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Biomedical subjects

C Baker

Publications and source records attributed to C Baker.

At least 37 records · Page 2Linked to original sources

A phase I study of adenovirus-mediated transfer of the human cystic fibrosis transmembrane conductance regulator gene to a lung segment of individuals with cystic fibrosis.

A third-generation adenoviral vector containing recombinant human cystic fibrosis transmembrane conductance regulator (CFTR) gene was delivered by bronchoscope in escalating doses to the conducting airway of 11 volunteers with cystic fibrosis. Assessments of dose-limiting toxicity (DLT), efficiency of gene transfer, and cell-mediated and humoral immune responses to vector administration were performed. DLT, manifest by flulike symptoms and transient radiographic infiltrates, was seen at 2.1 x 10(11) total viral particles. A highly specific assay for gene transfer was developed using in situ hybridization with an oligoprobe against unique vector sequence. Detectable gene transfer was observed in harvested bronchial epithelial cells (<1%) 4 days after vector instillation, which diminished to undetectable levels by day 43. Adenovirus-specific cell-mediated T cells were induced in most subjects, although only mild increases in systemic humoral immune response were observed. These results demonstrate that gene transfer to epithelium of the lower respiratory tract can be achieved in humans with adenoviral vectors but that efficiency is low and of short duration in the native CF airway.

Adenoviridae↗

Solution structure of the sodium channel inactivation gate.

The sodium channel initiates action potentials by opening in response to membrane depolarization. Fast channel inactivation, which is required for proper physiological function, is mediated by a cytoplasmic loop proposed to occlude the ion pore via a hinged lid mechanism with the triad IFM serving as a hydrophobic "latch". The NMR solution structure of the isolated inactivation gate reveals a stably folded core comprised of an alpha-helix capped by an N-terminal turn, supporting a model in which the tightly folded core containing the latch motif pivots on a more flexible hinge region to occlude the pore during inactivation. The structure, in combination with substituted cysteine mutagenesis experiments, indicates that the IFM triad and adjacent Thr are essential components of the latch and suggests differing roles for the residues of the IFMT motif in fast inactivation.

Amino Acid Sequence↗

Lung-sparing surgery after penetrating trauma using tractotomy, partial lobectomy, and pneumonorrhaphy.

OBJECTIVE: To evaluate the role of lung-sparing surgical techniques in the surgical management of penetrating pulmonary injuries. DESIGN: Retrospective case series. SETTING: Academic level I trauma center. PATIENTS AND METHODS: Forty patients underwent thoracic surgery for penetrating lung injuries during a 63-month period from January 1993 to March 1997. Five (12.5%) underwent anatomical lobectomy, 3 (7.5%) pneumonorrhaphy, 9 (22.5%) stapled wedge resection, and 23 (57.5%) stapled tractotomy. In total, 34 patients (85%) were treated with stapling techniques (1 anatomical lobectomy, 1 pneumonorrhaphy, 9 stapled wedge resections, and 23 stapled tractotomies) and 35 (87.5%) underwent had lung-sparing surgery for trauma. RESULTS: Morbidity and mortality rates were 40% and 5%, respectively. Patients who underwent anatomical lobectomy required longer mechanical ventilatory support, intensive care unit stay, and hospital stay and had a higher morbidity rate compared with patients who underwent lung-sparing surgery for trauma but had central and extensive pulmonary injuries. Stapled tractotomy was efficient in controlling bleeding and bronchial leaks, but, in 3 patients, parts of the divided lung parenchyma were devascularized and had to be resected. CONCLUSIONS: Lung-sparing surgery for trauma with the use of staplers can be used in the majority of patients with penetrating pulmonary injuries requiring operation. Stapled tractotomy is a rapid and effective method for controlling hemorrhage and air leaks.

Adult↗

Transforming growth factor-beta2 is elevated in skeletal muscle disorders.

The transforming growth factor betas (TGF-betas) are multifunctional growth factors that act on both fibroblasts and myosatellite cells. In rodent models of muscle diseases, high levels of TGF-beta2 are expressed by myogenic cells. We have examined whether the expression of TGF-beta2 is also elevated in diseased human muscles. The disorders examined were Duchenne muscular dystrophy, myotonic dystrophy, myotubular myopathy, spinal muscular atrophy, and amyotrophic lateral sclerosis. The levels of TGF-beta2 immunoreactivity were elevated in atrophic, necrotic, and regenerating fibers and in fibers with central nuclei or cytoplasmic masses, irrespective of whether fibrosis was present. We therefore suggest that TGF-beta2 is important for muscle repair and that the presence of a TGF-beta within a muscle only leads to fibrosis if certain other factors are present.

