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We investigated the effects of two different concentrations of sevoflurane, 0.4 minimum alveolar anesthetic concentration (MAC) and 1.0 MAC, on insulin secretion before, during, and after sevoflurane anesthesia using three successive intravenous glucose tolerance tests (IVGTT) in pigs with indwelling catheters. We also investigated changes in the levels of plasma glucose, catecholamines (epinephrine [E], norepinephrine [NE]), and cortisol (Cor). The pigs were grouped as awake, 0.4 MAC, or 1.0 MAC. Sevoflurane decreased the ratio of insulin/glucose (INS/GLU) in the basal condition (P < 0.05 awake versus 1.0 MAC) and during IVGTT (P < 0.01 awake versus 1.0 MAC and 0.4 MAC). These decreases were quickly reversible (control levels were regained within 2 h of the end of anesthesia), were probably dose-related, appeared not to be mediated by E, NE, or Cor. In addition, the INS/GLU ratio 2.5-4 h after the end of anesthesia was significantly higher in the anesthetized groups than in the awake group. We conclude that sevoflurane anesthesia has a rapidly reversible inhibitory effect on basal and glucose-stimulated insulin secretion, as do other inhaled anesthetics, and might induce insulin resistance.

Background: Chondroid chordoma is a rare variant of chordoma and is usually located in the sphenooccipital region. This tumor shows clinical and histologic features common to both conventional chordoma and low grade chondrosarcoma and has a better prognosis than either of those lesions. To our knowledge, there has been no English language report describing its cytologic features., Case: The cytologic features of skull base chondroid chordoma observed in intraoperative crush and touch preparations from a 33-year-old female are reported. Touch cytology revealed round or stellate cells distributed in a mucoid background without a typical epithelial cordlike arrangement. The cells had variably vacuolated cytoplasm and round or oval nuclei and showed slight cellular pleomorphism. May-Giemsa staining was superior to Papanicolaou staining in demonstrating the mucoid matrix and vacuolated cytoplasm of the tumor cells. Additionally, crush preparations were effective in demonstrating well-differentiated chondroid elements. Immunocytochemistry with positivity for S-100 protein and cytokeratins was an essential adjunct in the cytologic diagnosis of chordoma and helped in distinguishing it from other chondrogenic tumors., Conclusion: It is possible and advantageous to diagnose chondroid chordoma with a combination of cytologic and immunocytochemical studies of intraoperative crush and touch preparations in conjunction with clinical and radiographic information.

Purpose: This study was performed to predict incontinence following low anterior resection for rectal cancer., Methods: Preoperatively, 21 patients were evaluated via patient history and a physical examination that included anal manometric studies. Six months postoperatively, repeat manometric studies and clinical evaluations were performed to assess the level of continence. Degree of continence was graded based on severity of the dysfunction and grade of the continence score., Results: The formula used for predicted postoperative resting pressure is as follows: predicted postoperative resting pressure = 0.42 x preoperative resting pressure +1.56 x length of remaining rectum +12.37 (R2 = 0.58; P < 0.001). It was demonstrated that patients with low predicted postoperative resting pressures (< 30 mmHg) had incontinence, and those with high predicted postoperative resting pressures (> 35 mmHg) were continent. There were significant correlations between length of the remaining rectum and ratio of the decrease in maximum resting pressure (postoperative/preoperative maximum resting pressure; r = 0.63; P < 0.01)., Conclusions: Continence following low anterior resection may be influenced by maximum resting pressure function of the internal anal sphincter; if it is injured during surgery, incontinence will occur. We may be able to foretell incontinence by using the predicted postoperative resting pressure formula, which is calculated by using preoperative resting pressure measurements and then determining the length of the remaining rectum.

A 34-year-old male with a history of angina pectoris suddenly developed weakness in the right upper and lower limbs, and consulted our hospital. Computed tomography (CT) and magnetic resonance imaging (MRI) suggested cerebral infarction. Cerebral angiography revealed stenosis at the M1 portion of the left middle cerebral artery. Hypertension, diabetes, tobacco or hyperlipidemia were not considered as risk factors for cerebral infarction. The lipoprotein (a) [Lp(a)] level was high. In the present case, medication with a nicotinic acid agent, niceritrol, for hyperlipoproteinemia and low density lipoprotein (LDL) apheresis were performed. Concerning family history, the patient's mother and younger sister had hyperlipoproteinemia. Recent studies have reported that increased Lp(a) levels are an independent risk factor even in cerebral infarction and coronary artery disease. Measurement of Lp(a) levels and treatment for increased Lp (a) levels may be important.

