Sustained pyridoxine response in primary hyperoxaluria type 1 recipients of kidney alone transplant.

Combined liver kidney transplant is the preferred transplant option for most patients with primary hyperoxaluria type 1 (PH1) given that it removes the hepatic source of oxalate production and improves renal allograft survival. However, PH1 patients homozygous for the G170R mutation can develop normal urine oxalate levels with pyridoxine therapy and may be candidates for kidney alone transplant (KTx). We examined the efficacy of pyridoxine therapy following KTx in five patients homozygous for G170R transplanted between September 1999 and July 2013. All patients were maintained on pyridoxine posttransplant. Median age at transplant was 39 years (range 33-67 years). Median follow-up posttransplant was 8.5 years (range 0.2-13.9 years). At the end of follow-up, four grafts were functioning. One graft failed 13.9 years posttransplant due to recurrent oxalate nephropathy following an acute medical illness. After tissue oxalate stores had cleared, posttransplant urine oxalate levels were <0.5 mmol/24 h the majority of times checked. Calcium oxalate crystals were noted in only 3/13 allograft biopsies. This series suggests that a subgroup of PH1 patients demonstrate sustained response to pyridoxine therapy following KTx. Therefore, pyridoxine combined with KTx should be considered for PH1 patients with a homozygous G170R mutation.

Adults with intellectual disabilities and challenging behaviour: the costs and outcomes of in- and out-of-area placements.

BACKGROUND: People with severe challenging behaviour are vulnerable to exclusion from local services and removal to out-of-area placements if locally available supported accommodation is insufficient to meet their needs. There are concerns about the high costs and potentially poorer outcomes of out-of-area placements but relatively little is known about how costs and outcomes compare with provision for a similar population placed locally. METHODS: Costs, quality of care and a wide range of quality of life outcomes for 38 people with intellectual disabilities and challenging behaviour living in-area and 38 similar people living out-of-area were compared. The two groups were matched as far as possible on risk factors for out-of-area placement. The out-of-area group represented two-thirds of the total number of people who originated from the territory served by the largest specialist health service in Wales and were placed in residential settings at least 10 miles beyond its boundaries. RESULTS: There was a mixed pattern of quality of care and quality of outcome advantages between the two types of setting, although in-area placements had a greater number of advantages than out-of-area placements. Unexpectedly, out-of-area placements had lower total costs, accommodation costs and daytime activity costs. CONCLUSIONS: No overall conclusion could be reached about cost-effectiveness. A number of potential reasons for the differences in cost were identified. Although additional resources may be needed to provide in-area services for those currently placed out-of-area, government policy to provide comprehensively for those who want to live locally, irrespective of their needs, appears to be attainable.

Treatment and management of challenging behaviours in congregate and noncongregate community-based supported accommodation.

OBJECTIVES: To compare the nature and prevalence of use of procedures employed to treat and manage challenging behaviours across two approaches to providing community-based supported accommodation for people with intellectual disabilities (ID) and severe challenging behaviour: noncongregate settings where the minority of residents have challenging behaviour, and congregate settings where the majority of residents have challenging behaviour. SETTING: Community-based supported accommodation for people with ID and challenging behaviour. DESIGN: Longitudinal matched groups design. MAIN OUTCOME MEASURES: The nature and prevalence of use of procedures employed to treat and manage challenging behaviours. Observed and reported severity of challenging behaviours. RESULTS: Both types of settings were associated with low prevalence of use of behavioural technologies for the reduction of challenging behaviour (less than 15% of participants). In contrast, high proportions of participant received antipsychotic medication in both noncongregate (56%) and congregate (80%) settings. Congregate settings were associated with the increased use of physical restraint as a reactive management strategy, with over half of participants being in receipt of physical restraint by two or more members of staff. DISCUSSION: Changes in reported and observed challenging behaviour over a 10-month period were slight. The use of evidence-based behavioural technologies for the reduction of challenging behaviour may have led to better outcomes.

Hatchery-level predictive values for infectious pancreatic necrosis virus and Aeromonas salmonicida in Ontario, Canada.

