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Biomedical subjects

R Gray

Publications and source records attributed to R Gray.

At least 73 records · Page 4Linked to original sources
PubMed2002

Primary malnutrition. Can we always tell?

Patterns of disease in the English-speaking Caribbean have changed considerably over the past two decades. There has been a decrease in the incidence of common infectious diseases, an increase in the prevalence of chronic non-communicable disorders and an increase in the incidence and prevalence of HIV/AIDS. However, published estimates suggest that malnutrition continues to be a serious public health problem. It is possible that changing patterns of disease within the epidemiological transition may affect patterns of presentation of severe forms of childhood malnutrition. We have examined records of 435 children admitted to the clinical research ward of the Tropical Metabolism Research Unit (TMRU) from January 1, 1990, to December 31, 1999; among these were 25 children who were subsequently found to have severe childhood malnutrition (SCM) due to a defined medical or surgical disorder (i.e. secondary SCM). Among children with secondary SCM, the HIV/AIDS group was the largest and comprised 60% of these admissions. Regression analyses show that, over the ten-year period, there was a small, non-significant decline in the number of cases of primary SCM (incidence rate ratio, IRR = 0.99, 95% confidence interval = 0.96, 1.02, p = 0.98), while the number of cases of secondary SCM increased (IRR = 1.18, 95% CI = 1.03, 1.35, p = 0.02). These data are indicative of the need for continued vigilance in the evaluation of children who have clinical features of the syndromes of severe malnutrition and draw attention to the potential impact of HIV/AIDS in yet another area of healthcare delivery.

Child↗
PubMed2001

HIV incidence and sexually transmitted disease prevalence associated with condom use: a population study in Rakai, Uganda.

OBJECTIVE: Evidence of condom effectiveness for HIV and sexually transmitted disease (STD) prevention is based primarily on high-risk populations. We examined condom effectiveness in a general population with high HIV prevalence in rural Africa. METHODS: Data were from a randomized community trial in Rakai, Uganda. Condom usage information was obtained prospectively from 17,264 sexually active individuals aged 15-59 years over a period of 30 months. HIV incidence and STD prevalence was determined for consistent and irregular condom users, compared to non-users. Adjusted rate ratios (RR) of HIV acquisition were estimated by Poisson multivariate regression, and odds ratios of STDs estimated by logistic regression. RESULTS: Only 4.4% reported consistent condom use and 16.5% reported inconsistent use during the prior year. Condom use was higher among males, and younger, unmarried and better educated individuals, and those reporting multiple sex partners or extramarital relationships. Consistent condom use significantly reduced HIV incidence [RR, 0.37; 95% confidence interval (CI), 0.15-0.88], syphilis [odds ratio (OR), 0.71; 95% CI, 0.53-0.94] and gonorrhea/Chlamydia (OR, 0.50; 95% CI, 0.25-0.97) after adjustment for socio-demographic and behavioral characteristics. Irregular condom use was not protective against HIV or STD and was associated with increased gonorrhea/Chlamydia risk (OR, 1.44; 95% CI, 1.06-1.99). The population attributable fraction of consistent use for prevention of HIV was -4.5% (95% CI, -8.3 to 0.0), due to the low prevalence of consistent use in the population. CONCLUSIONS: Consistent condom use provides protection from HIV and STDs, whereas inconsistent use is not protective. Programs must emphasize consistent condom use for HIV and STD prevention.

Adolescent↗
PubMed2001

Global expression changes of constitutive and hormonally regulated genes during endometrial neoplastic transformation.

