Biomedical subjects

K Wheeler

Publications and source records attributed to K Wheeler.

At least 19 recordsLinked to original sources

PubMed2001

Development of a Tc-99m labeled sigma-2 receptor-specific ligand as a potential breast tumor imaging agent.

A novel in vivo imaging agent, 99mTc labeled [(N-[2-((3'-N'-propyl-[3,3,1]aza-bicyclononan-3alpha-yl)(2"-methoxy-5-methyl-phenylcarbamate)(2-mercaptoethyl)amino)acetyl]-2-aminoethanethiolato] technetium(V) oxide), [99mTc]2, displaying specific binding towards sigma-2 receptors was prepared and characterized. In vitro binding assays showed that the rhenium surrogate of [99mTc]2, Re-2, displayed excellent binding affinity and selectivity towards sigma-2 receptors (K(i) = 2,723 and 22 nM for sigma-1 and sigma-2 receptor, respectively). Preparation of [99mTc]2 was achieved by heating the S-protected starting material, 1, in the presence of acid, reducing agent (stannous glucoheptonate) and sodium [99mTc]pertechnetate. The lipophilic racemic mixture was successfully prepared in 10 to 50% yield and the radiochemical purity was >98%. Separation of the isomers, peak A and peak B, was successfully achieved by using a chiralpak AD column eluted with an isocratic solvent (n-hexane/isopropanol; 3:1; v/v). The peak A and peak B appear to co-elute with the isomers of the surrogate, Re-2, under the same HPLC condition. Biodistribution studies in tumor bearing mice (mouse mammary adenocarcinoma, cell line 66, which is known to over-express sigma-2 receptors) showed that the racemic [99mTc]2 localized in the tumor. Uptake in the tumor was 2.11, 1.30 and 1.11 %dose/gram at 1, 4 and 8 hr post iv injection, respectively, suggesting good uptake and retention in the tumor cells. The tumor uptake was significantly, but incompletely, blocked (about 25-30% blockage) by co-injection of "cold" (+)pentazocine or haloperidol (1 mg/Kg). A majority of the radioactivity localized in the tumor tissue was extractable (>60%), and the HPLC analysis showed that it is the original compound, racemic [99mTc]2 (>98% pure). The distribution of the purified peak A and peak B was determined in the same tumor bearing mice at 4 hr post iv injection. The tumor uptake was similar for both isomers, but the blood and peripheral tissue content for the isomer in peak B was higher than that for the isomer in peak A. It is evident that the isomer in peak A displayed significantly better tumor/blood and tumor/muscle ratios. The higher rate of in vivo metabolism was also confirmed by the higher thyroid uptake values for the isomer in peak B as compared to peak A. In summary, a 99mTc-labeled sigma receptor imaging agent, [99mTc]2, has demonstrated the feasibility of using a 99mTc-labeled agent for imaging sigma receptor expression in tumor cells. This is the first time a subtype-selective 99mTc-labeled agent for imaging sigma receptor sites is reported.

Adenocarcinoma↗

PubMed2001

HIV prevention in primary care: impact of a clinical intervention.

Discomfort, lack of confidence in skills, and environmental constraints may cause primary care providers to miss opportunities to discuss human immunodeficiency virus (HIV) risk with patients. We used a systems approach to address both intrapersonal and environmental barriers to HIV risk assessment and prevention counseling in a managed care clinical setting. The design was one-group pretest/posttest. The study took place in two primary care clinics of a large Pacific Northwest managed care organization. Participants (n = 49) included physicians, physician assistants, nurse practitioners, registered nurses, and social workers. The intervention included training, clarification of provider/staff roles, assess to tools and materials, and reminders/reinforcers. Outcome measures were provider attitudes, beliefs, outcome expectations, knowledge, confidence in skills, and perceived supports and barriers, measured by written pretest/posttest surveys administered 12 months apart. Seven months after the most intensive part of the intervention, providers' attitudes and beliefs were more favorable to HIV risk assessment and prevention counseling. They were less likely to express frustration with high-risk patients (decrease from 100% to 79% agreement, p = 0.001) and more confident that their advice would be effective with gay men and single adult heterosexuals (p = 0.002 and 0.005, respectively). They reported more confidence in their training in sexual history taking (p = 0.0003) and their skills assessing readiness for change (p = 0.007), and more support in practice environments. This study demonstrated that it is possible to affect important personal and environmental factors that influence primary care providers' HIV prevention behavior using an interactive, real-world systems approach. Further research is needed on providers' impact on patient behavior.

