use of condoms among local and international sex workers in Sydney.

OBJECTIVES: To compare indicators of sexual health and predictors of condom use for commercial sex among local and international female sex workers first attending an STD clinic. SETTING: A public STD clinic in Sydney, Australia. SUBJECTS: All sex workers first attending between June 1991 and May 1993. METHODS: Cross-sectional analysis of demographic, behavioural and morbidity data from proforma medical records. RESULTS: 91 local sex workers and 123 international sex workers (predominantly from Thailand, Malaysia and China) first presented during the study period. There were significantly higher prevalences of chlamydia (0 v. 15%, p = 0.0002), gonorrhoea (0 v. 14%, p = 0.0006), syphilis (0 v. 10%, p = 0.006) and clinical genital herpes (0 v. 5%, p = 0.04) among international sex workers. The only case of HIV infection was in an international sex worker. Inconsistent condom use for commercial sex was significantly more common among international sex workers (RR = 4.5; 95% CI 3.1-6.5). On multivariate analysis, inconsistent condom use in international sex workers was associated with a recent history of prostitution outside Australia (p = 0.04), while inconsistent condom usage among local sex workers was associated with increasing age (p = 0.003). CONCLUSIONS: These data illustrate the efficacy of condoms and the success of targeted education programmes in local sex workers in Sydney. By contrast, international sex workers continued to be at high risk of STDs. The international sex industry in Sydney requires enhanced culture-specific interventions. Immigration laws as they affect sex workers should also be reviewed.

Adult↗
PubMed1995

Are health undertakings effective in the follow-up of migrants for tuberculosis?

OBJECTIVE: To determine the rate of compliance of migrants issued with a health undertaking for tuberculosis requiring them to report within one month after arrival in Australia. DESIGN: Compliance was monitored prospectively between 1 November 1992 and 31 October 1993. SETTING: The Australian Government Health Service in Melbourne. PARTICIPANTS: 1660 migrants with a health undertaking for tuberculosis. MAIN OUTCOME MEASURE: Compliance with the undertaking (making initial contact and presenting for examination). RESULTS: The overall compliance rate was 58%, but 89% of those who made contact complied with their undertakings. There were significant differences in the compliance rates according to country of application (P < 0.001). It was estimated that about 150 people a year who require treatment for tuberculosis could be failing to comply with a health undertaking, eight of whom may require a full course of antituberculous chemotherapy. CONCLUSIONS: The administration of the current system of health undertakings for tuberculosis for migrants needs to be strengthened to increase compliance.

Australia↗
PubMed1995

Preliminary experience with the Endovascular Technologies bifurcated endovascular aortic prosthesis in a calf model.

PURPOSE: The purpose of this study was to develop a bifurcated endoluminal prosthesis for transfemoral placement in the aortoiliac position with a large-animal model that would simulate human implantation. METHODS: Fifteen calves (160 to 200 kg) underwent bilateral femoral artery exposure and transfemoral placement in the aortoiliac position of a bifurcated Dacron prosthesis, inserted through a 26F sheath with an over-the-bifurcation guide wire to retrieve the contralateral limb and secured proximally and distally with self-expanding attachment systems. The preferred location was determined before implantation and compared with final implant location by caliper measurements and angiography. Events during implantation, maneuvers used to accomplish accurate deployment, and final results, as judged by angiography and clinical evaluation, were recorded. Four animals survived and were used for chronic evaluation and healing by gross and microscopic studies. RESULTS: All grafts (n = 15) were patent at the end of the procedure. All (n = 7) noncrimped grafts had minor kinks in areas of curvature, whereas eight of eight crimped grafts (device modification) had none. Torque control of the body and individual limbs was necessary to correct twists before deployment in 10 of 15 grafts, with two greater than 30-degree twists remaining, which did not appear to affect flow. One implant was entirely deployed in the aorta because of parallax error, subsequently avoided by use of a marker board placed dorsally. Three premature deployments occurred, corrected by attachment system lock modification. The mean final implant position was within 2.9 +/- 1.4 mm (aortic), 1.6 +/- 1.1 mm, and 1.5 +/- 0.8 mm (contralateral and ipsilateral iliac limbs, respectively) of the intended position. Three of four animals intended for long-term evaluation were killed prematurely because of clinically evident spinal cord ischemia. Histologic sections at 2 weeks showed early wall repair without inflammatory cells and pannus ingrowth across the anastomosis. CONCLUSION: We conclude that implantation of a bifurcated endovascular prosthesis through the bilateral femoral approach is possible, provided the intended aortic implantation site (neck) is at least 12 mm in length (mean +/- 2 SD each direction). Torque control of each portion of the device will be needed in the majority of instances, with attention to parallax effect necessary for optimal placement. This animal model is not suitable for chronic graft evaluation because of its sensitivity for spinal cord ischemia. Healing data suggest graft incorporation similar to that of a surgically placed prosthesis.

Animals↗
PubMed1994

Efficient study designs to assess the accuracy of screening tests.