OBJECTIVE: Endometrioid endometrial carcinoma is caused by a combination of mutational events and hormonal factors. We used large-scale messenger RNA expression analysis to discover genes that distinguish neoplastic transformation and examine the patterns of tumor expression of those genes which are normally regulated during the menstrual cycle. METHODS: Expression of approximately 6000 unique genes was quantified in 4 normal (2 proliferative, 2 secretory) and 10 malignant endometria using Affymetrix Hu6800 GeneChip probe arrays. Expression differences between normal and malignant tissue groups were measured by a test of statistical significance comparing the individual t statistic for each gene to the distribution of maximum t statistics among all genes following 1001 permutations of the tissue group assignments (Permax test). Hormonally responsive genes, selected by comparison of proliferative and secretory subsets of normal endometria using a combination of filters applied to the group means and t test rankings, were then examined in the tumors. RESULTS: Fifty genes with a Permax <0.50 provided excellent discrimination between normal and malignant groups and were predominantly characterized by diminished expression levels in the cancers. We found that 100 genes which are hormonally regulated in normal tissues are expressed in a disordered and heterogeneous fashion in cancers, with tumors resembling proliferative more than secretory endometrium. CONCLUSION: Neoplastic transformation is accompanied by predominant loss of activity of many genes constitutively expressed in normal source tissues and absence of expression profiles which characterize the antitumorigenic progestin response.

Adult↗
PubMed2001

Hitting what one wants to hit and missing what one wants to miss.

When an observer gazes directly at a rigid spherical object moving at constant speed along a line directed at the head, both monocular and binocular retinal image correlates of time to collision (TTC) are available provided that the object is not too small. The monocular correlate is not available for very small objects and is invalid for rotating aspherical objects, while the binocular correlate is available only when the ratio (closing speed)/(distance) is sufficiently large. Both cues are maximally effective in the central visual field so it is helpful to foveate potential collision hazards. On the other hand, in the special case of prolonged periods of driving along a straight empty road it is important to vary the direction of gaze rather than continuously gazing straight ahead so as to avoid the local adaptation to retinal image expansion that can cause errors in judging TTC when only monocular information is available. A more benign effect of self-motion is a long-distance interaction between the TTC signal generated by the approaching object and the expanding flow pattern caused by self-motion. This interaction creates a margin of safety. We also discuss eye movement strategies in executing the following two tasks: estimating the direction of self-motion; hitting a cricket ball.

Automobile Driving↗
PubMed2001

Patient-health care provider communication during chemotherapy treatment: the perspectives of women with breast cancer.

Recognition that communication plays a central role in the provision of quality patient care has led to learning more about interactions between patients and their health care providers. The present study examined interactions between women with breast cancer and their cancer care specialists from the patients' perspective during the time the women underwent chemotherapy treatment. In total 40 women from two regional cancer centers were interviewed about their communication experiences. Prevalent themes identified from analysis of the interview transcripts could be classified into two main categories. One category focused on the nature of the information exchange and included the themes of interaction modes and the power of information. The second category reflected relationship issues and included the themes of roles and responsibilities and connectedness. From their narratives, several patient, professional, and contextual factors could be identified that influenced women's perceptions about the quality of their communication experience.

Adult↗
PubMed2001

Estrogen-receptor-directed neoadjuvant therapy for breast cancer: results of a randomised trial using formestane and methotrexate, mitozantrone and mitomycin C (MMM) chemotherapy.

BACKGROUND: We wanted to determine whether neoadjuvant systemic chemoendocrine therapy guided by the estrogen receptor (ER) status of the primary breast cancer, followed by conventional surgery and/or radiotherapy, reduces local and distant recurrence and improves survival compared with adjuvant treatment given conventionally postoperatively. PATIENTS AND METHODS: Two hundred ten patients with primary breast cancer (T1-T4, N0, N1-2) were randomised to receive treatment with neoadjuvant chemoendocrine therapy or conventional post-operative chemoendocrine therapy. Systemic therapy was based on the estrogen receptor (ER) status of the primary tumour obtained by trucut core biopsy. ER-negative patients received MMM chemotherapy (methotrexate (30 mg/m2), mitozantrone (7 mg/m2) and mitomycin (7 mg/m2) three-weekly for three months and ER-positive patients who were premenopausal received goserelin (3.75 mg monthly), and post menopausal women formestane (250 mg every two weeks) over three months. RESULTS: With a minimum of five years follow-up, there is no evidence of any survival benefit from the pretreatment neoadjuvant therapy regimen, with five year overall survival being 79% +/- 4.7% (neoadjuvant) and 87% +/- 3.4% (adjuvant). Similarly, there was no apparent benefit in terms of disease-free survival. There was, however, a significant reduction in the incidence of distant metastases in responders (4 of 51; 8%) compared with non-responders (17 of 49; 35%) (P < 0.01). There was a reduction in the need for surgery in responding patients with T1 and T2 tumours, since 10 of 74 (14%) had no detectable residual tumour, without any apparent increase in the risk of local or distant recurrence. CONCLUSION: In this study neoadjuvant treatment with endocrine or chemotherapy provided no obvious survival benefit to women with breast cancer. However, it does allow avoidance of surgery in some cases. Also, the patients whose tumours respond to neoadjuvant systemic therapy have a lower incidence of distant metastases after five year follow-up compared to those whose tumours fail to respond.

