Systemic effects of hyperthermic isolated lower limb perfusion with carboplatin and interferon-beta.

The changes in systemic circulation during hyperthermic isolated lower limb perfusion with carboplatin and interferon-beta were investigated in 19 patients with malignant melanoma. The cardiac output (CO) increased significantly (p < 0.01) from 3.81 +/- 0.22 L/min before the procedure to 5.30 +/- 0.49 L/min 1 h after hyperthermic perfusion. The double product (mean arterial pressure x heart rate) also increased significantly (p < 0.01) from 5,145 +/- 372 mm Hg/min to 6,760 +/- 486 mm Hg/min. In some patients, it increased to more than twice the control value. These changes were accompanied by an increase in body temperature, presumably caused by the systemic leakage of both warmed blood and interferon-beta. Blood chemistry data demonstrated no significant changes in the liver or renal function. However, the serum CPK level increased markedly on the first postoperative day, and persisted for 1 week, thus suggesting that some muscle damage occurred during the procedure. There was no operative death or severe complications. From these data, we concluded that hyperthermic isolated limb perfusion with interferon-beta is a relatively safe therapeutic method for malignant melanoma of the extremities. However, care should be taken in patients with ischemic heart disease who may suffer a heart attack due to the rapid increase in cardiac work during the procedure.

A case of CD56+ cutaneous aleukaemic granulocytic sarcoma with myelodysplastic syndrome.

We describe a 70-year-old man with cutaneous granulocytic sarcoma who presented with numerous cutaneous nodules but without any leukaemic involvement of the peripheral blood. The tumour cells were positive for lysozyme, peroxidase, CD11a, CD11c, CD33 and HLA-DR, and weakly positive for CD4 and CD14, suggesting granulocytic differentiation. The bone marrow at admission showed dysplasia of the erythrocytic and granulocytic lineage and complex chromosomal abnormalities in association with an increase in monocytes. The patient was diagnosed as having granulocytic sarcoma of monocytic lineage with concomitant myelodysplastic syndrome. In this case, tumour cells also expressed the neural cell adhesion molecule (CD56), which has been suggested as a possible risk factor for developing granulocytic sarcoma in acute myelogenous leukaemia.

Current techniques of hyperthermic isolated limb perfusion for malignant melanoma.

A retrospective study was conducted examining 25 patients with malignant melanoma who were treated by our new protocol for hyperthermic isolated limb perfusion. The characteristics of our techniques include: a lower priming volume of the extracorporeal circuit; a therapeutic temperature range of 40-41 degrees C with 60 min hyperthermic perfusion; a nominal perfusion flow rate of 500 ml/min in the lower limb and 200 ml/min in the upper limb; and combined carboplatin with interferon-beta as the adjuvant chemotherapy drug. In the lower extremity group, the arterial cannula size ranged from 8 to 14 F, while the venous cannula size ranged from 14 to 16 F. In the upper limb group, the arterial cannula size ranged from 6 to 8F and the venous cannula size ranged from 10 to 12F. No patient required any homologous blood transfusion postoperatively. No operative death or major complications occurred during the early postoperative period, confirming the safety of this treatment. Both optimal cannula size selection and maintaining perfusion temperature below 41 degrees C were judged to be important in elimination of vascular and deep tissue injury.

Immune thrombocytopenia due to Tranilast (Rizaben): detection of drug-dependent platelet-associated IgG.

Tranilast (Rizaben)-induced thrombocytopenia occurring in a 17-year-old man was reported. After withdrawal of the drug, he recovered within a week with oral prednisolone administration. Serological examination revealed no anti-platelet antibody, but platelet-associated IgG (PAIgG) was found. After incubation of peripheral blood of the patient with the drug in vitro, the level of PAIgG was significantly increased. These findings suggest the presence of a drug-dependent anti-platelet IgG in the patient's serum. This is the first report of immune thrombocytopenia caused by Tranilast. Our method for detecting drug-dependent platelet antibody in vitro is safe and useful for diagnosing drug-induced thrombocytopenia.

[Processing of emotional kanji words in the right hemisphere and the effect of handedness on the processing].

