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Biomedical subjects

R Newton

Publications and source records attributed to R Newton.

At least 19 recordsLinked to original sources
PubMed2007

Spectrum and presentation of pediatric malignancies in the HIV era: experience from Blantyre, Malawi, 1998-2003.

BACKGROUND: Data on childhood cancers in Africa are sparse, particularly since the spread of HIV. We aimed to document the frequency of pediatric cancers presenting to a large central hospital in Malawi, detailing the presenting features, initial investigations, and HIV status of these children. PROCEDURE: A retrospective audit of the spectrum and clinical presentation of cancers among children (<16 years) seen at Queen Elizabeth's Central Hospital (QECH), between 1998 and 2003. RESULTS: Seven hundred seven children with cancer were seen, the number of cases per year increased over the time period; 50% (351) had Burkitt lymphoma, 13% (89) had retinoblastoma, and 9% (61) had Kaposi sarcoma, with a variety of other tumors comprising the remainder. Kaposi sarcoma markedly increased in frequency over time. Histological verification of diagnosis was available for 49% (348). The proportion of children with cancer who were tested for HIV increased over time, but varied by cancer type. Amongst those tested, the seroprevalence was 93% (52/56) for children with Kaposi sarcoma, 4% (11/289) for those with Burkitt lymphoma, 31% (8/26) for those with other non-Hodgkin lymphomas, 7% (1/15) for those with Hodgkin disease, and 5% (5/103) for those with other cancers. CONCLUSIONS: The number of cases seen per year has increased over the study period for almost all cancers, but in particular for Kaposi sarcoma. Burkitt lymphoma remains the commonest pediatric tumor in Malawi. In the case of Burkitt lymphoma, non-Hodgkin lymphoma, and Kaposi sarcoma there is a significant difference in the presentation of HIV-seropositive and -seronegative children.

Burkitt Lymphoma↗
PubMed2006

Expression and regulation of prostaglandin E synthase isoforms in human myometrium with labour.

Since the controversies regarding the use of non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclo-oxygenase (COX)-2 antagonists for the treatment of preterm labour (PTL), more emphasis has been placed on investigating the terminal synthases involved in the production of prostaglandins (PGs) to allow more targeted therapy in PTL. Prostaglandin E(2) (PGE(2)) is synthesized by one of three enzymes, cytosolic prostaglandin E synthase (cPGES), microsomal PGES-1 (mPGES-1) and microsomal PGES-2 (mPGES-2). We have determined (i) the immuno-localization of all three PGES enzymes in lower segment pregnant human myometrium, (ii) the expression of PGES and COX-2 mRNA expression at term and preterm gestation with and without labour and (iii) the effect of interleukin (IL)-1beta on COX-2 and PGES mRNA and protein expression in human myometrial smooth muscle (HMSM) cell cultures. We show mPGES-1 protein located predominantly in myometrial and vascular smooth muscle cells (SMCs), whilst mPGES-2 protein is largely in stromal cells surrounding the SMC and cPGES is diffusely located throughout the myometrium. Expression of mPGES-2 mRNA increased with term labour and PTL and expression of COX-2 and mPGES-1 mRNA with term labour, whereas cPGES expression did not change. IL-1beta stimulated release of PGE(2) by HMSM cells and increased COX-2 and mPGES-1 mRNA and protein expression. Thus, COX-2 expression and mPGES-1 expression are co-ordinately up-regulated in lower segment myometrium with term labour and with IL-1beta treatment in HMSM cells.

Cells, Cultured↗
PubMed2006

Antibodies against six human herpesviruses in relation to seven cancers in black South Africans: a case control study.

