Search PubMed⌕ Search

Biomedical subjects

M McLean

Publications and source records attributed to M McLean.

At least 19 recordsLinked to original sources
PubMed2006

Veterinary waste disposal: practice and policy in Durban, South Africa (2001-2003).

In South Africa, until recently, veterinary waste has not been included in definitions of health care waste, and so has been neglected as a contributor to the hazardous waste stream. Despite the application of, for example, the "Polluter Pays" principle in South African environmental legislation, to generators of waste, which would include veterinarians, there appears to be little awareness of and even less enforcement of the legislation in this regard. This paper reports on a 2001-2003 survey of management practices of the five waste contractors servicing just over half of the veterinarians in Durban, South Africa's second largest city. Some of their activities, when evaluated in terms of the legislation, guidelines and policies relating to waste handling and disposal, were found to be non-compliant. Since any discussion on waste management should take cognisance of waste from generation to final disposal, the responsibility of veterinarians as waste generators is also discussed in the light of the recent developments in health care waste management in South Africa. This study presents a review of past and current policies, legislation and guidelines that have application to veterinary waste. This is the first study to address veterinary waste disposal in any South African city.

Animals↗
PubMed2006

Mother to child transmission of diabetes mellitus: does gestational diabetes program Type 2 diabetes in the next generation?

AIM: Type 2 diabetes is frequently familial. Hyperglycaemia in pregnancy might act in addition to genetic factors to cause diabetes in the children of mothers with gestational diabetes mellitus (GDM). The first manifestation of this in female offspring is likely to be GDM in their own pregnancies. We compared the incidence of GDM in daughters of diabetic mothers and diabetic fathers to determine if in utero exposure to hyperglycaemia increased the risk of a diabetes-prone phenotype in offspring. METHODS: We analysed the outcome of a GDM screening programme in women with a family history of diabetes in their mother (n = 535), father (n = 566), both parents (n = 77) or neither (n = 4672). RESULTS: GDM was twice as common in the daughters of diabetic mothers (11%) than diabetic fathers (5%, P = 0.002). Women with two diabetic parents were no more likely to have GDM than women with only a diabetic mother. CONCLUSIONS: Genetic predisposition to GDM should be equally shared by daughters of diabetic mothers and fathers. An excess of maternal transmission of diabetes is consistent with an epigenetic effect of hyperglycaemia in pregnancy acting in addition to genetic factors to produce diabetes in the next generation.

Diabetes Mellitus, Type 2↗
PubMed2005

Factors influencing the use of single vs multiple fractions of palliative radiotherapy for bone metastases: a 5-year review.

AIMS: Evidence from a number of randomised trials and meta-analyses supports the use of single-fraction radiotherapy for the palliation of painful bone metastases. This study explores patient and treatment factors that influence the choice of single compared with multiple-fraction radiotherapy for the treatment of bone metastases in clinical practice. MATERIALS AND METHODS: The Princess Margaret Hospital Palliative Radiation Oncology Program Database served as the basis for our report. All courses of treatment delivered for bone metastases were extracted. Courses were classified into single or multiple fractions. Clinical characteristics were compared between the two groups. RESULTS: Between 1998 and 2002, 882 courses of radiotherapy were delivered for the treatment of bone metastases, of which 283 (32%) were a single fraction. The proportion of single-fraction treatments was 37% in 1998, 30% in 1999 and 43% in 2000, but dropped to 26% and 28% in 2001 and 2002, respectively (P = 0.02). Patients treated with single fractions were significantly older (68 +/- 12 years vs 64 +/- 12 years), and had more weight loss and poor performance status. Single fractions included 20% of treatments in palliative irradiation of the spine, 36% in the pelvis and long bones, and 59% in the chest wall (P < 0.001). There was no significant difference in patients' gender, primary cancers, number of metastatic sites, treating physicians, enrollment in a clinical trial and general radiotherapy waiting time in our department. Multivariate analysis indicated age (P = 0.001), performance status (P < 0.001), anatomical site (P < 0.001) and year of radiotherapy (P = 0.006) as significant. CONCLUSION: One-third of palliative radiotherapy courses for bone metastases in our programme were given as single fractions. Performance status, age and anatomical site were significant factors affecting single compared with multiple fractionation. The variation in the use of single fractions over time may reflect the dynamic process of interpretation and application of evidence from clinical trials to practice.

