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Biomedical subjects

K McLaughlin

Publications and source records attributed to K McLaughlin.

At least 19 recordsLinked to original sources

Fasciola hepatica: ultrastructural effects of a combination of triclabendazole and clorsulon against mature fluke.

A study has been carried out to investigate the ultrastructural effects of triclabendazole (TCBZ) at half-normal concentration, clorsulon at half-normal concentration, and a combination of these two drugs against mature Fasciola hepatica. The Cullompton TCBZ-susceptible isolate was used for these experiments. Flukes were incubated for 24 h in vitro in TCBZ sulphoxide (7.5 microg/ml), clorsulon (5 microg/ml), or a combination of the two drugs. For the in vivo experiment, rats were dosed with TCBZ (5 mg/kg body weight), clorsulon (5 mg/kg body weight), or a combination of the two drugs, and flukes recovered after 48 h. Fine structural changes within the tegumental syncytium and tegumental cells were assessed by transmission electron microscopy. Treatment with the combination of drugs produced greater disruption to the flukes than the individual drugs at half-normal concentrations, both in vivo and in vitro; also than TCBZ.SO at normal concentration in vitro. The changes observed aid in the understanding of the gross changes to the tegumental surface described previously (Meaney M, Allister J, McKinstry B, McLaughlin K, Brennan GP, Forbes AB, Fairweather I. Parasitol Res 99:609-621, 2006). The results indicate that there are additive effects between TCBZ and clorsulon and suggest that the use of drug combinations would be of value in the treatment of TCBZ-resistant fluke.

Animals↗

Fasciola hepatica: morphological effects of a combination of triclabendazole and clorsulon against mature fluke.

A study has been carried out to investigate the morphological effects of half-strength triclabendazole (TCBZ), half-strength clorsulon, and a combination of these two drugs against mature Fasciola hepatica. The Cullompton TCBZ-susceptible isolate was used for these experiments. Flukes were incubated for 24 h in vitro in TCBZ sulphoxide (7.5 microg/ml), clorsulon (5 microg/ml), or a combination of the two drugs. For the in vivo experiment, rats were dosed with TCBZ (6.25 mg/kg body weight), clorsulon (5 mg/kg body weight), or a combination of the two drugs and flukes recovered after 48 h. Surface changes to the flukes were assessed by scanning electron microscopy. Treatment with the combination of drugs produced greater disruption to the flukes than the individual drugs at half-strength, both in vivo and in vitro. Disruption to the tegument of the flukes induced by the individual drugs at half-strength was relatively minor and less than that caused by the drugs at full-strength. The results suggest that there are additive effects between TCBZ and clorsulon, which may be indicative of synergy: the use of drug combinations would be of value in the treatment of triclabendazole-resistant fluke.

Animals↗

Progression of kidney dysfunction in the community-dwelling elderly.

Despite the high prevalence of chronic kidney disease among the elderly, few studies have described their loss of kidney function. We sought to determine the progression of kidney dysfunction among a community-based cohort of elderly subjects. The cohort included 10 184 subjects 66 years of age or older, who had one or more outpatient serum creatinine measurements during each of two time periods: 1 July to 31 December 2001 and 1 July to 31 December 2003. A mixed effects model, including covariates for age, gender, diabetes mellitus, and comorbidity, was used to determine the rate of decline in estimated glomerular filtration rate (eGFR, in ml/min/1.73 m2) per year over a median follow-up of 2.0 years. Subjects with diabetes mellitus had the greatest decline in eGFR of 2.1 (95% CI 1.8-2.5) and 2.7 (95% CI 2.3-3.1) ml/min/1.73 m2 per year in women and men, respectively. The rate of decline for women and men without diabetes mellitus was 0.8 (95% CI 0.6-1.0) and 1.4 (95% CI 1.2-1.6) ml/min/1.73 m2 per year. Subjects with a study mean eGFR<30 ml/min/1.73 m2, both those with and without diabetes mellitus, experienced the greatest decline in eGFR. In conclusion, we found that the majority of elderly subjects have no or minimal progression of kidney disease over 2 years. Strategies aimed at slowing progression of kidney disease should consider underlying risk factors for progression and the negligible loss of kidney function that occurs in the majority of older adults.

Aged↗

The influence of objectives, learning experiences and examination blueprint on medical students' examination preparation.