Adult↗

PubMed2000

Identification of domains responsible for signal recognition and transduction within the QUTR transcription repressor protein.

QUTR (qutR-encoded transcription-repressing protein) is a multi-domain repressor protein active in the signal-transduction pathway that regulates transcription of the quinic acid utilization (qut) gene cluster in Aspergillus nidulans. In the presence of quinate, production of mRNA from the eight genes of the qut pathway is stimulated by the activator protein QUTA (qutA-encoded transcription-activating protein). Mutations in the qutR gene alter QUTR function such that the transcription of the qut gene cluster is permanently on (constitutive phenotype) or is insensitive to the presence of quinate (super-repressed phenotype). These mutant phenotypes imply that the QUTR protein plays a key role in signal recognition and transduction, and we have used deletion analysis to determine which regions of the QUTR protein are involved in these functions. We show that the QUTR protein recognizes and binds to the QUTA protein in vitro and that the N-terminal 88 amino acids of QUTR are sufficient to inactivate QUTA function in vivo. Deletion analysis and domain-swap experiments imply that the two C-terminal domains of QUTR are mainly involved in signal recognition.

Base Sequence↗

PubMed2000

Emotional regulation and alexithymia: treatment implications for nurse practitioners.

It has been estimated that between 50% and 80% of all visits to nurse practitioners are for symptoms that are vague, without a specific diagnosis or cause. Such symptoms as headaches and pain, as well as other illnesses, may stem from difficulties in emotional regulation. Understanding that these individuals suffer from emotional dysregulation and alexithymia provides guidelines for assessment and treatment protocols. Integrating the holistic therapeutic strategies delineated in this article is essential for expert advanced practice.

Adult↗

PubMed1999

Integrating multidimensional stress management into a baccalaureate nursing curriculum.

The mandate for self-care for holistic nurses can be satisfied with a multidimensional stress management program. This article describes a quasiexperimental pilot study that assessed the need for such a program for senior students in a baccalaureate degree nursing program. Strategies are suggested to integrate these techniques into nursing education.

Adaptation, Psychological↗

PubMed1999

Evidence-based practice for nurse practitioners with clinical pathways.

Evidence-based practice is essential for clinical excellence for nurse practitioners (NPs). Client outcomes must be measured and clearly linked to measurable nursing interventions. To ensure evidence-based practice, clinical pathways can be used as a vehicle to implement care. Clinical pathways track outcomes and interventions, and provide a means for accurate documentation. This article discusses evidence-based practice and the use of clinical pathways by psychiatric NPs in two settings: home care and an outpatient psychiatric clinic.

Ambulatory Care↗

PubMed1998

Comparison of bone marrow transplant and chemotherapy for relapsed childhood acute lymphoblastic leukaemia: the MRC UKALL X experience. Medical Research Council Working Party on Childhood Leukaemia.

We examined the outcome of the 489 children with acute lymphoblastic leukaemia (ALL) who relapsed in the UKALL X trial, and produced graphical displays of adjusted comparisons of event-free survival (EFS) for chemotherapy versus bone marrow transplantation (BMT) from a sibling or volunteer unrelated donor, and autologous BMT (ABMT). EFS at 5 years was only 3% (95% CI 0-6%) for children who relapsed in the bone marrow (BM) within 2 years of diagnosis, irrespective of type of post-relapse treatment, whereas for those with late extramedullary relapse it was 66% (95% CI 48-85%). Comparison of the types of treatment did not show benefit for ABMT. For allogeneic BMT the overall reduction in the odds of an event was 26% (95% CI 1-51%) (2P= 0.05), resulting in an absolute increase in 5-year event-free survival of 14% (from 26.4% to 40.7%). New approaches are needed for children with early BM relapses whose prognosis is virtually hopeless with current therapy; however, a conventional chemotherapy approach may be justifiable for late extramedullary relapses. For the remaining patients (71%), with later BM or early extramedullary relapses, the optimal treatment is still not clear. This uncertainty warrants a formal randomized comparison of BMT and chemotherapy, to avoid the biases due to unmeasurable selection factors.

