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Biomedical subjects

D Swanson

Publications and source records attributed to D Swanson.

At least 19 recordsLinked to original sources
PubMed2001

Integrated therapy for locally advanced bladder cancer: final report of a randomized trial of cystectomy plus adjuvant M-VAC versus cystectomy with both preoperative and postoperative M-VAC.

PURPOSE: We conducted a phase III trial to investigate the timing of chemotherapy with respect to surgery for patients with resectable but high-risk urothelial cancer. The trial was also designed to evaluate the accuracy of clinical staging in patients with locally advanced cancer and the prognostic significance of chemotherapy-induced downstaging. PATIENTS AND METHODS: A total of 140 uniformly evaluated patients with locally advanced urothelial cancer were studied. Planned treatment was five cycles of chemotherapy (M-VAC: methotrexate, vinblastine, doxorubicin, and cisplatin) plus radical cystectomy and pelvic lymph node dissection. Patients were randomly assigned to receive either two courses of neoadjuvant M-VAC followed by surgery plus three additional cycles of chemotherapy, or, alternatively, to have initial cystectomy followed by five cycles of adjuvant chemotherapy. RESULTS: There were no significant differences in outcome between the two groups. By intent-to-treat, 81 patients (58%) remain disease-free, with median follow-up of 6.8 years. We confirmed a high rate of clinical understaging in this cohort, especially among patients showing lymphovascular invasion on biopsy. Patients with no residual muscle-invasive disease at cystectomy after neoadjuvant chemotherapy were likely to be cured. CONCLUSION: These results lend further support to the impression from small randomized trials that, in a high-risk cohort, there is an improved cure fraction by the combination of multiagent chemotherapy and surgery, although we found no preferred sequence. Importantly, it is possible to select appropriate patients for such therapy on the basis of clinical staging information. These results establish a benchmark of outcome for this cohort.

Adult↗
PubMed2001

Vision loss associated with a stiff neck complicating strabismus surgery.

An exotropic 60 year old suffered a scleral-choroidal penetration and vitreous hemorrhage during and after strabismus surgery on a highly myopic eye when her anesthetic airway management was complicated by her previously asymptomatic and unrecognized rigid cervical spine which placed both the surgeon and the anesthetist in disadvantaged positions both physically and medically. Restoration of vision and binocularity ultimately required vitrectomy and intraocular lens implantation.

Blindness↗
PubMed2000

Use of indium-111-labeled hepatocytes to determine the biodistribution of transplanted hepatocytes through portal vein infusion.

PURPOSE: Hepatocyte transplantation is useful for ex vivo gene therapy and liver repopulation. Methods for hepatic reconstitution were recently developed, but hepatocyte transplantation systems must be optimized. The authors report their experience with In-111 oxyquinolone labeling of a test dose of hepatocytes (108 cells) for noninvasive assessment of the biodistribution of transplanted hepatocytes in a 5-year-old child with omithine transcarbamoylase deficiency. MATERIALS AND METHODS: Donor hepatocytes (approximately 108) were radiolabeled using a commercially available In-111 oxyquinolone solution (specific activity of 1 mCi/ml). RESULTS: The overall labeling efficiency was 36.4%. A final dose of approximately 290 ,uCi of the In-111-labeled hepatocytes in 10 ml serum-free phosphate-buffered saline was infused percutaneously into the portal vein approximately 2.5 hours after their preparation. The study was performed 3 hours before cell transplantation (109 cells). Quantitative analysis of the biodistribution of In-111-labeled hepatocytes indicated that cells were predominantly localized in the liver immediately after portal vein-infused transplantation. The predominant hepatic distribution was persistent for as long as 7 days after the procedure, with an average liver-to-spleen ratio of 9.5 to 1. No significant pulmonary radiotracer uptake was present. CONCLUSION: These results indicate that In-111 labeling of hepatocytes is useful for the short-term noninvasive analysis of the biodistribution of transplanted hepatocytes.

Cell Movement↗
PubMed1999

Numerical chromosomal changes in DNA hypodiploid solid tumors: restricted loss and gain of certain chromosomes.

