Effectiveness of Bortezomib in a Patient With Acute Rejection Associated With an Elevation of Donor-Specific HLA Antibodies After Small-Bowel Transplantation: Case Report.

BACKGROUND: A significant association between donor-specific antibody (DSA) and graft rejection has recently been documented. However, confirmed strategy has not been established for DSA-associated rejection after intestinal transplantation (ITx). CASE REPORT: A 20-year-old male patient with chronic intestinal obstruction caused by hypoganglionosis of the entire intestine underwent cadaveric donor ITx with grafting performed on 232 cm of the small intestine, cecum, and a part of the ascending colon. On post-operative day (POD) 14, a histological evaluation showed an acute rejection of indeterminate grade. The patient had severe acute rejection on POD 16, which prompted us to administer bolus steroids and polyclonal anti-thymocyte antibody, along with baseline maintenance immunosuppression. The histopathological findings of the graft indicated typical acute cellular rejection, although C4d was positive. We then detected donor-specific HLA antibody. The patient initially responded well to the therapy and showed decreased histological rejection signs. However, the refractory low-grade rejection persisted in the graft. During this period, the patient showed increased levels of DSA, and we speculated that the persistent rejection was associated with DSA; thus, bortezomib was administered at this stage as a salvage therapy. This rejection was thereafter successfully controlled without severe adverse effect. Twenty-three months after ITx, the patient is currently alive with complete enteral autonomy. CONCLUSIONS: A case of acute graft rejection followed by a marked elevation of DSA is presented. In this particular case, a modified treatment protocol using bortezomib in addition to the typical immunosuppressive agents was effective.

Effect of remifentanil on plasma propofol concentration and bispectral index during propofol anaesthesia.

BACKGROUND: Propofol and remifentanil are commonly administered together in clinical anaesthesia, but the effect of remifentanil on the plasma concentration of propofol has yet to be established. The aim of the present study was to investigate the effect of remifentanil on plasma propofol concentrations (Cp) in the absence of surgical stimulation. METHODS: Thirty-eight patients undergoing elective gynaecologic surgery were randomly assigned to receive one of the three remifentanil doses (0, 0.5, or 1.0 µg kg⁻¹ min⁻¹). Anaesthesia was induced by a target-controlled infusion of propofol. After tracheal intubation, saline or remifentanil infusion was administered for 15 min. Mean arterial pressure (MAP), heart rate (HR), and bispectral index (BIS) were recorded and cardiac index (CI), blood volume, and indocyanine green disappearance ratio (K-ICG) were measured using a dye densitogram analyser before and 15 min after saline or remifentanil infusion. Cp was measured using high-performance liquid chromatography. RESULTS: HR, K-ICG, and BIS were significantly decreased in the remifentanil 0 µg kg⁻¹ min⁻¹ group. The decrease in MAP, HR, CI, and K-ICG was significantly lower in the remifentanil 0.5 and 1.0 µg kg⁻¹ min⁻¹ groups compared with the remifentanil 0 µg kg⁻¹ min⁻¹ group. Cp was significantly increased after remifentanil administration, but this had no influence on BIS. CONCLUSIONS: Remifentanil reduced the CI and increased the Cp, which may be related to a decrease in the K-ICG, but had no significant effect on the BIS.

Eosinophilic bronchiolitis indicating eosinophilic airway disease with overexpression of carcinoembryonic antigen in sinus and bronchiole: case report.

The present case showed eosinophilic bronchiolitis and sinusitis with an overexpression of carcinoembryonic antigen (CEA) in lung and sinus and an elevation of serum CEA level, both of which were improved by oral steroid therapy. A 54-year-old asthmatic woman had developed a shortness of breath on exertion, and the chest X-ray revealed diffuse centrilobular shadows. Her serum CEA level had increased gradually. Eosinophil infiltration and overexpression of CEA were demonstrated in both the lung and sinus by immunohistochemistry. Both the lung and sinus lesions, and the serum CEA level were improved by oral steroid therapy. No evidence of tumor was found by extensive examination. From this case, eosinophilic bronchiolitis was considered to be an airway disease like "eosinophilic sinobronchiolitis" through the common pathophysiology of CEA, and serum CEA level was a good marker of disease condition.

