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Biomedical subjects

D W Jones

Publications and source records attributed to D W Jones.

At least 91 records · Page 5Linked to original sources

An improved method for rapid and efficient radioiodination of iodine-123-IQNB.

UNLABELLED: The SPECT radioligand, 3-quinuclidinyl-4-[123I]iodobenzilate ([123I]IQNB), binds to muscarinic receptors and has generated interest as a potential agent for clinical SPECT. Unfortunately, cumbersome and inefficient radioiodination procedures have limited the practicality of [123I]IQNB SPECT imaging. METHODS: We report a rapid (5 min) and simple radioiodination procedure for preparing [123I]IQNB from a tri-n-butylstannyl precursor in a no-carrier-added reaction that yields high specific activity with radiochemical yield exceeding 60%. The radiochemical purity of the final product exceeds 95%. RESULTS: We have used this procedure to radioiodinate the four stereoisomers of [123I]IQNB. The procedure is highly reliable and reproducible. SPECT studies on a healthy human volunteer at 1, 2, 6 and 24 hr after injection of each of the four stereoisomers reveal expected differences in the kinetic and binding characteristics of the four stereoisomers. (R,S)-[123I]IQNB appears to be the SPECT agent of choice. CONCLUSION: Radioiodination of [123I]IQNB from our tri-n-butylstannyl precursor is simpler, more efficient and less expensive than previous techniques. The potential exists for a "kit" which would be practical in a typical clinical setting.

Adult↗

Differential cholinergic regulation in Alzheimer's patients compared to controls following chronic blockade with scopolamine: a SPECT study.

The effects of low-dose chronic scopolamine on measures of cerebral perfusion and muscarinic receptors were tested in eight Alzheimer's disease (AD) subjects and eight elderly controls. Single photon emission computed tomography (SPECT) scans using technetium-labelled hexamethypropylene amine oxide (99mTc-HMPAO) to measure cerebral perfusion before and after chronic scopolamine revealed a significant 12% increase in the normal controls (P < 0.01) while the AD subjects showed no significant change. In contrast, the controls showed decreased muscarinic binding as evidenced by 123I-quinuclidinyl-4-iodobenzilate (123I-QNB) labelling after chronic drug (-10%, P < 0.01) whereas the AD subjects showed increased 123I-QNB labelling (+8%, P < 0.05). The difference between AD and control subjects was even more marked when the ratio of I-QNB to HMPAO uptake was compared, pointing to a double dissociation in the SPECT results. These data cannot be explained by group differences in cerebral perfusion alone and suggest a differential sensitivity between AD and elderly controls to chronic cholinergic blockade.

Aged↗

Hypertension in East Asia.

Asians comprise the largest single ethnic group in the world and the fastest growing minority ethnic group within the United States. The prevalence of hypertension in most Asian groups is similar to that of non-Asians. The associations with hypertension are similar to those seen in Western populations. Body mass index is a surprisingly strong predictor of blood pressure, even in very lean Asian populations. Studies in Asian groups suggest that the prevalence of target organ disease as related to hypertension are dependent on other cardiovascular disease risk factors. Stroke is more common than heart disease in Asia. Hypertension treatment data in East Asia is sparse, and treatment methods vary widely. Hypertension control among the world's largest ethnic group remains a challenge.

Asia, Eastern↗

Normal asymmetry of the planum temporale in patients with schizophrenia. Three-dimensional cortical morphometry with MRI.

BACKGROUND: Abnormal cerebral anatomical lateralisation has been reported in schizophrenia and may implicate anomalous neurodevelopment in the aetiology of this disease. A popular recent hypothesis has predicted that such disturbances in normal lateralisation should be especially apparent in the morphology of the temporal lobes. METHOD: A temporal cortical region lying in the plane of the Sylvian fissure--known as the planum temporale--exhibits pronounced leftward asymmetry in normal right-handed males. We compared lateralisation of the planum temporale in schizophrenic and control males using MRI surface-rendering morphometry of the supratemporal cortex. RESULTS: Contrary to the lateralisation hypothesis, normal patterns of leftward planum asymmetry were detected in both the schizophrenic and control groups. Schizophrenics and controls also exhibited a predicted symmetry in the bilateral areas of Heschl's gyrus, a supratemporal cortical structure immediately anterior to the planum. CONCLUSION: These data do not support the notion that neurodevelopmental mechanisms of cerebral asymmetry are abnormal in schizophrenia.

Adult↗

Lateralized differences in iodine-123-IBZM uptake in the basal ganglia in asymmetric Parkinson's disease.

