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Biomedical subjects

M A Rose

Publications and source records attributed to M A Rose.

At least 19 recordsLinked to original sources

Impaired interferon-gamma production in response to live bacteria and Toll-like receptor agonists in patients with ataxia telangiectasia.

Ataxia telangiectasia (AT) is a pleiotropic autosomal recessive neurodegenerative disorder with associated immunodeficiency and cancer predisposition, caused by mutational inactivation of the ATM gene. Early death usually results from lymphoreticular malignancy or recurrent, chronic respiratory infections. Immune deficiency of AT patients is heterogeneous and involves both humoral and cellular responses. Reports on the number and integrity of immunocompetent cells in AT are conflicting. In the early phase of infection, the interleukin (IL)-12/interferon (IFN)-gamma axis plays a crucial role in first-line defence against pathogens. In a whole blood assay we studied the IL-12/IFN-gamma axis in the immune response of AT cells to the Toll-like receptor agonists lipopolysaccharide and heat-killed Staphylococcus aureus, as well as whole live M. bovis bacille Calmette-Guérin (BCG). The function of AT antigen-presenting cells was normal in terms of IL-12 production, while IFN-gamma production by T and natural killer (NK) cells was severely impaired, even in the presence of adequate co-stimulation by exogenous IL-12.

Adolescent↗

Immunoglobulins and immunogenicity of pneumococcal vaccination in preschool asthma.

Pneumococcal vaccination is advocated for asthmatics. Although routinely performed, data supplying evidence for this recommendation are limited. We examined the immunological background of 215 asthmatic children (2-5 year old) at a university children's hospital and compared the immunogenicity of the recommended pneumococcal vaccines. Testing encompassed serum immunoglobulins, immunoglobulin G (IgG)-subclasses, and pneumococcal antibodies against serotypes 4, 6B, 9V, 14, 18C, 19F and 23F. An infection-prone subgroup received one dose of 23-valent pneumococcal polysaccharide vaccine (PPV-23; n = 38, median age 45 months) or of 7-valent conjugate vaccine (PCV-7; n = 23; median age 35 months). Pneumococcal antibodies were determined again after 4 weeks. Low immunoglobulin- and/or IgG-subclass levels were found in 27 subjects (14 infection-prone). Prevaccination pneumococcal antibody levels ranged from 0.36 to 1.06 microg/ml, depending on the serotype. The percentage of subjects with putative protective antibody levels > or =1.0 microg/ml ranged only from 19.9% to 54.1%, over all. Postvaccination, antibody geometric mean concentrations increased significantly higher in PCV-7 vaccinees for serotype 14 (p < 0.01) and 23F (p < 0.05). Now the percentage of putatively protected subjects ranged from 40.9% (serotype 6B) to 90.9% (serotype 19F) following PCV-7 compared with 31.6% (serotype 6B and 23F) to 81.6% (serotype 19F) in PPV-23 vaccinees. Our data give further evidence for pneumococcal vaccination of asthmatic children. PCV-7 is at least as immunogenic as PPV-23. Moreover, for children suffering from persistent asthma, PCV immunisation should be considered.

Antibodies, Bacterial↗

Effectiveness of budesonide nebulising suspension compared to disodium cromoglycate in early childhood asthma.

OBJECTIVE: The optimal treatment for early childhood asthma remains controversial. Budesonide (BUD) has shown superiority over placebo in infants, and over disodium cromoglycate (DSCG) in children aged > 2 years. The aim of this double-blind, randomised, parallel-group study was to compare the effectiveness of nebulised BUD and DSCG in asthmatic children aged < 36 months. RESEARCH DESIGN AND METHODS: 82 infants (mean age 18.0 months [range, 11.6-31.2 months]) with suspected asthma (three exacerbations of dyspnoea and wheezing during the past 12 months, with one or more exacerbations in the past 3 months) were treated for 3 months with nebulised BUD (Pulmicort Respules) 0.5 mg/2 mL bid or DSCG 20 mg/2 mL tid. Follow-up was at 6 months. MAIN OUTCOME MEASURES AND RESULTS: Patients treated with BUD had a lower exacerbation rate than DSCG-treated patients after 3 months of treatment (5.4% vs. 31.7%; p = 0.003) and towards the end of follow-up (30% vs. 49%; p = 0.062). During treatment, days without cough were 80% and 65% for BUD and DSCG, respectively (p = 0.014), and nights without cough were 89% and 78%, respectively (p = 0.016). Side-effects were mild and of similar frequency in both groups. CONCLUSIONS: Inhaled nebulised BUD was well tolerated and more effective than nebulised DSCG in reducing the incidence of asthma exacerbations and days with symptoms. These beneficial effects of BUD were maintained throughout the 6-month follow-up.

