[Multimodal therapy improved carcinoid syndrome secondary to liver metastases of an atypical lung carcinoid tumor:a case report].

A 69-year-old male presented for an annual medical examination, and his chest X-ray showed an abnormal shadow. He presented to our hospital, and was diagnosed with typical carcinoid tumor of the lung by bronchoscopy. We recommended surgery, however the patient did not agree to the operation. One year later, two masses were detected in the liver. Ultrasound guided biopsy revealed that they were metastases from the atypical carcinoid tumor of the lung. We recommended chemotherapy, but he refused. Six months later, he was admitted to our hospital for symptoms of flushing, fever, watery diarrhea, and palpitations. We diagnosed this combination of symptoms as carcinoid syndrome, and started the administration of a long acting release (LAR) octreotide. The patient's symptoms improved, but did not resolve completely. We then performed a hepatic artery embolization for the liver metastases, and the symptoms resolved. However, viable lesions of the liver metastases slowly grew and caused a carcinoid crisis. By increasing the dosage of octreotide up to a continuous intravenous infusion of 1500µg/day, as well as LAR 30mg/4weeks, the patient recovered from the crisis. Hepatic artery embolization was performed shortly afterward. Because it was difficult to control the carcinoid syndrome by hepatic artery embolization alone, he underwent a resection of the liver metastases. After the hepatic resection, he has had no recurrence of carcinoid syndrome while still being treated with octreotide LAR.

Bone morphogenetic protein-4 modulates proliferation and terminal differentiation of fetal hepatic stem/progenitor cells.

Fetal hepatic stem/progenitor cells, called hepatoblasts, play central roles in liver organogenesis; however, molecular mechanisms regulating proliferation and terminal differentiation of such cells have not been completely elucidated. Bone morphogenetic protein-4 (BMP-4) is essential for the development of stem cells in various tissues, but its function in regulating the phenotype of hepatoblasts after the mid-gestational fetal stage remains unclear. The aim of this study is to clarify a functional role for BMP-4 in proliferation and terminal differentiation of murine hepatoblasts in mid-gestational fetal livers. METHODS: A functional role for BMP-4 in proliferation and terminal differentiation of murine hepatoblasts was validated by assay of colony formation, biliary luminal formation, and hepatic maturation using primary hepatoblasts in vitro. Molecular mechanisms regulating such effects of BMP-4 on primary hepatoblasts were also analyzed. RESULTS: Stimulation of BMP-4 upregulated phosphorylation of Smad1/5 in hepatoblasts. Bone morphogenetic protein-4 significantly suppressed colony formation of primary hepatoblasts in a dose-dependent manner, significantly suppressed cholangiocytic luminal formation of hepatoblasts, and promoted hepatic maturation of primary hepatoblasts. Stimulation of BMP-4 regulated the activation of several mitogen-activated protein kinases, such as extracellular signal-regulated kinase, Akt, p38 mitogen-activated protein kinase, and calcium/calmodulin-dependent protein kinase IIα in primary hepatoblasts. Moreover, Wnt5a, a molecule regulating cholangiocytic luminal formation, and BMP-4 coordinately suppressed proliferation and cholangiocytic luminal formation of hepatoblasts. CONCLUSION: This study shows that BMP-4-mediated signaling controls proliferation and terminal differentiation of fetal hepatic stem/progenitor cells.

Matrix metalloproteinase-14 mediates formation of bile ducts and hepatic maturation of fetal hepatic progenitor cells.

Fetal hepatic stem/progenitor cells, called hepatoblasts, play central roles in liver development; however, the molecular mechanisms regulating the phenotype of these cells have not been completely elucidated. Matrix metalloproteinase (MMP)-14 is a type I transmembrane proteinase regulating pericellular proteolysis of the extracellular matrix and is essential for the activation of several MMPs and cytokines. However, the physiological functions of MMP-14 in liver development are unknown. Here we describe a functional role for MMP-14 in hepatic and biliary differentiation of mouse hepatoblasts. MMP-14 was upregulated in cells around the portal vein in perinatal stage liver. Formation of bile duct-like structures in MMP-14-deficient livers was significantly delayed compared with wild-type livers in vivo. In vitro biliary differentiation assays showed that formation of cholangiocytic cysts derived from MMP-14-deficient hepatoblasts was completely impaired, and that overexpression of MMP-14 in hepatoblasts promoted the formation of bile duct-like cysts. In contrast, the expression of molecules associated with metabolic functions in hepatocytes, including hepatic nuclear factor 4α and tryptophan 2,3-dioxygenase, were significantly increased in MMP-14-deficient livers. Expression of the epidermal growth factor receptor and phosphorylation of mitogen-activated protein kinases were significantly upregulated in MMP-14-deficient livers. We demonstrate that MMP-14-mediated signaling in fetal hepatic progenitor cells promotes biliary luminal formation around the portal vein and negatively controls the maturation of hepatocytes.

