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Biomedical subjects

G E Kim

Publications and source records attributed to G E Kim.

At least 55 records · Page 3Linked to original sources

Phase II trial for combined external radiotherapy and hyperthermia for unresectable hepatoma.

Hepatocellular carcinoma is a major malignant disease in parts of Africa and Asia, including Korea. Surgical resection, which represents the best hope for cure, is limited by the extent of the disease and the high incidence of concurrent liver cirrhosis in Korea. We designed a phase II trial of combined external radiotherapy and hyperthermia for hepatocellular carcinoma that was unresectable due to either locally advanced lesions or associated liver cirrhosis so as to evaluate the efficacy and the safety of this combination regimen. This trial was performed at Yonsei Cancer Center between April 1988 and July 1988. External radiotherapy was delivered to a total dose of 3060 cGy/3.5 weeks. Hyperthermia was applied twice a week for a total of six treatment sessions using an 8-MHz radio-frequency capacitive-type heating device, i.e., Thermotron RF-8 and Cancermia. In all cases, hyperthermia was carried out within 30 min of the radiotherapy for a period of 30-60 min. The temperature in the tumor was measured by inserting a thermocouple into the tumor mass under ultrasonographic guidance in patients who did not have a bleeding tendency. The tumor response was assessed by CT scan after completion of the designed treatment. No complete response was obtained. However, a symptomatic improvement in abdominal pain was observed in 78.6% of cases and a partial response was achieved in 40% of the patients. The most important factor affecting the tumor response was the type of tumor (single massive, 71.4%; diffuse infiltrative, 20%; multinodular, 0; P < 0.005). The 1-year survival values determined for all patients and for the partial responders were 34% and 50%, respectively. The overall median duration of survival was 6.5 months. The median duration of survival for the partial responders was longer than that for the nonresponders (11 vs 5 months; P < 0.05). A mild degree of heat sensation, fever, first-degree burns of the skin, and nausea were observed as treatment-related adverse reactions. In conclusion, although this study is being continued, the results obtained thus for indicate that combined radiotherapy and hyperthermia seem to be effective in providing local tumor control and pain palliation in unresectable hepatocellular carcinoma while producing an acceptable level of toxicity.

Adult↗

Modification of intracellular pH and thermosensitivity.

The effects of amiloride (an inhibitor of Na+/H+ antiport), DIDS (an inhibitor of Na(+)-coupled and Na(+)-independent HCO3-/Cl- exchange) and nigericin (K+/H+ ionophore) alone and in various combinations on the intracellular pH (pHi) and thermosensitivity of SCK tumor cells were studied. Hyperthermia alone at 43 degrees C for 2 h decreased pHi of SCK cells by 0.15-0.20 pH units, as measured fluorometrically using the pH-sensitive dye BCECF. When the cells were treated with 0.5 mM amiloride at 37 degrees C, the pHi declined by 0.10-0.15 pH units at an extracellular pH (pHe) of both 7.2 and 6.6. Amiloride at 0.5 mM enhanced the thermal damage to SCK cells at pHe 6.6 but not at pHe 7.2. DIDS alone at 0.1 mM exerted no effect on pHi or cellular thermosensitivity. DIDS, however, enhanced the effects of amiloride in decreasing pHi and in increasing the thermoresponse of SCK cells, particularly at pHe 6.6. Treatment of the cells with nigericin at 0.1-1.0 micrograms/ml lowered the pHi and enhanced the thermosensitivity of the cells in a dose-dependent manner. Reductions in pHi and increases in thermosensitivity by nigericin at the lower concentration at pHe 6.6 were far greater than at pHe 7.2. When a mixture of 1.0 micrograms/ml nigericin, 0.5 mM amiloride, and 0.1 mM DIDS was present in the medium, the pHi rapidly decreased by about 0.3 and 0.4 pH units at pHe 7.2 and 6.6, respectively. This drug combination was also extremely effective in sensitizing SCK cells to heat, particularly at pHe 6.6. The fact that the thermosensitization by these drugs at pHe 6.6 is more pronounced than at pHe 7.2 and that intratumor environments are known to be acidic strongly suggested that it may then be possible to enhance the thermal damage with such drugs preferentially in tumors relative to normal tissues.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Role of induction chemotherapy in invasive cervical cancer.