Anti-Asthmatic Agents↗

Gabapentin: pharmacology and its use in pain management.

Although its exact mode of action is not known, gabapentin appears to have a unique effect on voltage-dependent calcium ion channels at the postsynaptic dorsal horns and may, therefore, interrupt the series of events that possibly leads to the experience of a neuropathic pain sensation. Gabapentin is especially effective at relieving allodynia and hyperalgesia in animal models. It has been shown to be efficacious in numerous small clinical studies and case reports in a wide variety of pain syndromes. Gabapentin has been clearly demonstrated to be effective for the treatment of neuropathic pain in diabetic neuropathy and postherpetic neuralgia. This evidence, combined with its favourable side-effect profile in various patient groups (including the elderly) and lack of drug interactions, makes it an attractive agent. Therefore, gabapentin should be considered an important drug in the management of neuropathic pain syndromes.

Acetates↗

Protein-dependent transition states for ribonucleoprotein assembly.

Native folding and splicing by the Saccharomyces cerevisiae mitochondrial bI5 group I intron RNA is facilitated by both the S. cerevisiae CBP2 and Neurospora crassa CYT-18 protein cofactors. Both protein-bI5 RNA complexes splice at similar rates, suggesting that the RNA active site structure is similar in both ribonucleoproteins. In contrast, the two proteins assemble with the bI5 RNA by distinct mechanisms and bind opposing, but partially overlapping, sides of the group I intron catalytic core. Assembly with CBP2 is limited by a slow, unimolecular RNA folding step characterized by a negligible activation enthalpy. We show that assembly with CYT-18 shows four distinctive features. (1) CYT-18 binds stably to the bI5 RNA at the diffusion controlled limit, but assembly to a catalytically active RNA structure is still limited by RNA folding, as visualized directly using time-resolved footprinting. (2) This mechanism of rapid stable protein binding followed by subsequent assembly steps has a distinctive kinetic signature: the apparent ratio of k(off) to k(on), determined in a partitioning experiment, differs from the equilibrium K(d) by a large factor. (3) Assembly with CYT-18 is characterized by a large activation enthalpy, consistent with a rate limiting conformational rearrangement. (4) Because assembly from the kinetically trapped state is faster at elevated temperature, we can identify conditions where CYT-18 accelerates (catalyzes) bI5 RNA folding relative to assembly with CBP2.

Allosteric Site↗

Does indirect speech promote nondirective genetic counseling? Results of a sociolinguistic investigation.

To date, research examining adherence to genetic counseling principles has focused on specific counseling activities such as the giving or withholding of information and responding to client requests for advice. We audiotaped 43 prenatal genetic counseling sessions and used data-driven, qualitative, sociolinguistic methodologies to investigate how language choices facilitate or hinder the counseling process. Transcripts of each session were prepared for sociolinguistic analysis of the emergent discourse that included studying conversational style, speaker-listener symmetry, directness, and other interactional patterns. Analysis of our data demonstrates that: 1) indirect speech, marked by the use of hints, hedges, and other politeness strategies, facilitates rapport and mitigates the tension between a client-centered relationship and a counselor-driven agenda; 2) direct speech, or speaking literally, is an effective strategy for providing information and education; and 3) confusion exists between the use of indirect speech and the intent to provide nondirective counseling, especially when facilitating client decision-making. Indirect responses to client questions, such as those that include the phrases "some people" or "most people," helped to maintain counselor neutrality; however, this well-intended indirectness, used to preserve client autonomy, may have obstructed direct explorations of client needs. We argue that the genetic counseling process requires increased flexibility in the use of direct and indirect speech and provide new insights into how "talk" affects the work of genetic counselors.

Decision Making↗

Visualizing induced fit in early assembly of the human signal recognition particle.

Assembly of almost all ribonucleoprotein complexes involves induced fit in the RNA and, thus, formation of one or more intermediate states. In assembly of the human signal recognition particle (SRP), we show that SRP19 binding to SRP RNA involves obligatory intermediates. An apparent discrepancy exists between the ratio of dissociation and association rate constants, determined in a partitioning experiment, and the equilibrium binding constant; this kinetic signature reflects formation of a stable intermediate in assembly of the ribonucleoprotein complex. Assembly intermediates were observed directly by time-resolved footprinting. SRP19 binds rapidly to SRP RNA to form an initial labile, but structurally specific, encounter complex involving both helices III and IV. Two subsequent steps of structural consolidation yield the native RNA-protein interface. SRP19 binding stabilizes helix IV in the region recognized by SRP54, consistent with protein-protein cooperativity mediated in part by mutual recognition of similar RNA structures. This mechanism illustrates principles general to ribonucleoprotein assembly reactions that rely on recruitment of architectural RNA binding proteins.

