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Biomedical subjects

C Brown

Publications and source records attributed to C Brown.

At least 235 records · Page 13Linked to original sources
PubMed1996

A murine RNA polymerase I promoter inserted into the herpes simplex virus type 1 genome is functional during lytic, but not latent, infection.

The development of herpes simplex virus as a vector for neuronal gene delivery is dependent upon the identification and characterization of promoter elements capable of driving long-term expression during latency. The majority of RNA polymerase II (pol II) promoters studied are active during acute infection but silenced during latency. In order to investigate the potential of a murine RNA polymerase I (pol I) promoter to drive reporter gene expression during lytic and latent infection, we describe the construction and characterization of two recombinant viruses; SC16 LAT neo and SC16 US5 neo. These viruses contain a pol I-encephalomyocarditis virus internal ribosome entry site (EMCV IRES)-neomycin phosphotransferase gene (neoR) cassette inserted into the non-essential major latency associated transcript (LAT) and US5 regions respectively. Pol I promoter activity could be detected in the rodent BHK cell line, but not the primate derived Vero cell line-- consistent with the known species specificity of such promoters. This activity was specific to a virus containing an active pol I promoter. However, in situ hybridization analyses of latently infected cervical dorsal root ganglia failed to detect pol I mediated transcription of the reporter gene indicating that the murine pol I promoter is silenced following the establishment of latency. Insertion of the pol I-EMCV IRES-neoR cassette into the major LAT locus resulted in the production of a hybrid LAT transcript during latency which was translocated to the cytoplasm of latently infected neurones.

Animals↗
PubMed1996

The social body and the biomechanical body: can they coexist in nurse education?

The curricula of tertiary nursing courses usually involve a number of complementary strands. These include biological sciences, social sciences, behavioural sciences, other support subjects and clinical units. These different strands each, to some extent, present the nursing student with a dilemma as they may present entirely different models of the body. Explorations of this dilemma show that students are also being presented with different models of illness and different conceptions of appropriate health care response to illness. The question is then raised as to which of these approaches most accurately reflects the realities of nursing practice.

Biomechanical Phenomena↗
PubMed1996

Nurses, doctors and the body of the patient: medical dominance revisited.

Medical dominance is one of the most obvious features of the health care system and is particularly apparent in the relationship between doctors and nurses. Reasons given for the subordination of nurses to doctors have included matters of gender, class and state patronage of medicine. This paper, through an examination of university curricula and journal content, explores the notion that control over the model of the body is a major way in which medicine preserves its dominance over nursing. One reason for medicine maintaining its superior position is that nursing is not challenging this model of the body.

Biomechanical Phenomena↗
PubMed1996

Protein kinase C isoforms in bovine aortic endothelial cells: role in regulation of P2Y- and P2U-purinoceptor-stimulated prostacyclin release.

1. Enhanced synthesis of prostacyclin (PGI2) and inositol polyphosphates in bovine aortic endothelial cells in response to ATP and ADP is mediated by co-existing P2Y- and P2U-purinoceptors. Here we examine the regulation of these responses by isoforms of protein kinase C (PKC). 2. Immunoblots with antisera specific for 8 different PKC isoforms revealed the presence of alpha, epsilon and zeta, while no immunoreactivity was found for beta, gamma, delta, eta and theta isoforms. PKC-alpha was largely cytosolic in unstimulated cells and almost all translocated to the membrane (Triton X-100 soluble) after a 1 min treatment with the PKC activating phorbol myristate acetate (PMA); PKC-epsilon was always in a Triton X-100 insoluble membrane fraction, while PKC-zeta was found in both soluble and membrane bound (Triton X-100 soluble) forms in the unstimulated cells and was unaffected by PMA. 3. Treatment with PMA for 6 h led to a 90% downregulation of PKC-alpha, while the immunoreactivity to the epsilon and zeta isoforms remained largely unchanged. 4. After either 10 min or 6 h exposure to PMA the PGI2 response to activation of both receptors was enhanced, while the inositol 1,4,5-trisphosphate response to P2Y-purinoceptor activation was substantially attenuated and the P2U-purinoceptor response was unchanged. Thus the PGI2 response to PMA under conditions when 90% of the PKC-alpha was lost resembles that seen on acute stimulation of PKC by PMA, and the PGI2 response does not correlate with phospholipase C response. 5. Inhibition of PKC with the isoform non-selective inhibitors, Ro 31-8220 and Go 6850 abolished the PGI2 response to both P2U- and P2Y-purinoceptor stimulation. However, Go 6976, which preferentially inhibits Ca2+ sensitive isoforms (such as PKC-alpha) and not Ca2+ insensitive isoforms (such as PKC-epsilon), had no effect on the PGI2 response. 6. The results show that there is a requirement for PKC in the stimulation of PGI2 production by endothelial P2Y- and P2U-purinoceptors. Both downregulation and inhibition studies show that PKC-alpha is not responsible for the regulation of the response to P2-purinergic stimulation, and imply that the response is mediated by PKC-epsilon (PKC-zeta is unresponsive to PMA), or an as yet uncharacterized PKC isoform.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

