Use of electroporation to accelerate the skin permeability enhancing action of oleic acid

Rat skin permeability after treatment by electroporation (newly developed frog type electrode, 100V, 10 pulses), oleic acid/propylene glycol (PG) and a combination of both were investigated using Fourier transformed infrared attenuated total reflectance (FT-IR/ATR) analysis. Electroporation immediately disordered the stratum corneum lipid structure up to a certain threshold level. This action lasted throughout the experiment. This may be attributed to the formation of long lifetime of metastable lipid structures, which may allow molecules to pass to the inside of the stratum corneum due to the electroporation-induced fluidized lipid membranes. Electroporation also altered the protein structure of the stratum corneum. When electroporation was combined with 0.05 M oleic acid/PG, uptake of oleic acid and PG into the stratum corneum was remarkably accelerated compared to the application of only 0.05 M oleic acid/PG to the skin. This indicates that electroporation enables oleic acid and PG to penetrate the stratum corneum easily by disrupting the structure of the latter. PG transfer into the dermis from the epidermis was accelerated, not because of the direct action of electroporation on the dermis, but because electroporation induced the rapidly disordering action of oleic acid on the stratum corneum. Lipid-soluble indomethacin permeated the skin more rapidly when the skin was treated with electroporation plus oleic acid/PG than with 0.05 M oleic acid/PG in vitro.     

Biweekly low-dose cisplatin and 5-fluorouracil combination chemotherapy for advanced gastrointestinal carcinoma

Biweekly intravenous infusions of low-dose cisplatin (CDDP) and 5-fluorouracil (5-FU) were evaluated in 80 patients with advanced or recurrent gastric, colorectal, pancreatic or gallbladder adenocarcinoma. CDDP was given biweekly at a dose of 15 mg/m2 infused for 30 minutes, and 5-FU 375 mg/m2 was infused for 2 hours as many times as possible. The response rate among patients with gastric cancer was 26%, colorectal cancer 10%, pancreatic cancer 7.7%, and gallbladder cancer 42.9%. The response rates were not so high, but the median survival time of patients with recurrent gastric cancer was 17.3 months, pancreatic cancer 6.7 months, and gallbladder cancer 10.7 months. A patient with unresected advanced pancreatic head cancer with liver and para-aortic lymph node metastases received this therapy 38 times, and lived for 54 months. No severe side effects occurred in any of these cases. Thus, this chemotherapy could well be effective for the outcome of cases of advanced gastrointestinal carcinoma.     

Cardiac valve replacement with Wada-Cutter prosthesis

The Wada-Cutter cardiac valve prosthesis, a hingeless valve, was developed and used clinically in 106 patients in whom 42 aortic valve replacements, 48 mitral valve replacements, 5 tricuspid valve replacements, and 11 multiple valve replacements were done. A continuous knotless suture technique was invariably employed for fixation of the prosthesis regardless of the type of operation.     

Small cell carcinoma of the esophagus responding to fourth-line chemotherapy with weekly paclitaxel

A patient was diagnosed with a small cell carcinoma of the esophagus (T4N1M1b by the International Union Against Cancer [UICC] classification) in October 2002, and initially received two courses of concurrent chemotherapy with 5-fluorouracil (5-FU; 400 mg/m² by continuous infusion; days 1–5 and 8–12) and cisplatin (40 mg/m² by drip infusion; days 1 and 8) and radiation therapy (2 Gy/day, days 1–5, 8–12, and 15–19; total, 30 Gy per course) with the second course given after a 2-week interval. Two courses of chemotherapy with 5-FU (800 mg/m²; days 1–5) and cisplatin (80 mg/m²; day 1) given after this was completed. Although a complete response had been confirmed, recurrence with multiple liver and lymph node metastases was detected 3 months after the cessation of the second course of chemotherapy. Although the patient received second-line chemotherapy with irinotecan (150 mg/m²; every 2 weeks) from June 2003, the disease progressed. Brain metastases developed during third-line chemotherapy with gemcitabine (1000 mg/m² weekly by drip infusion). The symptoms were attenuated after whole-brain radiation (30 Gy), and fourth-line chemotherapy using paclitaxel (80 mg/m²; weekly) was initiated from November 2003. A computed tomography scan 1 month after the first course of paclitaxel showed remarkable regression of the liver metastases. The treatment strategy used for treating small cell carcinomas of the lung may be applicable for these carcinomas of the esophagus.     