The probability and uncertainty of correctly classifying the IPNV and Aeromonas salmonicida status of fish-rearing and natural sites in Ontario were estimated through Monte Carlo simulations. Propagating several uncertain inputs showed the extent to which natural variability and our present lack of knowledge affect the probability of site misclassification. For the scenarios investigated, the site-level negative predictive values (SNPVs) were high and fairly constant. The site-level positive predictive values (SPPVs) - given a test specificity ranging between 0.999 and 1.0 - were much lower, more variable, and highly affected by cut-off point and sample size. Substantial uncertainty resides in classifying the pathogen status of test-positive sites, whereas much less uncertainty resides in classifying pathogen status of test-negative sites.

Predictors of owner response to companion animal death in 177 clients from 14 practices in Ontario.

OBJECTIVE: To identify predictors of grief and client desires and needs as they relate to pet death. DESIGN: Cross-sectional mail survey. SAMPLE POPULATION: 177 clients, from 14 randomly selected veterinary practices, whose cat or dog died between 6 and 43 days prior to returning the completed questionnaire. PROCEDURE: Veterinary practices were contacted weekly to obtain the names of clients whose pets had died until approximately 200 clients were identified. Clients were contacted by telephone, and a questionnaire designed to measure grief associated with pet death was mailed to those willing to participate within 1 to 14 days of their pet's death. The questionnaire measured potential correlates and modifiers of grief and included three outcome measures: social/emotional and physical consequences, thought processes, and despair. Demographic data were also collected. RESULTS: Approximately 30% of participants experienced severe grief. The most prominent risk factors for grief included level of attachment, euthanasia, societal attitudes toward pet death, and professional support from the veterinary team. CONCLUSIONS AND CLINICAL RELEVANCE: Bivariate and multivariate analyses highlighted the impact owners' attitudes about euthanasia and professional intervention by the veterinary team had on reactions to pet death. Owners' perceptions of societal attitudes, also a predictor of grief, indicate that grief for pets is different than grief associated with other losses.

Therapy for patients with high grade astrocytoma using intraarterial chemotherapy and radiation therapy.

BACKGROUND: High grade astrocytomas account for approximately 40% of all primary brain tumors. The median survival is approximately 8-10 months for patients with glioblastoma multiforme and 36 months for patients with anaplastic astrocytoma. The results of systemic chemotherapy in the treatment of brain tumors have been reported to be less than satisfactory, mainly because of the blood-brain barrier impermeability for chemotherapeutic drugs. Intraarterial chemotherapy has been an attractive alternative with which to overcome this problem. METHODS: Eighty-three patients with high grade astrocytoma (glioblastoma multiforme [63 patients] and anaplastic astrocytoma--[20 patients]) were treated with intraarterial (intracarotid and/or intravertebral) chemotherapy and radiation therapy between 1987 and 1997. Patients received cisplatin, 60 mg/m2, and etoposide, 40 mg/m2. Radiation therapy was delivered either after completion of the chemotherapy or concomitantly with the chemotherapy. RESULTS: Thirty-four of 71 evaluable patients with high grade astrocytoma (48%) responded to the chemotherapy. The median survival for patients with glioblastoma multiforme who received chemotherapy prior to radiation therapy was 20 months versus 7 months for those patients who underwent concomitant chemotherapy/radiation therapy. Patients with anaplastic astrocytoma who received chemotherapy prior to radiation therapy had a median survival of 45 months compared with 12 months for patients who received concomitant chemotherapy/ radiation therapy. The toxicity profile has been reported to be mild and well tolerated. CONCLUSIONS: Intraarterial chemotherapy for patients with glioblastoma multiforme, delivered prior to radiation therapy, appears to result in a median survival three times longer than that achieved with concomitant chemotherapy/radiation therapy. In addition, patients appear to survive substantially longer than they do after radiation therapy with the addition of systemic chemotherapy. Side effects are reported to be acceptable.

A modified two-step phage display selection for isolation of polycystin-1 ligands.

