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Biomedical subjects

L Hsu

Publications and source records attributed to L Hsu.

At least 91 records · Page 5Linked to original sources

Stroke prevention trial in sickle cell anemia.

Stroke occurs in 7-8% of children with Sickle Cell Disease (Hb SS) and is a major cause of morbidity. Rates of recurrence have been reduced from 46-90% to less than 10% through chronic blood transfusions. Prevention of first stroke, however, would be preferable because even one stroke can cause irreversible brain injury. Transcranial Doppler (TCD) ultrasound can detect arterial blood flow rates associated with subsequent stroke risk. By combining TCD screening and a potentially effective treatment, first stroke may be prevented. The Stroke Prevention Trial in Sickle Cell Anemia (STOP) is the first stroke prevention trial in Hb SS and the first randomized, controlled use of transfusion in Hb SS. This multi-center trial is designed to test whether reducing sickle hemoglobin to 30% or less with periodic blood transfusions will reduce first-time stroke by at least 70% compared to standard care. Primary endpoints will be clinically evident symptoms of cerebral infarction with consistent findings on Magnetic Resonance Imaging and Angiography (MRI/MRA) or symptomatic intracranial hemorrhage. Secondary endpoints will be asymptomatic brain lesions detected by MRI in brain areas not involved in primary endpoints. The design calls for a 6-month start-up interval, 18 months of TCD screening and randomization, and observation for stroke from entry through month 54. Key features of the trial are standardized TCD and MRI/MRA protocols interpreted blindly, and blinded adjudication of endpoints. The sample size (60 per treatment group) is based on prospective data relating TCD velocity to risk of stroke. A time-averaged mean velocity of > or = 200 cm/sec is associated with a 46% risk of cerebral infarction over 39 months. The sample size is sufficient to detect 70% reduction in the primary endpoint at 90% power. This trial will determine if transfusion is effective in the primary prevention of stroke. Secondary aims may further the understanding of the effects of transfusion on the brain and guide future research into cerebrovascular disease in Hb SS.

Adolescent↗

Posttraumatic stress disorder in veterans with spinal cord injury: trauma-related risk factors.

Trauma-related risk factors for posttraumatic stress disorder (PTSD) were examined in a sample of 125 veterans with spinal cord injury. Category of injury was found to be the most consistent predictor of PTSD diagnosis and symptom severity with paraplegia predicting more PTSD symptoms than quadriplegia. The occurrence of a head injury at the time of the trauma was found to predict PTSD symptom severity measures, but not PTSD diagnosis. Trauma recency consistently predicted Impact of Event score (IES) and was found to be related to current PTSD severity and lifetime PTSD diagnosis in multiple but not simple regression models. Trauma severity was found to be significantly related to self-reported PTSD symptoms and lifetime PTSD diagnosis in simple but not in multiple regression analyses. Type of trauma, alcohol or other drug (AOD) use during the trauma and loss of consciousness (LOC) during the trauma were not consistently associated with PTSD symptom severity or diagnosis.

Adult↗

A comparison of posttraumatic stress disorder in veterans with and without spinal cord injury.

The authors assessed effects of paraplegic and quadriplegic spinal cord injuries (SCIs) on posttraumatic stress disorder (PTSD) by comparing severity and prevalence of PTSD in these groups to a sample of controls who experienced traumatic injuries other than SCI. The authors found that veterans with quadriplegia reported significantly less severe current PTSD symptoms than controls who were not significantly different from veterans with paraplegia. These results suggest that sustaining a quadriplegic SCI decreases risk of current PTSD, whereas sustaining a paraplegic SCI is associated with greater risk of PTSD, although the risk is no greater than that incurred from experiencing the trauma itself.

Adult↗

Mapping of complex traits by single-nucleotide polymorphisms.

Molecular geneticists are developing the third-generation human genome map with single-nucleotide polymorphisms (SNPs), which can be assayed via chip-based microarrays. One use of these SNP markers is the ability to locate loci that may be responsible for complex traits, via linkage/linkage-disequilibrium analysis. In this communication, we describe a semiparametric method for combined linkage/linkage-disequilibrium analysis using SNP markers. Asymptotic results are obtained for the estimated parameters, and the finite-sample properties are evaluated via a simulation study. We also applied this technique to a simulated genome-scan experiment for mapping a complex trait with two major genes. This experiment shows that separate linkage and linkage-disequilibrium analyses correctly detected the signals of both major genes; but the rates of false-positive signals seem high. When linkage and linkage-disequilibrium signals were combined, the analysis yielded much stronger and clearer signals for the presence of two major genes than did two separate analyses.