Aged↗
PubMed2004

Tumour metabolites regulate tissue kallikrein in human umbilical vein endothelial cells.

Angiogenesis, the sprouting of new blood vessels, is tightly mediated via a myriad of endogenous factors. A pro-angiogenic alteration facilitates the formation of neovascular tumour networks, thereby providing mechanisms for uncontrolled growth. The kallikrein-kinin system is postulated to be pro-angiogenic since its components have been detected in both endothelial cells and tumour tissue. No studies have, however, focussed on the role of tissue kallikrein (TK) in human angiogenic endothelial cell-tumour interactions. This study has optimised a challenge model whereby endothelial cells are presented with neuroblastoma metabolites, and vice versa. Image analysis of immunoreactive TK revealed a dose-dependant, significant reduction of TK localisation within endothelial cells, while gene expression remained unchanged, the latter determined by in situ RT-PCR. Neuroblastoma cells, when challenged with endothelial cell metabolites, displayed no change in TK synthesis or localisation. Alterations in TK synthesis and/or storage by angiogenic endothelial cells may be mediated by tumour-released signals and possibly indicate a shift from a proteolytic to a mitogenic function of TK. The challenge model provides a relatively simple experimental system to study angiogenic factors in tumour-endothelial cell interaction, and is the first to localise both TK and its mRNA within angiogenic endothelial and tumour cells.

Animals↗
PubMed2004

Computed tomographic simulation in palliative radiotherapy: the Princess Margaret Hospital experience.

AIM: To examine the pattern of palliative radiation planning and the use of computed tomographic simulation (CTSIM) for this purpose. MATERIALS AND METHODS: We reviewed our department's external radiotherapy database for all courses of treatment with a palliative intent during the period of April to June 2002. Patient characteristics and treatment details were compared based on whether CTSIM had been used or not. RESULTS: During the above period, 593 courses of external radiation treatment were delivered with palliative intent in our department. Of these, 100 treatments (17%) were planned with the help of CTSIM. The mean age of patients with CTSIM (62.9 years) was not significantly different with the patients planned without CTSIM (63.6 years). CTSIM use varied by treatment location, being highest in mediastinum/oesophagus (48%) and pancreas/stomach (47%) treatments, and lowest in spine (6%), lung (3%) and long bones (4%) (P < 0.01). Only 3% of palliative treatments without CTSIM were prescribed using multiple/complex fields (all field arrangements more complex than a single field or two opposed parallel fields). Although significantly higher (P < 0.001), this proportion was also only 24% in the cases planned with CTSIM. Only 12% of treatments without CTSIM were prescribed with more than 5 fractions, whereas 32% of CT-simulated treatments included more than 5 fractions (P < 0.001). CONCLUSION: CTSIM was used much less frequently in our department's palliative radiotherapy compared with its use in radical treatments. The relatively low rate of multiple/complex fields planned in CT-simulated cases suggested that CTSIM was mostly used to improve tumour localisation. The optimal role of CTSIM in palliative radiotherapy will most probably evolve, based on an enhanced understanding of the implications from improved localisation and optimal planning techniques on clinical outcomes, patient convenience and resource accessibility.

Aged↗
PubMed2002

Symptom response after palliative radiotherapy for patients with brain metastases.

Whole brain radiotherapy (RT) is frequently used to palliate symptoms in patients with brain metastases, but the palliative benefit to patients has not been well documented. We conducted a longitudinal observational prospective study of patients receiving standard RT (20 Gray (Gy)/5 fractions) for symptomatic brain metastases. End-points were observer rating of neurological symptoms, patient-rated symptoms, performance status, neurological functional status, cognitive function and quality of life (QOL). Median survival for the 75 patients was 86 days (95% confidence interval (CI): 65-101 days). At 1 month, 19% of patients showed an improvement or resolution of presenting symptoms, 23% were stable and 55% had progressed or died. Patient-rated symptoms were increased at 1 month in comparison to baseline data. Only 4 patients had an improved performance status and 22 were stable. Many patients with brain metastases have a short life expectancy and may not benefit from even short duration radiation schedules. Further effort is needed to optimise patient selection and tailor treatment appropriately.

Adult↗
PubMed2002

Validation of the DLW method in Japanese quail at different water fluxes using laser and IRMS.