The identification of proteins that interact with polycystin-1, the product of the autosomal dominant polycystic kidney disease gene, is an important step towards understanding the molecular pathogenesis of the disease. We have developed a two-step approach for the efficient identification of potential polycystin-1 ligands using the T7 phage display system. The first enrichment step of 4-5 rounds of biopanning is followed by a second step of reverse protein overlay assay. Thus, the sequencing efforts are minimized to the analysis of only positive rather than randomly chosen clones from the enriched population as in the standard phage display approach. Most importantly, the modified approach immediately provides the confirmation of the specificity of interaction and discriminates between strong and weak interactions. Here we present several potential interactors with distinct regions of polycystin-1, representing high-affinity binding partners.

Sampling considerations for herd-level measurement of faecal Escherichia coli antimicrobial resistance in finisher pigs.

The objective of this study was to determine the most efficient means of sampling faeces of finisher pigs for accurate and precise farm-level estimates of antimicrobial resistance among faecal Escherichia coli. Resistance to tetracycline and gentamicin of 8250 isolates of E. coli from 55 finisher pigs on one farm was measured with a hydrophobic grid membrane filter method. The between-pig, within-pen component of variance in resistance was large (97.5%), while between-pen, within-room and between-room components were small (2.5% and 0%, respectively). Using these resistance data, the abilities of two sampling strategies to estimate prevalence were modelled with a Monte Carlo 'bootstrap' procedure. Compositing faecal samples from several pigs before testing produced unbiased and precise estimates of prevalence and is simpler technically than individual animal testing.

Toxicities related to intraarterial infusion of cisplatin and etoposide in patients with brain tumors.

Chemotherapy for malignant brain tumors has a limited efficacy largely due to restricted blood-brain barrier permeability for chemotherapeutic drugs. Intraarterial chemotherapy (IAC) has the advantage of increased uptake during the first passage of the drugs through tumor capillaries. Initial IAC trials had less than satisfactory results due to unacceptable toxicities. Between 1987 and 1996, 173 patients with primary and metastatic brain tumors were treated with intraarterial (intracarotid and/or intravertebral) cisplatin and etoposide (VP-16). Out of these, 168 patients, who received a total of 438 cycles, were evaluated for the incidence of toxicities. Patients received either cisplatin at 40 mg/m2 and VP-16 at 20 mg/m2 or cisplatin at 60 mg/m2 and VP-16 at 40 mg/m2. Nausea and vomiting were the most common toxicities (42 patients, 14% of cycles). Arterial puncture was associated with a 1.6% incidence of groin hematomas (6 patients), and a 0.7% incidence of failure to canulate the carotid or vertebral arteries (3 patients). Neurologic toxicities included headache (1.4% of cycles, 5 patients), focal seizures (1.4% of cycles, 5 patients), transient confusion and urinary retention/incontinence (1.9% of cycles, 8 patients), and blurred vision (0.9% of cycles, 4 patients). We have not seen visual loss, strokes, major vessel dissection or thrombosis, or myelosuppression. Toxicity incidence was higher in patients with metastatic brain tumors than in those with primary brain tumors (34% versus 17%, p < 0.001). It was also higher in patients who had brain radiation therapy (RT) prior to IAC than in those who had RT concomitant with IAC (31% versus 19%, p = 0.05). No significant difference in toxicity incidence was noticed between patients who received RT concomitant with IAC and those who received RT after IAC (19% and 23% respectively, p = 0.08). Intracarotid chemotherapy given prior to RT resulted in 23 months of median survival for patients with glioblastoma multiforme. Intraarterial chemotherapy with cisplatin and VP-16 is a relatively safe treatment modality, especially in patients with primary brain tumors who have not received brain radiotherapy.

Owner response to companion animal death: development of a theory and practical implications.

This study used an inductive research method known as grounded theory to develop a theory to describe owner response to the death of a pet. Participants were identified from 8 veterinary clinics in Wellington Country, Ontario. Eighty percent (8 of 10) of the practices approached agreed to participate and there was a 77% (44 of 57) participation rate by clients. Nondirective interviews were conducted with participants approximately 10 days following the death of their pet, and at 3, 6, and 12 mo thereafter. The theory developed suggests that people's reactions are best described as a social and psychological search for meaning. Factors that contributed to the search for meaning included societal values and norms, the cultural milieu of pet death, and the cultural milieu of veterinary medicine. Other factors, such as the participant's personal beliefs, life stage, critical life events, and animal attributes, either alleviated or aggravated the experience. The outcome for participants grieving the death of a pet was a self-governing approach to coping with the death. Practical implications and suggestions for veterinarians are presented.

