Defining the need for local therapy in locally advanced prostate cancer: an appraisal of the MRC PR07 study.
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Antineoplastic Agents, Hormonal↗
Biomedical subjects
R Cowan
Publications and source records attributed to R Cowan.
Bladder cancer: worse survival in women from deprived areas.
In a case-note review of 120 women and 227 men presenting with muscle-invasive bladder tumours in 1998, survival was worse for women in 3 years of follow-up, with the greatest difference, of 19.9%, at 6 months. For more deprived women, 6-month survival was 52.3%, and 32 (37.2%) presented with advanced disease, compared with 73.5%, and three (8.8%) for less deprived women.
Aged↗
An evaluation of gemcitabines differential radiosensitising effect in related bladder cancer cell lines.
The aim of this study was to establish the radiosensitising properties of gemcitabine in a pair of related bladder tumour cell lines with differential radiosensitivity. The radioresistant bladder tumour cell line MGH-U1 and its radiosensitive mutant clone, S40b (both p53 mutant), had SF(2) values (surviving fraction at 2 Gy) of 0.98 and 0.64, respectively (P<0.001). Colony-forming assays showed that at 0.01 microM gemcitabine radiosensitisation occurred only in the S40b cell line (dose-modifying factor (DMF)=1.4). At 0.3 microM (killing 50% of cells), both cell lines were radiosensitised; DMF=2.25 and 1.2 for MGH-U1 and S40b, respectively. These data suggest that gemcitabine is an effective radiosensitiser in bladder cancer cell lines, with greater sensitisation in the radioresistant parental line-a feature that should be useful in a clinical setting.
Antimetabolites, Antineoplastic↗
5alpha-Androstane-3alpha,17beta-diol activates pathway that resembles the epidermal growth factor responsive pathways in stimulating human prostate cancer LNCaP cell proliferation.
5alpha-Androstane-3alpha,17beta-diol (3alpha-diol) is considered to have no androgenic effects in androgen target organs unless it is oxidized to 5alpha-dihydrotestosterone (5alpha-DHT). We used microarray and bioinformatics to identify and compare 3alpha-diol and 5alpha-DHT responsive gene in human prostate LNCaP cells. Through a procedure called 'hypervariable determination', a similar set of 30 responsive genes involving signal transduction, transcription regulation, and cell proliferation were selected in 5alpha-DHT-, 3alpha-diol-, and epidermal growth factor (EGF)-treated samples. F-means cluster and networking procedures showed that the responsive pattern of these genes was more closely related between 3alpha-diol and EGF than between 5alpha-DHT and 3alpha-diol treatments. We conclude that 3alpha-diol is capable of stimulating prostate cell proliferation by eliciting EGF-like pathway in conjunction with androgen receptor pathway.
Anabolic Agents↗
Randomized controlled trial to assess the effectiveness of a videotape about radiotherapy.
In a randomized controlled trial, the additional provision of information on videotape was no more effective than written information alone in reducing pre-treatment worry about radiotherapy. Images of surviving cancer patients, however, may provide further reassurance to patients once therapy is completed.
Adult↗
Therapeutic ultrasound and wound closure: lack of healing effect on x-ray irradiated wounds in murine skin.
OBJECTIVE: To evaluate the efficacy of ultrasonography as a therapeutic agent in wound healing. DESIGN: Randomized, controlled trial. SETTING: University animal laboratory. ANIMALS: Male BALB/c mice randomly allocated to 5 groups. INTERVENTIONS: In group 1, mice were left untreated; in groups 2 through 5, a well-defined area on the dorsum was exposed to 20Gy x-ray irradiation. Seventy-two hours postirradiation, all mice were anesthetized by inhalation (isoflurane anesthetic) and a 7 x 7mm area wound made on the dorsum. All wounds were videotaped alongside a marker scale 3 times weekly until closure was complete. Mice in groups 4 and 5 were treated with pulsed therapeutic ultrasound for 5 minutes, 3 times weekly at 1 and 3MHz, respectively (intensity, 0.5W/cm(2)); mice in group 3 received placebo ultrasound. Subsequently, the area of each wound was measured from video by using an image analysis system. MAIN OUTCOME MEASURE: Wound closure as a fraction of day zero. RESULTS: Irradiation caused a significant (p < .01) delay in the rate of wound closure by day 11. However, neither placebo ultrasound nor treatment at 1 or 3MHz affected the closure rate. CONCLUSION: These findings provide little evidence that 1 or 3MHz ultrasound applied to a radiation-impaired wound stimulates wound closure in mice.
Analysis of Variance↗
Impact of a neuroscience intensive care unit on neurosurgical patient outcomes and cost of care: evidence-based support for an intensivist-directed specialty ICU model of care.
