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Biomedical subjects

C Mitchell

Publications and source records attributed to C Mitchell.

At least 37 records · Page 2Linked to original sources
PubMed2001

Vertical transmission of Kaposi's sarcoma-associated herpesvirus.

Little is presently known about the specific routes of transmission of Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus-8 (HHV-8). To investigate whether this agent might be transmitted vertically from mother to infant, we conducted a study on 89 KSHV seropositive mothers and their newborn infants. Thirteen mothers (14.6%) had KSHV DNA detected in their peripheral blood mononuclear cells (PBMC). Two of 89 samples drawn at birth from infants born to KSHV seropositive mothers had KSHV DNA detectable within their PBMC. These findings suggest that KSHV can be transmitted perinatally, but infrequently. Other routes of transmission such as horizontal transmission remain the most likely means of KSHV transmission.

Adolescent↗
PubMed2001

Virtual 2-D gel electrophoresis: visualization and analysis of the E. coli proteome by mass spectrometry.

Mass spectrometric surface analysis of isoelectric focusing gels provides an ultrasensitive approach to proteome analysis. This "virtual 2-D gel" approach, in which mass spectrometry is substituted for the size-based separation of SDS-PAGE, provides advantages in mass resolution and accuracy over classical 2-D gels and can be readily automated. Protein identities can be postulated from molecular mass (+/-0.1-0.2% for proteins of <50 kDa in size) and pI (+/-0.3 pH unit) and confirmed by MALDI in-source decay of the intact protein (providing sequence spanning up to 43 residues) or by peptide mass mapping following gel-wide chemical cleavage. Additionally, posttranslational modifications such as fatty acid acylation can be detected by the mass-resolved heterogeneity of component hydrocarbon chains. Sensitivity was evaluated by comparing the number of proteins detected by this method to equivalently loaded silver-stained 2-D gels. In the 5.7-6.0 pH range, E. coli is predicted to contain 435 proteins; virtual 2-D gels found 250 proteins ranging from >2 to <120 kDa in size present at levels to tens of femtomoles, as compared to the 100 proteins found by silver-staining 2-D gels. Extrapolating this result to the total theoretical proteome suggests that this technology is capable of detecting over 2500 E. coli proteins.

Amino Acid Sequence↗
PubMed2001

Accelerated treatment of breast cancer.

PURPOSE: Radiation therapy (RT) restricted to the tumor bed, by means of an interstitial implant, and lasting 4 to 5 days after lumpectomy was prospectively evaluated in early-stage breast cancer patients treated with breast-conserving therapy (BCT). The goals of the study were to determine whether treatment time can be reduced and whether elective treatment of the entire breast is necessary. MATERIALS AND METHODS: Between January 1993 and January 2000, 174 cases of early-stage breast cancer were managed with lumpectomy followed by RT restricted to the tumor bed using an interstitial implant. Each brachytherapy patient was matched with one external-beam RT (ERT) patient derived from a reference group of 1,388 patients treated with standard BCT. Patients were matched for age, tumor size, histology, margins of excision, absence of an extensive intraductal component, nodal status, estrogen receptor status, and tamoxifen use. Median follow-up for both the ERT and brachytherapy groups was 36 months. RESULTS: No statistically significant differences were noted in the 5-year actuarial rates of ipsilateral breast treatment failure or locoregional failure between ERT and brachytherapy patients (1% v 0%, P =.31 and 2% v 1%, P =.63, respectively). In addition, there were no statistically significant differences noted in rates of distant metastasis (6% v 3%, P =.24), disease-free survival (87% v 91%, P =.55), overall survival (90% v 93%, P =.66), or cause-specific survival (97% v 99%, P =.28). CONCLUSION: Accelerated treatment of breast cancer using an interstitial implant to deliver radiation to the tumor bed alone over 4 to 5 days seems to produce 5-year results equivalent to those achieved with conventional ERT. Extended follow-up will be required to determine the long-term efficacy of this treatment approach.

Actuarial Analysis↗
PubMed2001

The effect of depositional history on contaminated bed sediment stability.

Experiments were conducted in an annular flume using a commercially available kaolinite clay as well as contaminated bed sediment from Hamilton Harbour (Ontario) to assess their stability against erosion. Critical shear stress for erosion was measured under different conditions of bed formation (quiescently deposited beds and shear deposited beds) as well as with and without the presence of a biostabilized bed. Results suggest that a biostabilized bed and a bed formed under a flowing condition, similar to a river scenario, will be more resistant against erosion than will a non-biostabilized bed and a bed formed under quiescent conditions. Up to three cycles of erosion and flocculation/deposition were observed to occur within one experiment. These results suggest that the depositional history and biostabilization of river bed sediments need to be seriously considered within sediment and contaminant transport models if meaningful estimates of sediment and contaminant source, fate and effect are to be generated and used for the management of our aquatic ecosystems.

