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Biomedical subjects

E Kwan

Publications and source records attributed to E Kwan.

At least 55 records · Page 3Linked to original sources

Pharmacokinetics of diphenhydramine after dose ranging in nonpregnant ewes.

Studies were conducted to characterize the pharmacokinetics of diphenhydramine in nonpregnant ewes after iv administration of 25-, 50-, 100-, and 200-mg doses of diphenhydramine hydrochloride on a crossover basis. Plasma drug concentration versus time data exhibited multiexponential characteristics. The initial distribution half-life increased from 5 to 9 min and the elimination half-life from 34 to 68 min as the dose was increased. There was also an increase in the volume of distribution (from 3 to 6 L/kg) with increasing dose. The elimination half-life and the volume of distribution after a 200-mg dose were significantly greater than after a 25-mg dose. There was, however, a linear increase in AUC0 infinity as dose was increased. The average total body clearance (approximately 5 L/h/kg) remained unchanged regardless of dose. The free fraction of diphenhydramine determined by equilibrium dialysis averaged 0.229 +/- 0.080, and the extent of drug binding to plasma protein was independent of the drug concentrations encountered (30-780 ng/mL) in the nonpregnant sheep in vivo. Concentration-independent binding of the drug was also confirmed by in vitro binding studies over the drug concentration range 10-2000 ng/mL. Therefore, it appears that changes in the volume of distribution are likely to be a result of changes in tissue uptake or binding of the drug as a function of dose.

Animals↗

Chinese-white differences in the distribution of occlusive cerebrovascular disease.

The distribution of cerebrovascular lesions is affected by race. Blacks and Japanese have more intracranial occlusive cerebrovascular disease, while whites have more extracranial disease. Despite a high incidence of stroke in China, there are few formal studies of the distribution of vascular occlusive disease in Chinese populations. We compared clinical and angiographic features of 24 white and 24 Chinese patients with symptomatic occlusive cerebrovascular disease. In symptomatic vascular territories, whites had more severe (greater than or equal to 50% stenosis) extracranial lesions, while Chinese had more severe intracranial lesions. When we counted mild and severe lesions in a symptomatic territory, whites had more extracranial lesions while Chinese had more intracranial lesions. When we combined symptomatic and asymptomatic territories, whites had more extracranial lesions, while Chinese had more intracranial lesions. White patients reported more transient ischemic attacks. The distribution of lesions, however, was not explained by differences in incidence of transient ischemia, hypertension, diabetes, hypercholesterolemia, or ischemic heart disease between the groups. The preponderance of intracranial vascular lesions in Chinese patients is similar to that seen in blacks and Japanese. Racial differences in the occurrence of extracranial and intracranial lesions raise the possibility of a different underlying pathophysiology for the 2 locations.

Aged↗

Interventional neuroradiology in neuro-ophthalmology.

Endovascular neuroradiologic procedure is the treatment of choice for patients with symptomatic direct carotid cavernous fistulae (CCF) and dural arteriovenous fistulae (DAVF) that failed manual carotid artery/jugular vein compression. Preservation of visual function and the prevention of catastrophic intracranial hemorrhage are the prime therapeutic objectives. The choice of transarterial versus transvenous approach is dictated by the pathophysiology, pattern of venous drainage, and the risk/benefit ratio in each patient. In 180 patients with CCF, 95% have been cured with a combination of manual compression, transarterial or transvenous embolization, while 3% have significant complication. In patients with DAVF, transarterial and transvenous embolization has resulted in clinical cure in 77 and 90%, respectively; the complication rate is between 4-5%. Intra-aneurysmal embolization with silicone detachable balloons in its present stage of development is an acceptable alternative for patients with intracranial aneurysms not otherwise amenable to standard neurosurgical clipping. In aneurysms with a well-defined neck, aneurysm thrombosis with preservation of flow in the parent vessel has been accomplished in 90% of the patients treated. The complication rate in patients presenting with mass effect and subarachnoid hemmorrhage is 5 and 14%, respectively.

Adult↗

Effects of diphenhydramine in the fetal lamb after maternal or fetal administration.

The effects of diphenhydramine on fetal behavioral states, breathing activity, blood gas status, arterial pressure and heart rate have been investigated in the fetal lamb after maternal or fetal drug administration to steady state in chronically instrumented pregnant sheep. During maternal drug infusion there were declines in the percentage of low voltage electrocorticographic (ECoG) pattern 55-46%), the percentage of low voltage ECoG activity containing rapid eye movements (80-55%), the overall incidence of fetal breathing (42-21%) and in the amount of breathing during low voltage ECoG activity (67-36%). These sedative like effects occurred at fetal plasma drug concentrations (approximately 36 ng/ml) lower than those resulting in discernable central nervous system effects in adults. Drug infusion to fetus achieved higher fetal plasma drug levels (approximately 448 ng/ml) and resulted in a transient decline in arterial Po2 and pH, associated with transient tachycardia and vigorous breathing movements during the initial portion of the infusion. There was also a significant fall in the amount of low voltage ECoG pattern (51-26%) and marked increases in the amount of intermediate voltage pattern (8-46%), and an increase in the occurrence of rapid eye movements during this intermediate voltage pattern (8-63%). In summary, diphenhydramine elicits significant effects in the fetal lamb, the precise nature of which varies with drug concentration.

