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Biomedical subjects

L Hsu

Publications and source records attributed to L Hsu.

At least 109 records · Page 6Linked to original sources
PubMed1997

Regression calibration in failure time regression.

In this paper we study a regression calibration method for failure time regression analysis when data on some covariates are missing or mismeasured. The method estimates the missing data based on the data structure estimated from a validation data set, a random subsample of the study cohort in which covariates are always observed. Ordinary Cox (1972; Journal of the Royal Statistical Society, Series B 34, 187-220) regression is then applied to estimate the regression coefficients, using the observed covariates in the validation data set and the estimated covariates in the nonvalidation data set. The method can be easily implemented. We present the asymptotic theory of the proposed estimator. Finite sample performance is examined and compared with an estimated partial likelihood estimator and other related methods via simulation studies, where the proposed method performs well even though it is technically inconsistent. Finally, we illustrate the method with a mouse leukemia data set.

Animals↗
PubMed1997

Oxidation of methamphetamine and methylenedioxymethamphetamine by CYP2D6.

Methamphetamine (MeAmp) abuse has recently experienced a resurgence and approaches to the treatment of its addiction similar to those used with cocaine have been considered. As the treatment regimes are likely to use drugs whose metabolism is related to that of MeAmp, studies were initiated to establish the enzymology of the fate of MeAmp. This report describes investigations of the role of CYP2D6, the human isoform of the enzyme that catalyzes debrisoquine hydroxylation, in the 4-hydroxylation and N-demethylation of MeAmp. The results of studies with human liver microsomes including those from a genetically poor metabolizer with respect to CYP2D6, showing correlation between MeAmp and metoprolol hydroxylation and MDMA demethylenation, were consistent with a major involvement of CYP2D6 in the aromatic 4-hydroxylation of MeAmp. This was confirmed by studies with recombinant CYP2D6 expressed in yeast, which was also shown to effect the N-demethylation of MeAmp. The rate of the 4-hydroxylation reaction was substantially slower than the demethylenation of MDMA. In contrast to MeAmp, MDMA was not N-demethylated by CYP2D6. Since CYP2D6 participates in the major steps of MeAmp metabolism, pharmacokinetic interactions are likely with other drug substrates proposed for the treatment of MeAmp addiction. Furthermore, the genetic polymorphism associated with the enzyme could manifest itself in abnormal responses to MeAmp.

Cytochrome P-450 CYP2D6↗
PubMed1996

Developmental changes in endothelin A and endothelin B receptor subtypes in embryonic chick brains.

The kD and Bmax values for [125I]endothelin-1 ([125I]ET-1) binding to the brain membrane preparations of 3- to 20-day-old chick embryos were compared. The kD values differed only slightly during development. In contrast, the Bmax values varied six-fold during the embryonic stages examined and displayed two distinct peaks, on day 5 (204 +/- 13 fmol/mg protein, n = 3) and day 13 (110 +/- 4 fmol/mg protein, n = 7) of incubation. Displacement of [125I]ET-1 binding to 5- and 13-day-old embryonic brain membrane preparations was carried out using ET-3 and BQ-123, a selective ETA receptor antagonist, as competing ligands. The results suggest that the ETA receptor subtype is primarily synthesized at the beginning of development followed by the production of non-selective ETB receptor subtype at a later time.

Animals↗
PubMed1996

Image-guided surgery in a new magnetic resonance suite: preclinical considerations.

Surgical procedures require correct identification of exposed anatomy with concomitant localization amidst contiguous structures. In endoscopic procedures the surgeon is provided a real-time endoscopic view and is prepared with radiologic images. Here we present an overview of a methodology of localization using intraoperatively acquired magnetic resonance (MR) images in preparation for magnetic resonance imaging-guided endoscopic sinus surgery. The methodology centers around a unique prototype imaging device and operating environment. An "open" 0.5 Tesla MR unit has been created that allows complete access to the patient's head and neck while concomitant images are obtained. Illustrative examples of localization technique from cadaver experiments are presented, as well as insights into the host of concerns for anesthesia, equipment, surgical instrumentation, communications, and documentation.

