Jugular bulb oxygen saturation under propofol or sevoflurane/nitrous oxide anesthesia during deliberate mild hypothermia in neurosurgical patients

Sevoflurane and propofol have been widely used as anesthetic agents for neurosurgery. Recent evidence has suggested that the influence of these anesthetics on cerebral oxygenation may differ. In the present study, the authors investigated jugular bulb oxygen saturation (SjO2) during propofol and sevoflurane/nitrous oxide anesthesia under mildly hypothermic conditions. After institutional approval and informed consent, 20 patients undergoing elective craniotomy were studied. Patients were randomly divided to the group S/N2O (sevoflurane/nitrous oxide/fentanyl anesthesia) or the group P (propofol/fentanyl anesthesia). After induction of anesthesia, the catheter was inserted retrograde into the jugular bulb and SjO2 was analyzed. During the operation, patients were cooled and tympanic membrane temperature was maintained at 34.5 degrees C. SjO2 was measured at normocapnia during mild hypothermia and at hypocapnia during mild hypothermia. There were no statistically significant differences in demographic variables between the groups. During mild hypothermia, SjO2 values were significantly lower in group P than in group S/N2O. The incidence of SjO2 less than 50% under mild hypothermic-hypocapnic conditions was significantly higher in group P than in group S/N2O. These results suggest that hyperventilation should be more cautiously applied during mild hypothermia in patients anesthetized with propofol and fentanyl versus sevoflurane/nitrous oxide/fentanyl.     

Effects of increasing concentrations of propofol on jugular venous bulb oxygen saturation in neurosurgical patients under normothermic and mildly hypothermic conditions

BACKGROUND: Recent evidence suggested that propofol can deteriorate the cerebral oxygen balance compared with inhalational anesthetics. However, dose-related influences of propofol on cerebral oxygen balances were not clearly investigated. In the current study, the authors investigated the effects of increasing concentrations of propofol on jugular venous bulb oxygen saturation (Sj(O2)) in neurosurgical patients under normothermic and mildly hypothermic conditions. METHODS: After institutional approval and informed consent were obtained, 30 adult patients undergoing elective craniotomy were studied. Patients were randomly allocated to either normothermic or hypothermic group (n = 15 in each group). In the normothermic and hypothermic groups, tympanic membrane temperature was maintained at 36.5 degrees and 34.5 degrees C, respectively. Sj(O2) was measured at predicted propofol concentrations of 3, 5, and 7 microg/ml using a target-controlled infusion system in both groups. RESULTS: At a predicted propofol concentration of 3 microg/ml, there were no significant differences in Sj(O2) values between the normothermic and hypothermic groups, although the incidence of desaturation (Sj(O2) < 50%) was significantly higher in the normothermic group than in the hypothermic group (30% vs. 13%; P < 0.05). Sj(O2) values and the incidence of desaturation remained unchanged during the changes in predicted propofol concentration from 3 to 7 microg/ml both in the normothermic and hypothermic groups. CONCLUSION: The results indicated that the increasing concentrations of propofol did not affect Sj(O2) values in neurosurgical patients under normothermic and mildly hypothermic conditions.     

An evaluation of white matter injury after spinal cord ischemia in rats: a comparison with gray matter injury

We quantitatively assessed both gray and white matter injury after spinal cord ischemia in rats, and the relationship between the magnitude of gray and white matter injury was determined. Twenty-five male rats were anesthetized with isoflurane, and spinal cord ischemia (SCI) was induced by balloon intraaortic occlusion combined with hypotension. The animals were randomly allocated to one of the following three groups: animals with SCI for 12 min (SCI-12; n = 8), 15 min (SCI-15; n = 9), or those with sham operation (n = 8). Twenty-four hours after reperfusion, hindlimb motor function was assessed using the Basso-Beattie-Bresnahan scale scoring. Gray matter damage was assessed on the basis of the number of normal neurons in the ventral horn. White matter damage was assessed on the basis of the extent of vacuolation and amyloid precursor protein immunoreactivity in the ventral and ventrolateral white matter. There were significantly less normal neurons in the SCI-15 group compared with those in the SCI-12 and sham groups (P < 0.05). There was a significant positive correlation between the Basso-Beattie-Bresnahan scores and the number of normal neurons. The percentages of vacuolation areas in the SCI-15 group were significantly larger compared with those in the SCI-12 and sham groups (30% +/- 10% versus 9% +/- 7%, 0% +/- 0%, P < 0.05). Immunohistochemical analysis revealed increased amyloid precursor protein immunoreactivity in the swollen axons, especially in the SCI-15 group. There was a significant negative correlation between the number of normal neurons and percentages of vacuolation areas. These results indicate that both gray and white matter were injured after SCI in rats and the degree of white mater injury was correlated with the severity of gray matter injury after a relatively short recovery period.     

Unintentional intrapleural insertion of an epidural catheter: should we remove it or leave it in situ to provide perioperative analgesia?

We report three patients who had intrapleural insertion of an intended thoracic epidural catheter. These misplaced catheters were used for local anesthetic administration. Bupivacaine injection via these catheters in two cases was effective for reducing postoperative pain. We conclude that if an intended thoracic epidural catheter is found to be in the intrapleural cavity at the time of surgery and if correct replacement of the catheter into the epidural space is not believed to be feasible after surgery, then the administration of local anesthetic through the intrapleural catheter could be considered as a potential alterative analgesic method.     