Animals↗

The efficacy of tilted axial MRI of the CNS.

The angle between the straight axial plane and the orbito-meatal line was measured in 156 consecutive magnetic resonance examinations. Inconsistent head positioning caused this angle to vary by as much as 44 degrees. Careful positioning of the patient by the technologist can minimize this variability, leading potentially to improved image interpretation. To assess the merit of a standardized orientation for MR examinations of the head, straight axial and tilted axial MR scans were compared in 34 patients. The tilted images were obtained parallel to the orbitomeatal line and were found to be superior for visualization of the cerebellum. When correlative x-ray CTs are available or when an abnormality in the posterior fossa is suspected, tilted axial MR scans should be employed.

Brain Diseases↗

Purine nucleoside phosphorylase synthesis and turnover in human lymphoid cells.

We have studied the turnover and synthesis of purine nucleoside phosphorylase by using a polyclonal rabbit antiserum to this protein. The turnover of purine nucleoside phosphorylase was studied in the B lymphoblast cell, WI-L2, by specific immunoprecipitation of [3H]leucine-labeled proteins. The half-lives for total protein and purine nucleoside phosphorylase were 14.5 and 14.1 hr, respectively. For cells cultured in the presence of inosine the half-life of purine nucleoside phosphorylase was reduced to 11.2 hr. The synthesis of purine nucleoside phosphorylase was analyzed during phytohemagglutinin-stimulated T cell transformation by pulse labeling cells with [35S]methionine. Purine nucleoside phosphorylase synthesis increased greater than 10-fold during the first 12 hr of transformation and continued to a maximum of 30-fold. The relative rate of purine nucleoside phosphorylase labeled to total proteins was 0.04% in unstimulated T cells and increased to 0.18% 12 hr after stimulation. These studies identify some preferential synthesis of purine nucleoside phosphorylase during the early stages of T cell transformation.

B-Lymphocytes↗

DSA evaluation of the STA-MCA bypass.

Continuing improvements in intravenous DSA techniques have now shown it to be useful in the angiographic evaluation of STA-MCA bypass function. Both patent and non-patent bypasses were observed in this study. Diagnostically adequate spatial resolution and signal to noise ratio were achieved by electronic magnification and integration techniques. Patient positioning was important and the projection which gave optimal visualization of the STA-MCA bypass, free of vessel overlap, was a 40 degrees oblique, 20 degrees craniocaudal view on the side of interest. Intravenous DSA can complement, and in some cases may supplant, conventional arteriography in the radiologic evaluation of STA-MCA bypass surgery.

Cerebral Angiography↗

Specific CT findings in Krabbe disease.

Specific computed tomography (CT) findings in four patients with biochemically proven Krabbe disease included symmetric increased attenuation in the cerebellum, brainstem, thalami, caudate nuclei, and corona radiata before and in conjunction with decreased attenuation of white matter followed by atrophy at a later stage. Familiarity with the CT findings in the acute phase of Krabbe disease may assist clinicians in limiting the differential diagnosis and requesting appropriate laboratory tests.

Brain↗

T cell-derived glucosteroid response-modifying factor (GRMFT): a unique lymphokine made by normal T lymphocytes and a T cell hybridoma.

Mouse spleen cells and a murine T cell hybridoma, FS6 14.13.1, produce a glucosteroid response-modifying factor (GRMFT) after stimulation with concanavalin A. GRMFT blocks glucosteroid suppression of helper T cell function and the growth of granulocyte/macrophage progenitor cells in vitro. IL 1 also protects helper T cells and myeloid precursors from glucosteroid suppression. This suggests that GRMFT and IL 1 act congruently to ensure that an effective immune response is generated when endogenous glucosteroid levels are elevated. To understand the role of GRMFT in normal immune responses and in disease states characterized by imbalances in the immune system, we began to purify and characterize GRMFT. GRMFT appears to be distinct from other well-characterized T cell-derived factors. GRMFT is larger than IL 2 as determined by gel exclusion chromatography and is completely separated from IL 2 by isoelectric focusing. Furthermore, purified IL 2 does not have GRMFT activity. Purified IL 3 also lacks GRMFT activity, and conditions that inactivate immune interferon have no effect on GRMFT. Thus, GRMFT is different from IL 2, IL 3, and immune interferon. GRMFT also lacks activity in the thymocyte co-mitogenic assay and is therefore different from IL 1. Finally, FS6 14.13.1 reportedly does not produce TRF or CSF, which suggests that GRMFT is different from these molecules as well.

