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Biomedical subjects

G Morton

Publications and source records attributed to G Morton.

At least 19 recordsLinked to original sources

The role of serial free/total prostate-specific antigen ratios in a watchful observation protocol for men with localized prostate cancer.

OBJECTIVE: To examine the change in the free/total prostate specific antigen ratio (f/tPSA) with time and to assess the potential value of serial measurements of f/tPSA as a determinant of disease progression in untreated, low-to-intermediate grade prostate cancer (T1b-T2b N0M0, Gleason score < or = 7 and PSA < or = 15 ng/mL). PATIENTS AND METHODS: In a prospective single-arm cohort study from November 1995, patients were conservatively managed with watchful observation alone unless they met arbitrarily defined criteria (clinical, histological and biochemical) of disease progression. Patients were followed regularly and underwent blood tests including PSA and f/tPSA. The initial and mean f/tPSA and the rate of change of f/tPSA with time were evaluated against the rate constant for the PSA doubling time (PSATd). Correlation analyses were used to evaluate any association between baseline clinical variables and either the rate of change of f/tPSA or initial f/tPSA. RESULTS: As of December 2000, 161 of a total of 206 accrued patients had three or more f/tPSA measurements and formed the basis of the study (median age 70 years; median follow-up 2.7 years). The median initial f/tPSA was 0.16; there was a significant negative correlation between this value and the initial total PSA. The mean f/tPSA and rate of change of f/tPSA with time were significantly negatively correlated with the rate constant for PSATd. Also, the rate of change of f/tPSA correlated negatively with clinical T stage, but not with other baseline variables, including initial PSA, age and Gleason score. CONCLUSION: The f/tPSA in men with untreated, clinically localized prostate cancer varied widely. The negative correlation between the rate of change of f/tPSA with time and rate constant for PSATd suggests that both might provide valuable information to allow clinicians to develop a strategy for optimizing the timing of therapeutic intervention for those patients choosing watchful observation alone.

Adenocarcinoma↗

The role of serial transrectal ultrasonography in a 'watchful waiting' protocol for men with localized prostate cancer.

OBJECTIVE: To determine the value of serial 6-monthly transrectal ultrasonography (TRUS) in a cohort of men with localized prostate cancer who consented to a programme of watchful waiting with selective delayed intervention. PATIENTS AND METHODS: Since November 1995, 180 men were accrued into an ongoing prospective study of watchful waiting with selective delayed intervention; 174 patients enrolled before 31 December 1999 comprised the cohort for the present study. The prospectively collected clinical data, including the TRUS reports, were reviewed systematically. Twenty-eight men met the arbitrarily predefined criteria of disease progression and required definitive treatment. The TRUS findings were scored as being consistent with the clinical scenario (i.e. clinical, biochemical or histological progression) if they reported a new or enlarging hypoechoic peripheral zone lesion, or a > or = 30% increase in overall prostate volume at the time of progression. In 136 men who had undergone two or more serial TRUS examinations the relationships between the rate of change of prostate-specific antigen (PSA) and changes in both gland volume and the number of hypoechoic lesions were also examined. RESULTS: The group of 28 men who progressed to require radical intervention underwent 83 TRUS examinations (median number per patient, three). Two men underwent TRUS only once at baseline because of progression within 6 months. Of these 28 men, only seven had changes on TRUS that were regarded as being consistent with progression; all seven consisted of the growth of an existing nodule or the appearance of a new nodule. In only one case was this accompanied by an increase of > or = 30% in gland volume. In the 136 men who underwent two or more serial TRUS examinations (median three, maximum nine), there was no correlation between the rate of change of PSA and changes in either gland volume or the number of peripheral zone hypoechoic lesions. CONCLUSION: The use of serial TRUS in men with known but untreated prostate cancer is of limited value as a determinant of disease progression.

Clinical Protocols↗

Controversies in prostate cancer radiotherapy: consensus development.

