Kyoto islet isolation method: the optimized one for non-heart-beating donors with highly efficient islet retrieval

The availability of pancreata for clinical cadaveric islet transplantation is restricted to non-heart-beating donors (NHBDs) in Japan. This forced us to modify the current standard islet isolation protocol that was made up for brain-dead donors and make it suitable for NHBDs. The Kyoto islet isolation method is the one with induction of several steps based on the ideas both already reported literally and invented originally by ourselves. Using this islet isolation method, we isolated islets from 13 human pancreata of NHBDs and transplanted 11 preparations to six type-1 diabetic patients. The rate to meet release criteria of Edmonton protocol was 84.6%. Establishment of this method allowed us to begin a clinical islet transplantation program in Japan and to continue to perform the preparation of islets from NHBDs with high rate to meet the release criteria of the Edmonton protocol.     

Awake surgery for glioma resection in eloquent areas--Zurich's experience and review--

Awake surgery was performed in a series of 21 patients with gliomas in eloquent areas with the use of intraoperative electrical mapping. Gross total removal was performed in 18 patients. There was no operative mortality. Postoperative findings included no change in symptoms and signs in 10 patients, improvement of the preoperative deficit in 11 patients. Four patients had improved Karnofsky performance status (KPS) scores after surgery, 17 patients were stable, and no patient had lower KPS score. Extensive radical resection of gliomas prolongs the overall survival and improves the patient's quality of life. However, surgical resection of gliomas located within the sensorimotor or language areas remains a neurosurgical challenge in reducing eloquent neurological sequelae. Awake surgery with intraoperative functional mapping is a safe approach to maximize the extent of tumor removal and to minimize the resultant neurological deficits in the treatment of glioma involving the eloquent cortex.     

Intestinal tumorigenesis in Min mice is enhanced by X-irradiation in an age-dependent manner

We examined the effect of X-irradiation on intestinal tumorigenesis in Min (multiple intestinal neoplasia) mice. Single whole-body irradiation was given to mice of various ages from newborn to young adults. On the C57BL/6J (B6) background, X-irradiation increased tumor multiplicity of the small intestine exposed at ages from 2-3 days to 24-25 days, with a peak of 2.7-fold increase at 10-12 days of age; exposure at later ages resulted in only a slight increase. X-irradiation also increased colonic tumors; however, the susceptible age period appeared earlier than that of the small intestine; the peak value of 4.6-fold increase was observed in the exposure at around 2-3 days of age. Irradiation at 24 days or later ages showed almost no effect on the colonic tumor induction. On the (B6 x MSM)F1 background, X-irradiation resulted in 2.7-fold increase in the small intestinal tumors, but no increase in the colonic tumors, and besides, the age dependency observed in the small intestinal tumors was much attenuated. Collectively, we conclude that tumorigenic efficacy of X-irradiation in Min mice was determined by the combination of the target organ, the age at exposure, and the genetic background.     

Effects of a transfusion with a blood substitute (Fluosol-DA, 20%). Part II: Human cerebral blood flow

In 24 patients suffering from cerebrovascular diseases, alteration of the cerebral blood flow was investigated by means of the 133Xe clearance technique before and after the intravenous infusion of perfluorochemical suspension (Fluosol-DA, 20%, 10 ml/kg). Since perfluorochemicals exhibit high solubilities for not only oxygen but other kinds of gases, the partition coefficient of Xe (lambda tb) is considered to change depending on the amount of perfluorochemicals contained in the blood (Fct). The solubilities of Xe in the perfluorochemicals contained in the solution were then measured by gas chromatography to obtain an equation for lambda tb: lambda tb = 1.50/(Hct/100 + 12.48Fct/100 + 0.95). The cerebral blood flow was found to increase significantly by 10.1% in the lesional hemisphere and by 10.8% in the healthy one. The cortical small artery with a diameter between 0.1 and 0.2 mm appeared to dilate by 13% after its administration. From these results, the decrease of blood viscosity and some vasodilating effect of the solution might be responsible for the increase of the cerebral blood flow.     

Argatroban as an alternative to heparin in extracorporeal membrane oxygenation circuits

We investigated the anticoagulant effects of argatroban, a direct thrombin inhibitor, versus heparin in extracorporeal membrane oxygenation (ECMO) circuits. Three sham circuits were prepared according to our hospital's standard practice and run for six hours simultaneously. Two circuits were anticoagulated with argatroban (one with heparin in the wet prime and one without). One circuit had heparin in the initial prime and was then anticoagulated with heparin. We measured thrombin generation (prothrombin fragment 1+2, D-dimer and thrombin-antithrombin complexes), activated clotting times (ACTs) and partial thromboplastin times (aPTTs), and monitored thrombus formation using thromboelastography. ACTs were >1000 s in each circuit throughout assessment. No clot initiation was detected by thromboelastography. Thrombin generation was decreased in circuits anticoagulated with argatroban versus heparin, despite aPTTs being less prolonged. These results suggest that argatroban may be more efficacious than heparin for anticoagulation in ECMO. Additional studies are warranted to further evaluate argatroban in this setting.     

