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Biomedical subjects

K Mitchell

Publications and source records attributed to K Mitchell.

At least 55 records · Page 3Linked to original sources
PubMed1998

FADD: essential for embryo development and signaling from some, but not all, inducers of apoptosis.

FADD (also known as Mort-1) is a signal transducer downstream of cell death receptor CD95 (also called Fas). CD95, tumor necrosis factor receptor type 1 (TNFR-1), and death receptor 3 (DR3) did not induce apoptosis in FADD-deficient embryonic fibroblasts, whereas DR4, oncogenes E1A and c-myc, and chemotherapeutic agent adriamycin did. Mice with a deletion in the FADD gene did not survive beyond day 11.5 of embryogenesis; these mice showed signs of cardiac failure and abdominal hemorrhage. Chimeric embryos showing a high contribution of FADD null mutant cells to the heart reproduce the phenotype of FADD-deficient mutants. Thus, not only death receptors, but also receptors that couple to developmental programs, may use FADD for signaling.

Adaptor Proteins, Signal Transducing↗
PubMed1998

First sexual intercourse: anticipation and communication. Interviews with young people in England.

This study investigated anticipation and communication around first sexual intercourse through semi-structured interviews with young people (aged 16 to 29) in England. Ranging from surprise to pre-planning, several different levels of anticipation are explored. The main findings are as follows: communication plays a central role, mediating between the degree of anticipation and the degree to which first intercourse is wanted, protected and enjoyed. First intercourse tends to be characterized by silence, especially during early, spontaneous encounters. Silence does not imply lack of communication-non-verbal communication plays an important role. Where young people are ambivalent, verbal and non-verbal communication may send contradictory messages. The implications of the results for future safer sex campaigns are discussed.

Adolescent↗
PubMed1998

'Being there': learning through active participation.

Students engagement in learning is predicated not only on interest but on the perception of relevance to their needs. A hermeneutic interpretation of narrative student evaluation data from an introduction to nursing lecture course that was taught by means of a practice-based phenomenological approach revealed a pattern of student learning in which students moved from detachment to active participation in their learning. The stories shared by nurses in the practice setting were instrumental in introducing students to the world of nursing and facilitating a sense of belonging. Once engaged in the experience, students looked for opportunities to become active participants in their learning. A practice-based phenomenological approach to a theory course maximizes opportunities for student participation. Active reflection and integration allow students to make their own connections between theory and practice.

Curriculum↗
PubMed1998

Phase II study of liarozole in advanced non-small cell lung cancer.

The aim of this phase II study was to investigate the efficacy and tolerability of liarozole, a novel benzimidazole derivative, in non-small cell lung cancer (NSCLC). Liarozole 300 mg twice daily orally was evaluated in 14 patients with stage IIIB and IV NSCLC. 8 patients had received prior treatment with chemotherapy and/or radiotherapy. WHO toxicity grading and response criteria were used. Liarozole was well tolerated. Grade 2 toxicities included alopecia (1 patient), dermatological toxicity (5 patients), dry mouth (2 patients) and nausea and vomiting (2 patients). Leukocytosis was seen in 5 patients, including 2 cases with an elevated white cell count pretreatment. Liarozole was discontinued in 1 patient who developed intolerable progressive pruritus associated with an erythematous rash. No objective tumour response was seen, all 14 patients developing progressive disease within 4 months of commencing treatment. Liarozole was well tolerated but was ineffective as single agent therapy in the management of NSCLC. The side-effect profile was compatible with inhibition of retinoic acid degradation.

Administration, Oral↗
PubMed1998

Responsiveness to direct versus indirect hypnotic procedures: the role of resistance as a predictor variable.