The 386 cases of invasive cervical carcinoma treated with radiotherapy alone were statistically analyzed to delineate the high risk factors (HRFs) associated with a significantly high treatment failure rate; they were (1) stages III-IV, (2) lesion greater than or equal to 4.0 cm, (3) small cell carcinoma or adenocarcinoma, (4) stages I-II with lesion greater than or equal to 4.0 cm, and (5) lymphographic evidence of nodal metastasis. Then, chemoradiotherapy (induction chemotherapy plus subsequent radiotherapy) was instituted to 113 invasive cervical carcinoma patients with at least one such HRF. Each patient received two to three cycles of induction chemotherapy at about 3-week intervals. For squamous cell carcinoma, cisplatin, 100 mg/m2 iv, was followed immediately by 5-fluorouracil, 1000 mg/m2, as a 24-hr iv infusion x 5 days. For adenocarcinoma, cisplatin, 70 mg/m2 iv, on Day 1 was followed by cytoxan, 250 mg/m2, on Day 2, and adriamycin, 45 mg/m2, on Day 3. Five-year survival of these patients according to each HRF, in the above order, was 69.1, 67.2, 68.1, 78.3, and 79.5% after chemoradiotherapy, all significantly higher than 57.4, 53.0, 54.5, 48.0, and 48.8% by radiotherapy alone. Drug toxicities such as leukopenia, hepatotoxicity, nephrotoxicity, and hypomagnesemia were seen in 46.5, 53.2, 47.1, and 55.4% of all cycles, respectively. The toxicities altered drug schedule in 191 (61.2%) ongoing induction chemotherapy cycles. Our cisplatin-based induction chemotherapy is considered an effective preradiotherapy adjunct that can reduce treatment failure in HRF-associated invasive cervical carcinoma.

Adenocarcinoma↗

Effects of amiloride on intracellular pH and thermosensitivity.

Amiloride, a diuretic drug, is a potent inhibitor of Na+/H+ exchange through the plasma membrane, and has been reported to enhance thermal damage in tumor cells in vitro. We investigated the possible relationship between changes in the thermal response of SCK mouse mammary tumor cells in vitro and changes in intracellular pH (pHi) due to amiloride in the present study. At a concentration of 0.5 mM, amiloride reduced the shoulder (Dq) without causing significant change in the slope (Do) of the survival curve of SCK cells heated once at 43 degrees C. On the other hand, 0.5 mM of amiloride sensitized thermotolerant cells to heat as shown by a reduction in Do. The presence of amiloride during the interval between the first and second heatings slightly reduced or inhibited the development of thermotolerance. The pHi was measured with the BCECF fluorescence method. The presence of 0.5 mM amiloride significantly reduced pHi in both pH 7.2 and 6.6 medium. Heating the SCK cells at 43 degrees C in pH 7.2 or 6.6 medium also reduced the pHi. The combined effect of heat and amiloride in reducing the pHi of SCK cells was additive. These results suggest that the effects of amiloride on the thermal response of SCK cells might be mediated in part by a decrease in pHi. The possibility that the effects of amiloride on the thermal response of tumor cells are mediated by other biochemical changes, such as inhibition of protein synthesis, however, could not be ruled out.

Amiloride↗

Coexisting mycosis fungoides and Hodgkin's disease as a composite lymphoma: a case report.