Biosensing Techniques↗

Family functioning and social support in the adaptation of caregivers of children with sickle cell syndromes.

OBJECTIVE: To examine moderating effects of family functioning and social support on the relationship of child-related stressors to caregivers' psychological adaptation in a sample of caregivers of children with a chronic illness. METHOD: Participants were 67 caregivers of children and adolescents with sickle cell syndromes. We conducted MANOVAs and subsequent effect size calculations to determine if family functioning would buffer the effects of caring for difficult-to-manage children with this illness. RESULTS: Findings supported a moderator effect of family functioning on the association of children's externalizing behavioral problems to caregivers' symptoms of hostility. Greater levels of cohesive and adaptive family functioning buffered the potential detrimental effects of caring for children perceived as hard to manage. No significant associations were obtained between measures of caregivers' psychological adaptation and the severity of their children's disease. CONCLUSIONS: We make recommendations for family systems interventions, particularly for caregivers of children with behavior problems.

Adaptation, Psychological↗

Interactive magnetic resonance imaging-guided biopsy in the head and neck: initial patient experience.

Because of its excellent soft tissue resolution, magnetic resonance imaging (MRI) can optimize image guidance for interventional and surgical procedures. Notably, needle biopsy of head and neck lesions has been used for years, deeper lesions often requiring some form of image guidance. The closed space of diagnostic MRI scanners proves cumbersome for intervention. The authors report on the first head and neck image-guided biopsies performed in a new, investigational "open configuration" intraoperative MRI scanner. Vertical space between the scanner's upright coils gives access to the patient while imaging; image acquisition is as fast as 2 sec/image. Biopsies were performed on seven patients (parotid, parapharyngeal space, second cervical vertebra); five specimens were diagnostic. Both general anesthesia and intravenous sedation were used. The procedures were without complications. Imaging provided definition of anatomy to direct needle placement. Access to the patient allowed for both percutaneous and transoral approaches. The environment of the open magnet is well suited for biopsy of the head and neck, and near real-time intraoperative MRI has promise for guiding more complex head and neck procedures. Further study should optimize the quality of the images and the interactibility of localization and targeting and fully utilize MRI's three-dimensional imaging capabilities.

Adenoma, Pleomorphic↗

Computer-assisted three-dimensional reconstruction of head and neck tumors.

OBJECTIVE: Because head and neck tumors reside in a complex area, having a three-dimensional (3-D) model of the patient's unique anatomical features may assist in the delineation of pathology. The authors describe a new computer technique of 3-D anatomical reconstruction from two-dimensional computed tomography (CT) and magnetic resonance (MR) data and discuss how it represents a step forward in the continuing evolution of 3-D imaging. STUDY DESIGN: The authors selected three patients with solitary head and neck tumors and reconstructed their anatomy in a 3-D format for study. The tumors represented locations in the nose and central skull base (patient 1), temporal bone (patient 2), and neck (patient 3). MATERIALS AND METHODS: MR and CT images from the individual patients were electronically transferred to workstations in the Surgical Planning Laboratory of the authors' institution. Registration (or fusion) was carried out between the MR and CT images. The desired anatomic components underwent segmentation (identification and isolation). Assembly of the segmented images was performed and the resulting structures were integrated to produce a 3-D model. RESULTS: 3-D models of the following were constructed and displayed in an interactive format on high-capacity computer workstations: 1) a skull base sarcoma with extension into the nasopharynx and nose; 2) an acoustic neuroma with internal auditory canal involvement; and 3) a metastatic recurrence of a tongue base squamous cell carcinoma in the posterior triangle of the right side of the neck with extension to the skull base. CONCLUSION: The authors' Surgical Planning Laboratory has developed a 3-D reconstruction technique that has several new features. The models provided a very good 3-D interactive representation of the tumors and patient anatomy. The need now exists to develop this method of 3-D reconstruction of head and neck tumors for potential applications in treatment, research, and medical education.

Adult↗

Line scan diffusion imaging: characterization in healthy subjects and stroke patients.