BACKGROUND: DNA hypodiploidy is a unique and rare finding associated with aggressive behavior in solid tumors. Identifying the chromosomal changes underlying this feature may provide important information on the development and progression of these neoplasms. METHODS: Fluorescence in situ hybridization analysis using alpha-satellite probes for nine autosomes and the two sex chromosomes was performed on interphase cells from 27 solid tumors which had been shown to be DNA hypodiploid by flow cytometry. The chromosomal abnormalities were correlated with the DNA index and tumor subtypes. RESULTS: The data show mutually exclusive loss of certain chromosomes and compensatory gain of other chromosomes in different tumors. The net loss was slightly more than the net gain for the chromosomes tested. Polysomy of chromosome 7 and monosomy of chromosomes 17, X and loss Y were found in most tumors. Significant differential loss of chromosomes 6,10, and 12 among DNA hypodiploid breast, kidney and lung carcinomas was noted. CONCLUSIONS: Our study shows (i) gain of chromosome 7 and loss chromosome 17 in most DNA hypodiploid tumors, (ii) specific chromosomal loss was noted in breast and renal cell carcinomas, and (iii) that different mechanisms for DNA hypodiploid and hyperdiploid development may exist.

Adult↗
PubMed1996

Transcatheter subendocardial infusion. A novel technique for mapping and ablation of ventricular myocardium.

BACKGROUND: Catheter ablation with radiofrequency energy is feasible in a limited subset of patients with ventricular tachycardia. The purpose of this study was to evaluate a technique for mapping and ablation of ventricular myocardium with the use of transcatheter subendocardial infusion. METHODS AND RESULTS: A needle-tipped deflectable electrode catheter was used to deliver reagents to endocardial target sites. This was equipped with two central lumens to allow sequential administration of mapping and ablation injectants with minimal admixture. The mapping injectant consisted of a mixture of lidocaine, iohexal, and glycerin; the ablation injectant contained ethanol, iohexal, and glycerin. Infusion of the mapping injectant (1 cm3 over 3 or 5 seconds, n = 14) produced a stain on fluoroscopy and increased local capture threshold by 61%. No lesions resulted from mapping infusions. Infusion of the ethanol-containing injectant (n = 48) produced discrete lesions, with a mean volume ranging from 0.6 to 1.5 cm3. There was a direct relationship between infusion volume, infusion duration, and resultant lesion volume. Fibrosis in a region of healed myocardial infarction did not impair diffusion of the injectant or affect lesion dimensions. Microscopic analysis of chronic lesions showed a sharply demarcated border zone between fibrotic and normal myocardium. CONCLUSIONS: Transcatheter subendocardial infusion can be used to reversibly impair local excitability and mark an injection site fluoroscopically. Subendocardial injection of ethanol can predictably ablate a large volume of ventricular myocardium. Additional study of this system in an arrhythmia model will help to define its potential for mapping and ablation of hypotensive ventricular tachycardia.

Animals↗
PubMed1996

Optimal delivery of perioperative chemotherapy: preliminary results of a randomized, prospective, comparative trial of preoperative and postoperative chemotherapy for invasive bladder carcinoma.

PURPOSE: We performed a planned interim analysis of a randomized trial comparing initial to postoperative chemotherapy for bladder cancer. The purpose of our analysis was to detect early evidence of survival differences, tolerance to therapy influenced by the sequence of treatment, predictive value of clinical state and influence of methotrexate, vinblastine, doxorubucin and cisplatin (M-VAC) on bladder resectability. MATERIALS AND METHODS: A total of 100 consecutive patients were randomized to receive 2 M-VAC courses before and 3 courses after surgery (group 1) or 5 adjuvant M-VAC courses following cystectomy (group 2). Survival, clinical response, clinical and pathological stage, and toxicity were evaluated in this second timed interim analysis. RESULTS: Of all patients 70% received at least 4 M-VAC courses. Overall survival at 31.7 months (range 1.8 to 87.7) was similar in groups 1 (60%) and 2 (63%), and independent of clinical stage. Preoperative clinical staging accurately identified patients at high risk for recurrence, while 37 of the 48 group 2 patients (77%) were considered at high risk by pathological staging (P3b, P4a, node-positive and unresectable disease). Comparison of pathological stage revealed that 14 of the 51 group 1 patients (28%) achieved stage P0 while only 1 of the 48 group 2 patients (2%) had P0 disease at surgery (p= 0.00043). Disease was unresectable in 3 group 1 (6%) and 8 group 2 patients (17%, p= 0.09). Tolerance to treatment was not significantly different in the 2 study arms. CONCLUSIONS: No survival advantage was noted between neoadjuvant and adjuvant M-VAC in our interim analysis. However, results suggest that M-VAC chemotherapy may be effective in increasing the resectability of localized bladder cancer and may contribute to organ preservation. Clinical stage was a reliable predictor of pathological findings at surgery. Future studies can use clinical staging to determine therapy before surgery for the select stages that we treated. Identification of the subset likely to achieve complete pathological remission will permit the selection of patients for organ preservation strategies.

