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Biomedical subjects

J K Roh

Publications and source records attributed to J K Roh.

At least 127 records · Page 7Linked to original sources

Locally advanced unresectable gastric cancer successfully resected after neoadjuvant chemotherapy with FADE regimen.

The prognosis of unresectable advanced gastric cancer is extremely poor. We tried a neoadjuvant chemotherapy in locally advanced unresectable stomach cancer diagnosed by initial explo-laparotomy. After chemotherapy with the FADE regimen (5-fluorouracil + adriamycin + cisplatin + etoposide), the patient was diagnosed clinically as a complete response state on re-staging with radiological gastrointestinal study, fiber-gastroscopy and computerized tomography. During the second-look operation, the advanced cancer was completely resected and the pathological diagnosis was early gastric cancer (EGC) type IIc, stage II (T1N2Mo).

Adenocarcinoma↗

Comparison of adjuvant radiotherapy and chemoradiotherapy following surgery in stage IE and IIE primary gastrointestinal tract non-Hodgkin's lymphoma.

Forty patients (median age 49.6 years) were treated for primary gastrointestinal lymphoma between 1979 and 1989. There were twenty-three cases of gastric lymphoma and seventeen cases of intestinal lymphoma. Following surgery, seventeen patients received postoperative chemoradiotherapy (ACOP) by the sandwich technique, seven patients received postoperative radiotherapy, and sixteen patients did not receive any other form of adjuvant treatment. Nineteen patients were stage IE and twenty-one were stage IIE. Stage IE disease was more prevalent in the gastric lymphoma group than the intestinal lymphoma group (p less than 0.01). At a median follow-up of 17 months (1-102 + months), 17 of 19 stage IE patients and 15 of 21 stage IIE patients remained alive. The survival rate was 90% in the postoperative chemoradiotherapy group and 83.3% in the postoperative radiotherapy group at five years, and 42.7% in the surgery alone group at four years, which showed statistical significance (p less than 0.01, p less than 0.05, each). Statistically improved survival rates were achieved with a postoperative chemoradiotherapy modality in intestinal lymphoma (p less than 0.01), stage IIE (p less than 0.01), intermediate grade by NCI criteria (p less than 0.01), poorly differentiated lymphocytic lymphoma (p less than 0.05), and diffuse histiocytic lymphoma (p less than 0.01) according to Rappaport classification, compared to those of the surgically treated only group. Three local relapses occurred in the operation alone group, and one in the adjuvant radiotherapy group which occurred simultaneously with distant lymph node recurrence. The pathologic stage of all of these relapsed patients was stage IIE-2. These results suggest that adjuvant chemoradiotherapy in completely resected localized gastrointestinal non-Hodgkin's lymphoma can decrease local and systemic relapse resulting in long-term disease free survival and overall survival compared to operation alone.

Adolescent↗

Male breast cancer--a 20-year review of 16 cases at Yonsei University.

Sixteen cases of male breast cancer seen over a 20-year period were reviewed. The causes of cancer of the male breast are no better understood, but major alterations in hormonal environment could be a significant factor. Some clinical characteristics correspond well with the results of other series. The median age at presentation was 61.7 years. The most frequent initial symptom was a painless mass, and the incidences of nipple discharge, central tumor location, and axillary node involvement were high. Males also had a higher incidence of local advancement which was associated with a longer delay in seeking treatment and small breast tissue. The pathologic type was infiltrating ductal type in all cases except one, and all cases showed favorable nuclear grade. Estrogen receptor analysis was performed from the tumor of 2 patients. Both of them showed a high receptor level. There was no locoregional relapse in 5 patients who received adjuvant radiotherapy in contrast to the 2 relapses in 3 patients who underwent surgery alone. And three of the five patients who received radiotherapy suffered from systemic metastasis which suggested the important role of adjuvant chemotherapy as well as radiotherapy. In light of the encouraging results about adjuvant chemotherapy in the treatment for female breast cancer with axillary lymph node involvement, it would be desirable to extend this policy to male breast cancer.

Adenocarcinoma↗

Sister-chromatid exchanges in 52 Korean women living in the vicinity of an industrial complex.

Sister-chromatid exchanges (SCE) were examined in the peripheral lymphocytes of 52 Korean women living in the vicinity of an industrial complex. They were generally non-smokers ranging from 22 to 56 years of age. The mean SCE score of the volunteers was 6.01 +/- 0.15 (SE). Only coffee intake produced a significant increase of SCE by comparison with the mean SCE for those that did not take coffee. Other parameters, including alcohol intake, working in industry and the presence of hepatitis B surface antigen (HBsAg), did not produce an increase in SCE. There was no effect on SCE due to age.