Anesthesia↗
PubMed1996

Unusual manifestations of head trauma.

Head injury is the leading cause of death in young adults. More than 2 million head injuries occur each year in the United States. Accurate and rapid diagnosis is imperative for the successful management of the trauma patient. The radiologic findings of common manifestations of head trauma have been well described; however, the patient who presents in the post-traumatic period with atypical radiographic findings is at risk for misdiagnosis and delay in treatment. In this essay, we illustrate some unusual findings in head injury that may complicate diagnosis.

Adolescent↗
PubMed1996

Assessing familial aggregation of age at onset, by using estimating equations, with application to breast cancer.

In genetic research of chronic diseases, age-at-onset outcomes within families are often correlated. The nature of correlation of age-at-onset outcomes is indicative of common genetic and/or shared environmental risk factors among family members. Understanding patterns of such correlation may shed light on the disease etiology and, hence, is an important step to take prior to further searching for the responsible genes via segregation and linkage studies. Age-at-onset outcomes are different from those familiar quantitative or qualitative traits for which many statistical methods have been developed. In comparison with the quantitative traits, age-at-onset outcomes are often censored, i.e., instead of actual age-at-onset outcomes, only the current ages or ages at death are observed. They are also different from qualitative traits because of their continuity. Because of the complexity of correlated censored outcomes, few methods have yet been developed. A traditional approach is to impose a parametric joint distribution for the correlated age-at-onset outcomes, which has been criticized for requiring a stringent assumption about the entire distribution of age at onset. The purpose of this paper is to describe a method for assessing familial aggregation of correlated age-at-onset outcomes semiparametrically, by use of estimating equations. This method does not require any parametric assumption for modeling the age at onset. The estimates of parameters, including those quantifying the correlation within families, are consistent and have an asymptotic normal distribution that can be used to make inferences. To illustrate this new method, we analyzed two age-at-onset data sets that were obtained from studies conducted in the States of Washington and Hawaii, with the objective of quantifying the familial aggregations of age at onset of breast cancer.

Age of Onset↗
PubMed1995

Growth-promoting effects of endothelin-1 and endothelin-3 on chick embryos.

Chick embryos were treated with single or multiple doses of 0-250 pmol of endothelin-1 (ET-1) or endothelin-3 (ET-3) and their effects on development were examined in embryos ranging from 7 to 14 days in age. The overall sizes of the head, trunk, beak or wings were increased (5-14%) in ET-treated embryos. Additionally, the lengths or widths of the telencephalic or optic lobes and the diencephalon in the embryonic brains were also increased (4-14%). These effects were observed when the embryos were treated with ET for three consecutive days beginning on day 2 of incubation or from day 1-5. Similar results were obtained by a single injection given on the 5th day of incubation, but not on day 1 or 3. Morphological studies suggested that ET-1 and ET-3 promoted maturation rather than non-specific growth in size. Histological studies revealed that ET-treated brain tissues were more cellular and organized in appearance than control brains. There was no increased incidence of vascular abnormalities or structural malformations subsequent to ET-treatment. These results suggest that ET has growth factor-like effects and that treatment on and around the 5th day of incubation seemed to be most effective for the early phase in brain development in chick embryos.

Animals↗
PubMed1995

Dissection of the carotid and vertebral arteries: imaging with MR angiography.

Arterial dissection occurs when an intimal tear allows blood to enter the arterial wall, potentially compromising the lumen and reducing blood flow. Carotid and vertebral artery dissections typically occur after major trauma, although they also can arise spontaneously or after trivial injury. Arterial dissection has been associated with a variety of factors, including hypertension, fibromuscular dysplasia, Marfan syndrome, cystic medial necrosis, oral contraceptives, drug abuse (sympathomimetics), and infection [1-8]. It is important to recognize arterial dissection early so that prompt treatment can be initiated to prevent ischemic complications [1]. In this essay, we illustrate the use of MR angiography in the diagnosis of carotid and vertebral artery dissection.

Adolescent↗
PubMed1995

Cyclosporine neurotoxicity and its relationship to hypertensive encephalopathy: CT and MR findings in 16 cases.

