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Biomedical subjects

Richard Watson

Publications and source records attributed to Richard Watson.

14 recordsLinked to original sources

Prostate HDR radiation therapy: a comparative study evaluating the effectiveness of pain management with peripheral PCA vs. PCEA.

INTRODUCTION: High dose rate (HDR) brachytherapy is considered one of the most advanced treatment technologies currently available for treatment of localized prostate cancer. It gives the advantage of applying higher dose radiation, with greater precision, directly to the tumor while sparing healthy tissue and surrounding organs, thereby resulting in fewer side effects. In this facility, the treatment requires an overnight stay in the hospital, in a supine position, with a perineal template sutured to the perineum to prevent catheter movement or dislodgement. PURPOSE: To compare the effectiveness of pain management for men with prostate cancer being treated with HDR brachytherapy using a peripheral patient controlled analgesia (PCA) or patient controlled epidural analgesia (PCEA). METHOD: A comparative study was conducted evaluating the effectiveness of two pain management methods for men with prostate cancer receiving HDR brachytherapy. Pain assesments were conducted by scoring pain from the Foley catheter, interstitial catheter (perineal) and back (lumbosacral), using the Brief Pain Inventory Scale. RESULTS: Patients receiving pain management with the PCEA experienced significantly less pain. CONCLUSIONS: These finding suggest that use of PCEA with bupivacaine and fentanyl is more effective in managing pain related to HDR brachytherapy for prostate cancer, and results in a positive patient outcome thereby improving patient satisfaction.

Analgesia, Epidural↗

High nuclear S100A6 (Calcyclin) is significantly associated with poor survival in pancreatic cancer patients.

Recent studies have reported elevated levels of S100A6 in pancreatic ductal adenocarcinoma cells. Here, we describe a detailed analysis of S100A6 expression in benign (n = 32), malignant (n = 60), and premalignant pancreatic ductal cells [96 pancreatic intraepithelial neoplasias (PanIN) from 46 patients]. S100A6 staining was more intense in malignant cells than in benign cells (P = 0.0001). In malignant cells, staining was higher in the nucleus than in the cytoplasm (P = 0.003). Univariate analysis revealed a significant decrease in survival time for patients with high levels of nuclear (P = 0.01) but not cytoplasmic (P = 0.20) S100A6. No evidence was found for an association between nuclear S100A6 expression and other variables, including gender, age at surgery, tumor size or grade, nodal metastases, resection margin, vascular invasion, perineural invasion, p53 or Smad4 levels (both linked to survival in previous studies), or the p65 subunit of nuclear factor-kappaB (a potential regulator of S100A6). Although nodal metastases and resection margin involvement were also associated with poor survival (P = 0.06 in both cases), multivariate analysis suggests that nuclear S100A6 is a significant independent indicator of survival (P = 0.003). Whereas PanIN 1a lesions showed a general absence of S100A6 staining, there was a progressive increase in the proportion of positively stained PanINs with increasing PanIN grade. In particular, we observed an increase in the frequency and intensity of nuclear staining. Our results suggest that up-regulation of S100A6 is an early event in pancreatic cancer development and that elevated levels of nuclear S100A6 may affect clinical outcome.

Biomarkers, Tumor↗

Expression of hemagglutinin esterase protein from recombinant mouse hepatitis virus enhances neurovirulence.

Murine hepatitis virus (MHV) infection provides a model system for the study of hepatitis, acute encephalitis, and chronic demyelinating disease. The spike glycoprotein, S, which mediates receptor binding and membrane fusion, plays a critical role in MHV pathogenesis. However, viral proteins other than S also contribute to pathogenicity. The JHM strain of MHV is highly neurovirulent and expresses a second spike glycoprotein, the hemagglutinin esterase (HE), which is not produced by MHV-A59, a hepatotropic but only mildly neurovirulent strain. To investigate a possible role for HE in MHV-induced neurovirulence, isogenic recombinant MHV-A59 viruses were generated that produced either (i) the wild-type protein, (ii) an enzymatically inactive HE protein, or (iii) no HE at all (A. Lissenberg, M. M. Vrolijk, A. L. W. van Vliet, M. A. Langereis, J. D. F. de Groot-Mijnes, P. J. M. Rottier, and R. J. de Groot, J. Virol. 79:15054-15063, 2005 [accompanying paper]). A second, mirror set of recombinant viruses was constructed in which, in addition, the MHV-A59 S gene had been replaced with that from MHV-JHM. The expression of HE in combination with A59 S did not affect the tropism, pathogenicity, or spread of the virus in vivo. However, in combination with JHM S, the expression of HE, regardless of whether it retained esterase activity or not, resulted in increased viral spread within the central nervous system and in increased neurovirulence. Our findings suggest that the properties of S receptor utilization and/or fusogenicity mainly determine organ and host cell tropism but that HE enhances the efficiency of infection and promotes viral dissemination, at least in some tissues, presumably by serving as a second receptor-binding protein.

Animals↗

A residual deficit for global motion processing after acuity recovery in deprivation amblyopia.

