[Successful treatment applied to methicillin-resistant Staphylococcus aureus (MRSA) empyema after the operation for lung cancer; report of a case].

Empyema caused by methicillin-resistant Staphylococcus aureus (MRSA) remains an intractable infection producing high mortality. The authers report a case of MRSA empyema following video-assisted thoracic surgery (VATS) for lung cancer. The case was 73-year-old male with some risks such as pulmonary emphysema, decreased renal function, and previous history of brain infarction. He received wedge resection and the staple lines were wrapped with polyglycolic acid (PGA) felt. Ten days after the operation, he was complicated MRSA pyothorax. By thoracoscopic procedures under local anesthesia, fibrinopurulent tissues were cleaned and 3 of chest tubes were replaced. Intrathoracic infected space was cleaned with physiological saline solution. The patient made favorable progress and recovered. Further empyema has not been developed for 24 months. VATS under local anesthesia and irrigation technique was safe and so useful. Nowadays, PGA felt is often used to reinforce the staple lines of lung. PGA felt is an absorbable but artificial material. We have to care about infectious problems. However, we could control the MRSA pyothrax without removing the PGA felt.

[Usefulness of the thoracoscopic surgery under local anesthesia and irrigation for the patient with Bacillus cereus empyema; report of a case].

The case was 54-year-old male with some risks such as chronic heart failure, atrial fibrillation, and liver chirrhosis. He was admitted because of severe back pain and diagnosed as empyema by preoperative thoracentesis. By thoracoscopic procedures under local anesthesia, fibrinopurulent tissues were cleaned as much as possible and 3 of chest tubes were replaced. The final diagnosis was Bacillus cereus pyothorax by bacterial cultures of pleural effusion. Intrathoracic cavity was cleaned with physiological saline solution. The patient made favorable progress and recovered. Thoracoscopic surgery under local anesthesia with thoracic irrigation was so effective and safe methods to control the infection.

Role of ATP in the sensitivity to heat and the induction of apoptosis in mammalian cells.

Heat-induced cell death and apoptosis were studied with respect to intracellular ATP. Studies on the relationship between hyperthermic cell-killing at 44 degrees C and cellular ATP levels in four cell lines grown as monolayers and six cell lines grown in suspension showed good correlations between cellular ATP levels and the sensitivity to heat. D(0) values (the dose required to reduce survival in the linear portion of the response by 63%) linearly increased with an increase in cellular ATP levels. No such changes in sensitivity to heat were observed between the cells cultured at different cell densities, regardless of the change in the cellular ATP level. These results suggest that cellular intrinsic ability to supply ATP rather than the level of pooled ATP per se is responsible for the thermal response. Heat-induced apoptosis in L5178Y cells was observed following treatment at 42 degrees C for 70 min, 44 degrees C for 20 min or 47 degrees C for 3 min, which corresponded to surviving fractions of 25, 0.6 and 0.8%, respectively, but not at 47 degrees C for 20 min, indicating that mild heat shock induced apoptosis. 2-deoxyglucose (2DG) and 2,4-dinitrophenol (DNP) increased the sensitivity to heat and affected the mode of cell death. Cells treated with 2DG and DNP (2DG/DNP) were heated at 42 degrees C for 20 min, and then incubated at 37 degrees C for up to 2h in the presence or absence of 2DG/DNP. In the absence of 2DG/DNP, the cellular ATP level recovered to 76% of the control level and DNA ladder formation was observed, whereas in the presence of 2DG/DNP, the cellular ATP level was further decreased (3-7% of the control) and no DNA fragmentation was detected. These results suggest that the inhibition of ATP synthesis is closely associated with the enhancement of sensitivity to heat and that ATP is required for the induction of apoptosis.

Auditory triggered mental imagery of shape involves visual association areas in early blind humans.

