Impaired polymorphonuclear leukocyte function in chronically hemodialyzed patients with iron overload.
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Biomedical subjects
Publications and source records attributed to D J Kim.
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This study evaluated oral ingestion as the route of fluorescein administration for fluorescence assessment of skin perfusion. In 10 anesthetized rats, dorsal pedicle flaps were raised to produce graded perfusion; then fluorescein (7.5 mg/kg) was administered via an oropharyngeal tube. Quantification of skin fluorescence, performed with the fiberoptic fluorometer 45 minutes after dye ingestion, delineated a significant difference between the perfusion of flap regions that remained viable and those that subsequently became dystrophic (p less than 0.05). The precision was equivalent to that previously reported after intravenous dye. In addition, the gradual delivery of dye after oral administration permitted monitoring of slope of uptake and time to peak. Each of these pharmacokinetic parameters delineated a significant difference between viable and nonviable sections. As measures of relative change in fluorescence, they are independent of skin color and thickness. This feature suggests that the oral route actually may improve the accuracy and reliability of the fluorescein test.
Optimal anticancer treatment with cell cycle-specific antimetabolites requires maintenance of a cytotoxic drug level for a prolonged period of time. We explored the use of multivesicular liposomes as a slow-release depot of 1-beta-D-arabinofuranosylcytosine for intrathecal administration. The intrathecal half-life of the liposome-encapsulated drug was 148 h, in contrast to the half-life of 2.7 h for the unencapsulated free drug, in a Sprague-Dawley rat model. The prolonged maintenance of a therapeutic drug level may increase efficacy, and the elimination of the very high peak level may decrease toxicity.
The chemical-shift effect often degrades slice selectivity thereby degrading the contrast and spatial resolutions in a high-field NMR imaging. We propose a new pulse sequence which can compensate for this chemical-shift effect during slice selection. This technique provides correct slice definition as well as clear separation between water and lipid protons in high-field proton NMR imaging. Particular applications of this technique are 2D imaging with a thin-slice selection and chunk 3D imaging, where correction of the chemical-shift effect in slice selection is important. Another interesting application of the technique is chemical-shift-selective (CHESS) imaging. This technique does not require spectral-selective rf pulses and it takes advantage of the chemical-shift effect during slice selection. The latter is found to be useful for human in vivo chemical-shift imaging in high-field NMR. In this paper, the theoretical derivation of the proposed gradient reversal technique, its applications, and related experimental results are presented.
Liposomes containing cytosine arabinoside (ara-C) release drug slowly and can be used to maintain a locally high concentration of ara-C in the peritoneal cavity for intracavitary chemotherapy. However, a significant amount of active drug does reach the systemic circulation and contributes to systemic toxicity. We have devised a novel method of decreasing toxicity and increasing intraperitoneal half-life by pretreatment with "blank" liposomes containing no active drug. This technique has resulted in prolongation of intraperitoneal half-life of the liposomal ara-C from 21 h to 165 h, enabling maintenance of a therapeutic drug concentration even at 11 days after initial injection. One hundred percent cures (60-day survival) were achieved with a single-dose therapy begun 1 day after i.p. implantation of 10(6) L1210 leukemia cells.
The ether phospholipid 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (OM-GPC) is known to be a potent inhibitor of cell growth. Metabolic studies in both Raji and L1210 leukemic cells on OM-GPC, 3H-labeled in the methyl groups of the choline moiety, showed a (diacyl)-phosphatidylcholine as the only labeled metabolite. Since the formation of radiolabeled (diacyl)-phosphatidylcholine showed a direct correlation with cell death, we tested other lipid analogs. One of these compounds, hexadecylphosphocholine (He-PC), which was 3H-labeled in the methyl-choline groups, showed a formation of labeled (diacyl)-phosphatidylcholine similar to that found with OM-GPC. Again, there was a direct linear correlation between the formation of the labeled product and cell death. He-PC was found to be a potent cell toxin in in vitro experiments on cell cultures. However, analogs with an elongated phosphor to trimethylammonium distance showed no toxicity towards the cells in in vitro experiments. From the data, we conclude that the ether phospholipids are substrates for a phospholipase C or related enzyme. This substrate property may be responsible for the toxicity of the compounds in neoplastic cells.
Distribution and metabolic fate of radiolabeled hexadecylphosphocholine (He-PC) has been studied in mice. It is demonstrated that He-PC is well-absorbed from the intestinal tract, intravenous (IV) and oral administration lead to similar distributions throughout the body, the highest accumulation of radioactivity occurs in liver, lung and kidney, and the metabolic products are radioactive choline, phosphocholine and 1,2-diacylphosphatidylcholine. The occurrence of these metabolites indicates that phospholipases C and D may be involved in He-PC breakdown.