Efficacy of additional radiofrequency ablation after transcatheter arterial chemoembolization for intermediate hepatocellular carcinoma.

AIM: For intermediate hepatocellular carcinoma (HCC), transcatheter arterial chemoembolization (TACE) therapy is recommended in the guidelines as a monotherapy, although TACE is a non-curative therapy. The aims of the present study were to evaluate the efficacy of adding radiofrequency ablation (RFA) to TACE in patients with intermediate HCC, and to identify the factors that were associated with favorable survival in these patients. METHODS: Fifty-nine patients with intermediate HCC were enrolled in this retrospective study. Thirty-nine patients were treated with TACE alone and 20 patients were treated with additional RFA after TACE. RESULTS: The recurrence-free survival rates at 0.5, 1 and 2 years for the additional RFA group were 32%, 19% and 13%, respectively, and these were significantly higher than those of the TACE group (8%, 3% and 0%, respectively; log-rank test, P = 0.001). The cumulative survival rates of the additional RFA group were significantly higher than those of the TACE group (log-rank test, P = 0.002), although this significant difference was not found in the subgroup of treatment naive patients because of small sample size. Multivariate analysis indicated male sex, lower total bilirubin, lower α-fetoprotein, lower des-γ-carboxyprothrombin, newly recurrent HCC nodules within the last 12 months and additional RFA as independent factors that were significantly associated with favorable overall survival. CONCLUSION: Additional RFA of nodules insufficiently treated by TACE is effective therapy for obtaining favorable disease-free survival in patients with intermediate HCC, and leads to better overall survival particularly in recurrent patients.

Impaired induction of interleukin 28B and expression of interferon λ 4 associated with nonresponse to interferon-based therapy in chronic hepatitis C.

BACKGROUND AND AIM: Interferon (IFN) λ plays an important role in innate immunity to protect against hepatitis C viral (HCV) infection. Single nucleotide polymorphisms (SNPs) near IL28B (IFNλ3) are strongly associated with treatment response to IFNα therapy in chronic hepatitis C (CHC) patients. Recently, IFNλ4 related to IL28B-unfavorable allele was discovered. However, the impact of IFNλs on CHC is unknown. We aimed to investigate the mechanism underlying responsiveness to IFN-based therapy in CHC associated with SNPs near IL28B. METHODS: We evaluated the basal mRNA levels and ex-vivo induction of IFNλ expression including IFNλ4 in peripheral blood mononuclear cells (PBMCs) from 50 CHC patients treated with pegylated-IFNα/RBV. Furthermore, we investigated the effect of IFNλ4 on induction of IL28B in vitro. RESULTS: When PBMCs were stimulated with IFNα and polyinosinic-polycytidylic acid, IL28B induction was significantly lower in patients with IL28B-unfavorable genotype (rs12979860 CT/TT) than those with IL28B-favorable genotype (rs12979860 CC; P=0.049). IL28B induction was lower in nonresponders than in relapsers (P = 0.04), and it was also lower in nonsustained virological responder patients for triple therapy including NS3 protease inhibitors. IFNλ4 mRNA was detected in 12 of 26 patients with IL28B-unfavorable SNP, and IFNλ4 expression was associated with lower IL28B induction in patients with IL28B-unfavorable genotype (P=0.04) and nonresponse to IFNα therapy (P=0.003). Overexpression of IFNλ4 suppressed IL28B induction and promoter activation. CONCLUSIONS: Impaired induction of IL28B, related to IFNλ4 expression in PBMCs of IL28B-unfavorable patients, is associated with nonresponse to IFNα-based therapy for hepatitis C viral infection.