BACKGROUND: The influence of intended and informal curricula on examination preparation has not been extensively studied. This study aims to firstly describe how students utilized components of intended and informal curricula to guide examination preparation, and secondly to study the relationship between examination preparation and performance. METHODS: Students received a pre-examination questionnaire to identify components from the intended curriculum (objectives and examination blueprint), and informal curriculum (content emphasised during lectures and small groups), used during examination preparation. Multiple logistic regression was used to study the relationship between these variables and student performance (above versus at or below average). RESULTS: Eighty-one students participated. There was no difference in the proportions using the examination blueprint, content emphasised during lectures, and content emphasised during small groups (87-93%) but fewer students used objectives (35%, p < 0.001). Objectives use was associated with reduced odds of above average examination performance (adjusted odds ratio 0.27 [0.07, 0.97], p = 0.04). CONCLUSION: When preparing for the renal course examination, students were influenced at least as much by the informal as the intended curriculum. Of the two intended curriculum components, the examination blueprint appeared to be more widely used than the course objectives. This decreased use of objectives on examination preparation did not appear to have a detrimental effect on student performance.

Adult↗

Laparoscopic hand-assisted living donor nephrectomy: the Calgary experience.

Laparoscopic techniques, such as hand-assisted live donor nephrectomy (HALDN), have the potential to increase the number of living kidney donors. For these techniques to be acceptable, however, the standards for donor, recipient, and graft survival achieved by the open technique need to be matched. In this study we present the results of the first 20 HALDN procedures at our center. The 20 donors included nine men and 11 women of mean (+/-SD) donor age 41 (+/-10) years and mean donor weight 78 (+/-13) kg. Mean operative time was 174 (+/-32) minutes. Only one patient required an open conversion to procedure because of venous bleeding. All kidneys were successfully implanted; there were no episodes of primary nonfunction or delayed graft function. There were no surgical complications, either in the donor or the recipient. The range of postoperative stay was 3 to 5 days. One recipient died 62 days after transplant from influenza virus pneumonia. There were no other causes of graft loss. Our preliminary results suggest that HALDN is safe and is associated with short-term donor, recipient, and graft outcomes that are at least comparable to the standard open technique.

Adult↗

Serial changes in levels of IL-6 and IL-1beta in premature infants at risk for bronchopulmonary dysplasia.

The aim of this study was to define the inflammatory changes occurring in the lungs of infants at risk for bronchopulmonary dysplasia (BPD) over the first 28 days of life, and to define an optimal strategy for steroids therapy in the prevention of BPD. We measured levels of interleukin-6 (IL-6) and interleukin-1 beta (IL-1beta) in tracheal aspirate (TA) samples and blood of premature infants with severe respiratory distress syndrome RDS (n = 45) on the first day of life prior to initiation of surfactant therapy and on days 5-7, 12-14, 19-21, and 26-28. Levels of IL-6 and IL-1beta were determined with a commercially available enzyme-linked immunoassay. Logistic regression analyses were performed in order to examine differences in trends in levels of IL-6 and IL-1beta between groups of infants. Infants were divided into group I (n = 30, FiO(2) < or = 0.35 at 28 days) and group II (n = 15, FiO(2) > 0.35 based on their likelihood of developing BPD at 36 weeks postconceptional age (PCA). The infants were comparable with respect to mean ( +/- SEM) birth weight (895 +/- 33 g vs. 900 +/- 40 g), gestational age (27 +/- 0.38 weeks vs. 27 +/- 0.54 weeks), and severity of respiratory illness at entry into the study (mean airway pressure: 12 +/- 1 cmH(2)O vs. 12 +/- 1 cmH(2)O, and oxygen index: 15 +/- 2 vs. 19 +/- 4) (group I vs. group II, respectively). Logistic regression analyses failed to reveal any significant differences in linear trends of levels of IL-6 and IL-1beta in TA samples between both groups of infants. No particular pattern of change in levels of IL-6 or IL-1beta could be identified among groups of infants. Levels of IL-6 and IL-1beta in TA samples on the first day of life failed to predict the need for FiO(2) > 0.35 at 28 days of age. We could not identify an increasing trend or a specific pattern of changes in postnatal levels of IL-6 or IL-1beta in TA samples of infants who were at greater risk of developing BPD at 36 weeks PCA compared to infants who were not.

Bronchopulmonary Dysplasia↗

A schematic approach to diagnosing and resolving lecturalgia.

