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Biomedical subjects

L Anderson

Publications and source records attributed to L Anderson.

At least 55 records · Page 3Linked to original sources
PubMed1999

Lead: male-mediated effects on reproduction and development in the rat.

The present study was designed to determine the effect of relatively low levels of lead acetate (25 and 250 ppm) exposure on fertility and offspring viability in male Sprague-Dawley rats. Protein synthesis in 2-cell embryos was monitored by [35S] methionine labeling and two-dimensional SDS gel electrophoresis. Fertility was reduced in males with blood lead levels in the range 27-60 microg/dL. Lead was found to affect initial genomic expression in embryos fathered by male rats with blood lead levels as low as 15-23 microg/dL. Dose-dependent increases were seen in an unidentified set of proteins with a relative molecular weight of approximately 70 kDa (Mr). These results indicate that male-mediated effects of lead may be observed in the 2-cell embryo. The alteration observed in embryonic gene expression with paternal lead exposure may be useful for studying the role of the paternal contribution to the activation of the embryonic genome and protein synthesis in the early embryo.

Animals↗
PubMed1999

A comparison of the effect of rocuronium and vecuronium on heart rate during gynaecological laparoscopy.

The effect on intra-operative heart rate of two nondepolarising muscle relaxants, rocuronium and vecuronium, was compared in 116 fit out-patients undergoing gynaecological laparoscopic procedures. Both groups received an anaesthetic technique which differed only in the choice of muscle relaxant. Intra-operatively it was noted that patients given rocuronium (20 mg) had significantly fewer episodes of bradycardia (heart rate < 50 beat.min-1) than patients given vecuronium 4 mg (p < 0.05). Profound bradycardias (heart rate < 30 beat.min-1) did not occur in any of the patients in the rocuronium study group, whereas 5% of patients receiving vecuronium had a period of transient asystole. We conclude that, at the doses stated, rocuronium results in significantly fewer episodes of bradycardia than vecuronium when used as a muscle relaxant for laparoscopic gynaecological procedures.

Adult↗
PubMed1999

Antegrade visceral revascularisation via a thoracoabdominal approach for chronic mesenteric ischaemia.

OBJECTIVES: It has been suggested that patients with chronic visceral ischaemia are elderly and emaciated hence they may not tolerate antegrade visceral revascularisation via a thoracoabdominal approach. There are no studies to support this assumption. The purpose of this study is to assess the efficacy of this approach for the treatment of chronic visceral ischaemia. METHODS: Between 1988 and 1996, 10 patients underwent antegrade visceral revascularisation for chronic visceral ischaemia via a thoracoabdominal approach and were followed-up for a mean of 40 months. Eight patients were treated with aorto superior mesenteric artery bypass and implantation of the coeliac axis in the graft and two patients with aorto superior mesenteric bypass alone. Graft patency was monitored with duplex scanning. RESULTS: There were no postoperative deaths in this series. Two patients developed postoperative pulmonary infections and required intubation for a short period of time. All patients were discharged after a mean of 17 days (range 7-38). Follow up with duplex scanning revealed that all grafts were patent. One patient developed a high grade anastomotic stenosis which was followed by recurrence of the symptoms. This was dilated on three occasions by balloon angioplasty within a period of 17 months. On the last occasion a stent was placed and since the patient remains asymptomatic. CONCLUSIONS: Antegrade visceral revascularisation via a thoracoabdominal approach is a durable and effective method of relieving symptoms of chronic visceral ischaemia. The low morbidity in this series justifies larger studies in order to establish the true incidence of complications.

Aged↗
PubMed1999

Merosin-positive congenital muscular dystrophy: a large inbred family.