OBJECTIVE: The neurotoxic effects of cyclosporine therapy are well known but poorly understood. Imaging studies typically show subcortical edema predominantly affecting the posterior regions of the brain. We sought to determine the causes for these findings by comparing radiographic data with various clinical parameters. MATERIALS AND METHODS: In a 3-year period, 16 patients with neurologic findings attributed to cyclosporine therapy were examined with CT, MR imaging, or both. In most cases, imaging was performed both at the onset of the neurologic syndrome and after it had resolved. The radiographic findings were evaluated with respect to lesion location and changes over time. Various clinical and laboratory data obtained throughout the patients' hospital course were also reviewed, including cyclosporine levels, blood pressure values, hematologic data, and serum levels of cholesterol, magnesium, creatinine, and albumin. RESULTS: The only major factor associated with the neurotoxic effects of cyclosporine in all patients was systemic hypertension. Microangiopathic hemolytic anemia, thrombocytopenia, and hypoalbuminemia were also common, and patients usually displayed signs of sympathetic overactivation. The onset of neurologic symptoms was unrelated to serum levels of creatinine, magnesium, cholesterol, or cyclosporine. The clinical and radiographic findings of these patients were identical to those previously reported in patients with hypertensive encephalopathy. Findings resolved in all but one patient after reduction of blood pressure, with or without reduction in cyclosporine dose. In four patients, intracranial hemorrhages occurred during the hypertensive episode, resulting in one fatality. CONCLUSION: The clinical and radiologic findings in patients showing the neurotoxic effects of cyclosporine appear to be identical to those with hypertensive encephalopathy. Other associated factors, such as cyclosporine-induced vasculopathy or hypoalbuminemia may also play a role in the condition, and intracranial hemorrhage may occur owing to associated thrombocytopenia. Symptoms generally resolve after reduction of blood pressure, and follow-up is usually unnecessary in uncomplicated cases.

Adolescent↗
PubMed1995

The evolution of multiple sclerosis lesions on serial MR.

PURPOSE: To characterize temporal changes in signal intensity patterns of multiple sclerosis lesions on serial MR. METHODS: T1-, T2-, proton density-, and contrast-enhanced T1-weighted MR was performed on five patients with relapsing-remitting multiple sclerosis at least 22 times in the course of 1 year. RESULTS: Forty-three enhancing lesions and 1 new lesion that never showed enhancement were detected and followed for periods ranging from approximately 4 weeks to 1 year (total of 702 time points). At first detection the center of new lesions was brighter than the periphery (20 of 24 new lesions on proton density-weighted and 19 of 23 new lesions on contrast-enhanced images). On contrast-enhanced images, ring hyperintensity was predominant at time points later than 29 days. As lesions aged, a residual rim of "nonenhancing" hyperintensity often was noted on contrast-enhanced images. Some older lesions (> 1 year) showed similar appearance on unenhanced T1-weighted images. On proton density-weighted images ring hyperintensity was most frequent 2 to 4 months after lesion detection. The estimated average duration of gadopentetate dimeglumine enhancement was 1 to 2 months. CONCLUSIONS: A lesion evolution pattern relevant to MR was inferred. We believe that specific information about the histopathologic evolution of a lesion may be extracted not only from contrast-enhanced but also from nonenhanced serial MR. Assessment of drugs targeting specific phases of lesion evolution could benefit from quantitative pattern analysis of routine MR images.

Adult↗
PubMed1995

Characterization of human platelet IgG Fc receptor associated with membrane glycoprotein.