BACKGROUND: The lecture is a much used and much criticized teaching method. Lecturalgia (painful lecture) is a frequent cause of morbidity for both teachers and learners. The etiology of lecturalgia is multifactorial and multiple lecturing pathologies frequently coexist. The 'Clinical Presentation' curriculum at the University of Calgary encourages the use of 'schemes' that provide a scaffolding for learning and a starting point for approaching (clinical) problems. Thus far this approach has not been used to tackle teaching or learning problems. AIM: Our aim in this paper was to devise a schematic approach to diagnosing lecturing problems and to make evidence-based recommendations on how to resolve lecturing problems. We have suggested that causes of lecturalgia can be divided into three categories: poor judgement; poor organization; and poor delivery. Our proposed scheme is based upon these three categories that are then subcategorized. RESULTS: We have reviewed the medical education literature in an attempt to provide evidence-based recommendations for the remediation of lecturing problems within each subcategory. CONCLUSION: Where trial evidence is lacking we have made recommendations that are consistent with cognitive theory or expert opinion. Finally, where expert opinion does not exist, we have taken the liberty (literary license) of providing nonexpert opinion!

Curriculum↗

An economic evaluation of early versus late referral of patients with progressive renal insufficiency.

Patients with progressive renal insufficiency (PRI) who start renal replacement therapy (RRT) within 4 months of seeing a nephrologist (late referral) have increased morbidity, mortality, and health care costs. We performed an economic evaluation of early versus late referral of patients with PRI to a multidisciplinary clinic. A decision analysis was performed from the perspective of the health care provider, using a Markov model to simulate progression of PRI and survival of patients on RRT. Our simulated patient cohort comprised 1,000 patients with PRI and estimated creatinine clearance of 20 mL/min. The study time horizon was 5 years. Clinical and cost data were taken from published Canadian and U.S. data, where available. Where published data were lacking, we used data from our prospectively maintained database. The study intervention was attendance at a PRI clinic where patients receive treatment to slow the rate of renal progression, receive treatment of complications of PRI, and are prepared for RRT. Endpoints were total cost of patient care, patient life-years, patient life-years free of RRT, and hospital admission days. Early referral resulted in cost savings and improved patient survival along with more life-years free of RRT and fewer hospital inpatient days. Cost-effectiveness was unaffected by univariate sensitivity analyses. Cost-effectiveness decreased as rates of renal function loss for patients referred early versus late approximated each other. In conclusion, early referral of patients with PRI to a multidisciplinary clinic appears cost-effective.

Cost-Benefit Analysis↗

Evaluation of various corrections to the standardized uptake value for diagnosis of pulmonary malignancy.

OBJECTIVE: Standard uptake values (SUVs) are widely used for quantifying the uptake of 18F-fluorodeoxyglucose (18F-FDG) in tumours. The objective of this study was to evaluate the accuracy of SUVs for malignancy in lung nodules/masses and to analyse the effects of tumour size, blood glucose levels and different body weight corrections on SUV. METHODS: One hundred and twenty-seven patients with suspicious lung lesions imaged with 18F-FDG positron emission tomography (PET) were studied retrospectively. Pathology results were used to establish lesion diagnosis in all cases. SUVs based on maximum pixel values were obtained by placing regions of interest around the focus of abnormal 18F-FDG uptake in the lungs. The SUVs were calculated using the following normalizations: body weight (BW), lean body weight (LBW), scaled body surface area (BSA), blood glucose level (Glu) and tumour size (Tsize). Receivers operating characteristic (ROC) curves were generated to compare the accuracy of different methods of SUV calculation. RESULTS: The areas under the ROC curves for SUV(BW), SUV(BW+Glu), SUV(LBW), SUV(LBW+Glu), SUV(BSA), SUV(BSA+Glu) and SUV(BW+Tsize) were 0.915, 0.912, 0.911, 0.912, 0.916, 0.909 and 0.864, respectively. CONCLUSION: The accuracy of SUV analysis for malignancy in lung nodules/masses is not improved by correction for blood glucose or tumour size or by normalizing for body surface area or lean body weight instead of body weight.

Fluorodeoxyglucose F18↗

Acute interstitial nephritis due to omeprazole.

Omeprazole is a proton pump inhibitor that is used commonly in the treatment of acid-peptic disorders. Although omeprazole is generally well tolerated, serious adverse effects such as renal failure have been reported. Thus far, 17 cases of acute interstitial nephritis (AIN) secondary to omeprazole have been described. Another case of AIN is described in a 36-yr-old woman presenting with nausea, vomiting, weight loss, and a rising serum creatinine concentration. Omeprazole therapy had ceased 2 wk before admission. AIN was diagnosed by renal biopsy and corticosteroid therapy was initiated. After 4 wk of therapy the serum creatinine concentration had normalized. Among the reported cases in the literature, AIN was diagnosed after an average of 2.7 months of therapy with 20-40 mg of omeprazole daily. Recurrence was universal on rechallenge. Common symptoms included fatigue, fever, anorexia, and nausea. The classic triad of fever, rash, and eosinophilia was uncommon. Typical laboratory features included hematuria, proteinuria, pyuria, eosinophilia, and anemia. Management consisted of withdrawal of omeprazole and corticosteroid therapy in some patients. All but one patient recovered normal renal function. Corticosteroid therapy was well tolerated and may have been beneficial.