Breakthrough pain management using fentanyl buccal tablet (FBT) in combination with around-the-clock (ATC) opioids based on the efficacy and safety of FBT, and its relationship with ATC opioids: results from an open-label, multi-center study in Japanese cancer patients with detailed evaluation.

OBJECTIVE: Rapid analgesic onset opioids, particularly fentanyl buccal tablet, is preferable for managing breakthrough pain. The efficacy and safety of fentanyl buccal tablet and its association with around-the-clock opioids needs to be explored with an option of dose adjustments, more closely reflecting administration in clinical practice. The aim of the study was to assess the safety and efficacy of fentanyl buccal tablet in breakthrough pain management in combination with around-the-clock opioids with the dose adjustment option, and explore the dose adjustment's influence on breakthrough pain management using detailed evaluation. METHODS: The 12-week open-label, multi-center study was conducted throughout Japan. Cancer patients aged 20 years or older, experiencing persistent pain controlled with around-the-clock opioids and breakthrough pain with supplemental medications were enrolled. Fentanyl buccal tablet and around-the-clock opioid doses could be adjusted under protocol-specified conditions. Efficacy variables were assessed at each fentanyl buccal tablet administration. Safety was assessed mainly by adverse events. RESULTS: All efficacy variables showed sustained analgesic effect. Nearly half the patients stayed on the same dose; most fentanyl buccal tablet administrations did not require additional supplemental medications. Dose increase of fentanyl buccal tablet and around-the-clock opioids seemed to improve breakthrough pain intensity and frequency, respectively. Fentanyl buccal tablet and around-the-clock opioid doses were not strongly associated. Treatment-related adverse events were all common with opioid treatment and did not increase over time. CONCLUSIONS: Fentanyl buccal tablet can stably and safely manage breakthrough pain in cancer patients with independent dose adjustment based on detailed evaluation of each patient's condition. Breakthrough pain management using fentanyl buccal tablet with around-the-clock opioids at optimal doses may be an important factor in palliative care for cancer patients with breakthrough pain.

Actions of propofol on substantia gelatinosa neurones in rat spinal cord revealed by in vitro and in vivo patch-clamp recordings.

Propofol, an intravenous general anaesthetic, exerts anaesthetic actions through interaction with gamma-aminobutyric acid type A (GABA(A)) receptors in the supraspinal nervous system. However, whether propofol has any significant effects on synaptic transmission at the spinal level and whether it exhibits antinociceptive action is still not fully clarified. Spontaneous activity and stimulus-evoked responses of substantia gelatinosa (SG) neurones to noxious pinch stimuli were recorded using spontaneously breathing rats under propofol anaesthesia using in vivo whole-cell patch-clamp techniques. Precise actions of propofol on GABAergic and glycinergic inhibitory postsynaptic currents (IPSCs) as well as excitatory postsynaptic currents (EPSCs) in SG neurones were also analyzed in spinal cord slice preparations. At clinical doses (5 mg/kg), propofol reversibly depressed action potentials elicited by noxious mechanical stimuli applied to the skin in the majority (6/8) of SG neurons recorded under in vivo conditions. This depression may have been caused by interactions of propofol with GABA(A) receptors, as decay time of GABAergic sIPSCs was prolonged after propofol injection (128 +/- 11% of control, n = 5) with minimal effect on EPSCs. Although prolongation of IPSCs in vivo was reversible, IPSCs were progressively prolonged even after washout of propofol when the effect was tested using spinal cord slices. Propofol had a mild depressant effect on Adelta- and C-afferent-mediated EPSCs. We conclude that systemic bolus injection of propofol reversibly depressed nociceptive transmission, at least in part, by enhancing postsynaptic GABA(A) receptor-mediated responses in the SG.

The radiobiological effectiveness of carbon-ion beams on growing neurons.