Adult↗
PubMed1995

Interphase cytogenetics of renal cortical neoplasms. Correlation with DNA ploidy by flow cytometry.

The genotypic changes in 22 renal cortical neoplasms and 16 of the corresponding normal kidney tissues by fluorescence in situ hybridization (FISH) were studied using directly labelled probes for chromosomes 7, 8, 10, 11, 12, 17, 18, X, and Y, and by flow cytometry (FCM). DNA ploidy analysis revealed 8 DNA aneuploid and 14 DNA diploid neoplasms. The mean single spot hybridization in normal kidney was 5 +/- 0.9% for chromosomes 7, 8, 10, 11, 12, and the X in females. The mean single spot hybridization for chromosomes 17 and 18 was 14.9% and 18.5%, respectively. The mean number of more than two (> 2) hybridization signals in normal kidney cells for all autosomes and the X-chromosome in females was 3 +/- 1.2%. Significant chromosomal loss was restricted to chromosomes 8, 18, X, and Y. The net chromosomal gain and loss correlated with the DIs in aneuploid tumors. All DNA diploid neoplasms showed both chromosomal loss and gain with a tendency to a net loss. No apparent correlation between the chromosomal aberrations and the clinicopathologic factors was found in this cohort. Our study demonstrates that: (1) tissue specific controls may provide better information for definable performance criteria for this technique; (2) monosomy can more reliably be assessed on fresh samples; (3) chromosomal loss is confined to certain chromosomes; (4) DNA diploid tumors manifest heterogeneous gain and loss of various chromosomes with a tendency to a net loss; and (5) integrated FISH and FCM analysis provide more information on the chromosomal abnormalities of these neoplasms.

Adult↗
PubMed1995

Mamillothalamic tract transection blocks anterior thalamic training-induced neuronal plasticity and impairs discriminative offidance behavior in rabbits.

Rabbits with bilateral transecting lesions of the mamillothalamic tract, control (tract-sparing and sham) lesions, or no lesions, and chronic, fixed-position anterior ventral (AV) and medial dorsal (MD) thalamic and posterodorsal subicular complex unit recording electrodes were trained to step in an activity wheel in response to a 0.5 sec tone (CS+) in order to avoid a brief foot shock. The rabbits also learned to ignore a different tone (CS-) not predictive of shock. Behavioral acquisition was significantly retarded in rabbits with mamillothalamic tract transection compared to controls. When trained, transected rabbits failed to avoid the shock more often than controls. Mamillothalamic tract transection abolished and control lesions attenuated AV thalamic discriminative training-induced activity (i.e., development with training of greater discharges in response to the CS+ than to the CS-). Transection and control lesions attenuated AV thalamic excitatory training-induced activity (greater elicited activity during training than during unpaired tone-shock presentations before training) as well as AV thalamic "spontaneous" baseline unit activity. CS-elicited discharge magnitude was reduced by control lesions and it was further reduced by tract transecting lesions. Significant lesion-related changes were not found in the subicular or MD thalamic neuronal receptor. Mamillothalamic tract afferent information flow is thus essential for AV thalamic discriminative training-induced activity, excitatory training-induced activity, tone-elicited discharges and maintenance of conditioned avoidance responses. The effects of the control lesions suggested that afferents which course in parallel with and near the mamillothalamic tract may contribute to AV thalamic spontaneous activity and excitatory training-induced activity.

Animals↗
PubMed1994

"Stockless" cost reduction in the operating room.

St. Paul-Ramsey Medical Center in St. Paul, MN became one of the first hospitals in the United States to initiate a "stockless" par level inventory system. Successes with stockless led the hospital to look at implementing it in the OR to achieve a reduction of expense to revenue. Materiel Management and Surgical Services discussed a number of issues relevant to implementing a stockless program, including product flow, accuracy and cost of case carts and preference cards, item pricing, committed usage of items brought into the system and establishment of a steering committee. Specific OR issues and practices required evaluation and adjustment, such as the routine use of emergency direct ordering. Information systems support was brought in and a products committee established to do education and oversee the program. Savings for 1993-94 were $185,146.

Cost Savings↗
PubMed1992

An objective structured clinical examination for the licentiate: report of the pilot project of the Medical Council of Canada.