A rapid colour stabilization technique for radiochromic film dosimetry.

Various forms of GAFChromic film have been used for several years as radiographic media for measuring dose distributions of brachytherapy sources and small radiation fields. Upon irradiation the film changes colour and darkens with time post-irradiation. The darkening is most rapid in the first 24 h, and it has been suggested that for accurate dosimetry a waiting period of 24 h should occur before any optical density (OD) measurements are taken. A more rapid colour stabilization (RCS) procedure has been developed and is evaluated. The procedure consists of heating the film post-irradiation for a period of 2 h at 45 degrees C. The RCS procedure is compared with a control group and the dose response is tested for linearity, stability and reproducibility using two densitometers with light sources at different wavelengths (632.8 nm and 671 nm). The rise in net optical density (NOD) for the period 3-168 h is less than 3% for the RCS group as compared with 12% for the controls. In the first 24 h, the increase in NOD for the RCS samples is less than 0.5%, as opposed to 6% for the control group.

Androgen induction of urokinase gene expression in LNCaP cells is dependent on their interaction with the extracellular matrix.

Urokinase-type plasminogen activator (uPA) plays a central role in tissue remodeling and cell invasion. In the present study, we examined the expression of uPA in the prostate cancer cell lines LNCaP, DU-145 and PC-3. In contrast to DU-145 and PC-3, the androgen-responsive cell line LNCaP does not express uPA. However, seeding LNCaP cells on fibronectin-coated plates stimulated a low level of uPA expression which was further induced upon exposure of the cells to dihydrotestosterone (DHT). Concomitant with the expression of uPA, an androgen-regulated expression of uPA receptor (uPAR) was induced. These results suggest that the interaction of LNCaP cells with the extracellular matrix plays a dominant role in the androgen control of uPA and uPAR gene expression.

Individual and group antimicrobial usage rates on 34 farrow-to-finish swine farms in Ontario, Canada.

Antimicrobial drug-use was assessed on 34 farrow-to-finish operations that marketed at least 500 hogs/yr. These operations either did not use any antimicrobials or used narrow-spectrum or broad-spectrum antimicrobials in rations of post-weaning pigs. Total antimicrobial use was measured for two months after obtaining inventories and records of all antimicrobials used. The collection of empty medication bottles and inventories of drugs on hand was convenient for producers and useful for estimating or validating recorded treatment rates, particularly for antimicrobials that were used only in one class of pig. Treatment records, however, underestimated by approximately 35% the amounts used for 27/29 farm-antimicrobial combinations. Rates of individual-pig treatment varied from 0-24.1 pigs treated/1000 pig-days, with a median of 5.29. Most individual animal treatments were given to piglets and sows at parturition and penicillin was the most commonly used antimicrobial. Gentamicin was administered to suckling piglets on 19 of the farms.

Prevalences of resistance to seven antimicrobials among fecal Escherichia coli of swine on thirty-four farrow-to-finish farms in Ontario, Canada.

Fecal specimens were composited and a hydrophobic-grid membrane-filter method was used to measure antimicrobial resistance to ampicillin 16 micrograms/ml, carbadox 30 micrograms/ml, gentamicin 4 mu/ml, nitrofurantoin 32 micrograms/ml, spectinomycin 16 micrograms/ml, sulfisoxazole 32 micrograms/ml and tetracycline 8 micrograms/ml among 8119 Escherichia coli isolates from 68 fecal samples collected on 34 farrow-to-finish swine farms marketing over 500 hogs/yr. The overall prevalences of resistance to antimicrobials among these isolates were: ampicillin 29%, carbadox 3.5%, gentamicin 0.6%, nitrofurantoin 27%, spectinomycin 28%, sulfasoxizole 38% and tetracycline 71%. Thirty to seventy-six per cent of the variations in prevalences were explained by between-farm differences.

Associations among antimicrobial drug treatments and antimicrobial resistance of fecal Escherichia coli of swine on 34 farrow-to-finish farms in Ontario, Canada.

