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Background Previous studies showed that remifentanil-induced anesthesia can inhibit surgical stress response in non-diabetic adult patients and that low-dose glucose loading during anesthesia may attenuate fat catabolism. However, little is known about the influence of glucose loading on metabolism in elderly patients, whose condition may be influenced by decreased basal metabolism and increased insulin resistance. We hypothesized that, in elderly patients, intraoperative low glucose infusion may attenuate the catabolism of fat without causing harmful hyperglycemia during remifentanil-induced anesthesia. Methods Elderly, non-diabetic patients scheduled to undergo elective surgery were enrolled and randomized to receive no glucose (0G group) or low-dose glucose infusion (0.1 g/kg/hr. for 1 h followed by 0.05 g/kg/hr. for 1 h; LG group) during surgery. Glucose, adrenocorticotropic hormone (ACTH), 3-methylhistidine (3-MH), insulin, cortisol, free fatty acid (FFA), creatinine (Cr), and ketone body levels were measured pre-anesthesia, 1 h post-glucose infusion, at the end of surgery, and on the following morning. Results A total of 31 patients (aged 75–85) were included (0G, n = 16; LG, n = 15). ACTH levels during anesthesia decreased significantly in both groups. In the LG group, glucose levels increased significantly after glucose loading but hyperglycemia was not observed. During surgery, ketone bodies and FFA were significantly lower in the LG group than the 0G group. There were no significant differences in insulin, Cr, 3-MH, and 3-MH/Cr between the two groups. Conclusion Remifentanil-induced anesthesia inhibited surgical stress response in elderly patients. Intraoperative low-dose glucose infusion attenuated catabolism of fat without inducing hyperglycemia. Trial registration This study has been registered with the University hospital Medical Information Network Center (http://www.umin.ac.jp/english/). Trial registration number: UMIN000016189. The initial registration date: January 12th 2015.

Two types of amniotic fluid embolism (AFE) have been described : cardiopulmonary collapse type and disseminated intravascular coagulation (DIC) type, with the latter proposed as uterine type. This report describes a healthy 28-year-old woman who developed AFE during a cesarean section. Because of a previous cesarean section, the patient underwent an elective cesarean section, under combined spinal-epidural anesthesia, at 38 weeks of pregnancy. She began coughing 5 minutes after delivery of the fetus, subsequently becoming unconscious and developing glossoptosis and bradycardia. Her blood pressure decreased to 76/43 mmHg, and AFE was suspected. Her uterus was atonic, and she experienced persistent noncoagulant bleeding, with a final blood loss of 6300 ml. Considerable blood transfusion was required. The patient survived, and she and her baby were discharged without any sequelae on the eighth postoperative day. This patient met the Japanese criteria for clinical AFE, with an obstetrical DIC score of 21 meeting the criteria for obstetrical DIC. Early diagnosis and treatment likely resulted in patient survival. J. Med. Invest. 67 : 207-210, February, 2020.

Cholestatic drug-induced liver injury (DILI) is a type of hepatotoxicity. Its underlying mechanisms are dysfunction of bile salt export pump (BSEP) and multidrug resistance-associated protein 2/3/4 (MRP2/3/4), which play major roles in bile acid (BA) excretion into the bile canaliculi and blood, resulting in accumulation of BAs in hepatocytes. The sandwich-cultured hepatocyte (SCH) model can simultaneously analyze hepatic uptake and biliary excretion. Therefore, we investigated whether sandwich-cultured human induced pluripotent stem cell (iPS cell)-derived hepatocytes (SCHiHs) are suitable for evaluating cholestatic DILI. Fluorescent N-(24-[7-(4-N,N-dimethylaminosulfonyl-2,1,3-benzoxadiazole)]amino-3α,7α,12α-trihydroxy-27-nor-5β-cholestan-26-oyl)-2'-aminoethanesulfonate (tauro-nor-THCA-24-DBD, a BSEP substrate) was accumulated in bile canaliculi, which supports the presence of a functional bile canaliculi lumen. MRP2 was highly expressed in the Western blot analysis, whereas the mRNA expression of BSEP was hardly detectable. MRP3/4 mRNA levels were maintained. Of the 22 compounds known to cause DILI with BAs, 7 showed significant cytotoxicity. Most high-risk drugs were detected using the developed SCHiH system. However, a shortcoming was the considerably low expression level of BSEP, which prevented the detection of some relevant drugs whose risks should be detected in primary human hepatocytes.