Animals↗
PubMed2001

Alternative analysis of BOD removal in subsurface flow constructed wetlands employing Monod kinetics.

A new, mechanistic approach for design and analysis of subsurface flow (SSF) constructed wetlands is presented. The model is based on the assumption that the biological processes in wetlands, like other biological systems, exhibit Monod kinetics. A Monod approach fits well with observed wetland performance. It predicts first-order behaviour at low concentrations, that is, pollutant removal rates which increase with increasing pollutant concentration; and zero-order or saturated behaviour at high pollutant concentrations, that is, a maximum pollutant removal rate. A kinetic analysis of subsurface flow constructed wetlands exhibiting Monod kinetics reveals that loading rate, as well as the zero-order degradation rate constant, are essential parameters for efficient wetlands design for the removal of organic carbon. In particular, Monod kinetics enables the identification of an absolute maximum removal rate which is necessary to prevent undersizing in design. This is significant because it represents a theoretical upper bound on loading rate for wetlands design. The analysis is applied to wetlands data collected in North America by the US EPA in order to extract design criteria for BOD removal. It reveals that maximum loadings for SSF wetlands are at least 80 kg ha-1 d-1 for BOD. In addition, a new dimensionless performance efficiency parameter, omega, is presented as a more effective means of comparing wetland performance.

Biodegradation, Environmental↗
PubMed2001

Progressive reduction in treatment-related deaths in Medical Research Council childhood lymphoblastic leukaemia trials from 1980 to 1997 (UKALL VIII, X and XI).

In the last 20 years, the survival rate for children with acute lymphoblastic leukaemia (ALL) has markedly improved, largely owing to a decrease in relapses. However, children still die from complications of treatment and these are potentially preventable. We have analysed data from three large consecutive national protocols for ALL from 1980 to 1997 [Medical Research Council United Kingdom ALL (MRC UKALL) trials VIII, X and XI] to compare the incidence and causes of treatment-related deaths (TRD). The percentage of TRD has fallen from 9% to 2% (UKALL VIII to XI), largely as a result of a decrease in fatal infections. Deaths during induction have fallen from 3% to 1%, the main causes of death being bacterial, followed by fungal infection, while other causes, chiefly haemorrhage, have not declined. Remission deaths also decreased from 6% to 1%, particularly those deaths due to measles and pneumocystis carinii. More guidelines for surveillance and treatment of infections have been included within progressively more intensive protocols. Risk factor analysis showed increased TRD in patients with Down's syndrome, high leucocyte count and older age in UKALL XI. In contrast, the introduction of blocks of intensification was not associated with an increased death rate. While improved supportive care has reduced the incidence of TRD, there is still scope for further reduction by prompt treatment of suspected infection. Maintenance of herd immunity remains of vital importance in avoiding deaths from measles.

Antineoplastic Agents↗
PubMed2001

Localized paediatric orbital rhabdomyosarcoma: influence of imaging on treatment.

AIM: Orbital rhabdomyosarcoma is the most common primary malignant orbital tumour in children and has a good prognosis. The purpose of this paper was to review the imaging and consequent treatment of patients with localized orbital rhabdomyosarcoma from around the U.K. MATERIALS AND METHODS: Patients were identified through the U.K. Children's Cancer Study Group (UKCCSG) database. Investigations and therapy were dictated by the Malignant Mesenchymal Tumour '89 (MMT89) protocol. Imaging and radiological reports of 16 patients from 12 centres were reviewed. The number of patients receiving radiotherapy, timing of radiotherapy, and adherence to treatment protocols were assessed. RESULTS: Local radiologists' reports and imaging techniques varied between sequential examinations and centres. The imaging was adequate for management. No reports quoted measurements of the tumours. Treatment protocols were not always followed rigidly with regard to a residual mass at day 80 post-diagnosis. However, the protocol was not explicit for all outcomes. Fifteen out of 16 patients eventually received radiotherapy. CONCLUSION: There is no standardization of imaging between centres. The presence or absence of a post-therapeutic residue should be stated in the radiology report. Further investigation is needed to differentiate between fibrosis and recurrent tumour. Radiotherapy for residual mass at day 80 is probably more important than standardizing radiological technique.

Adolescent↗
PubMed2001

Fas/CD95 pathway induces mouse liver regeneration and allows for highly efficient retrovirus-mediated gene transfer.