PURPOSE: Recently carbon-ion beams have been reported to be remarkably effective for controlling various cancers with less toxicity and are thought to be a promising modality for cancer treatment. However, the biological effect of carbon-ion beams arising on normal neuron remains unknown. Therefore, this study was undertaken to investigate the effect of carbon-ion beams on neurons by using both morphological and functional assays. MATERIALS AND METHODS: Dorsal root ganglia (DRG) and sympathetic ganglion chains (SYMP) were isolated from day-8 and day-16 chick embryos and cultured for 20 h. Cultured neurons were exposed to carbon-ion beams and X-rays. Morphological changes, apoptosis and cell viability were evaluated with the Growth Cone Collapse (GCC), Terminal deoxynucleotidyl Transferase (TdT)-mediated deoxyUridine TriPhosphate (dUTP) nick End Labeling [TUNEL] assay and 4-[3-(4-iodophenyl)- 2-(4-nitrophenyl)- 2H-5-tetrazolio]- 1,3-benzenedisulfonate [WST-1] assays, respectively. RESULTS: Irradiation caused GCC and neurite destruction on a time- and irradiation dose-dependent manner. Changes in morphological characteristics were similar following either irradiation. Morphological and functional assays showed that day-8 neurons were more radiosensitive than day-16 neurons, whereas, radiosensitivity of DRG was comparable to that of SYMP. The dose-response fitting curve utilising both GCC and TUNEL labeling index showed higher relative biological effectiveness (RBE) values were associated with lower lethal dose (LD) values, while lower RBE was associated with higher LD values. CONCLUSION: Exposure to high-linear energy transfer (LET) irradiation is up to 3.2 more efficient to induce GCC and apoptosis, in early developed neuronal cells, than low-LET irradiation. GCC is a reliable method to assess the radiobiological response of neurons.

Amnestic concentrations of sevoflurane inhibit synaptic plasticity of hippocampal CA1 neurons through gamma-aminobutyric acid-mediated mechanisms.

BACKGROUND: The cellular mechanisms of anesthetic-induced amnesia are still poorly understood. The current study examined sevoflurane at various concentrations in the CA1 region of rat hippocampal slices for effects on excitatory synaptic transmission and on long-term potentiation (LTP), as a possible mechanism contributing to anesthetic-induced loss of recall. METHODS: Population spikes and field excitatory postsynaptic potentials were recorded using extracellular electrodes after electrical stimulation of Schaffer-collateral-commissural fiber inputs. Paired pulse facilitation was used as a measure of presynaptic effects of the anesthetic. LTP was induced using tetanic stimulation (100 Hz, 1 s). Sevoflurane at concentrations from amnestic (0.04 mm) to clinical concentrations (0.23-0.41 mm) were added to the perfusion solution. RESULTS: In the presence of 0.04 mm sevoflurane, the amplitude of population spikes was significantly depressed, and tetanic stimulation induced only posttetanic potentiation and then failure of LTP. These inhibitory effects were antagonized by bicuculline (10 microm), a gamma-aminobutyric acid type A receptor antagonist. Sevoflurane at 0.23-0.41 mm further depressed the amplitude of field excitatory postsynaptic potentials in a dose-dependent manner and completely blocked LTP. Bicuculline only partially antagonized 0.41 mm sevoflurane-induced profound inhibition of LTP. Sevoflurane at 0.23-0.41 mm, but not at 0.04 mm, significantly increased paired pulse facilitation, suggesting that sevoflurane has presynaptic actions to reduce glutamate release from nerve terminals. CONCLUSIONS: The current study provides evidence that amnestic concentrations of sevoflurane inhibit LTP of hippocampal CA1 neurons through gamma-aminobutyric acid-mediated mechanisms, and these actions seem to account for the effects of amnestic sevoflurane on synaptic plasticity.

Growth cone collapse and neurite retractions: an approach to examine X-irradiation affects on neuron cells.