Influence of hypobaric hypoxia on bispectral index and spectral entropy in volunteers.

BACKGROUND: Hypoxia has been shown to change electroencephalogram parameters including frequency and amplitude, and may thus change bispectral index (BIS) and spectral entropy values. If hypoxia per se changes BIS and spectral entropy values, BIS and spectral entropy values may not correctly reflect the depth of anaesthesia during hypoxia. The aim of this study was to examine the changes in BIS and spectral entropy values during hypobaric hypoxia in volunteers. METHODS: The study was conducted in a high-altitude chamber with 11 volunteers. After the subjects breathed 100% oxygen for 15 min at the ground level, the simulated altitude increased gradually to the 7620 m (25,000 ft) level while the subjects continued to breathe oxygen. Then, the subjects discontinued to breath oxygen and breathed room air at the 7620 m level for up to 5 min until they requested to stop hypoxic exposure. Oxygen saturation (SpO2), heart rate, 95% spectral edge frequency (SEF), BIS, response entropy (RE), and state entropy (SE) of spectral entropy were recorded throughout the study period. RESULTS: Of the 11 subjects, seven subjects who underwent hypoxic exposure for 4 min were analysed. SpO2 decreased to 69% at the 7620 m level without oxygen. However, SEF, BIS, RE, and SE before and during hypoxic exposure were almost identical. CONCLUSION: These data suggest that hypoxia of oxygen saturation around 70% does not have a strong effect on BIS and spectral entropy.

Rocuronium dose-dependently suppresses the spectral entropy response to tracheal intubation during propofol anaesthesia.

BACKGROUND: The Entropy Module anaesthesia monitor displays two spectral entropy-based indices, response entropy (RE) and state entropy (SE). The difference between RE and SE (RE-SE), which mainly reflects electromyography activation, is thought to indicate the adequacy of antinociception. Little is known, however, about the effects of neuromuscular blocking agents on the RE-SE. We investigated the effects of rocuronium on the RE-SE response to tracheal intubation. METHODS: Forty-four patients were randomly assigned to receive one of four rocuronium doses (0.3, 0.6, 0.9, and 1.2 mg kg(-1)). Anaesthesia was induced by propofol target-controlled infusion. Rocuronium was administered 2 min after anaesthesia induction. Tracheal intubation was performed 7 min after anaesthesia induction. Arterial pressure, heart rate (HR), bispectral index (BIS), RE, SE, and patient movement were recorded. RESULTS: All EEG-derived indices (BIS, RE, SE, and RE-SE) increased after tracheal intubation. The maximum increase in the indices after tracheal intubation was significantly suppressed by an increase in the rocuronium dose. Patient movement after tracheal intubation was suppressed by an increase in the rocuronium dose. All indices were higher in patients who moved during or after tracheal intubation than in those who did not move. Rocuronium dose did not affect the mean arterial pressure or HR in response to tracheal intubation. CONCLUSIONS: The RE-SE response to tracheal intubation was suppressed by increasing the rocuronium dose. Estimates of nociception using RE-SE should be interpreted carefully in different states of muscle paralysis during general anaesthesia.

Effect of cervical sympathetic trunk transection on renal sympathetic nerve activity in rats.

Stellate ganglion blockade (SGB) with a local anesthetic increases muscle sympathetic nerve activity in the tibial nerve in humans. However, whether this sympathetic excitation in the tibial nerve is due to a sympathetic blockade in the neck itself, or due to infiltration of a local anesthetic to adjacent nerves including the vagus nerve remains unknown. To rule out one mechanism, we examined the effects of cervical sympathetic trunk transection on renal sympathetic nerve activity (RSNA) in anesthetized rats. Seven rats were anesthetized with intraperitoneal urethane. RSNA together with arterial blood pressure and heart rate were recorded for 15 min before and 30 min after left cervical sympathetic trunk transection. The baroreceptor unloading RSNA obtained by decreasing arterial blood pressure with administration of sodium nitroprusside was also measured. Left cervical sympathetic trunk transection did not have any significant effects on RSNA, baroreceptor unloading RSNA, arterial blood pressure, and heart rate. These data suggest that there was no compensatory increase in RSNA when cervical sympathetic trunk was transected and that the increase in sympathetic nerve activity in the tibial nerve during SGB in humans may result from infiltration of a local anesthetic to adjacent nerves rather than a sympathetic blockade in the neck itself.

