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Biomedical subjects

F Y Hsieh

Publications and source records attributed to F Y Hsieh.

At least 19 recordsLinked to original sources

Design of Department of Veterans Affairs Cooperative Study no. 420: group treatment of posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a significant problem for a large number of veterans who receive treatment from the Department of Veterans Affairs (VA) health-care system. VA Cooperative Study 420 is a randomized clinical trial of group psychotherapy for treating PTSD among veterans who sought VA care. Participants at ten sites were randomly assigned to receive one of the two treatments: active treatment that embedded exposure therapy in a group context or comparison treatment that avoided trauma focus and instead addressed current interpersonal problems. Treatment was delivered weekly to groups of six participants for 30 weeks, followed by five monthly booster sessions. Follow-up assessments were conducted at the end of treatment (7 months) and the end of boosters (12 months) for all participants. Long-term follow-up data were collected for a subset of participants at 18 and 24 months. The primary outcome is PTSD severity; other symptoms, functional status, quality of life, physical health, and service utilization also were assessed. Data analysis will account for the clustering introduced by the group nature of the intervention. The pivotal comparison was at the end of treatment. Analyses of subsequent outcomes will concentrate on the question of the durability of effects. The study provides an example of how to address the unique challenges posed by multisite trials of group psychotherapy through attention to methodological and statistical issues. This article discusses these challenges and describes the design and methods of the study. Control Clin Trials 2001;22:74-88

Adult↗

Sample-size calculations for the Cox proportional hazards regression model with nonbinary covariates.

This paper derives a formula to calculate the number of deaths required for a proportional hazards regression model with a nonbinary covariate. The method does not require assumptions about the distributions of survival time and predictor variables other than proportional hazards. Simulations show that the censored observations do not contribute to the power of the test in the proportional hazards model, a fact that is well known for a binary covariate. This paper also provides a variance inflation factor together with simulations for adjustment of sample size when additional covariates are included in the model. Control Clin Trials 2000;21:552-560

Analysis of Variance↗

Predictors of emotional numbing, revisited: a replication and extension.

Litz et al. (1997), theorizing that emotional numbing (EN) is the result of emotional depletion caused by chronic hyperarousal, demonstrated that a cluster of hyperarousal symptoms was a robust predictor of EN symptoms. In the present study, these findings were replicated and extended in two multiple regression analyses of data from a large, multisite investigation (T. M. Keane et al., 1998) of psychophysiological responding by male combat veterans. The arousal (D) cluster of symptoms was again the most robust predictor of EN symptoms, whereas physiological indices of arousal and reactivity accounted for negligible amounts of variance in both regression equations. These findings underscore the possible link between disturbances related to arousal and the capacity of traumatized individuals to express and experience pleasant feelings.

Affect↗

A simple method of sample size calculation for linear and logistic regression.

A sample size calculation for logistic regression involves complicated formulae. This paper suggests use of sample size formulae for comparing means or for comparing proportions in order to calculate the required sample size for a simple logistic regression model. One can then adjust the required sample size for a multiple logistic regression model by a variance inflation factor. This method requires no assumption of low response probability in the logistic model as in a previous publication. One can similarly calculate the sample size for linear regression models. This paper also compares the accuracy of some existing sample-size software for logistic regression with computer power simulations. An example illustrates the methods.

Humans↗

Hypoplasia of the internal carotid artery with intercavernous anastomosis.

We report a symptomatic case of unilateral hypoplasia of the internal carotid artery with an intercavernous anastomosis, a very rare developmental anomaly. The symptoms were caused by occlusion of the proximal middle cerebral artery which possibly related to the haemodynamic stress caused by the anomalous intercavernous anastomosis.

Arteriovenous Anastomosis↗

Utility of psychophysiological measurement in the diagnosis of posttraumatic stress disorder: results from a Department of Veterans Affairs Cooperative Study.

This multisite study tested the ability of psychophysiological responding to predict posttraumatic stress disorder (PTSD) diagnosis (current, lifetime, or never) in a large sample of male Vietnam veterans. Predictor variables for a logistic regression equation were drawn from a challenge task involving scenes of combat. The equation was tested and cross-validated demonstrating correct classification of approximately 2/3 of the current and never PTSD participants. Results replicate the finding of heightened psychophysiological responding to trauma-related cues by individuals with current PTSD, as well as differences in a variety of other domains between groups with and without the disorder. Follow-up analyses indicate that veterans with current PTSD who do not react physiologically to the challenge task manifest less reexperiencing symptoms, depression, and guilt. Discussion addresses the value of psychophysiological measures for assessment of PTSD.