Experimental and clinical evidence indicates that the right hemisphere plays a special role in the processing of non-verbal emotional material. The possibility that verbal material may also be similarly processed in the hemisphere was investigated with a reading aloud task, with unilateral tachistoscopic presentation of emotional and non-emotional kanji words. Right-handed subjects, both male and female, participated in Experiment 1 and right and left-handed subjects of both sexes in Experiment 2. Results of Experiment 1 showed that response to non-emotional kanji words were more accurate in the right visual field than in the left, but no difference was found for emotional words. Results of Experiment 2 showed the word-emotionality by visual-field interaction effect on accuracy of both right- and left-handed subjects, but the effect was more pronounced for the right-handed. The results suggest that the right hemisphere processes emotional kanji words just as well as the left.

Increase in the peripheral lymphocyte populations expressing CD54 (ICAM-1) after hyperthermic isolated limb perfusion in patients with malignant melanoma: an analysis of four cases.

The lymphocytes isolated from perfused or non-perfused circulations before, during, and after hyperthermic isolated limb perfusion (HILP) in the four patients with malignant melanoma were analysed for the expression of CD54 (ICAM-1), CD58 (LFA-3), CD4, CD8, HLA class I and class II in order to investigate the mechanism(s) of the activation of such immunocompetent cells as natural killer (NK)-cells or T-lymphocytes by HILP. It was thus found that the lymphocyte populations expressing CD54 increased significantly 1 day after HILP in the four patients examined. The lymphocyte populations expressing CD58 apparently increased. It was also found that the NK-cell and T-lymphocyte activities increased during or after HILP in the present four cases as observed previously in the other melanoma patients. These results indicate that our HILP system may augment the immunological activities through the mechanisms of the induction of CD54 or CD58 expression in the peripheral lymphocytes of the melanoma patients who receive HILP.

The proliferative properties of tumor cells differentially correlate with the host immune responses in anogenital Bowen's disease.

Bowen's disease is a squamous cell carcinoma in situ that rarely invades into the underlying dermis. In order to evaluate the relationship between the cytological properties of the tumor cells and the host immune response, we have examined the expression of p53 and proliferating cell nuclear antigen (PCNA), and the number of mitotic cells, clumping cells, koilocytes, Langerhans cells (LCs) and dermal lymphoid cell infiltration in 18 cases of anogenital Bowen's disease. When compared with normal anogenital skins (n = 10), a statistically significant number of p53-positive cells, PCNA-positive cells, mitotic cells, clumping cells, koilocytes and dermal lymphoid cells was observed in the cases of Bowen's disease. Importantly, there existed a very strong correlation between the number of PCNA-positive tumor cells and the number of infiltrated dermal lymphoid cells. Moreover, the number of mitotic cells significantly correlated with the number of intratumoral LCs. The in situ hybridization technique for human papilloma virus (HPV) demonstrated that the HPV-infected Bowen's disease showed a similar histological and immunohistological pattern as the HPV-non-infected counterparts, except for increased koilocyte formation and decreased p53 positivity. The present data suggest that the proliferative activity of Bowen's disease significantly correlates with the host immune reaction, and that the host immune system may differentially recognize the different cytological properties of tumor cells in the Bowen's disease.

Kinetics of immunological parameters in patients with malignant melanoma treated with hyperthermic isolated limb perfusion.

Kinetics of immunological parameters such as natural killer (NK) cell activity and tritium-thymidine uptake rate of T lymphocytes by phytohemagglutinin stimulation were investigated using peripheral leukocyte fractions of melanoma patients treated with hyperthermic isolated limb perfusion (HILP). Also, serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) were quantified during and after HILP. It was found that NK cell activity was augmented during HILP, and T lymphocyte function was stimulated 24 h and 1 week after HILP with statistical significance. NK cell activities in the cells isolated from perfused and non-perfused circulations were equally augmented during HILP in two patients examined. Serum concentrations of sICAM-1 in the patients who received HILP also increased 24 h or even 1 week after HILP. The stimulation of these immune competent cells and upregulation of sICAM-1 by HILP were independent of the stages of melanoma patients at the time of HILP or the doses of agents which were used for the infusion during HILP. The origin of cells which shed sICAM-1 into the serum of the patients who received HILP remains to be further investigated.

