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Biomedical subjects

W Chandler

Publications and source records attributed to W Chandler.

15 recordsLinked to original sources
PubMed2000

Effects of hemofiltration on serum aprotinin levels in patients undergoing cardiopulmonary bypass.

OBJECTIVE: To determine the effects of hemofiltration on serum aprotinin levels during cardiopulmonary bypass (CPB) surgery. DESIGN: Prospective, randomized study. SETTING: University of Washington Medical Center, single institution. PARTICIPANTS: Patients undergoing cardiac surgery without contraindications to aprotinin administration. INTERVENTIONS: Patients were randomized to full-Hammersmith and half-Hammersmith dosing regimens of aprotinin and were further randomized to hemofiltration or no hemofiltration. MEASUREMENTS AND MAIN RESULTS: Serum aprotinin levels were studied before CPB, 60 and 120 minutes into CPB, and at the end of CPB before protamine administration. Each group experienced a decrease in serum aprotinin levels with the institution of CPB, attributable to hemodilution and redistribution of aprotinin outside of the vascular compartment. During CPB, aprotinin levels declined further, but no significant difference was observed between patients who received hemofiltration and those who did not. Hematocrit values were significantly higher at the end of CPB in the hemofiltration groups. Patients receiving half-Hammersmith dosing regimens maintained aprotinin levels throughout CPB, which have been shown to inhibit plasmin but were lower than levels previously shown to inhibit kallikrein. CONCLUSIONS: Hemofiltration during CPB did not significantly alter serum aprotinin levels in patients receiving half-Hammersmith and full-Hammersmith dosing regimens of aprotinin.

Adult↗
PubMed1997

Liver hemostasis using high-intensity focused ultrasound.

Liver hemorrhage, the major cause of death in hepatic trauma, is notoriously difficult to control. We report on the use of high-intensity focused ultrasound (HIFU) to arrest the bleeding from incisions made in rabbit livers. A HIFU transducer, with a spherically curved aperture of 6.34 cm2 area, a focal length of 4 cm and a frequency of 3.3 MHz was used. In approximately 94% of the incisions, the hemorrhage was reduced to a slow oozing of blood in less than 2 min. The maximum temperature of liver tissue around the incision area, during HIFU application, was measured to be 86 degrees C. The mechanism of hemostasis, confirmed by histological examination, appears to be coagulative necrosis of a volume of liver tissue around the incision. We believe that acoustic hemostasis, with the unique characteristic of "volume cauterization," offers a novel method for the management of liver hemorrhage and, thus, has major clinical implications.

Animals↗
PubMed1996

The effects of cardiopulmonary bypass on fibrin formation and lysis: is a normal fibrinolytic response essential?

Fibrinolytic activity in blood is regulated by a dynamic process that includes control of production, secretion, inhibition, and clearance of fibrinolytic proteins. The concentration of active tissue plasminogen activator (tPA) in the region of the thrombus controls the rate of fibrinolytic activation. We have developed a first-generation kinetic model that can be used to simulate the effects of secretion, inhibition, and clearance reactions on the concentrations of active tPA, active plasminogen activator inhibitor type 1 (PAI-1), and tPA/PAI-1 complex in the circulation. This model was used to estimate the rate and pattern of secretion of tPA and PAI-1 in individual subjects. We also undertook a laboratory evaluation of fibrinolysis in patients with a history of myocardial infarction. Elevated PAI-1 activity in the absence of elevations in other acute-phase proteins suggested an intrinsic increase in PAI-1 secretion in patients post-myocardial infarction. Cardiopulmonary bypass (CPB) results in a major increase in fibrinolytic activity that has been associated with an increased risk for hemorrhage. Fibrinolytic proteins were sampled from patients both during surgery and for 2 days postoperatively. Total tPA antigen rose throughout CPB and returned to baseline in the post-operative period. PAI-1 activity fell during the initial bypass and by the end of bypass had returned to baseline. On the first to second postoperative day there was a large increase in PAI-1 activity and a significant decrease in tPA activity. These data suggest that during this period there is a window of risk for a thromboembolic event. There was, however, a large individual variability in patient response to CPB.

Cardiopulmonary Bypass↗
PubMed1996

A source model for efficient brachytherapy computations with Monte Carlo.