Adolescent↗

Liquid chromatography/chemical reaction interface mass spectrometry as an alternative to radioisotopes for quantitative drug metabolism studies.

Chemical reaction interface mass spectrometry (CRIMS) was coupled on-line with HPLC using a Vestec particle beam interface. A helium-assisted nebulizer provided added stability with no loss in accuracy or precision as compared to the thermospray nebulizer at flow rates of up to 1.0 mL/min using isocratic conditions. However, mass spectral response was found to be solvent-dependent for both the helium-assisted and thermospray nebulizers. Postcolumn solvent addition of methanol eliminated solvent-dependent decreases in mass spectral response. This allowed gradient HPLC elutions to be performed. Under these conditions, the flow of solvent into the particle beam interface was 2.5 mL/min, so a conventional thermospray nebulizer had to be used instead of the helium-assisted nebulizer. Experiments were conducted with the antianxiety agent buspirone in order to validate the methodology. Metabolites from in vitro incubations of [15N]/[14C]buspirone with rat liver slices were analyzed by gradient LC/CRIMS and by gradient LC/[14C] radioactivity counting. The response from LC/CRIMS analysis for individual metabolites was then compared with that obtained by LC/[14C] radioactivity counting. An excellent correlation was observed between the two methods for metabolites with quite different HPLC characteristics. Thus, gradient LC/CRIMS in combination with stable isotopes provides an alternative to using radioisotopes for carrying out drug metabolism studies.

Animals↗

Magnetic resonance images of Tolosa-Hunt syndrome before and after steroid therapy.

Tolosa-Hunt syndrome (THS) is characterized by painful ophthalmoplegia due to idiopathic granulomatous inflammation of the cavernous sinus. Steroid therapy dramatically reverses the clinical signs and symptoms of THS. We report a typical case of THS, in which MRI showed a mass lesion in the right cavernous sinus with intermediate signal intensity on T1-weighted images, hypointensity on T2-weighted images and positive gadolinium enhancement. This 24-year-old man had three episodes of painful opthalmoplegia in a period of 9 months. The side of the involved cavernous sinus was different in the first and the second episodes of THS. The symptoms lasted for 1 month and the patient recovered spontaneously from these two episodes. In the third episode, the right pupil was also involved and the light reflex was lost. After steroid therapy, the ocular symptoms improved rapidly within 48 hours and the mass lesion in the right cavernous sinus on MRI was markedly diminished by the 7th day of treatment.

Adult↗

Kinetic monitoring of enzymatic reactions in real time by quantitative high-performance liquid chromatography-mass spectrometry.

The study of enzyme kinetics under steady-state conditions represents a common and very useful method for investigating the mechanisms of enzymatic reactions. We report the use of mass spectrometry (MS) coupled with HPLC for the kinetic analysis of enzymatic reactions in real time. The hydrolysis of dinucleotides with bovine pancreatic ribonuclease A (RNase A) and the substrate-specific hydrolysis of lactose with beta-galactosidase can be monitored using ion-spray (pneumatically assisted electrospray) mass spectrometry as a sensitive and specific detector for the native substrates. The resulting data can be used to calculate both KM and Vmax for each system. Kinetic parameters obtained for RNase A and beta-galactosidase paralleled those obtained by conventional techniques. These findings suggest the possibility of developing alternative techniques, based on mass spectrometric detection, for performing kinetic analyses of enzymatic processes where no simple spectrophotometric assay is feasible. In addition to enabling the determination of kinetic parameters for authentic substrates, and not chromogenic analogs, such assays would also be useful in situations where very high sensitivity and specificity are desired.

Animals↗

Production of aldosterone in isolated rat blood vessels.

Angiotensin I (Ang I), Ang II, angiotensinogen, and renin are formed locally in the vasculature. We undertook this study to determine whether the rat mesenteric artery produces aldosterone and to investigate the effects of adrenalectomy, an angiotensin-converting enzyme inhibitor, Ang II, or potassium on aldosterone production in vascular tissue. Isolated rat mesenteric arteries were perfused with Krebs-Ringer solution for 4 hours. The perfusate was collected and chromatographed in a reversed-phase high-performance liquid chromatographic (HPLC) system. The fraction corresponding to synthetic aldosterone was collected and analyzed by mass spectrometry. The aldosterone concentration in the perfusate from the adrenalectomized rats and rats treated with an angiotensin-converting enzyme inhibitor was measured using radioimmunoassay after HPLC separation. The mass spectra of synthetic aldosterone and aldosterone isolated from the perfusate of rat mesenteric arteries were identical. Aldosterone production in the mesenteric arteries of adrenalectomized rats was increased and of rats treated with an angiotensin-converting enzyme inhibitor was reduced compared with that of controls. Ang II (1.9 x 10(10) mol/L) and potassium (6.0 mmol/L) increased aldosterone production in mesenteric arteries. This study shows that the rat mesenteric artery produces aldosterone and that the intravascular renin-angiotensin-aldosterone system may contribute to vascular tone.