Large families with congenital muscular dystrophy are rare. We report a clinical, histopathological, immunocytochemical, electrophysiological, radiological and genetic study of 10 cases affected by "pure" CMD belonging to two generations of a large inbred Palestinian family. The disease showed autosomal recessive inheritance. All patients had generalised muscular weakness and hypotonia at birth without arthrogryposis. They had a relatively benign clinical course with stabilisation of the clinical picture at different ages and at variable degrees of severity. The pattern of muscle weakness and wasting was more marked in the proximal upper limb-girdle and trunk muscles. Lower limb muscles were more mildly involved. Serum CK was normal or moderately increased. All patients had normal intelligence, normal computed tomography (CT) scans of the brain and normal somatosensory evoked potentials (SEP). Electromyography (EMG) and muscle biopsy showed morphological changes compatible with muscular dystrophy. Immunocytochemistry for dystrophin, laminin alpha 2 of merosin, and for alpha, beta, gamma sarcoglycans was normal. Linkage analysis excluded all the known loci for CMD, including laminin alpha 2 on chromosome 6q2, the Fukuyama congenital muscular dystrophy locus on 9q3, the integrin alpha 7 locus on chromosome 12q13 and the recently identified locus on 1p35-36. The family we present is clinically and genetically distinct from the already mapped forms of congenital muscular dystrophy. Genetic studies are in progress to localise the gene responsible for this condition.

Adolescent↗
PubMed1999

The effect of wrist angle on electrically evoked hand opening in patients with spastic hemiplegia.

This paper studied the effect of wrist angle on the amount of hand opening achieved by electrical stimulation in people with spastic hemiplegia. With their forearm in pronation, subjects were asked to relax while their affected wrist was passively moved in steps of about 15 degrees from full flexion into extension. Trains of stimuli were applied to the long finger extensor muscles through surface electrodes on the forearm. At each wrist position stimulation was turned on for a few seconds until hand opening equilibrated. Wrist angle and fingertip positions were recorded using a three-dimensional (3-D) motion analysis system. Maximal displacements between thumbtip and each fingertip occurred when the wrist was fully flexed. As the wrist was extended, hand aperture achieved by electrical stimulation progressively declined, reaching zero at 40 degrees of wrist extension. We conclude that electrical stimulation can significantly increase the grasp aperture of the hemiplegic hand, but this is strongly dependent on wrist posture and accompanying voluntary effort.

Adolescent↗
PubMed1999

Staff recruitment challenges and interventions in agencies supporting people with developmental disabilities.

Recruitment challenges and costs were identified by administrators from 129 randomly selected agencies that provide residential, vocational, and other services to persons with developmental disabilities in Minnesota. Finding qualified applicants was the most difficult staffing problem reported. Common recruitment incentives included providing competitive benefits, allowing time off without pay, and offering paid leave time. Relatively few agencies used innovative strategies (e.g., bonuses for employees who recruit new workers). The average agency had vacancy rates of 6% in direct-support positions and 4% in first-line supervisor positions. On the basis of these findings, one could determine that the cost of advertising and overtime for vacant positions in Minnesota could approach $6.7 million per year.

Costs and Cost Analysis↗
PubMed1999

What do internal medicine residents need to enhance their diabetes care?

OBJECTIVE: To identify areas that should be targeted for improvement in care, we examined internal medicine resident practice patterns and beliefs regarding diabetes in a large urban hospital outpatient clinic. RESEARCH DESIGN AND METHODS: Internal medicine residents were surveyed to assess the frequency at which they performed key diabetes quality of care indicators. Responses were compared with recorded performance derived from chart and laboratory database reviews. Resident attitudes about diabetes were determined using the Diabetes Attitude Survey for Practitioners. Finally, an eight-item scale was used to assess barriers to diabetes care. RESULTS: Both self-described and recorded performance of recommended diabetes services short of national recommendations. For yearly eye examinations and lipid screening, recorded performance levels were similar to trainees' reports. However, documented inquiries about patient self-monitoring of blood glucose, performance of foot examinations, and urine protein screening were lower than trainees' reports. Some 49% of the residents selected a target HbA1c of 6.6-7.5% as an attainable goal, yet half of the patients using oral agents or insulin had HbA1c values > 8.0%. No differences in self-described or recorded performance were found by year of training. Most residents did not perceive themselves to need additional training related to diabetes care, and residents were generally neutral about patient autonomy. Patient nonadherence and time constraints within the clinic were most often cited as barriers to care. CONCLUSIONS: The study identifies several areas that require improvement in resident care of diabetes in the ambulatory setting. Because experience during training contributes to future practice patterns, developing a program that teaches trainees how to implement diabetes practice guidelines and methods to achieve optimal glycemic control may be key to future improvements in the quality of diabetes care.

Adult↗
PubMed1999

Thioguanine administered as a continuous intravenous infusion to pediatric patients is metabolized to the novel metabolite 8-hydroxy-thioguanine.

