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Biomedical subjects

M Watson

Publications and source records attributed to M Watson.

At least 19 recordsLinked to original sources
PubMed2006

The EORTC QLQ-HDC29: a supplementary module assessing the quality of life during and after high-dose chemotherapy and stem cell transplantation.

High-dose chemotherapy followed by haematopoietic stem cell transplantation can be associated with high physical and emotional distress levels and reduced quality of life. Systematic prospective measurement of impact of therapy on patient quality of life can aid treatment choices and provide better patient information. We describe the development of a high-dose chemotherapy questionnaire module to supplement the European Organisation for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-C30). Phases 1-3 of module development were conducted in United Kingdom, Germany, Austria and Norway, according to EORTC QOL Group guidelines. Forty-eight quality of life (QOL) issues were generated from the literature searches and interviews with health care professionals (n=24) and patients (n=92). This produced a 50 item provisional module. Further testing in 169 patients resulted in the QLQ-HDC29 module, containing 29 items, conceptualised into six multi-item scales and eight single items. The EORTC QLQ-C30, supplemented by QLQ-HDC29 will provide a comprehensive QOL measure for the international clinical trials of high-dose chemotherapy.

Adolescent↗
PubMed2006

Preptin, another peptide product of the pancreatic beta-cell, is osteogenic in vitro and in vivo.

Several hormones that regulate nutritional status also impact on bone metabolism. Preptin is a recently isolated 34-amino acid peptide hormone that is cosecreted with insulin and amylin from the pancreatic beta-cells. Preptin corresponds to Asp(69)-Leu(102) of pro-IGF-II. Increased circulating levels of a pro-IGF-II peptide complexed with IGF-binding protein-2 have been implicated in the high bone mass phenotype observed in patients with chronic hepatitis C infection. We have assessed preptin's activities on bone. Preptin dose-dependently stimulated the proliferation (cell number and DNA synthesis) of primary fetal rat osteoblasts and osteoblast-like cell lines at periphysiological concentrations (>10(-11) M). In addition, thymidine incorporation was stimulated in murine neonatal calvarial organ culture, likely reflecting the proliferation of cells from the osteoblast lineage. Preptin did not affect bone resorption in this model. Preptin induced phosphorylation of p42/p44 MAP kinases in osteoblastic cells in a dose-dependent manner (10(-8)-10(-10) M), and its proliferative effects on primary osteoblasts were blocked by MAP kinase kinase inhibitors. Preptin also reduced osteoblast apoptosis induced by serum deprivation, reducing the number of apoptotic cells by >20%. In vivo administration of preptin increased bone area and mineralizing surface in adult mice. These data demonstrate that preptin, which is cosecreted from the pancreatic beta-cell with amylin and insulin, is anabolic to bone and may contribute to the preservation of bone mass observed in hyperinsulinemic states such as obesity.

Animals↗
PubMed2006

Interchangeability of Hepatitis A boosters, Avaxim and Vaqta, in healthy adults following a primary dose of the combined typhoid/Hepatitis A vaccine Viatim.

This study investigated the suitability of Avaxim and Vaqta as Hepatitis A booster vaccines 6 months after priming with the combined Hepatitis A/typhoid vaccine, Viatim. One hundred and twenty adults were randomly assigned to one of the three groups. Group A (reference group) received Avaxim then Avaxim (n = 40), Group B received Viatim then Avaxim (n = 41) and Group C received Viatim then Vaqta (n = 39). One month after booster vaccination, anti-Hepatitis A virus (anti-HAV) antibodies geometric mean concentrations (GMC) of subjects primed with Viatim were non-inferior to the group primed and boosted with the monovalent Hepatitis A vaccine Avaxim. Anti-Salmonella typhi capsular polysaccharide virulence antigen (anti-Vi) GMCs in groups primed with Viatim were protective and all vaccines were well-tolerated. Therefore, Viatim may be used as a primary HAV vaccine with either Avaxim or Vaqta as Hepatitis A boosters and it will provide the same protection as two doses of Avaxim.