Within the past few years, an increasing number of reports of Hodgkin's disease following the diagnosis of, and frequently coexisting with, mycosis fungoides have appeared. Previously, Hodgkin's disease found in the lymph nodes of the patient diagnosed as mycosis fungoides was considered as a transformed form of the mycosis fungoides. But, now it has been proven that Hodgkin's disease and mycosis fungoides are histologically and immunohistochemically distinct disease entities. We report a well-documented case of a man who developed Hodgkin's disease and mycosis fungoides simultaneously as a composite lymphoma. Our case emphasizes the importance of considering the diagnosis of another lymphoma in patients with mycosis fungoides who have lymphadenopathy. The cutaneous mycosis fungoides and the Hodgkin's disease should be treated as an independent disease.

Adult↗

The influence of Fluosol-DA and carbogen breathing on the antitumor effects of cyclophosphamide in vivo.

The effects of Fluosol-DA, an oxygen-carrying perfluorochemical emulsion, and carbogen breathing alone or in combination on the antitumor activity of cyclophosphamide (CTX) in vivo were investigated. The addition of 12 ml/kg Fluosol-DA immediately prior to CTX treatment exerted no effect on the antitumor effect of CTX on the RIF-1 tumor in C3H mice. On the other hand, carbogen breathing alone for 8 h significantly enhanced the antitumor effect of CTX, with a dose-modification factor of 1.29 +/- 0.07. The combination of Fluosol-DA and carbogen breathing further increased the effect of CTX, with a dose-modification factor of 1.63 +/- 0.05. There was no significant difference in animal lethality within the treatment groups. It was concluded that Fluosol-DA in combination with carbogen breathing may be useful for the enhancement of CTX chemotherapy of human neoplasms.

Administration, Inhalation↗

Primary malignant lymphomas of the central nervous system: radiotherapy results in 12 cases.

Twelve patients with primary lymphomas of the central nervous system were treated in the Department of Radiation Oncology, Yonsei University College of Medicine, between 1976 and 1987. There were seven males and five females ranging from 19 to 63 years of age. They had single (6 cases) or multiple (6 cases) discrete intracerebral nodules. All patients were treated with radiation therapy. Surgical resection was performed in five cases and intrathecal chemotherapy with methotrexate was performed in seven cases after radiotherapy. All patients except one had received whole brain irradiation with a median dose of 4000 cGy. The radiation dose for a primary tumor was 4800-6000 cGy (median 5560 cGy). Initial response to radiation was excellent with a 91.7% complete response rate, but late recurrences were noted and the median survival was 42.3 months. Intracranial recurrences were observed in two patients who received less than 4000 cGy to the whole brain without intrathecal chemotherapy. Although intracranial recurrence was not seen in the patients receiving intrathecal chemotherapy after radiation, a high incidence of necrotizing leukoencephalopathy was noted. High dose irradiation with a minimum of 4000 cGy to the whole brain and more than 5000 cGy to the primary tumor is recommended for the treatment of primary CNS lymphomas. Combined use of chemotherapy should be carefully attempted because of the increased toxicity.

Adult↗

Cooperative clinical studies of hyperthermia using a capacitive type heating device GHT-RF8(Greenytherm).

Yonsei Cancer Center developed an RF(Radiofrequency) capacitive type heating device, GHT-RF8(Greenytherm) in cooperation with Green Cross Medical Corp., Korea in 1986 for the first time in Korea. Cooperative clinical studies of hyperthermia for the treatment of cancer using GHT-RF8 were conducted by Yonsei Cancer Center in collaboration with the Presbyterian Medical Center, Chonju, Korea. A total of forty patients with various histologically proven malignant tumors, including superficial (N = 13) and deep-seated tumors (N = 27), were treated with this newly developed heating device in conjunction with radiotherapy (N = 38) or chemotherapy (N = 2) at two different institutes between October 1986 and September 1987. These patients were locally far advanced or recurrent cases and considered to be refractory to conventional cancer treatment modalities. Radiotherapy was given in 200cGy per day, five times a week fractionations with a total tumor dose of 50-60Gy in 5-6 weeks. Within an hour after radiotherapy, the RF capacitive type of hyperthermia was given two times a week for a total of 4-10 treatment sessions and an attempt was made to maintain the tumor temperature at 41-45 degrees C for 30-60 minutes. Of forty patients treated, 14 patients with deep-seated tumors showed complete response and 20 patients showed partial response. The overall response rate was 85% (34 out of 40 patients) and only 6 patients showed no response. Complications from this treatment were mainly burns, superficial first degree burn in 2 cases, second degree in 4 cases and subcutaneous fat necrosis was observed in 2 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Abnormal innervation of lower limb epineurial arterioles in human diabetes.