Analysis of patient data from a new neuroscience intensive care unit (NSICU) permitted evaluation of whether such a specialty ICU favorably altered clinical outcomes in critically ill neuroscience patients, and whether such a care model produced an efficient use of resources. A retrospective review was performed to compare (1) the clinical outcomes, as defined by percent mortality and disposition at discharge, between patients with a primary diagnosis of intracerebral hemorrhage treated in 1995 in medical or surgical ICUs and those treated in the same medical facility in an NSICU in 1997; and (2) the efficiency of care, as defined by length of ICU stay, total cost of care, and specific resource use, between patients treated in the NSICU and national benchmark standards for general ICUs during the 1997 fiscal year (FY). In the latter, extracted patient population data on neurosurgery patients requiring ICU treatment during FY 1997 were used with the following adjacent-disease related group (A-DRG)-coded diseases: craniotomy with and without coma or intracerebral hemorrhage, and skull fracture with and without coma lasting longer than 1 hour. Outcome measures of percent mortality and disposition at discharge in patients with intracerebral hemorrhage were significantly improved (P < .05), compared with those in a similar cohort treated 2 years earlier in a general ICU setting. Also, patients treated in the NSICU had shorter hospital stays (P < .01 ) and lower total costs of care (P < .01) than a national benchmark. The data suggest that a neuroscience specialty ICU arena staffed by specialty-trained intensivists and nurses is beneficial.
Aged↗
Coculture of bladder urothelial and smooth muscle cells on small intestinal submucosa: potential applications for tissue engineering technology.
PURPOSE: Small intestinal submucosa is a xenogenic, acellular, collagen rich membrane with inherent growth factors that has previously been shown to promote in vivo bladder regeneration. We evaluate in vitro use of small intestinal submucosa to support the individual and combined growth of bladder urothelial cells and smooth muscle cells for potential use in tissue engineering techniques, and in vitro study of the cellular mechanisms involved in bladder regeneration. MATERIALS AND METHODS: Primary cultures of human bladder urothelial cells and smooth muscle cells were established using standard enzymatic digestion or explant techniques. Cultured cells were then seeded on small intestinal submucosa at a density of 1 x 105 cells per cm.2, incubated and harvested at 3, 7, 14 and 28 days. The 5 separate culture methods evaluated were urothelial cells seeded alone on the mucosal surface of small intestinal submucosa, smooth muscle cells seeded alone on the mucosal surface, layered coculture of smooth muscle cells seeded on the mucosal surface followed by urothelial cells 1 hour later, sandwich coculture of smooth muscle cells seeded on the serosal surface followed by seeding of urothelial cells on the mucosal surface 24 hours later, and mixed coculture of urothelial cells and smooth muscle cells mixed and seeded together on the mucosal surface. Following harvesting at the designated time points small intestinal submucosa cell constructs were formalin fixed and processed for routine histology including Masson trichrome staining. Specific cell growth characteristics were studied with particular attention to cell morphology, cell proliferation and layering, cell sorting, presence of a pseudostratified urothelium and matrix penetrance. To aid in the identification of smooth muscle cells and urothelial cells in the coculture groups, immunohistochemical analysis was performed with antibodies to alpha-smooth muscle actin and cytokeratins AE1/AE3. RESULTS: Progressive 3-dimensional growth of urothelial cells and smooth muscle cells occurred in vitro on small intestinal submucosa. When seeded alone urothelial cells and smooth muscle cells grew in several layers with minimal to no matrix penetration. In contrast, layered, mixed and sandwich coculture methods demonstrated significant enhancement of smooth muscle cell penetration of the membrane. The layered and sandwich coculture techniques resulted in organized cell sorting, formation of a well-defined pseudostratified urothelium and multilayered smooth muscle cells with enhanced matrix penetration. With the mixed coculture technique there was no evidence of cell sorting although matrix penetrance by the smooth muscle cells was evident. Immunohistochemical studies demonstrated that urothelial cells and smooth muscle cells maintain the expression of the phenotypic markers of differentiation alpha-smooth muscle actin and cytokeratins AE1/AE3. CONCLUSIONS: Small intestinal submucosa supports the 3-dimensional growth of human bladder cells in vitro. Successful combined growth of bladder cells on small intestinal submucosa with different seeding techniques has important future clinical implications with respect to tissue engineering technology. The results of our study demonstrate that there are important smooth muscle cell-epithelial cell interactions involved in determining the type of in vitro cell growth that occurs on small intestinal submucosa. Small intestinal submucosa is a valuable tool for in vitro study of the cell-cell and cell-matrix interactions that are involved in regeneration and various disease processes of the bladder.
Child↗
Characterization of cultured bladder smooth muscle cells: assessment of in vitro contractility.