UNLABELLED: We used equilibrium analysis of SPECT data from patients with asymmetric Parkinson's disease to determine if lateralized differences in the striatal uptake of [123I]IBZM correlate with asymmetry in clinical findings and, by inference, with lateralized differences in the concentration of extracellular dopamine. METHODS: Twelve patients with asymmetric clinical signs of idiopathic Parkinson's disease were injected with a bolus of [123I]IBZM, and multiple SPECT scans recorded the time course of radioligand uptake. The time integral method was used to estimate peak specific binding, so that a ratio of specific-to-nonspecific binding in the left and right striatum of each subject at equilibrium could be determined. Nine patients also had 99mTc-HMPAO SPECT scans which were examined for evidence of blood flow asymmetries. RESULTS: Paired t-tests comparing [123I]IBZM uptake revealed significantly greater (mean = 7.3%) availability of dopamine-D2 receptors in the basal ganglia contralateral to maximal clinical signs. Differences in receptor availability correlated significantly with differences in every measure of the clinical assessment. No significant differences in regional cerebral blood flow between the two sides were observed with 99mTc-HMPAO. CONCLUSION: These results demonstrate the ability of [123I]IBZM SPECT to reveal clinically meaningful variations in striatal dopamine receptor availability in patients with asymmetric Parkinson's disease. The equilibrium analysis technique used to determine these findings is a simple and robust method of measuring relative receptor availability and may be useful in studying other illnesses where dysfunction of dopaminergic neurotransmission is suspected.

Adult↗

Bioavailability of digoxin tablets in healthy volunteers.

The bioavailability of digoxin generic tablets manufactured in Korea (formulations A & B) were compared to a standard (formulation C; Lanoxin brand digoxin, Burroughs Wellcome, USA) in 12 healthy Korean male volunteers (mean age 31.4 years) in a single dose, randomized, complete block crossover study. Using a Latin square design, each of the subjects was randomized to the order number and allocated to each of the three treatments of 0.5 mg oral digoxin. Digoxin concentrations in serum and urine samples collected for 48 hours after dosing were measured by fluorescence polarization immunoassay and radioimmunoassay, respectively. Treatments were compared by using nonlinear least squares regression analysis to evaluate the following pharmacokinetic parameters: maximum serum concentration (Cmax); time of maximum serum concentration (Tmax); area under the serum concentration-time curve for 0-12 hours (AUC0-12); and cummulative urinary excretion for 0-48 hours (CUE0-48). Mean AUC0-12, Cmax, and CUE0-48 values for formulations B and C were significantly different from formulation A (p < 0.001), but not significantly different from each other. Based on AUC0-12 and CUE0-48, respectively, the relative availability of formulation B was 87.5% and 89.6% and the relative availability of formulation A was 43% and 35% when compared to formulation C (the standard).

Adult↗

Arthrogenic quadriceps inhibition and rehabilitation of patients with extensive traumatic knee injuries.

1. The relationship between joint damage, quadriceps weakness and arthrogenic muscle inhibition was investigated in eight patients who had sustained extensive traumatic knee injury. Isometric and isokinetic quadriceps and hamstring voluntary strength, and quadriceps arthrogenic muscle inhibition during isometric contractions, were measured before and after 4 weeks (approximately 100 h) of intensive rehabilitation. 2. Compared with the uninjured leg, before rehabilitation the injured leg had larger amounts of quadriceps arthrogenic muscle inhibition (P < 0.025), quadriceps (P < 0.0001) and hamstring (P < 0.0001) weakness and severe functional joint instability. There was a negative correlation between the amount of arthrogenic muscle inhibition and quadriceps voluntary contraction force (P < 0.025). 3. After rehabilitation in the injured leg there were small hamstring strength increases (P < 0.05-0.025), but no overall significant quadricep strength increase. Arthrogenic muscle inhibition was statistically unchanged. Severe functional joint instability was still reported by all patients. 4. Previous studies have shown that minimal joint damage evokes relatively less arthrogenic muscle inhibition that does not impede rehabilitation. These data indicate that greater joint damage is associated with greater arthrogenic muscle inhibition, quadriceps weakness and joint instability. Furthermore, intensive rehabilitation had little affect on either quadriceps arthrogenic muscle inhibition or atrophy.

Adult↗

Body mass index and blood pressure in Korean men and women: the Korean National Blood Pressure Survey.

