Search PubMed⌕ Search

Biomedical subjects

C Lee

Publications and source records attributed to C Lee.

At least 883 records · Page 49Linked to original sources

Effect of using warfarin plasma concentrations in Bayesian forecasting of prothrombin-time response.

The predictive performance of a Bayesian computer program using prothrombin-time (PT) response data with and without warfarin plasma concentrations to forecast patients' PTs at the time of hospital discharge was evaluated. A log-linear pharmacokinetic-pharmacodynamic model was used to describe and predict warfarin dose response in patients recently started on warfarin sodium. Individual patients' pharmacodynamic variables relating warfarin concentration to clotting-factor synthesis were obtained by Bayesian nonlinear regression analysis. Pharmacokinetic values for warfarin clearance and volume of distribution were either calculated using nonlinear regression from measured plasma warfarin concentrations or estimated based on literature-derived population regression equations. Percent mean absolute prediction error (precision) and prediction error (bias) for PT predictions were compared among and between analysis methods that used only literature data to estimate PT response and methods that used zero to five PTs with or without warfarin plasma concentrations. Eleven women and eight men completed the study. Predictions after four days of warfarin therapy using PT measurements beginning after either the first or third warfarin dose were clinically useful regardless of whether warfarin concentrations were used in the predictions. Predictions using fewer than four PT measurements were imprecise and biased. The Bayesian method in this study provided good predictions of PTs immediately before hospital discharge based on warfarin dosing and PT response after either four or five days of therapy. The use of warfarin plasma concentrations in the pharmacokinetic-pharmacodynamic model used here appears unwarranted.

Adolescent↗

Hemodynamic pharmacology of p-chloroamphetamine, a serotonin agonist, in conscious rats.

The hemodynamic effects of p-chloroamphetamine (PCA), an indirect serotonin (5-HT) agonist, were studied in conscious, unrestrained rats. PCA caused an immediate hypotension and bradycardia followed by a dose-dependent increase in mean arterial pressure (MAP), which lasted for 15 to 60 min, associated with variable effects on heart rate. An intermediate dose increased MAP and resistance in hindquarter and mesenteric, but not renal, vascular beds. The pressor effect of PCA was blocked by prazosin and by 6-hydroxydopamine plus adrenal demedullation, but not by 6-hydroxydopamine or adrenal demedullation separately. Ganglionic blockade with chlorisondamine or beta adrenoceptor blockade with propranolol potentiated the pressor response to PCA, whereas several manipulations of central 5-HT systems (fluoxetine, methysergide and 5,7-dihydroxytryptamine) reduced but did not eliminate the hypertension observed after PCA. The initial bradycardia and hypotension were abolished by chlorisondamine or atropine but not reduced by any other pretreatment, whereas the variable heart rate response was converted to a marked, sustained tachycardia by ganglionic blockade or atropine and to a consistent bradycardia by propranolol and peripheral sympathectomy. The data suggest that PCA causes an immediate central or reflex vagal activation to decrease heart rate and MAP, followed by a central 5-HT-mediated increase in sympathetic activity that increases MAP. Most of the pressor effect observed between 5 and 30 min after PCA appears to be mediated by a direct effect on release of norepinephrine and epinephrine from sympathetic nerve terminals and the adrenal medulla, respectively. Only a minor part of the hemodynamic response to PCA appears to be attributable to its effect on release of 5-HT in the brain.

Adrenal Medulla↗

Somata-selective lesions induced by cobaltous chloride: a parametric study.

Repeated injections of cobaltous chloride destroy neuronal somata while sparing fibers-of-passage. This effect is dose-dependent and excess cobalt destroys fibers-of-passage as well as somata. By manipulating the concentration and volume of cobaltous chloride injected into rat lateral geniculate nuclei, we defined a range of parameters producing highly selective destruction of somata for regions 1 mm in diameter or smaller.

Animals↗

Acid phosphatase in the rat prostate: comparison with other organs.

Properties of acid phosphatase in the rat ventral prostate were compared with those in seven other organs in adult male rats by the electrophoretic mobility in acrylamide gels, susceptibility to reactions with inhibitors, and by their response to castration and subsequent testosterone replacement. The enzyme in the spleen exhibited the highest values of Km and Vmax. These values in the prostate, the liver, and the kidney showed an intermediate level, while the lowest level was found in the heart, the lung, the adrenals, and the seminal vesicle. Upon electrophoresis, a total of six isoenzyme bands were resolved. Two major zones of activity were noted. They were the slow-moving anodal bands (isoenzymes 1,2, and 3) and the fast-moving cathodal bands (isoenzymes 4,5, and 6). The spleen possessed the highest number of isoenzymes (bands 1,2,4,5 and 6) and the prostate had three (bands 1,2, and 3). The heart contained only one (band 2). Two isoenzymes (bands 1 and 2) were found in remaining organs. Results of the effects of inhibitors showed that NaF inhibited all six isoenzymes, while L(+)tartrate inhibited mainly those in the anodal zone. D(-)tartrate and formaldehyde showed no significant inhibition to any of the isoenzymes. PCMB (para-chloromercuribenzoic acid) was found to be a specific inhibitor for isoenzyme 3. Upon castration in the hosts, the enzyme activity in the prostate, the liver, and the seminal vesicle was significantly reduced. This reduction in enzyme activity involved all isoenzymes in these three organs, but isoenzyme 3 in the prostate disappeared completely after castration. The activities of these isoenzymes were restored by testosterone replacement. These results indicate that acid phosphatase in rat tissues has multiple forms; each has its own electrophoretic mobility in acrylamide gels, sensitivity to inhibitors, and response to hormonal manipulation. Isoenzyme 3 is specific to the prostate and is uniquely sensitive to PCMB inhibition and to androgen stimulation.