PURPOSE: The contractile properties of in vitro cultured bladder smooth muscle cells (SMC) are unknown. This study characterized the in vitro contractile response of human and rat bladder SMC to several pharmacological agonists known to induce in vivo contraction of intact bladder muscle. MATERIALS AND METHODS: Human and rat bladder SMC were seeded separately within attached collagen lattices. Contractility of SMC was analyzed by measuring alterations in lattice diameter after exposure and release to the following contractile agonists: carbachol (10(-7)-10(-3) microM), calcium-ionophore (10 microM), lysophosphatidic acid (LPA) (1 microM), endothelin (0.1 microM), KCl (3.33 mmicroM) angiotensin II (10 microM), and serotonin (100 microM). Results were recorded as a mean reduction of the lattice diameter. In addition, immunohistochemical analysis for phenotypic markers of smooth muscle cell differentiation was performed on bladder SMC cultured within collagen lattices. Human palmar fascia fibroblasts, which have been previously well characterized by in vitro contractility and immunohistochemistry, were tested in parallel and used as controls for all the above experiments. RESULTS: Human SMC had significant contractile responses to calcium-ionophore (31% +/- 4 relative percent contraction, p <0.05), LPA (34% +/- 4, p <0.05), and endothelin (37 +/- 5%, p <05). There was no significant contraction in response to carbachol, angiotensin II, KCl, or serotonin. Rat bladder SMC had a similar contractile response but did not contract in response to endothelin. In contrast to human and rat bladder SMC, fibroblasts did not contract to calcium-ionophore. CONCLUSIONS: In vitro cultured bladder SMC demonstrate loss of contractile response to normal in vivo pharmacologic agonists. Both human and rat bladder SMC can be distinguished in vitro from fibroblasts based upon their lack of contractile response to calcium- ionophore. These results demonstrate the ability to further characterize cultured bladder SMC with in vitro contractility. Further characterization is essential if we are to advance our understanding of the clinical applicability of in vitro studies utilizing cultured bladder SMC.
Animals↗
Left-ventricle boundary detection from nuclear medicine images.
We present here a new algorithm for segmentation of nuclear medicine images to detect the left-ventricle (LV) boundary. In this article, other image segmentation techniques, such as edge detection and region growing, are also compared and evaluated. In the edge detection approach, we explored the relationship between the LV boundary characteristics in nuclear medicine images and their radial orientations: we observed that no single brightness function (eg, maximum of first or second derivative) is sufficient to identify the boundary in every direction. In the region growing approach, several criteria, including intensity change, gradient magnitude change, gradient direction change, and running mean differences, were tested. We found that none of these criteria alone was sufficient to successfully detect the LV boundary. Then we proposed a simple but successful region growing method--Contour-Modified Region Growing (CMRG). CMRG is an easy-to-use, robust, and rapid image segmentation procedure. Based on our experiments, this method seems to perform quite well in comparison to other automated methods that we have tested because of its ability to handle the problems of both low signal-to-noise ratios (SNR) as well as low image contrast without any assumptions about the shape of the left ventricle.
Heart Ventricles↗
A randomized trial comparing methotrexate and vinblastine (MV) with cisplatin, methotrexate and vinblastine (CMV) in advanced transitional cell carcinoma: results and a report on prognostic factors in a Medical Research Council study. MRC Advanced Bladder Cancer Working Party.
Transitional cell carcinomas may arise at any site within the urinary tract and are a source of considerable morbidity and mortality. In particular, patients with metastatic disease have a poor prognosis, with less than 5% alive at 5 years. A multicentre randomized trial comparing methotrexate and vinblastine (MV) with cisplatin, methotrexate and vinblastine (CMV) in advanced or metastatic transitional cell carcinoma was conducted in the UK. From April 1991 to June 1995, 214 patients were entered by 16 centres, 108 randomized to CMV and 106 to MV. A total of 204 patients have died. The hazard ratio (relative risk of dying) was 0.68 (95% CI 0.51-0.90, P-value = 0.0065) in favour of CMV. This translates to an absolute improvement in 1-year survival of 13%, 16% in MV and 29% in CMV. The median survival for CMV and MV was 7 months and 4.5 months respectively. Two hundred and eight patients objectively progressed or died. The hazard ratio was 0.55 (95% CI 0.41-0.73, P-value = 0.0001) in favour of CMV. Two hundred and nine patients symptomatically progressed or died. The hazard ratio was 0.48 (95% CI 0.36-0.64, P-value = 0.0001) in favour of CMV. The most important pretreatment factors influencing overall survival were WHO performance status and extent of disease. These two factors were used to derive a prognostic index which could be used to categorize patients into three prognostic groups. We conclude that the addition of cisplatin to methotrexate and vinblastine should be considered in patients with transitional cell carcinoma, taking into account the increased toxicity.