Monte Carlo techniques have the potential for producing accurate brachytherapy dose distributions in heterogeneous finite geometries. However, for routine clinical use, computational speed must be adequate. A fast, all-particle, CT-based Monte Carlo code called PEREGRINE is being developed at Lawrence Livermore National Laboratory for radiation treatment planning. As one feature, the code will produce accurate dose distributions from brachytherapy sources in heterogeneous geometries. For efficiency, brachytherapy sources in this model are treated as points or line segments. Radiation is emitted with the proper energy spectrum and (perhaps anisotropic) angular distribution. In particular, for anisotropic emission the polar angle is determined by a random-number driven empirical function constructed from a source's measured or precomputed fluence emission pattern. Source model parameters are presented for iodine and iridium sources. While designed for the PEREGRINE program, this source model can be used in any Monte Carlo code.

Biophysical Phenomena↗
PubMed1995

Changes in transfusion therapy and reexploration rate after institution of a blood management program in cardiac surgical patients.

A retrospective study was performed to determine the impact of a coagulation and transfusion management program on blood utilization in 1,079 sequential patients for myocardial revascularization and open ventricle or combined procedures. Four hundred and eighty-eight patients (group 1) before, and 591 patients (group 2) after institution of thromboelastography (TEG)-guided coagulation were studied and compared for transfusion requirements, donor exposure, and the incidence of reoperation for hemorrhage. Group 2 patients had a significantly lower incidence of overall transfusion (78.5% v 86.3%) during hospitalization and in total transfusion in the operating room (57.9% v 66.4%). The incidence of each transfusion subtype was also significantly lower in group 2 patients. Actual total median donor exposure was 8 in group 1 patients and 6 exposures in group 2 patients. Mediastinal reexploration for hemorrhage was 5.7% before institution of TEG-based coagulation monitoring and 1.5% in TEG-monitored patients. Use of TEG monitoring before reexploration has decreased the cost and potential risk for patients undergoing CABG surgery.

Blood Coagulation↗
PubMed1989

Effects of central and peripheral dopamine antagonism on aldosterone secretion: evidence for adrenal mechanism.

Both domperidone (DOMP) and metoclopramide (MCP) are D2 receptor antagonists, MCP being a central and peripheral dopamine antagonist, whereas DOMP is exclusively a peripheral antagonist. MCP, but not DOMP, has been shown to stimulate aldosterone production. To elucidate whether aldosterone stimulation by dopamine antagonism is centrally mediated, we injected DOMP (28 micrograms/kg body wt) via a cannula into the third ventricle in Sprague-Dawley rats. Plasma aldosterone and renin concentration were measured before and 15 min after the injection. Centrally administered DOMP resulted in an increment in plasma aldosterone (23.8 +/- 7.4 ng/dl) that was not significantly greater than that induced by vehicle alone (15.8 +/- 4.5 ng/dl). This increase was inhibited by pretreatment with dexamethasone (100 micrograms three times daily) and attenuated by captopril (1 mg/kg ip) but not by L-beta-3,4-dihydroxyphenylalanine (30 mg/kg), thus reflecting a stress effect. Similarly, central administration of MCP (21 micrograms/kg) resulted in a significant rise in plasma aldosterone. This increase, however, was eliminated by pretreatment with dexamethasone and attenuated by captopril. Peripherally administered DOMP (280 micrograms/kg) had no effect on plasma aldosterone. The effect of DOMP and MCP on aldosterone secretion by freshly obtained adrenal capsules was also tested. Angiotensin II and MCP, but not DOMP, induced a dose-dependent increase in aldosterone secretion, with a maximal increment (15.7 +/- 5.8 ng.mg capsular protein-1.10 min-1; 50% increase) with MCP at 10(-7) M (P less than 0.01 compared with controls). Dopamine completely inhibited this MCP-induced rise in aldosterone release.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1986

Effects of intraventricular methotrexate on cerebrospinal fluid monoamine metabolites in rhesus monkeys.

Previous work suggested that methotrexate (MTX) may cause encephalopathy by inhibiting biosynthetic pathways for dopamine and serotonin in the brain. We examined this issue by measuring the neurotransmitter metabolites homovanillic acid and 5-hydroxyindoleacetic acid in the lumbar CSF of rhesus monkeys receiving continuous intracerebroventricular infusions of MTX or dichloromethotrexate. Infusion of the lowest dose (0.05 mg/day) produced a large (300%) rise in homovanillic acid levels and a modest elevation in 5-hydroxy-indoleacetic acid. During higher dose infusion, which was associated with clinical encephalopathy, the biogenic amine metabolites fell from their previous elevated levels. In one encephalopathic monkey, an injection of 1 mg of leucovorin produced a marked elevation in CSF monoamine metabolites within 1 hour and rapid clinical recovery. In contrast, leucovorin produced no change in monoamine metabolites in control animals. The data suggest that MTX may block egress of monoamine metabolites from CSF at the lower doses and suppress neurotransmitter turnover at toxic doses which cause encephalopathy. Serial measurements of CSF monoamine metabolites deserve further investigation as biochemical markers for toxic effects of MTX on neuronal metabolism in the CNS.

