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Biomedical subjects

C Brown

Publications and source records attributed to C Brown.

At least 181 records · Page 10Linked to original sources
PubMed1998

Endothelin-converting enzyme: ultrastructural localization and its recycling from the cell surface.

The potent vasoconstrictor endothelin-1 (ET-1) is secreted constitutively by endothelial cells and has been implicated in the pathophysiology of several cardiovascular diseases. It is generated from its inactive intermediate, big ET-1, through the action of endothelin-converting enzyme (ECE). Using several complementary techniques, we have demonstrated that ECE is present at the cell surface and on intracellular vesicles and that it recycles from the cell surface in endothelial cells. This is the first ultrastructural localization of ECE in lung and the first time big ET-1 and ECE have been colocalized by immunogold in a vesicular population, 50 to 100 nm in diameter. In addition, by double immunogold staining of ultrathin cryosections, we have localized ECE together with angiotensin-converting enzyme on the luminal membrane of endothelial cells. With cell surface biotinylation of a transformed rat endothelial cell line and of human umbilical vein endothelial cells, we have confirmed the presence of ECE on the plasma membrane. After treatment of endothelial cells with chloroquine, ECE and trans-Golgi network 38 protein were shown by immunofluorescence staining to localize to the same intracellular compartment.

Animals↗
PubMed1998

In situ hybridization with riboprobes: an overview for veterinary pathologists.

In situ hybridization using nonradioactively-labeled RNA probes is a technique that combines understanding of basic molecular biology and histopathologic interpretation. Recombinant or PCR technology can be used to produce probes that hybridize with a wide variety of cellular genes and infectious agents. Hybridization conditions can be optimized for each probe/target combination.

Animals↗
PubMed1998

Charcot restraint orthotic walker.

Five patients (three with insulin dependent diabetes mellitus (IDDM), one with noninsulin dependent diabetes mettlitus (NIDDM), and one with hereditary sensorimotor neuropathy (HSMN)) with stage 1 Charcot's neuroarthropathy involving the midfoot and or subtalar and ankle joints were fitted with a Charcot restraint orthotic walker (CROW). The rationale for this orthotic management was to maintain a plantigrade foot for ambulation and to protect the joints and skin by the uniform transfer or distribution of weight over the foot until the time when the pathology reached the stage of coalescence. The patients were able to fully bear weight and to ambulate with the CROW. All patients noted varying measures of improvement in symptoms and function at an average 12-month follow-up. The CROW is a useful orthosis in the armamentarium for treating neuroarthropathy of the pedal joints.

Adult↗
PubMed1998

Phase II study of "dose-dense" high-dose chemotherapy treatment with peripheral-blood progenitor-cell support as primary treatment for patients with advanced ovarian cancer.

PURPOSE: We performed a pilot phase II study to evaluate the potential for delivery of rapidly sequenced high-dose chemotherapy treatments rescued with autologous peripheral-blood progenitor cells (PBP) in patients with previously untreated, advanced ovarian cancer. PATIENTS AND METHODS: A single cycle of mobilization was used, primed with cyclophosphamide (CPA)/paclitaxel (Txl) and filgrastim (granulocyte colony-stimulating factor [G-CSF]), followed by three cycles of high-dose carboplatin (CBDCA)/Txl and one cycle of high-dose melphalan (MEL), each rescued by PBP. We then analyzed the outcome for a total of 56 consecutive patients treated with high-dose chemotherapy as part of this program. RESULTS: In the phase II pilot, 21 patients were enrolled. There were no treatment-related deaths through 98 high-dose treatments, although 34 treatments were complicated by hospitalization, primarily for neutropenic fever. Seventy-six percent of patients experienced grade 3 to 4 gastrointestinal toxicity and 62% experienced grade 2 to 3 neuropathy. Five of 15 (33%) patients who underwent second-look surgery attained a pathologic complete response. In the overall analysis, 56 patients were reviewed. Forty-four patients were assessable for response by second-look surgery or clinical progression. Fifteen of 44 patients achieved a pathologic complete response (34%). The pathologic complete response rate in optimal-disease patients was 12 of 22 (55%), while only three of 22 (13%) suboptimal stage III and IV patients achieved a pathologic complete response. CONCLUSION: The Gynecologic Oncology Group has initiated a pilot phase II trial of this approach in patients with optimally debulked stage III ovarian cancer. There is no evidence to support the use of this or other aggressive regimens outside of a clinical trial.