Logistic regression was used to model associations between antimicrobial treatment and resistance among fecal Escherichia coli of finisher pigs at the farm level. Four sets of potential risk factors representing different levels of refinement of antimicrobial use on farms were modelled on resistance to antimicrobials. Final models for each antimicrobial were constructed from treatment and management variables significant on initial screening, and corrections for overdispersion were made. In general, in-feed antimicrobial treatment of pigs was more consistently associated with an increased risk of resistance than individual-animal treatment. Antimicrobial treatment in starter rations was significant in final models of resistance to ampicillin, carbadox, nitrofurantoin, sulfisoxizole, and tetracycline. Treatment in grower-finisher rations was significantly associated with resistance to ampicillin, spectinomycin, sulfisoxizole, and tetracycline. There was little evidence that in-feed antimicrobials increased the risk of resistance to gentamicin, which is a drug used only for individual-pig treatment in this study population. These results suggest that antimicrobial medication of rations of post-weaning pigs selects for and maintains antimicrobial resistance among E. coli of finisher pigs. Although resistance was common on farms that did not medicate rations of post-weaning pigs, the results indicate that antimicrobial use does increase the risk of resistance to the antimicrobials studied.

Measurement of antimicrobial-resistant Escherichia coli in pig feces with a hydrophobic grid membrane filter interpreter system.

Hydrophobic grid membrane filter technology was used to measure resistance among Escherichia coli in pig fecal samples to ampicillin, sulfisoxazole, and tetracycline. The method accurately measured resistance, with sensitivities ranging from 96.5 to 99.5% and specificities ranging from 87.0 to 98.3%, and it identified E. coli with 96% confidence.

Breast radiotherapy and lymphedema.

BACKGROUND: Breast radiotherapy has a low incidence of long term complications. Lymphedema is the most commonly reported complication and adversely affects the quality of life of the breast carcinoma patient. Although its incidence is decreasing, lymphedema still remains a significant concern for patients and their physicians. With the indications for radiotherapy in breast carcinoma management broadening, current strategies to prevent radiation-related lymphedema should be applied and new strategies should be developed. METHODS: A review of the literature addressing lymphedema as a complication of radiotherapy in breast carcinoma management was performed. RESULTS: Arm, breast, and truncal edema occur after primary breast carcinoma management. The literature supports the view that radiotherapy contributes to arm and breast edema. Lymphedema occurs most commonly in patients who have both axillary radiotherapy and surgery, is often triggered by a soft tissue infection, and is more common in obese patients. The incidence of arm edema is decreasing due to more conservative surgical treatment of the axilla and possibly due to more conservative management of the breast. Trends in breast edema are less discernible. Single-modality treatment of the axilla is associated with a very low incidence of arm edema. CONCLUSIONS: Lymphedema continues to be a problem in the care of the breast carcinoma patient. More conservative surgery combined with careful patient selection for nodal radiotherapy reduces its incidence. Radiotherapy technique, prompt treatment of soft tissue infections, and weight loss in obese patients each can contribute to prevention. The risk of lymphedema is greatly surpassed by the benefits of radiotherapy in the care of the breast carcinoma patient.

Antimicrobial drug use and related management practices among Ontario swine producers.

A mail survey of swine producers in Ontario was undertaken during 1991 to describe the types, frequency, and motives for antimicrobial use. Two hundred operations that marketed fewer than 350 hogs per year, and 800 that marketed more than 350 per year were sent questionnaires, 63% of which were completed and returned. Most operations (86%) added antimicrobials to starter (weanling pig) rations, while fewer (29%) added these drugs to finisher pig rations. The most commonly used antimicrobials were tylosin, carbadox, and furazolidone in weanling pigs, and tylosin, lincomycin, and tetracycline in finishers. Water medication of grower-finisher pigs was practised on 25% of farms; 80% of farms had injected at least some grower-finisher pigs with antimicrobials in the 12 mo preceding the survey. Approximately 20% of operations that added antimicrobials to finisher rations did so for growth promotion purposes only, while others used them for disease treatment, prevention, control, or a combination of reasons. Among those not using antimicrobials in finisher rations, 83% did not believe they were necessary and 37% were concerned about the potential for residues in marketed hogs.