PURPOSE: In a case of bilateral deprivation amblyopia due to congenital cataracts, the global motion sensitivity for stimuli that were well within the passband of the amblyopic visual system were assessed. METHODS: A stochastic global motion stimulus was used, comprising spatially narrow elements with varied spatial frequency, density, contrast, and area distribution. To determine threshold, a two-alternate, forced-choice direction discrimination task was used. RESULTS: There was a selective deficit for global motion processing that was not due to the visibility of the stimuli and was nonselective for spatial scale. The eye with the more complete recovery (acuity 20/20) from pattern deprivation in childhood exhibited the more severe global motion deficit. discussion. The results suggest a primary extrastriate deficit in the dorsal pathway, possibly involving the middle temporal (MT) and the medial superior temporal (MST) cortical areas, that is unrelated to the acuity deficit thought to be in area V1. A similar deficit has recently been shown in strabismic amblyopia.

Amblyopia↗

Backing Bush.

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Letter↗

The effect of pranlukast on allergen-induced bone marrow eosinophilopoiesis in subjects with asthma.

We investigated the mechanisms by which leukotriene receptor antagonists decrease airway eosinophil number. In a randomized, double-blind crossover study, we examined the effects of 2 weeks of treatment with pranlukast 300 mg twice a day or placebo on allergen-induced changes in airway eosinophil number and bone marrow eosinophil progenitors in 15 subjects with mild asthma. Pranlukast treatment for 2 weeks decreased mean sputum eosinophil count from 0.15 x 10(6)/g (5.3% of cells) before treatment to 0.02 x 10(6)/g (0.7% of cells) after treatment (p < 0.05), whereas placebo did not. Pranlukast also decreased the eosinophil count (5.6% at 7 hours and 7.5% at 24 hours) (p < 0.05) after allergen inhalation compared with placebo (13.8% at 7 hours and 15.3% at 24 hours). There was a similar trend for sputum cells immunostaining for EG2, eotaxin, interleukin-5, and regulated upon activation, normal T cell expressed and secreted. Pranlukast also significantly attenuated the allergen-induced increase in the number of bone marrow eosinophil/basophil cfu (mean 0.3) at 24 hours compared with placebo (mean 6.2). The proportion of CD34(+) cells expressing the eotaxin receptor CC chemokine receptor 3, 24 hours after allergen inhalation, was also reduced by pranlukast. We conclude that, the cysteinyl leukotriene receptor antagonist, pranlukast, attenuates allergen-induced increase in airway eosinophils by decreasing bone marrow eosinophilopoiesis and airway chemotactic and eosinophilopoietic cytokines.

Adult↗

Role for cysteinyl leukotrienes in allergen-induced change in circulating dendritic cell number in asthma.

BACKGROUND: Dendritic cells are important antigen-presenting cells. After an allergen inhalation, their numbers rapidly decrease in circulation and increase in the airway mucosa. OBJECTIVE: To investigate whether allergen-induced changes in the number of circulating dendritic cells are mediated by cysteinyl leukotrienes. METHODS: In a randomized, double-blind, crossover study, we examined the effects of 2 weeks of treatment with pranlukast (a cysteinyl leukotriene 1 [CysLT1] receptor antagonist) 300 mg twice daily and placebo on allergen-induced changes in airway responses and circulating dendritic cells in 15 subjects with mild asthma. We examined by flow cytometry, before and at 3 hours and 24 hours after allergen inhalation, the proportion of myeloid (CD33+) and plasmacytoid (CD123+) dendritic cells (HLA-DR+, CD14-, CD16-) among all peripheral blood mononuclear cells. The fraction of dendritic cells expressing CysLT1 receptor was also determined. RESULTS: Compared with placebo, pranlukast significantly attenuated both the maximum early (by 55%) and the late (by 39%) asthma responses, the allergen-induced methacholine airway hyperresponsiveness, and the increase in macrophage inflammatory protein 1alpha and 3alpha in induced sputum. A significantly greater proportion of CD33+ cells (55%) expressed CysLT1 receptor compared with CD123+ cells (11%). Consistent with this, pranlukast prevented the allergen-induced decrease in CD33+ dendritic cells at 3 hours postallergen (mean Delta from baseline, +4.4%) compared with placebo (mean Delta, -8.4; P <.05), but not CD123+ cells. CONCLUSION: Pretreatment with pranlukast attenuated allergen-induced airway responses and the decrease in circulating myeloid dendritic cells, demonstrating a novel role of cysteinyl leukotrienes in dendritic cell trafficking.

Adult↗

Modelling consultation rates in infancy: influence of maternal and infant characteristics, feeding type and consultation history.

