The relationship between cytokeratin expression in bladder washings and resected tumour specimens.
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Biomedical subjects
Publications and source records attributed to J McKnight.
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CONTEXT: Alcohol is increasingly recognized as a factor in many boating fatalities, but the association between alcohol consumption and mortality among boaters has not been well quantified. OBJECTIVES: To determine the association of alcohol use with passengers' and operators' estimated relative risk (RR) of dying while boating. DESIGN, SETTING, AND PARTICIPANTS: Case-control study of recreational boating deaths among persons aged 18 years or older from 1990-1998 in Maryland and North Carolina (n = 221), compared with control interviews obtained from a multistage probability sample of boaters in each state from 1997-1999 (n = 3943). MAIN OUTCOME MEASURE: Estimated RR of fatality associated with different levels of blood alcohol concentration (BAC) among boaters. RESULTS: Compared with the referent of a BAC of 0, the estimated RR of death increased even with a BAC of 10 mg/dL (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.2-1.4). The OR was 52.4 (95% CI, 25.9-106.1) at a BAC of 250 mg/dL. The estimated RR associated with alcohol use was similar for passengers and operators and did not vary by boat type or whether the boat was moving or stationary. CONCLUSIONS: Drinking increases the RR of dying while boating, which becomes apparent at low levels of BAC and increases as BAC increases. Prevention efforts targeted only at those operating a boat are ignoring many boaters at high risk. Countermeasures that reduce drinking by all boat occupants are therefore more likely to effectively reduce boating fatalities.
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The 'Covalent Switching' hypothesis suggests that a strongly conserved tryptophan residue acts as a mediator of electron-transfer flow between redox partners in cytochrome P-450 systems [Baldwin, Morris and Richards (1991) Proc. R. Soc. London B 245, 43-51]. We have investigated the effect of alteration of the conserved tryptophan (Trp-97) in cytochrome P-450 BM3 (P-450 102) from Bacillus megaterium. Replacement of Trp-97 with Ala, Phe or Tyr results in a decrease in the natural haem content and alters the resting spin state of the remaining haem in the purified mutant enzymes. However, kinetic analyses indicate that the mutant enzymes retain high levels of catalytic activity. C.d. and e.p.r. spectroscopy also reveal little alteration in secondary structure or change in the pattern of haem ligation. These findings cast doubt on the covalent switching mechanism of intermolecular electron flow in the P-450s, but indicate that this residue plays a role in the association of the haem prosthetic group.
The mandate of public health departments has been, and continues to be, to provide and deliver a variety of health programs and services pertinent to local circumstances and needs. Public health nurses are the largest group of health care professionals who deliver these services. The objectives of this paper are to identify what policy makers expect of public health nurses related to community development for health, and to describe the educational components necessary for baccalaureate nursing curricula if these expectations are to be met.
The optical, low temperature magnetic circular dichroism (MCD) and EPR spectra of low-spin Fe(III) cytochrome P-450 BM-3 from Bacillus megaterium, and its imidazole adduct have been measured. The MCD spectra locate new transitions over 600-700 nm and 800-1300 nm. The latter are assigned to porphyrin (a1u)-Fe(III) (dyz) charge-transfer (CT) transitions. In the case of the imidazole adduct the energy of this transition fits well to the theoretical model of Gadsby and Thomson [Gadsby, P. M. A. & Thomson, A. J. (1990) J. Amer. Chem. Soc 112, 5003-5011]. For the native enzyme, the energy of the CT band suggests co-ordination by a strongly H-bonded water ligand and the axial thiolate form of cysteine. Two transitions between 600-700 nm are detected in both derivatives. A theoretical analysis and fit of the MCD magnetisation properties shows that these transitions are polarised XY and XZ, respectively. They are assigned as thiolate sulphur py-d-shell and pz-d-shell CT transitions, analogous to the well known 695 nm band of methionine-histidine co-ordinated haem as in cytochrome c. They should prove usefully diagnostic of cysteine/Fe(III) conformational changes or protonation.
Educational programs for nurses are becoming increasingly reliant on clinicians in hospitals and other health care agencies to act as preceptors for their students. Often there is no formal preparation for this role, nor are rewards provided by the educational institutions. This paper describes a collaborative effort between a university and a college program to prepare and reward nurses who work as preceptors with students in their settings.
1. The gene CYP102 encoding cytochrome P-450 BM-3 and subgenes encoding the cytochrome P-450 and cytochrome P-450 reductase domains have been cloned in Escherichia coli. 2. The protein products of these genes have been overexpressed and purified to homogeneity. 3. The cytochrome P-450 domain is purified in the ferric low-spin state, but is readily converted into the high-spin state by addition of the substrate palmitate (Ks = 1 microM). The cytochrome P-450 reductase domain readily reduces cytochrome c. Mixing the two domains reconstitutes only about one-thousandth of the fatty acid hydroxylase activity associated with the intact cytochrome P-450 BM-3. 4. The X-band e.p.r. spectra of both the cytochrome P-450 domain and intact cytochrome P-450 BM-3 give g-values indicating low-spin ferric haem. The spectra are virtually identical with those of the equivalent form of cytochrome P-450 cam indicating that the haem ligation in cytochrome P-450 BM-3 is identical with that of cytochrome P-450 cam. 5. Resonance Raman spectra of the substrate-free and substrate-bound forms of the cytochrome P-450 domain are given. Spectral differences in comparison with cytochrome P-450 cam may reflect subtle electronic differences between the respective haem environments.
