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Biomedical subjects

C Mitchell

Publications and source records attributed to C Mitchell.

At least 55 records · Page 3Linked to original sources
PubMed2000

Benefit of intensified treatment for all children with acute lymphoblastic leukaemia: results from MRC UKALL XI and MRC ALL97 randomised trials. UK Medical Research Council's Working Party on Childhood Leukaemia.

Treatment of children with acute lymphoblastic leukaemia (ALL) aims to cure all patients with as little toxicity as possible and, if possible, to restrict further intensification of chemotherapy to patients with an increased risk of relapse. However in Medical Research Council (MRC) trial UKALL X two short myeloablative blocks of intensification therapy given at weeks 5 and 20 were of benefit to children in all risk groups. The successor trials, MRC UKALL XI and MRC ALL97, tested whether further intensification would continue to benefit all patients by randomising them to receive, or not, an extended third intensification block at week 35. After a median follow-up of 4 years (range 5 months to 8 years), 5 year projected event-free survival was superior at 68% for the 894 patients allocated a third intensification compared with 60% for the 887 patients who did not receive one (odds ratio 0.75, 95% CI 0.63-0.90, 2P = 0.002). This difference was almost entirely due to a reduced incidence of bone marrow relapses in the third intensification arm (140 of 891 in the third intensification arm vs. 171 of 883 in the no third intensification, 2P = 0.02). Subgroup analysis suggests benefit of the third intensification for all risk categories. Overall survival to date is no different in the two arms, indicating that a greater proportion of those not receiving a third intensification arm and subsequently relapsing can be salvaged. These results indicate that there is benefit of additional intensification for all risk subgroups of childhood ALL.

Adolescent↗
PubMed2000

Joint liaison psychiatry-diabetes clinic: a new specialist service.

AIMS: Specialist diabetes clinics have an established role in prevention and management of complications. As psychological problems are usually treated separately from diabetes centres, the role of a specialist psychiatrist within a teaching hospital was assessed. The aims of the study were to describe referral patterns, specific psychiatric conditions and treatments offered. RESULTS: During weekly outpatient sessions over a 12-month period, 31 patients were referred with a wide range of psychiatric diagnoses. One-third of patients were seen on the day and two-thirds within 2 weeks of referral. Treatments included anti-depressant medication, counselling and cognitive behaviour therapy. Successful discharge was obtained in 10 subjects and eight were undergoing continued treatment. CONCLUSIONS: The range of specific diagnoses requiring psychiatric supervision supported the role of specifically trained personnel as seen in a joint liaison psychiatry-diabetes service.

Adult↗
PubMed2000

The treatment of Wilms' tumour: results of the United Kingdom Children's cancer study group (UKCCSG) second Wilms' tumour study.

The aims of the UKW2 study were: (1) to further refine treatment for stage I and II favourable histology (FH) patients; (2) to consolidate the UKW1 results for stage III FH patients; (3) to improve the outlook for patients with inoperable primary tumours and those patients with stage IV and unfavourable histology disease. Treatment consisted of primary nephrectomy, wherever possible, followed by chemotherapy and radiotherapy, as dictated by stage and histology. Treatment was refined successfully for stage I and II FH patients. The 4-year event-free survival for these two groups was 94% and 91%, respectively. Stage III FH patients had a 4-year event free survival of 84%. The outlook for patients with clear cell sarcoma of the kidney is as good as for patients with favourable histology, whilst that for patients with anaplastic or rhabdoid variants remains poor. The outlook for the majority of children with Wilms' tumour is now excellent.

Adolescent↗
PubMed2000

Assessment of endothelial cell proliferation in primary breast carcinoma and its association with axillary lymph node status.

The correlation between angiogenesis as assessed by endothelial cell proliferation in blood/lymphatic vessels in primary breast carcinomas, and axillary lymph-node metastasis was studied using a case-control design. Primary breast carcinomas, < 2 cm in diameter, from 26 axillary node positive patients (case), were compared with neoplasms from 45 node-negative patients (control). Vascularity, as assessed by vessel density, and endothelial cell proliferation were measured in a single tissue section using a double immunohistochemical staining technique using MIBI (Ki-67) and FVIII antibodies. No association between vascularity and node status was found (P > 0.70). Node positive breast carcinomas had, on average, significantly smaller proliferating vessels (140+/-7 microm in perimeter) in the primary lesion when compared with node negative tumours (164+/-7 microm in perimeter (P < 0.02). In addition, the frequency of relatively small vessels (less than 180 microm in perimeter) with proliferating endothelium was higher in node positive carcinomas than lymph-node negative neoplasms (P < 0.03). This association between node status and the size and frequency of blood/lymphatic vessels with proliferating endothelium in primary carcinoma may have important implications in metastasis.