The GU Radiation Oncologists of Canada (GUROC) had a consensus meeting in November 2000 to discuss and develop consensus on four controversial areas: risk assessment of localized prostate cancer, conformal radiotherapy, role of brachytherapy in prostate cancer and combined hormonal therapy and radiotherapy for prostate cancer. The meeting was a success and resulted in consensus being achieved on a number of areas. The group agreed on three risk groupings: low risk, intermediate risk and high risk localized prostate cancer based on clinical stage, Gleason score and PSA level. The participants agreed that based on available toxicity data from randomized controlled trials, conformal treatment techniques should be offered to patients receiving prostatic radiotherapy. Consensus was reached on the role of dose escalation in each of the three risk groups and is summarized in the article. At present there is insufficient evidence from randomized clinical trials to recommend the use of brachytherapy over current other standard therapy (radical prostatectomy or external beam radiotherapy). Non randomized published studies show promising short and intermediate term results. Where ever possible patients should be approached about participation in ongoing RCT's evaluating brachytherapy versus current other standard therapy. Outside a clinical trial the participants felt permanent seed implants should be considered an acceptable treatment option for appropriate patients with low risk prostate cancer. Based on randomized controlled trials the group agreed that patients with high risk disease should be treated with prolonged (up to 2-3 years) adjuvant hormonal therapy. Part of this hormonal treatment may be given in a neoadjuvant fashion. The group agreed that adjuvant hormones should not be routinely used in low and intermediate risk patients. Neoadjuvant hormones have been demonstrated to improve outcome in patients with bulky tumors. The role of neoadjuvant hormones in other patients with intermediate and low risk prostate cancer is unclear and will be clarified with the publication of recently completed studies. The consensus meeting strongly endorsed continued accrual to current studies investigating clinically relevant questions.

Antineoplastic Agents, Hormonal↗

Impact of obesity and leptin treatment on adipocyte gene expression in Psammomys obesus.

We examined the effects of leptin treatment on the expression of key genes in adipocyte metabolism in Psammomys obesus (P. obesus), a polygenic rodent model of obesity. Lean and obese P. obesus were given three daily intraperitoneal injections of either saline or leptin (total of 45 mg/kg per day) for 7 days. In lean animals, leptin treatment led to reductions in food intake, body weight and fat mass. Pair-fed animals matched for the reduction in food intake of the lean leptin-treated animals demonstrated similar reductions in body weight and fat mass. In obese P. obesus, leptin treatment failed to have any effect on body weight or body fat mass, indicating leptin resistance. Lipoprotein lipase, hormone-sensitive lipase and peroxisome proliferator activated receptor gamma 2 mRNA levels were significantly reduced in lean leptin-treated animals, whereas pair-fed animals were similar to lean controls. Uncoupling protein 2 and glycerol phosphate acyltransferase were also reduced in the lean leptin-treated animals, but not significantly so. Obese animals did not show any gene expression changes after leptin treatment. In conclusion, high circulating concentrations of leptin in lean P. obesus resulted in decreased gene expression of a number of key lipid enzymes, independent of changes in food intake, body weight and fat mass. These effects of leptin were not found in obese P. obesus.

Adipocytes↗

Leptin resistance in a polygenic, hyperleptinemic animal model of obesity and NIDDM: Psammomys obesus.

OBJECTIVE: To investigate the effects of leptin administration to Psammomys obesus, a polygenic animal model of obesity and type 2 diabetes mellitus. DESIGN: Longitudinal intervention study utilising three separate leptin treatment protocols lasting 7-14 d. MEASUREMENTS: Body weight and food intake were measured daily, body fat and muscle content were estimated by carcass analysis on completion of the study. Blood glucose, plasma insulin, leptin, triglycerides and cholesterol were measured at baseline and twice each week during the study. RESULTS: Relatively high doses of leptin were required to significantly reduce food intake and body fat content in lean Psammomys obesus, but had no discernible effect on their obese littermates. CONCLUSION: As a species, Psammomys obesus appear to be relatively insensitive to the effects of leptin administration, compared with other rodents. Obese Psammomys obesus are leptin resistant relative to their lean littermates.

Animals↗

Prevalence and patterns of the use of complementary therapies among prostate cancer patients: an epidemiological analysis.

PURPOSE: We determine the prevalence and patterns of the use of complementary therapies among patients with and those at high risk for prostate cancer. MATERIALS AND METHODS: A cross-sectional survey was performed of men presenting to 2 urban tertiary urology clinics for prostate cancer evaluation or followup, and those attending a prostate cancer support group. All men diagnosed with and those at high risk (positive family history or abnormal prostate specific antigen) for prostate cancer were eligible for study. A 9-item self-administered, anonymous questionnaire about complementary therapies was administered. RESULTS: Of 357 patients who received the survey 155 from the urology clinics and 113 from the support group responded, for a total response rate of 75%. Of the patients presenting to urology clinics and the support group 27.4 and 38.9% with and 25.8 and 80% at high risk for prostate cancer, respectively, used some form of complementary therapy. The use significantly differed according to disease status (p = 0.001), and was highest among men who were clinically disease-free after radical therapy. Of the patients 24% did not inform the urologist of using alternative therapy. CONCLUSIONS: The prevalence of the use of complementary therapy among patients with or at increased risk for prostate cancer was high and dependent on the disease state. Urologists should be aware of this pattern of use, and consider the potential effects when assessing patients for and with prostate cancer.

Aged↗

Target position variability throughout prostate radiotherapy.

