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Biomedical subjects

B Rogers

Publications and source records attributed to B Rogers.

At least 19 recordsLinked to original sources

Using intranasal lidocaine to reduce food intake.

OBJECTIVE: Develop a dose-response curve for the effect of intranasal lidocaine on food intake. DESIGN: Healthy obese subjects had food intake, ratings of hunger, desire to eat, craving and fullness measured at lunch after an overnight fast. Four treatments were given as nose drops (0.5-0.6 ml per nostril) 5 min before the meal in a double-blind manner with a four period crossover design including a 7-day washout between periods. The treatments were saline, 2.5, 10 and 25 mg lidocaine per nostril. The order of administration was randomly assigned to each subject. Electrocardiograms, vital signs, chemistry panels, complete blood counts (CBC) and nasal inspections were carried out before and after each dose. SUBJECTS: Forty-seven subjects were screened, 34 were randomized and 20 subjects completed all four study periods in the trial. The subjects were 39+/-12.5 (s.d) years of age, had a weight of 91+/-13.0 kg, a height of 167+/-10.3 cm, 56% were women, 47% were African-American and 53% were Caucasian. MEASUREMENTS: Food intake, rating of hunger, desire to eat, craving and fullness are measures of efficacy. Adverse events, electrocardiograms, vital signs, chemistry panels, nasal inspections, CBC and physical exams are measures of safety. RESULTS: The mean reduction in food intake vs saline control in the 20 subjects completing all four study periods was 3.3+/-7% (s.d), 4.2+/-8.5% and 7.4+/-7.3% in the 2.5 mg, 10 and 25 mg per nostril groups, respectively (P=NS). Hunger and desire to eat in subjects who completed at least one study period decreased dose dependently (P<0.03, at the 25 mg per nostril dose). There were no clinically significant changes in safety measures, electrocardiograms, vital signs, chemistry panels, CBC or nasal inspections. CONCLUSION: Intranasal lidocaine reduced hunger and the desire to eat, but this did not translate into a significant reduction in food intake suggesting that intranasal lidocaine will not have value in treating obesity.

Administration, Intranasal↗

Nonviral ocular gene transfer.

In this study, we explored the use of electroporation or media that promote lipoplex formation for nonviral gene transfer in the eye. There was no detectable staining for LacZ after subretinal, intravitreous, or periocular injection of a plasmid containing a CMV promoter expression cassette for LacZ, but when plasmid injection in each of the three sites was combined with electroporation, there was efficient transduction. Specific staining for LacZ was seen in retinal pigmented epithelial (RPE) cells after subretinal injection of a plasmid containing a vitelliform macular dystrophy 2 (VMD2) promoter expression cassette, demonstrating that this approach can be used to evaluate purported tissue-specific promoters in vivo. Electroporation with 10 V/mm resulted in strong LacZ staining, but was damaging to photoreceptors; substantial transduction with no evidence of retinal damage was seen using 3.4 V/mm. Staining for LacZ was also seen after subretinal or periocular, but not intravitreous, injection of plasmid DNA in medium containing 40% Lipofectamine2000 (Lf). Injection of 40% Lf into the subretinal space caused damage to photoreceptors, but subretinal injection of plasmid DNA in medium containing 10% NeuroPorter resulted in transduction of RPE cells with no adverse effects on retinal morphology or function as assessed by electroretinograms (ERGs). After either electroporation or lipofection, LacZ staining was detectable for at least 14 days, and could be reinduced by a second procedure. These data suggest that electroporation or lipofection can be used as experimental tools for ocular gene transfer to evaluate tissue-specific promoter fragments or to evaluate the effects of transgene expression in the retina. Also, with additional optimization, nonviral gene transfer may prove to be a valuable approach for the treatment of retinal and choroidal diseases.

Animals↗

Improving tapping mode atomic force microscopy with piezoelectric cantilevers.