In Japanese quail (Coturnix c. japonica; n = 9), the doubly labeled water (DLW) method ((2)H, (18)O) for estimation of CO(2) production (l/day) was validated. To evaluate its sensitivity to water efflux levels (r(H(2))O(e); g/day) and to assumptions of fractional evaporative water loss (x; dimensionless), animals were repeatedly fed a dry pellet diet (average r(H(2))O(e) of 34.8 g/day) or a wet mash diet (95.8 g/day). We simultaneously compared the novel infrared laser spectrometry (LS) with isotope ratio mass spectrometry. At low r(H(2))O(e), calculated CO(2) production rate exhibited little sensitivity to assumptions concerning x, with the best fit being found at 0.51, and only little error was made employing an x value of 0.25. In contrast, at high r(H(2))O(e), sensitivities were much higher with the best fit at x = 0.32. Conclusions derived from isotope ratio mass spectrometry and LS were similar, proving the usefulness of LS. Within a threefold range of r(H(2))O(e), little error in the DLW method is made when assuming one single x value of 0.25 (recommended by Speakman JR, Doubly Labelled Water. Theory and Practice. London: Chapman & Hall, 1997), indicating its robustness in comparative studies.

Animal Feed↗
PubMed2001

Introducing a reward system in assessment in histology: a comment on the learning strategies it might engender.

BACKGROUND: Assessment, as an inextricable component of the curriculum, is an important factor influencing student approaches to learning. If assessment is to drive learning, then it must assess the desired outcomes. In an effort to alleviate some of the anxiety associated with a traditional discipline-based second year of medical studies, a bonus system was introduced into the Histology assessment. Students obtaining a year mark of 70% were rewarded with full marks for some tests, resulting in many requiring only a few percentage points in the final examination to pass Histology. METHODS: In order to ascertain whether this bonus system might be impacting positively on student learning, thirty-two second year medical students (non-randomly selected, representing four academic groups based on their mid-year results) were interviewed in 1997 and, in 1999, the entire second year class completed a questionnaire (n = 189). Both groups were asked their opinions of the bonus system. RESULTS: Both groups overwhelming voted in favour of the bonus system, despite less than 45% of students failing to achieve it. Students commented that it relieved some of the stress of the year-end examinations, and was generally motivating with regard to their work commitment. CONCLUSIONS: Being satisfied with how and what we assess in Histology, we are of the opinion that this reward system may contribute to engendering appropriate learning approaches (i.e. for understanding) in students. As a result of its apparent positive influence on learning and attitudes towards learning, this bonus system will continue to operate until the traditional programme is phased out. It is hoped that other educators, believing that their assessment is a reflection of the intended outcomes, might recognise merit in rewarding students for consistent achievement.

Achievement↗
PubMed2001

Outbreak of cryptosporidiosis linked with a farm event.

AIM: To investigate an outbreak of cryptosporidiosis linked to a two-day farm educational event in the Wellington region. Methods. The outbreak was investigated by carrying out a site visit and interviewing cases (or their parents) identified through notifications to Wellington Regional Public Health. RESULTS: Twenty confirmed cases were linked to the event. Nineteen were aged under seven years. The most likely route of infection was the hand-to-mouth transfer of the parasite after touching an infected animal. CONCLUSIONS: To our knowledge this is the first outbreak of cryptosporidiosis associated with a farm event reported in New Zealand. Farm animals, particularly calves, are likely to carry cryptosporidiosis and other microorganisms that are pathogenic in humans. This outbreak highlights the need for organisers of similar events to implement preventive measures such as hand washing facilities and reminders. Adults supervising young children should also be vigilant in enforcing hand washing following animal contact.

Adolescent↗
PubMed2001

Novel MRI contrast agent for molecular imaging of fibrin: implications for detecting vulnerable plaques.