Adult↗
PubMed1998

Quality care for cardiology patients.

To evaluate outcome measures in a cardiology unit, patient satisfaction was measured. Patients consistently related problems in two areas: pain management and the waiting period before their procedure. After a major system change, patient satisfaction increased 16% and 29% respectively.

Heart Diseases↗
PubMed1998

Immunophenotypic characterization of simian immunodeficiency virus-infected dendritic cells in cervix, vagina, and draining lymph nodes of rhesus monkeys.

Significant progress has been made in understanding the biology of heterosexual transmission of HIV by utilizing the simian immunodeficiency virus (SIV)/rhesus monkey animal model. Our previous studies have shown that SIV-infected cells within the stratified squamous epithelium of the vagina have a dendritic morphology. However, the type of cell infected was not conclusively determined. The purpose of the present study was to immunophenotype the SIV-infected cells in the lower reproductive tract and genital lymph nodes of the female rhesus monkey. Vagina, cervix, and iliac lymph node from eight chronically SIV-infected adult female monkeys were examined for this study. None of the animals had histologic evidence of opportunistic infections or genital tract pathogens other than SIV. Combined in situ hybridization and immunohistochemistry were used to detect SIV RNA and to determine the immunophenotype of SIV-infected cells in tissue sections and cytospin preparations of cells from the tissues. We now show that SIV-infected cells were most common in iliac lymph node and that the majority of infected cells in the lymph node were T lymphocytes. SIV-infected macrophages, Langerhans' cells, and dendritic cells were also found in the lymph node. SIV-infected cells were found within the epithelium and lamina propria of the vagina. Although most of the infected cells were T cells, a significant proportion (approximately 40%) of the SIV-infected cells in cytospin preparations from explant cultures of vagina and cervix were Langerhans' cells. SIV-infected T cells in the lower genital tract were commonly associated with focal mononuclear cell infiltrates. SIV-infected macrophages were rarely found in the genital tract. The present study provides the first direct demonstration that Langerhans' cells and dendritic cells in the genital tract and lymph nodes are infected with SIV in vivo. Thus, dendritic cells, in general, and Langerhans' cells, in particular, are important reservoirs for HIV/SIV replication in vivo.

Animals↗
PubMed1998

Epidermal growth factor-induced growth inhibition requires Stat1 activation.

Epidermal growth factor (EGF) is a mitogen for most epithelial cells. Paradoxically, the growth of some cultured cell lines, containing high numbers of EGF receptors, are inhibited by EGF. Here we demonstrate that growth inhibition by EGF in several cell lines correlates with the activation of the signal transducer and activator of transcription (Stat) 1. In contrast, in normal fibroblasts and several cell lines that are growth stimulated by EGF, we observed no or very transient activation of Stat1. A causal association between Stat1 activation by EGF and growth inhibition was suggested by the expression of a dominant-negative Stat1 in A431 cells, resulting in the loss of Stat1 DNA binding and concomitant resistance to growth inhibition by EGF. We conclude that, in the cells examined, EGF-induced arrest of growth requires activated Stat1.

Cell Cycle↗
PubMed1998

Bridging the gap between science and practice: insight to researchers from practitioners.

Five policy advocates and practitioners provide recommendations to researchers to make research data more usable, accessible, and applicable for the field of human immunodeficiency virus (HIV) prevention among injecting and other drug users. Translating research into usable information will facilitate its use within political and policy discussions. When researcher and practitioners truly work together in a common enterprise, the result will be powerful HIV prevention programs that will save lives.

Communication Barriers↗
PubMed1998

Pelvic floor rehabilitation: conservative treatment for incontinence.

Pelvic floor rehabilitation is used to treat stress urinary incontinence, urge, and fecal incontinence as well as other pelvic floor musculature disorders. When treating patients, it is important to thoroughly assess the pelvic floor. In addition to evaluating the urinary system, sexual and bowel functions must also be considered. Treatment plans should be devised on an individual basis according to the evaluation findings. Rehabilitation goals should be established. The patient must understand the function of her urinary system and the role she must play in its control. Muscle retraining is achieved through a personalized exercise program. This program may be augmented by manual techniques, biofeedback or electrical stimulation. While the Agency for Health Care Policy and Research (AHCPR) does endorse the use of behavioral modalities in treating urinary incontinence, the use of bladder retraining and pelvic floor rehabilitation is not always recommended when indicated, nor accessible for all patients who require it. More research is needed, in addition to ongoing public and professional education on behavioral interventions in order to underline the advantages of this form of treatment for incontinence.

