Biodegradation and biocompatibility of polyorganophosphazene

We investigated biodegradation and biocompatibility of poly(organophosphazenes). We prepared poly(organophosphazenes) having different side chain groups. The blood compatibility of poly(organophosphazenes) containing fluorinated side groups, poly(bis[trifluoroethoxy]phosphazene) (PbFP) and poly([trifluoroethoxy][ethyl glycinate]phosphazene) (PFGP), without heparinization were evaluated in vitro. The deformation and aggregation of platelets adhered on PbFP and PFGP were not observed and they suppressed platelet activation. Additionally, PbFP and PFGP showed a higher degradation rate, despite their high hydrophobic nature. We found that the high mobility of water in PbFP and PFGP was one of the important factors facilitating their degradation. Their polymer structures were formed in a more open nature, indicating that water easily attacked the backbone of the phosphorus and nitrogen atoms in the poly(organophosphazene). On the other hand, the proliferation of HeLa cells cultured on poly(organophosphazene) was reduced compared with that on the control tissue culture polystyrene.     

Minilaparotomy approach to terminal ileal Crohn's disease

The feasibility and safety of a minilaparotomy approach to terminal ileal Crohn's disease have not been fully elucidated. The purpose of this study was to compare early outcomes utilizing this technique as an alternative to conventional approaches. Nine patients with terminal ileal Crohn's disease (but no complicating enteric fistulas) who underwent minilaparotomy between January 1998 and September 2000 were studied prospectively. The minilaparotomy approach entails a complete surgical procedure performed through a skin incision of less than 7 cm. Ten similar patients who underwent conventional laparotomy between January 1995 and December 1997 served as the control group. Age, gender, body weight, height, body mass index, number of prior laparotomies, operating times, operative blood loss, and types of operative procedure were similar for cases and controls. The length of the laparotomy incision in the minilaparotomy approach group was significantly shorter than that in the conventional approach group (median length 6.0 vs. 16.5 cm; p <0.05). Postoperative intervals until initial standing and walking were significantly shorter for minilaparotomy patients than conventional surgery patients (p <0.05 and p <0.05, respectively), whereas postoperative intervals until passing flatus, urinary catheter removal, and tolerance of liquids and solids did not differ for the two groups, nor did the analgesic requirement or postoperative hospital stay. Postoperative complications developed in two conventional-group patients; none was noted with the minilaparotomy approach. Our data suggest that the minilaparotomy approach to terminal ileal Crohn's disease without an enteric fistula is feasible, safe, and less invasive than the conventional approach.     

Intracranial germinoma with syncytiotrophoblastic giant cells in the cerebellopontine angle--case report

A 23-year-old man presented with a 3-week history of left hearing disturbance and left facial nerve paresis. T1-weighted magnetic resonance (MR) imaging showed an iso-intense mass in the left cerebellopontine angle (CPA), with homogeneous enhancement with gadolinium-diethylenetriaminepenta-acetic acid. T2-weighted MR imaging showed the mass as heterogeneously iso- to hyperintense. Gross total removal of the tumor was achieved. Histological examination revealed that the tumor was a germinoma with syncytiotrophoblastic giant cells. Whole central nervous system irradiation with cisplatin-etoposide chemotherapy was performed postoperatively. He has been in good condition with no sign of recurrence for 7 years. Intracranial germ cell tumors in the CPA are very rare. Total surgical removal followed by irradiation and chemotherapy will provide a good outcome.     

Prospective study of extended segmentectomy for small lung tumors: the final report

BACKGROUND: Minimal resection of small lung tumors is still controversial. This study was conducted to clarify whether this type of operation is acceptable. METHODS: From January 1992 to December 1994, 73 patients were registered in a multiinstitutional trial of limited resection for peripheral lung tumors less than 2 cm in diameter. The operative procedure consisted of extended segmentectomy in which the cut line of the lung was beyond the burdened segment, confirming N0 disease by intraoperative lymph node examination of frozen sections. The operation was changed to other procedures if the report was positive. RESULTS: All the patients were observed more than 5 years. There were no perioperative deaths and no major complications. A total of 55 patients were finally enrolled in this study. Ten patients died postoperatively, 4 of lung cancer and the remaining 6 died of other diseases, with no signs of recurrence. The 5-year survival rate, excluding these 6 patients, was 91.8%; for all patients including those who died it was 81.8%. A total of 18 patients were not included in this study for various reasons. The decrease in forced vital capacity was 11.3% +/- 9.8% compared with the preoperative value. CONCLUSIONS: Extended segmentectomy is an alternative method as a standard operation for patients with small peripheral lung tumors, and the loss of lung function is minimal. However, patient selection must be strict, with intraoperative pathologic examination, and a wide margin to the lesion beyond the burdened segment is mandatory.     

Impairment of insulin signaling in human skeletal muscle cells by co-culture with human adipocytes

Adipocyte factors play a major role in the induction of insulin resistance in skeletal muscle. To analyze this cross-talk, we established a system of co-culture of human fat and skeletal muscle cells. Cells of three muscle donors were kept in co-culture with cells of various fat cell donors, and insulin signaling was subsequently analyzed in myocytes. Insulin-induced tyrosine phosphorylation of insulin receptor substrate (IRS)-1 was completely blocked, with unaltered expression of IRS-1. Troglitazone increased insulin action on IRS-1 phosphorylation, in both the absence and presence of co-culture. Insulin-regulated activation of Akt kinase in the myocytes was significantly reduced after co-culture, with troglitazone restoring insulin action. Addition of tumor necrosis factor (TNF)-alpha (2.5 nmol/l) to myocytes for 48 h reduced IRS-1 expression and inhibited IRS-1 and Akt phosphorylation comparable to the effect of co-culture. Lower doses of TNF-alpha were ineffective. After co-culture, TNF-alpha in the culture medium was below the detection limit of 0.3 pmol/l. A very low level of resistin was detected in the supernatant of myocytes, but not of adipocytes. In conclusion, the release of fat cell factors induces insulin resistance in human skeletal muscle cells; however, TNF-alpha and resistin appear not to be involved in this process.     