Robot-assisted laparoscopic radical prostatectomy (RALRP) is commonly performed in the surgical treatment of prostate cancer. However, the steep Trendelenburg position (25) and pneumoperitoneum required for this procedure can sometimes cause hemodynamic changes. Although blood pressure is traditionally monitored invasively during RALRP, the ClearSight system (BMEYE, Amsterdam, The Netherlands) enables a totally noninvasive and simple continuous blood pressure and cardiac output monitoring based on finger arterial pressure pulse contour analysis. We therefore investigated whether noninvasive continuous arterial blood pressure measurements using the ClearSight system were comparable to those obtained invasively in patients undergoing RALRP. Ten patients scheduled for RALRP with American Society of Anesthesiologists physical status I-II were included in this study. At each of the seven defined time points, noninvasive and invasive blood pressure measurements were documented and compared in each patient using Bland-Altman analysis. Although the blood pressure measured with the ClearSight system correlated with that measured invasively, a large difference between the values obtained by the two devices was noted. The ClearSight system was unable to detect blood pressure accurately during RALRP, suggesting that blood pressure monitoring using this device alone is not feasible in this small patient population. J. Med. Invest. 65:69-73, February, 2018.

We investigated the effectiveness of the ClearSight system for hemodynamic management during kidney transplantation for a recipient. The recipient was to receive a kidney transplant from his mother under general anesthesia. We used continuous noninvasive finger-cuff-based monitoring of blood pressure, provided by the ClearSight system, and stroke volume variation to predict fluid responsiveness. We used of a balanced anesthetic technique and stringent monitoring standards to ensure a successful outcome for the patient. This case demonstrated that ClearSight has the potential to improve patient monitoring in hemodynamically stable patients who received kidney transplantation under general anesthesia. J. Med. Invest. 65:139-141, February, 2018.

Aims Geranylgeranylacetone (GGA) is commonly utilized to protect the gastric mucosa in peptic ulcer disease. Recently GGA has been shown to protect the myocardium from ischemia/reperfusion by activating heat shock proteins. However, the exact mechanism as to how GGA activates these protective proteins is unknown. Caveolae and caveolin-3 (Cav-3) have been implicated in ischemia, anesthetic, and opioid induced cardiac protection. Given the lipophilic nature of GGA it is our hypothesis that GGA induced cardiac protection requires caveolae and Cav-3. Main methods We used an in vivo mouse model of ischemia–reperfusion injury and performed biochemical assays in excised hearts. Key findings GGA treated control mice revealed increased caveolae formation and caveolin-3 in buoyant fractions, mediating heat shock protein 70 activation. Furthermore, control mice treated with GGA were protected against ischemia/reperfusion injury whereas Cav-3 knockout (Cav-3 KO) mice were not. Troponin levels confirmed myocardial damage. Finally, Cav-3 KO mice treated with GGA were not protected against mitochondrial swelling whereas control mice had significant protection. Significance This study showed that caveolae and caveolin-3 are essential in facilitating GGA induced cardiac protection by optimizing spatial and temporal signaling to the mitochondria.

Pharmacological preconditioning, including that with geranylgeranylacetone (GGA) and volatile anesthetics, has been shown to confer cardiac protection from ischemia/reperfusion injury although the mechanisms for this protection are poorly understood. Caveolins, integral membrane proteins that act as scaffolding proteins in caveolar membranes, localize molecules involved in cardiac protection. We have tested the hypothesis that caveolin-3 (Cav-3), the predominant isoform in cardiac myocytes, is essential for the synergistic effect observed between GGA and volatile anesthetics.Mice were randomly assigned to receive GGA, isoflurane [0.5 and 1.0 minimum alveolar concentration (MAC)], or GGA + isoflurane (0.5 MAC). An in vivo mouse model of ischemia/reperfusion injury was tested in wild-type and Cav-3 knockout mice, and the infarct size was determined. Biochemical assays were also performed in excised hearts.Geranylgeranylacetone and therapeutic isoflurane (1.0 MAC) independently reduced infarct size (31.6 ± 6.1 and 28.0 ± 5.0% of the area at risk, respectively; n = 10) as compared to the controls (45.8 ± 9.4%; n = 10). The combination GGA + sub-therapeutic isoflurane (0.5 MAC) further decreased the infarct size to 19.3 ± 5.1% (n = 10). Preconditioning [GGA, isoflurane (1.0 MAC), and GGA + isoflurane] increased the amount of Cav-3 protein in the discontinuous sucrose-gradient buoyant fractions. Additionally, cardiac protection was not observed in Cav-3 knockout mice following the administration of GGA, isoflurane, and GGA + isoflurane.Combined administration of GGA + isoflurane had a synergistic effect, enhancing the protection against myocardial infarction to a greater extent than either drug alone. This beneficial effect is mediated by Cav-3 expression.