Stable gene transfer into hepatocytes has been proposed to compensate for genetic deficiencies that affect liver function, or to deliver diffusible factors into the circulation. This strategy can be achieved using retroviral vectors; however, cell division must occur. We describe a simple and reproductive method that enables the induction of hepatocyte replication in a controlled fashion, thus allowing an efficient in vivo retroviral liver transduction that is applicable to mouse models of human genetic disorders. The approach is based on liver susceptibility to apoptosis via the Fas/CD95 pathway. We show that, 4 days following a single Fas agonist antibody (JO2) injection, hepatocyte replication occurs, the intensity of which is correlated with the level of the induced hepatic cytolysis. This treatment enables in vivo liver transduction, and its efficiency also correlates with the level of hepatic cytolysis. When recombinant retroviral vectors were infused intravenously during the period of hepatocyte replication, 15.4% +/- 1.7% of the hepatocytes were transduced, reaching up to 32.5%.

Alanine Transaminase↗
PubMed2001

End-of-life care in the pediatric intensive care unit: attitudes and practices of pediatric critical care physicians and nurses.

OBJECTIVE: To determine the attitudes and practices of pediatric critical care attending physicians and pediatric critical care nurses on end-of-life care. DESIGN: Cross-sectional survey. SETTING: A random sample of clinicians at 31 pediatric hospitals in the United States. MEASUREMENTS AND MAIN RESULTS: The survey was completed by 110/130 (85%) physicians and 92/130 (71%) nurses. The statement that withholding and withdrawing life support is unethical was not endorsed by any of the physicians or nurses. More physicians (78%) than nurses (57%) agreed or strongly agreed that withholding and withdrawing are ethically the same (p < .001). Physicians were more likely than nurses to report that families are well informed about the advantages and limitations of further therapy (99% vs. 89%; p < .003); that ethical issues are discussed well within the team (92% vs. 59%; p < .0003), and that ethical issues are discussed well with the family (91% vs. 79%; p < .0002). On multivariable analyses, fewer years of practice in pediatric critical care was the only clinician characteristic associated with attitudes on end-of-life care dissimilar to the consensus positions reached by national medical and nursing organizations on these issues. There was no association between clinician characteristics such as their political or religious affiliation, practice-related variables such as the size of their intensive care unit or the presence of residents and fellows, and particular attitudes about end-of-life care. CONCLUSIONS: Nearly two-thirds of pediatric critical care physicians and nurses express views on end-of-life care in strong agreement with consensus positions on these issues adopted by national professional organizations. Clinicians with fewer years of pediatric critical care practice are less likely to agree with this consensus. Compared with physicians, nurses are significantly less likely to agree that families are well informed and ethical issues are well discussed when assessing actual practice in their intensive care unit. More collaborative education and regular case review on bioethical issues are needed as part of standard practice in the intensive care unit.

Adult↗
PubMed2001

A randomized, double-blind study of triple nucleoside therapy of abacavir, lamivudine, and zidovudine versus lamivudine and zidovudine in previously treated human immunodeficiency virus type 1-infected children. The CNAA3006 Study Team.

OBJECTIVES: Abacavir (ABC) is a potent inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. We compared the efficacy, safety, and tolerability of combination therapy with ABC, lamivudine (3TC), and zidovudine (ZDV) versus 3TC and ZDV in antiretroviral experienced HIV-1-infected children over 48 weeks. METHODS: Two hundred five HIV-1-infected children who had received previous antiretroviral therapy and had CD4(+) cell counts >/=100 cells/mm(3) were stratified by age and by previous treatment. Participants were randomly assigned to receive ABC (8 mg/kg twice daily [BID]) plus 3TC (4 mg/kg BID) and ZDV (180 mg/m(2) BID; ABC/3TC/ZDV group) or ABC placebo plus 3TC (4 mg/kg BID) and ZDV (180 mg/m(2); 3TC/ZDV group). Participants who met a protocol-defined switch criteria (plasma HIV-1 RNA >0.5 log(10) copies/mL above baseline at week 8 or >10 000 copies/mL after week 16) had the option to switch to open-label ABC plus any antiretroviral combination or continue randomized therapy or withdraw from the study. RESULTS: The Kaplan-Meier estimates (95% confidence interval) of the proportion of participants who maintained HIV-1 RNA levels </=10 000 copies/mL for 48 weeks or more was significantly better in the ABC/3TC/ZDV group compared with the 3TC/ZDV group: 33% (23%-42%) versus 21% (13%-29%). At week 48, the proportions of participants with HIV-1 RNA </=10 000 copies/mL were 36% versus 26% for the ABC/3TC/ZDV and 3TC/ZDV groups, respectively, by intent-to-treat analysis. For the subgroup of participants with baseline HIV-1 RNA >10 000 copies/mL, a significantly higher proportion of participants in the ABC/3TC/ZDV group had HIV-1 RNA </=10 000 copies/mL compared with the 3TC/ZDV group (29% vs 12%) but no difference was observed in the subgroup of participants with baseline HIV-1 RNA </=10 000 copies/mL (78% vs 72%). The median changes from baseline in CD4(+) cell counts were greater in the ABC/3TC/ZDV group than in the 3TC/ZDV group. Few participants (3%) experienced abacavir-related hypersensitivity reaction. CONCLUSIONS: ABC, in combination with 3TC and ZDV, provides additional antiretroviral activity over 48 weeks, compared with combination therapy with 3TC and ZDV in antiretroviral experienced HIV-1-infected children. ABC was safe and generally well-tolerated and should be considered an active component of combination antiretroviral therapy in this pediatric population.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Identification of Anopheles aquasalis as a possible vector of malaria in Guyana, South America.