Empirical research attempting to demonstrate that indirectly phrased hypnotic suggestions result in greater responsiveness than do direct approaches generally has not shown any differences on formal hypnotizability scales. However, empirical research in related areas along with clinical observation suggests that client resistance might be a crucial moderating variable. Specifically, participants with greater resistance would be expected to be more responsive to indirect approaches, whereas those with low levels of resistance would be more responsive to direct hypnotic procedures. To test this hypothesis, participants were given either a standardized test of hypnotic responsiveness that used direct suggestions (Harvard Group Scale of Hypnotizability) or a comparable indirect scale (Alman Wexler Indirect Hypnotic Susceptibility Scale) followed by administration of a measure of resistance (Therapeutic Reactance Scale). The hypothesis was not confirmed, in that those with higher (or lower) reactance/resistance did not score differently than those on either the indirect or direct hypnotizability measures.

Adolescent↗
PubMed1998

Cerebrovascular adaptation after unilateral carotid artery ligation in the rat: preservation of blood flow and ATP during forebrain ischemia.

To investigate long-term adaptations after unilateral carotid artery ligation, the effect of forebrain ischemia on cerebral blood flow and ATP levels was determined at various times after ligation. Unilateral carotid artery ligation was performed in male Wistar rats 0, 3, or 7 days before forebrain ischemia. Laser-Doppler blood flow was monitored bilaterally over the parietal cortex and ATP was measured in the subadjacent cortex of both hemispheres at the end of a 10-minute episode of ischemia. In the 0-day group, forebrain ischemia reduced cortical blood flow to 12% +/- 8% (mean +/- SD) of preischemic values and lowered cortical ATP to 26% +/- 35% of control levels in the ipsilateral hemisphere. Delaying the onset of forebrain ischemia for 3 days after carotid artery ligation significantly improved cortical blood flow (29% +/- 12%, P < 0.05) and ATP levels (92% +/- 11%, P < 0.05) in the ipsilateral hemisphere. Delaying forebrain ischemia for 7 days also significantly improved ipsilateral blood flow (36% +/- 11%, P < 0.05) and ATP levels (81% +/- 29%, P < 0.05) compared with the 0-day group. In the contralateral hemisphere, the reduction in blood flow and ATP levels was not significantly altered by delaying the onset of forebrain ischemia for 3 or 7 days. These results show that unilateral carotid artery ligation induces long-term vascular adaptations that improve the collateral circulation and preserve ATP levels during a subsequent episode of ischemia.

Adaptation, Physiological↗
PubMed1998

Staphylococcus succinus sp. nov., isolated from Dominican amber.

Two bacterial isolates, designated AMG-D1T and AMG-D2, were recovered from 25-35-million-year-old Dominican amber. AMG-D1T and AMG-D2 biochemically most closely resemble Staphylococcus xylosus; they differ physiologically from other staphylococci. Fatty acid analysis and comparisons with extensive databases were unable to show relatedness to any specific taxon. Moreover, AMG-D1T and AMG-D2 contain tuberculostearic acid and meso-diaminopimelic acid, characteristic of the G + C-rich coryneform bacteria, as opposed to L-lysine characteristic of staphylococci. AMG-D1T and AMG-D2 have a G + C ratio of 35 mol%. Phylogenetic analysis with the 16S rRNA gene indicated that AMG-D1T and AMG-D2 were most closely related to Staphylococcus equorum, S. xylosus, Staphylococcus saprophyticus and other novobiocin-resistant staphylococci. Stringent DNA-DNA hybridization studies with AMG-D1T revealed similarities of 38% with S. equorum, 23% with S. xylosus and 6% with S. saprophyticus. The results indicate that AMG-D1T and AMG-D2 represent a novel species, which was named Staphylococcus succinus sp. nov. The type strain of the new species is AMG-D1 (ATCC 700337).

Amber↗
PubMed1998

Women HIV sexual risk takers: related behaviors, interpersonal issues, and attitudes.