Toxicological approaches in screening drugs that cause drug-induced liver injury (DILI) are urgently needed to reduce the risk of developing DILI and avoid immense costs resulting from late-stage drug withdrawal from clinical trials. Cholestatic DILI is characterized by bile acid (BA) accumulation in hepatocytes, typically caused by drug-induced inhibition of important bile transporters, such as bile salt export pump (BSEP) and multidrug resistance-associated protein 2/3/4 (MRP2/3/4). Therefore, NTCP expression is essential for construction of an in vitro hepatocellular toxicity evaluation system. Here, we investigated whether sandwich-cultured HepG2-hNTCP-C4 (SCHepG2-hNTCP-C4) cells were applicable for evaluation of cholestatic DILI. In SCHepG2-hNTCP-C4 cells, NTCP and MRP2/4 expression levels were comparable to those in human primary hepatocytes; however, BSEP expression was low. In addition, the substrates tauro-nor-THCA-24 DBD and CDF confirmed the functionality of NTCP and MRP2, respectively. When 22 known hepatotoxins were exposed to BAs to evaluate cholestatic DILI, cytotoxicity in SCHepG2-hNTCP-C4 cells was more frequent than that in SCHepG2 cells. Thus, SCHepG2-hNTCP-C4 cells may be useful preclinical screening tools to predict the risk of cholestatic DILI induced by drug candidates. However, further studies are needed to determine why the cholestatic cytotoxicity of some compounds would be still insufficient in SCHepG2-hNTCP-C4 cells.

Purpose To determine reproducibility of the femoral condyle cartilage volume (CV) in cross-sectional and longitudinal studies using various 3D imaging techniques at 1.5 T and 3 T. Materials and Methods In 21 subjects with osteoarthritis, magnetic resonance imaging (MRI) including four different sequences (sagittal 3D fat suppressed spoiled gradient-echo [SPGR] at 1.5 T, fat suppressed fast low angle shot [FLASH] at 3 T, water-excitation dual echo steady state [DESS] at 3 T, and water-excitation multiecho data image combination [MEDIC] at 3 T) were acquired at baseline and ∼1 year later. The CV measured using semiautomated segmentation software by three readers was analyzed. Results The mean of the interclass correlation coefficient between each reader from SPGR, FLASH, DESS, and MEDIC was 0.899, 0.948, 0.943, and 0.954, respectively. The mean CV (×104 mm3) measured by each reader from SPGR/FLASH/DESS/MEDIC sequences was the following in this order: 1.34/1.52/1.50/1.35, 1.21/1.43/1.40/1.27, 1.22/1.37/1.36/1.22, and 1.17/1.36/1.35/1.21 by readers 1, 2, 3 (first analysis), and 3 (second analysis), respectively. There was no statistically significant difference in CV between any readers in any sequences. The CV measured on FLASH and DESS tended to be greater than that on SPGR or MEDIC. Conclusion Inter- and intraobserver reproducibility of cartilage segmentation using semiautomated software was validated. Although there was no statistical significance, there was a tendency of under- or overestimating CV by each sequence. J. Magn. Reson. Imaging 2014;39:972–977. © 2013 Wiley Periodicals, Inc.

Background Exendin-4, an exogenous glucagon-like peptide-1 receptor (GLP-1R) agonist, protects the heart from ischemia/reperfusion injury. However, the mechanisms for this protection are poorly understood. Caveolae, sarcolemmal invaginations, and caveolins, scaffolding proteins in caveolae, localize molecules involved in cardiac protection. We tested the hypothesis that caveolae and caveolins are essential for exendin-4 induced cardiac protection using in vitro and in vivo studies in control and caveolin-3 (Cav-3) knockout mice (Cav-3 KO). Methods Myocytes were treated with exendin-4 and then incubated with methyl-β-cyclodextrin (MβCD) to disrupt caveolae formation. This was then followed by simulated ischemia/reperfusion (SI/R). In addition, cardiac protection in vivo was assessed by measuring infarct size and cardiac troponin levels. Results Exendin-4 protected cardiac myocytes (CM) from SI/R [35.6 ± 12.6% vs. 64.4 ± 18.0% cell death, P = 0.034] and apoptosis but this protection was abolished by MβCD (71.8 ± 10.8% cell death, P = 0.004). Furthermore, Cav-3/GLP-1R co-localization was observed and membrane fractionation by sucrose density gradient centrifugation of CM treated with MβCD + exendin-4 revealed that buoyant (caveolae enriched) fractions decreased Cav-3 compared to CM treated with exendin-4 exclusively. Furthermore, exendin-4 induced a reduction in infarct size and cardiac troponin relative to control (infarct size: 25.1 ± 8.2% vs. 41.4 ± 4.1%, P