Adult↗

Hypesthetic ataxic hemiparesis in a thalamic lacune.

Right hemiparesis with an ipsilateral hypesthesia and ataxia developed in a 57-year-old man. Magnetic resonance imaging showed a left thalamic lacune bordering the medial portion of the posterior limb of the internal capsule. This finding implicated some pathogenetic mechanism of ataxic hemiparesis.

Ataxia↗

Mesencephalic hemorrhage--a report of 3 cases.

We studied three patients with spontaneous mesencephalic hemorrhages. All presented with some degree of impaired consciousness and abnormal ocular movements. One patient had a convergence-retraction nystagmus with a unilateral hemorrhage confined to the dorsal midbrain. Another patient showed left third nerve palsy due to a unilateral hemorrhage that involved ventral midbrain. The third patient revealed left internuclear ophthalmoplegia with ataxia due to a pinpoint hemorrhage in the tegmentum of the left midbrain. The patients survived and major neurologic deficits recovered, but abnormal ocular movements persisted.

Adult↗

Histopathologic study on muscle diseases among Koreans (274 muscle biopsy analysis).

All the diagnostic muscle biopsy cases were collected from the file of Department of Pathology, Seoul National University Hospital during June 1976 to December 1978. Slides were reviewed and correlated with clinical informations. Two hundred seventy four cases showed pathological changes, which were classified into six large groups (Table 1). Neurogenic atrophy was most common, 97 cases (35%), including 71 cases of motor neuron disease and 22 cases of peripheral neuropathy. Muscular dystrophy was seen in 92 cases (34%), and Duchenne type was the commonest among them (51 cases). Fifty seven cases showed inflammatory myopathy, making 20% of all cases. There were four cases of congenital myopathy and 13 cases showed various muscle diseases.

Adult↗

Phase II study of cyclophosphamide, doxorubicin, and vincristine (CAV) and etoposide plus cisplatin (EP) alternating chemotherapy combined with radiotherapy in small cell lung cancer.

The development of drug resistance is the major limiting factor influencing the survival of patients with small cell lung cancer (SCLC). We have thus examined the activity of cyclophosphamide, doxorubicin and vincristine (CAV) alternating with etoposide and cisplatin (EP) in 35 patients with SCLC. The treatment courses were alternated every 3 or 4 weeks. After induction chemotherapy, patients with limited disease (LD) received thoracic radiotherapy (5000 cGy), prophylactic cranial irradiation (3000 cGy) and maintenance chemotherapy and patients with extensive disease (ED) received maintenance chemotherapy only. In this group of 35 patients, 13 had limited disease (LD) and 22 had extensive disease (ED). After completion of the therapy, 100% of the patients with LD achieved complete plus partial remission (CR + PR) and 68% of the patients with ED achieved CR + PR. The median survival time was 66 weeks (15.3 months) in patients with LD and 44 weeks (10.2 months) in patients with ED. The over all survival for patients with LD was superior to that for patients with ED (p less than 0.05). Also, median response duration for patients with LD (35 wks) was longer than that for patients with ED (17 weeks) (p less than 0.05). The primary site was the most vulnerable site to relapse (18 patients). Toxicity was mild to moderate and acceptable, and there were no treatment-related deaths. These results suggest that the alternation of CAV and EP is effective treatment strategy in the management of SCLC. A randomized controlled study will be required to discriminate the actual effect of this alternating regimen.

Adult↗

Therapeutic and pharmacological studies of tetrachloro(d,l-trans)1,2-diaminocyclohexane platinum (IV) (tetraplatin), a new platinum analogue.