Acid Phosphatase↗

Water imbibition in the rat prostate during castration-induced regression.

The present study was conducted to examine changes in water concentration in the ventral prostate of adult rats at different intervals following castration. The prostatic dry weight was obtained by drying the fresh prostate at 70 degrees C for at least 110 hr and the prostatic water content was calculated from its wet and dry weight. Under normal conditions, the prostatic water concentration ranges from 81.9 to 82.7% in uncastrated rats. The prostatic water concentration started to increase at 8 hr postcastration (83.1%) but this increase was not statistically significant. By 16 hr postcastration, the prostatic water concentration (83.8%) became significantly higher than that of the uncastrated animals. In rats of day 1 to day 10 postcastration, the prostate contained significantly more water (84.4%-84.7%) than those in uncastrated animals. By day 21 postcastration, the prostatic water concentration (81.5%) was not significantly different from that of uncastrated rats. Unlike the prostate, the skeletal muscle did not significantly change the water concentration following castration. The 51Cr-EDTA space in the prostate was not significantly different in rats before and after castration. These results indicate that water imbibition in the rat prostate is associated with an active period of prostatic regression and that the change in the 51Cr-EDTA space during prostatic regression is not the major cause of water imbibition in the tissue. Therefore, the present findings suggest that castration-induced water imbibition in the rat prostate is caused by an increase in the intracellular water space.

Adrenalectomy↗

Two-dimensional characterization of prostatic acid phosphatase, prostatic specific antigen and prostate binding protein in expressed prostatic fluid.

Specimens of pooled prostatic fluid, collected by rectal massage from men under 50 years of age with no apparent prostatic disorders, were subjected to two-dimensional gel electrophoresis to study the composition of its proteins. In a preliminary study, a total of 57 major protein groups were detected. In the present study, we attempted to identify, in the two-dimensional gels, those that are related to prostate-associated proteins, i.e., prostatic acid phosphatase (PAP), prostatic specific antigen (PSA), and prostate binding protein (PBP). Individual proteins were recognized by the procedure of Western Blot using specific antisera with peroxidase-antiperoxidase as the staining reagent. Each protein spot in the two-dimensional gel was expressed, along the abscissa, by its isoelectric point (pI) and, along the ordinate, by the molecular weight (MW). PAP consisted of a train of more than ten protein spots that occupied an area in the gel from pI 7.0, MW 45,000 to pI 6.0, MW 50,000. Four protein spots with a MW of 34,000 and a pI range of 8.2-8.8 were identified as PSA. PBP was observed as having three protein spots that were located at pI 5.6-6.6 with a single MW of 15,000. For PAP and PSA, additional protein spots with lower MWs also stained positively with the specific antisera, suggestive of the presence of degradative products of these proteins. Following the removal of the serum-related proteins by an extensive absorption with anti-human serum antibody by affinity chromatography, the prostatic fluid contained 27 major groups of non-serum proteins. These non-serum proteins in the prostatic fluid included PAP, PSA, PBP, and their related smaller molecular species. These results indicate that the prostatic fluid contains PAP, PSA, PBP and that their presence and the patterns of their distribution in the two-dimensional gels should be considered as the characteristic property of the prostatic secretions.

Acid Phosphatase↗

The radiographic distinction of degenerative slippage (spondylolisthesis and retrolisthesis) from traumatic slippage of the cervical spine.

In a review of 42 cases of degenerative arthritis of the cervical spine and 22 cases of cervical spine trauma with an observed anterior slippage (spondylolisthesis) or posterior slippage (retrolisthesis) of the vertebral bodies of 2 mm or more, characteristic features were observed which allowed distinction between degenerative and traumatic slippage of the cervical spine. In degenerative slippage the shape of the articular facets and width of the facet joint space may remain normal; however, in most cases the articular facets become "ground-down" with narrowing of the facet joint space and the articular facets themselves becoming thinned or ribbon-like. In traumatic slippage the articular facets will either be normally shaped or fractured and the facet joint space will be abnormally widened. Plain radiographs will usually allow this distinction to be made; however, in difficult cases polytomography may be required.

Adult↗

Community exercise programs: follow-up difficulty and outcome.