To establish whether the indicators of oxygen metabolism reflects the improvement in tissue oxygenation during therapy, twelve rabbits subjected to progressive hemorrhage followed by retransfusion were studied. The changes in oxygen delivery (DO2), oxygen consumption (QO2), oxygen extraction ratio (O2ER), arterial lactate concentration, venous-arterial difference in PcO2 (v-aDPcO2) and arterio-venous difference in pH (a-vDpH) were analyzed during two phases (above and below) the critical DO2 with the regression coefficient (slope). The main findings during the transfusion were: a) the slope, when compared during the two phases was not significantly different for O2ER, v-aDPcO2 or a-vDpH, while during hemorrhage each variable showed a significantly different slope, b) in the phase below the critical DO2, the slope was significantly less steep than that during hemorrhage for lactate and v-aDPcO2, c) in the phase above the critical DO2, lactate alone had significantly steeper slope than that during hemorrhage. In conclusion, it is suggested that the changes in QO2 best reflect the recovery from tissue hypoxia.

To investigate if sevoflurane saturates the metabolic capacity of the enzymes responsible for sevoflurane at clinically-used concentration ranges, we compared plasma fluoride levels and urinary excretion of inorganic fluoride in piglets after (1) low concentration sevoflurane anesthesia versus (2) high concentration sevoflurane anesthesia. Eleven male piglets, weighing 18-23.5 kg, were randomly divided into two groups: 1) L group: five animals were anesthetized for two hours with sevoflurane at 0.8% end-tidal concentration (0.4 MAC); 2) H group: six animals were anesthetized for two hours with sevoflurane at 3.0% end-tidal concentration (1.4 MAC). Plasma inorganic fluoride levels, blood sevoflurane concentration, urinary inorganic fluoride concentration and urine volume were measured. The blood sevoflurance concentration in both groups reached their plateau levels 30 min after the start of anesthesia. The plateau levels in the H and L groups were 275-306 microM and 105-115 microM, respectively. The plasma fluoride concentrations reached plateau levels 60 min after the start of anesthesia in both groups. The H group showed significantly higher plasma fluoride levels than the L group during sevoflurane anesthesia. The H group also showed significantly higher urinary excretion of inorganic fluoride than the L group. Therefore, metabolite production levels in the H group were significantly higher than the L group. These results suggest that low concentration sevoflurane anesthesia did not saturate the metabolic capacity of the enzymes responsible for defluorination of sevoflurane in piglets.

In patients, plasma concentrations of sevoflurane metabolites may be independent of inspired sevoflurane concentration over a defined dose range. In contrast, studies using rabbits have found that plasma concentrations and urinary excretion of fluoride ion are dose-dependent up to 3% inspired sevoflurane. We measured sevoflurane metabolite concentrations in adult male Sprague-Dawley rats and related them to inspired sevoflurane concentrations. When plasma concentrations and urinary excretion of metabolites were measured in vivo, they were dependent on inspired anesthetic concentration at concentrations less than 1.25%, but became less dose-dependent at higher anesthetic concentrations. Sevoflurane metabolism by precision-cut liver slices in vitro became dose-independent at more than 10-30 microM sevoflurane. No evidence of substrate inhibition was observed. These data provide evidence that sevoflurane metabolite concentrations are almost independent of inspired anesthetic concentration over at least part of the clinically used concentration range.

Thymidine phosphorylase (dThdPase) is an angiogenic enzyme and seems to be related to an angiogenesis in human colorectal carcinoma. The incidence of dThdPase-positive cells was significantly correlated with microvessel count in 21 human colorectal carcinomas. Interleukin 1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF-alpha), interferon alpha (IFN-alpha) interferon gamma (IFN-gamma) induce dThdPase activity in human cancer cell lines. To study whether this phenomenon occurs in the human colorectal carcinomas, we examined the correlation between dThdPase activity and the expression levels of IL-1 alpha, TNF-alpha, IFN-alpha and IFN-gamma in colorectal carcinoma tissues. dThdPase activity was assayed by the methods of Friedkin and Robert, and the expression level of IL-1 alpha, TNF-alpha, IFN-alpha and IFN-gamma was determined by ELISA. dThdPase activity was significantly correlated with the amount of IL-1 alpha (n = 19, r = 0.347, P = 0.0001), INF-alpha (n = 18, r = 0.717, P = 0.008), and IFN-gamma (n = 4, r = 0.9777, P = 0.0234) in human colorectal carcinomas. However, the dThdPase activity was not correlated with the amount of TNF-alpha (n = 21, r = 0.235, P = 0.2682). These results suggested that the expression levels of IL-1 alpha, IFN-alpha and IFN-gamma are correlated with dThdPase activity in human colorectal carcinomas and that these cytokines may cause angiogenesis by inducing the expression of dThdPase.