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The human leukemia cell lines K562, HL60, and Raji and the mouse leukemia cell line L1210 showed a differential susceptibility to the action of the alkyl-lysophospholipid (ALP) 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3). After 48 hours, the 50% growth-inhibition doses (ID50) of ET-18-OCH3 were found to be 0.78 microgram/ml (HL60), 1.53 microgram/ml (Raji), 4.41 micrograms/ml (K562), and 5.05 micrograms/ml (L1210), as determined by [3H]thymidine incorporation. At the same time, cell viability was determined by trypan blue exclusion and revealed median lethal doses (LD50) of 3.5 micrograms/ml (HL60), 15 micrograms/ml (Raji), 24 micrograms/ml (L1210), and 38 micrograms/ml (K562). Since O-alkyl cleavage enzyme previously was suggested as being important in the detoxification of cytotoxic ALPs, the enzyme activity was compared with the susceptibility to ET-18-OCH3 in the distinct cell lines. In comparison to an approximate sevenfold to elevenfold (ID50 and LD50, respectively) difference in the susceptibility of the above leukemia cell lines to ET-18-OCH3, no significant difference in the specific activities (0.13-0.21 nmol/min/mg) of the O-alkyl cleavage enzyme was found in the above leukemia cell lines. Therefore, the differential sensitivity of the above lines investigated cannot be explained by differences in O-alkyl cleavage enzyme activity. Experiments with radiolabeled ET-18-OCH3 in Raji cells suggest, rather, a critical role for phospholipases C and/or D in ALP metabolism.
The uptake of 14C-labeled aminoglutethimide into the brain was investigated in the rat after intracarotid injection according to the method of Oldendorf, as well as in cisternal cerebrospinal fluid obtained by suboccipital puncture after i.v. injection of the drug. The brain uptake index of aminoglutethimide after intracarotid injection was 30.7 + 2.4%. Cerebrospinal fluid/blood quotients after i.v. drug injection were 0.53 at 10 min and 0.26 at 60 min. The results of both methods clearly show that aminoglutethimide easily penetrates the blood brain barrier.
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An easily performed and reproducible method is described for the antidromic determination of conduction velocity in the saphenous nerve. Eighty nerves were studied in 40 healthy subjects and the mean values obtained were as follows: latency 3.6 +/- 0.4 msec, conduction velocity 41.7 +/- 3.4 m/sec, amplitude 9.0 muV. This new technique should be useful in the electrodiagnostic evaluation of peripheral neuropathy, femoral neuropathy and saphenous nerve entrapment syndrome.
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BACKGROUND: We assessed the clinical and computed tomographic (CT) features of localized cystic disease of the kidney and how these features differentiate this disease from other renal cystic diseases. METHODS: Medical records and CT scans of seven patients with localized cystic disease were reviewed retrospectively. Pathologic confirmation in five patients was done by surgery. The subjects consisted of four males and three females, with an age range of 29-74 years. RESULTS: Localized cystic disease in five patients was an incidental finding. Clinical presentations in the other two patients included dark urine color, palpable flank mass, and generalized weakness. There was no patient with impairment of renal function associated with renal cystic disease. Six patients had cystic renal lesions in the left kidneys, and one patient had lesions in the right kidney. Six patients had cysts in a localized area in the affected kidney, and the remaining patient had diffuse involvement of the entire kidney. The upper pole was most frequently involved. CT appearance was characterized by multiple, variable size cysts conglomerated to islets of cysts that were separated by the normal renal parenchymal band. CONCLUSION: Localized cystic disease of the kidney has characteristic CT findings that distinguish it from other renal cystic diseases, making follow-up without surgical intervention possible.
BACKGROUND: To describe the characteristic magnetic resonance imaging (MRI) findings of gallbladder adenomyomatosis in two cases. METHODS: Two patients had abdominal MRI findings of gallbladder adenomyomatosis confirmed at cholecystectomy. RESULTS: The surgical specimen showed findings typical of adenomyomatosis, including marked thickening of both epithelial and muscular elements with multiple Rokitansky-Aschoff sinuses. On gadolinium-enhanced spoiled gradient-echo images and single-shot fast spin-echo images, mild gallbladder wall thickening with multiple intramural cystic components from Rokitansky-Aschoff sinuses were readily visualized. CONCLUSION: Adenomyomatosis of the gallbladder can be detected and diagnosed from MRI findings.
To characterize the immune response in haemorrhagic fever with renal syndrome, serial changes in immune effector cells were measured in 14 patients. Significant findings included initial elevations of all major leucocyte populations, increases in suppressor T cells and B cells, decreases in helper/suppressor cell ratios, and a dramatic increase in activated T cells. These changes were most marked in severely ill patients. Changes reverted to normal over approximately one week.