Tetrachloro(d,l-trans)1,2-diaminocyclohexane platinum (IV) (tetraplatin), a new platinum analogue, showed greater therapeutic efficacy after i.p. administration than either cis-dichlorodiammineplatinum (II) (cisplatin) or cis-diammine-1,1-cyclobutanedicarboxylate platinum (II) (carboplatin) in mice bearing i.p. implanted L1210 leukemia. At an optimal dose of 5.7 mg/kg/injection given as a single dose on days 1, 5, and 9, tetraplatin increased the median life span over controls by more than 566% with 5 of 8 long-term (50-day) survivors. In contrast, cisplatin at the same optimal dose increased survival by 186% with 2 of 8 long-term survivors, and carboplatin at an optimal dose of 75.6 mg/kg/injection increased survival by only 120% with no long-term survivors. Tetraplatin also was more effective than cisplatin when treatment was delayed until days 3, 7, and 11 after i.p. implant. A combination of tetraplatin and Adriamycin in mice bearing i.p. implanted L1210 leukemia produced more long-term survivors over a wider range of doses than could be achieved with either drug alone. Tetraplatin at 5.7 mg/kg/injection and Adriamycin at 3 mg/kg/injection on days 1, 5, and 9 increased survival by more than 566% with 8 of 8 50-day survivors. Using the same treatment schedule, combinations of tetraplatin with either cisplatin, carboplatin, daunomycin, or 5-fluorouracil did not produce therapeutic efficacy greater than that seen with tetraplatin alone. The in vitro cellular uptake of platinum by L1210 cells at 37 degrees C was about 4-fold higher after exposure to tetraplatin compared to cisplatin following a 2-h incubation at the two concentrations examined (2.5 and 5 micrograms/ml). Comparative pharmacological studies were performed in rats at a single dose of 3 mg/kg i.v. The t1/2 beta for total platinum in plasma was 29.10 h (7.47 h for unbound platinum) after the administration of tetraplatin and 23.70 h (13.09 h for unbound platinum) after cisplatin. By 48 h the urinary excretion of platinum after tetraplatin and cisplatin was 30.1% and 41.4%, respectively. Tissue distribution of platinum was similar after either complex. Thus, tetraplatin has similar pharmacological properties to cisplatin and like cisplatin is a candidate for combination chemotherapy. However, tetraplatin may be superior to cisplatin in some therapeutic situations based on its greater efficacy against selected tumors.

Animals↗

Effect of bacterial growth-inhibiting ingredients on the Ames mutagenicity of medicinal herbs.

A solvent fractionation method was introduced to screen for mutagenicity in 10 medicinal herbs being consumed in Korea. The Ames mutagenicity test result of Scutellariae and Rhei was significantly increased by eliminating growth-inhibiting substances through solvent fractionation of the crude extract. It is suggested that a physicochemical pretreatment should reduce the false-negative results which are caused by the presence of growth-inhibiting substances in complex mixtures.

Anti-Bacterial Agents↗

Comparative pharmacokinetics of free doxorubicin and doxorubicin entrapped in cardiolipin liposomes.

The comparative pharmacokinetics of free doxorubicin and doxorubicin entrapped in cardiolipin liposomes was evaluated in rats at a dose of 6 mg/kg i.v. Doxorubicin was entrapped in cardiolipin liposomes by using 11.2 mumol of drug, 5.6 mumol of cardiolipin, 28.5 mumol of phosphatidylcholine, 19.5 mumol of cholesterol, and 11.1 mumol of stearylamine. The peak plasma concentration with free doxorubicin at 5 min was 1.7 micrograms/ml which was reduced to 0.3 micrograms/ml by 1 h. With cardiolipin liposomes, the peak plasma concentration of doxorubicin achieved at 5 min was 20.9 micrograms/ml. The plasma levels of doxorubicin decreased gradually and by 1 h the drug concentration in plasma was 10 micrograms/ml. The plasma levels of free doxorubicin and doxorubicin entrapped in liposomes were fitted to a 3-compartment computer model. The terminal half-life with free doxorubicin in plasma was 17.3 h whereas it was 69.3 h with drug entrapped in liposomes. The area under the plasma concentration curve with liposomal doxorubicin was 81.4 micrograms X h X ml-1 compared to 1.95 micrograms X h X ml-1 observed with free doxorubicin. The steady state volume of distribution with free doxorubicin was about 23-fold higher than liposomal doxorubicin. The terminal half-life with free doxorubicin in cardiac tissue was 17.9 h compared to 12.6 h with drug encapsulated in liposomes. The terminal half-lives in liver and spleen following administration of liposomal doxorubicin were 15- and 2.3-fold higher, respectively, compared to free drug; furthermore, the concentration X time values of liposomal doxorubicin in liver were 26-fold higher and in spleen 6-fold higher than the free drug. Free doxorubicin and doxorubicin entrapped in liposomes demonstrated 17 and 20% excretion in bile of the injected dose, respectively, in rats. The present studies demonstrate that liposomal encapsulation of doxorubicin significantly alters its pharmacokinetics in plasma and tissues compared to free drug.

Animals↗

Distribution and removal of cadmium from milk.