PURPOSE: To quantify the variability in prostate and seminal vesicle position during a course of external beam radiotherapy, and to measure the proportion of target variability due to setup error. METHODS AND MATERIALS: Forty-four weekly planning computerized tomography (CT) studies were obtained on six patients undergoing radiotherapy for prostate cancer. All patients were scanned in the radiotherapy treatment position, supine with an empty bladder, with no immobilization device. All organs were outlined on 3-mm-thick axial CT images. Anterior and lateral beam's eye view digitally reconstructed radiographs and multiplanar reformatted images were generated. The position of the prostate and seminal vesicles relative to the isocenter location as set that day was recorded for each CT study. Target position relative to a bony landmark was measured to determine the relative contribution of setup error to the target position variability. RESULTS: The seminal vesicle and prostate position variability was most significant in the anterior-posterior (AP) direction, followed by cranial-caudal (CC) and mediolateral (ML) directions. Setup error contributed significantly to the total target position variability. Rectal filling was associated with a trend to anterior movement of the prostate, whereas bladder filling was not associated with any trends. Although most deviations from the target position determined at the initial planning CT scan were within 10 mm, deviations as large as 15 mm and 19 mm were seen in the prostate and seminal vesicles respectively. Target position variations were evenly distributed around the initial target position for some patient studies, but unpredictable patterns were also seen. From a simulation based on the observed variability in target position, the AP, CC, and ML planning target volume (PTV) borders around the clinical target volume (CTV) required for target coverage with 95% certainty are 12.4 mm, 10.3 mm, and 5.6 mm respectively for the prostate and 13.8 mm, 8.6 mm, and 3.9 mm respectively for the seminal vesicles. CONCLUSION: Target position variability is significant during prostate radiotherapy, requiring large PTV borders around the CTV. This target position variability may be potentially reduced by improving the setup accuracy.

Humans↗

Isolation and identification of piperacillin amide as an impurity in piperacillin.

Piperacillin amide (IV) was successfully identified as the predominant impurity in commercial lots of piperacillin monohydrate (III). The impurity was isolated via a preparative liquid chromatographic scheme utilizing Florisil as the adsorbent and a mobile phase of water-acetonitrile (4:96, v/v). The isolated component had nearly the same reverse-phase HPLC properties as piperacillin and was chemically and thermally unstable. This labile impurity was spectroscopically identified by field desorption (FD), fast atom bombardment (FAB) with collision activation decomposition (CAD), and desorption chemical ionization (DCI) mass spectrometries , and NMR and IR spectrometries . Identity was confirmed on comparison of the chromatographic and spectrometric data of the impurity with an independently synthesized sample of piperacillin amide.

Chemical Phenomena↗

Measurement of strabismus in shortened exam lanes versus the 20-foot lane.

The angle of strabismus was compared in 62 patients when measured at 10 feet and in a 20-foot mirrored system, to measurements at 20 feet. Several divergence excess type exodeviations were measured as being significantly less, relative to the 20-foot measurements. High accommodative convergence/accommodation ratio type esotropes were often measured as being significantly higher in the 10-foot room, relative to the 20-foot measurements. Having a shortened or mirrored lane for strabismus measurement could significantly alter the mode of treatment or amount of surgery in strabismus patients and possibly yield a less than optimal result in strabismus management.

Esotropia↗

Adherence of Neisseria meningitidis to human epithelial cells.

Carrier strains of Neisseria meningitidis are recovered almost solely from the posterior pharynx and they are often nongroupable or rough. Invasive strains can be serogrouped (encapsulated). We studied adherence of both carrier- and patient-derived serogroupable and nongroupable meningococci to buccal epithelial and posterior pharyngeal cells. Fresh meningococcal isolates attached significantly better to pharyngeal than to buccal cells (P = 0.01). Strains that could be serogrouped adhered less than nongroupable strains (P less than 0.05). Meningococci passed in vitro became hemagglutinin negative and nonpiliated. Hemagglutinin-negative meningococci always adhered less to both epithelial cell types than the hemagglutinin-positive variants of the same strain. These results indicate that meningococcal pili probably mediate attachment to oropharyngeal cells, but encapsulation may reduce adherence. Localization of meningococci in the posterior pharynx is in part explained by the receptivity of the epithelial cells in this area for meningococci.

Cheek↗

Management of the incontinent patient. Practical guidelines for home care.

Probably no condition produces such an emotive reaction on the part of both patient and care-giver as that of incontinence. It has profound implications psychosocially to both parties, and is often erroneously viewed as an inevitable corollary of the ageing process, being one of the most damning hallmarks of decline, and a potent cause of rejection. This article suggests practical ways in which incontinence can be coped with at home.

Attitude↗