The growth cone is a structure at the terminal of a neurite that plays an important role in the growth of the neurite. The growth cone collapse assay is considered to be a useful method to quantify the effects of various factors on nerve tissue. Here, we investigated the effect of x-irradiation on growth cones and neurites and also the comparative radiosensitivity of different neurons. Dorsal root ganglia and sympathetic chain ganglion were isolated from day-8 and -16 chick embryos and cultured for 20 h. Neurons were then exposed to x-irradiation and morphological changes were quantitatively evaluated by growth cone collapse assay. Cell viability was examined using TUNEL and WST-1 assays. The results showed that radiation induced growth cone collapse and neurite retraction in a time- and exposure-responsive manner. Growth cone collapse, apoptosis and WST-1 assays showed that no significant difference between the neurons throughout the study period (p > or = 0.5) after irradiation. Both types of day-8 neurons were more radio-sensitive than day-16 neurons (p < or = 0.05). The time course of the growth cone collapse was significantly correlated with the apoptotic and cell viability responses at different irradiation doses. Growth cone collapse may represent a useful marker for assaying the effect of x-irradiation on normal cell neurons.

[Cases of femoral nerve palsy after radical prostatectomy].

Although postoperative femoral neuropathy is an uncommon complication occurring after pelvic surgery, we experienced several cases of femoral nerve palsy in patients after radical prostatectomy. All cases had neither previous vascular nor peripheral nerve disease. To investigate the possible etiology, we compared the difference in age, height, body weight, body mass index (BMI), duration of surgery, and volume of bleeding in patients with or without femoral nerve palsy. Although age and volume of bleeding were similar in groups, height, body weight, BMI, and duration of surgery in nerve palsy group (n = 5) were significantly larger than those without nerve palsy (n = 9). To evade these complications, inappropriate stretching and prolonged compression of the nerve during surgery, two major mechanisms of the neuropathy, were asked not to do to urological surgeons. In addition, intravenous patient-controlled analgesia (IV-PCA) was also used for postoperative analgesia instead of epidural analgesia. After these strategies, we found that the frequency of femoral nerve palsy had considerably decreased. Patients received physical therapy and showed nearly total neurological recovery. We report here unusual complication following major pelvic surgery, and discuss the possible etiology and some strategies for prevention of this injury.

Effects of selective iNOS inhibition on systemic hemodynamics and mortality rate on endotoxic shock in streptozotocin-induced diabetic rats.

The purpose of this study was to examine whether selective iNOS inhibition can restore the hemodynamic changes and reduce the nitrotyrosine levels in the cerebral cortex of rats with streptozotocin-induced diabetes during endotoxin-induced shock. The study was designed to include three sets of experiments: (1) measurement of changes in systemic hemodynamics, (2) measurement of biochemical variables, including iNOS activity and nitrotyrosine formation in the brain, and (3) assessment of mortality rate. Rats were randomly divided into four groups: group 1, control; group 2, LPS: Escherichia coli endotoxin, 10.0 mg/kg (i.v.) bolus; group 3 (i.v.) LPS and L-N6-(1-iminoethyl)-lysine (L-NIL), 4mg/kg (i.p.); and group 4, LPS and NG-nitro-L-arginine methyl ester (L-NAME), 5 mg/kg (i.p.). In nondiabetic rats, administration of L-NIL prevented the hemodynamic and biochemical changes, and increases in plasma nitrite and cerebral nitrotyrosine levels induced by LPS. Administration of L-NAME partially prevented these LPS-induced changes. On the other hand, in diabetic rats, administration of L-NIL only partially prevented the hemodynamic and biochemical changes, and increases in plasma nitrite and cerebral nitrotyrosine levels associated with LPS. Administration of L-NAME, however, had no effects on these LPS-induced changes in diabetic rats. There was a significant difference in nitrotyrosine levels between nondiabetic and diabetic rats in groups 2, 3, and 4 at 2 and 3 h after the treatment (at 3 h; nondiabetic--control, 4.6 +/- 0.4; LPS (i.v.), 8.9 +/- 1.0, LPS (i.v.) + L-NIL, 4.7 +/- 0.5; LPS (i.v.) + L-NAME, 7.1 +/- 0.9; diabetic--control, 5.5 +/- 0.4; LPS (i.v.), 13.6 +/- 1.2; LPS (i.v.) + L-NIL, 9.0 +/- 0.9; LPS (i.v.) + L-NAME, 13.0 +/- 1.0; densitometric units). Insulin therapy resulted in a decrease in iNOS activity (at 3 h: 1.0 +/- 0.5 fmol mg min), nitrotyrosine formation (at 3 h; 5.0 +/- 0.5, densitometric units), and mortality rates (30% at 6 h, 50% at 12 h) in the LPS (i.v.) + L-NIL group of diabetic rats. Selective iNOS inhibition in diabetic rats could not improve hemodynamic instability, chemical changes, iNOS activity, and nitrotyrosine formation during septic shock compared with the improvements observed in nondiabetic rats. Tight glucose control along with administration of L-NIL can result in more effective restoration of the biochemical changes of septicemia in diabetic rats. Thus, hyperglycemia may be one of the mechanisms related to the aggravation of endotoxin-induced shock.