Adult↗
PubMed2006

The feasibility and results of a population-based approach to evaluating prostate-specific antigen screening for prostate cancer in men with a raised familial risk.

The feasibility of a population-based evaluation of screening for prostate cancer in men with a raised familial risk was investigated by studying reasons for non-participation and uptake rates according to postal recruitment and clinic contact. The levels of prostate-specific antigen (PSA) and the positive predictive values (PPV) for cancer in men referred with a raised PSA and in those biopsied were analysed. First-degree male relatives (FDRs) were identified through index cases (ICs): patients living in two regions of England and diagnosed with prostate cancer at age < or =65 years from 1998 to 2004. First-degree relatives were eligible if they were aged 45-69 years, living in the UK and had no prior diagnosis of prostate cancer. Postal recruitment was low (45 of 1687 ICs agreed to their FDR being contacted: 2.7%) but this was partly due to ICs not having eligible FDRs. A third of ICs in clinic had eligible FDRs and 49% (192 out of 389) agreed to their FDR(s) being contacted. Of 220 eligible FDRs who initially consented, 170 (77.3%) had a new PSA test taken and 32 (14.5%) provided a previous PSA result. Among the 170 PSA tests, 10% (17) were > or =4 ng ml(-1) and 13.5% (23) tests above the age-related cutoffs. In 21 men referred, five were diagnosed with prostate cancer (PPV 24%; 95% CI 8, 47). To study further the effects of screening, patients with a raised familial risk should be counselled in clinic about screening of relatives and data routinely recorded so that the effects of screening on high-risk groups can be studied.

Age of Onset↗
PubMed2006

Feasibility of familial PSA screening: psychosocial issues and screening adherence.

This study examined factors that predict psychological morbidity and screening adherence in first-degree relatives (FDRs) taking part in a familial PSA screening study. Prostate cancer patients (index cases - ICs) who gave consent for their FDRs to be contacted for a familial PSA screening study to contact their FDRs were also asked permission to invite these FDRs into a linked psychosocial study. Participants were assessed on measures of psychological morbidity (including the General Health Questionnaire; Cancer Worry Scale; Health Anxiety Questionnaire; Impact of Events Scale); and perceived benefits and barriers, knowledge; perceived risk/susceptibility; family history; and socio-demographics. Of 255 ICs, 155 (61%) consented to their FDRs being contacted. Of 207 FDRs approached, 128 (62%) consented and completed questionnaires. Multivariate logistic regression revealed that health anxiety, perceived risk and subjective stress predicted higher cancer worry (P = 0.05). Measures of psychological morbidity did not predict screening adherence. Only past screening behaviour reliably predicted adherence to familial screening (P = 0.05). First-degree relatives entering the linked familial PSA screening programme do not, in general, have high levels of psychological morbidity. However, a small number of men exhibited psychological distress.

Aged↗
PubMed2006

Factors associated with emotional and behavioural problems among school age children of breast cancer patients.

To identify factors linked with emotional and behavioural problems in school age (6- to 17-year-old) children of women with breast cancer. Reports of children's emotional and behavioural problems were obtained from patient mothers, their healthy partners, the children's teacher and adolescents using the Child Behaviour Checklist and Mental Health subscale of the Child Health Questionnaire. Parents reported on their own level of depression and, for patients only, their quality of life. Family functioning was assessed using the Family Assessment Device and Cohesion subscale of the Family Environment Scale. Using a cross-sectional within groups design, assessments were obtained (N=107 families) where the patients were 3-36 months postdiagnosis. Risk of problems in children were linked with low levels of family cohesion, low affective responsiveness and parental over-involvement as reported by both child and mother. Adolescents reported family communication issues, which were associated with externalising behaviour problems. Maternal depression was related to child internalising problems, particularly in girls. Whether the mother was currently on or off chemotherapy was not associated with child problems nor was time since cancer diagnosis. These findings held across child age. Where mothers have early stage breast cancer, a substantial minority of their school-aged children have emotional and behavioural problems. Such cases are characterised by the existence of maternal depression and poor family communication, rather than by the mother's treatment status or time since diagnosis. Targeted treatments, which focus on maternal depression and family communication may benefit the children and, through improved relationships, enhance the patients' quality of life.