Animals↗
PubMed1985

Tissue culture of human and canine thoracic duct endothelium.

Endothelial cells from the canine or human thoracic duct were harvested using 0.2% collagenase digestion and grown in Media 199 supplemented with fetal bovine serum. The canine endothelial cells grew to confluence (4.4 to 12 X 10(4) cells/cm2) in 6 to 10 d; doubling times ranged from 1.5 to 2.8 d. There was a minimum critical density for cell growth between 5000 and 10 000 cells/cm2. The canine endothelial cells have been maintained in culture for periods up to 11 mo. The human thoracic duct endothelial cells are more difficult to grow and maintain. Endothelial cells were isolated from 5 out of 35 human thoracic ducts and grew for periods of up to 2 wk before degenerating. Both human and canine endothelial cells were Factor VIII positive. It has thus been demonstrated that it is possible to grow canine and, less easily, human thoracic duct endothelium in tissue culture.

Animals↗
PubMed1984

Primary Kaposi's sarcoma of the head and neck.

Kaposi's sarcoma is a cutaneous neoplasm commonly arising in the extremities, and rarely in the mucosa or skin of the head and neck. We discuss nine cases of Kaposi's sarcoma arising in the head and neck region, retrieved from the files of the Armed Forces Institute of Pathology, together with 74 cases from the literature. The commonest mucosal locations include the conjunctiva, palate, tongue, tonsils, and gums; common cutaneous sites are the eyelids, nose, ears, and face. Prognosis, sex distribution, and susceptible population groups for the head and neck tumor are similar to those for the commoner peripheral cutaneous form. Seventy percent of patients were 50 years or older; 15% of tumors occurred in children under 16 years. Children under 16 years were more likely to have initial head and neck involvement. In our series, 7 of 11 tumors in children initially involved the conjunctiva or skin of the eyelid. Recently the incidence of Kaposi's sarcoma has been increasing in patients with acquired immunodeficiency syndrome. The age of incidence for this group is lower; more tumors occur on the upper body, skin, and mucosal surfaces of the head and neck; and the prognosis is poorer than in traditional cases of Kaposi's sarcoma.

Adolescent↗
PubMedDate not supplied

Implanted system for intraventricular drug infusion in central nervous system tumors.

We have developed a totally implanted drug delivery system capable of maintaining constant cerebrospinal fluid (CSF) drug levels through continuous intraventricular infusion in outpatients. This system was used to infuse methotrexate (MTX) intraventricularly in seven patients with incurable CNS malignancies. One patient with meningeal diffuse histiocytic lymphoma, five patients with grade III--IV astrocytomas, and one patient with melanoma metastatic to the brain were treated with this system for 4--40+ weeks. The system consists of an Infusaid pump (Metal Bellows Corp, Sharon, MA), implanted subcutaneously in the infraclavicular fossa, which delivers a drug-containing solution at a set rate (3--5 mg/day) through a subcutaneous silastic catheter to a Rickham ventriculostomy reservoir and into a lateral ventricle. System placement and maintenance were readily tolerated. Constant MTX infusion at rates of 0.5--10 mg/day generated corresponding constant CSF drug levels in the range of 2--30 microM. Simultaneous serum MTX levels were undetectable (less than 0.01 microM), indicative of a 200- to 3000-fold selective regional concentration advantage for this approach. CNS toxic effects included transient meningism and fever (four patients), transverse myelitis (one), and the development of a diffuse hypodensity of the white matter on computerized tomographic scan which was not associated with any neurologic deficit (two). The usual systemic toxic effects (myelosuppression and mucositis) of MTX were not seen. The patient with meningeal lymphoma has had a complete remission of meningeal disease continuing past 10 months. Computerized tomography showed that three of the five high-grade astrocytomas had 25% size reductions in tumors lasting 2--6 months. This system may provide a means for improved treatment of meningeal tumor although its role in the treatment of intraparenchymal brain tumors is less clear. Of greater consequence, however, is the demonstrated ability of this system to maintain a controlled CSF drug level which should prove useful in many areas of therapeutic research.

Adult↗