Adult↗
PubMed2001

Effect of induction chemotherapy and tandem cycles of high-dose chemotherapy on outcomes in autologous stem cell transplant for metastatic breast cancer.

We assessed the effect standard-dose induction chemotherapy and tandem cycles of high-dose chemotherapy (HDC) have on outcomes in metastatic breast cancer. One hundred and one women with metastatic breast cancer were enrolled in two non-randomized phase II studies. The first group of 64 patients (induction group) received four cycles of docetaxel 75 mg/m2 and doxorubicin 50 mg/m2. The next 37 patients did not receive induction (no induction group). Both groups received two (tandem) cycles of HDC. Blood-derived stem cells were collected after the first HDC cycle, processed using CD34+ cell selection and then reinfused after the second HDC cycle. Outcomes were compared between the two groups and also to patients participating in the Philadelphia (inter-group) randomized metastatic breast cancer transplant trial (PBT-01). Intent-to-treat analysis revealed no significant differences in complete response rates (37.5% vs 27%; P = 0.20), overall response (75% vs 71%), median progression free survival (PFS) (11.9 vs 8 months; P = 0.24) and overall survival (OS) (>36 vs 25 months; P = 0.16), in the induction vs no induction groups, respectively. Adjusting for differences in known baseline characteristics, induction group patients were found to have significantly longer PFS (P = 0.002), OS (P = 0.01) and more frequent conversion from a partial to complete response (58% vs < or = 13%, P < or = 0.0002) when compared with PBT-01 patients. Induction chemotherapy administered prior to tandem cycles of HDC does not appear to adversely affect outcomes in metastatic breast cancer patients. Outcomes in our induction group also compare favorably with those observed in PBT-01 and warrant further clinical investigation.

Adult↗
PubMed2001

The use of outcome measures to evaluate the efficacy and tolerability of antipsychotic medication: a comparison of Thorn graduate and CPN practice.

Assessing the tolerability and efficacy of treatment with antipsychotic medication is a vital part of mental health care. Research has suggested that many side-effects go undetected by clinicians and there is a need to use standardized assessment tools to ensure that treatments are comprehensively evaluated. The training of Community Psychiatric Nurses (CPNs), who provide much of patients' care, should focus on enhancing skills in using such assessments. This study aimed to examine differences in the use of standardized assessments of antipsychotic side-effects and psychopathology by CPNs and Thorn graduates who had received additional training in delivering psychosocial interventions. A questionnaire was sent to 240 Thorn graduates and CPNs practising in England, with an overall adjusted response rate of 54%. Thorn graduates reported using significantly more standardized assessments of side-effects and psychopathology than CPNs. A trend in both groups towards the use of measures that relied on patient self-report of side-effects was observed. This study identified important deficiencies in current CPN practice. A programme of targeted training may be a more realistic and efficient method of enhancing medication management practices in large numbers of CPNs compared to the more expensive and time-consuming Thorn programme.

Adult↗
PubMed2001

Exploring the link between time to collision and representational momentum.