Adolescent↗
PubMed2006

Cytokine expression profiles of bovine lymph nodes: effects of Mycobacterium bovis infection and bacille Calmette-Guérin vaccination.

Cytokine expression in lymph nodes from cattle inoculated intranasally with Mycobacterium bovis was compared to that of non-infected animals using real-time polymerase chain reaction. The effect of M. bovis infection, 4 months post-challenge, was to suppress the expression of anti-inflammatory cytokines interleukin (IL)-4 and IL-10 as well as the pro-inflammatory cytokines tumour necrosis factor (TNF) and IL-6. Expression of interferon (IFN)-gamma and IL-12 was maintained. Animals vaccinated with bacille Calmette-Guérin responded differently to challenge with M. bovis. In particular, no decrease in expression of IL-4 or IL-6 was observed following challenge of vaccinated animals and decreased IFN-gamma was detected. Also, vaccinated animals had higher levels of IL-4 and IL-10 transcripts compared to unvaccinated animals following challenge. These changes in cytokine expression levels led to a significant shift in the IFN-gamma/IL-4 or IFN-gamma/IL-10 ratio within the lymph node following challenge. Challenged animals generally showed a strong Th1 bias that was not seen in animals vaccinated prior to challenge. An inverse correlation between the level of pathology and bacterial load within the lymph node and the expression of IL-4, IL-10 and TNF was also observed. These results suggest that in the lymph nodes of cattle with established tuberculosis and a persisting bacterial infection, maintenance of the pro-inflammatory response in combination with a suppressed anti-inflammatory response may control the infection but contribute to host-induced tissue damage. Vaccination, which reduces the bacterial load and consequently the IFN-gamma response, may result in less suppression of anti-inflammatory cytokines.

Animals↗
PubMed2006

Influenza related hospitalisations in Sydney, New South Wales, Australia.

BACKGROUND: Routine influenza vaccination for children aged 6-23 months has recently been recommended in the United States. Accurate assessment of influenza related burden of illness in children could support similar recommendations in other settings. However, routinely available data underestimate the role of influenza in causing hospitalisation, and indirect estimation methods face difficulties controlling for the concurrent circulation of respiratory syncytial virus (RSV). Recent studies from Hong Kong and the United States have used differing methods to estimate the true burden of influenza related hospitalisation, with disparate results. METHODS: Retrospective population based study of children less than 18 years of age from Sydney, Australia, 1994 to 2001. Using two previously reported methods, estimates of annual hospitalisation rates attributable to influenza were derived by comparison of mean hospitalisation rates for acute respiratory disease during periods of high influenza activity and low RSV activity (defined using virological surveillance data) and periods where both influenza and RSV activity were low. These estimates were compared to rates of hospitalisation where influenza was recorded as the principal discharge diagnosis. RESULTS: Hospitalisation rates attributable to influenza were up to 11 times higher, depending on the age group and method used, compared to rates calculated from principal discharge diagnosis codes. CONCLUSIONS: Although there remains considerable uncertainty in estimating influenza related morbidity by methods using excess hospitalisations, even minimum estimates of disease burden warrant consideration of routine influenza immunisation for all children less than 2 years of age. Such estimates, derived from principal discharge diagnosis codes, are available in most settings.

Acute Disease↗
PubMed2006

Lactoferrin and bone; structure-activity relationships.