A new subdural probe for combined intracranial pressure (ICP) and cerebral blood flow (CBF) monitoring

Summaey We report the development of a new subdural probe for combined intracranial pressure (ICP) and cerebral blood flow (CBF) monitoring with near infrared spectroscopy (NIRS) and indocyanine green (ICG) dye dilution. For NIRS a conventional subdural ICP monitoring probe was supplied with two fiber bundles and 90-degree prisms. Injections of 25mg ICG were performed. Regional values for the mean transit time of ICG (rmtt_ICG), cerebral blood flow (rCBF) and cerebral blood volume (rCBV) were calculated. With prototypes of the probe in two patients with intracerebral haemorrhage 18 comparative measurements obtained simultaneously with conventional NIRS (optodes placed on the skin) and the subdural NIRS probe were performed. The new subdural NIRS probe allows combined monitoring of ICP and cerebral hemodynamics in the brain directly, without the influence of extracerebral tissue.     

Estimation of cerebral oxygenation and hemodynamics in cerebral vasospasm using indocyaningreen dye dilution and near infrared spectroscopy: a case report

Changes in cerebral hemodynamics and oxygenation patterns in cerebral vasospasm might be underestimated if transcranial doppler sonography and angiography findings are considered singularly. This report describes preliminary findings in further development of a noninvasive method that estimates regional cerebral oxygenation and perfusion. A 50-year-old patient suffering from cerebral vasospasm after subarachnoid hemorrhage before and after superselective papaverine infusion was examined. Measurements were taken by using a technique combining indocyaningreen dye dilution and near infrared spectroscopy. Our first results suggest that the technique could be suitable for estimation of cerebral hemodynamics. This noninvasive technique can be performed at the bedside and in special environments, such as neurocritical care units. It seems to be safe, easy to perform, and less time-consuming than conventional techniques. Combination of indocyaningreen dye dilution and near infrared spectroscopy might become a powerful tool in the detection and treatment of cerebral vasospasm causing delayed cerebral ischemic deficit. Further larger-scale investigations are necessary to evaluate the diagnostic accuracy of this technique. Our preliminary observations however, based on measurements before and after superselective papaverine infusion in vasospastic vessels, helped to clarify the influence of extracerebral contamination on the cerebral near infrared spectroscopy signal in the adult head.     

Treatment strategy for cervical node metastasis from squamous cell carcinoma of the oropharynx

The purpose of this study is to ascertain the role of neck surgery and radiation therapy for cervical lymph node metastasis in oropharyngeal cancer patients. We reviewed 217 previously untreated patients with squamous cell carcinoma of the oropharynx who were treated at the Cancer Institute Hospital in Tokyo between 1971 and 1995. The N stage distribution was; N0: 83(38.2%), N1: 42(19.4%), N2a: 23(10.6%), N2b: 27(12.4%), N2c: 33(15.2%), and N3: 9(4.2%). A predominance of cervical node metastases in level II and III was revealed and there were no skip metastases outside of level II and III. The control rate of cervical metastasis for each N stage was; N0: 96.9%, N1: 90.0%, N2a: 76.5%, N2b: 62.5%, N2c: 50.0%, and N3: 0%. Definitive irradiation provided sufficient treatment for small nodes, when the primary tumor growth was well controlled by radiation therapy. Neck dissection was necessary for more advanced neck metastases. Selective limited neck dissection (level II and III) is recommended for N0 and N1 patients, and modified or classical RND is considered to be better for most cases with N2 and N3.     

Germline SDHD mutation in paraganglioma of the spinal cord

Hereditary paraganglioma of the head and neck is associated with germline mutations in the SDHD gene, which encodes a mitochondrial respiratory chain protein. Paragangliomas of the central nervous system are very rare, occur almost exclusively in the cauda equina of the spinal cord and are considered non-familial. In the present study, we screened 22 apparently sporadic paragangliomas of the cauda equina for SDHD mutations. One spinal paraganglioma and similar cerebellar tumours that developed 22 years later in the same patient contained a missense mutation at codon 12 (GGT-->AGT, Gly-->Ser) and a silent mutation at codon 68 (AGC-->AGT, Ser-->Ser). There was no family history of paragangliomas but DNA from white blood cells of this patient showed the same sequence alterations, indicating the presence of a germline mutation. All other cases of spinal paraganglioma had the wild-type SDHD sequence, except one case with a silent mutation at codon 68 (AGC-->AGT, Ser-->Ser). This is the first observation indicating that inherited SDHD mutations may occasionally cause the development of paragangliomas in the central nervous system.