AIMS AND METHODS: The association between body mass index (BMI) and blood pressure is well known in relatively obese populations. The purpose of the present study was to investigate the relationship between BMI and blood pressure in a lean population. Through cluster sampling, individuals aged > 30 years in 190 out of 154,082 districts were selected for study. Among 25,567 eligible individuals, measurements of blood pressure and BMI were made in 22,354. RESULTS: The BMI for males was 22.8 +/- 2.7 kg/m2 and for females was 23.4 +/- 3.2 kg/m2 (means +/- SD). Over a BMI range from 16 to 31 kg/m2 the relationships between BMI and systolic and diastolic blood pressure were almost linear. Over the BMI range 25-31 kg/m2 (overweight-to-obese) each BMI unit was associated with a difference of 1.0 mmHg in diastolic blood pressure. Over the BMI range 16-25 kg/m2 (normal-to-lean) each BMI unit was associated with a difference of 0.89 mmHg in diastolic blood pressure. CONCLUSION: We conclude that a strong association between BMI and blood pressure exists for lean as well as for obese subjects.

Adult↗

Mercury vapour suppression by various liquid media.

Fresh and used photographic fixer, Merconvap and water were evaluated for their ability to suppress the vapourization of mercury. Mercury vapour concentration above the four test storage liquids was measured at various times between 10 min and 335 days, using a mercury vapour measuring instrument. The data were analysed using a Student-Newman-Keuls multiple comparison test (P = 0.05). The results showed that fresh and used fixer and Merconvap suppressed the vapourization of mercury to below the detection limit of the measuring instrument (0.01 mg/m3). Water was much less effective compared with the other liquids and showed an increase in mercury vapour concentration with log t.

Copper↗

Theophylline disposition in Korean patients with congestive heart failure.

OBJECTIVE: This study proposed to determine the systemic disposition of theophylline in Korean adult patients during decompensated congestive heart failure compared with disposition after recovery. DESIGN: An experimental, prospective, self-controlled, nonrandomized design was used. SETTING: The study was performed in a general community hospital located in Pusan, Korea. PATIENTS: Eight nonsmoking elderly Korean patients with decompensated congestive heart failure presenting to the emergency department were included in the study. Consecutive patients who met entrance criteria were selected. All patients completed the study. INTERVENTIONS: A single dose of aminophylline 6 mg/kg was administered by intravenous infusion over 30 minutes. Standard methods of congestive heart failure therapy were used in each patient, including bed rest, restriction of sodium, and drug therapy including digoxin. After compensation of congestive heart failure was achieved, the theophylline infusion was repeated. OUTCOME MEASURES: Serum theophylline concentrations were measured at 2, 6, 12, and 18 hours after completion of the dose at baseline and following treatment. RESULTS: A clinically and statistically significant improvement in mean theophylline total body clearance was demonstrated following treatment (from 21.7 +/- 2.8 to 43.4 +/- 4.7 mL/kg/h [mean +/- SEM]; p < 0.01). Comparison of these results with a computer model based on literature averages of peoples of all nationalities showed significant underprediction of theophylline clearance both before (p < 0.05) and after (p < 0.01) treatment. The theophylline elimination half-life prior to treatment was 18.2 +/- 2.2 hours and decreased to 9.1 +/- 0.8 hours following treatment (p < 0.01). There was no statistical difference between the computer-model predicted initial theophylline half-life and the measured value, but the model significantly underpredicted the improvement following treatment. CONCLUSIONS: The improvement in theophylline clearance demonstrated in this study appears to be greater than that reported for Western patients. This has practical application to the calculation of appropriate theophylline maintenance dosage regimens in Korean patients with cardiac failure. These data support the need for consideration of racial differences in individualizing dosage regimens. We suggest that all kinetic models, whether software supported or not, should consider incorporating ethnic origin as a demographic factor that helps select the proper model for individual patients.

Aged↗

Lack of effect of hydrocholorthiazide on total cholesterol.

To determine the effect of hydrochlorothiazide on total cholesterol, baseline total cholesterol and blood pressure were determined in 618 hypertensive subjects in a hypertension clinic in Pusan, Korea. After 12-24 months (mean follow-up time 14 months), total cholesterol and blood pressure measurements were repeated. In the group whose therapy included hydrochlorothiazide (n = 436), total cholesterol fell by 8 +/- 39 mg/dL. Those not treated with a diuretic (n = 182) had an identical fall in total cholesterol of 8 +/- 42 mg/dL (P < 0.001 for change from baseline). Patients with a baseline total cholesterol > 200 mg/dL were asked to reduce intake of saturated fat. Change in total cholesterol for 180 patients on this diet and hydrochlorothiazide was -24 +/- 31 mg/dL (P < 0.0001); for 71 patients on the diet and non-diuretic therapy, change was -22 +/- 35 mg/dL (P < 0.0001). There was no change in total cholesterol in either drug group for those with a baseline value < or = 200 mg/dL. It is concluded that in this group of Korean patients on a relatively low-fat diet, a low dose of hydrochlorothiazide had no adverse effect on total cholesterol at 14 months, and hydrochlorothiazide nor other agents prevented a beneficial effect of further reduction of saturated fat on total cholesterol.