This article summarizes improvements to the speed, simplicity and versatility of tapping mode atomic force microscopy (AFM). Improvements are enabled by a piezoelectric microcantilever with a sharp silicon tip and a thin, low-stress zinc oxide (ZnO) film to both actuate and sense deflection. First, we demonstrate self-sensing tapping mode without laser detection. Similar previous work has been limited by unoptimized probe tips, cantilever thicknesses, and stress in the piezoelectric films. Tests indicate self-sensing amplitude resolution is as good or better than optical detection, with double the sensitivity, using the same type of cantilever. Second, we demonstrate self-oscillating tapping mode AFM. The cantilever's integrated piezoelectric film serves as the frequency-determining component of an oscillator circuit. The circuit oscillates the cantilever near its resonant frequency by applying positive feedback to the film. We present images and force-distance curves using both self-sensing and self-oscillating techniques. Finally, high-speed tapping mode imaging in liquid, where electric components of the cantilever require insulation, is demonstrated. Three cantilever coating schemes are tested. The insulated microactuator is used to simultaneously vibrate and actuate the cantilever over topographical features. Preliminary images in water and saline are presented, including one taken at 75.5 microm/s-a threefold improvement in bandwidth versus conventional piezotube actuators.

Journal Article↗

Actions taken to cope with depression at different levels of severity: a community survey.

BACKGROUND: Many people with symptoms of psychological distress do not seek professional help. Little is known about the actions taken by these people to reduce their symptoms. The present study aimed to assess, in a community sample, actions taken to cope with depression at different levels of psychological distress. METHOD: A postal survey was carried out with 6618 adults living in Canberra and south-east New South Wales, Australia. Measures covered psychological distress and a checklist of actions taken to cope with depression in the previous 6 months. RESULTS: Actions taken to cope with depression could be classified as: intensification of everyday strategies, initiation of new self-help (including complementary therapies, non-prescription medication and dietary changes) and seeking professional help. Use of everyday strategies peaked with mild psychological distress, new self-help showed a peak in moderate distress, while professional help-seeking peaked in severe distress. CONCLUSION: Self-help strategies are very commonly used, particularly in mild-moderate psychological distress. More evidence is needed to evaluate their effectiveness, so that optimal self-help can be encouraged.

Adaptation, Psychological↗

Phase I trial of multiple cycles of high-dose carboplatin, paclitaxel, and topotecan with peripheral-blood stem-cell support as front-line therapy.

PURPOSE: To determine the safety and feasibility of delivering multiple cycles of front-line high-dose carboplatin, paclitaxel, and topotecan with peripheral-blood stem-cell (PBSC) support. PATIENTS AND METHODS: Patients were required to have a malignant solid tumor for which they had received no prior chemotherapy. Mobilization of PBSC was achieved with either filgrastim alone or in combination with cyclophosphamide and paclitaxel. Patients then received three or four cycles of high-dose carboplatin (area under the concentration-time curve [AUC] 16), paclitaxel (250 mg/m(2)), and topotecan (10-15 mg/m(2)), with the latter two agents administered as 24-hour infusions and supported with PBSC and filgrastim. Cycles were repeated every 28 days. RESULTS: Twenty patients were enrolled onto the trial and were assessable for toxicity and clinical outcome. Dose-limiting toxicities were stomatitis and prolonged hematopoietic recovery. The maximum-tolerated dose of topotecan was 12.5 mg/m(2) when given with high-dose carboplatin and paclitaxel for three cycles. Four cycles were able to be given with a dose of topotecan of 10 mg/m(2). The pharmacokinetics of each compound were not affected by the other agents. Eleven (85%) of 13 patients with assessable disease responded. CONCLUSION: Multiple cycles of high-dose carboplatin, paclitaxel, and topotecan can be safely administered with filgrastim and PBSC support. The recommended doses for phase II study are carboplatin AUC 16, paclitaxel 250 mg/m(2), and topotecan 10 mg/m(2). Trials are currently being conducted with this regimen as front-line treatment in patients with advanced ovarian cancer and extensive small-cell carcinoma. This approach remains experimental and should be used only in the context of a clinical trial.