OBJECTIVE: Our objective was to evaluate a new scanning method, MR line scan diffusion imaging, and assess the apparent diffusion coefficient in the brains of healthy subjects and stroke patients. SUBJECTS AND METHODS: Line scan diffusion imaging without cardiac gating or head restraints was implemented on low- (0.5 T) and medium- (1.5 T) field-strength scanners with conventional hardware. Diffusion-weighted images were obtained in six healthy subjects and eight stroke patients. Unidirectional diffusion encoding was used for fast localization of stroke lesions. For further characterization, orthogonal diffusion encoding was applied, and the trace of the apparent diffusion coefficient was calculated. Single-shot diffusion-weighted echoplanar imaging served as the reference standard. For healthy subjects, imaging was repeated four times on each scanner. Mean and relative precision of the apparent diffusion coefficient trace values were calculated for each pixel. In stroke lesions and adjacent normal tissue, apparent diffusion coefficient trace values were determined. RESULTS: In the 108 scans obtained, line scan diffusion imaging proved to be robust, virtually free of artifact (independent of slice location and orientation), reproducible, and rapid for localization of a stroke. Scan time for 14 slices at 7-mm thickness was 8 min at 0.5 T and 7 min at 1.5 T. Image qualities with line scan diffusion imaging and single-shot diffusion-weighted echoplanar imaging were comparable. At 1.5 T, precision was essentially the same for line scan diffusion imaging (4.3%) and echoplanar imaging (4.7%). With line scan diffusion imaging at 0.5 T and 1.5 T, normal paraventricular apparent diffusion coefficient trace values averaged 0.71 microm2/msec, and with echoplanar imaging these values averaged 0.69 microm2/msec. In acute lesions apparent diffusion coefficient trace values were low, and in chronic lesions these values were high. CONCLUSION: Line scan diffusion imaging on low- and medium-field-strength MR scanners equipped with conventional hardware was reliable and practical for measuring brain apparent diffusion values, which can be applied to the early diagnosis, and hence timely management, of stroke.

Adult↗

MR-guided endoscopic sinus surgery.

We describe an interactive, intraoperative imaging-guided method for performing endoscopic sinus surgery (ESS) within a vertically open MR system. The procedure was performed with intraoperative imaging using a 0.5-T magnet with a 56-cm vertical gap. Interactive control of imaging planes was accomplished by optical tracking with two infrared light-emitting diodes mounted on an aspirator probe. The probe's position defined the location of the orthogonal imaging planes. Twelve patients with varying degrees of sinus disease underwent ESS with MR imaging guidance. Patients had acute and chronic sinusitis, nasal polyposis causing airway obstruction, or tumor requiring tissue biopsy. All procedures were performed with the patients under general anesthesia. The integration of endoscopy with optical tracking and intraoperative interactive imaging allowed localization of anatomic landmarks during ESS. No complications were encountered.

Acute Disease↗

The load dependence of kinesin's mechanical cycle.

Kinesin is a dimeric motor protein that transports organelles in a stepwise manner toward the plus-end of microtubules by converting the energy of ATP hydrolysis into mechanical work. External forces can influence the behavior of kinesin, and force-velocity curves have shown that the motor will slow down and eventually stall under opposing loads of approximately 5 pN. Using an in vitro motility assay in conjunction with a high-resolution optical trapping microscope, we have examined the behavior of individual kinesin molecules under two previously unexplored loading regimes: super-stall loads (>5 pN) and forward (plus-end directed) loads. Whereas some theories of kinesin function predict a reversal of directionality under high loads, we found that kinesin does not walk backwards under loads of up to 13 pN, probably because of an irreversible transition in the mechanical cycle. We also found that this cycle can be significantly accelerated by forward loads under a wide range of ATP concentrations. Finally, we noted an increase in kinesin's rate of dissociation from the microtubule with increasing load, which is consistent with a load dependent partitioning between two recently described kinetic pathways: a coordinated-head pathway (which leads to stepping) and an independent-head pathway (which is static).

Animals↗

Clinical and neuroradiographic manifestations of eastern equine encephalitis.

BACKGROUND: Eastern equine encephalitis occurs principally along the east and Gulf coasts of the United States. Recognition of the neuroradiographic manifestations of eastern equine encephalitis could hasten the diagnosis of the illness and speed the response to index cases. METHODS: We reviewed all cases of eastern equine encephalitis reported in the United States between 1988 and 1994. The records of 36 patients were studied, along with 57 computed tomographic (CT) scans and 23 magnetic resonance imaging (MRI) scans from 33 patients. RESULTS: The mortality rate was 36 percent, and 35 percent of the survivors were moderately or severely disabled. Neuroradiographic abnormalities were common and best visualized by MRI. Among the patients for whom MRI scans were available, the results were abnormal for all eight comatose patients as well as for all three noncomatose patients who subsequently became comatose. The CT results were abnormal in 21 of 32 patients with readable scans. The abnormal findings included focal lesions in the basal ganglia (found in 71 percent of patients on MRI, and in 56 percent on CT), thalami (found in 71 percent on MRI and in 25 percent on CT), and brain stem (found in 43 percent on MRI and in 9 percent on CT). Cortical lesions, meningeal enhancement, and periventricular white-matter changes were less common. The presence of large radiographic lesions did not predict a poor outcome, but either high cerebrospinal fluid white-cell counts or severe hyponatremia did. CONCLUSIONS: Eastern equine encephalitis produces focal radiographic signs. The characteristic early involvement of the basal ganglia and thalami distinguish this illness from herpes simplex encephalitis. MRI is a sensitive technique to identify the characteristic early radiographic manifestations of this viral encephalitis.

