Antitumor activity of five new platinum complexes having a glycolate leaving ligand.

In an attempt to develop a new anticancer platinum complex with greater or equivalent antitumor activity but reduced side effects compared with cisplatin (CDDP), a series of new platinum complexes having a glycolate leaving ligand was synthesized. Among them, five complexes were selected for further development on the basis of adequate water solubility, low nephrotoxicity and high antitumor activity in a murine system. The chemosensitivity of these five complexes was examined in MTT assay against two human pulmonary adenocarcinoma cell lines, PC-9 and PC-14, and two human stomach adenocarcinoma cell lines, MKN-45 and KATO III. Their IC50 and relative antitumor activity (RAA) values were compared with those of CDDP and 254-S, a second-generation platinum complex with a glycolate leaving ligand under phase III clinical trial. The lowest mean IC50 value was observed in CDDP, followed by SKI 2034R and SKI 2033R. In this study, the antitumor activity was evaluated in terms of RAA values and SKI 2034R showed the highest RAA value. The order of RAA values was SKI 2034R > CDDP > SKI 2032R > SKI 2033R > SKI 2030R > SKI 2029R > 254-S. Based on the RAA order, we have recommended SKI 2034R as the most promising candidate for further development of a clinically useful platinum complex.     

Nephron Sparing Surgery for De Novo Renal Cell Carcinoma in an Allograft Kidney: A Case Report

De novo renal cell carcinoma in a renal allograft is rare and has special implications in renal transplant recipients. We describe a patient with a renal allograft who developed a de novo renal cell carcinoma in the functioning renal allograft 258 months after transplantation. The patient underwent enucleation of the tumor because preoperative MRI showed it was well-encapsulated. A DNA banding study showed that the tumor originated from the donor. Indications for conservative renal surgery in renal cell carcinoma have been increasing. Accordingly, 1 option in the treatment of de novo renal cell carcinoma in a functioning renal allograft is enucleation as a method of nephron sparing surgery.     

Cyclosporine overcomes cold preservation/reperfusion injury of liver graft: Chemokine release and liver ultrastructure

There is a growing body of evidence that the cytokine, tumor necrosis factor-α (TNF-ga), plays an important role in the development of hepatic ischemia/reperfusion injury. We found that the immunosuppressants, cyclosporine-A (CsA), azathioprine, and FK506, have protective effects on such injury. The purpose of the present study was to elucidate mechanisms involved in these beneficial effects of the immunosuppressant, CsA, on liver injury following cold preservation and transplantation, with special reference to the suppression of TNF-α release. Rat livers were stored in Euro-Collins solution (EC) at 4°C for 6h and orthotopically transplanted. The animals allotted to two groups: group A (untreated controls) and group B (CsA pretreatment of recipients). CsA (10 mg/kg, p.o.) was given for 3 consecutive days preoperatively. CsA pretreatment of the recipients significantly improved the 2-week survival rate (0/6 for group A, 3/6 for group B;P<0.05) and this was associated with a significant decrease in serum TNF-α levels 2h posttransplantation (group A, 69.8±15.7 pg/ml; group B, 22.8±6.8; mean±SEM;n=12 each;P<0.05) and amelioration of sinusoidal endothelial injury, assessed by electron microscopy. Plasma endotoxin levels following reperfusion of the grafts were not altered by the CsA therapy. Morphologically, CsA pretreatment of the recipients did not alter activation of Kupffer cells. CsA pretreatment of the recipient aids in preventing cold preservation/reperfusion injury of the liver graft, possibly by modulating effects of TNF-α.     

Potentiation of radiation response in human carcinoma cells in vitro and murine fibrosarcoma in vivo by topotecan, an inhibitor of DNA topoisomerase I.

DNA topoisomerase I, a nuclear enzyme important for solving topologic problems arising during DNA replication, has been identified as a principal target of a plant alkaloid, 20(s)-camptothecin. In view of the profound biochemical effects of camptothecin and its analogues on DNA replication and the differential cytotoxic effects on human tumors in xenografts, experiments were performed to determine whether topotecan, a camptothecin analogue, would potentiate the radiation effects on human carcinoma cells in culture and murine fibrosarcoma in mice. Cell culture studies showed that a dose dependent reduction in cell survival was obtained with a 4 hr exposure of the drug following irradiation of cells. No enhancement of cell killing was seen when cells were treated with the drug before irradiation. Preliminary in vivo tumor studies showed a significant radiosensitizing effect of topotecan that was both drug dose (20 mg/kg) and time sequence (4 hr before irradiation) dependent. There was no enhanced skin reaction following the combined treatments.     