Amyotrophic Lateral Sclerosis↗

Dynamic exercise normalizes resting blood pressure in mildly hypertensive premenopausal women.

BACKGROUND: Dynamic exercise acutely and transiently lowers resting blood pressure in hypertensive men and is termed postexercise hypotension (PEH). We examined 18 premenopausal women (7 hypertensive and 11 normotensive) to determine if PEH occurs in women and to elucidate possible hemodynamic and hormonal mechanisms. METHODS AND RESULTS: Patients wore an ambulatory blood pressure monitor throughout the day after 40 minutes of a rest sham session and 40 minutes of cycle exercise, of which 30 minutes was performed at 60% of maximal oxygen consumption. Cardiac output and total systemic vascular resistance were determined by Doppler echocardiography before and 15 minutes after sham and exercise. Catecholamines, plasma renin activity, and beta-endorphin were measured over this same period. PEH occurred only in the hypertensive women. Systolic, diastolic, and mean arterial blood pressure decreased in the hypertensive women by a mean of 9.5 +/- 2. 8 mm Hg (P <.01), 6.7 +/- 2.4 mm Hg (P <.05), and 7.7 +/- 2.4 mm Hg (P <.05), respectively, for up to 7 hours after versus before exercise, whereas blood pressure was similar in the normotensive women (P >.05). After exercise, total systemic vascular resistance was lower (P <.01), and cardiac output, catecholamines, and plasma renin activity were greater (P <.01) than before exercise in both groups of women. CONCLUSIONS: PEH was observed for up to 7 hours after exercise in mildly hypertensive women and was not explained by the hemodynamic and hormonal adjustments that occurred after exercise. The magnitude and duration of PEH may be sufficient to normalize the blood pressure of certain hypertensive women throughout most of the day.

Adult↗

Effectiveness of cognitive therapy training.

Despite growing demands for effective training there remains a lack of convincing evaluations. Reviews of the training literature specify the need for multiple measures, homogeneous therapies, generalization assessments and longitudinal designs. The present analysis responds by evaluating the training of 20 mental health professionals in cognitive therapy (CT). The evaluation focussed on changes in the professionals' competence and its generalization to their patients' coping strategies (N = 20). Results indicated that a 40 day training programme led to significantly higher post-training competence scores and to improved patient coping. The implications for professional training and its evaluation are discussed.

Adult↗

Evaluation of pediatric cervical spine injuries.

To compare historical features, clinical examination findings, and radiographic results among pediatric patients with cervical spine injury (CSI), a retrospective review of patients who were diagnosed with CSI was undertaken. Two main groups were identified: radiographically evident cervical spine injury (RESCI), and spinal cord injury without radiographic abnormality (SCIWORA). Demographic, historical, clinical, and radiographic information was obtained from patients' charts and analyzed to determine factors associated with CSI and to determine the efficacy of the various radiographic views. Seventy-two children, ages from 1 month to 15 years (median age, 9 yrs), were included in the study. Sports-related injuries were the most common. Forty patients had RESCI and 32 had SCIWORA. Forty-nine (80%) of all the patients had abnormal findings on neck examination, and six (16%) of the RECSI group had abnormal neurological findings. Lateral radiographs had a sensitivity for CSI of 79%; a three-view radiographic series had a sensitivity of 94%. All patients with CSI who were clinically asymptomatic had both a high-risk injury mechanism and a distracting injury. CSI should be suspected in any child with abnormal findings on neck or neurological examination. A minimum of three radiographic cervical spine views should be obtained in the evaluation of CSI in children. Even in the face of a three-view series, CSI should be suspected in patients with an abnormal neck or neurological exam, high-risk mechanism of injury, or distracting injury.

Adolescent↗

Development of an activities of daily living scale to screen for dementia in an illiterate rural older population in India.