Allosteric Regulation↗

Global connections in a changing world: Romanian and U.S. nurses unite.

This article describes an international, interdisciplinary, university partnership project to collaborate with health professionals in the city of Cluj-Napoca, Transylvania, Romania, to improve the health status of Romanian workers. Academic and service-based public health nurses from the United States used the model of community competence in outlining the nursing aspect of the project. This model guided the assessment, objectives, collaborative activities, and the outcome evaluation of the project. The dimensions of the model (e.g., commitment, self-other awareness, articulateness, conflict accommodation, management of relations with larger society, and leadership) were used within the context of the political and social environment of the international community.

Community Health Nursing↗

Coping styles of caregivers of children with HIV/AIDS: implications for health professionals.

In a study to examine the coping styles and quality of life of non-parental caregivers of children with HIV/AIDS, 25 non-parental caregivers used confrontive coping most often and passive and emotive coping much less often. The two most frequently used coping styles were prayer and efforting to maintain some control over the situation. Quality of life correlations showed that support from family/friends was significantly related to all of the quality of life subscales. Time spent caring for the HIV-positive child was significantly inversely related to all aspects of quality of life. The conclusions drawn from the study were that interventions are needed to help support caregivers of children with HIV/AIDS. Examples of primary, secondary, and tertiary prevention measures for health professionals are discussed.

Acquired Immunodeficiency Syndrome↗

Evidence for direct interaction of ketamine with alpha 1- and beta 2-adrenoceptors.

1. Ketamine has a number of effects that suggest that it may interact with alpha- and beta-adrenoceptors. To date, the experimental evidence for this has been indirect and has been based on physiological studies using competitive blocking agents. In the present study we sought to determine from receptor binding studies whether ketamine binds directly to alpha- and beta-adrenoceptors. 2. Membrane preparations of alpha 1- and beta 2-adrenergic binding sites were obtained from urinary bladder and urethrae of sheep. These binding sites were characterized by saturation analyses using [3H]-prazosin for alpha 1-adrenoceptor binding sites and [125I]-cyanopindolol (CYP) for the beta 2-adrenoceptor binding sites. The receptors were further characterized by displacement studies using selective and non-selective antagonists. 3. Studies in which ketamine was used to displace [3H]-prazosin revealed a Kd of 3.40 +/- 1.23 x 10(-3) mol/L for ketamine binding to alpha 1-adrenoceptors. Displacement studies of [125I]-CYP by ketamine showed a Kd of 0.35 +/- 0.03 x 10(-3) mol/L for ketamine binding to beta 2-adrenoceptors. 4. We conclude that ketamine interacts directly with both alpha 1- and beta 2-adrenoceptors and that such interactions probably explain the reported effects of this agent on the vasculature and the bronchial tree.

Adrenergic alpha-Antagonists↗

Effect of an AIDS education program for older adults.

The purpose of this study was to examine the effect of an age-specific AIDS education program on HIV/AIDS knowledge, perceived susceptibility to AIDS, and perceived severity of AIDS in older adults. The health belief model served as a framework. The age-specific AIDS education program was developed based on a knowledge, beliefs, and behaviors survey of 458 older adults at senior citizen centers. The program included case study presentations of actual older people with AIDS along with an emphasis on myths identified in the initial survey. There was a significant increase in total knowledge about AIDS (p < .001), perceived susceptibility (p < .01), and perceived severity (p < .001) after the educational program. Based on the results of this study, nurses are in an excellent position to provide primary and secondary AIDS prevention strategies for all age groups, including the older adult population.

Acquired Immunodeficiency Syndrome↗

Attitudes toward condom use among female college students.

The purpose of this study was to explore attitudes toward condom use, identify the frequency of condom usage, and examine the relationship between attitudes and condom use among sexually active female college students. This descriptive study used a convenience sample of 47 female college students attending a rural county family planning clinic. Students who reported condom use scored significantly higher on the Condom Attitudes Scale than those not using condoms. Other significant differences between condom and noncondom users were noted. The results provide insight into strategies for improving safer sexual behavior through nursing interventions for college populations.

Adolescent↗

Evaluation of oncology registry follow-up methods.