Adult female mosquitoes were collected in Mahdia, Guyana, to determine the incidence of malaria in Anopheles species found during the month of June 2000. Centers for Disease Control miniature white (incandescent) light traps, model 512, and miniature black (ultraviolet) light traps, model 912, were used to capture female mosquitoes. Numbers of mosquitoes collected were compared between white and black light traps and between traps set outside and inside of buildings. Adult female Anopheles mosquitoes were identified and an ELISA dipstick test for Plasmodium vivax and Plasmodium falciparum was performed on each mosquito. An aquasalis, An oswaldoi, and An braziliensis were attracted to white light traps. An triannulatus and An darlingi were collected from black light traps. Approximately the same numbers of all female Anopheles mosquitoes 28/45 (62%) were caught inside buildings as outside. Numbers of female non-anopheles mosquitoes captured in light traps varied between the traps set outside of buildings and inside of buildings with bright light traps collecting 91/122 (75%). A total of 45 Anopheles mosquitoes were captured and 122 non-anopheles species. Of the two known vectors of malaria in Guyana, An darlingi mosquitoes were not infected with P vivax but An aquasalis was found to be a carrier. The findings of this study suggest a need for further surveying and identification of current malaria vectors in Guyana.

Animals↗
PubMed2000

The Andro Project: physiological and hormonal influences of androstenedione supplementation in men 35 to 65 years old participating in a high-intensity resistance training program.

BACKGROUND: Since the passage of The Dietary Supplement Health and Education Act in 1994, there has been a flood of new "dietary" supplements promoting anti-aging benefits such as the enhancement of growth hormone or testosterone levels. Androstenediol and androstenedione are such products. This study's purpose was to elucidate the physiological and hormonal effects of 200 mg/d of oral androstenediol and androstenedione supplementation in men aged 35 to 65 years while participating in a 12-week high-intensity resistance training program. METHODS: Fifty men not consuming any androgenic-enhancing substances and with normal total testosterone levels, prostate-specific antigen, hemoglobin, and hematocrit, and with no sign of cardiovascular or metabolic diseases participated. Subjects were randomly assigned to a placebo, androstenediol (diol), or androstenedione (dione) group using a double-blind study design. Main outcomes included serum sex hormone profile, body composition assessment, muscular strength, and blood lipid profiles. RESULTS: During the 12 weeks of androstenedione or androstenediol use, a significant increase in the aromatization by-products estrone and estradiol was observed in both groups (P =.03). In the dione group, total testosterone levels significantly increased 16% after 1 month of use, but by the end of 12 weeks, they returned to pretreatment levels. This return to baseline levels resulted from increases in aromatization and down-regulation in endogenous testosterone synthesis based on the fact that luteinizing hormone was attenuated 18% to 33% during the treatment period. Neither androstenediol nor androstenedione enhanced the adaptations to resistance training compared with placebo for body composition or muscular strength. However, both androstenediol and androstenedione supplementation adversely affected high-density lipoprotein cholesterol (HDL-C) levels, coronary heart disease risk (representing a 6.5% increase), and each group's respective (low-density lipoprotein cholesterol [LDL-C]/HDL-C)/(apolipoprotein A/apolipoprotein B) lipid ratio (diol: +5.2%; dione: +10.5%; P =.05). In contrast, the placebo group's HDL-C levels increased 5.1%, with a 12.3% decline in the (LDL-C/HDL-C)/(apolipoprotein A/apolipoprotein B) lipid ratio. These negative and positive lipid effects occurred despite no significant alterations in body composition or dietary intakes in the supplemental groups or placebo group, respectively. CONCLUSIONS: Testosterone precursors do not enhance adaptations to resistance training when consumed in dosages recommended by manufacturers. Testosterone precursor supplementation does result in significant increases in estrogen-related compounds, dehydroepiandrosterone sulfate concentrations, down-regulation in testosterone synthesis, and unfavorable alterations in blood lipid and coronary heart disease risk profiles of men aged 35 to 65 years.