Complications of craniofacial resection for malignant tumors of the skull base: report of an International Collaborative Study

BACKGROUND: Advances in imaging, surgical technique, and perioperative care have made craniofacial resection (CFR) an effective and safe option for treating malignant tumors involving the skull base. The procedure does, however, have complications. Because of the relative rarity of these tumors, most existing data on postoperative complications come from individual reports of relatively small series of patients. This international collaborative report examines a large cohort of patients accumulated from multiple institutions with the aim of identifying patient-related and tumor-related predictors of postoperative morbidity and mortality and set a benchmark for future studies. METHODS: One thousand one hundred ninety-three patients from 17 institutions were analyzed for postoperative mortality and complications. Postoperative complications were classified into systemic, wound, central nervous system (CNS), and orbit. Statistical analyses were carried out in relation to patient characteristics, extent of disease, prior radiation treatment, and type of reconstruction to determine factors that predicted mortality or complications. RESULTS: Postoperative mortality occurred in 56 patients (4.7%). The presence of medical comorbidity was the only independent predictor of mortality. Postoperative complications occurred in 433 patients (36.3%). Wound complications occurred in 237 (19.8%), CNS-related complications in 193 (16.2%), orbital complications in 20 (1.7%), and systemic complications in 57 (4.8%) patients. Medical comorbidity, prior radiation therapy, and the extent of intracranial tumour involvement were independent predictors of postoperative complications. CONCLUSIONS: CFR is a safe surgical treatment for malignant tumors of the skull base, with an overall mortality of 4.7% and complication rate of 36.3%. The impact of medical comorbidity and intracranial tumor extent should be carefully considered when planning therapy for patients whose tumors are amenable to CFR.     

Acute inflammatory sensorimotor polyradiculoneuropathy associated with immune thrombocytopenic purpura

Although acute inflammatory polyneuropathy (AIP) and immune thrombocytopenic purpura (ITP) are both believed to be immune-mediated disorders, only a few cases have been reported in which these two diseases co-existed. We describe a case of a 67-year-old patient who developed quadriparesis, ophthalmoplegia and severe sensory impairment along with thrombocytopenia. Detailed examinations, including the measurement of anti-ganglioside antibodies and anti-glycoprotein-IIb-IIIa-IgG-producing B-cells, revealed that he developed AIP and ITP. By reviewing past similar reports, we noticed that AIP associated with ITP tends to manifest severe sensory impairment and is often preceded by upper respiratory tract infection, but not by gastrointestinal infection.     

Immunohistological study for estrogenic activities of nitrophenols in diesel exhaust particles

We recently isolated 3-methyl-4-nitrophenol (4-nitro-m-cresol; PNMC) and 4-nitro-3-phenylphenol (PNMPP) from diesel exhaust particles (DEP) and identified them as vasodilators and xenoestrogens. The estrogenic activity of PNMC and PNMPP was further examined by using immunohistochemical staining of proliferating cell nuclear antigen (PCNA) in uterine luminal epithelium of ovariectomized 25-d-old immature female rats injected with PNMC and PNMPP subcutaneously for 2 d. Significant increases were observed in uterine luminal epithelium in PCNA positive cells of animals receiving 10 and 100 mg/kg PNMC and 0.1 mg/kg PNMPP compared with controls. These results clearly show the estrogenic activity of PNMC and PNMPP by cell proliferation on the uterine luminal epithelium.