Coronary restenosis.

Return of angina within 6 months of a catheter-based treatment of coronary artery disease usually reflects restenosis due to an overly aggressive local healing response to the procedure-related arterial injury. The restenotic lesion should be treated aggressively. Patients with preexisting diabetes mellitus, renal failure requiring hemodialysis, and left anterior descending artery lesions should be considered to be at exceedingly high risk for clinically significant restenosis. Exercise testing is indicated for all patients who experience a return of their angina within 6 months of an interventional procedure. Nurse practitioners in the primary care setting may be the first clinicians to hear of the return of angina. Patients should always be reassured that repeat intervention is almost always possible and is generally effective in providing long-term relief. New devices (in particular the Palmaz-Schatz stent) may help reduce the likelihood of restenosis, to the extent that they provide a large acute post-treatment lumen diameter that is more tolerant of intimal hyperplasia without producing significant narrowing. Until adjunctive drug therapy is found that effectively reduces the local tissue response to interventional therapy, all clinicians involved in caring for patients following such procedures will need to be vigilant and knowledgeable about recognizing and treating restenosis.

Angioplasty, Balloon, Coronary↗
PubMed1996

Angiotensin II-stimulated phospholipase C responses of two vascular smooth muscle-derived cell lines. Role of cyclic GMP.

Vascular smooth muscle cells of the spontaneously hypertensive rat (SHR) are known to show increased responsiveness to angiotensin II (Ang II) compared with cells of normotensive control Wistar-Kyoto rats (WKY). We investigated the hypothesis that differential levels of cGMP lead to the different responsiveness of the cells, using vascular smooth muscle cells in culture. cGMP levels in extracts of SHR-derived cells were lower than those of WKY-derived cells. This was true for both unstimulated cells and cells treated with equal concentrations of either sodium nitroprusside or S-nitroso-N-acetylpenicillamine. Stimulation of cells with Ang II did not affect levels of cGMP but increased levels of inositol 1, 4, 5-trisphosphate (IP3) and Ca2+, which were greater in SHR- than in WKY-derived cells. When SHR and WKY cells were preincubated with different concentrations of S-nitroso-N-acetylpenicillamine to generate similar cGMP levels in each cell type, the subsequent IP3 response to Ang II was the same in the two cell types. To reduce any influence of cGMP on responses, we permeabilized the cells with alpha-toxin. Stimulation of alpha-toxin-permeabilized the cells with high Ca2+ revealed an IP3 response in SHR- but not WKY-derived cells. Similarly, permeabilized SHR cells responded to Ang II but WKY cells did not. However, GTP and GTP gamma S elevated IP3 in both cell types. Taken together, these results indicate that the low response of WKY cells can be accounted for by the inhibitory influence of cGMP. However, when this inhibition is removed by permeabilization, further differences between the cells are revealed that will contribute to the elevated SHR response.

Angiotensin II↗
PubMed1996

Fluorodeoxyglucose-positron emission tomography in the detection and staging of lung cancer.