We investigated the effects of allopurinol on renal damage following renal ischemia. Male Wistar rats weighing 250-300 g were classified into enflurane and allopurinol groups and anesthetized for 5 minutes using 1.7 MAC of enflurane in 30% oxygen. Then the left renal artery was dissected and clamped. Arterial occlusion was performed under 1.3 MAC enflurane for 30 minutes. Anesthesia was maintained for an additional 90 minutes after releasing the clip. In the allopurinol group, the rats were administered with allopurinol 3 mg.kg-1 intravenously prior to renal ischemia. At the end of anesthesia and 24 hours after the discontinuation of anesthesia, the necrotic areas, kidney weight/body weight ratios, gamma-GTP and NAG activities of the kidney which had been clamped were examined. Urinary gamma-GTP and NAG activities and serum inorganic fluoride concentrations were also measured. The necrotic area was significantly smaller in the allopurinol group than in the enflurane group. The activity of gamma-GTP in the kidney was higher in the allopurinol group than in the enflurane group. The kidney weight/body weight ratio was lower in the allopurinol group than in the enflurane group. There was no difference in serum inorganic fluoride concentration between the allopurinol and enflurane groups. These results suggest that allopurinol decreases renal damage following renal ischemia under enflurane anesthesia.

The effects of halogenated inhalational anesthetics, viz. halothane, enflurane, isoflurane and sevoflurane, on ischemic rat kidneys were studied through the response of renal gamma-glutamyl transpeptidase in the brush border of proximal tubules to monoclonal antibodies. Brush border staining characteristics were evaluated as follows: a) continuous (normal), b) discontinuous (damaged) and c) indistinct (necrotic). The isoflurane group had significantly fewer damaged and/or necrotic proximal tubules compared to the other groups. These results suggest that isoflurane is the most appropriate inhalational anesthetic when renal circulation is impaired.

Effects of 2% halothane, 1.5% sevoflurane, 1.5% enflurane, and 1.2% isoflurane on hepatic dysfunction were studied using rat hepatocytes incubated in media containing 95% or 5% O2. The effects of anesthetics on hepatic perfusion were eliminated by incubation of hepatocytes for 45 minutes with each combination of anesthetic and oxygen concentration. After incubation, viability of hepatocytes was assayed by the LDH latency test. Enzyme (GPT, GOT, LDH) activities, lactate concentration and pyruvate concentration in the incubation medium were measured. The concentrations of adenine nucleotides and inorganic phosphorous in the liver were determined. Anesthetics administered in 95% O2 did not produce significant decreases in viability and enzyme release compared to 95% O2 alone. Halothane, sevoflurane, and isoflurane administered in 5% O2 produced significant decreases in viability and enzyme releases compared to 95% O2 alone. In groups administered 95% O2 there was a significant relationship between viability and energy charge in hepatocytes (P < 0.01). In the 5% O2 groups, there were significant relationships between viability and ATP in hepatocytes (P < 0.01) or L/P ratio in incubation medium (P < 0.01). These results suggest that the combination of anesthetics and hypoxia produce hepatotoxicity. Destruction of energy status might be the cause of hepatotoxicity.

1) The urinary 5-S-CD contents in malignant melanoma subjects (n = 135) and non-melanoma subjects (n = 204) were measured by HPLC. These results suggest that, as a biochemical marker, periodic measurement of urinary 5-S-CD is quite useful for evaluating the determinations of stage classification (UICC, 1987), and the detection of metastases, the therapeutic efficacy of operation or immunochemotherapy against malignant melanoma. 2) Quantitative analyses of 5-S-CD values in tissues from primary malignant melanoma lesions (n = 24) and pigmentary tumors other than melanomas (n = 136) showed 80.6-821.4 ng/mg and N.D.-55.0 ng/mg respectively. In view of the above findings, it was suggested that the pigmentary tumors can be diagnosed as malignant melanoma if the 5-S-CD value in the tissues is higher than 100 ng/mg.