Thiopurine antimetabolites have been in clinical use for more than 40 years, yet the metabolism of thiopurines remains only partially understood. Data from our previous pediatric phase 1 trial of continuous i.v. infusion of thioguanine (CIVI-TG) suggested that TG was eliminated by saturable mechanism, with conversion of the drug to an unknown metabolite. In this study we have identified this metabolite as 8-hydroxy-thioguanine (8-OH-TG). The metabolite coeluted with the 8-OH-TG standard on HPLC and had an identical UV spectrum, with a lambda(max) of 350 nm. On mass spectroscopy, the positive ion, single quad scan of 8-OH-TG yielded a protonated molecular ion at 184 Da and contained diagnostic ions at m/z 167, 156, 142, and 125 Da. Incubation of TG in vitro with partially purified aldehyde oxidase resulted in 8-OH-TG formation. 8-OH-TG is the predominant circulating metabolite found in patients receiving CIVI-TG and is likely generated by the action of aldehyde oxidase.

Aldehyde Oxidase↗
PubMed1999

Regional hospital improves efficiency with co-generation retrofit.

Feasibility analysis of the co-generation retrofit of the Red Deer Regional Hospital pointed to a reasonable payback of capital cost and increased efficiency in operation of the facility. Budget restrictions nearly stopped the project from proceeding. Innovative construction procedures proposed by the Facility Management Group, in particular, Mr Keith Metcalfe, Director of Maintenance, allowed a worthwhile project to reach successful completion. We feel that this model can perhaps be used by similar facilities in the future to achieve their energy efficiency goals.

Alberta↗
PubMed1998

Ganciclovir chemoablation of herpes thymidine kinase suicide gene-modified tumors produces tumor necrosis and induces systemic immune responses.

The goal of this work was to identify potential host immune responses to thymidine kinase (TK) suicide gene-modified tumors undergoing chemoablation induced by the prodrug ganciclovir (GCV). The aims were to measure the efficacy and specificity of immunity induced against unmodified tumor, to identify qualitative or quantitative changes in the host response to TK+ tumors undergoing chemoablation that may contribute to the induction of antitumor immunity, and to compare critically the induction of immunity by chemoablation of TK-modified tumors with that of other methods of immunization in this tumor model and in response to other well-defined model antigens. Animals treated with TK+ tumors and GCV developed specific resistance to rechallenge with unmodified tumor. GCV induced significant tumor necrosis, which was associated with a pronounced host cell infiltrate composed of polymorphonuclear cells, both CD4+ and CD8+ T lymphocytes, and increased intratumoral IL-12. Cyclophosphamide-treated mice exhibited no such host response despite the induction of tumor necrosis. CTL responses to defined antigens in TK+ cells were greater in animals treated with prodrug than were those in animals not treated with prodrug but harboring live TK+ cells. Similar degrees of immunity were produced by immunization with irradiated cells.

Animals↗
PubMed1998

High dose rate intraoperative radiation therapy (HDR-IORT) as part of the management strategy for locally advanced primary and recurrent rectal cancer.

PURPOSE: Primary unresectable and locally advanced recurrent rectal cancer presents a significant clinical challenge. Local failure rates are high in both situations. Under such circumstances, there is a significant need to safely deliver tumoricidal doses of radiation in an attempt to improve local control. For this reason, we have incorporated a new approach utilizing high dose rate intraoperative radiation therapy (HDR-IORT). METHODS AND MATERIALS: Between 11/92-12/96, a total of 112 patients were explored, of which 68 patients were treated with HDR-IORT, and 66 are evaluable. The majority of the 44 patients were excluded for unresectable disease or for distant metastases which eluded preoperative imaging. There were 22 patients with primary unresectable disease, and 46 patients who presented with recurrent disease. The histology was adenocarcinoma in 64 patients, and squamous cell carcinoma in four patients. In general, the patients with primary unresectable disease received preoperative chemotherapy with 5-fluorouracil (5-FU) and leucovorin, and external beam irradiation to 4500-5040 cGy, followed by surgical resection and HDR-IORT (1000-2000 cGy). In general, the patients with recurrent disease were treated with surgical resection and HDR-IORT (1000-2000 cGy) alone. All surgical procedures were done in a dedicated operating room in the brachytherapy suite, so that HDR-IORT could be delivered using the Harrison-Anderson-Mick (HAM) applicator. The median follow-up is 17.5 months (1-48 mo). RESULTS: In primary cases, the actuarial 2-year local control is 81%. For patients with negative margins, the local control was 92% vs. 38% for those with positive margins (p = 0.002). The 2-year actuarial disease-free survival was 69%; 77% for patients with negative margins vs. 38% for patients with positive margins (p = 0.03). For patients with recurrent disease, the 2-year actuarial local control rate was 63%. For patients with negative margins, it was 82%, while it was 19% for those with positive margins (p = 0.02). The disease-free survival was 47% (71% for negative margins and 0% for positive margins) (p = 0.04). Prospective data gathering indicated that significant complications occurred in approximately 38% of patients and were multifactorial in nature, and manageable to complete recovery. CONCLUSION: HDR-IORT using our technique is versatile, safe, and effective. The local control rates for primary disease compare quite well with other published series, especially for patients with negative margins. For patients with recurrent disease, locoregional control and survival are especially encouraging in patients with negative resection margins. Further follow-up is needed to see whether these encouraging data will continue.