Glycolysis is increased in tumor tissues. [18F]fluoro-2-deoxy-D-glucose (FDG) is a glucose analogue radiopharmaceutical used in positron emission tomography (PET) to trace glucose metabolism. We investigated the sensitivity and specificity of FDG-PET imaging in the diagnosis and staging of lung cancer. One hundred and seven patients who had abnormal chest roentgenograms underwent whole-body PET imaging using FDG. PET scan results were classified as positive or negative based on the presence or absence of increased FDG uptake in the lung and/or in the mediastinum. All 82 patients with lung cancer had increased FDG uptake in the lungs, whereas only 12 of 25 patients with nonmalignant diseases had increased FDG uptake. Sixteen lung cancer patients with mediastinal metastases had increased FDG uptake in the mediastinum, of whom three had no lymphadenopathy on computed tomography of the chest. Sixteen lung cancer patients without mediastinal nodal involvement had no FDG uptake in the mediastinum. Seven of these patients had lymphadenopathy on computed tomography. FDG-PET imaging is 100% accurate in predicting mediastinal involvement in patients with lung cancer. It is 100% sensitive and 52% specific in predicting the malignant nature of a chest radiographic abnormality.

Adenocarcinoma↗
PubMed1996

Lung function in premature rabbits treated with recombinant human surfactant protein-C.

We report the activity of recombinant human surfactant apoprotein-C (rSP-C[Cys]2) and various phospholipids in a preterm rabbit model of respiratory distress syndrome (RDS). Mixtures of rSP-C(Cys)2 and certain phospholipids had similar activity (lung compliance and lung pressure-volume behavior) to rabbit surfactant in this model. The activity of rSP-C(Cys)2 was maximal at 1 mol% protein and varied significantly with the phospholipid composition. Chemically synthesized SP-C had similar activity to rSP-C(Cys)2. Deletion of six amino-terminal residues did not affect function. Substitution of cysteines and cysteine6 with adjacent serines (rSP-C[Ser]2) by site-specific mutagenesis minimized aggregation of rSP-C but did not affect activity. Palmitoylation of cysteine5 and cysteine6 in rSP-C (rSP-C[C16]2) did not enhance the activity of rSP-C(Cys)2. We conclude that bacterial expression is a practical source of functional SP-C, and that nonacylated forms of SP-C may be useful adjuvants to phospholipids in the treatment of RDS and possibly other forms of acute lung injury.

Animals↗
PubMed1996

Treatment outcomes for primary care patients with major depression and lifetime anxiety disorders.

OBJECTIVE: Major depression occurs with generalized anxiety disorder and panic disorder in up to 60% of psychiatric and primary care patients. This comorbidity has been associated with greater severity of depression, poorer psychosocial functioning, and poorer treatment outcomes in psychiatric samples. This study examined the clinical outcomes for depressed primary care patients with and without a lifetime anxiety disorder. METHOD: A total of 157 primary care patients who met criteria for major depression were randomly assigned to standardized interpersonal psychotherapy or pharmacotherapy with nortriptyline and were assessed at baseline and at 4 and 8 months on severity of depression, psychosocial functioning, and health-related functioning. RESULTS: Depressed patients with a comorbid anxiety disorder presented with significantly more psychopathology and tended to prematurely terminate treatment more frequently than patients with major depression alone. Both standardized depression-specific treatments were effective for depressed patients with and without a comorbid generalized anxiety disorder, although time to recovery was longer for the former. Patients with lifetime panic disorder showed poor recovery in response to psychotherapy or pharmacotherapy. CONCLUSIONS: Standardized psychotherapy and pharmacotherapy are effective for patients with major depression with and without a generalized anxiety disorder. However, the longer time to recovery for the former group and lack of response to these treatments by patients with lifetime panic disorder suggest that primary care physicians should carefully assess history of anxiety disorder among depressed patients so as to select a proper intervention.

Adolescent↗
PubMed1996

Winter seasonal affective disorder: a follow-up study of the first 59 patients of the National Institute of Mental Health Seasonal Studies Program.