Previous research has shown that when a moving object is occluded prior to collision with another stationary object, observers tend to consistently underestimate the physical/actual time to collision (TTC). We examined whether mislocalization of the initial point of disappearance plays any role in this underestimation. To assess the contribution of mislocalization, we coupled a standard TTC paradigm with a representational-momentum paradigm. Representational momentum refers to the tendency to mislocalize the remembered stopping point of a moving object as being too far forward along an actual or implied path of motion. Using identical displays we found large representational-momentum shifts and consistent underestimation of TTC. When the displays were modified to disambiguate the point of disappearance, representational momentum was absent or significantly reduced and underestimates of TTC were effectively eliminated. These results strongly suggest that the represented point of disappearance is an important factor in TTC estimation and that systematic forward displacement of this point may partially explain frequently observed underestimation.

Cues↗
PubMed2001

Prediction of node-negative breast cancer outcome by histologic grading and S-phase analysis by flow cytometry: an Eastern Cooperative Oncology Group Study (2192).

Histologic evaluation and reporting of invasive breast cancer has effectively used Nottingham combined histologic grade (NCHG). This approach to predict outcome in invasive breast cancer has not been tested in multicenter cooperative trials. Histologic slides from selected breast cancer cases entered on node-negative Eastern Cooperative Oncology Group trials were assigned grades. Two pathologists evaluated cases for NCHG defined from differentiation, mitotic index, and nuclear grade. The study population consisted of separate samples from low- and high-risk strata, where low risk was estrogen receptor positive with a tumor size of less than 3 cm and high risk was estrogen receptor negative or tumor size greater than or equal to 3 cm. The rate of agreement was generally good, with 80% of cases classified the same for mitotic count and 76% of the cases classified the same for combined grade. There were no cases disagreeing from the lowest to the highest of the three categories. The median follow-up is 11.6 years, but for analysis of survival, this was truncated at 5 years. Mitotic index and combined grade as assessed by both pathologists showed significant associations with survival. High combined histologic grade was predictive for response to cyclophosphamide/methotrexate/5-fluorouracil (CMF) with survival differences at 5 years of 30% in the treated high-grade patients over the untreated patients. Overall, it is clear that pathologists can have close agreement in assignment of combined histologic grades, with highly significant prediction in univariate and borderline significance in multivariate analysis in prognostication of time to recurrence as well as survival. Thus, stratification used in these trials was highly prognostic as hoped, leaving a role for histologic grading in these relatively large tumors, more powerful than S-phase analysis in this series. In the subgroups of high-risk patients randomized between CMF and observation, there was a suggestion that the high-combined-grade group was predictive of treatment efficacy. We conclude that a combined histologic grade with defined criteria may be reliably assigned by practiced pathologists using readily available criteria, and that the measure may be of use in prognostication and prediction of therapeutic responsiveness when done in a technically ideal fashion.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Systematic review of patient and nurse attitudes to depot antipsychotic medication.

BACKGROUND: Depot antipsychotic medication is used widely in the treatment and prophylaxis of severe mental illness. AIMS: To review the literature on patient and nurse satisfaction with, and attitudes towards, depots. METHOD: A systematic search of Medline, Embase, PsycINFO, CINAHL and The Cochrane Library was undertaken, along with citation searches. Studies were selected if satisfaction/attitude data were described in the title or abstract and original data were included. Study quality was rated. RESULTS: The search produced 1374 articles; 22 articles met the inclusion criteria, 18 of which were cross-sectional surveys. Of the 12 studies with relevant data, 10 conveyed a positive opinion of depot medication. Five out of six studies comparing depot with oral medication showed patient preference for depot. CONCLUSIONS: High-quality data examining patient and nurse attitudes regarding depot antipsychotics are sparse. What data there are show a positive attitude to depots from patients. Future randomised controlled trials should include satisfaction as an outcome.

Administration, Oral↗
PubMed2001

beta-Adrenergic regulation of IL-6 release from adipose tissue: in vivo and in vitro studies.