The maintenance of the mechanical integrity of the skeleton depends on bone remodeling, the well-coordinated balance between bone formation by osteoblasts and bone resorption by osteoclasts. The coupled action of osteoblasts and osteoclasts is regulated by the action of many local and circulating hormones and factors as well as central regulation by a neurological mechanism. We have previously shown that lactoferrin can promote bone growth. At physiological concentrations, lactoferrin potently stimulates the proliferation and differentiation of primary osteoblasts and acts as a survival factor. Lactoferrin also affects osteoclasts, potently inhibiting their formation. In vivo, local injection of lactoferrin results in substantial increases in bone formation and bone area. In a critical bone-defect model in vivo, lactoferrin was also seen to promote bone growth. The mitogenic effect of lactoferrin in osteoblast-like cells is mediated mainly through low-density lipoprotein-receptor protein-1 (LRP1), a member of the low-density lipoprotein-receptor-related proteins that are primarily known as endocytic receptors; however, LRP1 is not necessary for the anti-apoptotic actions of lactoferrin. Lactoferrin also induces the activation of p42/44 mitogen-activated protein kinase (MAPK) signalling and the PI3-kinase-dependent phosphorylation of Akt in osteoblasts. In this study, we examined other properties of lactoferrin and the way they affect osteogenic activity. The degree of glycosylation, iron-binding, and the structure-activity relationships indicate that lactoferrin maintains osteogenic activity in deglycosylated, holo, and apo forms, and in with various small fragments of the molecule. These data suggest that lactoferrin signals through more than 1 membrane-bound receptor to produce its anabolic skeletal effects, and that it signals through diverse pathways. We conclude that lactoferrin might have a physiological role in bone growth and healing and a potential therapeutic role as an anabolic factor in osteoporosis.

Amino Acid Sequence↗
PubMed2005

The association of respiratory viruses, temperature, and other climatic parameters with the incidence of invasive pneumococcal disease in Sydney, Australia.

BACKGROUND: Increases in incidence of invasive pneumococcal disease (IPD) during the colder months of the year in temperate regions are well recognized, but few detailed studies of possible interactions are available. We examined the relationship between virus activity, climatic parameters, and IPD during a winter in which there were separate peak incidences of influenza and respiratory syncytial virus (RSV) infection. METHODS: We performed an ecological study that correlated population-based data on IPD and respiratory virus activity in the year 2000 in metropolitan New South Wales, Australia, with climatic parameters, including weekly mean maximum and minimum temperature, relative humidity, rainfall, and wind speed. RESULTS: In children, RSV activity was significantly positively correlated with IPD activity (r = 0.578; P = .002) but not with influenza virus activity. There was a weak inverse relationship between parainfluenza virus activity and IPD activity (r = -0.401; P = .043) and a stronger inverse relationship between weekly mean maximum temperature (r = -0.458; P = .001), weekly mean minimum temperature (r = -0.437; P = .001), and IPD activity. In adults, there was no significant correlation between RSV or influenza virus activity alone and IPD, but the combination of RSV and influenza was significantly correlated with IPD (r = 0.481; P = .013). CONCLUSIONS: This study suggests that RSV infection and influenza contribute to IPD incidence peaks differently for children than for adults. Data from other geographic areas and more rigorous study designs are required to confirm these findings.

Adult↗
PubMed2005

Long-term outcomes of laparoscopic surgery for colorectal cancer.

Multiple reports have outlined the potential benefits of the laparoscopic approach to colon surgery. Recently, randomized control trials have demonstrated the safety of applying these techniques to colorectal cancer. This study examined the long-term follow-up assessment of patients after laparoscopic colorectal cancer resections and compared them with a large prospective database of open resections. A total of 231 resections were performed for adenocarcinoma of the colon or rectum between 1992 and 2004. Of these 231 resections, 93 were rectal (40.3%) and 138 were colonic (59.7%). A total of 8 (3.2%) of the resections were performed as emergencies, and 27 (11.7%) were converted to open surgery. The mean follow-up period was 35.84 months (range, 0-132 months). The disease recurred in 51 of the patients (22.1%) before death, involving 14 (6.1%) local and 37 (16%) distant recurrences. Only two patients had wound recurrences (0.8%), and both patients had widespread peritoneal recurrence at the time of diagnosis. The overall survival rate was 65.3% at 60 months and 60.3% at 120 months. The disease-free survival rate was 58% at 60 months and 56% at 120 months. Laparoscopic techniques can be applied to a wide range of colorectal malignancies without sacrificing oncologic results during a long-term follow-up period.