HIV and AIDS is a growing health risk for heterosexual women, particularly women of color (Centers for Disease Control and Prevention, 1997). Our research identified 5 types of HIV sexual risk taking in 3 independent samples of adult women from a New England Community: Group A women were noted by low to moderate levels of the 4 risk markers (i.e., unprotected vaginal sex, perceived partner-related risk, number of sexual partners, and unprotected anal sex); Group B women reported very high frequency of unprotected vaginal sex; Group C women were characterized by unprotected anal sex; Group D women had high perceived partner risk; and Group E women reported extremely high levels on all 4 HIV risk markers. Sexual risk groups were validated by demonstrating significant differences among groups on relevant behaviors, interpersonal experiences, and attitudes. Compared to other women, higher risk types reported greater behavioral risk practices (substance use, prostitution, diverse sexual experience), interpersonal risk experiences (sexual abuse, violence), initiation sexual assertiveness, and attitudinal risks (psychosocial distress). They reported less interpersonal assurance (surety of own and partner's HIV status), sexual assertiveness (for condom use and partner communication), psychosocial strengths (sexual self-acceptance), and transtheoretical readiness for change (condom use efficacy, readiness to consider condoms). Results provide additional support for the multifaceted model of HIV risk and the transtheoretical model. Suggestions for specifically focused interventions are given, depending on the pattern of sexual risk taking.

Adolescent↗
PubMed1997

Methicillin-resistant Staphylococcus aureus (MRSA) in nursing homes in a major UK city: an anonymized point prevalence survey.

An anonymized point-prevalence survey of methicillin-resistant Staphylococcus aureus (MRSA) carriage was conducted amongst a stratified random sample of nursing home residents in Birmingham, UK, during 1994. Microbiological sampling from noses, fingers and the environment was undertaken. Information about potential risk factors for the acquisition of MRSA was gathered. MRSA was isolated from cultures of the nose or fingers of 33 of the 191 residents who took part in the study (17%) but only 1 of the 33 positive residents had a clinical infection. Although just 10 of the 87 environmental samples were MRSA positive, there was some environmental contamination in most homes. Risk factors for MRSA carriage were hospital admission within the last year (relative prevalence 2.09, 95% CI 1.13-3.88; P < 0.05) and surgical procedures within the last year (relative prevalence 4.02, 95% CI 2.18-7.43; P = 0.002). Phage-typing of the strains revealed similarities with those circulating in Birmingham hospitals. These findings suggest that the prevalence of MRSA in nursing homes in Birmingham was high, and that the strains may have originated in hospitals.

Bacteriophage Typing↗
PubMed1997

Metyrapone pre-treated inferior petrosal sinus sampling in the differential diagnosis of ACTH-dependent Cushing's syndrome.

BACKGROUND: Inferior petrosal sinus sampling (IPSS) is a useful investigative technique in the differential diagnosis of ACTH-dependent Cushing's syndrome. Diagnostic accuracy is improved by the administration of corticotrophin releasing-factor (CRF) during the procedure to stimulate ACTH secretion. We hypothesized that, given the unavailability of CRF in Australia, stimulation of ACTH secretion from tumorous corticotrophs with metyrapone treatment before IPSS may be useful. AIMS: To describe our clinical experience with a novel diagnostic test, and to compare results between IPSS with and without metyrapone pre-treatment. SETTING: Metropolitan, Australian university teaching hospital. PATIENTS: 18 patients were studied on 21 occasions: three with Cushing's disease without metyrapone treatment prior to IPSS (M-), 11 with Cushing's disease with metyrapone pretreatment (M+), three with ectopic ACTH syndrome, and one with pseudo-Cushing's syndrome. TREATMENT: Patients received oral metyrapone, median dose 750 mg 6 hourly, for 24 h before IPSS. RESULTS: No major side effects were noted. Metyrapone increased serum 11-deoxycortisol concentration to a median of 400 nmol/l (range 36-1310) on the morning of the test. Radiological confirmation of correct catheter placement was shown in 36/42 inferior petrosal sinuses (86%). Median peak central: peripheral ACTH ratios were 9.8 for M- pituitary adenomas (range 5.7-13.6), 12.9 for the technically successful M+ pituitary adenomas (range 8-54.1), and 1.6 for M+ ectopic ACTH syndrome cases (range 1.2-3.4). Repeat studies in unoperated patients with ectopic ACTH syndrome showed ratios < 1.6. IPSS showed median peak ACTH concentrations of 190 ng/l for M- pituitary adenomas (range 83-205), 595 ng/l for the technically successful M+ pituitary adenomas (range 80-7630; P = 0.035 compared to M-), and 62 ng/l for M+ ectopic ACTH syndrome cases (range 47-220). IPSS correctly identified the pituitary source of ACTH production in all cases of Cushing's disease (except one technical failure where MRI revealed a lesion). MRI scanning correctly identified a lesion in 3/14 operated Cushing's disease cases. IPSS correctly lateralized 1/3 M- and 7/8 M+ Cushing's disease cases where the procedure was technically successful and surgical descriptions adequate. Pituitary exploration revealed a visible lesion in 75% of cases corresponding to the side predicted by IPSS; 'blind' hemi-hypophysectomy was performed on the side predicted from IPSS in the remainder. All cases of Cushing's disease were cured or improved following surgery, with a median follow-up of 2.8 years (range 0.7-5.9). CONCLUSIONS: Metyrapone pre-treated inferior petrosal sinus sampling is safe, and appears to induce high ACTH output from pituitary corticotroph adenomas. The technique has allowed accurate localization and treatment of pituitary corticotroph microadenomas.