BACKGROUND: Severity of illness, sociodemographic factors, and breastfeeding have been identified as predictors of consultation rates in infants, and prescriptions for antibiotics have been found to increase future consultation rates in older children. The Baby Check trial (1996-1998) provided detailed information about consultations for 935 babies during their first 6 months. AIMS: To investigate potential predictors of consultation rates in babies. DESIGN OF STUDY: A 6-month cohort study of newborn babies originally enrolled into a randomised controlled trial. Maternal and infant characteristics were collected from hospital discharge records. Primary care consultation data for each baby were collected by case note review. SETTING: Thirteen general practices in Glasgow. METHOD: Multilevel models were used to analyse the number of consultations for each baby during its first 26 weeks, dependent upon the baby's age, the calendar month, maternal and infant characteristics, and previous consultations. RESULTS: The strongest predictors of consultation rates were previous consultations, particularly during the preceding week. Breastfed babies and those with older mothers consulted less often. A multilevel model was better than a fixed effects model, with considerable variation in consultation rates between babies. CONCLUSION: Infants' consultation rates over time can be analysed using multilevel models, if details of primary care consultations are available. These models can incorporate the effects of fixed variables and those that change during the follow-up period. Our findings add to previous research linking breastfeeding with reduced morbidity in infancy, and for that reason breastfeeding should continue to be promoted in primary care.

Adult↗

Mothers' use of and attitudes to BabyCheck.

A copy of BabyCheck was sent to 497 mothers shortly after the birth of their baby. Six months later they were sent a questionnaire asking about their use of and attitudes to, BabyCheck. Questionnaires were returned by 323 (65%) mothers; 215 (67%) of them reported reading BabyCheck, the majority found it easy to understand (74%) and agreed with the advice (67%). Eighty-four (26%) of the mothers who returned the questionnaires reported using BabyCheck when their baby was ill; of these, 71% agreed with the advice and 65% trusted the advice. None of the mothers had used the complete range of tests. This lead to our conclusion that BabyCheck is well accepted among mothers but is not used routinely as part of mothers' response to illness in their babies. BabyCheck requires introductory education to ensure that parents score all the tests and that the predictive power of BabyCheck is not compromised. Further evaluation of BabyCheck is needed to find its ideal role in the assessment and monitoring of infant illness.

Attitude to Health↗

Immunohistochemical localization of the retinoic Acid receptors in human prostate.

Retinoic acid receptors (RARs) are nuclear transcription factors that mediate the effects of retinoids. Aberrant expression and regulation of RARs have been linked to various malignancies, including steroid-related breast and cervical cancers. Our previous results also suggest that prostate cancer is associated with altered RAR signaling. To understand the relationship between RAR signaling and prostate cancer, the current study examined the cellular distribution of RAR-alpha, -beta, and -gamma in human prostate tissues exhibiting different pathologic conditions. In histologically normal epithelium, both RAR-alpha and -gamma were present throughout the epithelium with minimal nuclear accumulation. RAR-beta was present only in basal epithelial nuclei. On the contrary, RAR-alpha was significantly increased in the nuclei of luminal epithelial cells, and both RAR-beta and -gamma were increased in basal and luminal epithelial nuclei in glands exhibiting benign prostatic hyperplasia (BPH). RAR-alpha was also increased in luminal epithelial nuclei in glands exhibiting prostatic intra-epithelial neoplasia (PIN). In these glands, RAR-beta was persisting in basal epithelial nuclei that were also RAR-gamma positive. In low- and intermediate-grade cancerous glands, RAR-alpha was also significantly increased in luminal epithelial nuclei, and a strong RAR-gamma signal was seen in some cells. RAR-beta was absent in these glands. Both RAR-alpha and -gamma were also increased in high-grade cancer cells. In conclusion, current results demonstrated changes in cellular distribution of RAR-alpha and -gamma in human prostate tissues exhibiting different pathologies. These results suggest links between altered RAR signaling and deregulated cell growth and/or tumorigenic transformation of prostate epithelial cells.

Humans↗

Prospective study of quality of life of patients receiving treatment for prostate cancer.

BACKGROUND: No research was found that compared quality of life (QOL) outcomes of prostate cancer patients receiving intensity-modulated radiation therapies with prostate cancer patients receiving radical prostatectomy. OBJECTIVES: To (a) describe differences in QOL before and after three types of treatment for prostate cancer: radical prostatectomy, intensity-modulated radiation therapy + seed implantation (permanent brachytherapy), or intensity-modulated radiation therapy + high dose rate radiotherapy (temporary brachytherapy); and (b) investigate demographic, physical, and psychosocial variables that impact QOL of men with prostate cancer. METHODS: Data were collected on three occasions: baseline (prior to treatment), 1 month, and 3 months after beginning treatment. Measures included biographic data, physiological, and psychological measures. Analysis of variance and hierarchical regression were used to examine patterns, describe differences, and identify predictors of QOL in the three treatment groups. QOL was conceptualized as a multidimensional construct that included physical, psychological, social, and functional well-being and prostate cancer concerns. RESULTS: Groups differed significantly in bowel and urinary symptom scores and prostate cancer concerns at baseline, and in urinary and depressive symptoms at 3 months. There were no significant group differences at 1 month. DISCUSSION: Significant differences were found in QOL as measured with the Functional Assessment of Cancer Treatment-Prostate after treatment with radical prostatectomy, intensity-modulated radiation therapy + seed implantation, or intensity-modulated radiation therapy + high dose rate radiotherapy. Findings may provide healthcare providers with knowledge about treatment sequelae for prostate cancer, enable healthcare providers to educate patients about QOL outcomes of treatment for prostate cancer, and enable patients to make more informed treatment decisions.

Adult↗