OBJECTIVE: to develop a measure of activities of daily living appropriate for use in assessing the presence of dementia in illiterate rural elderly people in India. DESIGN: identification of relevant items, pre-testing of items and refinement of administrative procedures and scoring in four successive groups of 30 subjects each, pilot testing in a group of 100 subjects comparable to those for whom the measure is intended, administration to a representative sample of 387 people aged 55 and older, and assessment of the reliability of the final measure. SETTING AND SUBJECTS: age-stratified random sample of older men and women in rural areas of Ballabgarh, Northern India. RESULTS: the original pool of 35 items covering mobility, instrumental and personal care activities was reduced to an 11-item unidimensional scale (to which an additional item on mobility was added) with internal consistency (Cronbach's alpha)=0.82, perfect inter- and intra-rater reliability, test-retest reliability (intraclass correlation)=0.82 (any disability) and 0.92 (unable to perform for 'mental' reasons). Women, older subjects, the totally illiterate and subjects with poorer cognitive function performed significantly more poorly (P < or = 0.02 for all). PRODUCT: a brief, reliable and valid activities of daily living measure, with norms, which is appropriate for use in assessing dementia in illiterate rural elderly people in India.

Activities of Daily Living↗

Oxidative damage to proteins of bronchoalveolar lavage fluid in patients with acute respiratory distress syndrome: evidence for neutrophil-mediated hydroxylation, nitration, and chlorination.

OBJECTIVE: To assess the degree, source, and patterns of oxidative damage to bronchoalveolar lavage proteins as a modification of amino acid residues in patients with acute respiratory distress syndrome (ARDS). DESIGN: Prospective, controlled study. SETTING: Adult intensive care unit of a postgraduate teaching hospital. PATIENTS: Twenty-eight patients with established ARDS were studied and compared with six ventilated patients without ARDS and 11 normal healthy controls. INTERVENTIONS: Supportive techniques appropriate to ARDS. MEASUREMENTS AND MAIN RESULTS: Evidence of oxidative modification of bronchoalveolar lavage fluid protein, indicative of the production of specific reactive oxidizing species, was sought using a high-performance liquid chromatography technique. Bronchoalveolar lavage fluid samples from patients with ARDS, ventilated intensive care controls, and normal healthy controls were analyzed. Concentrations of orthotyrosine were significantly higher in the ARDS group than in either control group (7.98 + 3.78 nmol/mg for ARDS, 0.67 + 0.67 for ventilated controls, and 0.71 + 0.22 for healthy controls; p < .05). Chlorotyrosine concentrations were also significantly increased in the ARDS group over either control group (4.82 + 1.07 nmol/mg for ARDS, 1.55 + 1.34 for ventilated controls, and 0.33 + 0.12 for healthy controls; p < .05). Nitrotyrosine concentrations were similarly significantly increased in the ARDS groups compared with each control group (2.21 + 0.65 nmol/mg for ARDS, 0.29 + 0.29 for ventilated controls, and 0.06 + 0.03 for healthy controls; p < .05). Chlorotyrosine and nitrotyrosine concentrations showed significant correlations with myeloperoxidase concentrations in bronchoalveolar lavage fluid, measured using an enzyme-linked immunosorbent assay in patients with ARDS. These findings suggest a possible relationship between inflammatory cell activation, oxidant formation, and damage to proteins in the lungs of these patients CONCLUSIONS: Overall, our data strongly suggest heightened concentrations of oxidative stress in the lungs of patients with ARDS that lead to significantly increased oxidative protein damage.

Adolescent↗

RANTES production by cultured primate endometrial epithelial cells.

PROBLEM: RANTES (regulated upon activation, normal T cell expressed and secreted), is a chemokine with monocyte, macrophage, T lymphocyte, and eosinophil attractant and activating activities. This mediator has been detected in the peritoneal fluid of patients with endometriosis and in cultures of stromal cells from human endometrial and endometriotic tissue. To determine if endometrial epithelial cells were also a potential source of this mediator, primate endometrial epithelial cells were cultured in vitro and the constitutive and stimulated production of RANTES in these cultures was measured. METHOD OF STUDY: Uterine tissue was obtained from Macaca nemestrina monkeys and the endometrial epithelial cells were isolated and placed in culture for 24-72 hr. RANTES was measured in cell extracts and culture fluids by enzyme-linked immunosorbent assay (ELISA). RESULTS: Constitute release of RANTES was low, ranging from 28-52 ng/mL but addition of interferon gamma (INF-gamma) or the combination of IFN-gamma and tumor necrosis factor alpha (TNF-alpha) produced a marked increase in RANTES production. The greatest release, which was nearly 500-fold greater than the basal level, was observed at 72 hr with the combined addition of TNF-alpha and INF-gamma. Nearly 90% of the stimulated RANTES was released into culture fluids, while cell associated RANTES was minimal constituting only 11.2% of the total. CONCLUSION: These findings indicate that endometrial epithelial cells can produce and release RANTES. This chemokine may be an important attractant and activator of macrophages, T lymphocytes and/or eosinophils in the uterus during the reproductive cycle or implantation.