Adrenalectomy↗

Determination of trace impurities of peptides and alkaloids by capillary electrophoresis-ion spray mass spectrometry.

Two different mixtures have been analyzed by CE-UV-MS using selected ion monitoring (SIM) conditions to evaluate whether this technique can detect trace impurities in such mixtures. The first mixture consisted of two bioactive peptide analogues which included Lys-bradykinin (kallidin) and Met-Lys-bradykinin. The presence of 0.1% Lys-bradykinin was detected by SIM CE-MS but not by CE-UV at the 0.1% level as it migrated from the capillary column prior to the major component, Met-Lys-bradykinin. The second mixture consisted of two antibacterial alkaloids, berberine and palmatine. The presence of 0.15% palmatine was detected by CE-UV and SIM CE-MS at the 0.15% level as it migrated from the capillary column following the major component, berberine. These results suggest that SIM CE-MS offers the necessary separation efficiencies and sensitivity to provide a complementary analytical determination of trace components in such sample mixtures.

Alkaloids↗

Synthesis of corticosterone in the vascular wall.

Extra-adrenal steroid 21-hydroxylation and 11 beta-hydroxylation occur in a variety of human tissues. This study was undertaken to determine whether the rat mesenteric artery produces corticosterone and to demonstrate the CYP11B1 mRNA in the vascular tissue. Isolated rat mesenteric arteries were perfused with Krebs-Ringer solution for 4 h. The perfusate was collected and chromatographed in a reverse-phase HPLC system. The fraction corresponding to synthetic corticosterone was collected and analyzed by mass spectrometry. The concentration of corticosterone in the perfusate from the adrenalectomized rats was measured using radioimmunoassay after separation with the HPLC system. The mass spectra of synthetic corticosterone was identical with corticosterone isolated from the perfusate of the rat mesenteric arteries. The radioactive peak of corticosterone was detected in the perfusate after perfusing the mesenteric artery with Krebs-Ringer solution containing [14C]-pregnenolone. The expression of CYP11B1, 11B2, and 11A mRNA was detected in the mesenteric artery using a RT-PCR. The production of corticosterone in the vascular wall was increased in the adrenalectomized rats compared with that of the controls. This study shows that the rat mesenteric artery produces corticosterone, and the corticosterone synthase is existed in the vasculature.

Animals↗

Comparing sample size formulae for trials with unbalanced allocation using the logrank test.

This paper compares the sample size formulae given by Schoenfeld, Freedman, Hsieh and Shuster for unbalanced designs. Freedman's formula predicts the highest power for the logrank test when the sample size ratio of the two groups equals the reciprocal of the hazard ratio. The other three formulae predict highest powers when sample sizes in the two groups are equal. Results of Monte Carlo simulations performed for the power of the logrank test with various sample size ratios show that the power curve of the logrank test is almost flat between a sample size ratio of one and a sample size ratio close to the reciprocal of the hazard ratio. An equal sample-size allocation may not maximize the power of the logrank test. Monte Carlo simulations also show that, under an exponential model, when the sample size ratio is toward the reciprocal of the hazard ratio, Freedman's formula predicts more accurate powers. Schoenfeld's formula, however, seems best for predicting powers with equal sample size.

Clinical Trials as Topic↗

Locations of cerebral infarctions in tuberculous meningitis.

The locations of cerebral infarctions were studied in 14 patients with tuberculous meningitis (TBM) and 173 patients with noninflammatory ischemic stroke (IS). In patients with TBM, 75% of infarctions occurred in the "TB zone" supplied by medial striate and thalamoperforating arteries; only 11% occurred in the "IS zone" supplied by lateral striate, anterior choroidal and thalamogeniculate arteries. In patients with IS, 29% of infarctions occurred in the IS zone, 29% in the subcortical white matter, and 24% in (or involving) the cerebral cortex. Only 11% occurred in the TB zone. Bilaterally symmetrical infarctions of the TB zone were common with TBM (71%) but rare with IS (5%).