Possible involvement of spinal noradrenergic mechanisms in the antiallodynic effect of intrathecally administered 5-HT2C receptor agonists in the rats with peripheral nerve injury.

Intrathecal administration of serotonin type 2C (5-HT(2C)) receptor agonists produces an antiallodynic effect in a rat model of neuropathic pain. In the present study, we characterized this effect pharmacologically. Allodynia was produced by tight ligation of the fifth (L5) and sixth (L6) lumbar spinal nerves on the left side, and was measured by applying von Frey filaments to the left hindpaw. 6-chloro-2-(1-piperazinyl)-pyrazine (MK212; 100 microg) and 1-(m-chlorophenyl)-piperazine (mCPP; 300 microg) were used as 5-HT(2C) receptor agonists. Intrathecal administration of these agonists resulted in an antiallodynic effect. Intrathecal administration of atropine (30 mug), a muscarinic receptor antagonist, and yohimbine (30 microg), an alpha(2)-adrenoceptor antagonist, reversed the effects of 5-HT(2C) receptor agonists. Intrathecal pretreatment with 6-hydroxydopamine, an adrenergic neurotoxin, inhibited the antiallodynic effect of MK212. These results suggest that spinal noradrenergic mechanisms are involved in the antiallodynic effects of intrathecally administered 5-HT(2C) receptor agonists. Previously, we demonstrated that intrathecal administration of 5-HT(2A) receptor agonists also produced antiallodynic effects, and the effects were not reversed by yohimbine. Taken together, these findings suggest that 5-HT(2A) and 5-HT(2C) receptors in the dorsal horn of the spinal cord might be involved in alleviating neuropathic pain by different mechanisms.

Autologous bone marrow transplantation and hyperbaric oxygen therapy for patients with thromboangiitis obliterans.

Many patients suffering from severe ischemic limb disease inevitably experience amputation, despite intensive therapies. Sympathectomy and hyperbaric oxygen therapy are optional therapies for patients with peripheral circulation disorders. Recently, several clinical studies have established that implantation of bone marrow-mononuclear cells into ischemic limbs increases collateral vessel formation. In the present study, autologous implantation of bone marrow-mononuclear cells was prescribed to 7 patients with ischemic limbs because of peripheral arterial disease. Although the extent of the improvement was not consistent among the 7 cases, all of the patients experienced some improvement in their symptoms. Transcutaneous oxygen partial pressure measured in a hyperbaric chamber increased in 5 patients. No side effects were observed. In conclusion, combined use of autologous bone marrow transplantation and hyperbaric oxygen therapy may be safe and effective for achievement of therapeutic angiogenesis.

[Anesthetic management of a patient with post-emetic rupture of the esophagus induced by a foreign body].

Post-emetic spontaneous rupture of the esophagus (Boerhaave's syndrome) is still a life-threatening condition, despite recent advances in thoracic surgery and critical care medicine. Because a case report on anesthetic management of this condition is rare, we report here successful management of a 46-yr-old man with spontaneous esophageal rupture following forceful vomiting. He suddenly developed severe back pain and acute respiratory distress after vomiting during dinner and was brought to our emergency department. Examination on admission revealed an increased respiratory rate of 20 min(-1) with SpO2 97% with a facemask (O2, 3 l x min(-1)), a pulse rate of 100 min(-1), and a blood pressure of 138/88 mmHg. Upper gastrointestinal endoscopy showed a foreign body and CT examination revealed subcutaneous emphysema. He was diagnosed as spontaneous rupture of the esophagus. Emergency T-tube drainage was therefore scheduled. After semi-awake intubation with midazolam, general anesthesia was maintained with O2 (50%), N2O, sevoflurane (2%), and vecuronium infusion. A bronchial blocker was used for one lung ventilation to facilitate thoraco-abdominal approach. A careful attention should be paid to tracheal intubation to avoid any increase in intra-abdominal pressure to prevent further spillage of gastric contents into the mediastinum through the perforation. A transmural tear in the anterior wall of the esophagus was found and the foreign body (boiled meat) was removed. The patient recovered uneventfully and could be extubated on the first day in the ICU. It should be noted that successful management of this disease depends on accurate diagnosis and appropriate choice of treatments.