Biofeedback, Psychology↗
PubMed1997

Symptomatic improvement of premenstrual dysphoric disorder with sertraline treatment. A randomized controlled trial. Sertraline Premenstrual Dysphoric Collaborative Study Group.

CONTEXT: Premenstrual dysphoric disorder is an important cause of symptoms and functional impairment in menstruating women. OBJECTIVE: To evaluate the efficacy of sertraline hydrochloride for treatment of premenstrual dysphoria by measuring changes in symptom expression and functional impairment. DESIGN: Two screening cycles followed by 1 single-blind placebo cycle and 3 cycles of randomized, double-blind, placebo treatment. SETTING: Twelve university-affiliated outpatient psychiatry and gynecology clinics. PATIENTS: Of the 447 women who requested participation, 243 met criteria for premenstrual dysphoric disorder and were randomized; 200 women completed the study. INTERVENTION: A flexible (50-150 mg) daily dose of sertraline hydrochloride. MAIN OUTCOME MEASURES: The Daily Record of Severity of Problems, Hamilton Rating Scale for Depression, Clinical Global Impression Scale, and Social Adjustment Scale. RESULTS: Mean (+/-SD) total daily symptom scores decreased significantly (P<.001) in the sertraline-treated (64+/-22 to 44+/-19) compared with the placebo-treated (62+/-22 to 54+/-24) groups. Significant improvement (P<.05) was found for all clinically derived symptom clusters (depressive, physical, and anger/irritability symptoms). Hamilton Rating Scale for Depression scores decreased by 44% and 29% in the sertraline and placebo groups, respectively (P<.002). End-point global ratings showed much or very much improvement in 62% of the active treatment group and 34% of the placebo treatment group (P<.001). Reported functional impairment was substantial at baseline. Improvement in psychosocial functioning with treatment was similar to what is found in studies of major depression. CONCLUSIONS: Sertraline was significantly better than placebo for treatment of premenstrual dysphoria as reflected by symptomatic improvement and change in reported functional impairment. Serotonin reuptake inhibitors such as sertraline are useful therapeutic options for women with premenstrual dysphoria.

1-Naphthylamine↗
PubMed1997

Birth of a western lowland gorilla (Gorilla gorilla gorilla) following in vitro fertilization and embryo transfer.

A 21-year-old multiparous female exhibiting 31-41 day menstrual cycles was given hFSH (225 IU/day, Metrodin 75, from cycle day 3 through 9 (menses = day 1) and hCG (10,000 IU, Profasi, on day 10 to stimulate follicular development. At 35 h after hCG, under isoflurane (AErrane) anesthesia, follicles were aspirated by controlled suction under transvaginal ultrasound guidance. Metaphase II oocytes (n = 11) were placed in modified human tubal fluid (mHTF, 100 microliters) medium under oil at 37 degrees C in humidified 5% CO2. Frozen semen, collected by voluntary ejaculation, was thawed (70 degrees C H2O bath, 6 sec), diluted slowly, centrifuged, and resuspended in mHTF, and 160,000 motile spermatozoa/ml were added at 6 h after oocyte recovery. At 21 h postinsemination (p.i.) eight oocytes were at the two-cell stage, five were cryopreserved, and three were cultured to the six- to eight-cell stage in mHTF with granulosa cells before transcervical uterine transfer at 47 h p.i. using a Teflon catheter. Micronized progesterone (400 mg/d) was orally administered for 10 weeks posttransfer (p.t.). Ultrasound examination revealed a single fetus at 15 weeks p.t., and unassisted delivery of a live 1.37 kg female infant occurred at 29 weeks. Am. J. Primatol. 41:247-260, 1997.

Animals↗
PubMed1997

Comparing the mental health needs of female and male incarcerated juvenile delinquents.

The present study was undertaken to survey the prevalence of mental disorder in juvenile justice facilities and to compare the mental health needs for females and males. Girls displayed significantly more mental health needs than boys. The estimated prevalence of mental disorder for boys was 27%, compared with 84% for girls. The difference is highly significant and is discussed in terms of service system issues in juvenile justice that affect males and females differently.

Adolescent↗
PubMed1997

Systematic assessment of social phobia in clinical practice.