BACKGROUND: Molecular imaging of thrombus within fissures of vulnerable atherosclerotic plaques requires sensitive detection of a robust thrombus-specific contrast agent. In this study, we report the development and characterization of a novel ligand-targeted paramagnetic molecular imaging agent with high avidity for fibrin and the potential to sensitively detect active vulnerable plaques. METHODS AND RESULTS: The nanoparticles were formulated with 2.5 to 50 mol% Gd-DTPA-BOA, which corresponds to >50 000 Gd(3+) atoms/particle. Paramagnetic nanoparticles were characterized in vitro and evaluated in vivo. In contradistinction to traditional blood-pool agents, T1 relaxation rate as a function of paramagnetic nanoparticle number was increased monotonically with Gd-DTPA concentration from 0.18 mL. s(-1). pmol(-1) (10% Gd-DTPA nanoparticles) to 0.54 mL. s(-1). pmol(-1) for the 40 mol% Gd-DTPA formulations. Fibrin clots targeted in vitro with paramagnetic nanoparticles presented a highly detectable, homogeneous T1-weighted contrast enhancement that improved with increasing gadolinium level (0, 2.5, and 20 mol% Gd). Higher-resolution scans and scanning electron microscopy revealed that the nanoparticles were present as a thin layer over the clot surface. In vivo contrast enhancement under open-circulation conditions was assessed in dogs. The contrast-to-noise ratio between the targeted clot (20 mol% Gd-DTPA nanoparticles) and blood was approximately 118+/-21, and that between the targeted clot and the control clot was 131+/-37. CONCLUSIONS: These results suggest that molecular imaging of fibrin-targeted paramagnetic nanoparticles can provide sensitive detection and localization of fibrin and may allow early, direct identification of vulnerable plaques, leading to early therapeutic decisions.

Animals↗
PubMed2001

A prospective study of factors predicting clinically occult spinal cord compression in patients with metastatic prostate carcinoma.

BACKGROUND: The objective of this study was to identify clinical parameters that predict occult subarachnoid space or spinal cord (SAS/SC) compression, as determined by magnetic resonance imaging (MRI), in patients with metastatic prostate carcinoma. METHODS: A prospective study was performed in which 68 patients with bone metastases from prostate carcinoma and a normal neurologic examination underwent MRI of the entire spine after documentation of clinical, X-ray, and bone scan parameters potentially predictive of occult SAS/SC compression. RESULTS: Occult SAS/SC compression was diagnosed in 22 patients (32%) using MRI. Nine patients (13%) had compressions at two discontinuous spinal levels. Extensive disease on bone scan, the duration of continuous hormonal therapy prior to study entry, and hemoglobin concentration were found to predict SAS/SC compression by univariate analysis. The extent of disease on bone scan and the duration of continuous hormonal therapy were independent predictors of SAS/SC compression by multivariate analysis (P = 0.02 and P = 0.04, respectively). The risk of occult SAS/SC compression increased from 32% to 44% in patients with a bone scan that showed > 20 metastases as the duration on hormones increased from 0 to 24 months. The risk in patients with fewer metastases increased from 11% to 17% over the same interval. The presence or absence of back pain was not predictive of SAS/SC compression. CONCLUSIONS: Patients who are at high risk for occult SAS/SC compression can be identified using clinical parameters and readily available diagnostic tests. These high-risk patients should undergo MRI screening with the aim of diagnosing and treating spinal cord compression before the development of neurologic deficits that may be irreversible.

Aged↗
PubMed2001

Adjuvant and salvage radiation therapy after radical prostatectomy for adenocarcinoma of the prostate.

PURPOSE: To evaluate the outcome of adjuvant and salvage radiotherapy (RT) after radical prostatectomy (RP) for clinically localized prostate cancer using conventional clinical end-points, and the biochemical relapse-free rate (bRFR). METHODS: Between 1987 and 1994, 113 node negative, hormonally naïve men received RT 1 month to 12 years after RP. Adjuvant RT was given for positive resection margins and/or pT3 disease. Salvage RT was given for a persistently elevated prostatic specific antigen (PSA), a rising PSA, or palpable recurrence post RP. Clinical and biochemical endpoints determined outcome. Log-rank testing and the Cox proportional hazards model identified factors predictive for biochemical relapse free rate. RESULTS: Median follow-up after RT was 3.7 years (range 0.2-9 years). Five-year clinical local control was 95% for patients with no palpable evidence of disease and 59% for those with palpable recurrence (P < 0.0001). 5-year bRFR was 81% for adjuvant RT, 19% for salvage of biochemical recurrence, 0% for patients with palpable disease (P < 0.0001). Improved bRFR for adjuvant and salvage RT was predicted by a Gleason score < 7 vs. 7 vs. > 7 (hazard ratio 1.53; 95% CI 0.99-2.35) and an undetectable pre-RT PSA vs. PSA < 2.0 ng/ml vs. PSA > 2.0 ng/ml (hazard ratio 3.81; 95% CI 2.47-5.87). Seminal vesicle involvement was not a statistically significant independent predictor of bRFR. CONCLUSIONS: The most favourable bRFR was observed for adjuvant therapy. Salvage was most successful with a pre-RT PSA < 2.0 ng/ml, or Gleason score < 7. Few patients with a pre-RT PSA > 2.0 ng/ml were salvaged, and none with palpable recurrence. These patients require investigation of alternative salvage strategies.