Acute Disease↗

The Southern Alberta Renal Program database: a prototype for patient management and research initiatives.

The Southern Alberta Renal Program (SARP) database was developed to respond to an urgent need for local information on clinical outcomes, laboratory information, and health care costs, and to enable our local renal program to monitor the implementation of established clinical practice guidelines. The database captures detailed demographic, clinical, and laboratory information and is unique by also capturing comorbidity, health-related quality of life and costing information for patients with end-stage renal disease (ESRD) in southern Alberta, storing the information in one common database. By collecting information on patient comorbidity, health outcomes and costs, the SARP database has enabled many quality assurance initiatives as well as research opportunities for projects involving patients with ESRD. Due to the availability of links with other available local clinical and administrative databases, information is collected with a minimal need for manual data entry. This type of database is a method by which health programs could improve the quality of patient care. Programs caring for patients with chronic medical conditions such as ESRD should examine how computer databases could assist in clinical care and improve the efficiency with which that care is delivered to their patients.

Acute Kidney Injury↗

Increased risk for posttransplant lymphoproliferative disease in recipients of liver transplants with hepatitis C.

Posttransplant lymphoproliferative disease (PTLD) is associated with immunosuppression and lymphotrophic viral infections. Hepatitis C virus (HCV) has been identified as a risk factor for non-Hodgkin's lymphoma, but no association between HCV and PTLD has been shown. To investigate this possibility, we identified patients with HCV who received their first orthotopic liver transplant at our unit between January 1, 1992, and December 31, 1996, and compared them with contemporary liver transplant recipients without HCV for incidence and risk factors for PTLD and survival. Fifty-seven patients with HCV and 127 patients without HCV were compared. There was no age difference (52 v 53 years; P =.85), but there were more men in the HCV group (man-woman ratio, 2.1:1 v 0.9:1; P =.006). No difference was observed in the follow-up period, graft survival, rejection episodes, or use of different immunosuppressive regimes (P >.05 for all). Four patients with HCV (7%) developed PTLD compared with 1 patient without HCV (0.8%; P =.02). The relative odds for developing PTLD in patients with HCV were 9.5. All patients who developed PTLD were administered OKT3 induction therapy. These data suggest that PTLD may be more prevalent in patients undergoing liver transplantation for HCV-related liver disease who also receive OKT3, and that HCV infection may be a risk factor for developing PTLD.

Adolescent↗

Presentation, survival and prognostic markers in AA amyloidosis.

We reviewed 43 patients with AA amyloidosis who presented to our unit between 1985-1999: 70% had an underlying chronic rheumatological diagnosis. Median (95% CI) patient survival from time of diagnosis was 52.9 months (9.4-96.6) and median renal survival was 18 months (3.2-32.8) Twenty-four patients have died; 42% of deaths were due to infection, while renal failure accounted for 12.5%. Presenting factors which adversely influenced outcome were a low serum albumin and a high 24-h urinary albumin excretion (p=0.007 and p=0.003, respectively). Stepwise multivariate regression analysis identified albuminuria and presenting creatinine clearance as significant predictors. (p=0.005 and p=0.035, respectively). Mean C-reactive protein (CRP) throughout follow-up correlated weakly but not significantly with survival off dialysis (p=0.06). Change in creatinine clearance correlated with albuminuria. (r(2)=40%, p=0.001)

Adolescent↗

Universal antenatal group B streptococcus screening? The opinions of obstetricians and neonatologists within Australia.

Group B streptococcus (GBS) is the leading infectious cause of morbidity and mortality in Australian newborns. Although intrapartum chemoprophylaxis is recommended to reduce the risk of neonatal GBS transmission and disease, controversy exists as to the best method to select women 'at risk' for this treatment. Our study aimed to survey the opinions of obstetricians and neonatologists currently in practice in Australia on GBS screening and treatment. Of the 488 obstetricians and 68 neonatologists currently in practice who responded to the survey, 271 obstetricians (56%) and 40 neonatologists (61%) supported universal antenatal screening. Of those respondents who did not support a universal antenatal screening policy, 196 (93%) and 24 (92%) of the obstetricians and neonatologists respectively, supported antenatal screening based on risk factors. This diversity in practitioner opinion highlights the lack of certainty in the literature as to the best management strategy to prevent neonatal GBS sepsis.

Anti-Bacterial Agents↗