Animals↗

Reliability of a drug history questionnaire (DHQ).

Drug abusers' self-reports are vital to clinical and research endeavors, yet few studies have explicitly examined the test-retest reliability of drug abusers' reports of their pretreatment drug use. The present study evaluated the test-retest reliability of drug abusers' reports of (a) lifetime drug use using a drug history questionnaire (DHQ), and (b) demographic and drug-related events. Intraclass and Pearson correlation coefficients revealed reasonably good reliability for most reports of drug use and related events. Further research needs in this area are discussed.

Adolescent↗

A unique BRCA1 mutation identified in Mongolia.

This is a case report of genetic assessment conducted on a family residing in the third world where two sisters have presented with early onset ovarian cancer. Protein truncation testing and DNA sequencing identified a unique mutation on exon 11 (3452delA) of the BRCA1 gene. Buccal swab testing of three siblings and three offspring showed that half of the family members carried the same mutation. Currently, genetic testing in third-world countries is conducted within research budgets, as testing is not affordable or locally available for such high-risk families. Unique mutations in the BRCA1 gene that are expressed in geographically isolated groups will be useful in genetic counseling and preventative maneuvers. The only preventive management strategy available in the third world is prophylactic surgery.

Adenocarcinoma↗

Thrombus in vertebrobasilar dolichoectatic artery treated with intravenous urokinase.

BACKGROUND: Vertebrobasilar dolichoectasia is often found in patients with posterior circulation ischemia. Brain ischemia is caused by abnormal flow in the dilated artery and obstruction of paramedian arteries or intraluminal thrombus with artery-to-artery embolism. We report a patient with vertebrobasilar dolichoectasia and luminal thrombus treated with intravenous urokinase who did well but died 2 months later of subarachnoid hemorrhage. CASE DESCRIPTION: A 60-year-old man developed right-hand clumsiness, dysarthria and ataxia. Computed tomography showed vertebrobasilar dolichoectasia and thrombus in the basilar artery. Symptoms quickly resolved on heparin but recurred on warfarin and again resolved on heparin. Two weeks later, while on warfarin and aspirin 325 mg, he developed hand numbness, oscillopsia and ataxia. Symptoms again resolved on heparin. Angiography showed severe dolichoectasia of the distal right vertebral artery and basilar artery. A large mural thrombus was detected in the ventral part of the distal basilar artery narrowing the lumen by 50%. He was treated with intravenous urokinase 4,400 units/kg as a bolus followed by 4,400 units/kg/h for 12 h. Repeat angiography showed almost complete recanalization and improved filling of basilar artery branches. He was maintained on warfarin and aspirin 81 mg and had no further ischemic episodes. He died 2 months later of rupture of the basilar artery and subarachnoid hemorrhage. CONCLUSION: Some patients with thrombosis of vertebrobasilar dolichoectactic arteries continue to have ischemic symptoms despite adequate anticoagulation. Intravenous thrombolysis may be effective in reducing the risk of stroke, but the risk/benefit ratio needs to be assessed in each patient.

Arteriovenous Malformations↗

A partial transient effect of short-term growth hormone (GH) treatment in short non-GH deficient prepubertal children.

This study reports the growth of 11 short non-GH deficient children before, during short-term GH therapy for 1 year and for 2 years after the cessation of treatment. The mean growth velocity increased significantly (p < 0.0001) from the pretreatment mean of 4.6 (SD = 0.95) cm/year to 8.4 (SD = 1.1) cm/year after 1 year of GH treatment without accelerated advancement of skeletal maturation. The serum IGF-1 levels also increased significantly with treatment. In nine children who remained prepubertal followed for one year after GH treatment, the mean growth velocity increased from 4.5 (SD = 0.69) cm/year before treatment to 8.7 (SD = 1.28) cm/year after 1 year of GH treatment (p < 0.0001). After stopping GH treatment, the growth velocity decreased significantly (p < 0.001) to 2.4 (SD = 0.68) cm/year during the first year of follow-up. In the six prepubertal children followed up for 2 years after treatment, the mean growth velocity was 4.1 (SD = 1.04) cm/year which was not significantly different from the pretreatment growth velocity. The significant decrease in growth velocity during the first post-treatment year could not be explained by the usual fall of growth velocity with increasing age in prepubertal children. Our results indicate that the effect of one year of GH treatment on height gain is partly transient and cast doubt on the efficacy of short-term GH therapy in short non-GH deficient patients.

Age Determination by Skeleton↗