[Transient hyperglycemia following intra-peritoneal irrigation with 5% glucose in a patient with pseudomyxoma peritonei].

Pseudomyxoma peritonei is a condition characterized by the production of a large amount of mucopolysaccharide by a neoplastic epithelium. Although surgical removal of the mucinous ascites may be attempted, complete removal of the material is difficult. Thus, intra-peritoneal lavage with the liquid containing glucose or dextrose has been advocated to prevent reaccumulation of the mucus and complications such as bowel obstruction requiring repeated surgery. We report a case showing transient hyperglycemia following intra-peritoneal irrigation with 5% glucose in a patient with psudomyxoma peritonei. The patient was a 72-year-old woman. Preoperatively, she had hypertension and angina pectoris; but no history of glucose intolerance. Serum glucose was 92 mg x dl(-1). General anesthesia was induced with propofol (100 mg), vecuronium (6 mg), and fentanyl, and maintained with oxygen (33%), nitrous oxide and sevoflurane (1-2%). A mucinous tumor was found with a great deal of mucinous ascites. To remove the mucus and prevent subsequent re-accumulation, intra-peritoneal irrigation with 5% glucose in water was performed. Shortly after this procedure, the patient was found to be hyperglycemic (serum glucose 266 mg x dl(-1)) with normal oxygenation and hemodynamic data. The patient recovered uneventfully and could be extubated soon after surgery. Serum glucose level returned to 154 mg x dl(-1) one hour after surgery. Therefore, we think that this acute hyperglycemic condition, presumable due to intra-peritoneal irrigation, was transient. It is important to be aware of this dangerous complication associated with intra-peritoneal glucose instillation. Glucose monitoring during and after irrigation with glucose or dextrose is recommended.

The effect of positive end-expiratory pressure ventilation on propofol concentrations during general anesthesia in humans.

The present study investigated the effects of positive end-expiratory pressure (PEEP) on propofol concentrations in humans. Eleven patients undergoing elective surgery were enrolled in this study. Anesthesia was induced with propofol, then maintained using 60% nitrous oxide in oxygen, fentanyl 10-20 microg/kg and continuous infusion of propofol. Vecuronium was used to facilitate the artificial ventilation of the lungs. Propofol was administered to all subjects via target-controlled infusion to achieve a propofol concentration of 6.0 microg/mL at intubation and 2.0 microg/mL after intubation. Before, during and after PEEP level of 10 cmH(2)O, cardiac output (CO) and effective liver blood flow (LBF) was measured using indocyanine green as an indicator and blood propofol concentration was determined using high-performance liquid chromatography. Data are expressed as median and range. After PEEP of 10 cmH(2)O was applied, CO and effective LBF was significantly decreased from 5.5 (3.8-6.8) L/min to 4.5 (3.2-5.8) L/min (P < 0.05), 0.78 (0.65-1.21) L/min to 0.65 (0.50-0.89) L/min (P < 0.05), respectively. Propofol concentration was significantly increased from 2.21 (1.46-2.63) microg/mL to 2.45(1.79-2.89) microg/mL (P < 0.05). These data indicate that propofol concentrations can be increased by PEEP, suggesting the possibility of overdosing following PEEP.

Tetracaine at a small concentration delayed nerve growth without destroying neurites and growth cones.