Adult↗

Production of butyrylcholinesterase by Caco-2 cells: lack of relationship with triglyceride production.

Elevated levels of butyrylcholinesterase activity occur under a number of hypertriglyceridemic conditions, including diabetes and obesity. This study examines whether butyrylcholinesterase activity has a direct effect on triglyceride production, using Caco-2 cells, a human intestinal adenocarcinoma cell line. Caco-2 cells were incubated with 500 microM oleate to stimulate triglyceride production, and butyrylcholinesterase activity was measured in the cellular homogenate. Butyrylcholinesterase activity was approximately 3 x 10(-3) micromol/min per milligram protein. Although triglyceride production increased by almost five-fold after 18 h of stimulation with oleate, butyrylcholinesterase activity was not increased. Furthermore, inhibition of butyrylcholinesterase activity using 1 mM tetraisopropylpyrophosphoramide did not significantly affect triglyceride production or secretion. Human insulin (100 microU/ml) increased the production of butyrylcholinesterase without increasing triglyceride production. This demonstrates that stimulation of fatty acid production and butyrylcholinesterase activity occur by independent mechanisms and suggests that their correlation in hyperlipidemic conditions is not due to a direct relationship in production in situ.

Butyrylcholinesterase↗

Three new phenolic compounds from a manipulated plant cell culture, Mirabilis jalapa.

Bioassay-guided fractionation of an organic extract of the cell mass from a manipulated plant cell culture of Mirabilis jalapa led to the isolation and subsequent identification of three new phenolic compounds, 1, 2, and 3. The isoflavone 1 and dehydrorotenoid 2 were identified as the principal antifungal principles from this plant cell culture with IC(50)'s of 25 and 48 microg/mL, respectively, against the test organism, Candida albicans DSY1024. The rotenoid 3 was inactive at 200 microg/mL in this assay.

Antifungal Agents↗

The pleitropic drug ABC transporters from Saccharomyces cerevisiae.

The Saccharomyces cerevisiae genome contains 16 genes encoding full-size ABC transporters. Each comprises two nucleotide binding folds (NBF) alternating with transmembrane domains (TM). We have studied in detail three plasma membrane multidrug exporters: Pdr5p (TC3.A.1.205.1) and Snq2p (TC3.A.1.205.2) which share NBF-TM-NBF-TM topology as well as Yor1p (TC3.A.1.208.3) which exhibits the reciprocal TM-NBF-TM-NBF topology. The substrate specificity of Pdr5p, Snq2p and Yor1p are largely, but not totally, overlapping as shown by screening the growth inhibition by 349 toxic compounds of combinatorial deletants of these three ABC genes. Multiple deletion of 7 ABC genes (YOR1, SNQ2, PDR5, YCF1, PDR10, PDR11 and PDR15) and of two transcription activation factors (PDR1 and PDR3) renders the cell from 2 to 200 times more sensitive to numerous toxic coumpounds including antifungals used in agriculture or medicine. The use of the pdr1-3 activating mutation and when necessary of the PDR5 promoter in appropriate multideleted hosts allow high levels of expression of Pdr5p, Snq2p or Yor1 p. These overexpressed proteins exhibit ATPase activity in vitro and confer considerable multiple drug resistance in vivo. The latter property can be used for screening specific inhibitors of fungal and other ABC transporters.

ATP-Binding Cassette Transporters↗

Phase II trial of induction high-dose chemotherapy followed by surgical resection and radiation therapy for patients with marginally resectable non-small cell carcinoma of the lung.