Two cases of metastatic malignant melanoma of the lower limb treated with hyperthermic isolated limb perfusion and concomitant infusion of either carboplatin or beta-interferon.

Two cases of metastatic malignant melanoma of the lower limb who were treated successfully with hyperthermic isolated limb perfusion are reported. One patient was infused with cisdiammine (1.1-cyclobutanedicarboxylate) platinum (II) (carboplatin, Paraplatin, Bristol-Myers Squibb Company, New Jersey, USA), and the other was infused with human natural beta-interferon (Feron, Toray, Tokyo, Japan), via the external iliac artery. The first case showed a remarkable suppression of the growth of multiple metastatic melanoma nodules associated with numerous melanophage infiltrations, as shown histopathologically after the operation. The patient's serum level of 5-S-cysteinyl dopa decreased for the two months following the treatment. In the second case, new formation of metastatic melanoma nodules was completely suppressed for up to 12 months following the operation. Analysis of immunological parameters showed that the number of peripheral CD8+ lymphocytes gradually and constantly increased after the operation, while that of CD4+ lymphocytes transiently increased and then returned to the pre-operative level. Natural killer activity transiently decreased to a slight degree 4 days after the operation and then returned to the pre-operative level 21 days after the operation. Side effects, such as nausea, vomiting and leg discomfort, were seen in the patient (Case 1) treated with carboplatin, but were completely reversible. These results suggest that hyperthermic isolated limb perfusion with concomitant infusion of carboplatin or beta-interferon is effective in suppressing the growth of metastatic malignant melanomas of the lower limb.

Hyperthermic isolated limb perfusion with intra-arterial administration of carboplatin and/or interferon-beta for the treatment of malignant melanoma of the leg.

Our experiences of hyperthermic isolated limb perfusion with administration of carboplatin, interferon-beta or a combination of both are reported. Administration of high doses of these reagents was well tolerated by patients with melanoma without severe complications after the treatment. A total of 8 patients underwent this therapeutic modality. Remarkable clinical improvement was seen in the first patient, who was in Stage III at the time of the perfusion. Histopathological findings indicated severe damage to the melanoma cells after the operation. Prophylactic hyperthermic perfusion was performed in 6 other patients with Stage II-III melanoma of the lower limb. None of them have shown any signs of recurrence 1-10 months later. The activities of natural killer cells or T lymphocytes appeared to be increased when the perfusion was carried out with concomitant administration of both carboplatin and interferon-beta. These results suggest that hyperthermic isolated limb perfusion with carboplatin and/or interferon beta administration is effective in patients with advanced stage melanoma.

Antioxidant and radical scavenging effects of aged garlic extract and its constituents.

The antioxidant properties of three garlic preparations and organosulfur compounds in garlic have been determined. Aged garlic extract inhibited the emission of low level chemiluminescence and the early formation of thiobarbituric acid-reactive substances (TBA-RS) in liver microsomal fraction initiated by t-butyl hydroperoxide. However, the water extracts of raw and heat-treated garlic enhanced the emission of low level chemiluminescence. Among the variety of organosulfur compounds, S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC), the major organosulfur compounds found in aged garlic extract, showed radical scavenging activity in both chemiluminescence and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays, indicating that these compounds may play an important role in the antioxidative activity of aged garlic extract.

Handedness and cerebral hemispheric differences in memory for pictorial organization.

Handedness and cerebral hemispheric differences were investigated with regard to the way pictorial information is stored in long-term memory. Left- and right-handed men were required to remember a series of pictorial scenes that were organized or unorganized with respect to real-world configurations. Memory for these scenes was measured with half-field presentations of detail probes and whole-scene probes. There were no differences between the two visual fields in latency. An Organization x Probe interaction was found for accuracy scores for positive responses in the right visual field but not the left visual field. Furthermore, a three-way interaction (Organization x Probe x Visual Field) was significant among right-handers but not among left-handers. Findings are discussed in terms of hemispheric differences in long-term memory and hemispheric specialization referring to handedness.

