Influences of splanchnic nerve blockade on endocrine-metabolic responses to upper abdominal surgery

Twelve patients undergoing gastrectomy received combined epidural and splanchnic nerve blockade (Group E&S), and changes in plasma ACTH, cortisol, glucose and FFA were compared with those undergoing gastrectomy under general anaesthesia (Group G) or epidural analgesia alone (Group E). Plasma ACTH increased in all groups on the day of operation and was significantly higher in Group G than the other groups. Levels of ACTH in Group E&S were lower than Group E, but the differences were not significant. Cortisol response in Group G was most pronounced and prolonged. This cortisol response was significantly attenuated in Group E and was further inhibited in Group E&S. Blood glucose and FFA increased in Groups G and E during the operation but the increase was significantly less in Group E. In Group E&S, glucose and FFA concentrations showed practically no change throughout the study, being significantly lower than in Group E. The results indicated that the splanchnic nerve is responsible for producing endocrine-metabolic responses to gastric surgery even under epidural blockade.     

Permeation characteristics of a hydrophilic basic compound across a bio-mimetic artificial membrane

In the present study, the permeation characteristics of a hydrophilic basic compound (HBC) in a bio-mimetic parallel artificial membrane permeability assay (bio-mimetic PAMPA) were investigated in detail. The bio-mimetic PAMPA membrane was constructed on a hydrophobic filter by impregnating a lipid solution consisting of phosphatidylcholine (0.8%, w/w), phosphatidylethanolamine (0.8%, w/w), phosphatidylserine (0.2%, w/w), phosphatidylinositol (0.2%, w/w), cholesterol (1.0%, w/w), and 1,7-octadiene (97.0%, w/w). The pH-permeability curve (pH 3-10), the effect of lipid composition, concentration dependency (0.02-2.00 mM), and inhibition by other cationic compounds, were investigated for several HBCs. Ketoprofen and methylchlorpromazine were also employed as an acidic and a quaternary ammonium compound, respectively. At pH 3-6, the permeability of timolol, a HBC, was higher than expected from the pH-partition hypothesis, especially in the PI-containing membrane, whereas the pH-permeability curve of ketoprofen followed the pH-partition hypothesis. Permeation of HBC was saturable and inhibited by basic and quaternary ammonium compounds. Similar results were also found for methylchlorpromazine. The permeation characteristics of HBC observed in the present study are not usually expected in a passive permeation process across an artificial membrane. The participation of facilitated permeation of cationic species was suggested, in addition to a simple passive diffusion of un-dissociated species. Ion pair transport was suggested as a possible permeation mechanism of cationic species. However, further investigation is necessary to clarify the reason for the permeation characteristics of HBC.     

Induction chemoradiotherapy and surgical resection for selected stage IIIB non-small-cell lung cancer

BACKGROUND: Combination chemotherapy using an oral combination of uracil and tegafur (UFT) plus cisplatin and concurrent thoracic radiotherapy is reported to have a high response rate and less toxicity for locally advanced non-small-cell lung cancer (NSCLC) patients. We performed a phase II trial using this chemoradiotherapy as an induction treatment. METHODS: Patients with marginally resectable stage IIIB NSCLC, an age younger than 70 years, a performance status of 0 or 1, and good organ function were eligible. The UFT (400 mg/m(2)) was administered orally on days 1 through 14 and 22 through 35 and cisplatin (80 mg/m(2)) was injected intravenously on days 8 and 29. Radiotherapy with a total dose of 40 Gy was delivered in 20 fractions from day 1. A surgical resection was performed from 3 to 6 weeks after completing the induction treatment. RESULTS: Twenty-seven patients, 18 male and 9 female with a median age of 56 years and ranging from 36 to 69 years, were entered into the phase II trial. Clinical T4 and N3 cancers were observed in 22 and 7 patients, respectively. Twenty-five (93%) achieved a partial response. The most frequently observed adverse event was grade 3 leukopenia in 26%. Of 25 patients who underwent a thoracotomy, 22 had a tumor resection. In all 22 patients a complex resection including a resection of the superior vena cava, carina, and vertebrae was required. Operative morbidity and mortality rates were 36% and 4% respectively. The calculated 1-year and 3-year survival rates of all 27 patients were 73% and 56% respectively. CONCLUSIONS: Chemotherapy using UFT plus cisplatin and concurrent radiotherapy as induction treatment and a surgical resection for patients with marginally resectable stage IIIB NSCLC is feasible and promising. However it is difficult to conduct multi-institutional trials even for selected stage IIIB disease as a complex resection in almost all patients is necessary.     

Long-term survivors in resected and nonresected small cell lung cancer.