5-fluorouracil (5-FU) concentrations in peripheral blood, portal blood, normal and cancer tissues were evaluated in 26 patients with colorectal cancer after SF-SP administration (800 mg/day for 10 days). Thymidine phosphorylase activity in cancer tissues was also evaluated. 5-FU concentration in cancer tissues was significantly higher than that in other three specimens, and much higher than 0.05 microgram/g which was reported to be the minimum effective concentration. 5-FU concentration in portal blood was lower than MEC (0.05 microgram/ml). As for the relationship with the pathological features of cancer, the protruding lesions showed a higher 5-FU concentration than the ulcerative ones, and the lesions invaded only to submucosa or proper muscle showed a higher concentration than others. 5-FU concentration ratio in cancer tissues per in peripheral blood (T/B ratio) was related to thymidine phosphorylase activity. The higher was the thymidine phosphorylase activity, the greater T/B ratio. The results suggest that the tumor with higher thymidine phosphorylase activity might have a more pronounced anticancer efficacy of 5-FU.

Adsorption therapy, which treats the autoimmune disease by the selective removal of pathogenic substances from the blood, is an active subject. In this therapy, bioactive molecules such as antigen, antibodies and protein A are usually used as affinity-ligands. The disadvantages of using these substances as affinity-ligands are the availability, sterilizability, and ability to cause antigenic reactions. After surveying hundreds of synthetic compounds, it was found that polyacrylic beads [Eupergit C (EC)] immobilized covalently with sulfathiazole (ST) are an ideal biomimetic ligand for the selective adsorption of IgG (24.3 +/- 0.4 mg IgG/g wet beads). In an in vitro study, this adsorbent selectively removed the antiacetylcholine (AChR) receptor antibody of myasthenia gravis (MG) patients. Further experiments demonstrated that the Fab fragment was adsorbed three times more efficiently than the Fc fragment of IgG.

To develop a biochemical diagnosis for malignant melanomas, 5-S-cysteinyldopa in the tissues of malignant melanomas and other pigmented tumors were quantitatively analysed. The mean 5-S-CD value from primary melanotic melanoma lesions was 202.4 ng/mg (80.6-821.4) and those of metastatic melanoma lesions was 214.0 ng/mg (96.2-520.0). There was no significant differences in these 5-S-CD values between the types of primary lesions. On the other hand, the 5-S-CD values from pigmented tumors other than melanomas, such as Spitz nevus, dysplastic nevus, pigmented basal cell epithelioma, and melanoepithelioma Bloch II were less than 55 ng/mg. From these results it is thought that pigmented tumors can be diagnosed as malignant melanomas, if the 5-S-CD values in the tissues are over 100 ng/mg. The mean 5-S-CD values of pigmented macules of SSM was 734.5 ng/mg (320.0-1666.3) and those of ALM was 1.8 ng/mg (0.7-3.6). These data suggest that the biochemical diagnoses of SSM in situ can be based on 5-S-CD values, the diagnoses of ALM in situ can not.

The structural polypeptides of molluscum contagiosum virus (MCV) obtained from the skin lesions of patients were examined by SDS-polyacrylamide gel electrophoresis. At least 40 polypedtides from purified virions were detected on SDS-polyacrylamide gel by a highly sensitive silver stain. Two of the structural polypeptides of the nine isolates were different in their migration rate in SDS-polyacrylamide gel. Following controlled degradation virions the two variable polypeptides were shown to be located in the surface or subsurface layers.