Journal Article↗
PubMed2000

End-of-life care in the pediatric intensive care unit after the forgoing of life-sustaining treatment.

OBJECTIVE: To describe the attitudes and practice of clinicians in providing sedation and analgesia to dying patients as life-sustaining treatment is withdrawn. STUDY DESIGN: Prospective case series of 53 consecutive patients who died after the withdrawal of life-sustaining treatment in the pediatric intensive care unit at three teaching hospitals in Boston. Data on the reasons why medications were given were obtained from a self-administered anonymous questionnaire completed by the critical care physician and nurse for each case. Data on what medications were given were obtained from a review of the medical record. RESULTS: Sedatives and/or analgesics were administered to 47 (89%) patients who died after the withdrawal of life-sustaining treatment. Patients who were comatose were less likely to receive these medications. Physicians and nurses cited treatment of pain, anxiety, and air hunger as the most common reasons, and hastening death as the least common reason, for administration of these medications. Hastening death was viewed as an "acceptable, unintended side effect" of terminal care by 91% of physician-nurse matched pairs. The mean dose of sedatives and analgesics administered nearly doubled as life-support was withdrawn, and the degree of escalation in dose did not correlate with clinician's views on hastening death. CONCLUSION: Clinicians frequently escalate the dose of sedatives or analgesics to dying patients as life-sustaining treatment is withdrawn, citing patient-centered reasons as their principle justification. Hastening death is seen as an unintended consequence of appropriate care. A large majority of physicians and nurses agreed with patient management and were satisfied with the care provided. Care of the dying patient after the forgoing of life-sustaining treatment remains underanalyzed and needs more rigorous examination by the critical care community.

Analgesics↗
PubMed2000

Relationships between environmental factors and lung function of asthmatic subjects in south east Queensland, Australia.

Few panel studies have investigated the relationships between air pollutants and air spora and lung function change in asthmatic subjects. This article examines the association of outdoor air pollutant concentrations and air spora with the decrease in lung function (measured by morning peak expiratory flow) of two groups of asthmatic subjects in the subtropical environment of South East Queensland, Australia. Lung function responses were stratified by age, allergy status, and location, and seasonal effects were examined. Allergy status and age were found to be important, with air pollutants such as ozone and particles associated with decreases in lung function in allergic individuals older than 15 years. Fungal spore counts were strongly associated with a decrease in lung function in allergic adults, especially in those over 54 years, only in seasons when these air spora peak. Analysis for the entire study period indicates that the effect of ozone on peak expiratory flow in the allergic group can sometimes be confounded by air spora effects, indicating that in a subtropical climate the impact of ozone on asthma severity can be accurately estimated only when the confounding effects of air spora are included.

Adolescent↗
PubMed2000

UT-A2: a 55-kDa urea transporter in thin descending limb whose abundance is regulated by vasopressin.

The renal urea transporter gene (UT-A) produces different transcripts in the inner medullary collecting ducts (UT-A1) and thin descending limbs of Henle's loop (UT-A2), coding for distinct proteins. Peptide-directed rabbit polyclonal antibodies were used to identify the UT-A2 protein in renal medulla of mouse and rat. In the inner stripe of outer medulla, an antibody directed to the COOH terminus of UT-A recognized a membrane protein of 55 kDa. The abundance of this 55-kDa protein was strongly increased in response to chronic infusion of the vasopressin analog 1-deamino-[8-D-arginine]vasopressin (DDAVP) in Brattleboro rats, consistent with previous evidence that UT-A2 mRNA abundance is markedly increased. Immunofluorescence labeling with the COOH-terminal antibody in Brattleboro rats revealed labeling in the lower portion of descending limbs from short-looped nephrons (in the aquaporin-1-negative portion of this segment). This UT-A labeling was increased in response to DDAVP. Increased labeling was also seen in descending limbs of long-looped nephrons in the base of the inner medulla. These results indicate that UT-A2 is expressed as a 55-kDa protein in portions of the thin descending limbs of Henle's loop and that the abundance of this protein is strongly upregulated by vasopressin.