OBJECTIVE: The purpose of this study was to characterize the long-term course of patients with seasonal affective disorder. METHOD: The first 59 patients with winter seasonal affective disorder who had entered winter protocols were retrospectively followed up after a mean interval of 8.8 years. Detailed life charts were constructed through use of a semistructured interview and collateral records. RESULTS: The disorder of 25 patients (42%) remained purely seasonal, with regular recurrences of winter depression and no depression or treatment through any summer. The course of illness was complicated by varying degrees of nonseasonal depression in 26 patients (44%). The disorders of eight patients (14%) had fully remitted. Certain features of the group with complicated seasonal affective disorder suggested that they were more severely ill. Twenty-four patients (41%) continued to use light treatment regularly throughout the follow-up period. Light treatment was preferred to medication for winter recurrences, although antidepressants had been used in the winter by most (63%) of the patients who still used lights at follow-up. CONCLUSIONS: The pattern of winter depressions and summer remissions remained fairly persistent over time in this group of patients. The temporal distribution of depressive episodes both within and across individual patients was consistent with the results of several recent follow-up studies of seasonal affective disorder, providing support for the predictive and construct validity of the Rosenthal et al. diagnosis of winter seasonal affective disorder. Light treatment, while remaining a safe and satisfactory treatment for many, may be insufficient for more severely ill patients. The appearance of nonseasonal depressions in patients with winter seasonal affective disorder may be associated with greater severity of illness and less responsiveness to light treatment.

Antidepressive Agents↗
PubMed1996

Primary or working memory in frontal lobe epilepsy: An 18FDG-PET study of dysfunctional zones.

INTRODUCTION: We previously demonstrated that patients with frontal lobe epilepsy show deficits on a visual working memory paradigm and that this paradigm produces increased 18FDG uptake in the dorsolateral prefrontal cortex (DPFC), premotor cortex, angular and supramarginal gyri, basal forebrain, and ventral frontal poles of normal subjects when compared with a control task. We hypothesized that subjects with frontal lobe epilepsy would have impaired frontal activation during this task. METHODS: One resting and two activated images were obtained with 18FDG-PET in 15 subjects and 14 controls. One was a delayed (DMS) and one an immediate (IMS) match to sample paradigm. Discriminant and factor analyses were used to analyze the data, supplemented by selected t tests. RESULTS: No differences in glucose uptake were found between the DMS and IMS in the epilepsy subjects, in distinct contrast to controls. A comparison between controls and epilepsy subjects showed differences both ipsilateral and contralateral to the epileptic focus in the frontal regions involved in the task, with small changes in nonfrontal, task-related regions as well. The task itself brought out or highly exaggerated differences seen at rest. There was weak evidence that other frontal and temporal regions were attempting to compensate for the DPFC deficit. CONCLUSION: A unilateral epileptic focus is capable of suppressing function along a large task-related circuit ipsilateral and contralateral to the focus. Peripheral cortical regions compensate poorly for the area of dysfunction.

Adult↗
PubMed1996

Visual working memory in primary generalized epilepsy: an 18FDG-PET study.

It is generally believed that patients with primary generalized epilepsy have normal cognition and neuroimaging studies. We have previously shown that patients with juvenile myoclonic epilepsy (JME) have impaired visual working memory. In this study we examined relative regional changes in 18FDG uptake during a visual working memory paradigm in patients with JME. At rest, there were regional decreases in relative glucose uptake compared to controls. Unlike control subjects, increased activity in the dorsolateral prefrontal cortex was not found during the working memory task. Other regions with increased uptake in controls, such as premotor cortex and basal frontal cortex, also showed no increases, whereas medical temporal structures appeared to play a role in JME but not in control subjects' task performance. The data suggest that JME, a type of primary generalized epilepsy, may suffer from cortical disorganization that affects both the epileptogenic potential and frontal lobe cognitive functioning.

Adult↗
PubMed1996

Influence of instrumental activities of daily living assessment method on judgments of independence.

OBJECTIVE: Occupational therapists frequently evaluate instrumental activities of daily living (IADL) performance with interviews and observation of simulated tasks. This study examined the congruence of judgments of independence when comparing task performance assessed by interview and simulation with task performance assessed by observation in the natural environment. METHOD: Twenty persons with severe mental illness were selected through convenience sampling and evaluated on two IADL tasks (making a purchase in a store and using the bus). The participants were evaluated on each task with two methods of assessment: interview and simulation and observation in the natural environment. RESULTS: Results indicated inconsistent performance across assessment approaches and tasks and supported the importance of considering contextual features in understanding the complexity of performance in the natural environment. A trend toward false positives was found in which several participants were judged independent on the IADL assessment but could not perform the same tasks in the natural environment. CONCLUSION: Occupational therapists should be cautious when making judgments of independence on the basis of interview and observation of simulated tasks. Evaluating IADL performance in the persons' natural environment may provide more accurate information.