Expression of the SART1 tumor-rejection antigens in colorectal cancers

PURPOSE: Colorectal cancer is one of the major causes of cancer death in the world, including in the United States and Japan. We recently identified the tumor-rejection antigen gene SART1, which encodes both the SART1₂₅₉ antigen expressed in the cytosol of epithelial cancers and the SART1₈₀₀ antigen expressed in the nucleus of the majority of proliferating cells. This study investigated the expression of these tumor antigens to explore a potential molecule for specific immunotherapy of colorectal cancer patients. METHODS: SART1 antigens were investigated by Western blotting in six colorectal cancer cell lines and in 33 colorectal cancer tissues. The cancer cell lines were tested for their ability to stimulate interferon- production by the human-leukocyte-antigen-A24-restricted and SART1-specific cytotoxic T lymphocytes and were also tested for their susceptibility to the lysis by the cytotoxic T lymphocytes. RESULTS: The SART1₂₅₉ antigen was detected in the cytosol of four of six cancer cell lines, 13 of 33 (39 percent) cancer tissues, and 0 of 20 nontumorous colorectal tissues. The SART1₈₀₀ antigen was expressed in the nucleus of all the colorectal cancer cell lines, 18 of 33 (55 percent) cancer tissues, and 0 of 20 nontumorous tissues. The human-lymphocyte-antigen-A24-restricted and SART1-specific cytotoxic T lymphocytes killed the human-lymphocyte-antigen-A24⁺ SART1₂₅₉ ⁺ cancer cells. CONCLUSIONS: The SART1₂₅₉ antigen could be an appropriate target molecule for specific immunotherapy of approximately 40 percent of the human-lymphocyte-antigen-A24⁺ patients with colorectal cancer.Supported in part by a Grant-in-Aid from the Ministry of Education, Science, Sports, and Culture of Japan and by a Health Science Research Grant for Research on Human Genome and Gene Therapy from the Ministry of Health and Welfare of Japan.Presented at the meeting of the American Association for Cancer Research, Philadelphia, Pennsylvania, April 10 to 14, 1999, and at the World Congress of Surgery of the ISS/SIC, International Surgical Week ISW 99, Vienna, Austria, August 15 to 20, 1999.     

Expression of SART3 antigen and induction of CTLs by SART3-derived peptides in breast cancer patients

We recently reported the SART3 tumour-rejection antigen as possessing tumour epitopes capable of inducing HLA-class I-restricted cytotoxic T lymphocytes (CTLs). This study investigated expression of the SART3 antigen in breast cancer to explore an appropriate molecule for use in specific immunotherapy of breast cancer patients. The SART3 antigen was detected in all of the breast cancer cell lines tested, 30 of 40 (75%) breast cancer tissue samples, and 0 of 3 non-tumourous breast tissue samples. SART3 derived peptides at positions 109-118 and 315-323 induced HLA-A24 restricted CTLs that reacted to breast cancer cells from the peripheral blood mononuclear cells (PBMCs) of breast cancer patients. Therefore, the SART3 antigen and its peptides could be an appropriate molecule for use in specific immunotherapy of the majority of HLA-A24-positive breast cancer patients.     

Molecular basis of T cell-mediated recognition of pancreatic cancer cells

Pancreatic cancer continues to be a major unsolved health problem in the world. The prognosis of pancreatic cancer is extremely poor with a median survival of 3-4 months and the 5-year survival being 1-4%. This poor prognosis is primarily because of a lack of effective therapies, and thus development of new treatment modalities is needed. One of these treatments could involve specific immunotherapy, for which elucidation off the molecular basis of T cell-mediated recognition of cancer cells is required. We report here six different genes and 19 immunogenic epitopes from pancreatic adenocarcinoma cells and T-cell receptor beta usage of HLA-A2-restricted CTL clones reacting to some of these epitopes. Sixteen of 19 epitopes were found to possess the ability to induce HLA-A2-restricted CTL activity in the peripheral blood lymphocytes of patients with pancreatic and also colon adenocarcinomas. These results should provide a scientific basis for the development of specific immunotherapy for pancreatic and colon cancer patients.     

Ran, a small GTPase gene, encodes cytotoxic T lymphocyte (CTL) epitopes capable of inducing HLA-A33-restricted and tumor-reactive CTLs in cancer patients.

PURPOSE: The purpose is to identify a gene coding for tumor-associated antigen and peptide capable of inducing CTLs reactive to tumor cells with a HLA-A33-restricted fashion to provide scientific basis for specific immunotherapy to HLA-A33+ cancer patients. EXPERIMENTAL DESIGN: An expression gene-cloning method was used to identify the tumor-associated antigen gene. Northern blot analysis and immunohistochemistry were used to examine the mRNA and protein expression levels in various cells and tissues, respectively. Synthetic peptides were examined for their ability to induce HLA-A33+ tumor-reactive CTLs in peripheral blood mononuclear cells from cancer patients. RESULT: A gene of small GTPase, Ran, which controls the cell cycle through the regulation of nucleocytoplasmic transport, mitotic spindle organization, and nuclear envelope formation, was found to encode epitopes recognized by the HLA-A33-restricted CTLs established from T cells infiltrating into gastric adenocarcinoma. The expression of the Ran gene was increased in most cancer cell lines and cancer tissues at both the mRNA and protein levels. However, it was not enhanced in the surrounding normal cells or tissues. It was also undetectable in normal tissues as far as tested. Ran-derived peptides at positions 48-56 and 87-95 could induce CD8+ peptide-specific CTLs reactive to tumor cells from HLA-A33+ epithelial cancer patients in a HLA class I-restricted manner. CONCLUSIONS: Because of its increased expression in cancer cells and involvement in malignant transformation and/or the enhanced proliferation of cancer cells, the two Ran-directed peptides could be potent candidates in use for specific immunotherapy against HLA-A33+ epithelial cancers.