BACKGROUND: Infections with certain human herpesviruses have been established as risk factors for some cancer types. For example, Epstein-Barr Virus is considered a cause of Burkitt's lymphoma and other immunosuppression related lymphomas, Hodgkin lymphoma, and nasopharyngeal cancer. Several other human herpesviruses have been linked to cancers but the totality of evidence is inconclusive. METHODS: We conducted a systematic sub-study from within an ongoing case control study of adult black South Africans to investigate the relationship between antibodies to six human herpesviruses and seven cancer groups that may be caused by infectious agents. Subjects had incident cancers of the oral cavity (n = 88), the cervix (n = 53), the prostate (n = 66), Hodgkin lymphoma (n = 83), non-Hodgkin lymphoma (n = 80), multiple myeloma (n = 94) or leukaemia (n = 203). For comparison, patients with other cancers (n = 95) or cardiovascular disease (n = 101) were randomly selected from within the study. Patients were interviewed and their blood was tested for IgG antibodies against HSV-1, HSV-2, VZV, EBV-EBNA, CMV and HHV-6 using enzyme linked immunosorbent assays. Because these viruses are highly prevalent in this population, optical density results from the assays were used as an indirect, quantitative measure of antibody level. RESULTS: There was significant variation in the mean log antibody measures for HSV-2, VZV, CMV and HHV-6 between the disease groups. However, none of the specific cancer groups had significantly higher mean log antibody measures for any of the viruses compared to either control group. In a more detailed examination of seven associations between cancers and herpesviruses for which there had been prior reports, two statistically significant associations were found: a decreasing risk of myeloid leukaemia and an increasing risk of oral cancer with increasing tertiles of antibodies against HHV-6 compared to all other patients (p-trend = 0.03 and 0.02, respectively). Odds ratios for the top tertile compared to the bottom tertile were 0.58 (95%CI 0.3-1.0) for myeloid leukaemia and 2.21 (95% CI 1.1-4.3) for oral cancer. CONCLUSION: In this population, using these tests for IgG, neither mean antibody measure nor high antibody measure against human herpesviruses 1-6 was strongly associated with any of the seven cancer groups. However, we may not have had sufficient power to detect weak associations or associations with a sub-type of cancer if they were present.

Journal Article↗
PubMed2006

A prospective study of Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus in adults with human immunodeficiency virus-1.

Antibody titres against Kaposi's sarcoma associated herpesvirus (KSHV or human herpesvirus 8 (HHV-8)) and Epstein-Barr virus (EBV) were examined in people who subsequently developed Kaposi's sarcoma and non-Hodgkin's lymphoma, within randomised controlled trials of antiretroviral therapy in adults infected with the human immunodeficiency virus-1 (HIV). For each case of Kaposi's sarcoma (n=189) and each case of non-Hodgkin's lymphoma (n=67), which developed after randomisation, one control was randomly selected from other trial participants, after matching for age, sex, ethnicity, mode of HIV transmission, type of treatment received and period of follow-up. Using sera taken an average of two and a half years before the diagnosis of cancer, titres of antibodies against KSHV latent (LANA) and lytic (K8.1) antigens and against EBV (VCA) antigens were investigated in relation to subsequent risks of cancer by calculating odds ratios (OR) using conditional logistic regression. Latent antibodies against KSHV were detectable among 38% (72 out of 189) of Kaposi's sarcoma cases and 12% (23 out of 189) of their controls (OR=4.4, 95% confidence intervals (CI) 2.3-8.3, P<0.001). The OR for Kaposi's sarcoma increased with increasing antilatent KSHV antibody titre (chi(2)(1) for trend=32.2, P<0.001). Lytic antibodies against KSHV were detectable among 33% (61 out of 187) of Kaposi's sarcoma cases and 19% (36 out of 187) of their controls (OR=2.0, 95% CI 1.2-3.4, P=0.003) and the OR for Kaposi's sarcoma increased with increasing antilytic KSHV antibody titre (chi(2)(1) for trend=6.2, P=0.02). Virtually, all cases and controls had anti-EBV antibodies detected and the OR for non-Hodgkin's lymphoma associated with a doubling of the anti-EBV antibody titre was estimated to increase by a multiplicative factor of 1.3 (95% CI 0.9-1.7, P=0.1). Kaposi's sarcoma was not associated with antibody levels against EBV (P=0.4) and non-Hodgkin's lymphoma was not associated with antibodies against KSHV (latent P=0.3; lytic P=0.5). Adjustment for CD4 count at the time of sample collection made no material difference to any of the results. In conclusion, among human immunodeficiency virus infected people, high levels of antibodies against KSHV latent and lytic antigens are strongly associated with subsequent risk of Kaposi's sarcoma but not non-Hodgkin's lymphoma. Antibody titre to EBV does not appear to be strongly associated with subsequent risk of Kaposi's sarcoma or non-Hodgkin's lymphoma in HIV infected people.

Adult↗
PubMed2006

Corneo-conjunctival carcinoma in Uganda.