Adolescent↗

PubMed1998

Interpretations of antibody responses to Salmonella enterica serotype enteritidis gm flagellin in poultry flocks are enhanced by a kinetics-based enzyme-linked immunosorbent assay.

Many regulatory and diagnostic programs for the detection of Salmonella enterica serotype Enteritidis infection in commercial poultry flocks have relied on rapid Pullorum agglutination tests to screen birds because of the shared antigens of S. enterica Enteritidis and S. enterica Pullorum and Gallinarum; however, the use of the enzyme-linked immunosorbent assay (ELISA) format affords better analytical sensitivity than crude agglutination tests. In this study, we adapted our earlier conventional indirect ELISA, using gm flagellin as the antigen, to a kinetics-based, computer-controlled ELISA (KELA). The KELA was used to screen for flagellin antibody from three commercial flocks: (i) a large flock involved in a U.S. Department of Agriculture trace back from a human S. enterica Enteritidis foodborne outbreak (n = 3,209), (ii) a flock infected with the endemic S. enterica Enteritidis serotype but which also had multiple other Salmonella serotypes (n = 65), and (iii) an S. enterica Pullorum-infected flock (n = 12). The first flock (S. enterica Enteritidis prevalence of 2.45% based on culture) provided a field test of the KELA and allowed the calculation of diagnostic sensitivity (D-Sn) and diagnostic specificity (D-Sp). With a cutoff of 10 (used for screening flocks [i.e., high sensitivity]), the KELA has a D-Sn of 95.2% and a D-Sp of 18.5%; with a cutoff of 140 (used in confirmatory flock testing [i.e., high specificity]), the KELA has a D-Sn of 28.0% and a D-Sp of 99.1%. We found that with a cutoff of 60 (D-Sn = 63.1%; D-Sp = 91.6%), we could eliminate reactions in the KELA caused by other non-S. enterica Enteritidis salmonellae. The KELA was also compared to two commercial rapid Pullorum tests, the Solvay (D-Sn = 94.9%; D-Sp = 55.5%) and the Vineland (D-Sn = 62.0%; D-Sp = 75.3%).

Animals↗

PubMed1998

Health teaching needs of clients with serious and persistent mental illness: client and provider perspectives.

1. Clients are interested in health education regardless of age, sex, or primary Axis I diagnosis. 2. Contrasts between staff and client ratings suggest that results support the practice of assessing clients' own perceptions of their needs in treatment planning and developing educational programs. 3. Items ranked as having most interest to clients included: psychiatric medication and side effects; getting what you need from the mental health system; and ways to solve problems.

Adult↗

PubMed1998

Role-modeling experience improves nursing students' attitudes toward people living with AIDS.

Two groups of student nurses were given on AIDS Knowledge/Attitudes survey before different clinical experiences. Group One worked with nurses experienced in the care of persons living with AIDS (PLWA) on a high-acuity unit with many AIDS patients. The other group were precepted on a acute-care unit with no AIDS patients. Outcomes measures revealed significantly better student attitude scores for Group One on scales measuring (1) avoidance intentions to working with PLWA and (2) attitude toward homosexuals.

Acquired Immunodeficiency Syndrome↗

PubMed1997

Patient, visitor, and nurse evaluations of visitation for adult postanesthesia care unit patients.

Although PACU visitation for children is sometimes encouraged, most families of adult postoperative patients continue to be excluded from PACUs in this country. At an academic medical center, an open visitation policy for adult postoperative patients was evaluated by eliciting patient, visitor, and nurse evaluations of visitation for adult patients from 181 families. Commonly cited reasons for restricting PACU visitation were not identified as problems by the vast majority of respondents. Even when some aspect of a PACU visit was disturbing, patients and families expressed a desire for visitation. The results of this evaluation of a change in practice led to permanent implementation of an open visitation policy in this PACU.

Adult↗

PubMed1997

Predicting patients' deterioration and recovery.