Animals↗
PubMed2000

Vasopressin-mediated regulation of epithelial sodium channel abundance in rat kidney.

Sodium transport is increased by vasopressin in the cortical collecting ducts of rats and rabbits. Here we investigate, by quantitative immunoblotting, the effects of vasopressin on abundances of the epithelial sodium channel (ENaC) subunits (alpha, beta, and gamma) in rat kidney. Seven-day infusion of 1-deamino-[8-D-arginine]-vasopressin (dDAVP) to Brattleboro rats markedly increased whole kidney abundances of beta- and gamma-ENaC (to 238% and 288% of vehicle, respectively), whereas alpha-ENaC was more modestly, yet significantly, increased (to 142% of vehicle). Similarly, 7-day water restriction in Sprague-Dawley rats resulted in significantly increased abundances of beta- and gamma- but no significant change in alpha-ENaC. Acute administration of dDAVP (2 nmol) to Brattleboro rats resulted in modest, but significant, increases in abundance for all ENaC subunits, within 1 h. In conclusion, all three subunits of ENaC are upregulated by vasopressin with temporal and regional differences. These changes are too slow to play a major role in the short-term action of vasopressin to stimulate sodium reabsorption in the collecting duct. Long-term increases in ENaC abundance should add to the short-term regulatory mechanisms (undefined in this study) to enhance sodium transport in the renal collecting duct.

Animals↗
PubMed2000

Health benefits achieved through the Seventh-Day Adventist Wellness Challenge program.

CONTEXT: The Wellness Challenge program introduces the philosophy of the healing power of God and stresses the importance of developing a sense of spirituality in conjunction with the promotion of good health. OBJECTIVE: To employ scientific rigor to the outcome measures of the Seventh-Day Adventist Wellness Challenge program. DESIGN: A 2-tailed, paired sample t test. SETTING: East Pasco Medical Center in Zephyrhills, Fla. PARTICIPANTS: 165 participants. INTERVENTION: Presurvey, 21-day outpatient wellness intervention; postsurvey, 6 weeks after completion of the program. MAIN OUTCOME MEASURES: Changes in behaviors related to cigarette smoking, alcohol use, eating patterns, exercise, water consumption, rest, relaxation, and time spent outdoors, as well as demographic data. RESULTS: Statistically significant differences were found between the pre- and postprogram clinical and laboratory test results for the participants' blood pressure, weight, glucose levels, and cholesterol at .05 alpha. Furthermore, self-health improvements measured by a pre- and postsurvey response confirmed statistically significant improvement in participants' willingness to improve their lifestyle behaviors for a potentially greater quality of life. CONCLUSION: The Wellness Challenge program offers ways to reduce risk factors related to chronic disease while improving the quality of life within an adult population by allowing people to slowly incorporate newly acquired tools into their everyday life.

Christianity↗
PubMed1999

Characteristics of rural dust events shown to impact on asthma severity in Brisbane, Australia.

Wind erosion in arid inland Australia leads to dust plumes which can pass over populated coastal areas in Eastern Australia, such as Brisbane. Such events can lead to concerns about respiratory health problems because they significantly increase the fine particle component of atmospheric aerosols. This paper examines the particulate characteristics of 11 dust events in Brisbane and associations with daily diary records (peak expiratory flow, symptoms) of people with asthma, and hospital emergency attendances for asthma during a number of seasons between 1992 and 1994. These dust events are frequently, but not always, characterised by higher particulate levels and higher ratios of fine to coarse particulates. The results indicate that a number of dust events were significantly associated with changes in asthma severity, but general relationships could not be determined. Given that the phenomenon of wind-blown dust is not isolated to the Australian continent, these findings raise important questions about the effects of wind-blown dust in other parts of the world.

Adolescent↗
PubMed1999

Absolute and relative rewarding properties of fructose, glucose, and saccharin mixtures as reflected in anticipatory contrast.

