Complementary and alternative medicine use by patients enrolled onto phase I clinical trials.

Purpose: To describe the prevalence, clinical characteristics, and pattern of use of complementary and alternative medicine (CAM) in patients enrolled onto phase I trials.

Patients And Methods: Questionnaires were administered to 108 patients with advanced malignancies enrolled onto phase I chemotherapy trials at the Mayo Clinic Comprehensive Cancer Center (Rochester, MN). CAM was classified into two modalities, pharmacologic and nonpharmacologic.

Subtypes of anal incontinence associated with bowel dysfunction: clinical, physiologic, and psychosocial characterization.

Background: We hypothesized that functional anal incontinence with no structural explanation comprises distinct pathophysiologic subgroups that could be identified on the basis of the predominant presenting bowel pattern.

Methods: Consecutive patients (n = 80) were prospectively grouped by bowel symptoms as 1) incontinence only, 2) incontinence + constipation, 3) incontinence + diarrhea, and 4) incontinence + alternating bowel symptoms. The Hopkins Bowel Symptom Questionnaire, the Symptom Checklist 90-R, and anorectal manometry were completed.

Enterochromaffin cells and 5-HT signaling in the pathophysiology of disorders of gastrointestinal function.

Disorders of gastrointestinal function are common and significantly reduce quality-of-life, as well as negatively impacting healthcare costs. Consequently, there is much interest in understanding the pathogenesis of these disorders. Increasing, albeit as yet limited, evidence has implicated alterations in 5-hydroxytryptamine (5-HT) release, and the subsequent interaction of 5-HT with specific 5-HT receptor subtypes, in the altered gut function of patients with irritable bowel syndrome (IBS) and other functional bowel diseases.

CFTR is a monomer: biochemical and functional evidence.

Although the CFTR protein alone is sufficient to generate a regulated chloride channel, it is unknown how many of the polypeptides form the channel. Using biochemical and functional assays, we demonstrate that the CFTR polypeptide is a monomer. CFTR sediments as a monomer in a linear, continuous sucrose gradient.

Use of the Cobra catheter for targeted temperature management during cardiopulmonary bypass in swine.

Background: The purpose of this investigation was to determine whether temperatures of the aortic arch and descending aortic circulations could be controlled independently during cardiopulmonary bypass with a cannula possessing an endoaortic baffle (Cobra; Cardeon, Cupertino, Calif).

Methods: After Institutional Animal Care and Use Committee approval, 12 pigs weighing 60 kg were started on bypass through a sternotomy. A dual-lumen endoaortic cannula with a deployable baffle was used for arterial cannulation.

Functional analysis of the C-terminal boundary of the second nucleotide binding domain of the cystic fibrosis transmembrane conductance regulator and structural implications.

The cystic fibrosis transmembrane conductance regulator (CFTR) contains two nucleotide-binding domains (NBDs) or ATP-binding cassettes (ABCs) that characterize a large family of membrane transporters. Although the three-dimensional structures of these domains from several ABC proteins have been determined, this is not the case for CFTR, and hence the domains are defined simply on the basis of sequence alignment. The functional C-terminal boundary of NBD1 of CFTR was located by analysis of chloride channel function [Chan, Csanady, Seto-Young, Nairn and Gadsby (2000) J.

Nucleoside triphosphate pentose ring impact on CFTR gating and hydrolysis.

Alterations in the pentose ring of ATP have a major impact on cystic fibrosis transmembrane conductance regulator (CFTR) function. Both 2'- and 3'-deoxy-ATP (dATP) accelerate ion channel openings and stabilize open channel structure better than ATP. Purified wild-type CFTR hydrolyzes dATP.

The First Nucleotide Binding Domain of Cystic Fibrosis Transmembrane Conductance Regulator Is a Site of Stable Nucleotide Interaction, whereas the Second Is a Site of Rapid Turnover.