Aged↗
In vivo MR spectroscopy of human dementia.
Nuclear MR spectroscopy in low and medium magnetic fields yields well-resolved natural abundance proton and decoupled phosphorus spectra from small (1-10 mL) volumes of brain in vivo in minutes. With this tool, neurochemical research has advanced through identification and noninvasve assay of a specific neuronal-cf2Ncf1-acetylaspartate, glial (cf2myocf1-inositol)-markers, energetics and osmolutes, and neurotransmitters (glutamate, GABA). From these simple measurements, several dozen disease states are recognized, including birth injury, and white matter and Alzheimer disease. Together, these tools are having a major impact on neuroscience and clinical medicine.
Alzheimer Disease↗
In vivo magnetic resonance spectroscopy of human brain: the biophysical basis of dementia.
Nuclear magnetic resonance spectroscopy (MRS) in low and medium magnetic fields yields well-resolved natural abundance proton and decoupled phosphorus spectra from small (1-10 cc) volumes of brain in vivo in minutes. With this tool, neurochemical research has advanced through identification and non-invasive assay of specific neuronal--(N-acetylaspartate), glial (myo-inositol)--markers, energetics and osmolytes, and neurotransmitters (glutamate, GABA). From these simple measurements, several dozen disease states are recognized, including birth injury, and white matter and Alzheimer disease. Addition of stable isotopes of carbon (in man) or nitrogen (in experimental animals) has provided in vivo assays of enzyme flux through glucose transport, glycolysis, TCA-cycle, and the glutamine-glutamate-GABA system. Finally, a number of xenobiotics are recognized with heteronuclear NMR techniques. Together, these tools are having a major impact on neuroscience and clinical medicine. Through diagnosis and therapeutic monitoring, a new generation of in vivo metabolite imaging is expected with the advent of conforming RF coils and higher field NMR systems.
Animals↗
The gene for the naevoid basal cell carcinoma syndrome acts as a tumour-suppressor gene in medulloblastoma.
Individuals with naevoid basal cell carcinoma (Gorlin) syndrome are at increased risk of developing medulloblastoma in childhood. We have shown that approximately 5% of patients with Gorlin syndrome will develop this complication in the first few years of life, and in addition 10% of patients with medulloblastoma diagnosed at age 2 years or under have Gorlin syndrome. One out of three medulloblastomas occurring in patients with Gorlin syndrome was shown to have lost the wild-type allele on 9q, indicating that the Gorlin locus probably acts as a tumour suppressor in the development of this tumour. We have also confirmed this role in a basal cell carcinoma (BCC) from the same individual. Information from these families would suggest that Gorlin syndrome is more common than previously recognized and may not always be diagnosed on clinical grounds alone even in middle life.
Basal Cell Nevus Syndrome↗
Even More Precisely Assessing Children's Understanding of the Order-Irrelevance Principle
There are conflicting views of when children understand that the cardinality of a set is independent of the order in which the objects are counted. Some discrepancies between studies using similar tests may be due to children interpreting the experimenter as questioning the accuracy of their counting. Three studies are reported of children between 3 and 6 years old. In Experiments 1 and 2, more expected a count in a different order to yield the same number when they did not have to do any counting than when they had to count or monitor a puppet's counting. However, some also expected subtraction not to affect cardinality. In Experiment 3 substantially more children predicted correctly whether a recount would yield the same number than what the number would be. These variations may reflect the power of forms of questioning to orient the child toward principles or practice.
Journal Article↗
Within-subject comparison of speech perception benefits for congenitally deaf adolescents with an electrotactile speech processor and a cochlear implant.
This study assessed speech perception benefits for three congenitally deaf adolescents who used an electrotactile speech processor (Tickle Talker(TM)) and subsequently went on to use a Nucleus Minisystem 22 cochlear implant. Both devices provided significant and comparable benefits for all children in the device plus lipreading condition. All children benefited from the additional information provided by either the Tickle Talker(TM) or the cochlear implant, and were able to perceive speech information with these devices that was not available through either aided residual hearing or lipreading. None of the three children were able to understand open-set words or sentences using either hearing aids alone or Tickle Talker(TM) alone, without the aid of lipreading. Two of the children showed significant open-set speech perception benefits while using their cochlear implant alone.
Adolescent↗
State medical boards' position on chaperones.
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Humans↗
A reexamination of the cell-lineage data of E. O. Powell.
E. O. Powell carried out numerous experiments observing cell-generation times on bacteria. His statistical methodology, though quite advanced 40 years ago, can be enhanced by better models of dependence, by advanced computational methods, and by judicious use of robust methods. We reexamine Powell's data, focussing on his main interest in establishing whether there were indeed dependencies in generation times between cells with close filial connections.
Analysis of Variance↗