The combination of carboplatin and paclitaxel is an active regimen in non-small cell lung cancer (NSCLC). Historically, patients with stage III disease have manifested higher response rates than patients with metastatic disease, and patients achieving a pathologic complete response to induction chemoradiation therapy prior to surgery have shown better long-term outcome. Based upon our pilot data using high-dose carboplatin and paclitaxel, we designed a phase II trial in patients with marginally resectable stage IIIA NSCLC. Ten patients, with bulky nodal stage IIIA disease, initially received etoposide (2 g/m2) and granulocyte colony-stimulating factor (G-CSF) to mobilize peripheral blood stem cells (PBSC). Two cycles, 28 days apart, of carboplatin (AUC 12 in seven patients; AUC 16 in three patients) and paclitaxel (250 mg/m2) were administered with filgrastim (5 microg/kg) and PBSC support. After re-evaluation, patients underwent a thoracotomy followed by radiotherapy (44-60 Gy) if deemed resectable, or radiotherapy alone (60 Gy) if not resectable. The median age was 58.5 years (48-66) with a median ECOG performance status of 0 (0-1). Histology was adenocarcinoma in seven patients; the remainder had either squamous cell, large cell or bronchoalveolar carcinoma. Based on CT radiography, the overall response rate was 40%. Eight of ten patients underwent resection with four right pneumonectomies, three right upper lobectomies and one wedge resection of the right upper lobe. Six patients had a complete resection. Of eight patients resected, four were downstaged by induction therapy, three remained unchanged and one was found to have more extensive disease. The remaining two patients developed metastatic disease while receiving chemotherapy. The median dose of postoperative radiotherapy was 54 Gy (35-66 Gy). Actual median follow-up for all patients was 89 weeks (25 to 136+). The actuarial median overall survival was 124 weeks (25 to 136+) and time to progression was 57 weeks (17 to 136+). The median dose of carboplatin delivered expressed as mg/m2 was 779 (615-1540). Neutropenic fever occurred in two patients during the initial mobilization cycle only. The median number of units of RBC and/or platelets transfused was 0 (0-2 and 0-6, respectively). There were no significant non-hematologic toxicities. High-dose induction chemotherapy with stem cell rescue is feasible and safe with an acceptable response rate. Thoracotomy, including pneumonectomy and postoperative radiotherapy, were well tolerated by patients after undergoing high-dose induction chemotherapy with no apparent increase in peri-operative morbidity. The pathologic complete response rate was low--one out of ten patients. These results indicate that dose escalation of induction chemotherapy does not improve response rates even in this highly selected patient population. Accordingly, the complexity and potential toxicity of high-dose chemotherapy, as delivered in this trial as neoadjuvant treatment of non-small cell lung cancer, is not warranted.

Adenocarcinoma↗

Evaluation of interventions to prevent needlestick injuries in health care occupations.

OBJECTIVE: The objective of this study was to evaluate interventions that reduce or prevent needlestick injuries in health care occupations. METHODS: Cochrane Collaboration search strategies to locate studies that evaluated interventions to reduce needlestick injuries in health care occupations were used. Studies were selected if they met the following criteria: (1) interventions were evaluated in the defined population; (2) interventions were randomized, with a comparison group(s); (3) outcomes were objectively measured and had interpretable data. Eleven studies met inclusion criteria. The main outcomes of interest were changes in the number of glove or skin perforations and changes in amount of skin contamination. RESULTS: Three studies found a decrease in glove or skin perforations when double gloves or combinations of gloves were used by surgeons and their assistants. One study found an increase in glove perforations but a decrease in hand contamination. Three studies evaluated the effectiveness of specialized needles in reducing needlestick injuries during surgical wound closure with decreases in glove or skin perforations reported. Protective devices were evaluated in three studies and significant reductions in glove perforations were found with the use of a needleless intravenous system and surgical assist device. One study evaluated a "no-touch" technique used by surgeons during wound closure and found a significant decrease in the number of glove perforations compared to the traditional "hand-in" method of closure. CONCLUSIONS: Few randomized controlled trials have been employed to evaluate the effectiveness of interventions to reduce needlestick injuries in health care occupations. The majority of the studies evaluated interventions during surgical procedures, rather than during patient care on nursing units, probably because the latter is more difficult to observe.