AIMS: Since 1990, the incidence of conjunctival neoplasia has more than tripled in Uganda. It is known to be associated with exposure to solar ultraviolet radiation and to infection with the human immunodeficiency virus-1 (HIV). However, little is known about the most effective treatments. In this study, we report surgical outcomes among people with corneo-conjunctival squamous neoplasia in Uganda and investigate the role of HIV infection and other factors in the aetiology of the tumour. METHODS: Country-wide enrolment of participants; removal and histology of suspect lesions; HIV counselling and testing; home visiting of participants to determine outcomes. RESULTS: In 67 months between 1995 and 2001, 476 participants were enrolled (262 female, 214 male, median age 32 years). A total of 463 (97%) had eye-conserving removal of the lesion and 13 had other surgery. For 414, the histology was squamous neoplasia (184 invasive carcinoma, 230 intraepithelial). The prevalence of HIV infection in cases was 64%. In all, 96% were followed up for a median period of 32 months (range 0-81) after eye-conserving surgery during which time 13 (3.2%) had a recurrence. CONCLUSIONS: Surgery resulted in a low recurrence rate during the follow-up period and had minimal complications. The prevalence of HIV among cases was higher than expected on the basis of data from the general population, although about a third of cases were HIV-negative and had normal CD4 counts. No new cofactors were identified.

Adolescent↗
PubMed2006

Specialist dermatology clinics for organ transplant recipients significantly improve compliance with photoprotection and levels of skin cancer awareness.

BACKGROUND: Organ transplant recipients (OTRs) have 100-fold increased risk of developing squamous cell carcinomas. Cumulative exposure to ultraviolet radiation is the main risk factor and there is evidence that lack of dermatological surveillance may be responsible for poor levels of knowledge and photoprotection among OTRs. OBJECTIVES: This study evaluated whether routine consultation in a specialist OTR dermatology clinic improves understanding of skin cancer risk and compliance with photoprotection measures. METHODS: A cross-sectional questionnaire-based study was performed in a specialist OTR dermatology clinic at Bart's and the London NHS Trust, London, U.K. The subjects were 399 white-skinned patients under surveillance in a renal transplant clinic, who were sent a postal questionnaire from the renal transplant clinic. The main outcome measures were responses to the questionnaire regarding photoprotective practices and skin cancer risk awareness. RESULTS: Two hundred and ninety-two of 399 (73%) responded, of whom 89% had previously attended the specialist dermatology clinic. Ninety-six per cent recalled receiving photoprotection advice at least once (85% from dermatologists); 92% reported use of sunscreen; 88% specifically dressed to photoprotect themselves; 96% directly avoided sun exposure during summer; 68% were aware that an increased risk of skin cancer was the reason that extra photoprotective measures were important after a transplant. Photoprotective measures and level of skin cancer awareness were significantly lower in those responders who had never attended the specialist clinic. No obvious bias was identified among nonresponders. CONCLUSIONS: Skin cancer awareness and compliance with photoprotective measures in our patient population is generally greater than previously reported, suggesting that delivery of educational messages regarding skin cancer may be improved if provided in a specialist dermatological setting.

Cross-Sectional Studies↗
PubMed2006

Beyond the dogma: novel beta2-adrenoceptor signalling in the airways.

beta(2)-Adrenoceptor agonists evoke rapid bronchodilatation and are the mainstay of the treatment of asthma symptoms worldwide. The mechanism of action of this class of compounds is believed to involve the stimulation of adenylyl cyclase and subsequent activation of the cyclic adenosine monosphosphate (cAMP)/cAMP-dependent protein kinase cascade. This classical model of beta(2)-adrenoceptor-mediated signal transduction is deeply entrenched, but there is compelling evidence that agonism of beta(2)-adrenoceptors can lead to the activation of multiple effector pathways, which now compels researchers in academia and the pharmaceutical industry alike to think beyond the traditional dogma. Therefore, the regulation by beta(2)-adrenoceptor agonists of responses, including airways smooth muscle tone and the secretory capacity of the epithelium and pro-inflammatory/immune cells, may be highly complex, involving both cAMP-dependent and -independent mechanisms that, in many cases, may act in concert. In this article, the current status of beta(2)-adrenoceptor-mediated signalling in the airways is reviewed in the context of understanding mechanisms that may underlie both the beneficial and detrimental effects of these drugs in asthma symptom management.

Adrenergic beta-Agonists↗
PubMed2005

Effects of ultrasound on maternal-fetal bonding: a comparison of two- and three-dimensional imaging.