BACKGROUND: The accuracy and completeness of oncology (tumor) registry patient follow-up information directly affects the validity of the oncology registry system for determining outcomes, as a quality assurance measure, and for research activities. At this institution, if a hospital-based patient encounter has not been identified during the previous year, a follow-up letter is sent to the attending physician to obtain current information about the patient. Difficulties using this method include (1) correct identification of the appropriate physician (2) constraints on physician and staff time to provide information, and (3) accuracy, currentness, and completeness of information provided. METHODS: A study was conducted to compare the accuracy and completeness of the oncology registry patient follow-up information obtained from three sources: responses from the patient, responses from the physician, and affiliated clinic chart reviews. Seven hundred ninety-one patient and physician letters were sent during a 2-month period, and 122 clinic charts were reviewed. RESULTS: Physicians responded more frequently than patients (82% vs. 58%) (P < 0.003). From the responses received, requested information regarding recurrence, treatment, quality of survival, and survival was obtained most frequently from patients. However, it was difficult to ascertain information about cancer status from patient responses. Patients supplied more current follow-up information than physicians or the clinic chart reviews. CONCLUSIONS: A follow-up system that delivers accurate and complete information while maintaining efficiency is a critical aspect of an oncology registry. Requesting follow-up information from the patient before physician contact or chart review allows for more current information while maintaining accuracy regarding cancer recurrence, treatment, quality of survival, and survival. Consequently, staff time required for obtaining follow-up information from physicians and/or chart reviews is lessened and costs decreased.

Data Collection↗

Recognition and evaluation of oncology-related symptoms in the emergency department.

STUDY OBJECTIVE: To identify the oncology patient population presenting to the emergency department and examine the causes and clinical management of oncology symptoms in the ED. DESIGN: Retrospective review of 5,640 adult patients, with the following variables identified for oncology patients presenting to the ED: age, sex, cancer type, cancer stage, previous cancer treatment, previous hospitalization, presenting symptoms, treatment provided in the ED, admission and discharge data, and day, time, and length of ED visit. SETTING: Community teaching hospital with annual ED census of 31,000. PARTICIPANTS: All adult oncology patients who presented to the ED during the study period. We identified these patients by cross-referencing ED logs and tumor registry records. RESULTS: Cancer history was identified for 284 of the 5,640 adult ED admissions (5%). Forty-three percent (n = 122) of the 284 patients with cancer history had an oncology-related ED visit. The most common symptoms of these patients were gastrointestinal (48%), pain (40%), neurologic (38%), cardiac (25%), and pulmonary (23%). Ten percent of patients with oncology-related ED visits died during the admission, and 48% died within 1 year of the ED visit. CONCLUSION: Oncology patients present to the ED with symptoms of undiagnosed malignancy, complications of cancer treatment, and acute disease-related symptoms. Knowledge of an individual's cancer history and ability to recognize oncologic symptoms are important to the management of oncology patients.

Aged↗

Knowledge of human immunodeficiency virus and acquired immunodeficiency syndrome, perception of risk, and behaviors among older adults.

In a study of knowledge and beliefs about human immunodeficiency virus among older persons, 458 senior center participants completed a questionnaire derived from the Health Belief Model. The older adults had a fairly good knowledge base about acquired immunodeficiency syndrome (AIDS). Although they recognized the seriousness of the disease, they generally did not believe that they were susceptible to AIDS. Those who expressed an interest in receiving AIDS education had significantly higher perceived susceptibility scores than those who did not. African American respondents were statistically more interested in AIDS education than white or Hispanic respondents. Recommendations for interventions and further research are discussed.

Acquired Immunodeficiency Syndrome↗

Phase II trial of external beam radiation with etanidazole (SR 2508) for the treatment of locally advanced prostate cancer.

PURPOSE: To evaluate the efficacy and toxicity of the addition of etanidazole (ETA) to external beam radiation. METHODS AND MATERIALS: Fifty eight previously untreated patients with locally advanced adenocarcinoma of the prostate were entered on a Phase II trial of etanidazole (ETA) combined with standard external beam radiation therapy. ETA was given concurrently with irradiation. Four patients received less than 25% of the intended dose of ETA and were ineligible for further analysis. The stage of the remaining patients were T2c-11, T3-39, T4-1, bulky local recurrence after prostatectomy-1, and T3, N1-2. RESULTS: Forty-five of 54 patients (83.3%) achieved a clinical complete response (CCR) in the prostate and seminal vesicles as judged by digital rectal exam (DRE). Responses were rapid with a median time to CCR of 3.4 months, range 0-22.8 months. Local control was maintained in 82% of the patients who achieved a CCR. Fifteen of 32 eligible patients with a normal DRE underwent prostate biopsies from 12-20 months after treatment, seven had negative biopsies (46.6%). Distant metastases occurred in 18 patients (33.3%). Pretreatment prostatic specific antigen (PSA), Gleason score, and stage were not associated with treatment outcome in a univariate analysis. CONCLUSION: While ETA plus radiation was associated with a rapid CCR, the overall treatment outcome of these patients appeared to be similar to published reports of patients receiving RT alone. The rapid response rate may imply biologic activity of the ETA. In future trials, it may be reasonable to focus on patients at lower risk for the subsequent development of distant disease.

Adenocarcinoma↗