Evaluation Studies as Topic↗

Reported quality of life of people with spinal cord injuries: a longitudinal analysis of the first 6 months post-discharge.

STUDY DESIGN: A repeated measures design was employed with measures taken on two observational periods during the first 6 months post-discharge from hospital. OBJECTIVES: To investigate the perceived importance of specific needs implicated in the development of quality of life (QOL), and the extent to which these aspects have been achieved, in a group of people with spinal cord injury (SCI) living in the community. SETTING: The National Spinal Injuries Centre, Stoke Mandeville Hospital and the general community. METHODS: The study sample comprised 24 spinal cord injured patients discharged from a national rehabilitation centre following a rehabilitation programme. The Quality of Life and Needs Assessment Questionnaire was completed by participants at 1 and 6 months post discharge. RESULTS: No significant differences were found between the importance that participants attributed to specific needs at months 1 and 6 post discharge. Moreover, no significant differences were found between the extent to which these needs were met at 1 and 6 months post discharge. CONCLUSION: The reported quality of life of people who have a spinal cord injury remains stable during the first year following discharge.

Female↗

Alpha-synuclein expression in central nervous system tumors showing neuronal or mixed neuronal/glial differentiation.

Alpha-synuclein (alpha-synuclein) is a member of a family of cytoplasmic proteins found predominantly and abundantly in the brain, and concentrated in pre-synaptic nerve terminals, near vesicles. We hypothesized that an antibody to alpha-synuclein could be a useful marker of neuronal differentiation in central nervous system (CNS) tumors. Twenty tumors known to have neuronal or mixed neuronal/glial differentiation ( 11 gangliogliomas, 2 anaplastic gangliogliomas, 5 gangliocytomas, and 2 ganglioneuroblastomas), 5 central neurocytomas, and 1 dysembryoplastic neuroepithelial tumor (DNET) were immunostained with a mouse monoclonal antibody raised against human alpha-synuclein. Intense cytoplasmic staining, in some instances extending into the perikarya, was seen in 6 of 11 gangliogliomas, 2 of 2 anaplastic gangliogliomas, and 2 of 2 ganglioneuroblastomas. Alpha-synuclein-positive cells were usually large in size, resembled dysmorphic neurons, and were variably immunoreactive for anti-neurofilament and/or anti-synaptophysin antibodies. In contrast, central neurocytomas, gangliocytomas, and the DNET were negative for cytoplasmic alpha-synuclein expression. Our findings indicate that alpha-synuclein is expressed within the neuronal component of mixed tumors of the CNS displaying more than 1 histophenotype, and/or showing different degrees of anaplasia. Based on currently available data, we conclude that cytoplasmic alpha-synuclein expression is a marker of maturing neurons in these tumors.

Cell Differentiation↗

Occupational health surveillance, screening, and prevention activities in occupational health nursing practice.

Occupational health nursing practice is broad and encompasses surveillance, screening, and prevention activities as part of the scope of practice. While there has been some controversy about who is responsible for these activities, it is clear occupational health nurses play a pivotal role in overseeing, managing, implementing, and evaluating these programs. In fact, recent OSHA standards have included broad language that permits licensed health care professionals acting within their legal scope of practice to conduct medical and health surveillance activities. While the contributions of occupational health nurses are well documented, little is known about the degree and emphasis in practice related to surveillance, screening, and prevention programs. This study examined the scope of independent and interdependent practice by occupational health nurses related to these activities and found 71% of occupational health nurses had overall responsibility for program management, and the majority performed surveillance, screening, and prevention functions as independent practice. Physician supervision for any of these activities ranged from only 0% to 8% in reporting. The results of this study validate the independent functioning in scope of occupational health nursing practice related to surveillance, screening, and prevention activities while recognizing the contributions all providers make to a healthy work force.

Cross-Sectional Studies↗