OBJECTIVES: The purpose of this study was to evaluate the effect of two-dimensional (2DUS) compared to three-dimensional ultrasound (3DUS) imaging on the maternal-fetal bonding process. METHODS: Fifty mothers who had 2DUS and 50 who had 2DUS and 3DUS were included in the study. A postpartum survey by telephone interview was carried out to assess maternal-fetal bonding. Bonding was evaluated by analysis of extent of prenatal image sharing, maternal ability to form a mental picture of the baby and mother's comments about their ultrasound images. Data were analyzed using the independent t-test, Chi-square and Mann-Whitney U-tests. RESULTS: Mothers who received 3DUS showed their ultrasound images to more people (median, 27.5; interquartile range, 14.5-40.0) than mothers receiving 2DUS alone (median, 11.0; interquartile range, 5.0-25.5) (P < 0.001, Z = -3.539). Eighty-two percent of the subjects screened with 3DUS had a greater tendency to form a mental picture of the baby postexamination compared to 39% of the 2DUS subjects (P < 0.001, Z = -3.614). Mothers receiving a 3DUS study were more likely to receive comments on the similarities/differences of the neonate compared to those having 2DUS studies. Furthermore, 70% of the mothers receiving 3DUS felt they 'knew' the baby immediately after birth vs. 56% of the mothers receiving 2DUS (P = 0.009, Z = -2.613). Both 2DUS and 3DUS experiences were positive, however, the comments made by the mothers undergoing 3DUS (n = 18) were more exclamatory (amazed, wonderful, fabulous) than those undergoing 2DUS (n = 4). Patients having a 3DUS examination consistently scored higher than those having a 2DUS examination alone for all categories of maternal-fetal bonding. CONCLUSION: 3DUS appears to more positively influence the perceptions of mothers to their babies postbirth compared to 2DUS. Specifically, mothers who had 3DUS showed their ultrasound images to a greater number of people compared to mothers who had 2DUS alone and this may represent mother's social support system. 3DUS may have a greater impact on the maternal-fetal bonding process.

Adult↗
PubMed2005

Association of body size estimation and age in African-American females.

This cross-sectional research study tested the hypothesis that body image estimates of African-American females differ as a function of age. To test this hypothesis, body image estimates of 379 African-American females, ranging in age from 16 to 96 years, were contrasted as a function of age group, while statistically controlling body mass index. Three body size estimates, current body size, ideal body size, and reasonable body size were measured using the Body Image Assessment for Obesity. The discrepancies between current and ideal body size estimates and between current and reasonable body size estimates were also analyzed to assess for differences in body size dissatisfaction. The study found that younger African-American women (16 to 35 years) differed from older African-American women (>35 years) on measures of body size dissatisfaction. Women in the age range of 26 to 35 years reported higher estimates of current body size in comparison to women older than 35 years. The youngest age group (16 to 25 years) reported thinner ideal body size goals in comparison to women who were slightly older (26 to 35 years) and women who were older than 75 years. The pattern of body image estimates across a large age range suggests that younger African-American women, in comparison to older African-American women, may have body images that may make them more susceptible to eating disorders.

Adolescent↗
PubMed2005

Efficacy of an internet-based behavioral weight loss program for overweight adolescent African-American girls.

OBJECTIVE: This randomized controlled trial tested the efficacy of an internet-based lifestyle behavior modification program for weight management in African-American girls. DESIGN: African-American girls were randomly assigned to an interactive behavioral internet program or an internet health education program, the control condition. The behavioral intervention included internet counseling and was highly interactive. The control intervention was a passive (non-interactive) educational program. Parents were also participants in the study. Participants in both treatment groups met in face-to-face sessions on four occasions over the first 12 weeks of a 6-month intervention. SUBJECTS: The study enrolled 57 African-American adolescent girls (ages 11 to 15 years) who were overweight or obese and had at least one biological parent who was obese [body mass index (BMI) >30 kg/m2]. Of the 57 participants, 50 (88%) completed the 6-month trial. MEASUREMENTS: Outcome data, including BMI, body weight, body composition, dietary intake, and weight loss behaviors were collected at baseline and 6-months later. A computer server tracked utilization of the websites. Participation in the program was measured by number of "hits" on the website. RESULTS: Compared to the control condition, adolescents in the behavioral treatment lost more body fat (group difference =1.6% body fat) and parents lost significantly more body weight (group difference =2.1 kg). Utilization of the behavioral website by adolescents and parents was associated with positive outcome. Dietary fat intake was lowered for adolescents and parents in the behavioral treatment group. CONCLUSION: An internet-based behavioral intervention was superior to internet-based health education and yielded decreased body fat for adolescent girls and decreased body weight for parents.

Absorptiometry, Photon↗
PubMed2004

Low socioeconomic status and risk for infection with human herpesvirus 8 among HIV-1 negative, South African black cancer patients.