Adjuvants, Immunologic↗

The helping process in couples during recovery from heart attack: a single case study.

This single case study aimed to illustrate help-intended communication in couples, in particular how a husband and wife attempted to help each other with adjusting to the husband's recent myocardial infarction. The study employed a semi-structured communication task to gather samples of the couple's helping interactions: the couple had two conversations in which they alternated helper and discloser roles. Quantitative and qualitative data were obtained from the couple and from expert raters (observers) about their perspectives of the conversations. The observers' ratings and verbal response mode patterns indicated that the conversations were characterized by low levels of empathy and exploration of feelings and relatively high levels of helper disclosure and advice; overall, the observers found the conversations to be somewhat unhelpful. In contrast, the couple rated the conversations more positively; the 'helpful events' they identified consisted of their partner disclosing a new piece of information and giving advice. The results were discussed in terms of the unique features of helping in close relationships.

Communication↗

From chaos to order: a nursing-based psycho-education program for parents of children with attention-deficit hyperactivity disorder.

A psycho-education program for parents of children with attention-deficit hyperactivity disorder (ADHD) is described. This intervention strategy is based on the nursing theory Modeling and Role Modeling developed by Erickson, Tomlin, and Swain to help people cope with stressors by facilitating the development of self-care knowledge and self-care resources, and by promoting self-care action. Key components of the program are an emphasis on pattern recognition and pattern management, the fostering of insider and outsider knowledge, and an emphasis on the strengths of participants and of their children with ADHD.

Adaptation, Psychological↗

An exploration of methodological pluralism in nursing research.

The purpose of this article is to describe some important differences in methodological perspectives within the discipline of nursing. Four research traditions (empiric analytic, grounded theory, Heideggerian hermeneutic, and participatory action research) and the philosophical assumptions that inform them are presented. The discussion touches on criticisms that arise from within and from outside each tradition, as well as how each addresses the usefulness of research. Finally, ways in which specialized language is simultaneously necessary and problematic in advancing scholarly debate are illuminated.

Humans↗

Practical issues in cognitive screening of elderly illiterate populations in developing countries. The Indo-US Cross-National Dementia Epidemiology Study.

The study of the epidemiology of dementia, specifically Alzheimer's disease, in developing countries requires specialized instruments and personnel. Cultural and sub-cultural differences among populations are highly relevant to the design of such instruments. Over and above the cultural issues, it is widely recognized that low education and illiteracy pose considerable challenges to reliable and valid cognitive screening. The overall objectives of the Indo-US Cross-National Dementia Epidemiology Study were: a) to determine the prevalence and incidence of, and risk factors for, Alzheimer's and other dementias in a defined Indian community; and b) to compare these results with those found in a defined American community. To achieve these epidemiological objectives, our first task was to develop, systematically and empirically, suitable cognitive and activities assessment screening instruments for use in India, which would 1) be culturally fair, psychometrically sound, and valid for a population with little or no education; 2) be optimally sensitive and specific for dementia; and 3) allow not only the identification but also the more detailed characterization of dementia, and of normal and abnormal cognitive aging. In this paper we address the practical issues involved in the development and administration of the modified cognitive screening battery in our rural Indian context.

Aging↗

Paired-associate learning is unaffected by combined hippocampal and parahippocampal lesions in homing pigeons.

To examine whether the avian hippocampus-parahippocampus (HF) is necessary for nonspatial, paired-associate learning, as has been suggested for rodents, HF-lesioned and control homing pigeons were tested on a visual paired-associate learning task. Both groups learned equally well to discriminate trials that consisted of a stimulus preceded by its paired associate from trials that consisted of a stimulus preceded by stimuli from other paired associates (mispair trials), even when a mispair was experienced for the first time. The groups also learned equally well not to respond to 2 stimuli that were never rewarded. The results demonstrate that HF lesions do not impair nonspatial paired-associate learning in birds, suggesting that the role of HF in nonspatial cognition differs between birds and mammals.

Analysis of Variance↗