The Medical Council of Canada (MCC) administers a qualifying examination for the issuance of a license to practice medicine. To date, this examination does not test the clinical skills of history taking, physical examination, and communication. The MCC is implementing an objective structured clinical examination (OSCE) to test these skills in October 1992. A pilot examination was developed to test the feasibility, reliability, and validity of running a multisite, two-form, four-hour, 20-station OSCE for national licensure. In February 1991, 240 volunteer first- and second-year residents were tested at four sites. The candidates were randomly assigned to one of two forms of the test and one of two sites for two of the four sites. Generalizability analysis revealed that the variance due to form was 0.0 and that due to site was .16 compared with a total variance of 280.86. The reliabilities (inter-station) were .56 and .60 for the two forms. Station total-test score correlations, used to measure station validity, were significant for 38 of the 40 stations used (range .14-.60). The results of the OSCE correlated moderately with the MCC qualifying examination; these correlations were .32 and .35 for the two test forms. Content validity was assessed by postexamination questionnaires given to the physician examiners using a scale of 0 (low) to 10 (high). The physicians' mean ratings were: importance of the stations, 8.1 (SD, 1.8); success of the examination in testing core skills, 8.1 (SD, 1.6); and degree of challenge, 7.8 (SD, 2.1). The results indicate that a full-scale national administration of an OSCE for licensure is feasible using the model developed. Aspects of validity have been established and strategies to augment reliability have been developed.

Canada↗
PubMed1991

Assessment of clinical skills of residents utilizing standardized patients. A follow-up study and recommendations for application.

OBJECTIVE: To determine the reliability and validity of "standardized patients" to assess clinical performance of internal medicine residents. DESIGN: Each resident spent 2 half-days interacting with 19 standardized patients (nonphysicians taught to portray patients in a reproducible fashion). Each resident was asked to obtain focused histories, perform relevant physical examinations, and provide patient education or counseling. At the end of each 10- to 15-minute encounter, the resident was asked to identify positive findings on physical examination and to prioritize a differential diagnosis. Other, more traditional indicators of clinical skills were also obtained. PARTICIPANTS: Three hundred ten residents from nineteen internal medicine training programs in the New England region of the United States. RESULTS: Reproducible estimates of data gathering and interviewing skills were achieved with 1 day of testing. Validity analyses were difficult to interpret because of the lack of an external "gold standard." However, faculty judgments of performance from reviewing videotapes corresponded with standardized-patient-based scores. Differences in group performance were also demonstrated across years of training and between U.S. or Canadian and foreign medical graduates. CONCLUSIONS: Systematic and effective procedures for developing standardized-patient-based test materials and for training standardized patients have been developed. This technique is best used for measuring data gathering and interviewing skills. Correlations with commonly used evaluation methods were generally low; this may be because standardized patients measure different skills. Local use of this technique by residency programs and the development of regional consortia sharing resources, costs, and expertise are advocated.

Clinical Competence↗
PubMed1991

Discordance between accumulation of C-14 deoxyglucose and Tl-201 in reperfused myocardium.

Radiolabeled deoxyglucose (FDG) has been advocated as a marker of viability of reperfused myocardium during acute infarction. However, data for such recommendation are few. We investigated cardiac deposition of C-14 deoxyglucose (C-14 DG) and of Thallium -201 (Tl-201) in rabbits subjected to coronary occlusion (15, 30, 60 or greater than 100 min) and reperfusion (75 min and 24 h). Measured myocardial concentrations of C-14 DG and Tl-201 in macroautoradiograms were quantitatively correlated in a 24 h reperfusion group with presence of myocardial necrosis evaluated by light microscopy. The major finding in this investigation was that with 30 min or 60 min of ischemia followed by reperfusion there were myocardial regions with significant hypoperfusion (Tl-201) and histologic necrosis. However, in the same myocardial areas, the deposition of C-14 DG was not correlated with the extent of necrosis (r = 0.27). Also, the deposition of C-14 DG in acute myocardial infarction was higher than that of Tl-201 (P = 0.05 by paired T test and by nonparametric Wilcoxon's test). It was also demonstrated that when the occlusion time was varied (15-130 min) and early reperfusion was provided for 75 min or omitted altogether, the myocardial accumulation of Tl-201 was variable and that myocardial sequestration of C-14 DG was higher than perfusion in central and peripheral portions of the area-at-risk. These observations do not support a role for the use of radiolabeled deoxyglucose for the detection of myocardial viability in recently infarcted cardiac muscle.

Animal Nutritional Physiological Phenomena↗
PubMed1991

A new dosing schedule for gentamicin in blood pythons (Python curtus): a pharmacokinetic study.