Effect of landiolol on bispectral index and spectral entropy responses to tracheal intubation during propofol anaesthesia.

BACKGROUND: beta1-Adrenoceptor antagonists suppress the haemodynamic and arousal responses to tracheal intubation. The Entropy Module shows two spectral entropy-based indices, response entropy (RE) and state entropy (SE). The difference between RE and SE (RE-SE) may reflect nociception during general anaesthesia. In the present study, we investigated the effect of landiolol on entropy indices in response to tracheal intubation. METHODS: A total of 60 patients were randomly assigned to receive saline (Group S), remifentanil (Group R), or landiolol (Group L). Anaesthesia was induced by propofol target-controlled infusion. Two minutes after the induction of anaesthesia, infusion with vecuronium bromide and remifentanil, landiolol, or saline was initiated. Tracheal intubation was performed 7 min after anaesthesia induction. Arterial pressure, heart rate (HR), bispectral index (BIS), and entropy indices were recorded. RESULTS: In Group S, RE increased significantly after tracheal intubation, but there was no significant increase in BIS or SE. These increases in RE were abolished in Groups R and L. RE-SE increased significantly after tracheal intubation in Group S, whereas no increase in RE-SE was observed in Groups R and L. Increases in mean arterial pressure and HR after tracheal intubation were suppressed in Groups R and L compared with Group S. CONCLUSIONS: RE increased in response to tracheal intubation, whereas BIS and SE did not. Landiolol and remifentanil suppressed the increase in RE after tracheal intubation with significant inhibition of RE-SE difference.

Imaging findings of radiation-induced sarcoma of the head and neck.

We set out to retrospectively review the clinical and imaging features of patients with post-radiation sarcoma, especially in the head and neck region. We reviewed the records of 4194 patients with carcinoma of the head and neck region who had a history of radiation. They had undergone CT and/or MRI. Medical records were reviewed for the primary diagnosis, radiation history and latency period to the development of sarcoma. The patients included four men and two women with a mean age of 64.5 years. The mean latency period for the development of sarcoma was 11.5 years. Primary diagnoses were maxillary carcinoma, nasopharyngeal carcinoma, adenoid cystic carcinoma of the oral floor, tonsilar carcinoma, soft palate carcinoma and tongue carcinoma. Histopathological examinations revealed osteosarcoma, spindle cell sarcoma, chondrosarcoma, malignant peripheral nerve sheath tumour, spindle cell carcinoma and malignant fibrous histiocytoma, respectively. Common findings were a heterogeneous and well-enhanced soft tissue mass and bone destruction. There is at present little or no prospect for the effective prevention of radiation-induced sarcoma of the head and neck. This emphasizes the importance of the earliest possible diagnosis for such patients. The imaging findings are not diagnosis specific, but strict follow-up within the radiation field by CT and MRI and an appreciation of the expected latency period may help to provide the diagnosis. When radiotherapy is performed for head and neck neoplasms, periodic follow-up observations may be necessary for many years.

Entropy indices vs the bispectral index for estimating nociception during sevoflurane anaesthesia.