ACTH Syndrome, Ectopic↗
PubMed1996

The synergistic relationship between ethics and quality improvement: thriving in managed care.

Financial issues are encroaching upon health care decisions at a rapid pace in today's managed care arena. An examination of the parallel historical perspectives of bioethics, health care reimbursement, and quality improvement reveals that, by integrating an ethical framework with the quality improvement process, health care professionals can preserve patient-centered care. The article demonstrates the strength of this combined approach using restraints as an example.

Delivery of Health Care↗
PubMed1996

A prospective multicenter study demonstrating clinical benefit with a new accelerometer-based DDDR pacemaker. Dromos Dr Investigators Group.

From November 1994 to October 1995, 63 patients (average age 66 years; 41 men) from 15 centers implanted with the Biotronik Dromos DR and Ergos TC 03 pulse generators were prospectively screened with an exercise test in the DDD mode for the presence of chronotropic incompetence (CI). Both pulse generators incorporate an identical accelerometer-based motion sensor. CI was defined as a maximum heart rate < 60% of age predicted maximum heart rate or 100 beats/min. Twenty-five patients (40%) met the criteria for CI. Two weeks later, CI patients were required to complete paired metabolic exercise testing in the DDD and DDDR modes on consecutive days with a 24-hour rest period. The order of testing was randomized and performed double blinded to minimize potential biases. Three patients who did not reach the anaerobic threshold (AT) and one patient who was unable to perform the metabolic testing were excluded from the analysis. Compared to the DDD mode, there were statistically significant improvements in the DDDR mode for all five endpoints: heart rate (84 +/- 3.6 vs 113 +/- 3.5 beats/min; P < 0.0001); total exercise time (8.23 +/- 0.71 vs 9.15 +/- 0.65 min; P = 0.0005); maximum VO2 (17.76 +/- 1.36 vs 20.43 +/- 1.75 mL/kg per min; P = 0.0001); VO2 at AT (13.1 +/- 0.87 vs 14.59 +/- 0.79 mL/kg per min; P < 0.01); and exercise time to AT (5.65 +/- 0.61 vs 6.33 +/- 0.53 min; P = 0.02). In conclusion, the results of paired metabolic exercise tests with the Dromos DR and Ergos TC 03 pulse generators demonstrate a clear clinical benefit using the accelerometer-based sensor in the CI patient.

Acceleration↗
PubMed1996

Utility of the routine chest X-ray after "over-wire" venous catheter changes.