Previous neuroimaging studies identified a large network of cortical areas involved in visual imagery in the human brain, which includes occipitotemporal and visual associative areas. Here we test whether the same processes can be elicited by tactile and auditory experiences in subjects who became blind early in life. Using positron emission tomography, regional cerebral blood flow was assessed in six right-handed early blind and six age-matched control volunteers during three conditions: resting state, passive listening to noise sounds, and mental imagery task (imagery of object shape) triggered by the sound of familiar objects. Activation foci were found in occipitotemporal and visual association areas, particularly in the left fusiform gyrus (Brodmann areas 19-37), during mental imagery of shape by both groups. Since shape imagery by early blind subjects does involve similar visual structures as controls at an adult age, it indicates their developmental crossmodal reorganization to allow perceptual representation in the absence of vision.

Long-term local intensive preoperative chemotherapy and joint-preserving conservative surgery for osteosarcoma around the knee.

This study evaluated conservative joint-sparing surgery for patients with osteosarcoma around the knee. Of 23 patients with stage IIB osteosarcoma around the knee, 5 were treated with long-term (30-56 weeks) local intensive preoperative chemotherapy consisting of high-dose methotrexate, intra-arterial and intravenous cisplatinum, doxorubicin, and hyperthermic isolated regional perfusion. More conservative resection, sparing the knee joint, was performed with smaller sufficient surgical margin in these 5 patients, preserving good limb function. Excellent local effects were achieved in the resected specimens. These results suggest long-term local intensive preoperative chemotherapy, including intra-arterial cisplatin and hyperthermic isolated regional perfusion, help control local tumor and allow for more conservative surgery.

Mantle cell lymphoma of the rectum at an early stage: a case report.

We report a very rare early-stage case of mantle cell lymphoma, which arose from the rectum. A 60-year-old man presented with a small elastically hard polypoid lesion in the rectum. The lesion was 1.2 x 1.2 cm in size. As a preoperatively barium enema and endoscopy suggested a benign tumor of the rectum, he underwent local excision of a rectal polypoid mass transanally under spinal anesthesia. However, histological examination revealed a malignant lymphoma, because the lesion was histologically characterized by solid growths of small to medium-sized round cells. Furthermore, immunohistochemical tests revealed B-cell marker positivity and CD5 positivity, but cyclin D1 negativity. Since it was reported that lymphomas with a mantle cell lymphoma morphology and CD5 expression, but without cyclin D1 overexpression, exist in about 10% of mantle cell lymphoma cases, we diagnosed his disease as mantle cell lymphoma. To our knowledge, this is the first reported case of an early-stage mantle cell lymphoma, originating from the rectum.

Interleukin-18 in human milk.

We analyzed IL-18 levels of human milk. Colostrum contained significantly higher levels of IL-18 compared with early milk and mature milk. By stepwise multiple linear regression analysis, preterm delivery and pregnancy complications of mothers significantly correlated with high levels of IL-18 in human milk (p = 0.0007 and 0.0018, respectively). There was a significant correlation between the levels of IL-18 and soluble Fas ligand in colostrum (p = 0.0003). IL-18 was detected in actively secreting epithelial cells in lactating mammary gland by immunohistochemical staining. These results suggest that IL-18 in colostrum plays an important role in host defense of high-risk neonates.

Effect of low-calcium hemodialysate on bone metabolism.

In the present study, we investigated the kinetics of bone metabolism by determining serum bone metabolic markers and quantifying bone mineral density by dual-energy X-ray absorptiometry to clarify the effect of long-term use of low-calcium hemodialysate on bone metabolism. After changing the calcium concentration in the dialysate from 3.0 mEq/l to 2.5 mEq/l, serum intact parathyroid hormone level, serum highly sensitive parathyroid hormone level, and serum bone metabolic markers were determined in ten patients with chronic nondiabetic renal insufficiency during 1 year. The doses of an oral phosphate binder and activated vitamin D were carefully regulated to control serum ionized calcium levels and serum inorganic phosphorus levels. Bone mineral density was determined at the distal 1/3 and 1/6 of the radius on the nonshunt side. As a result, the required amount of oral phosphate binder was increased; however, there was no need to significantly increase the amount of activated vitamin D. Intact parathyroid hormone showed no significant variation, but the highly sensitive parathyroid hormone was significantly increased. There were no significant changes in any bone metabolic markers or in bone mineral density. From these study results, it was found that it was difficult to increase the dose of activated vitamin D even if low-calcium hemodialysate was used, and that during use of the low-calcium hemodialysate the serum level of parathyroid hormone tended to increase but led to neither acceleration of bone turnover nor a decrease in bone mineral density.

