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.     

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.     

Induction of epithelial progenitors in vitro from mouse embryonic stem cells and application for reconstruction of damaged cornea in mice

PURPOSE: Severe ocular surface diseases and injuries cause loss of the corneal limbal epithelium, leading to re-epithelialization by bulbar conjunctival cells, resulting in vascularization of the cornea, conjunctival scarring, and loss of visual acuity. In this study, the optimal culture condition for induction of differentiation of epithelial progenitor cells from embryonic stem (ES) cells was determined for use in transplantation to damaged cornea in mice. METHODS: Mouse ES cells were cultured on Petri dishes coated with several extracellular matrix proteins, and the markers for epithelial cells were analyzed with RT-PCR and Western blot analysis. The optimal condition for induction of epithelial progenitor cells was determined, and the progenitors were transplanted onto mouse eyes with corneal epithelia that had been damaged by exposure to n-heptanol. RESULTS: Epithelial progenitors were successfully induced by culturing mouse ES cells on type IV collagen for 8 days. These progenitors expressed keratin (K)12, which is specific to corneal epithelial cells, and cell surface CD44 and E-cadherin, both of which are essential in corneal epithelial wound healing. Complete re-epithelialization of the corneal surface occurred within 24 hours after transplantation. The resultant corneal epithelial cells expressed markers of the grafted cells, and no teratomata were observed during the follow-up period. CONCLUSIONS: Epithelial progenitors were successfully induced in vitro from ES cells and were applicable as grafts for treating corneal epithelial injury. ES cells may become an unlimited donor source of corneal epithelial cells for corneal transplantation and may restore useful vision in patients with a deficiency of limbal epithelial cells. This is an important first trial toward assessing the use of ES cells to reconstruct corneal epithelial cells.     

Mild hypothermia can enhance pial arteriolar vasodilation induced by isoflurane and sevoflurane in cats

OBJECTIVE: Volatile anesthetics have been shown to dilate cerebral vessels. Recent evidence suggests that mild hypothermia can alter vascular reactivity of the cerebral vessels. However, the effect of mild hypothermia on volatile anesthetic-induced vasodilation of cerebral vessels is unknown. In the present study, we investigated the effect of mild hypothermia on pial arteriolar vasodilation induced by isoflurane and sevoflurane in cats. DESIGN: Prospective, randomized, experimental study with repeated measures. SETTING: Investigational animal laboratory. SUBJECTS: Forty cats were used for the study of systemic administration of volatile anesthetics, and 22 cats were used for the study of topical administration of volatile anesthetics. INTERVENTIONS: This study was approved by the Animal Experiment Committee of Nara Medical University. Animals were anesthetized with pentobarbital to maintain suppressive electroencephalographic patterns, which were introduced to measure direct effects of anesthetic agents after removing metabolic effects. The cranial window technique, combined with microscopic video recording, was used for the measurement of small (50-100 microm) and large (100-200 microm) pial arteriolar diameter in an experiment. Animals were randomly assigned to either a normothermic (37 degrees C) or a hypothermic group (33 degrees C). Desired temperatures were maintained by using a water blanket. In the first phase of the study, the effect of hypothermia on pial arteriolar vasodilation induced by systemic administration of isoflurane or sevoflurane was assessed. Each cat received isoflurane or sevoflurane at 0.5, 1.0, 1.5, and 2.0 minimum alveolar anesthetic concentrations, and the diameter of pial arterioles was measured. In the second group of animals, the direct effect of isoflurane and sevoflurane on pial vessels was evaluated. The artificial cerebrospinal fluid bubbled with isoflurane or sevoflurane (minimum alveolar anesthetic concentrations of 1 or 3) was topically administered in the cranial window. MEASUREMENTS AND MAIN RESULTS: Systemic and topical administration of isoflurane and sevoflurane produced significant dilation of both small and large pial arterioles in a dose-dependent manner during normothermia. In the hypothermic group, vasodilation of small pial arterioles by systemic administration of isoflurane and sevoflurane at a high concentration was significantly larger than in the normothermic group (p <.05). Vasodilation of both small and large pial arterioles by topical administration of isoflurane and sevoflurane was significantly greater in the hypothermic group than in the normothermic group (p <.05). CONCLUSIONS: These results suggest that pial arteriolar vasodilation induced by isoflurane and sevoflurane can be enhanced by mild hypothermia in cats anesthetized with pentobarbital.     

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.     

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.     

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.     

UDP-Gal: betaGlcNAc beta1, 3-galactosyltransferase,polypeptide 3 (GALT3) is a tumour antigen recognised by HLA-A2-restricted cytotoxic T lymphocytes from patients with brain tumour

Patient prognosis in the case of malignant brain tumours is generally poor, despite significant improvements in the early detection of the tumours, and thus the development of new treatment modalities is needed. One of the most prominent modalities is specific immunotherapy, for which the elucidation of antigenic molecules of malignant brain tumours recognized by T cells is essential. We report here a gene, UDP-Gal: betaGlcNAc beta1, 3-galactosyltransferase, polypeptide 3, encoding three epitope peptides recognised by tumor-reactive cytotoxic T lymphocytes in an HLA-A2-restricted manner. Two of the three peptides possessed an ability to induce HLA-A2-restricted and tumour-reactive cytotoxic T lymphocytes from peripheral blood mononuclear cells of patients with brain tumours. These peptides may be useful in the peptide-based specific immunotherapy for patients with malignant brain tumours.     

Non-mutated tumor-rejection antigen peptides elicit type-I allergy in the majority of healthy individuals

IgE-mediated type-I allergy is generally considered to be a hypersensitivity reaction to foreign antigens, and it is believed that self-antigens do not evoke this type of allergy. We report here, for the first time, that non-mutated self-antigen peptides identified as tumor-rejection antigen peptides recognized by HLA class I-restricted and tumor-specific cytotoxic T lymphocytes (CTLs) elicited a type-I allergy in the majority of healthy individuals. Peptide-specific IgE was detectable in sera from certain cases, although the levels did not always correlate with those of type-I allergy. Repeated vaccinations of nonallergic peptides derived from the same antigens possessing allergic peptides resulted in the suppression of both allergic peptide-specific IgE responses and type-I allergy, providing evidence for a new approach to the development of peptide-based desensitization.