As in other adenine nucleotide binding cassette (ABC) proteins the nucleotide binding domains of the cystic fibrosis transmembrane conductance regulator (CFTR) bind and hydrolyze ATP and in some manner regulate CFTR ion channel gating. Unlike some other ABC proteins, however, there are preliminary indications that the two domains of CFTR are nonequivalent in their nucleotide interactions (Szabo, K., Szakacs, G.

Profound reduction in brain embolization using an endoaortic baffle during bypass in swine.

Background: Cerebral embolization during cardiopulmonary bypass is an important cause of neurologic injury. This study determined whether an endoaortic baffle catheter (Cardeon Cobra Catheter; Cardeon Corporation, Cupertino, CA) could substantially reduce cerebral embolization in a swine cardiopulmonary bypass model.

Methods: Sixteen 60 kg pigs underwent cardiopulmonary bypass; 8 animals with the Cobra baffle (Cardeon Corporation, Cupertino, CA) deployed, and 8 with the same cannula without baffle deployment.

Cerebral hyperthermia and cardiac surgery: consequences and prevention.

Temperature management during cardiac surgery deserves considerable attention because it has broad effects, altering virtually every physiologic process, including oxygen demand, blood flow, cardiac output, and coagulation. Temperature is also important in cardiac surgery because virtually all patients undergo significant temperature change. These changes can be unique in mammalian physiology both with regard to their magnitude and rate of change.

Doxorubicin and paclitaxel in the treatment of advanced breast cancer: efficacy and cardiac considerations.

Doxorubicin and paclitaxel are highly active agents in the treatment of advanced breast cancer. Although early trials of the combination reported high response rates, an unexpectedly high incidence of congestive heart failure observed on two of the early trials was cause for much concern. More recently, clinical trials that have limited the cumulative doxorubicin dose to 400 mg/m2 or below when given in combination with paclitaxel have not observed an increase in cardiac toxicity.

Ongoing and planned adjuvant trials with trastuzumab.

HER-2 (c-erbB-2, neu) is an important prognostic and predictive factor in breast cancer. Clinical trials utilizing a humanized version of the anti-HER-2 murine monoclonal antibody 4DS, trastuzumab (Herceptin; Genentech Inc, South San Francisco, CA), have shown antitumor activity in patients with HER-2-positive metastatic breast cancer. Improved response and survival rates have been shown when trastuzumab was added to first-line combination chemotherapy with anthracycline/cyclophosphamide or paclitaxel, compared to the same chemotherapy alone.

Intracardiac ectopic thyroid.

Intracardiac ectopic thyroid is a rare lesion. We present a case of successful excision of thyroid tissue obstructing the right ventricular outflow tract and provide a literature review. In all cases reported to date, the ectopic tissue arose from the ventricular septum and extended to the outflow tract.

Differential perfusion: a new technique for isolated brain cooling during cardiopulmonary bypass.

Background: The purpose of this study was to determine the feasibility of differential perfusion of the aortic arch and descending aorta during cardiopulmonary bypass using a cannula designed for aortic segmentation.

Methods: Pigs weighing 57 kg (n = 8), underwent cardiopulmonary bypass using the dual lumen aortic cannula. An inflatable balloon separated proximal (aortic arch) and distal (descending aorta) ports.

Effect of cerebral embolization on regional autoregulation during cardiopulmonary bypass in dogs.

Background: Embolization during cardiopulmonary bypass probably alters cerebral autoregulation. Therefore, using laser Doppler flowmetry we investigated the cerebral blood flow velocity changes in response to changes in arterial pressure, before and after embolization in a canine bypass model.

Methods: After Institutional Animal Care and Use Committee approval, 8 anesthetized dogs had a laser Doppler flow probe positioned over the temporoparietal dura.

HER-2 as a Prognostic, Predictive, and Therapeutic Target in Breast Cancer.