The purpose of this study was to identify patient cues that expert nurses identify as a patient moves to/from deterioration and/or recovery. The sample of 33 nurses was drawn from a medical intensive care unit (MICU). Data were collected through interviews regarding nurses' knowledge about caring for patients with acute gastrointestinal bleeding, heart failure/post-myocardial infarction, and pulmonary edema. Using the constant comparative technique, cues were identified and grouped into early, imminent, and late patterns for deterioration and into categories of early, midway, and complete for recovery. Rationales for the nurses' decisions included memories of patients with similar cues, using multiple not single cues, and clustering both physiological and psychological cues together. This study is a beginning effort toward validating nurses' intuitiveness and provides knowledge about expert practice that can be taught to novice practitioners and incorporated into protocols for care.

Adult↗

PubMed1997

The combination of in situ hybridization and immunohistochemical analysis: an evaluation of Her2/neu expression in paraffin-embedded breast carcinomas and adjacent normal-appearing breast epithelium.

The combination of in situ hybridization and immunohistochemical techniques can successfully identify viral DNA/RNA in specific subsets of cellular populations. We recently modified this method to evaluate amplification of the oncogene Her2/neu and overexpression of its protein c-erbB-2 in a series of 15 breast carcinomas. This combination allows the simultaneous evaluation of the oncogene and its corresponding protein expression in single cells and specific cellular populations in histologic tissue sections. Double staining demonstrated heterogeneity within breast carcinomas. In addition, both nuclear and cytoplasmic signals were often detected in morphologically normal-appearing adjacent breast epithelium. The ability to view both the oncogene and its corresponding protein in single cells offers a unique look at the biology of c-erbB-2.

Breast↗

PubMed1996

Co-ligation of surface IgM and CD40 on naive B lymphocytes generates a blast population with an ambiguous extrafollicular/germinal centre cell phenotype.

We have previously shown that dual occupancy of sigM and CD40 - essential receptors in T-dependent B cell responses - by antibodies held on CD32-L cells results in the rapid proliferation of resting human B lymphocytes in a cytokine-independent manner. Here we report the detailed phenotype of the blast population emerging in such cultures. By 3 days the levels of CD19 and CD20 have increased 4- and 2-fold respectively: such high level expression of these two pan-B markers is characteristic of cells of germinal centre (GC) origin. B cells co-stimulated via sIgM and CD40 express low level CD23 and almost half become CD5(+); they also acquire CD38 and - importantly - CD77, both of these being selective markers of GC B cells. Expression of sigM and IgD is down-regulated on these cells and a minor, but significant, population of IgG+ cells appears. In marked contrast to GC B cells, the population proliferating in response to dual occupancy of sigM and CD40 has up-regulated and strongly expresses CD44. Morphologically, the cells are heterogeneous but there is a dominant blastic cell type with relatively scanty cytoplasm and having multiple nucleoli, both of which are characteristic of centroblasts; nevertheless, these cells remain morphologically distinct from freshly isolated GC B cells and do not show hallmark features of centrocytes. Although there is substantial cell death occurring by days 6-7 in these cultures, there is no morphological evidence for apoptosis. Thus, the proliferating population that emerges from the dual engagement of antigen receptor and CD40 on resting B cells appears to be bestowed with some features of GC B cells but has others which are incompatible with that particular stage of differentiation. The possibility that it might represent (i) a blast stage that is transitional between activation in T zones and entry into the follicle or (ii) a precursor population that colonizes the primary follicle prior to GC formation is discussed.

ADP-ribosyl Cyclase↗

PubMed1996

Treatment related deaths during induction and in first remission in acute lymphoblastic leukaemia: MRC UKALL X.