The purpose of this review is to propose a systematic approach to the assessment of social phobia for monitoring treatment outcome in clinical settings. A selection of measures is available, including questionnaires and structured interviews varying in length, complexity, and content. To design an assessment protocol for a particular patient or patient population, the clinician needs to be familiar with the characteristics of these available measures. The measures selected for detailed description and discussion here: (a) are specifically designed to assess social anxiety and social phobia, (b) have been demonstrated to have acceptable psychometric characteristics, and (c) have been utilized in treatment outcome research. Five questionnaire measures will be reviewed: (1) the Social Phobia and Anxiety Inventory (SPAI) (Turner et al., 1989a: Psychol Assessment 1:35-40), (2) the Social Interaction and Anxiety Scale (SIAS) (Mattick and Clarke, 1989 in Heimberg et al., 1992), (3) the Social Phobia Scale (SPS) (Mattick and Clarke, 1989 in Heimberg et al., 1992: Behav Therapy 23:53-73), (4) the Fear of Negative Evaluation Scale (FNES) (Watson and Friend, 1969: J Consult Clin Psychol 33:448-457), and (5) The Social Anxiety and Distress Scale (SADS) (Watson and Friend, 1969: J Consult Clin Psychol 33:448-457). Two interview measures will be reviewed, the Liebowitz Social Anxiety Scale (LSAS) (Liebowitz, 1987: Modern Problems Pharmacopsych 22:141-173) and Brief Social Phobia Scale (BSPS) (Davidson et al., 1991: J Clin Psychiatry 52:48-51). Measures developed for specific subgroups, including patients with speech anxiety and musical performance anxiety, as well as the application of other evaluation methods, such as the Behavioral Assessment Test, will also be discussed. Guidelines for selecting appropriate social phobia measures for varying clinical and research situations will be proposed that take into consideration the strengths and weaknesses of these methods.

Anxiety Disorders↗
PubMed1997

Phase I study of tirapazamine and cisplatin in patients with recurrent cervical cancer.

OBJECTIVES: Tirapazamine (SR 4233) is a benzotriazine compound exhibiting substantial differential toxicity for hypoxic cells. A large enhancement in tumor cell killing has been demonstrated in preclinical studies when tirapazamine was combined with cisplatin. This phase I study was undertaken to establish a safe dose combination of tirapazamine and cisplatin when administered to patients with recurrent cervical carcinoma. METHODS: Tirapazamine was administered as an intravenous infusion over 2 hr, followed 1 hr later by cisplatin intravenously over 1 hr, every 21 days. All patients received prophylactic antiemetics consisting of ondansetron, dexamethasone, and lorazepam. The planned dose escalation levels of tirapazamine were 195, 260, 330, and 390 mg/m2. The cisplatin dose was fixed at 75 mg/m2. RESULTS: A total of 12 patients were treated with 43 courses of therapy. Patients were heavily pretreated. Eleven of the 12 had prior radiotherapy and 5 of the 12 had prior cisplatin-based chemotherapy. A maximally tolerated dose of 330 mg/m2 was defined for this patient population. The dose-limiting toxicity was nausea and vomiting. All 12 patients were also evaluated for response. Two major responses were seen (17%). In addition, there were three minor responses (25%) and 4 patients achieved disease stabilization (33%). All major and minor responses were seen at the highest dose level tested of 330 mg/m2. CONCLUSIONS: Tirapazamine and cisplatin is an interesting drug combination in the treatment of cervical cancer. Phase II testing is planned.

Adult↗
PubMed1997

Equivalent responses to lexical and nonlexical visual stimuli in occipital cortex: a functional magnetic resonance imaging study.

Stimulus-related changes in cerebral blood oxygenation were measured using high-resolution functional magnetic resonance imaging sequentially covering visual occipital areas in contiguous sections. During dynamic imaging, healthy subjects silently viewed pseudowords, single false fonts, or length-matched strings of the same false fonts. The paradigm consisted of a sixfold alternation of an activation and a control task. With pseudowords as activation vs single false fonts as control, responses were seen mainly in medial occipital cortex. These responses disappeared when pseudowords were alternated with false font strings as the control and reappeared when false font strings instead of pseudowords served as activation and were alternated with single false fonts. The string-length contrast alone, therefore, is sufficient to account for the activation pattern observed in medial visual cortex when word-like stimuli are contrasted with single characters.

Adult↗