Between January 1994 and October 1997, we interviewed 2576 black in-patients with newly diagnosed cancer in Johannesburg and Soweto, South Africa. Blood was tested for HIV-1 and HHV-8 antibodies and the study was restricted to 2191 HIV-1 antibody-negative patients. We examined the relationship between infection with HHV-8 and sociodemographic and behavioural factors using unconditional logistic regression models. Of the 2191 HIV-1 negative patients who did not have Kaposi's sarcoma, 854 (39.1%) were positive for antibodies against the latent nuclear antigen of HHV-8 encoded by orf73 in a immunofluorescence assay. Infection with HHV-8 was independently associated with increasing age (P trend = 0.02). For females, independent risk factors also included working in a paid domestic capacity (OR 1.63, 95% CI 1.09-2.44, P = 0.02), defining occupational status as economically non-active unemployed (OR 1.70, 95% CI 1.06-2.72, P = 0.03), having a state pension or being on a disability grant (OR 1.49, 95% CI 1.05-2.11, P = 0.02), using oral contraceptives (OR 1.43, 95% CI 1.03-1.99, P = 0.03) and having a delayed age at menarche (P trend = 0.04). The relationship between these variables and HHV-8 antibody status requires further, prospective study.

Adult↗
PubMed2004

Human papillomaviruses and cancer in Uganda.

In a case-control study in Uganda, we examined associations between different cancer sites or types in relation to antibodies against human papillomaviruses (HPV)-16, -18 and -45. For each cancer site or type, the control group comprised all other cancers excluding those known, or thought to be associated with HPV infection (cancers of the uterine cervix, penis and eye). Among controls the seroprevalence of antibodies was 11% (68/616) against HPV-16, 5% (29/605) against HPV-18 and 6% (35/605) against HPV-45. Antibodies against HPV-16 were significantly associated with only two cancers: uterine cervix [prevalence of antibodies 27% (51/191); odds ratio (OR) 2.0, 95% confidence interval (CI) 1.2-3.1, P=0.01] and penis [prevalence of antibodies 27% (4/15); OR 6.4, 95% CI 1.7-24.3, P=0.01]. For both cancers, the risk increased with increasing anti-HPV-16 antibody titre (Ptrend=0.01 for each). No cancer site or type was significantly associated with antibodies against HPV-18 and -45.

Adult↗
PubMed2004

Coxsackie B virus serology and Type 1 diabetes mellitus: a systematic review of published case-control studies.

BACKGROUND: Enteroviruses, in particular Coxsackie B4, have been implicated in the aetiology of Type 1 diabetes mellitus, but the epidemiological evidence has not been systematically evaluated. METHODS: Systematic review of evidence from published controlled studies of the relationship between Coxsackie B virus serology and incident or prevalent Type 1 diabetes mellitus. Studies were identified through a Medline search (1966 to 2002), supplemented by references from identified papers and hand search of relevant journals. All studies (full papers, abstracts or letters) with data adequate for calculation of unadjusted odds ratios (with 95% confidence intervals) for Type 1 diabetes mellitus in relation to Coxsackie B virus serology were included. RESULTS: The review included 26 case-control studies; no cohort study met the inclusion criteria. Odds ratios for Type 1 diabetes mellitus in serology-positive vs. serology-negative subjects ranged from 0.2 to 22.3. For Coxsackie B (any serotype) 7/13 studies had point estimates significantly greater than 1.0 (P < 0.05). For Coxsackie B3, Coxsackie B4 and Coxsackie B5-specific assays, 1/11, 6/17 and 1/11 studies, respectively, had point estimates significantly greater than 1.0. Summary odds ratios were not calculated because of doubts about the validity of individual study estimates, heterogeneity between studies, and the possibility of publication bias. CONCLUSIONS: The results of these studies are inconsistent and do not provide convincing evidence for or against an association between Coxsackie B virus infection and Type 1 diabetes mellitus. Better designed studies using effective assays are needed to resolve this important issue.

Case-Control Studies↗
PubMed2003

Infection with Kaposi's sarcoma-associated herpesvirus (KSHV) and human immunodeficiency virus (HIV) in relation to the risk and clinical presentation of Kaposi's sarcoma in Uganda.

A case-control study from Uganda found that the risk of Kaposi's sarcoma increased with increasing titre of antibodies against Kaposi's sarcoma-associated herpesvirus (KSHV) latent nuclear antigens, independently of HIV infection. Clinically, widespread Kaposi's sarcoma was more frequent among patients with HIV infection than in those without, but was not related to anti-KSHV antibody titres.

Adolescent↗