Lidocaine transport through living rat skin using alternating current.

The purpose of the study was to determine whether lidocaine could be transported through living rat skin using alternating current and to determine whether lidocaine transport depends on voltage. The drug delivery cell was originally constructed for the application of an electric field. Hairless rats were anaesthetised using sevoflurane, and a tracheotomy was performed. The drug delivery cell, with lidocaine solution in the donor cell, was placed on the abdominal skin. Samples were collected from the subcutaneous tissue using a microdialysis probe inserted into the abdominal subcutaneous tissue, and the lidocaine concentrations in the samples were determined using high-performance liquid chromatography. The lidocaine concentration in the rat skin increased in time, and voltage-dependency was approximately linear. The lidocaine concentration after the application of 20 V for 21 min was about ten-fold higher than that observed after 21 min of passive diffusion. Lidocaine was successfully transported through living rat skin in a voltage- and time-dependent manner. This drug delivery cell may contribute to local anaesthesia and pain management of human skin.

Application of a mandibular nerve block using an indwelling catheter for intractable cancer pain.

We report a case in which a mandibular nerve block using an indwelling catheter was employed for pain management in a terminal case of orofacial cancer. The patient was a 74-year-old female weighing 27 kg. She had a 27-month history of mouth floor and tongue cancer. The cancer recurred and spread to bilateral face and neck. The severest pain mainly originated from the right mandibular region. Two steps of pain relief were performed for the patient. First, pain control using 1% lidocaine or 0.25% bupivacaine administered intermittently or continuously through an indwelling catheter in the mandibular nerve was performed for 1 week to estimate the amount of pain relief thereby obtained. Second, a neurolytic block was applied to the mandibular nerve through the catheter. After the neurolytic block, the total dosage of morphine and diclofenac remained unchanged for 2 months. We conclude from the present case that this technique is an excellent means of obtaining long-term pain control in patients with intractable orofacial cancer pain.

A mechanism of the high frequency AC iontophoresis.

The efficiency and the voltage dependence of the AC iontophoresis were studied in vitro. Two cylindrical glass cells separated by a cellophane film were used, where the donor cell was filled with the solution of target electrolytes and the receptor cell with distilled water. The sinusoidal AC voltage with a frequency of 1 kHz was applied between the two platinum plates located at the opposite ends of two cells. The time variation of the ion concentration was evaluated by measuring the impedance of the solution in the receptor cell. The transportation velocity of the ions increased with the amplitude of the voltage applied between two platinum plate electrodes apart 20 mm up to approximately 15 V, and leveled off above approximately 15 V. A theoretical model is proposed on the AC iontophoresis, where each ion moves together with the surrounding water molecules when it is hydrated. The effective Stokes radius of an ion is assumed to be half of the whole size of the ion with hydrating water molecules. When the external alternating electric field strongly vibrates the ion, the ion-dipole interactions between the ion and water molecules are broken, resulting in the reduced effective Stokes radius, which leads to the increase of the diffusion efficiency.

Clinical predictors of recurrence site after hepatectomy for metastatic colorectal cancer.

BACKGROUND/AIMS: Surgical resection of hepatic colorectal metastasis may produce long-term survival and cure; however, a significant proportion of patients will have intrahepatic and/or extrahepatic recurrence with a poor prognosis. The aim of this study was to define clinical predictors of recurrence site after hepatectomy in terms of stratifying patients for adequate adjuvant trials to improve the prognosis. METHODOLOGY: Clinical, pathologic, and outcome data for 70 consecutive patients undergoing hepatectomy for colorectal metastasis isolated to the liver were reviewed retrospectively, and all data were analyzed by the logistic multivariate regression model. RESULTS: Recurrence in the remnant liver was seen in 60% of patients, and recurrence in the lung was found in 34% of patients. Number of liver tumors was the only significant and independent predictor of recurrence in the remnant liver (P = 0.048). All patients with three or more tumors experienced recurrence. Location of liver tumors lying adjacent to the hepatic vein, which was confirmed by preoperative imaging techniques, was the only significant and independent predictor of recurrence in the lung (P = 0.020). CONCLUSIONS: Number and location of liver tumors would be the significant and independent clinical predictors of recurrence site after hepatectomy for metastatic colorectal cancer. This might be useful for justification and selection of effective adjuvant trials after surgery.

The impact of interferon gamma receptor expression on the mechanism of escape from host immune surveillance in hepatocellular carcinoma.

Interferon gamma (IFN-gamma) plays an important role in host defense mechanism and participates in the progression of chronic liver disease. IFN-gamma exerts its pleiotrophic effects by transcriptional regulation of expression of numerous genes, such as major histocompatibility complex (MHC) class I and Fas, through interaction with IFN-gamma receptor (IFN-gamma-R). Although hepatocytes in normal liver express weak or no IFN-gamma-R, those in acute and chronic liver disease up-regulate its expression. A study using IFN-gamma-R alpha-chain knock-out mice revealed the actions of IFN-gamma on tumor cells as an extrinsic tumor-suppressor mechanism. However, it is unclear whether or how hepatocellular carcinoma (HCC) blocks the signal transduction of IFN-gamma to evade host immune surveillance. We examined the expression of IFN-gamma-R and IFN-gamma-inducible genes in 44 cases with HCC using real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. In noncancerous liver tissues (n = 38), IFN-gamma-R expression on the cell surface was up-regulated in 27 cases. In IFN-gamma-R-negative cases (n = 15), tumor size was larger (P =.032), serum alpha-fetoprotein (AFP) level was higher (P =.001), intrahepatic and extrahepatic metastasis was more common (P =.044 and.013, respectively), and Ki-67 labeling index (LI) was higher (P =.041), compared with IFN-gamma-R-positive cases. Accordingly, the evasion mechanism may play an important role in progression, especially metastasis, in HCC. The significant correlation between the status of IFN-gamma-R and the expression of Fas and MHC implies that the loss of IFN-gamma-R might contribute to the mechanism of escape from host immune rejection in HCC.