Effect of the Chinese herbal medicine, Bakumondo-to, on airway hyperresponsiveness induced by ozone exposure in guinea-pigs.

OBJECTIVE: Bakumondo-to (Maimendong tang) is a Chinese herbal medicine that has been used as an anti-tussive agent. However, the effects of Bakumondo-to on airway hyperresponsiveness are unknown. We examine whether Bakumondo-to can inhibit airway hyperresponsiveness induced by ozone. METHODOLOGY: Measurements of airway responsiveness and plasma extravasation and bronchoalveolar lavage (BAL) were performed before and after ozone exposure (3 p.p.m., 2 h). Guinea-pigs were anaesthetized with pentobarbital sodium and mechanically ventilated. Airway responsiveness was determined by an inhalation of doubling concentration of histamine, and the concentration of histamine required to produce a 200% increase in R(L) (PC200) was calculated by log-linear interpolation. Plasma extravasation was evaluated by measuring the extravasation of Evans blue dye in the airway. RESULTS: Ozone produced significant airway hyperresponsiveness and plasma extravasation, with an influx of neutrophils in BAL fluid. Bakumondo-to (400 mg/kg p.o.) significantly inhibited airway hyperresponsiveness, but had no effect on neutrophil influx or plasma extravasation. CONCLUSIONS: We demonstrated that Bakumondo-to can attenuate airway hyperresponsiveness induced by ozone without affecting airway inflammation, which suggests that Bakumondo-to may act on the subsequent mechanisms after the induction of inflammation, such as mediator release.

Enzymatic synthesis of N-acetylglucosaminyl-cyclodextrin by the reverse reaction of N-acetylhexosaminidase from jack bean.

Novel heterobranched cyclodextrins (CDs), N-acetylglucosaminyl-cyclodextrins (GlcNAc-CD), were synthesized from a mixture of GlcNAc and alpha, beta, or gamma CD by the reverse reaction of N-acetylhexosaminidase from jack bean. Optimum pH and temperature for the production of GlcNAc-alpha CD by N-acetylhexosaminidase were pH 4.9 and 50-70 degrees C, respectively. The maximum yield of GlcNAc-alpha CD was 17.5% (mol/mol) at the concentration of 1 M GlcNAc and 0.25 M alpha CD. The reverse reaction product, GlcNAc-alpha CD, was separated into two peaks by HPLC analysis on the ODS column. Their structures were identified as 6-O-beta-D-N-acetylglucosaminyl-alpha CD and 2-O-beta-D-N-acetylglucosaminyl-alpha CD by FAB-MS and NMR spectroscopies. N-Acetylhexosaminidase from jack bean also synthesized N-acetylgalactosaminyl-alpha CD from N-acetylgalactosamine and alpha CD.

[Unusual form of ulcerative colitis].

Segmental colitis which showed the similar findings of ulcerative colitis and right-sided colitis with back-wash ileitis has been considered as the unusual form of ulcerative colitis. Today, we have few opportunities to come across those cases, because modern diagnosis of colon disease could make differential diagnosis easily with the sense of broad spectrum of IBD. We presented three cases of segmental colitis and one case of so-called indeterminate colitis associated of carcinoma in the cecum and discussed the clinical significance for diagnosis and finding the step of studying the etiology of IBD. Especially, in the third case, thirteen years old man was showing the sign of early stage of Crohn disease with non-caseating granuloma in the biopsy specimen at first, the findings of the segmental ulcerative colitis with crypt abscess were seen after six months in the second examination. To observe the detail changes of the mucosal lesion in this kind of cases will present the new idea for studying the etiology of IBD.

Hyperthermic isolated regional perfusion for the treatment of osteosarcoma in the lower extremity.