Pharmacokinetics of the garlic compound S-allylcysteine.

The pharmacokinetic behavior of S-allylcysteine (SAC), one of the biologically active transformation products from garlic, was investigated after oral administration to rats, mice, and dogs. SAC was rapidly and easily absorbed in the gastrointestinal tract and distributed mainly in plasma, liver, and kidney. The bioavailability was 98.2, 103.0, and 87.2% in rats, mice, and dogs, respectively. SAC was mainly excreted into urine in the N-acetyl form in rats; however, mice excreted both SAC and the N-acetyl form. The half-life of SAC was longer in dogs than in rats and mice.

Melanocyte chemotactic factor produced by skin metastases of a breast carcinoma.

A 65-year-old woman underwent right modified radical mastectomy for a malignant lesion which had developed just below the right nipple. Two years after the operation, skin lesions composed of dark brown to black, pigmented, papular lesions developed in the precordia. A biopsy revealed this to be a cutaneous metastasis of the previous breast carcinoma. However numerous pigment blockade melanocytes were also found in the tumor nests, located in and/or beneath the epidermis. Although a black-colored breast carcinoma has been reported, the presence of pigment blockade melanocytes was not determined. Culture of the tumor nest recovered a population of melanocytes as well as the carcinoma cells. Boyden chamber analysis revealed the presence of a chemotactic factor for melanocytes in the culture medium. This seems to be the first documentation of melanocyte incorporation in breast carcinoma tissue.

Action pattern of Bacillus sp. no. 7-M chitosanase on partially N-acetylated chitosan.

The hydrolyzate of partially N-acetylated chitosan by Bacillus sp. No. 7-M chitosanase was separated by gel filtration on Bio-Gel P-2. Sugar compositions and sequences of the oligosaccharides were identified by exo-splitting with beta-GlcNase, fast atom bombardment mass spectroscopy, and proton NMR spectroscopy. In addition to chitooligosaccharides, (GlcN)2, (GlcN)3, and (GlcN)4, hetero-chitooligosaccharides such as (GlcN)2.GlcNAc.(GlcN)2, GlcN.GlcNAc.(GlcN)3, (GlcN)2.GlcNAc.(GlcN)3, and GlcN.GlcNAc.(GlcN)4 were detected. These results indicate that Bacillus sp. No. 7-M chitosanase is absolutely specific toward the GlcN.GlcN bonds in partially N-acetylated chitosan and at least three GlcN residues were necessary to the hydrolysis of chitosan by chitosanase.

Factor XIIIa expression in pseudo-Kaposi sarcoma.

A 39-year-old man had pseudo-Kaposi sarcoma on his left foot. A biopsy specimen obtained from a cutaneous lesion showed increased numbers of vascular spaces, proliferation of fibroblast-like spindle cells, and deposition of hemosiderin in the dermis. Immunohistochemically, proliferative fibroblast-like spindle cells around the vessels were positive for anti-factor XIIIa antibody. Excessive heat radiation was detected from the skin lesions by thermography.

[Clinical study of centrifugal pump bypass as an auxiliary technique for surgical treatment of descending thoracic aorta].

Left heart bypass or arterial bypass using a centrifugal pump (Bio-pump bypass) with a H-PSD shunt tube was performed as an auxiliary technique for the treatment of descending thoracic aorta in 13 cases. Hemodynamic differences during aortic clamp were compared between cases using Bio-pump bypass and 4 cases of axillo-femoral temporary bypass which were carried out in the first term. Furthermore, in Bio-pump bypass cases, the bypass route was investigated from the point of view of operative complications in relation to bypass technique. Peripheral blood pressure and urinary output during aortic clamp were significantly increased in the Bio-pump bypass group. Those results indicated that the Bio-pump bypass was useful as an auxiliary technique especially for high risk patients with low renal function. In particular, left heart bypass was a beneficial technique which was not affected by modality or region of disorder in the descending thoracic aorta. However, this technique should be selected carefully for patients with cardiac disease, for instance severe left ventricular hypertrophy, because two cases of operative complications consisting of pericardial effusion related to the bypass technique were experienced in this study.