Rats preferred 2% fructose (F) to 2% glucose (G) in daily 5-min two-bottle preference tests, but preferred 8% G to 8% F with the same testing procedure. In four subsequent experiments brief (3 min) once-per-day sequential presentations of two F or two G solutions showed the following results. Anticipatory negative contrast (suppressed intake of the initial solution) was greater with quantitative variations in fructose (2% F followed by either 8, 16, or 32% F) than was the case when the same concentrations of G were paired. No contrast occurred with qualitative pairings of the two sugars--instead G enhanced the intake of F whether it was presented before or after F. A solution of 0.15% saccharin produced more suppression (contrast) of 2% glucose than of 2% fructose. Also, mixtures of 0.15% saccharin with either sugar (2 or 8% F or G) enhanced absolute intake of the sugars but did not substantially increase their contrast-producing properties--suggesting a distinction between absolute and relative rewarding properties of sugar/saccharin mixtures. In summary, anticipatory negative contrast can be produced by either taste or postingestive factors but the relationship between two-bottle preference, absolute reward value (as reflected in consumption in noncontrast conditions), and relative reward value (measured by the capacity to produce contrast) is complex.

Animals↗
PubMed1999

The relation between meal size and the time between meals: effects of cage complexity and food cost.

Certain popular models of the regulation of food intake predict a positive correlation between the size of a meal and the preceding and/or following intermeal interval. However, the reported strength of these prandial correlations has varied widely in the literature. To determine what factors may influence the strength of these relationships, we measured the timing of and amount consumed in meals of laboratory rats as a function of 1) whether they were housed in isolation or with partial access to peers or a running wheel, 2) whether they were disturbed daily or weekly for maintenance procedures, and 3) whether food was free or contingent on operant responding. We also compared two definitions of "meal" and "intermeal interval." Strong prandial correlations were found only occasionally. Caging, food cost, and maintenance frequency did not affect the size of the correlations, although these factors did influence the rats' meal patterns. We conclude the regulation of food intake cannot be explained by models relying on a regular relationship between meal size and intermeal interval.

Analysis of Variance↗
PubMed1999

Testing for HIV: current practices in the academic ED.

The objective of this study was to determine common practices for testing for Human Immunodeficiency Virus (HIV), particularly in patients with other sexually transmitted diseases (STD) in emergency departments (ED) with residency training in Emergency Medicine. Via mail, 112 directors of academic emergency medicine programs in the United States were surveyed. Surveys from 95 academic institutions were completed, returned, and included in the analysis. Three EDs (3%) routinely tested for HIV in patients with suspected STD. HIV testing was performed in the ED in 54% of responding institutions under special circumstances such as employee testing after occupational exposures (54%), cases of rape (46%), and suspicion of HIV infection by clinical manifestations other than suspected STD (36%). Based on the results it was determined that academic EDs do not routinely test for HIV in patients suspected of having a STD and have variable testing practices and policies regarding other possible HIV exposures.

AIDS Serodiagnosis↗
PubMed1999

Toxicity of nitrogen oxides and related oxidants on mycobacteria: M. tuberculosis is resistant to peroxynitrite anion.

OBJECTIVE: To test the toxicity of reactive nitrogen intermediates (RNI), including authentic nitric oxide (NO), nitrogen dioxide (NO2), and peroxynitrite anion (ONOO-), a potent oxidant derived from NO and superoxide anion, on various mycobacterial strains including M. tuberculosis. DESIGN: Relatively avirulent mycobacteria including M. smegmatis and BCG, as well as the pathogenic M. Bovis Ravenel and M. tuberculosis Erdman and the clinical isolate M160 (also known as the C strain) were tested for their susceptibility to the toxic effects of NO, NO2, and ONOO-, Deaerated, NO-saturated solutions as well as an anaerobic in vitro system in which mycobacteria can be exposed to desired concentrations of authentic NO or NO2, were employed in these studies. An in vitro ONOO- killing assay was used to examine the adverse effects of this NO-derived oxidant on the various strains of mycobacteria. RESULTS: Both NO and NO2 exhibit antimycobacterial activity, with the former being more potent. Results obtained using ONOO- killing assay revealed that while avirulent mycobacteria including BCG and M. smegmatis are susceptible to this NO-derived oxidant, the virulent Erdman strain of M. tuberculosis and M. bovis, as well as the clinical tuberculous isolate M160, are remarkably resistant. CONCLUSION: These results suggest that the interactions between RNI and various species of mycobacteria could be highly specific. And since activated macrophages produce peroxynitrite, the significance of the ONOO- resistance of M. tuberculosis strains in relation to intracellular survival deserves further investigation.

Adult↗