BACKGROUND: It is now possible to acquire and process raw EEG and frontal EMG signals to produce two spectral-entropy-based indices (response entropy and state entropy) reflective of analgesic and hypnotic levels during general anaesthesia (with the Datex-Ohmeda S/5 Entropy Module, Datex-Ohmeda, Helsinki, Finland). However, there are no data available on the accuracy of the Entropy Module in estimating nociception during sevoflurane anaesthesia. METHODS: Forty female patients were enrolled in the present study. Each patient was allocated randomly to one of four end-tidal sevoflurane concentration (ET(sev)) groups (1.3, 1.7, 2.1 or 2.5%). A BIS Sensor (Aspect Medical Systems, Newton, MA) and an Entropy Sensor (Datex-Ohmeda) were applied side-by-side to the forehead. The bispectral index (A-2000 BIS Monitor, version 3.4, Aspect Medical Systems), response entropy, state entropy and patient movement were observed after electrical stimulation (20, 40, 60 and 80 mA, 100 Hz, 5 s) and after skin incision during sevoflurane anaesthesia (1.3, 1.7, 2.1 or 2.5%). Accuracy of the EEG variables in differentiating the intensity of electrical stimulation was estimated by the prediction probability (P(K)) values. RESULTS: Response entropy and state entropy [median, (range)] before skin incision were significantly lower in patients who did not move [29 (15-41) and 24 (14-41)] than in those that did [38 (24-53) and 37 (24-52)], but there was no significant difference in BIS. All EEG variables increased significantly (P<0.0001 for all) with increases in the intensity of electrical stimulation. The difference between response entropy and state entropy increased with increases in the electrical stimulation (P<0.0001). However, no EEG variables could differentiate the intensity of the electrical stimulations accurately because of low P(K)-values (P(K)<0.8). CONCLUSION: Noxious stimulation increased the difference between response entropy and state entropy. However, an increase in the difference does not always indicate inadequate analgesia and should be interpreted carefully during anaesthesia.

Halothane enhances dopamine metabolism at presynaptic sites in a calcium-independent manner in rat striatum.

BACKGROUND: We have previously reported that halothane anaesthesia increases the extracellular concentration of dopamine (DA) metabolites in the rat striatum with no change in DA. Although the metabolism of catecholamines is a source of oxidative stress, there is little information about DA metabolism and anaesthesia. We assessed the mechanism(s) of enhanced DA metabolism induced by halothane. METHODS: Microdialysis probes were implanted into male Sprague-Dawley rats and perfused with artificial cerebrospinal fluid (CSF). The dialysate was injected directly into an HPLC every 20 min. Each group of rats (n=5-7) was administered saline, apomorphine 100 microg kg(-1), pargyline 7.5 or 75 mg kg(-1), reserpine 2 mg kg(-1) or alpha-methyl-p-tyrosine (AMPT) 250 mg kg(-1). Another set of rats was perfused with artificial CSF containing tetrodotoxin (TTX) 1 microM or calcium-free CSF containing 10 mM EGTA. Rats were anaesthetized with halothane 0.5 or 1.5% 1 h after pharmacological treatments. RESULTS: In rats pretreated with apomorphine, despite a decrease in DA concentration, halothane induced a increase in DA metabolites. Pargyline (high dose) and reserpine completely and AMPT partially antagonized the increase in DA metabolites induced by halothane anaesthesia. TTX perfusion reduced the increase in DA, whereas calcium-free CSF perfusion did not. CONCLUSIONS: Our data suggest that halothane accelerates DA metabolism at presynaptic sites by releasing DA from reserpine-sensitive storage vesicles to the cytoplasm in a calcium-independent manner. The metabolic oxidative stress of inhalation anaesthesia requires future investigation.

Comparison of isoflurane and propofol-fentanyl anaesthesia in a swine model of asphyxia.

BACKGROUND: There have been few studies comparing the response to asphyxia and the effectiveness of typical cardiopulmonary resuscitation (CPR) using exogenous epinephrine administration and manual closed-chest compression between total intravenous anaesthesia (TIVA) and inhalational anaesthesia. METHODS: Twenty pigs were randomly assigned to two study groups anaesthetized using either 2% end-tidal isoflurane (n=10) or propofol (12 mg x kg(-1) h(-1))-fentanyl (50 microg x kg(-1)) (n=10). Asphyxia was induced by clamping the tracheal tube until the mean arterial pressure (MAP) decreased to 40% of the baseline value (40% MAP time). The tracheal tube was declamped at that point, and CPR was performed. Haemodynamic parameters and blood samples were obtained before the induction of asphyxia, at 1-min intervals during asphyxia, and 1, 2, 3, 5, 10, 30 and 60 min after asphyxia. RESULTS: TIVA maintained the MAP against hypoxia-hypercapnia stress significantly longer than isoflurane anaesthesia (mean (SD) 40% MAP time 498 (95) and 378 (104) s respectively). In all animals in the isoflurane group, spontaneous circulation returned within 1 min of the start of CPR. In six of the TIVA animals, spontaneous circulation returned for 220 (121) s; spontaneous circulation did not return within 5 min in the remaining four animals. CONCLUSIONS: Although TIVA is less prone than isoflurane anaesthesia to primary cardiovascular depression leading to asphyxia, TIVA is associated with reduced effectiveness of CPR in which resuscitation because of asphyxic haemodynamic depression occurs.