Human platelets express IgG Fc receptors (Fc gamma R). Previously we reported that circulating immune complexes (CIC) inhibited fibrinogen binding to platelet glycoprotein IIb/IIIa complex (GPIIb/IIIa) and that isolated Fc gamma R were recognized by monoclonal antibodies (mAb's) to GPIIb and GPIIIa (J.Lab. Clin. Med. 117:209-217, 1991). In this study, we further characterized the properties of the Fc gamma R and the activity associated with GPIIb/IIIa. Binding of Fc portion of human IgG (Fc) to the platelet Fc gamma R associated with GPIIb/IIIa complex, unlike fibrinogen receptor, did not require divalent cations. The Fc gamma R bound to immobilized immune complex were recognized by mAb's to GPIIb, GPIIIa, GPIIb/IIIa. Preincubation of platelet extract with fibrinogen inhibited the binding of heat-aggregated IgG (HAG) to the extract. Flow cytometry of whole platelets revealed inhibition of mAb binding to GPIIb/IIIa, when platelets were incubated with Fc fragments or HAG. Using platelet extract coated to microtiter plates, similar findings were noted with Fc and HAG. The dissociation of GPIIb/IIIa complex by incubating platelet extract at 37 degrees C in the presence of EDTA caused a marked decrease in the binding of GPIIb and GPIIIa to the immobilized immune complex. Activation of intact platelets with ADP resulted in an increased binding of HAG to the platelets, indicating that an augmented Fc gamma R activity is associated with the activation of GPIIb/IIIa. These results suggest a close relationship of the Fc gamma R activity to the fibrinogen binding site (GPIIb/IIIa complex).

Adenosine Diphosphate↗
PubMed1995

Human platelet Fc receptors: binding kinetics of Fc derivatives to the receptors.

Human platelets are known to carry Fc receptors (Fc R), but the binding characteristics between ligands and Fc gamma R has not been well elucidated. In this study, we investigated the binding kinetics of IgG Fc fragments (Fc) to Fc R, the association and dissociation characteristics of the ligands to and from Fc gamma R using enzymatically modified Fc fragment derivatives. Approximately 60 minutes and 90 minutes were needed at 37 degrees C and 22 degrees C, respectively, for complete saturation of the Fc binding sites with horseradish peroxidase-conjugated Fc (HPO-Fc). Heat aggregated IgG (HAG) had a greater affinity for the Fc gamma R than Fc monomers. Additional binding of HAG was observed even after the binding sites were saturated with Fc monomers. This could be explained by different binding sites available only for immune complexes or by the partial dissociation of binding sites saturated with Fc by HAG. Further, we noted partial dissociation of HPO-Fc, when HAG was added after saturation of the binding sites with HPO-Fc. In a subsequent experiment, we compared the relative affinities of chemically or enzymatically modified Fc derivatives for Fc gamma R. HAG, which was used as a model for CIC, had a greater affinity for platelet Fc gamma R than IgG monomer and Fc derivatives. Pepsin-digestion of Fc caused a total loss of its affinity for the Fc gamma R, whereas b-mercaptoethanol-treated Fc fragments demonstrated substantial binding to the Fc gamma R. These results indicate that the pepsin digestion affects the Fc portion and causes a disruption in the area of the Fc which is essential for the recognition by the platelet Fc gamma R. On the other hand, cleavage of disulfide bridges by beta-mercaptoethanol resulted in a marked increase in affinity for the Fc gamma R. On the other hand, enzymatic cleavage of the carbohydrate moieties of Fc did not alter the affinity of Fc fragments for the Fc gamma R, indicating that the carbohydrates play an insignificant role or are not involved in their binding to the Fc gamma R.

Binding Sites↗
PubMed1994

Evaluation of cerebral aneurysms with helical CT: correlation with conventional angiography and MR angiography.

PURPOSE: To evaluate detection of intracranial aneurysms with helical computed tomography (CT) and compare the results with those of conventional angiography and magnetic resonance (MR) angiography. MATERIALS AND METHODS: Twenty-one patients with 30 intracranial aneurysms were studied with helical CT and conventional angiography; 17 of the patients (24 aneurysms) also underwent MR angiography. RESULTS: All aneurysms 3 mm or larger in greatest dimension were seen with helical CT and MR angiography; no aneurysms smaller than 3 mm were apparent with either modality. Of the 21 aneurysms demonstrated with both helical CT and MR angiography, 11 were seen equally well with both techniques; six were seen better with helical CT owing to flow-related or motion artifact at MR angiography, and four were seen better with MR angiography because calcium partially obscured them at helical CT. CONCLUSION: Helical CT is a promising noninvasive method of imaging the intracranial vasculature and is comparable with standard MR angiographic techniques in demonstrating aneurysms.

Cerebral Angiography↗