Distribution of added cadmium in milk systems and the feasibility of removing cadmium were investigated. In milk containing 1 ppm cadmium, 96% of the added cadmium chloride was dispersed in the skim milk fraction, and 3% was associated with the cream fraction. Cadmium was not bound strongly to any protein fraction. The association of cadmium with acid casein, whey proteins, and the fat globule membrane was 18,6, and .5% of total added cadmium. With a 5-min exposure thiosuccinylated amino-ethyl cellulose, thionitrocarboxyphenylated aminoethyl cellulose, and reduced human hair removed 72, 70, and 30%, respectively, of added cadmium in skim milk previously equilibrated for 2 h at 37 C. Increasing equilibration time beyond 24 h had no effect on removal efficiency whereas increasing pH decreased cadmium removal markedly.

Animals↗

Distribution and removal of added mercury in milk.

Distribution patterns of added mercury in raw whole milk after equilibration for 30 min and 2 h at 37 C showed a distribution among acid casein, whey proteins, fat globule membrane, and soluble fat globule membrane of 33, 28, 16, and 2%. On the basis of protein content, the fat globule membrane had the highest amount of mercury. Mercury added to milk as mercuric chloride was removed by treatment with thiolated aminoethyl celluloses and reduced human hair. In a 5 min treatment, 70, 43, and 41% of the mercury was removed by thiosuccinylated aminoethyl cellulose, thionitrocarboxyphenylated aminoethyl cellulose, and reduced human hair, respectively, from whole milk initially containing 1 ppm mercury and equilibrated for 2 h at 37 C prior to treatment. After treatment for 60 min, 82, 52, and 64% of the mercury was removed by thiosuccinilated aminoethyl cellulose, thionitrocarboxyphenylated aminoethyl cellulose, and reduced hair, respectively. However, increasing incubation temperature and time prior to treatment decreased the removal efficiencies. Thiosuccinilated aminoethyl cellulose and reduced human hair showed increasing efficiency directly with pH, while thionitrocarboxyphenylated aminoethyl cellulose showed the opposite effect and had higher affinity for mercury at pH 5.5 than at pH 7.5. Moreover, the rate of removal of mercury at 4 C compared to 37 C was much slower. The removal of mercury from soluble casein and soluble whey proteins was more efficient than from micellar casein. Protein, lactose content, and pH of milk were not changed by the polymer treatments.

Animals↗

Synergistic embryotoxicity of combination pyrimethamine and folic acid in rats.

The increased embryotoxicity of pyrimethamine (PYM) with concomitant oral dosing of folic acid (FA) was examined in rats. The preventive effects of folinic acid (FNA) on PYM embryotoxicity were also examined. Six groups were constructed: PYM I (PYM 1.2 mg/kg/day), FA (FA 50 mg/kg/day), PYM I+FA (1.2 and 50 mg/kg/day, respectively), PYM II (2.7 mg/kg/day), PYM II+FNA (2.7 and 12 mg/kg/day, respectively), and a vehicle control group. The agents were administered for 11 days from day 7 throughout 17 of gestation. PYM and FA were administered by gavage and FNA was administered intraperitoneally. Visceral and skeletal malformations were observed in the fetuses of both PYM I+FA and PYM II groups; these included dilatation of the lateral ventricle and fused ribs. No malformed fetuses were observed in the fetuses of the other four groups. External malformations were observed only in the fetuses of PYM II groups; these included cleft palate, cleft lips, and brachygnathia, among others. These results show that the concomitant gavage dosing of FA augments PYM embryotoxicity. The preventive effects of FNA were also confirmed.

Abnormalities, Drug-Induced↗

Teratogenic effects of DA-125, a new anthracycline anticancer agent, in rats.

DA-125 is a new anthracycline antitumor antibiotic derived from adriamycin. Preclinical studies suggest that it may have greater activity and less cardiac toxicity than adriamycin. The potential of DA-125 to induce embryotoxicity was investigated in the Sprague-Dawley rat. One hundred twenty mated SD rats (sperm in vaginal lavage = day 0) were distributed among three treated groups and a control group. DA-125 was given at dose levels of 0, 0.1, 0.3, and 1.0 mg/kg/day administered intravenously to pregnant rats from days 7 to 17 of gestation. All dams were subjected to caesarean section on day 20 of gestation. At 1 mg/kg/day, reduced food intake, reduced body weight, and decreased spleen weight were observed in dams. An increase in the resorption rate and a reduction in the fetal weight were also found. In addition, various types of external, visceral, and skeletal malformations occurred at an incidence of 11.9, 41.8, and 14.5%, respectively. Characteristic malformations included exencephaly, gastroschisis, cleft lip, dilatation of lateral and third ventricles, and fused ribs, among others. There were no signs of maternal toxicity or embryotoxicity at 0.1 and 0.3 mg/kg. The results show that DA-125 is teratogenic at a minimally maternally toxic dose in rats.

Abnormalities, Drug-Induced↗