Adenocarcinoma↗
PubMed2005

[Nasopharyngeal carriage of Streptococcus pneumoniae in healthy children, 2 to 24 months of age, in New-Caledonia].

OBJECTIVES: The aims of this study were to determine the prevalence of pneumococcal nasopharyngeal carriage in New-Caledonian children less than two years of age, to define risk factors for carriage, and to document the serotypes present in New Caledonia prior to the implementation of the conjugate pneumococcal vaccine. METHOD AND RESULTS: From August 2002 to April 2003, nasopharyngeal samples were collected on 1040 children less than two years of age during scheduled visits to dispensaries for routine immunization. Of the 1040 samples, 544 (52%) were positive for Streptococcus pneumoniae. The percentage of pneumococcal strains with reduced susceptibility to penicillin (PRSP) was 21%. Several risk factors for pneumococcal carriage were identified. These included the Province that the child lived in, the ethnic group, age, and having a sibling less than 6 years of age. Risk factors for carriage of PRSP carriage were similar but also included additional risk factors such as attendance at day care and a history of antibiotic treatment. The eight most frequent serotypes were 6B, 19F, 14, 23F, 6A, 19A, 11A, and 16F. These serotypes accounted for 60% of all strains detected. The most frequent serotypes of PRSP were 14, 9 V, 19F, 23F, and 6B. They were more often identified in european children and 80% were vaccine serotypes. However, overall 250/544 (46%) of all pneumococcal isolates were those included in the 7 serotype vaccine.

Anti-Bacterial Agents↗
PubMed2005

Men's decision-making about predictive BRCA1/2 testing: the role of family.

Men who have a family history of breast and/or ovarian cancer may be offered a predictive genetic test to determine whether or not they carry the family specific BRCA1/2 mutation. Male carriers may be at increased risk of breast and prostate cancers. Relatively little is known about at-risk men's decision-making about BRCA1/2 testing. This qualitative study explores the influences on male patients' genetic test decisions. Twenty-nine in-depth interviews were undertaken with both carrier and noncarrier men and immediate family members (17 male patients, 8 female partners, and 4 adult children). These explored family members' experiences of cancer and genetic testing, decision-making about testing, family support, communication of test results within the family, risk perception and risk management. Implicit influences on men's testing decisions such as familial obligations are examined. The extent to which other family members--partners and adult children--were involved in testing decisions is also described. It is demonstrated that mothers of potential mutation carriers not only perceive themselves as having a right to be involved in making this decision, but also were perceived by their male partners as having a legitimate role to play in decision-making. There was evidence that (adult) children were excluded from the decision-making, and some expressed resentment about this. The implications of these findings for the practice of genetic counseling are discussed.

Attitude↗
PubMed2005

Influence of psychological response on breast cancer survival: 10-year follow-up of a population-based cohort.

The possibility that psychological response within a few weeks of a breast cancer diagnosis can influence the outcome of the disease is a contentious issue. Psychological response, including helplessness/hopelessness, fighting spirit and depression was assessed in early-stage breast cancer patients between 1 and 3 months post-diagnosis, in order to ascertain effect on cancer prognosis. Patients were followed up for a period of 10 years in order to clarify the effect of psychological response on disease outcome. After 10 years, there is a continuing effect of helplessness/hopelessness on disease-free survival (adjusted hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.11-2.11) but not of depression (adjusted HR for overall survival for 'cases' 2.43, 95% CI 0.97-6.10). Longer follow-up also indicates that a high fighting spirit confers no survival advantage. The results showed that, in patients who were disease-free at 5 years, their baseline helpless/hopeless response still exerted a significant effect on disease-free survival beyond 5 (and up to 10) years. The effect is therefore maintained for up to 10 years of follow-up. Clinicians may wish to screen for helplessness around the time of diagnosis in order to target psychological care resources. Further large studies, with similarly prolonged follow-up, are needed to replicate this effect and clarify its mechanism of action.