Adenocarcinoma↗
PubMed1998

A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers.

Genetic and biochemical studies in lower eukaryotes have identified several proteins that ensure accurate segregation of chromosomes. These include the Drosophila aurora and yeast Ipl1 kinases that are required for centrosome maturation and chromosome segregation. We have identified two human homologues of these genes, termed aurora1 and aurora2, that encode cell-cycle-regulated serine/threonine kinases. Here we demonstrate that the aurora2 gene maps to chromosome 20q13, a region amplified in a variety of human cancers, including a significant number of colorectal malignancies. We propose that aurora2 may be a target of this amplicon since its DNA is amplified and its RNA overexpressed, in more than 50% of primary colorectal cancers. Furthermore, overexpression of aurora2 transforms rodent fibroblasts. These observations implicate aurora2 as a potential oncogene in many colon, breast and other solid tumors, and identify centrosome-associated proteins as novel targets for cancer therapy.

3T3 Cells↗
PubMed1998

Mycophenolate mofetil reduces the risk of acute rejection less in African-American than in Caucasian kidney recipients.

BACKGROUND: Multicenter clinical trials have shown that mycophenolate mofetil (MMF) reduces the risk of acute rejection, but it is unknown whether African-Americans constitute a subgroup of recipients less likely to benefit from MMF. METHODS: This study compared the acute rejection rates within 6 months of kidney transplantation in MMF-treated transplant patients with those on azathioprine (AZA) at a single center. The study population consisted of 353 consecutive recipients of cadaver or living donor kidney transplants. African-Americans constituted 43% of the patients on AZA and 49% of the patients on MMF. Variables used in a Cox regression analysis included MMF immunosuppression, recipient race, type of transplant, delayed graft function, postoperative immune induction, average cyclosporine trough level, and HLA mismatch. RESULTS: Significantly fewer patients on MMF experienced a biopsy-proven rejection episode than those treated with AZA (24% vs. 42%, respectively; relative risk [RR]=0.57, P=0.001). This decrease in risk was greater in Caucasian transplant recipients (MMF vs. AZA: 16% vs. 46%, RR=0.35, P < 0.001) than in African-American patients (32% vs. 36%, RR=0.88, P=0.6). Within each race stratum, the mean cyclosporine trough levels averaged over 2-week intervals were nearly identical for AZA- compared with MMF-treated patients. In the regression model, the effect of MMF on the incidence of rejection was again less in African-American than in Caucasian patients. CONCLUSIONS: Kidney recipients treated with MMF have a significantly lower risk of acute rejection within 6 months of transplantation than those given AZA. This reduction in risk is significantly less in African-American recipients than Caucasians.

Adult↗
PubMed1998

Missense mutations in the chromosome 14 familial Alzheimer's disease presenilin 1 gene.

Mutations in the presenilin genes (PS-1 and PS-2) cause early onset autosomal dominant Alzheimer's disease (AD). Eight early-onset, autopsy-documented familial AD kindreds were screened for mutations in PS-1, and seven different mutations were identified. Three of these were new mutations (G209V, A426P, and E120D), two were previously reported mutations in new families, and three mutations were confirmed in previously published families. Two of these new mutations are found within predicted transmembrane domains (TMDs 4, 7, and 8). The A426P mutation is the most C-terminal PS-1 mutation identified to date.

Adult↗