Effect of phenylephrine injected into the nucleus tractus solitarius of Sprague-Dawley rats and spontaneously hypertensive rats

In alpha-chloralose-anesthetized Sprague-Dawley (SD) rats with unilateral nucleus tractus solitarius (NTS) lesions, injection of the alpha(1)-adrenergic receptor agonist phenylephrine into the contralateral NTS dose-dependently increased arterial pressure (AP). Bunazosin (0.1 nmol) or prazosin (0.36 nmol), an alpha(1)-adrenergic receptor antagonist, also increased AP. When injected into the NTS, pre-treatment with phenylephrine (10 nmol) or both antagonists abolished the cardiovascular effects of glutamate and acetylcholine. In contrast, pre-treatment with prazosin or methylatropine did not alter the effect of phenylephrine. Phenylephrine (30 nmol) injected into the NTS abolished aortic depressor nerve (ADN) evoked-responses. The pressor effect of phenylephrine in the NTS was exaggerated in spontaneously hypertensive rats (SHR). These results suggest that when injected into the NTS, the effect of phenylephrine may be due to a baroreflex blockade resulting from direct modulatory actions or non-specific neuronal alterations rather than stimulating the alpha(1)-adrenergic receptor. Additionally, this effect is enhanced in SHR.     

Clinical significance of nm23 expression and chromosome 17 numerical aberrations in primary gastric cancer

The metastasis suppressor gene nm23 located on chromosome 17 might be one of the targets in deletions of chromosome 17. In this study, we analyzed the expression of nm23 and chromosome 17 aberrations in gastric cancer and assessed their clinicopathological and prognostic significance. In 103 gastric cancer patients, we examined nm23 expression by immunohistochemistry and detected chromosome 17 aberrations by fluorescence in situ hybridization. There was a significant difference in the expression of nm23 among differentiated histologic types (well > moderately > poorly) (p < 0.01). Negative expression of nm23 correlated with depth of invasion (p < 0.01), lymph node metastasis (p < 0.05), lymphatic invasion (p < 0.05), venous invasion (p < 0.05), poor prognosis (p < 0.05), and chromosome 17 loss (p < 0.05). Chromosome 17 aberrations broadly correlated with clinicopathological variables and were associated with poor prognosis (p < 0.05). Univariate analyses identified nm23 (p < 0.05), chromosome 17 aberrations (p < 0.05), tumor size (p < 0.01), depth of invasion (p < 0.0001), lymph node metastasis (P < 0.001), hepatic metastasis (p < 0.01), peritoneal dissemination (p < 0.01), and lymphatic invasion (p < 0.01) as significant prognostic factors. Multivariate analysis showed that expression of nm23 and chromosome 17 aberrations were not independent prognostic indicators. Our results indicate that negative expression of nm23 and chromosome 17 numerical aberrations correlate with tumor progression and poor prognosis but are not independent prognostic indicators.     

Prognostic factors in patients with hepatocellular carcinoma treated by transcatheter arterial embolization

BACKGROUND: Transcatheter arterial embolization induces marked antitumor response in patients with hepatocellular carcinoma, but the survival benefit of transcatheter arterial embolization remains to be determined. This study investigated prognostic factors in patients with advanced hepatocellular carcinoma treated by transcatheter arterial embolization. METHODS: A total of 128 consecutive patients with non-resectable hepatocellular carcinoma, who had undergone transcatheter arterial embolization between May 1990 and August 1998, were analyzed to investigate prognostic factors. RESULTS: Median survival time and survival proportions at 1, 3 and 5 years were 3.3 years, 92.0, 54.6 and 23.4%, respectively. By multivariate analysis using the accelerated failure time model, age <60 years, hepatitis C virus antibody positivity, serum albumin >3.5 g/dl, absence of portal vein invasion and serum alpha-fetoprotein level <400 ng/ml were significantly associated with favorable survival. For clinical application, we also propose a prognostic equation with combination of specific prognostic factors, by which survival curves of each patient could be predicted directly. CONCLUSION: The findings of the current study may be helpful in predicting the life expectancy of hepatocellular carcinoma patients treated by transcatheter arterial embolization and in designing future clinical trials of transcatheter arterial embolization for hepatocellular carcinoma.     

Diagnostic clues for early pancreatic cancer

Pancreatic cancer is still a difficult diagnostic and therapeuticchallenge. Its prognosis is extremely poor because the diseaseis generally recognized at a very advanced stage and its clinicalcourse is very rapid. Surgery is the only curative treatmentfor pancreatic cancer and outcome is related mainly to tumorstage. This aggressive approach is effective only if the tumorsare detected at an early stage. Early symptoms of pancreaticcarcinoma, including weight loss, anorexia, epigastric discomfortand back pain, are often non-specific and vague (1), so diagnosismay be considerably delayed. In many patients with small pancreaticcancer which has a possibility of cure, the tumor was incidentallydetected in laboratory tests and/or imaging. We must try toconvert such incidental discovery into more certain diagnosis. The mortality rate from pancreatic cancer, which is almostequal to the incidence