Evaluating a screening test often requires estimation of test sensitivity and specificity with appropriately narrow confidence intervals and at least cost. If the major cost is the reference ("gold") standard, savings arise from reducing the large number of test negatives that are verified by the reference standard. On the basis of the formulae of Begg and Greenes (Biometrics 1983;39:207-15), the authors determine the optimal sampling strategy for test positives and test negatives to minimize the total sample size that needs to be verified for a given confidence interval width for sensitivity. Unless sensitivity is very high, verifying more test positives and fewer test negatives than would occur with equal sampling fractions is appropriate. For example, if the sensitivity is 0.7 and the specificity is 0.99, the optimal sampling strategy is for 6.2% of those verified to be test positives, compared with 1.7% in the case of equal sampling fractions. At a disease prevalence of 0.01, the 3.3-fold increase in test positives results in a saving of about 15% in the test negatives and 11% in the total verified sample size. Overall, savings are about 50% for a sensitivity of 0.3, but are negligible when sensitivity is greater than 0.8. Optimal sampling strategies for sensitivity do not materially alter confidence intervals for specificity. Figures are presented from which readers can easily obtain the optimal sampling strategy given an estimate of specificity, approximated by the proportion of screenees who are test negative, and the range of likely sensitivity.

Algorithms↗
PubMed1994

Mortality and cancer incidence of workers exposed to chrysotile asbestos in the friction-products industry.

Three studies provide data on this topic. The largest was at the Ferodo factory in the U.K. There was no evidence of an overall excess in mortality from all causes, and in particular no increase in mortality due to lung cancer. Also, there was no evidence of any dose-response effect for lung cancer. There were 13 mesotheliomas but for 10 of these there had been exposure to crocidolite whilst working on a special contract that only a small minority of the workforce were involved in. Another one had worked in an asbestos-cement factory for 20 years. This left two mesotheliomas, one unconfirmed, for which the only known exposure was to chrysotile asbestos. The second study was of a plant in Connecticut. There was a significant increase in mortality due to respiratory cancer, but this excess was greatest in those with less than 1 year's exposure and was unrelated to cumulative exposure. No mesotheliomas occurred. The third study was of two factories in Ontario manufacturing automotive components. There was a non-significant increase in lung cancer mortality but the majority of these had not worked in the departments where asbestos was used. There were two unconfirmed mesotheliomas, one of whom had worked with friction materials. In conclusion, the three studies show that, if there are any effects on mortality due to working in the manufacture of friction materials, these effects must be small.

Asbestos, Serpentine↗
PubMed1993

Does motion-induced grouping modulate the flanker compatibility effect?: A failure to replicate Driver & Baylis.

Several experiments explored the possibility that motion-induced grouping would modulate the spatial distribution of the flanker compatibility effect (FCE). Subjects were required to make a speeded decision about a central target letter embedded in a five letter string. On each trial the identity of the near or far letters was either compatible or incompatible with the correct response while the remaining letters were neutral. In contrast to the findings of Driver & Baylis (1989), when the far distractors and the target moved together while the near distractors remained stationary, we did not find that the FCE for the far distractors was greater than the FCE for the stationary near distractors. Moreover, the pattern of response latencies in this moving condition were not different from what we observed when all letters remained stationary. Accuracy was affected, but not in the direction predicted by the view that attention is directed to perceptual groups. Modulation of the distribution of attention in response to motion-induced grouping is not a robust phenomenon. Nevertheless, a simple spotlight model of attention is challenged by demonstrations in the literature that perceptual grouping mediated by static properties such as closure, colour and good continuation strongly influence the spatial distribution of the FCE and that the allocation of attention in search is strongly influenced by stimulus motion.

Adult↗
PubMed1993

Neoplastic disorders after pediatric heart transplantation.

BACKGROUND: Because of their life-long requirement for immunosuppressive therapy, neoplastic disorders could represent a significant threat to long-term survival in infants and children after heart transplantation. This study determined the incidence and clinical spectrum of neoplastic disorders in 80 pediatric patients who underwent heart transplantation between 1974 and 1992. METHODS AND RESULTS: Follow-up ranged from 6 to 189 months (mean, 50.0 months). Tumors occurred in 10 patients (12.5%). Time to detection ranged from 3.3 to 139.2 months (mean, 52.7 months). Tumor incidence was greatest in 9 patients transplanted before the cyclosporine era (44%) compared with the subsequent 71 patients (8.5%, P < .05). There was no increase in risk related to sex, age, underlying disease, or blood type; however, patients with tumors received higher initial doses of cyclosporine and prednisone and had more rejection episodes in the first 3 months (P < .05). There was an increased risk associated with anti-thymocyte globulin (33%, P < .05) but not with OKT3 (6%, P = NS). There were eight lymphoproliferative disorders (four B-cell, one T-cell, three not determined) and one hepatocellular and one squamous cell carcinomas. Six cases of lymphoproliferative disorder had in situ evidence of Epstein-Barr virus. Patients were treated by reducing immunosuppression (7), radiotherapy (2), and chemotherapy (1). There were five deaths: two tumor related and the others due to rejection, renal failure, and infection. Of 5 survivors, 1 had tumor recurrence 4 years after diagnosis, and 4 are disease free. CONCLUSIONS: Tumors represent a small but serious long-term risk to pediatric heart transplant recipients. The incidence in children transplanted in the cyclosporine era is similar to that in adults, and the majority of tumors are lymphoproliferative disorders that often regress by reducing immunosuppression.

Actuarial Analysis↗