Gentamicin is frequently used in the treatment of aerobic Gram-negative infections in reptiles. Pharmacokinetic data to ensure proper dosing are scant, especially for large snakes. A pharmacokinetic study of gentamicin was therefore conducted in four blood pythons. Snakes were given intramuscular injections of either 2.5 mg kg-1 or 3.0 mg kg-1 loading dose followed by 1.5 mg kg-1 at 72 and 96 hours. A linear pharmacokinetic relationship between gentamicin serum concentrations and time was demonstrated in each of the four snakes studied. Peak serum concentrations occurred six to 10 hours after injection and ranged from 4.6 to 8.9 micrograms ml-1. Half-life was variable and ranged from 32 to 110 hours. Total body clearance and apparent volume of distribution varied little between the individual snakes studied. There was no evidence of renal toxicity. For blood pythons a loading dose of 2.5 mg kg-1 followed by 1.5 mg kg-1 at 96 hour intervals is recommended. If higher concentrations are desired, a loading dose of 3.0 mg kg-1 followed by 1.5 mg kg-1 at 96 hours can be given. These dosing schedules will provide serum concentrations in excess of the minimum inhibitory concentrations for most aerobic Gram-negative bacilli that are pathogenic in snakes; gentamicin accumulation with subsequent renal dysfunction should not occur.

Animals↗
PubMed1991

Cefonicid versus clindamycin prophylaxis for head and neck surgery in a randomized, double-blind trial, with pharmacokinetic implications.

Perioperative single-dose antibiotic prophylaxis of cefonicid was compared with clindamycin in a prospective, randomized, double-blind trial of patients undergoing oncologic head and neck surgery. Antibiotics were administered intravenously beginning 1 to 2 h preoperatively. Cefonicid, 1 g, was given as a single dose. Clindamycin, 600 mg, was administered every 8 h for a total of four doses. Blood and wound drainage samples were collected for 24 h following the dose of cefonicid and assayed for total and free cefonicid concentrations, using reverse-phase high-performance liquid chromatography. Although total concentrations of cefonicid in both serum and wound drainage exceeded the MIC for 90% of the isolates of common bacterial pathogens for 24 h, free concentrations in serum and wound drainage (11.0 and 14.9% of total concentrations) were subinhibitory within 6 h following administration. Free concentrations of cefonicid in the postoperative wound drainage were subinhibitory for the entire study period, both perioperatively and postoperatively. Postoperative wound infection occurred significantly (P less than 0.05) more frequently in patients receiving cefonicid (24%) as compared with those receiving clindamycin (8.2%). The relatively low free levels of cefonicid achieved in serum and wound drainage were attributed to the high degree of protein binding (89% in serum) and may be related to the poor clinical outcome.

Cefonicid↗
PubMed1991

Use of ciprofloxacin versus use of aminoglycosides for therapy of complicated urinary tract infection: prospective, randomized clinical and pharmacokinetic study.

The efficacy of oral ciprofloxacin was compared with that of parenteral aminoglycoside for therapy of complicated urinary tract infection in a prospective randomized trial. The setting was a chronic-care Veterans Administration facility in which long-term bladder catheterization and resistant bacteria were common. Sixty-five consecutive patients were stratified for presence and type of bladder catheter, the presence of Providencia and Pseudomonas aeruginosa organisms versus other urinary pathogens, and renal dysfunction. A pharmacokinetic study of ciprofloxacin concentrations in serum and urine was performed with selected patients. Urinary catheters were present in 94%. All patients were symptomatic, and 58.5% had fever. Ciprofloxacin, 500 mg every 12 h orally, was compared with parenteral aminoglycoside for 7 to 10 days. Clinical response, defined by resolution of symptoms and fever at 5 to 9 days posttherapy (short-term) and 28 to 30 days posttherapy (long-term), was essentially identical for both treatment groups. Bacteriologic response, defined by sterile urine cultures, showed that ciprofloxacin was significantly more efficacious (P = 0.0005) than aminoglycoside at 5 to 9 days posttherapy. However, by 28 to 30 days, the response rate was essentially identical. Emergence of resistance to the study antibiotic was seen in 62 and 70% of those who did not show a bacteriological response and were receiving ciprofloxacin and aminoglycosides, respectively. Concentrations of ciprofloxacin and aminoglycoside in the urine substantially exceeded the MIC for the urinary pathogens isolated, although these concentrations did not correlate with short-term bacteriologic response for either antibiotic. Ciprofloxacin was efficacious in complicated urinary tract infection compared with the current standard of parenteral aminoglycoside among catheterized patients with relatively resistant bacteria.

Administration, Oral↗