Adolescent↗

Population-based family study designs: an interdisciplinary research framework for genetic epidemiology.

Most complex traits such as cancer and coronary heart diseases are attributed either to heritable factors or to environmental factors or to both. Dissecting the genetic and environmental etiology of complex traits thus requires an interdisciplinary research strategy. Genetic studies generally involve families and investigate familial aggregations of traits, segregation of major disease genes, and locations of disease genes on the human genome, the latter of which can be identified via linkage analysis. Epidemiologic studies often use population-based case-control studies to establish the role of specific environmental factors. Integrating both objectives, genetic epidemiology is to assess the associations of environmental factors with disease status, to quantify the aggregation of cases within families, to characterize putative disease genes via segregation analysis, and to localize disease genes via linkage analysis with genetic markers. To accomplish these objectives through designed studies, we propose a class of population-based family study designs, which are formed by choosing among sampling designs at three stages. The objectives of sampling at these three stages are 1) combined aggregation and association analysis, 2) combined segregation, aggregation, and association analysis, and 3) combined linkage, segregation, aggregation, and association analysis. These designs form an interdisciplinary research framework for genetic epidemiology. Our preliminary exploration of this framework and related analytic methods indicates that population-based family study designs retain the efficiency of linkage analysis for localizing disease genes without losing the property of being population-based, and they will therefore allow an assessment of a joint contribution of genetic and environmental factors to complex traits.

Case-Control Studies↗

A population-based family study (II): Segregation analysis.

We used segregation analysis to investigate the genetic etiology of the disease in Problem 2A. Under the assumption of a dominant major gene, our analysis suggests a major gene with relative risk of 58 and an allele frequency of 0.013. Under an additive gene assumption, it appears that there may be two genes with relative risks of 39 and 17 and allele frequencies of 0.015 and 0.075, respectively.

Case-Control Studies↗

[Design, clinical suitability and future aspects of a 0.5 T MRI special system for interventional use].

PURPOSE: To develop a superconducting magnetic resonance (MR) imager that provides direct access to the patient and permits interactive MR-guided interventional procedures. MATERIALS AND METHODS: A 0.5-T superconducting magnet that allows a region of vertical access to the patient was designed and constructed. This magnet was integrated with newly designed shielded gradient coils, flexible surface coils, nonmagnetic displays, position-monitoring probes and device-tracking instrumentation. RESULTS: The magnet homogeneity was 12.3 ppm or better, and the gradient field was linear to within 1% over an imaging region of 30 cm in diameter. The signal-to-noise ratio was 10% higher than in a comparable 0.5-T superconducting imager. Images were obtained in several anatomic regions with use of routine pulse sequences. Interactive image plane selection and near real-time imaging, with use of fast gradient-recalled echo sequences were demonstrated at a rate of one image every 1.5 s. More than 240 procedures (including open brain surgery) have been successfully performed within this environment. CONCLUSIONS: MR-guided interventional and surgical procedures can be performed with full patient access using an open-configuration, superconducting MR magnet with near real-time imaging and interactive image plane control.

Endoscopes↗

Seroprevalence of and risk factors for hepatitis A infection among young homosexual and bisexual men.

To evaluate hepatitis A infection among young homosexual and bisexual men, 411 men aged 17-22 years were surveyed at 26 public venues in San Francisco and Berkeley. Seroprevalence of hepatitis A infection was 28.0% (95% confidence interval [CI], 23.7%-32.6%). Recent infection was evident in 3.3% of susceptible men (95% CI, 1.6%-5.9%). Independent predictors of hepatitis A infection were Latino ethnicity (odds ratio [OR] = 5.3; 95% CI, 3.1-8.9), having > or = 50 lifetime male sex partners (OR = 1.8; 95% CI, 1.1-3.0), less than high school education (OR = 2.2; 95% CI, 1.2-4.1), and being a high school graduate (OR = 1.7; 95% CI, 1.0-2.9). Independent predictors of recent infection were less than high school graduate (OR = 7.6; 95% CI, 1.9-30.5), insertive anal intercourse (OR = 5.6; 95% CI, 1.0-32.8), and sharing needles without cleaning them (OR = 32.1; 95% CI, 3.0-346). Hepatitis A is a common infection in young homosexual men and is associated with sexual and drug-using behaviors.

Adolescent↗