Adult↗

Bilateral putaminal necrosis caused by methanol poisoning: a case report.

Bilateral putaminal necrosis is characteristic of methanol poisoning. A 31-year-old male alcoholic had headache, impaired consciousness, neck stiffness, roving eyes with dilated unreactive pupils, papilloedema, abdominal pain, vomiting, and severe metabolic acidosis after a binge. Abnormalities of the cerebrospinal fluid included an initial pressure of 240 mmH2 O, RBC 286/mm3, WBC 8/mm3, and protein 179 mg/dl. Peritoneal dialysis was performed on the 2nd day after drinking. A blood test for methanol was not performed until the 5th day, and its results was negative. However, computed tomography (CT) on the 3rd day showed necrosis and hemorrhage of bilateral putamina and the cerebral cortex, and post-contrast enhancement of meninges. On the 22nd day, a CT revealed further changes: necrosis of bilateral subcortical white matter, and post-contrast gyral enhancement at the otherwise normal-looking areas of the cerebral cortex. We suggest that, in certain situations, the characteristic CT findings are helpful in the diagnosis of methanol poisoning.

Adult↗

Persistent interictal aphasia after repeated partial seizures: a case report.

We reported a case of persistent interictal aphasia after repeated partial seizures. This 64-year-old man, left-handed and literate, developed repeated right facial twitching associated with head turning to the right or transient loss of awareness since October 30 1991. Persistent aphasia between seizures occurred from November 4. An electroencephalogram (EEG) on November 6 showed an epileptic focus over the left frontal area. Tc-99m HMPAO brain single photon emission computed tomography (SPECT) performed one and half and hour after an attack on November 7 showed focal hyperperfusion over the left frontal area. The aphasia recovered on November 7 after the seizures had been stopped. Follow-up EEG and Tc-99m HMPAO brain SPECT done on November 11 and November 14 respectively were normal.

Aphasia↗

Optic nerve head and nerve fiber layer in Alzheimer's disease.

We compared (1) the differences in the retinal nerve fiber layer between 26 patients with Alzheimer's disease and 30 age- and race-matched normal controls with use of blue-light high-resolution photography, (2) the differences in disc pallor between 30 patients with Alzheimer's disease and 32 controls with use of a boundary-tracking program and fundus photographs, and (3) the topographic disc variables between 26 patients with Alzheimer's disease and 36 controls with use of an optic nerve head analyzer. A higher proportion of patients with Alzheimer's disease had detectable nerve fiber damage as seen by red-free photography compared with controls. Although the pallor area-to-disc area ratio was not significantly different between patients with Alzheimer's disease and controls, the patients with higher pallor area-to-disc area ratios had higher Alzheimer's Disease Assessment Scale (ADAS) scores and longer durations of disease. Patients had an increased cup-to-disc ratio and cup volume and decreased disc rim area compared with controls. These variables also correlated significantly with ADAS scores and the duration of disease. The correlation among the optic nerve head changes and the ADAS scores in patients with Alzheimer's disease suggests a potential role for optic nerve head analysis in monitoring the progression of Alzheimer's disease and in assessing the effectiveness of any treatments developed.

Aged↗

Atypical presentations of tuberculous meningitis--a case report.

A case of tuberculous meningitis, proved by cerebrospinal fluid (CSF) cultures, is reported due to atypical findings in CSF. This 19-year-old man developed subacute headache and fever for 2 weeks, followed by focal seizure and left hemiparesis. Initial CSF study showed hemorrhagic lymphocytic pleocytosis with mildly elevated protein and normal sugar content, mimicking viral or postinfectious meningoencephalitis. Follow-up CSF studies showed polymorphonuclear pleocytosis. A concomitant bacterial meningoencephalitis was suspected, though repeated CSF cultures did not isolate any bacteria. The activity of adenosine deaminase in CSF was 12 U/L, highly suggestive of tuberculous meningitis. Magnetic resonance imaging (MRI) showed only a focal meningoencephalitis in the right lateral frontal cortex. Due to progressive deterioration of the clinical status, umbrella therapy, including antimycobacterial drugs and strong antibiotics were given. At a later time, growth of tubercle bacilli was reported in the CSF cultures. Follow-up study of MRI 4 months later, showed thick abnormal enhancement in the basal cisterns and obstructive hydrocephalus, typical findings of chronic basal meningitis.

Adenosine Deaminase↗