BACKGROUND: An expanded understanding of the biology of breast cancer has led to the identification of the HER-2 receptor as an important growth factor. This receptor possesses intrinsic tyrosine kinase activity and has been associated with aggressive biological behavior and poor clinical outcome. METHODS: Data have been reviewed regarding the role of HER-2 expression as a prognostic variable, as a predictive factor for response to chemotherapy and hormonal therapies, and as a directed therapeutic target for breast cancer.

Effect of temperature and PaCO2 on cerebral embolization during cardiopulmonary bypass in swine.

Background: Patients experience cerebral embolization during cardiopulmonary bypass (CPB). This study determined if alterations in temperature and/or PaCO2 can reduce cerebral and ocular embolization.

Methods And Results: Forty-four pigs underwent CPB: 24 animals at 28 degrees C, and 20 at 38 degrees C.

Bypass flow, mean arterial pressure, and cerebral perfusion during cardiopulmonary bypass in dogs.

Objective: To determine if normal cardiopulmonary bypass (CPB) pump flows maintain cerebral perfusion in the context of reduced mean arterial pressure at 33 degrees C.

Design: A prospective investigation.

Setting: Animal CPB research laboratory.

5-HT3 antiemetic therapy for patients with breast cancer.

Antiemetic treatment should be considered for breast cancer patients receiving moderately emetogenic chemotherapy. Although the extent of chemotherapy-induced emesis is largely dependent on the emetogenic potential of the specific agents employed, patient characteristics such as age and sex also contribute. Recent clinical studies show that treatment with the currently available 5-HT3 antagonists effectively reduces the incidence of chemotherapy-induced nausea and vomiting and improves quality of life in a substantial number of these patients.

Relationship between cardiopulmonary bypass flow rate and cerebral embolization in dogs.

Background: Cerebral embolization is a primary cause of cardiac surgical neurologic morbidity. During cardiopulmonary bypass (CPB), there are well-defined periods of embolic risk. In theory, cerebral embolization might be reduced by an increase in pump flow during these periods.

Current management of metastatic breast cancer.

The medical approach to the management of metastatic breast cancer has changed through the years following the introduction of new cytotoxic agents and the demonstration of their antitumor activity. In general, combination drug regimens are the initial treatments of choice when chemotherapy is indicated for patients with metastatic breast cancer. However, the single-agent activity of some of the newer agents rivals that of older combination chemotherapy treatments.

Paclitaxel in Breast Cancer.

Paclitaxel has emerged as an important agent in the treatment of breast cancer. The efficacy and tolerability of this agent, as well as its lack of cross-resistance with anthracyclines, have spurred intensive clinical investigation worldwide. Optimization of paclitaxel dose and scheduling and evaluation of the drug in combination regimens are a central focus of investigations.

Paclitaxel plus nonanthracycline combinations in metastatic breast cancer.

The results of several phase II and some phase III studies are now available in which the combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and nonanthracycline agents are evaluated. The studies demonstrate the activity and feasibility of these combinations, which achieved response rates of 40% to 80% and median time to progression that exceeded 6 months. The potential role of these combinations compared with older non-paclitaxel-containing regimens, in improving quality of life, response rate, and survival in patients with metastatic breast cancer, however, await the results of prospective, randomized phase III trials.

p27kip1: a multifunctional cyclin-dependent kinase inhibitor with prognostic significance in human cancers.

p27kip1 (p27) is a member of the universal cyclin-dependent kinase inhibitor (CDKI) family. p27 expression is regulated by cell contact inhibition and by specific growth factors, such as transforming growth factor (TGF)-beta. Since the cloning of the p27 gene in 1994, a host of other functions have been associated with this cell cycle protein.

Quantification and distribution of cerebral emboli during cardiopulmonary bypass in the swine: the impact of PaCO2.

Background: Patients undergoing cardiac surgery have a substantial incidence of neurologic complications related to cerebral embolization during cardiopulmonary bypass. The purpose of this study was to determine if adjustments in the arterial carbon dioxide (PaCO2) level can reduce cerebral and ocular embolization.

Methods: Twenty pigs underwent cardiopulmonary bypass at 38 degrees C.