BACKGROUND: In order to reduce the systemic toxity of cisplatin and to increase the effect on the local tumor, facilitating limb-preserving procedures, we have been using hyperthermic isolated regional perfusion (HIRP) for the treatment of osteosarcoma in addition to preoperative chemotherapy. MATERIALS AND METHODS: Twenty patients with an osteosarcoma in a lower extremity were treated with both preoperative chemotherapy and HIRP. RESULTS: The chemotherapeutic effects of preoperative chemotherapy with HIRP was grade III in 6, and grade IV (no viable cell areas observed) in 7. The surgical margins could be reduced in these 13 cases of good responders showing over 90% necrosis (grade III or grade IV), which mainly involved postnecrotic fibrosis and osteosclerosis. CONCLUSION: HIRP can help to control the tumor locally. A more conservative operation was then possible in cases of good responders to preoperative chemotherapy with HIRP.

CAST, a novel CD3epsilon-binding protein transducing activation signal for interleukin-2 production in T cells.

Antigen recognition through T cell receptor (TCR)-CD3 complex transduces signals into T cells, which regulate activation, function, and differentiation of T cells. The TCR-CD3 complex is composed of two signaling modules represented by CD3zeta and CD3epsilon. Signaling through CD3zeta has been extensively analyzed, but that via CD3epsilon, which is also crucial in immature thymocyte development, is still not clearly understood. We isolated cDNA encoding a novel CD3epsilon-binding protein CAST. CAST specifically interacts in vivo and in vitro with CD3epsilon but not with CD3zeta or FcRgamma via a unique membrane-proximal region of CD3epsilon. CAST is composed of 512 amino acids including a single tyrosine and undergoes tyrosine phosphorylation upon TCR stimulation. Overexpression of two dominant-negative types of CAST, a minimum CD3epsilon-binding domain and a tyrosine-mutant, strongly suppressed NFAT activation and interleukin-2 production. These results demonstrate that CAST serves as a component of preformed TCR complex and transduces activation signals upon TCR stimulation and represents a new signaling pathway via the CD3epsilon-containing TCR signaling module.

Modification of release rates of cyclosporin A from polyl(L-lactic acid) microspheres by fatty acid esters and in-vivo evaluation of the microspheres.

Biodegradable microspheres containing cyclosporin A (CyA, cyclosporine) were prepared using poly(L-lactic acid) (PLA) and poly(lactide-co-glycolide)(PLGA) by a solvent evaporation method. CyA was efficiently entrapped in PLA, PLGA(50/50) and PLGA(75/25) microspheres in a range of 81-85%. CyA released constantly from PLA microspheres without any lag time, whereas the drug from PLGA(50/50) and PLGA(75/25) microspheres was released after lag time of about 1 and 3 weeks, respectively. Addition of fatty acid esters enhanced the release rates of CyA from PLA microspheres. In-vivo study was performed using rats with adjuvant-induced arthritis. PLA microspheres with ethyl myristate sustained high blood levels of CyA compared with the microspheres with no additives over 4 weeks. In addition, the PLA microspheres improved the symptoms such as the decrease in body weight and the increase in paw swelling occurred by adjuvant-induced arthritis in rats. Consequently, the release rate of CyA from PLA microspheres can be improved by adding fatty acid esters and PLA microspheres with fatty acid esters seem to be a useful dosage form for autoimmune disease therapy.

The serum interleukin 8 level reflects hepatic mitochondrial redox state in hyperthermochemohypoxic isolated liver perfusion with use of a venovenous bypass.