A quantitative ultrastructural analysis was made of the terminal innervation of epineurial arterioles in the sural nerve of 6 diabetic and 6 non-diabetic patients of comparable age (mean +/- SD: 68 +/- 9 non-diabetic, 65 +/- 16 diabetic) with end stage peripheral vascular disease. The results demonstrated specific differences, identifiable morphometrically, in the pattern of innervation of epineurial vessels of diabetics compared with non-diabetics. The differences were: 1) in the diabetic group the proportion of perivascular axons found less than 7 microns from the nearest smooth muscle cell was significantly less than in the non-diabetic group (p less than 0.001); 2) the mean distance of the axons from their effector sites, the vascular smooth muscle cells, was nearly twice as far in the diabetic group compared with the non-diabetic group (p less than 0.05); and 3) the mean absolute number of axons less than 7 microns from the arteriole in the diabetic group was significantly less than in the non-diabetic group (p less than 0.01). These results demonstrate that the neuropathy associated with diabetes mellitus also involves the autonomic terminal innervation of some blood vessels. In addition, this neuropathy selectively affects the vasomotor nerves closer than 7 microns to the media.

Aged↗

Cervical vertebral angioplasty for brain stem ischemia.

Fifty-eight patients underwent unilateral vertebral arterial reconstructions over a 16-year period. Thirty-four underwent carotid operations as well. The first 18 patients underwent vertebral arterial reconstructions in conjunction with carotid endarterectomy as mandated in the Joint Study of Extracranial Arterial Occlusion as a Cause of Stoke. The next 40 underwent vertebral procedures for either brain stem symptoms alone, or for combined cerebral cortical and stem symptoms for specific indications after flow-obstructing carotid lesions had been corrected, but symptoms failed to subside. The surgical procedure consisted of subclavian-vertebral angioplasty except in one patient who underwent a subclavian distal-vertebral bypass graft to the level of the second cervical vertebral body. Syncopal episodes occurred as a major symptom in 16 and was controlled by either carotid and vertebral or vertebral artery operation alone except in four who also required cardiac pacemakers and one who needed correction of aortic stenosis. The long-term follow-up reveals that the stroke rate per average year for the first 14 years of follow-up was 1.2% per patient year with only five strokes having occurred in 410 patient years of follow-up and 70% of the patients having sustained no new neurologic episodes at the fourteenth year. Survival, however, was 45% at the fourteenth year with most deaths caused by myocardial infarction. The surgical procedure of vertebral angioplasty is indicated when bilateral vertebral arterial flow-obstructing lesions are found in patients with brain stem ischemia including drop attacks and syncopal episodes if flow-obstructing carotid lesions have been corrected and symptoms persist. The surgical procedure can be performed with a high degree of safety. The differential diagnosis of drop attacks and syncope in this age group should include, in addition to vertebrobasilar arterial insufficiency, transient cardiac arrhythmias, aortic stenosis, and convulsive disorders.

Brain Stem↗

Lumbar sympathectomy in end stage arterial occlusive disease.