Local anesthetics have direct neurotoxicity and induce growth cone collapse when applied to neurons at large concentrations. However, the effects of prolonged exposure to local anesthetics at a small concentration have never been studied. We examined whether neurite growth was slowed by tetracaine at small concentrations in chick embryo dorsal root ganglions. The effects of tetracaine were examined microscopically and by a neurite growth rate assay, quantitative morphologic assay, growth cone collapse assay, and Western blot assay. Neurite growth 24 and 48 h after application was delayed significantly when tetracaine was applied at a concentration larger than 5 microM. Filopodia of growth cones retracted, and their number was significantly decreased 24 and 48 h after the application of 10 and 20 microM of tetracaine. The quantity of actin in cell bodies increased, contrary to the effect on neurites and growth cones, where actin decreased 48 h after the application of 5, 10, and 20 microM of tetracaine. In conclusion, continuous exposure to tetracaine at small concentrations delayed neurite growth, reduced the number of filopodia, and decreased actin content.

The comparative effects of sevoflurane versus isoflurane on cerebrovascular carbon dioxide reactivity in patients with diabetes mellitus.

The use of volatile anesthetics has been reported to alter cerebrovascular carbon dioxide (CO2) reactivity. We examined the comparative effects of sevoflurane versus isoflurane on cerebrovascular CO2 reactivity in 40 patients with diabetes mellitus. Anesthesia was maintained with either 1.0 minimum alveolar anesthetic concentration of sevoflurane or 1.0 minimum alveolar anesthetic concentration of isoflurane in 33% oxygen and 67% nitrous oxide. A 2.5-MHz pulsed transcranial Doppler probe was attached to the patient's head at the right temporal window for continuous measurement of mean blood flow velocity in the middle cerebral artery. After establishing baseline middle cerebral artery velocity values and cardiovascular hemodynamics, we increased end-tidal CO2 by decreasing ventilatory frequency by 2-5 breaths/min and repeated the measurements. These were then used to calculate absolute and relative CO2 reactivity. Absolute CO2 reactivity was less in insulin-treated patients with either sevoflurane or isoflurane compared with those patients on oral antidiabetic drugs or dietary therapy (sevoflurane group: diet = 2.6 +/- 0.6; oral antidiabetic drug = 2.5 +/- 0.8; insulin = 1.6 +/- 0.8*; isoflurane group: diet = 3.3 +/- i0.7; oral antidiabetic drug = 3.4 +/- 0.7; insulin = 1.9 +/- 0.7* cm.s(-1).mm Hg(-1); *P < 0.05, respectively). Relative CO2 reactivity showed a similar pattern in the diet-controlled and oral antidiabetic groups, absolute and relative CO2 reactivities were lower with sevoflurane versus isoflurane. Hence, we conclude that cerebrovascular CO2 reactivity in insulin-dependent patients is impaired under both sevoflurane and isoflurane anesthesia.

The effects of volatile anesthetics on intraoperative monitoring of myogenic motor-evoked potentials to transcranial electrical stimulation and on partial neuromuscular blockade during propofol/fentanyl/nitrous oxide anesthesia in humans.

The aim of the present study was to compare the influence of volatile anesthetics on transcranial motor-evoked potentials (tcMEP) in humans anesthetized with propofol/fentanyl/nitrous oxide and on partial neuromuscular blockade (NMB). The authors studied 35 ASA I and II patients who were undergoing elective craniotomy and brain tumor resection. The patients were randomized to one of three groups to receive halothane (HAL), isoflurane (ISO), or sevoflurane (SEV). Anesthetic depth was initially adjusted using the bispectral index to 40+/-5, and NMB was adjusted to 40%-50% of one twitch of train of four (T1) after recovery from intubation. MEPs with train of five square-wave pulses were elicited using screw electrodes placed in the skull over C3-C4. After craniotomy, the inhalational agent was introduced at 0.5 MAC and then 1.0 MAC (20 minutes each), and the effects on MEPs, NMB, and hemodynamic variables were studied. A decrease in BIS and systolic blood pressure was observed with all agents. Both SEV and ISO at 1.0 MAC significantly decreased train-of-four ratio from 38.4+/-18.1 at control to 19.0+/-9.7 and from 35.3+/-12.4 to 26.1+/-13.7, respectively (P<0.001), but not HAL at 1.0 MAC. The amplitudes of tcMEPs were significantly reduced by all agents at 1.0 MAC, with the effect being less in HAL at 0.5 MAC. We have shown that HAL had a lesser suppressive effect on MEPs than either ISO or SEV at 0.5 MAC, which was partially due to a lesser degree of NMB.