Embryology of the human fetal hippocampus: MR imaging,anatomy, and histology.

PURPOSETo identify changes in the embryology of the hippocampus responsible for its adult anatomy.METHODSTen human fetal specimens ranging from 13 to 24 weeks'' gestational age were examined with MR imaging. Dissections and histologic sections of 10 different specimens of similar ages were compared with MR imaging findings.RESULTSAt 13 to 14 weeks'' gestation, the unfolded hippocampus, on the medial surface of the temporal lobe, surrounds a widely open hippocampal sulcus (hippocampal fissure). At 15 to 16 weeks, the dentate gyrus and cornu ammonis have started to infold. The hippocampal sulcus remains open. The parahippocampal gyrus is larger and more medially positioned. The CA1, CA2, and CA3 fields of the cornu ammonis are arranged linearly. The dentate gyrus has a narrow U shape. By 18 to 20 weeks, the hippocampus begins to resemble the adult hippocampus. The dentate gyrus and cornu ammonis have folded into the temporal lobe. The hippocampus and subiculum approximate each other across a narrow hippocampal sulcus. The CA1-3 fields form an arc and the CA4 field has increased in size within the widened arch of the dentate gyrus.CONCLUSIONMR imaging of fetuses provides a developmental basis for understanding hippocampal anatomy.     

RETT's syndrome in Korea--report of two cases

Rett's syndrome(RS) is a progressive neurodegenerative disorder characterized by exclusive occurrence in females, autistic behavior, dementia, gait ataxia, loss of purposeful use of the hands with stereotypic hand movement, and seizures. Initially RS was considered to be very rare; however, recent reports suggest that the prevalence is considerably higher and occurrence is world-wide. Because the pathophysiological process remains unknown, the diagnosis of RS is based mainly on its characteristic clinical features and course. We experienced two cases of RS which, to our knowledge, are the first reported in Korea. It is quite possible that many patients with RS not yet being diagnosed in Korea.     

Pure sensory stroke. Clinical-radiological correlates of 21 cases.

BACKGROUND: Although pure sensory stroke is a relatively common lacunar syndrome, the responsible lesions are often unidentified because of their small size. I reported 21 cases of pure sensory stroke in which the lesions could be identified by head computed tomography and/or magnetic resonance imaging and correlated the clinical findings with the radiological lesions. SUMMARY OF REPORT: Eleven patients had thalamic strokes. Lacunes confined to the posterolateral part of the thalamus were found in nine cases, and hemorrhages of relatively large size were found in two. Five patients showed a loss of all sensory modalities, but six with very small lacunes showed minor or restricted sensory changes. Seven patients with lacunes or hemorrhages in the lenticulocapsular region or corona radiata showed abnormalities of spinothalamic tract sensation. Two patients with a small lacune and a hemorrhage in the pontine tegmentum showed a selective sensory deficit of the medial lemniscal type. One patient with a small cortical infarct showed a cortical sensory loss that was preceded by cortical sensory transient ischemic attacks. CONCLUSIONS: Pure sensory stroke can occur with lesions in various areas of the somatosensory system. Hemisensory deficits of all modalities usually are associated with a relatively large lacune or hemorrhage in the lateral thalamus, whereas tract-specific or restricted sensory changes suggest very small strokes in the sensory pathway from the pons to the parietal cortex.     

Intervention program for obese school children.

The purpose of this study was to implement and evaluate a program for obese school children. A pretest-posttest design was utilized. Data was collected related to weight status, skinfold measurements, self-esteem, and nutritional knowledge. A convenience sample of 26 children, in the fourth to sixth grades, completed this 9-week program. The results indicate that self-esteem increased significantly (p less than .001) between the pretest and posttest interval. Weight status and nutritional knowledge showed no improvement. Exercise was difficult to assess on self-report, therefore no conclusions were were drawn in relation to this variable. Future research will be directed toward refining this intervention program.