Sixty-one patients had lumbar sympathectomies performed for end stage occlusive vascular disease manifested by gangrene of less than one-half of the foot, ulcerating ischemic lesions, rest pain or rapidly progressive markedly limiting intermittent claudication. The operative procedure was standardized to permit removal of the lowermost preganglionic fiber at the level of the crus of the diaphragm and the ganglionated chain to the crossing of the iliac vessels. The immediate postoperative mortality was 6.5% from cardiac causes. Over all improvement rate was 60% while early amputation rate was 40% for the entire group. Those patients with rest pain had the poorest prognosis with an amputation rate of 53%. The results are compared to other groups and factors of patient selection, anatomy of the sympathetic chain in relation to operative technique, physiology of decentralization versus devervation are discussed. The procedure is worthwhile in patients who are not candidates for arterial reconstruction who are faced with the prospect of early amputation.

Amputation, Surgical↗

The evolution of early fibromuscular lesions hemodynamically induced in the dog renal artery. I. Light and transmission electron microscopy.

In view of the important roles of arterial intimal fibromuscular lesions as precursors of atherosclerotic plaque and occlusive lesions in arterial reconstructions, a model has been developed for the rapid hemodynamic induction of these lesions by anastomosis of the dog right renal artery to the inferior vena cava. Light and transmission electron microscopic observations were made on the arterial shunt after periods of rapid flow ranging form 10 minutes to 2 hours to identify initial factor(s) and evolutionary mechanisms in the etiology of the lesions. The sequence of events included aberrations in ruthenium red staining of the endothelial luminal membrane at 10 minutes, multilayered thickening of the subendothelial basement membrane (BM) at 15 minutes, and initial reorientation and migration of smooth muscle cells (SMC) into the intima along with the appearance of areas of degeneration of the internal elastic lamina (IEL) at 30 minutes. The endothelial cells were still intact in some areas overlying the SMC migration and IEL degeneration, but they were separating from the surface in other such areas. As subendothelium became exposed, some platelet adherence was noted. By 2 hours, the entire wall reaction was fully developed. Initial observations indicate that in the evolution of this hemodynamically induced lesion visible alteration in the endothelial cells is not prerequisite to degeneration of the underlying IEL and reorientation and migration of medial SMC.

Animals↗

Lower-limb amputation for occlusive vascular disease.

A small series of 58 patients who required amputation because of gangrene of the lower limb with nonreconstructable arteries at New York University Medical Center illustrates the manner in which application of some of these principles achieved primary healing of 78% in below-knee amputation and rehabilitation rate of as high as 90% using simple nonrigid dressings.

Adult↗

Intermittent claudication: its natural course.

Of more than 600 patients seen for intermittent claudication by this group and not primarily considered for surgery, 104 had angiographic studies and are the basis for this report. The follow-up period varied from 6 months to 8 years, with a mean of 2.5 years. Classification by severity of claudication revealed 33 with less than one block, 36 with two blocks, and 35 with two or more blocks, foot, calf, or thigh claudication. Eighty-two remained stable or improved and 22 worsened. Of the 22 who worsened, 16 had only worsening of claudication (six of them requiring arterial reconstruction) and six progressed to gangrene and required amputations. Of the 82, 66 either had marked improvement of claudication or remained sufficiently stable not to require any operative intervention. Sixteen required arterial reconstruction for persistent, intolerable, or incapacitating claudication. Five of the six amputees were from the less than one half block claudication group. Angiographic studies were significant only in relation to the below-knee runoff in that three of 25 with less than one vessel runoff, two of 23 with one to two vessel runoff, and one of 56 with two to three vessel runoff came to amputation, regardless of the pattern of more proximal arterial occlusions. The study suggests that intermittent claudication is relatively benign, with only 5.8 percent coming to amputation in a 2.5 year mean follow-up. Prognosis is determined by the severity of below-knee arterial involvement and apparent inability to compensate for ischemia via the collateral circulation since only 12.5 percent of those with the most pronounced involvement came to amputation.

Amputation, Surgical↗