The benefits of achieving a long term event free survival of 60-70% by using increasingly intense treatment regimens must be weighed against the increased risk of treatment toxicity. From 1985 to 1990, 1612 children with childhood acute lymphoblastic leukaemia (ALL) in the UK were treated on MRC UKALL X with intensive induction therapy, central nervous system directed therapy (cranial irradiation and intrathecal methotrexate), and continuing treatment for two years. There was a randomisation to receive blocks of additional intensification treatment at five weeks, 20 weeks, not at all, or both. The five year disease free survival was 71% for children randomised to two blocks of intensification, a 14% improvement on children randomised to no intensification treatment. Treatment related mortality in this national multicentre study has been analysed for induction and first remission (including those after intensification treatment). There were 38 induction deaths, 2.3% and 53 deaths in first remission, 3.3% (including those from a second malignancy). Thirty one (84%) of the induction deaths followed an infection: bacterial in 22 and fungal in nine. Thirty seven infective remission deaths occurred: bacterial in 11, viral in 16, fungal in seven, and three caused by Pneumocystis carinii pneumonia. Ten of these deaths followed a block of intensification treatment. The majority of noninfective remission deaths followed the development of a second tumour. Risk analysis for an induction death showed girls and children with Down's syndrome to be at greater risk. For deaths in first remission analysis showed an increased risk for bone marrow transplant (BMT) patients and children with Down's syndrome. There was no effect of age and leucocyte count for either group. Most significantly when BMT patients were excluded from the analysis, intensification treatment did not increase the risk of remission death.

Adolescent↗

PubMed1996

Mental health concerns of Canadian adolescents: a consumer's perspective.

OBJECTIVE: To evaluate the mental health of adolescent students in Metropolitan Toronto. METHOD: A survey was developed by adolescents for adolescents to evaluate adolescent mental health. The survey was completed by 486 secondary school students in Metropolitan Toronto. RESULTS: The findings of this consumer-directed survey show that the majority of teenagers are not overwhelmed by stress and generally exhibit healthy coping behaviours. Violence is identified as an important concern and help-seeking behaviour for mental health issues, when it occurs, is directed primarily towards the family and teachers rather than physicians. CONCLUSION: A number of important issues regarding mental illness, including its identification and treatment, were not considered by teens to be part of their mental health concerns. The implications of these findings for the development of community-based mental health programs for adolescents are discussed.

Adaptation, Psychological↗

PubMed1995

Physician views about treating low back pain. The results of a national survey.

STUDY DESIGN: Physicians were surveyed regarding their beliefs about treatment efficacy for patients with low back pain. OBJECTIVE: To document physician beliefs about the efficacy of specific treatments and the extent to which these beliefs correspond to current knowledge. SUMMARY OF BACKGROUND DATA: Little is known about physician beliefs regarding the efficacy of specific back pain treatments. METHODS: A national random sample of 2897 physicians were mailed questionnaires that asked about 1) the treatments they would order for hypothetical patients with low back pain and 2) the treatments they believed were effective for back pain. Responses were compared with guidelines suggested by the Quebec Task Force on Spinal Disorders. RESULTS: Almost 1200 physicians responded. More than 80% of these physicians believed physical therapy is effective, but this consensus was lacking for other treatments. Fewer than half of the physicians believed that spinal manipulation is effective for acute or chronic back pain or that epidural steroid injections, traction, and corsets are effective for acute back pain. Bed rest and narcotic analgesics were recommended by substantial minorities of physicians for patients with chronic pain. The Quebec Task Force found little scientific support for the effectiveness of most of the treatments found to be in common use. CONCLUSIONS: The lack of consensus among physicians could be attributable to the absence of clear evidence-based clinical guidelines, ignorance or rejection of existing scientific evidence, excessive commitment to a particular mode of therapy, or a tendency to discount the efficacy of competing treatments.

Adult↗

PubMed1995

Acoustic characteristics of American English vowels.

The purpose of this study was to replicate and extend the classic study of vowel acoustics by Peterson and Barney (PB) [J. Acoust. Soc. Am. 24, 175-184 (1952)]. Recordings were made of 45 men, 48 women, and 46 children producing the vowels /i,I,e, epsilon,ae,a, [symbol: see text],O,U,u, lambda,3 iota/ in h-V-d syllables. Formant contours for F1-F4 were measured from LPC spectra using a custom interactive editing tool. For comparison with the PB data, formant patterns were sampled at a time that was judged by visual inspection to be maximally steady. Analysis of the formant data shows numerous differences between the present data and those of PB, both in terms of average frequencies of F1 and F2, and the degree of overlap among adjacent vowels. As with the original study, listening tests showed that the signals were nearly always identified as the vowel intended by the talker. Discriminant analysis showed that the vowels were more poorly separated than the PB data based on a static sample of the formant pattern. However, the vowels can be separated with a high degree of accuracy if duration and spectral change information is included.

Adult↗