Adult↗
PubMed2000

Therapeutic liver repopulation in a mouse model of hypercholesterolemia.

Liver repopulation constitutes an attractive approach for the treatment of liver disorders or of diseases requiring abundant secretion of an active protein. We have described previously a model of selective repopulation of a normal liver by Fas/CD95-resistant hepatocytes, in which we achieved up to 16% hepatocyte repopulation. In the present study, we investigated the therapeutic efficacy of this strategy. With this aim, apolipoprotein E (ApoE) knockout mice were transplanted with Fas/CD95-resistant hepatocytes which constitutively express ApoE. Transplanted mice were submitted to weekly injections of non-lethal doses of the Fas agonist antibody Jo2. After 8 weeks of treatment, we obtained up to 30% of the normal level of plasma ApoE. ApoE secretion was accompanied by a drastic and significant decrease in total plasma cholesterol, which even fell to normal levels. Moreover, this secretion was sufficient to markedly reduce the progression of atherosclerosis. These results demonstrate the efficacy of this repopulation approach for correcting a deficiency in a protein secreted by the liver.

Animals↗
PubMed2000

Autopsy consent practice at US teaching hospitals: results of a national survey.

BACKGROUND: Autopsy rates continue to fall despite the enduring benefit of the procedure to families and medical science, yet there are few data about the consent process itself. OBJECTIVE: To evaluate the current practice of obtaining autopsy consent, by assessing the consent forms currently in use, the knowledge and attitudes of chief residents on the procedure, and the expert opinion of pathologists in those institutions. DESIGN: Cross-sectional survey. SETTINGS AND PARTICIPANTS: One hundred twenty-seven US teaching hospitals. RESULTS: Of all autopsy consent forms we surveyed, 84.7% contained 7 of 10 elements recommended by the College of American Pathologists. Only 7.1% of institutions supplied educational materials for the physician, as recommended by the College of American Pathologists. Overall, 50.1% of chief residents reported deficiencies in their knowledge of the autopsy procedure. Correspondingly, greater than 74.5% felt that educational materials would be beneficial for physicians and the family. Finally, 93.3% of chief residents believed that a limited autopsy should be offered to families, while 68 (90%) of 76 pathologists at these institutions believed that limited autopsies are an unsatisfactory alternative to the complete procedure. CONCLUSIONS: Chief residents at US teaching hospitals reported substantial deficiencies in their knowledge about autopsy and desire more training on the consent process. Autopsy consent forms are often lacking information that might help physicians and families in making an educated choice about autopsy. Teaching institutions need to reevaluate the training for the autopsy consent practice.

Autopsy↗
PubMed2000

A preclinical model of hepatocyte gene transfer: the in vivo, in situ perfused rat liver.

Delivering retroviruses targeted to hepatocytes in vivo involves the injection of retroviruses directly into the portal vein. The aim of this work was to establish a clinically relevant system for retrovirus-mediated gene transfer in a new model of in vivo, in situ perfused rat liver and to study the transgene expression. At 24 h after partial hepatectomy, the liver was completely excluded from the splanchnic circulation using an extracorporeal shunt. Two independent normothermal, oxygenated perfusion systems were used. First, liver perfusion was carried out with a recirculating system (1 h). Culture supernatant containing retroviruses (1.5 x 10(8) ffu/ml, beta-galactosidase gene) was used as perfusate. Then the liver perfusion was maintained for more 30 min in a single liver passage system using culture medium without retroviruses as perfusate. High hepatocyte transduction rates (up to 34.4%) were obtained. PCR analysis showed no provirus in extrahepatic organs. Viral titrations performed simultaneously (inflow and outflow liver lines) showed that after 1 h of perfusion (up to 30 successive liver passages) retroviruses were still detected in the liver outflow perfusate (up to 2.0 x 10(7) ffu/ml). Washing the liver for 30 min dramatically decreased the leakage of retroviruses in the outflow. In order to be of clinical use, the injection of retroviruses targeted to hepatocytes in vivo should be done while the liver is completely excluded from the splanchnic circulation to avoid any extrahepatic retrovirus diffusion.

Animals↗