The use of follow-up assessments to determine maintenance following behavior change programs is widely recognized as essential. It is often difficult to contact all previous participants, and evidence from alcohol abuse programs suggests that data from those people most readily contacted are not representative of overall outcomes. This study examines the relationship between the difficulty of follow-up and the reported maintenance of regular physical activity 6 months after the completion of a community-based fitness program. Ninety percent of 372 participants were contacted, and those easier to contact reported a significantly greater amount of current exercise. It is concluded that as large a percentage of former participants as possible must be contacted in order to conduct meaningful follow-up studies.

Adult↗

Magnetic resonance imaging of the sella turcica and parasellar region. A clinical-radiographic evaluation with computed tomography.

Thirty-one magnetic resonance (MR) scans and computed tomography (CT) scans were obtained on 25 patients in whom lesions involving the sella turcica or parasellar region were clinically suspected. Surgical pathologic studies were available in 19 cases. Twenty-two of the MR scans were of diagnostic value equivalent to that of the corresponding CT studies. In two small meningiomas, an empty sella, and a sphenoid-middle fossa tumor, MR technology failed to delineate the pathologic process adequately. In the remaining five patients, MR either more convincingly demonstrated the pathologic anatomy or yielded diagnostic information not present in the CT study. In view of the absence of ionizing radiation, high degree of tissue contrast and spatial resolution, and multiplanar capability, magnetic resonance scanning will probably become the initial imaging modality of choice in patients suspected of harboring sellar and parasellar tumors.

Adolescent↗

Site-specifically modified 111In labelled antibodies give low liver backgrounds and improved radioimmunoscintigraphy.

Site-specific modification of monoclonal antibodies at their oligosaccharide had previously been demonstrated to produce excellent 111In imaging in a xenograft model using a Brown Norway (BN) rat lymphoma and a rat anti-BN MHC monoclonal antibody [Lee C. et al. Fed. Proc. Abstr. 43 3014 (1984)]. These results are due, in part, to lack of liver uptake, so we wanted to evaluate the extent of hepatic uptake observed with different monoclonal antibodies in normal mice. Biodistribution data were obtained for four monoclonal antibodies by first modifying each antibody at its carbohydrate with a diethylenetriaminepentaacetic acid (DTPA) derivative. The antibodies were then labelled with 111In and injected into normal mice. Images were obtained 24 h post-injection, and at 48 h the mice were dissected and the tissue-to-blood (T:B) ratios determined. T:B ratios were approximately 1 (or less) for every organ evaluated, indicating minimal non-specific uptake into these organs. Data is also presented for the BN-rat system which shows excellent localization into the tumor xenograft and low non-specific organ uptake. These data indicate that modification of antibodies site-specifically at their oligosaccharide results in minimal non-specific uptake into non-target tissues and enhanced localization into the tumor target, and that this may represent a preferred method for production of 111In labelled antibodies.

Animals↗

Site-specific covalent modification of monoclonal antibodies: in vitro and in vivo evaluations.

A strategy for covalent modification of monoclonal antibodies utilizing the oxidized oligosaccharide moieties on the molecule was evaluated and compared to more conventional methods. As judged by quantitative in vitro measurements, a monoclonal antibody conjugate prepared via the oligosaccharides retained the homogeneous antigen binding property and affinity of the unmodified antibody. In contrast, conjugates of the same antibody, modified to the same degree on either lysines or aspartic and glutamic acid side chains, were heterogeneous in their antigen binding and had lowered affinity. In vivo biodistribution and nuclear-imaging experiments were also performed with a second monoclonal antibody and a tumor xenograft model. Antibodies modified on the oligosaccharides with either a peptide labeled with iodine-125 or a diethylenetriaminepentaacetic acid chelate with indium-111 localize into target tumors more efficiently than the same antibody radiolabeled on either tyrosines or lysines. These in vivo results, when compared to those reported in the literature for conventionally modified antibodies, suggest that oligosaccharide modification of monoclonal antibodies is a preferred method of preparing conjugates.

Animals↗

Value of continuous monitoring of mixed venous blood oxygen saturation in the management of critically ill patients.

Continuous SVO2 measurement using a triple-lumen flow-directed pulmonary artery catheter with fiberoptic filaments has been described. The purpose of this study was to identify whether the availability of SVO2 as a continuously monitored signal could have altered patient management decisions made by the medical staff on the basis of clinical and laboratory data and signals currently used in ICUs. Subjects for this study were 15 critically ill patients requiring arterial cannulation and insertion of a pulmonary artery catheter. The central processor of the device was placed in a specially constructed wooden box in such a way as to conceal the digital display of the signal. The folded paper used for a continuous 72-h recording of the signal was also not available to the personnel managing the patient. In detailed and repeated assessments of the patient's status, the medical team managing the patient entered on a special form all clinical and laboratory data as well as medical decisions made. At the end of each study the SVO2 value recorded at each assessment was entered on the form. The investigators then determined whether knowledge of SVO2 would have changed the clinical decision actually made. The SVO2 signal was continuously recorded for a total of 1065 h and 173 individual assessments. The SVO2 signal as measured by the Oximetrix device was compatible with decisions made on the basis of standard measurements used in the ICU in a majority of cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