1. The relationship of the mesenteric inflammation with intestinal loop deformities was made clear and changes of these deformities were examined with time, using experimental model rabbits. 2. The above rabbit was laparotomized and was caused to develop mesenteritis by applying acetic acid onto sigmoid mesentery and descending colic mesentery, then the abdomen was closed. Subjects were divided into 2 groups (A and B); A group and B group were re-laparotomized 3-7 and 21 days later, respectively and were observed for mesentery and loop appearance, then were extirpated for sigmoid colon and descending colon with mesenterium attached thereto. Roentgenograms were taken first with attachment of mesentery, secondly there-without. Then, the intestinal canal was opened and the mucosal surface was observed, together with bleeding and blood flow disturbance in the depth of the wall in transmitted light. 3. As a result, the following conclusions were obtained: 1) Macroscopically, mesentery was marked with redness for A group and with thickening and twitch due to cicatricial contraction for B group. 2) A group near to the third day showed remarkable shortening, narrowing and marginal irregularity of the loop, which disappeared with time and were scarcely observed for B group; these deformities were considered to involve mesenteric inflammations and ischemia caused by secondary blood flow disturbance. 3) A group near to the 7th day and B group showed remarkable angulation, distortion and coil-like appearance; these deformities are considered to have been caused by thickening (stiffness) of the mesentery and its attachment and twitch-distortion due to cicatricial contraction. 4) Coil-like appearance disappeared upon cutting off the mesentery from the loop.(ABSTRACT TRUNCATED AT 250 WORDS)

The metabolites of fentanyl (l), which has been widely used as a neuroleptic analgesic agent, were identified in urine of rats by gas chromatography-mass spectrometry combined with a stable-isotope tracer technique. After the oral administration of an equimolar mixture of l and deuterium-labeled l (l/l-d5), the urinary metabolites were extracted with chloroform at pH 9.0. Extracts were derivatized and analyzed by GC/MS. Metabolites were identified by the presence of doublet ion peaks separated by 5 amu, and chemical structures were established from analyses of fragmentation pathways. The metabolites were identified as 4-N-(N-propionylanilino)-piperidine, 4-N-(N-hydroxypropionylanilino)piperidine, 4-N-(N-propionylanilino) hydroxypiperidine, 1-(2-phenethyl)-4-N-(N-hydroxypropionylanilino)piperidine and 1-(2-phenethyl)-4-N-(N-propionylanilino)hydroxypiperidine. These metabolites, together with unchanged l, were also detected in urine of rats receiving l/l-d5 intravenously, by selected-ion monitoring of the specific cluster ions.

The authors studied the relationship between the level of aggressivity in 12 aggressive preschoolers and five hypothesized pathogenic variables: constitutional, lack of maternal attunement to the child's needs, passive experience of aggression, parental overindulgence and the presence of a precipitant. The data tend to support a strong predictive association between the pathogenic variables as a group and the level of aggressivity, although the results must be regarded as preliminary because of the small number of cases.

Although fentanyl has been used widely as a short-acting narcotic analgesic, its metabolism in humans has not been clarified. In this study, three fentanyl metabolites were identified in the urine of eight surgical patients receiving 0.3-0.5 mg of fentanyl intravenously. The metabolites 4-N-(N-propionylanilino)piperidine, 4-N-(N-hydroxypropionylanilino)piperidine and 1-(2-phenethyl)-4-N-(N-hydroxypropionylanilino)piperidine, and unchanged fentanyl were identified by GC-mass spectrometry in urine collected 6 h after administration. Fentanyl and its main metabolite, 4-N-(N-propionylanilino)piperidine, were determined quantitatively in the urine of five additional patients receiving 0.5 mg fentanyl intravenously. Urinary excretion of fentanyl and 4-N-(N-propionylanilino)-piperidine during the first 12 h after injection accounted for 0.3-4.0% and 26 to 55% of the dose, respectively.

The antishock effects of gabexate mesilate (FOY) were investigated in rats subjected to hemorrhagic hypotension, with particular attention focused on the stabilizing effects of hepatic lysosomes. The survival time of rats treated with FOY, infused for 2 hours intravenously at a rate of 50 mg/kg/hr, was significantly prolonged, accompanied by a tendency to decreased activity of plasma lysosomal enzymes. FOY, at a concentration of 10(-3) M, exerted a significant decrease in the extralysosomal release of acid phosphatase (15%, P less than 0.05), beta-glucuronidase (25%, P less than 0.05) and cathepsin D (25%, P less than 0.02) following hyposmotic labilization of lysosomes. Although the release of lysosomal enzymes might be counterbalanced by 50 mg/kg/hr of FOY, favorable cytochemical findings indicating stabilization of lysosomal membranes were consistently observed. The data suggest that FOY has antishock properties, and that these properties are caused, at least partially, by the stabilization of lysosomes.