This paper presents an educational model that follows the General Systems approach and illustrates the advancement of gerontological nursing education in Canada. The model's primary focus is placed on baccalaureate education, the mandate of the nursing discipline group. The paper also touches briefly on Masters and Doctoral education. Implications for use of this model in nursing education are then linked to nursing care of the elderly.
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We compared high-dose ketoconazole (800 mg/kg per day, orally) with amphotericin B (0.5 mg/kg per day, intravenously) for empirical antifungal therapy in a prospective, randomized study of persistently or recurrently febrile granulocytopenic cancer patients. Among 97 patients eligible for empirical antifungal therapy, 20 (21%) of these patients were ineligible for randomization to ketoconazole treatment because of their inability to tolerate oral medications. Among 72 patients eligible for randomization, 64 were assessable (32 in each arm of the study). Five of six patients with proved fungal infections who were randomized to receive ketoconazole treatment required crossover to amphotericin B treatment because of progressive infection. The conditions of three of these five patients improved after receiving amphotericin B. The frequency of transaminase elevation was higher in those receiving ketoconazole, while the frequency of azotemia was higher in those receiving amphotericin B. Bioavailability of ketoconazole was unpredictable. Amphotericin B remains the drug of choice for empirical antifungal therapy in granulocytopenic patients; whereas, lack of a parenteral formulation, ineffectiveness against proved mycoses, and unreliable bioavailability preclude high-dose ketoconazole from being an appropriate compound for this purpose.
Several groups have described the efficacy of interleukin 2 (IL-2) plus lymphokine-activated killer (LAK) cells in the treatment of cancer patients with significant response rates noted in patients with renal cell cancer and malignant melanoma; however, the optimum regimen remains undefined. The Biological Response Modifiers Program of the National Cancer Institute conducted two consecutive Phase I/II studies evaluating the toxicity and clinical efficacy of different methods of IL-2 and LAK cell therapy. In the first trial, we modified the standard Rosenberg regimen by decreasing the duration of priming in an attempt to reduce the toxicity related to this phase of the therapy and thereby administer more IL-2 doses with the LAK cells. In the second trial, we used a continuous i.v. infusion IL-2 regimen and altered both the leukapheresis procedure and the LAK cell culture techniques based on our in vitro and preclinical studies suggesting that 2-day LAK cells were superior. Thirty cancer patients received i.v. bolus IL-2 at 100,000 units/kg every 8 h for 3 days during priming and for 5 days during LAK cell administration. A second group of 22 cancer patients received IL-2 by continuous i.v. infusion at 3 x 10(6) units/m2 for 5 days during priming and an additional 5 days of IL-2 with the LAK cell phase of the treatment. The timing of the start of the leukapheresis procedures, their duration and number, and the LAK cell culture techniques differed in the two trials. Overall, 52 patients with various cancers were treated. The toxicities associated with each regimen were similar to those seen in other IL-2 plus LAK cell trials. Four patients (one each with melanoma and diffuse large cell lymphoma and two with renal cell cancer) exhibited partial responses lasting 2, 4, 10, and 15+ mo. Serial tumor biopsies from treated patients demonstrated that therapy can produce a marked mononuclear cell infiltrate and an increase in HLA-DR expression on tumor cells. There was no difference in the overall response rate between the two regimens, but toxicity was less with continuous i.v. infusion IL-2. The 5-day continuous i.v. infusion regimen resulted in significantly higher rebound lymphocytosis, cell yield from leukapheresis, and number of LAK cells harvested from culture.
Nurses returning to work after obtaining their baccalaureate degree in nursing find increased expectations to participate in student and staff clinical education. Often these nurses are not prepared for this role. This paper describes a project that involved final year post-diploma registered nurse students in the clinical teaching of second year basic degree students in a baccalaureate nursing programme. Results of a pilot study to determine if the perceptions of the students involved in the teaching project changed following the experience, show a more positive change in teacher behaviours in these student tutors compared to students doing a traditional clinical experience. Course evaluations indicate the experience increased knowledge and comfort in clinical teaching and point to positive changes in the perceptions of behaviours conducive to clinical teaching.
This article describes the experiences of five community health nursing faculty who are jointly appointed between McMaster University School of Nursing and the Hamilton-Wentworth Department of Public Health Services in Hamilton, Ontario, Canada. The appointees are actively involved in service, education, and research activities within the teaching health unit, a specially funded project of the Ontario Ministry of Health. Various kinds of consultation and expertise are offered by joint appointees to staff and management within the Department of Public Health Services. The amount of time and effort invested in a particular activity or project varies as staff, students, and joint appointees each make their contributions. Several lessons are learned in acting out our diverse roles in this exciting and challenging service environment.
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