The Seldinger technique is commonly used to change central venous access catheters in the Intensive Care Unit. These catheters are routinely being changed to prevent septic complications. Some of these changes are performed by an "over-wire" technique. To assess the utility of postprocedural chest X-rays on critically ill patients after an over-wire catheter change, we followed 68 patients after they had 80 catheter changes. This study assesses catheter position by use of a postprocedural X-ray. During the study, we found no misplaced catheters and minimum symptomatology in 80 patients. The trauma/critical care fellows performing the procedures rated them as easy in 97.5 percent of the changes. The conclusion of the study is that, if the catheter change is technically easy and the patient has no symptoms, a postprocedural X-ray is not necessary.

Bacterial Infections↗
PubMed1996

Methyl DNA adducts, DNA repair, and hypoxanthine-guanine phosphoribosyl transferase mutations in peripheral white blood cells from patients with malignant melanoma treated with dacarbazine and hydroxyurea.

Dacarbazine (DTIC) is a DNA-methylating drug used in the treatment of malignant melanoma. Among the DNA dducts induced by DTIC are N7-methylguanine (N7-meG) and O6-methylguanine (O6-meG). The latter adduct, in particular, may be important in the mutagenic as well as the cytotoxic activity of DTIC. Repair of O6-meG is carried out by the enzyme O6-alkylguanine-DNA-alkyltransferase (AGT) by a process which results in its autoinactivation. N7-meG is lost from DNA partly spontaneously and partly by enzymatic depurination followed by excision repair of the resulting apurinic site. The purpose of this study was to determine the in vivo kinetics of formation and repair of O6-meG and N7-meG and the changes in AGT in peripheral WBCs with repeated doses of DTIC, and to determine the effects on these processes of concomitant administration of hydroxyurea. In addition, we examined the induction of mutations at the HPRT gene locus. Thirty-four patients with malignant melanoma received 1.0 g/m2 DTIC i.v. every 3 weeks. Hydroxyurea was added to the second and subsequent doses of DTIC in 19 patients. The concentrations of O6-meG, N7-meG, and AGT in peripheral blood lymphocytes were determined up to 24 h after each of the first two doses of DTIC. Mutations at the HPRT gene locus were determined using the T-cell clonal assay. Peak O6-meG levels were detected 1 and 4 h after the first and second dose of DTIC, respectively. AGT concentrations declined to 56.7% (range, 40.3-76.9%) and 55.0% (range, 45.4-58.9%) of pretreatment levels 24 h after the first and second doses of DTIC, respectively, and were still approximately 25%below their initial levels just prior to administration of the second dose of DTIC. An increase in formation of O6-meG was observed at all time points after the second dose of DTIC (P = 0.0001), which was not affected by cotreatment with hydroxyurea (P > 0.5). There was a negative correlation between pretreatment AGT levels and the O6-meG concentration at 24 h after therapy (r = -0.554, P = 0.014). N7-meG levels peaked at 6 h after DTIC therapy and were not significantly influenced by the cycle number. Cotreatment with hydroxyurea tended to be associated with lower levels of N7-meG (P = 0.08). There was no correlation between either O6-meG or N7-meG levels and the grade of neutropenia. On the basis of a limited series of blood samples analyzed, there was no firm evidence that chemotherapy with DTIC resulted in induction of HPRT mutations in lymphocytes. In conclusion, repeated administrations of DTIC resulted in higher concentrations of O6-meG, probably due to reduction in cellular AGT. Hydroxyurea did not significantly influence the kinetics of O6-meG, and N7-meG adduct formation. There was no significant induction of HPRT gene mutations with DTIC. This study suggests that sequencing of DTIC doses should be evaluated using the time course of cellular AGT depletion and DNA adduct formation to achieve higher cytotoxic efficiency.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Competent patients, incompetent decisions.

We describe the epidemiologic aspects of dialysis withdrawal, the role of patient autonomy and of medical beneficence in the decision to discontinue dialysis, and the conditions under which limits may be placed on patient autonomy. A case is presented that provides insight into the issues involved in making such decisions and that should provoke further discussion on the role of "medical guidelines" for dialysis refusal and withdrawal.

Beneficence↗