UNLABELLED: Circulating IL-6 levels are elevated in obesity. Although IL-6 is expressed in adipose tissue, neither its regulation nor cell of origin is well characterized. Here we investigated the beta-adrenergic regulation of IL-6 release in a combination of studies on humans and animals in vivo and cultured adipocytes in vitro. Human in vivo study: Human volunteers were infused with isoproterenol, norepinephrine, or saline [4 M:4F; mean (SD) age 35.5 (5.8) yr; body mass index 24.6 (4.2) kg/m(-2)]. Plasma IL-6 levels increased during a 3-h infusion of isoproterenol (P = 0.01) and fell 2 h post infusion (P = 0.05). IL-6 levels did not change significantly with either norepinephrine or saline. Murine in vivo study: C57BL6/J male mice were injected ip with dobutamine (beta(1) agonist), clenbuterol (beta(2)), CL316243 (beta(3)), or saline placebo. Plasma IL-6 levels at 3 h were increased by clenbuterol (P = 0.02) and CL316243 (P = 0.02) but not dobutamine (P = 0.51), compared with placebo. IN VITRO STUDIES: In human peripheral blood cells, lipopolysaccharide treatment enhanced secretion of IL-6 (vs. controls; P < 0.001), whereas isoproterenol inhibited IL-6 secretion (P = 0.012) and norepinephrine had no significant effect. In contrast, isolated human adipocytes and differentiated 3T3F442A adipocytes all rapidly secreted IL-6 in response to adrenergic agonists (P < 0.01, compared with untreated cells). We conclude that beta 2/beta 3 adrenoceptor stimulation on adipocytes, rather than macrophages, may be responsible for the increases in plasma IL-6 concentrations observed during sympathetic activation and in obesity.

Adipocytes↗
PubMed2001

Hypopituitarsim is associated with triglyceride enrichment of very low-density lipoprotein.

The dyslipidemia associated with hypopituitarism may contribute to increased vascular mortality. The atherogenic potential of lipoproteins is determined not only by concentration but also by their composition. We therefore studied very low-density lipoprotein composition and apolipoprotein B kinetics in 16 hypopituitary subjects and 16 controls. Hypopituitarism was associated with reduced high-density lipoprotein cholesterol (0.98[0.82-1.18] vs. 1.35[1.15-1.41] mmol/liter, P < 0.001) and increased triglyceride concentrations (1.64[1.09-2.77] vs. 1.12[0.66-1.67] mmol/liter, P = 0.01). Total (P = 0.76) and low-density lipoprotein cholesterol (P = 0.56) concentrations were similar. Very low-density lipoprotein- triglyceride was significantly increased (1.48[1.02-2.55] vs. 0.9[0.31-2.30] mmol/liter, P = 0.004), but very low-density lipoprotein cholesterol levels were similar (P = 0.93). The molar ratios of very low-density lipoprotein-triglyceride:apolipoprotein B (6193[4283-9566] vs. 3599[3188-6854], P = 0.005) and very low-density lipoprotein-triglyceride:cholesterol (2.8[1.98-3.78] vs. 1.6[1.44-2.80], P < 0.003) were significantly increased; very low-density lipoprotein-cholesterol:apolipoprotein B molar ratios (P = 0.93) were similar. Very low-density lipoprotein apolipoprotein B fractional synthetic rate (a measure of apolipoprotein B catabolism, P = 0.42) and pool size (P = 0.63) were similar. The very low-density lipoprotein apolipoprotein B absolute synthetic rate (a measure of apolipoprotein B synthesis) tended to be higher in hypopituitarism (17.7[2.91-19.50] vs. 26.6[19.64-28.05] mg/kg per day, P = 0.24) but failed to reach statistical significance. The absolute synthetic rate, and hence very low-density lipoprotein production, correlated with very low-density lipoprotein triglyceride:apolipoprotein B ratio (P = 0.02, Rs = 0.63), suggesting that triglyceride enrichment of very low-density lipoprotein is important in the mechanism underlying very low-density lipoprotein overproduction in hypopituitarism. Because triglyceride-enriched lipoproteins are proatherogenic, this may contribute to the vascular mortality observed in hypopituitarism. The reasons for these observations are unknown; GH deficiency or routine endocrine replacement may be important.

Adenoma↗