Activities of Daily Living↗
PubMed1996

Smoking policy and cessation in an inner-city hospital.

Hospital policies regarding cigarette smoking can affect the smoking habits of employees, patients, and visitors. Successful smoking policy development and impact have been reported in a number of hospitals. These reports have been from financially secure or university hospitals. This article reports on the policy experience at Interfaith Medical Center, a public hospital serving an economically disadvantaged black inner-city community. Policy implementation and smoking cessation efforts were directed by a broad-based hospital committee. An employee survey demonstrated support for a policy restricting but not banning smoking (89% of nonsmokers, and 80.2% of smokers). Among smoking employees, 87.6% wanted to quit. A policy restricting smoking to designated areas in the cafeteria and coffee shop was enacted. Health fairs and smokeout contests were enthusiastically received and resulted in short-term cessation verified by exhaled carbon monoxide levels. Assemblies where ex-smokers were given "Hall of Fame" certificates, "stop smoking" art contests, and a "stop smoking hotline" generated further cessation activity. The department of medicine, in cooperation with the National Heart, Lung, and Blood Institute's Smoking Education Program, set up a training program for residents on how to help patients quit. Overall, the smoking prevalence, attitudes, and enthusiasm to quit were similar to previous reports in financially secure hospitals. Unfortunately, lack of resources and staff turnover led to dissolution of the program. Institutional stability and a funding source are critical for the long-term success of hospital smoking cessation programs.

Adult↗
PubMed1996

Cell proliferation and apoptosis in prostate cancer--correlation with pathologic stage?

Gleason grade, especially at low and high ends of the spectrum, is a known predictor of pathologic stage. What are needed are predictors of stage with Gleason sum 5 to 7 tumors, which encompasses the majority of clinically organ-confined tumors. In this study, we analyzed whether cell proliferation and apoptosis (programmed cell death) were correlated with stage in men with clinically organ-confined Gleason sum 6 to 7 cancer. We studied 98 radical prostatectomies with the following pathologic stages: organ-confined disease (n = 28); capsular penetration (n = 28); seminal vesicle invasion (n = 21); and pelvic lymph node metastases (n = 21). Histological sections from the radical prostatectomies were stained for cell proliferation using MIBI antibody (Ki-67) and for apoptosis using the TUNEL technique. The extent of staining was recorded as the number of positive cells per 1000 cells. Overall daily growth (kp) was calculated as: kp = (ki/2) - (apoptosis/0.5), based on the time of prostate cancer to undergo mitosis and apoptosis per day. Using logistic regression analysis, pathologic stage did not correlate with cell proliferation, apoptosis, or overall daily growth. These parameters also did not distinguish between Gleason sum 6 and Gleason sum 7 tumors. We supplemented these cases with examples of Gleason sum < or = 4 and Gleason sum > or = 8 to study cell proliferation and cell death in the full spectrum of Gleason grades. There was a significant difference (P = 0.005) in cell proliferation between Gleason sum > or = 6 and Gleason sum < or = 4 tumors, but apoptosis and daily growth were not significant. We conclude that cell proliferation and apoptosis do not correlate with pathological stage in clinically organ-confined cancer with Gleason sum 6 or 7, but that cell proliferation can distinguish between high (Gleason sum > or = 6) and low (Gleason sum < or = 4) grade tumors.

Apoptosis↗
PubMed1996

A review of subcalcaneal heel pain and plantar fasciitis.

Pain beneath the heel is a common and sometimes very debilitating condition. Although usually described as ¿plantar fasciitis' it can be caused by several different conditions. Adequate treatment is aided by determining which cause or causes of subcalcaneal pain is present in a particular patient. This article discusses the approach to the diagnosis and management of pain underneath the calcaneus.

Calcaneus↗