Long-term survival (greater than or equal to 3 years) was evaluated in 164 patients with small cell lung cancer (SCLC). Thirty-seven patients underwent surgical resection, and 127 did not. All but one resected patient received combination chemotherapy. Of the 20 (12%) long-term survivors, 13 (35%) were resected, and 7 (6%) were not. Eleven of these resected patients had pathologically confirmed stage I disease. All of the 7 nonresected patients achieved complete remission by treatment, 6 of these having presented with limited disease. In addition, all patients received thoracic irradiation combined with chemotherapy. Two of the 20 patients who survived beyond 3 years developed a second malignancy 11.3 and 12 years, respectively, after initial treatment for SCLC. In conclusion, surgical resection for stage I, and probably stage II SCLC followed by chemotherapy may be an appropriate therapeutic approach. For advanced limited disease, thoracic irradiation, in addition to chemotherapy, seems to improve long-term survival.     

Expression of Bcl-2 on leukocytes in prostatic fluid from patients with acute and chronic prostatitis

 In our continuing investigation to clarify the significance of leukocytosis and its prolongation in prostatic fluid (PF) from prostatitis patients, we investigated whether expression of the antiapoptotic gene Bcl-2 on leukocytes in prostatic fluid has any relation with prolonged leukocytosis in prostatitis. The subjects were eight patients with acute bacterial prostatitis (ABP) and eight with nonbacterial prostatitis (NBP) with a history of more than 2 years. Twelve micrograms of protein obtained from leukocytes in PF were subjected to Western blot analysis. Bcl-2 was expressed in seven of eight (87.5%) and six of eight (75.0%) patients with NBP and ABP, respectively. Quantitative density analysis of the Bcl-2 band did not show any statistically significant differences between patients with NBP and those with ABP. These results suggest that the expression of antiapoptotic Bcl-2 on leukocytes in PF is not a cause of leukocyte longevity in long-term prostatitis. Received: November 13, 2002 / Accepted: February 28, 2003     

Protection of hepatic cells from apoptosis induced by ischemia/reperfusion injury by protein therapeutics

Aim: Apoptosis is involved in hepatic ischemia/reperfusion injury. The protein FNK, constructed from an anti-apoptotic protein Bcl-x(L), exhibits the stronger anticell death activity. We evaluated the effect of FNK on apoptosis after hepatic ischemia and reperfusion, using FNK-overexpressing transgenic mice and the HIV/Tat protein-transduction-domain (PTD) that mediates the introduction of FNK into cells when fused with FNK (PTD-FNK). Methods: Mice were given hepatic ischemic insult for 90 min followed by reperfusion for 3 h. FNK overexpression was determined by immunohistochemistry and Western blot. PTD-FNK was intraperitoneally injected into wild mice 3 h before the insult. Liver injury was determined by the caspase activation, DNA fragmentation, and hematoxylin-eosin and terminal deoxynucleotidyl transferase-mediated dUTP- digoxigenin nick-end labelling (TUNEL) stainings. Results: In FNK-transgenic mice, FNK overexpression inhibited the activation of caspase 3/caspase 3-like activity and DNA fragmentation caused by the injury. In wild mice preinjected with PTD-FNK, PTD-FNK significantly inhibited the caspase activation and DNA fragmentation, reduced the area of liver vacuolization, and protected hepatic cells surrounding blood vessels, irrespective of central or portal veins, from the ischemia/reperfusion damage. Conclusions: FNK inhibits apoptotic death due to the ischemia/reperfusion injury. Our results provide the reasonable expectation of therapeutic protein PTD-FNK for clinical applications, such as transplantation, to protect against ischemia/reperfusion injury.     

Effect of immobilization on vitamin D status and bone mass in chronically hospitalized disabled stroke patients.

OBJECTIVE: To assess the influence of immobilization upon vitamin D status and bone mass in chronically hospitalized, disabled, elderly patients following stroke. DESIGN: cross-sectional study. SETTING: Department of geriatric neurology in a Japanese hospital. SUBJECTS: 129 chronically hospitalized, disabled, elderly stroke patients and 28 age-matched controls. RESULTS: We observed a deficiency of both 1,25-dihydroxyvitamin D (1,25-[OH]2D; 24.3 pg/ml) and 25-hydroxyvitamin D concentrations (25-OHD; 11.7 ng/ml) in stroke patients compared with controls. A high serum ionized calcium (mean; 2.648 mEq/l) was an independent determinant of the Barthel index (66) and 1,25-[OH]2D. When the patients were categorized into three groups by 25-OHD level (deficient, insufficient and sufficient), there was no difference in the mean 1,25-[OH]2D levels. Parathyroid hormone levels were normal or low and did not correlate with 25-OHD. Serum bone turnover variables and bone mineral density (BMD) of the second metacarpal in patients were significantly decreased compared to control subjects. Independent determinants of BMD included Barthel index, 25-OHD and 1,25-[OH]2D. CONCLUSIONS: 1,25-[OH]2D deficiency in immobilized stroke patients is not caused by substrate (25-OHD) deficiency but by hypercalcaemia. Immobilization-induced hypercalcaemia may inhibit parathyroid hormone secretion and thus 1,25-[OH]2D production, resulting in decreased BMD. Immobilization itself also may be responsible for decreased BMD. Exogenous 1,25-[OH]2D (calcitriol) rather than dietary vitamin D supplementation may be required in disabled elderly stroke patients who have a deficiency of 1,25-[OH]2D in order to prevent hip fractures, which frequently occur in this population.