Adenocarcinoma↗
PubMed2001

Radiotherapy for brain metastases: defining palliative response.

BACKGROUND AND PURPOSE: Most patients with brain metastases are treated with palliative whole brain radiotherapy (WBRT). There is no established definition of palliative response. The aim of this study was to develop and test clinically useful criteria for response following palliative WBRT. MATERIALS AND METHODS: A prospective study was conducted of patients with symptomatic brain metastases treated with WBRT (20 Gy/5 fractions) and standardised steroid tapering. Assessments included observer rating of neurological symptoms, patient-completed symptom checklist and performance status (PS). Response criteria were operationally defined based on a combination of neurological symptoms, PS and steroid dose. RESULTS: Seventy-five patients were accrued. At 1 month, presenting neurological symptoms were improved in 14 patients, stable in 17, and worse in 21; 23 patients were not assessed, mainly due to death or frailty. Using response criteria defined a priori, 15% (95% CI 7-23%) of patients were classified as having a response to RT, 25% no response, and 29% progression; 27% were deceased at or soon after 1 month. A revised set of criteria was tested, with less emphasis on complete tapering of steroids: they increased the proportion of patients responding to 39% (95% CI 27-50%) but didn't change the large proportion who did not benefit (44%). CONCLUSIONS: Clinical response to RT of patients with brain metastases is multifactorial, comprising symptoms, PS and other factors. Assessment of degree of palliation depend on the exact definition used. More research is needed in this important area, to help validate criteria for assessing palliation after WBRT.

Adult↗
PubMed2001

Squamous cell carcinoma of the oesophagus treated with radiation and 5-fluorouracil, with and without mitomycin C.

A retrospective analysis was performed of patients with squamous cell carcinoma of the oesophagus without evidence of distant metastases, who were treated with radical intent. Between 1981 and 1984, and 1989 and 1991, 98 patients were treated with radiation, 5-fluorouracil (5-FU) and mitomycin C; and between 1984 and 1989, 133 patients were treated with radiation and 5-FU without mitomycin C. Actuarial survival and local control were assessed, and prognostic factors were identified for both endpoints. The standard dose of radiation prescribed was 52 Gy to the 95% isodose in 20 fractions over 4 weeks. 5-FU was given by continuous infusion as 1 g/m2 (maximum 1.5 g)/day, for 4 days. Patients who received mitomycin C were given 10 mg/m2 (maximum 18 mg) on day 1. Survival and local relapse-free rates were estimated using the method of Kaplan and Meier, and the Cox proportional hazards model was used to evaluate possible prognostic factors, including the effect of mitomycin C administration. The median survival was 15.4 months (95% confidence interval 12.7-17.2) with 31% 2-year survival (standard error (SE) 3%), and 13% 5-year survival (SE 2%). In the multivariate analysis, lower radiation dose and younger age were the only statistically significant prognostic factors for reduced overall survival and reduced relapse-free rate respectively. There was no difference in survival (chi(2) = 0.07, 1 degree of freedom (df), P=0.79) or local relapse-free rate (chi2 = 0.39, 1 df, P = 0.53) between patients treated with or without mitomycin C. The treatment was well tolerated. Further studies are required to determine the most effective combination of radiation and chemotherapy or other radiation sensitizers for squamous cell carcinoma of the oesophagus.

Aged↗
PubMed2001

Corticotrophin-releasing hormone and human parturition.

Corticotrophin-releasing hormone (CRH), the hypothalamic peptide that controls function of the pituitary-adrenal axis in response to stress, is expressed in abundance in the human placenta and is present in high concentrations in maternal and fetal plasma during late pregnancy. A number of lines of evidence now imply a role for this hormone in the control of parturition and fetal maturation in humans. It has been proposed that CRH, through interactions with oestrogen, adrenal steroids, prostaglandins and oxytocin, establishes positive-feedback loops that initiate parturition and labour. Excessive production of placental CRH has also been linked to preterm labour. However, there are a number of significant gaps in our knowledge of the function of this peptide in pregnancy. This review examines current evidence regarding the putative role of CRH in human parturition.

Animals↗