Adolescent↗
PubMed2005

Does genetic counseling have any impact on management of breast cancer risk?

Despite there being an increasing literature on the impact of cancer genetic counseling on risk perception and mental health, there is a lack of data describing impact on risk management. Genetic counseling and testing for cancer predisposition genes aims to improve the future health of those at high risk through appropriate surveillance and screening. However, management of breast cancer risk in women with a family history of this disease is an area of controversy. Counseling services may recommend specific risk management options to women, who then rely on their local screening service to make provision. This study investigated the impact of genetic counseling on management of breast cancer risk in women attending Cancer Family Clinics. A total of 293 women attending four genetic clinics were enrolled. Rates of breast self-examination, clinical breast examination, mammography, biopsy, detected cancers, and other screenings were documented. Participants' perceived benefits and barriers to mammography were assessed along with cancer worry. Results show that rates of mammography, clinical breast examination, and breast self-examination were increased following clinic attendance (p < 0.001). Women in the under 35 age-group had limited access to screening. Rates for biopsy and detected cancers were low. Women reported positive attitudes to mammography, with few reported barriers. Contrary to previous studies, there was no evidence that anxiety about breast cancer impedes uptake of health surveillance methods. Genetic counseling had a positive impact on management of breast cancer risk. Whether this translates into future health gains remains to be established.

Adult↗
PubMed2005

Communication about genetic testing in families of male BRCA1/2 carriers and non-carriers: patterns, priorities and problems.

This qualitative interview study explored the way in which information about predictive BRCA1/2 testing and its implications for children is disseminated within the families of at-risk men who undergo genetic testing. Twenty-nine in-depth interviews were carried out with family members [male patients (n = 17), their partners (n = 8) and adult children (n = 4)]. These explored the following themes: experiences of cancer and genetic testing, decision-making about testing and the communication of test results and genetic information within the immediate family. The interviews revealed that both male patients and their partners perceive themselves, rather than health professionals, as responsible for disclosing information about genetic testing and genetic risks to their children. Parents described three different communication strategies for the disclosure of genetic information to their children: complete openness, limited disclosure and total secrecy. The adoption of a particular communication strategy was justified in terms of children's rights to information vs their parental duties to protect their children from anxiety-provoking information. Some of the problems arising from the adoption of different disclosure patterns are identified and the implications for clinical practice are discussed.

Adult↗
PubMed2005

Distribution of Streptococcus pneumoniae serotypes responsible for penicillin resistance and the potential role of new conjugate vaccines in New Caledonia.

Invasive pneumococcal disease is a significant cause of morbidity and mortality worldwide. The aim of this study was to establish the serotypes responsible for pneumococcal disease and the serotypes responsible for penicillin resistance in Noumea, New Caledonia. Isolates of Streptococcus pneumoniae from all body sites referred to the Microbiology Department of the Pasteur Institute in New Caledonia between May 1999 and May 2001 had serotyping and susceptibility testing performed. Basic demographic data on patients were also collected. A total of 298 isolates were included in the study. The most common serotypes were types 1 (20%), 23F (10%), 12F (8%), 19F (8%), and 6B (5%). The serotype distribution differed significantly with age, site of collection, and ethnicity. Overall, 280 of 298 (94%) of the isolates had serogroups that are included in the 23-valent vaccine. However, only 14 of 20 (70%) of the isolates associated with invasive disease from children younger than 5 years of age and 26 of 113 (23%) of invasive isolates from patients more than 5 years of age were included in the new 7-valent conjugate vaccine. Overall, reduced susceptibility to penicillin was found in 43 of 298 (14.4%) of the isolates, with 13% falling into the intermediate resistance category and only 5 (2%) being high-level resistant. A higher prevalence of penicillin resistance occurred in younger age groups and in European patients and involved specifically certain serotypes. The 7-valent conjugate pneumococcal vaccine has potential benefit for the New Caledonian population under 5 years of age and should be considered for future vaccines schedules.

Adult↗