Induction of anesthesia with ketamine reduces the magnitude of redistribution hypothermia.

UNLABELLED: Hypothermia after induction of general anesthesia results largely from core-to-peripheral redistribution of body heat. Both central inhibition of tonic thermoregulatory vasoconstriction in arteriovenous shunts and anesthetic-induced arteriolar and venous dilation contribute to this redistribution. Ketamine, unique among anesthetics, increases peripheral arteriolar resistance; in contrast, propofol causes profound venodilation that other anesthetics do not. We therefore tested the hypothesis that induction of anesthesia with ketamine causes less core hypothermia than induction with propofol. Twenty patients undergoing elective surgery were randomly assigned to anesthetic induction with either 1.5 mg/kg ketamine (n = 10) or 2.5 mg/kg propofol (n = 10). Anesthesia in both groups was subsequently maintained with sevoflurane and 60% nitrous oxide in oxygen. Forearm minus finger, skin-temperature gradients <0 degrees C were considered indicative of significant arteriovenous shunt vasodilation. Ketamine did not cause vasodilation just after induction, whereas propofol rapidly induced vasodilation. Core temperatures in the patients given ketamine remained significantly greater than those in the patients induced with propofol. These data suggest that maintaining vasoconstriction during induction of anesthesia reduces the magnitude of redistribution hypothermia. IMPLICATIONS: Core hypothermia during the first hour of anesthesia was less after induction of anesthesia with ketamine than propofol. Maintaining arteriovenous shunt vasoconstriction during induction of anesthesia reduces the magnitude of redistribution hypothermia.

Relation between initial blood distribution volume and propofol induction dose requirement.

BACKGROUND: Propofol induction dose is variable and depends on many factors, including initial volume of distribution and early disposition. The authors hypothesized that preadministration blood distribution volumes, cardiac output (CO), and hepatic blood flow (HBF) could be examined to establish a propofol induction dose. METHODS: Propofol dose required to reach loss of consciousness, when infused at infusion rate per lean body mass (LBM) of 40 mg x kg(-1) x h(-1), was determined in 75 patients aged 11-85 yr. CO, blood volume (BV), central blood volume (CBV), and HBF were measured with indocyanine green pulse spectrophotometry. Univariate least squares linear regression analysis was used to individually analyze the relation between propofol induction dose and patient characteristics, including LBM, baseline distribution volumes, CO, and HBF. Stepwise multiple linear regression models were used to select important predictors of induction dose. RESULTS: Although there was a significant correlation between the induction dose and each of the eight variables of age, sex, LBM, hemoglobin, CO, BV, CBV, and HBF, only factors of age (partial r = -0.655), LBM (partial r = 0.325), CBV (partial r = 0.540), and HBF (partial r = 0.357) were independently associated with the induction dose (R2 = 0.85) when all variables were included in a multivariate model. CONCLUSIONS: At a constant propofol infusion rate of 40 mg x kg(-1) x h(-1) as a function of LBM in patients with American Society of Anesthesiologists physical status I or II, the induction dose can be determined from four variables: age, LBM, CBV, and HBF.

Histologic study of the regeneration process of human hair follicles grafted onto SCID mice after bulb amputation.