BACKGROUND: We have recently developed a simple method of hyperthermochemohypoxic isolated liver perfusion (HILP) as a regional therapy for unrecognized liver micrometastases. However, little is known about the influence of HILP on cytokine production and liver function. We investigated the influence of HILP on interleukin 8 (IL-8) production and the hepatic mitochondrial function and assessed the relationship between these 2 parameters. We also measured the serum tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) levels to examine the involvement of HILP-induced cytokines in the tumor response. METHODS: Sixteen patients with metastatic liver tumors were randomly assigned to undergo hepatectomy with HILP (group A, n = 9) or hepatectomy alone (group B, n = 7). The isolated liver was perfused for 30 minutes with Ringer's lactate solution containing chemotherapeutic agents warmed to 42 degrees C to 43 degrees C without oxygenation. RESULTS: The serum IL-8 levels in group A were markedly increased, with peaks at 3 hours after reperfusion, which was significantly higher than levels in group B (P < .01). In group A the arterial ketone body ratio, which reflects the hepatic mitochondrial redox state, decreased during perfusion and was gradually restored to the preperfusion level 1 hour after reperfusion. However, in group B it decreased during hepatectomy but rapidly recovered 5 minutes after hepatectomy. There was a significant negative correlation between the peak serum IL-8 level and the initial velocity of arterial ketone body ratio recovery for the first 5 minutes after reperfusion r = -0.83, P < .001). The serum TNF-alpha and IL-1 beta were temporarily detected only in 3 of 9 patients in group A. CONCLUSIONS: We have shown that HILP resulted in augmented IL-8 release but not TNF-alpha and IL-1 beta and that the serum IL-8 level reflects the hepatic mitochondrial redox state. These findings suggest that IL-8 production may be associated with hepatic mitochondrial impairment during ischemia. This work may contribute to new therapeutic strategies not only for hepatic ischemia reperfusion injury but also for metastatic liver tumors.

Hyperthermo-chemo-hypoxic isolated liver perfusion for hepatic metastases: a possible adjuvant approach.

As a possible intraoperative adjuvant approach to treating hepatic metastases we developed a method of hyperthermo-chemo-hypoxic isolated liver perfusion in combination with hepatic resection. This method was applied to 11 patients with colorectal hepatic metastases between 1992 and 1995. One patient died on postoperative day 14 of hepatic failure (9% mortality), the cause of which was live temperature that reached 42.9 degree C, which seems to be the maximum limit for thermal toxic effect on the human liver. The other 10 patients tolerated the perfusion well, with mild hepatic and non systemic toxicity after minor or even major hepatic resection; the serum aminotransferase and total bilirubin levels returned to normal levels by postoperative day 14. Only one of eight patients (13%) for whom cytotoxic drugs were added to the perfusate (mitomycin C 10 micrograms/ml or cisplatin 2 micrograms/ml) had hepatic recurrence by 19 months after the perfusion (mean follow-up 25.8 months; median 23 months; range 8-57 months). Two patients were alive with no evidence of disease at 13 and 57 months, respectively after the perfusion; the other five patients had postperfusion extrahepatic recurrences (median: 19 months; range 7-20 months). In contrast, hepatic metastases recurred 7 and 20 months after the perfusion, respectively, in the two patients not given a cytotoxic drug.

The efficacy of hyperthermia combined with radiation therapy for high-grade soft tissue sarcoma.

BACKGROUND: We have investigated the efficacy of preoperative hyperthermia combined with radiation therapy (HIRP) in cases of soft tissue sarcoma (STS) that could be consequently treated with limb salvage. MATERIALS AND METHODS: Thirteen patients with STS in an extremity received HIRP at our institution. Local hyperthermia for 1 hour was administered eight to ten times. Radiation therapy (40-60 Gy) was administered at 2 Gy per session. The operation was performed at 2 or 3 weeks after HIRP. RESULTS: Limb salvage surgery was achieved in 12 patients. No local recurrence was observed during a mean follow-up of 27 months. 7 patients had shown only a partial response to the HIRP. There was no correlation between the histological response and the observed reduction in tumor volume. CONCLUSIONS: The results of this study suggested that HIRP was an effective local treatment for limb salvage in limb-threatening STS.

[Our initial experience with SMANCS in TAE for liver cancer].

To evaluate the efficacy and adverse reaction of SMANCS, we reviewed 10 cases treated by TAE with SMANCS among 896 cases treated by TAE for liver cancer during the past three years at our institute. Our criteria for using SMANCS were as follows: a) reduced effectiveness of past TAE with Lipiodol, hydrophilic drugs and gelatin sponge; b) sufficient caliber and blood flow in the hepatic artery; and c) good hepatic function. The 1- and 2-year survival rates after treatment with SMANCS were 50% and 25%, respectively. The 3- and 5-year survival rates after initial treatment (first TAE, etc.) were 40% and 20%, respectively. There were no significant complications in clinical course, however, subsequent hepatic arteriogram often showed arterial change that may interfere with further regional therapy for the liver.