Adult↗

Sylvian fissure asymmetries in monozygotic twins: a test of laterality in schizophrenia.

To address prior reports that schizophrenia is associated with loss of normal brain asymmetry and that it might be linked to a defect of a gene controlling cerebral lateralization, we measured on three-dimensional cortical renderings from magnetic resonance imaging (MRI) scans the lengths and angles of the sylvian fissures in 10 normal monozygotic (MZ) twin pairs (n = 10 pairs) and in 10 MZ pairs discordant for schizophrenia (n = 10 pairs). We confirmed in both sets of twins the expected normal asymmetries of length and angle of the sylvian fissure. We also confirmed that the length asymmetry occurs solely in the region of the planum temporale. In the discordant twins, affected and unaffected twins did not differ in asymmetry measures, thus failing to support an association between illness per se and diminished asymmetry. Moreover, the discordant twins as a group did not differ from the normal twins as a group, thus failing to confirm the hypothesis of a genetic association with abnormal asymmetry. The implications of variations in methodology and patient samples are discussed.

Adult↗

Effects of doxazosin and hydrochlorothiazide on lipid levels in Korean patients with essential hypertension.

Because none of the major studies used to document adverse or beneficial metabolic effects of antihypertensive drugs were made of non-Western patients with a non-Western diet, we compared doxazosin and hydrochlorothiazide in Korean patients receiving a Korean diet to determine if one regimen is superior to the other in terms of efficacy, adverse metabolic effects, or both. The randomized, double-blind, parallel study of Korean hypertensive patients compared the effects of oral doxazosin (mean +/- SD dose, 10.3 +/- 6.3 mg/day) and oral hydrochlorothiazide (44.0 + 11.0 mg/day) on blood pressure (BP) and lipid metabolism. The results of 48 patients treated for 20 weeks are reported here. Systolic (p < 0.001) and diastolic (p < 0.001) BP (SBP, DBP) were significantly lower in both groups at the end of the treatment period. Doxazosin significantly increased high-density-lipoprotein (HDL) cholesterol from a baseline of 1.10 +/- 0.31 to 1.27 +/- 0.30 mM (p < 0.05) and HDL/total cholesterol from 0.25 +/- 0.1 to 0.28 +/- 0.1 mM (p < 0.01). Hydrochlorothiazide significantly increased triglyceride from a baseline of 1.63 +/- 0.71 to 2.02 +/- 0.87 mM (p < 0.05). In contrast to Western studies, hydrochlorothiazide demonstrated no adverse effect on total, low-density-lipoprotein (LDL), or HDL cholesterol, or on HDL/total cholesterol. Indeed, HDL cholesterol was increased by 0.16 mM (p < 0.01). As in Western patients, doxazosin is effective for treatment of essential hypertension in Koreans and has no adverse effects but some beneficial effects on lipids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Measurement of brain activity with bolus administration of contrast agent and gradient-echo MR imaging.

This study was performed to measure changes in cerebral blood volume (CBV) associated with visual activation by use of bolus administration of contrast agent and conventional, clinically configured magnetic resonance (MR) hardware and software. Fast gradient-recalled acquisition in the steady state technique was used to study five healthy subjects during visual activation and a control dark state. MR images were obtained every 2.048 seconds for 2 minutes. A bolus of gadopentetate dimeglumine was injected during visual stimulation and darkness. Cine images produced from the series of rapid images clearly depicted arterial, capillary, and venous phases. Analysis of serial concentration maps derived from the rapid images revealed expected differences between the relative CBV of gray matter and that of white matter, as well as significantly increased relative CBV in calcarine cortex during visual activation versus the control state (mean increase, 15.24%; range, 6.41%-27.78%; P < .05). These results confirm those reported in echo-planar imaging studies and demonstrate that brain function can be assessed with the bolus method by means of MR imaging hardware and software with conventional clinical configurations.

Blood Volume↗