This study examines histologically the degeneration and subsequent regeneration processes of human hair follicles whose bulb is severely damaged. Human scalp hair follicles were isolated and grafted onto immunodeficient mice after their bulb was amputated. On day 14, thickening and corrugation of the vitreous membrane, apoptosis of follicular keratinocytes, and regression of the lower portion of the follicles were observed. By day 20, mesenchymal cells had accumulated around the lower end of the follicles. From day 14 through 50, the follicular regression and apoptosis continued, and between days 30 and 40 the follicles became maximally shortened, and the vitreous membrane disappeared. By day 50 the lower end of the follicles had become cup-shaped, and the cup surrounded an aggregate of mesenchymal cells that corresponded to the dermal papilla. By day 60, all the grafted follicles had developed into anagen VI follicles, and the apoptosis had ceased. These results indicate that human scalp hair follicles whose bulb is completely destroyed enter into dystrophic telogen after restoration of the dermal papilla, then into anagen, and that the duration of the dystrophic telogen is shorter than that of the normal hair cycle.

3D-MR mammography-guided breast conserving surgery after neoadjuvant chemotherapy: clinical results and future perspectives with reference to FDG-PET.

BACKGROUND: Three dimensional MR Mammography (3D-MRM) can detect tumor extension more accurately than mammography or ultrasound. There are two shrinkage patterns observed by 3D-MRM after neoadjuvant chemotherapy. Concentric shrinkage is a good indication for breast conserving surgery. On the other hand, a dendritic pattern was represent ductal spread. Therefore, we developed MRM guided mapping to aid BCS for tumors showing a dendritic pattern. METHODS: Fifteen patients consisting of 8 stage II (T > 3.5 cm) cases and 7 stage IIIa cases aged 39 to 61 years (mean 47-8 years) were treated with AT neoadjuvant chemotherapy with the aim of performing breast conserving surgery. All patients were examined by 3D-MRM before and after neoadjuvant chemotherapy. Breast conserving surgery indications were determined by tumor volume reduction and shrinkage patterns on 3D-MRM. Supine position mapping using MRM was performed for dendritic type tumors. FDG-PET was simultaneously performed for one case with bilateral breast cancer. RESULTS: Breast conserving surgery was performed for 13 of the 15 cases. One case underwent re-operating and mastectomy because of a positive margin. One case had microscopically positive margin and received boost radiation. Therefore, 11 of 15 cases (73.3%) underwent BCS and achieved negative margins under MRM guidance. PET scanning can detect residual tumor and occult metastasis but it is not suitable for mapping because of its spatial resolution. CONCLUSIONS: 3D-MRM is a useful modality to select appropriate cases for breast conserving surgery after neoadjuvant chemotherapy. FDG-PET can also detect residual tumor or occult metastasis but it may not be suitable for mapping. Because both examinations have potential, further evaluation of their clinical efficacy is necessary.

Optimal propofol plasma concentration during upper gastrointestinal endoscopy in young, middle-aged, and elderly patients.

BACKGROUND: Suitable propofol plasma concentrations during gastroscopy have not been determined for suppressing somatic and hemodynamic responses in different age groups. METHODS: Propofol sedation at target plasma concentrations from 0.5 to 4.0 microgram/ml were performed randomly in three groups of patients (23 per group) who were undergoing elective outpatient gastroscopy: ages 17-49 yr (group 1), 50-69 yr (group 2), and 70-89 yr (group 3). Plasma propofol concentration in which 50% of patients do not respond to these different stimuli were determined by logistic regression: verbal command (Cp50ls), somatic response to gastroscopy (Cp50endo), and gag response to gastroscopy (Cp50gag). Hemodynamic responses were also investigated in the different age groups. RESULTS: Cp50ls concentrations were 2.23 microgram/ml (group 1), 1.75 microgram/ml (group 2), and 1.40 microgram/ml (group 3). The Cp50endo values in groups 1 and 2 were 2.87 and 2.34 microgram/ml, respectively, which were significantly higher than their respective Cp50ls values. Cp50endo value in group 3 was 1.64 microgram/ml, which was close to its Cp50ls value. Because of a high degree of interpatient variability, Cp50gag could not be defined. Systolic blood pressure response decreased with increasing propofol concentrations. CONCLUSIONS: The authors determined the propofol concentration necessary for gastroscopy and showed that increasing age reduces it. Propofol concentration that suppresses somatic response induces loss of consciousness in almost all young patients.