We describe a case of a 39-year-old woman diagnosed with placenta percreta complicated by massive hemorrhage during a cesarean section. At 27 weeks of gestation, she underwent an emergency cesarean section under general anesthesia for vaginal bleeding and an intrauterine infection. Soon after delivery, a massive hemorrhage was encountered while attempting to separate the placenta percreta from the bladder wall. Although total abdominal hysterectomy and partial cystectomy were performed, massive hemorrhaging persisted. Bleeding was finally controlled following bilateral internal iliac artery embolization. We used a cell salvage device and a rapid infuser for hemodynamics stabilization. Total blood loss was 47,000 mL, and anesthesia time was 12 h and 47 min. The patient was discharged on the 32(nd) postoperative day without major complications. Placenta accreta can be associated with life-threatening hemorrhage and it is vital to plan accordingly preoperatively.

Background: It has been well demonstrated a positive association between the magnitude of host antibody response and periodontal disease status. Previous studies also reported that Porphyromonas gingivalis-specific IgG subclass antibodies were elevated in sera from adult periodontitis patients. However, the role and the association of these IgG subclass antibodies to the development of periodontal diseases are poorly understood. Aim: The aim of present investigation was to examine the relation of serum IgG subclass antibody levels and alveolar bone loss in treated and untreated periodontitis patients. Methods: Serum samples were taken from 20 treated and maintained periodontitis patients (SPT patients), 30 untreated patients and 19 periodontally healthy subjects. We determined the IgG subclass antibody titers to P. gingivalis whole cells using an enzyme-linked immunosorbent assay (ELISA). Subgingival plaque samples were taken from the mesio-buccal surface of 6 randomly selected teeth of SPT patients and evaluated for the presence of P. gingivalis by immunofluorescence microscopy. Clinical measurements were also taken including full mouth intraoral radiographs to measure interproximal alveolar bone loss at baseline (BLS1) and at a 5-year recall visit in the SPT patients (BLS2). Results: Our results indicated that both patient groups had detectable levels of IgG1, IgG2, and IgG4. Significantly higher IgG1 was observed in both patient groups compared to the healthy subjects. The untreated patients also exhibited significantly elevated IgG2 response (p

A case of a patient associated with Williams syndrome undergoing aortoplasty for supravalvular aortic stenosis is presented.Williams syndrome is a rare disease associated with a characteristic facies, supravalvular aortic stenosis, and mental retardation. A 15-yr-old girl with Williams syndrome underwent aortoplasty for supravalvular aortic stenosis. Anaesthesia was induced with fentanyl and thiamylal, and maintained with nitrous oxide, oxygen, sevoflurane, and continuous intravenous infusion of fentanyl. Supravalvular aortic stenosis was evaluated using a multiplane transesophageal echocardiography (TEE) probe before and after repair.Multiplane TEE was found to be very useful for anaesthetic management in a patient with Williams syndrome undergoing aortoplasty for supravalvular aortic stenosis.

Lubag disease is a genetic X-linked dystonia-parkinsonism syndrome afflicting Filipino men. This disease is characterized by dystonia dominating the first 10-15 years of the disorder, which is associated with or replaced by parkinsonian features in later years of life. A 49-year-old man with Lubag disease underwent general anesthesia for deep brain stimulation (DBS) surgery. Anesthesia was maintained mainly with propofol, remifentanil, rocuronium bromide, and sevoflurane. During magnetic resonance imaging, the patient was anesthetized with midazolam, fentanyl, and rocuronium bromide. The surgery was completed safely using these anesthetic agents. After DBS, some symptoms including involuntary movement improved within 10 days.

Hypocatalasemic mice were treated with N-methyl-N-nitrosourea (MNU) in their drinking water or gastric intubation for 16 weeks or were given N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in their drinking water for 6 months. With MNU treatment in the drinking water, well differentiated tumors were observed in the glandular stomachs of one male (4%) and 5 female (15%) animals. Sarcomas of the dermis also appeared in 10 males (40%). Adrenal lesions developed in I I females (35%) along with kidney, ovary, and uterus tumors. In the Group given MNU intubation, squamous cell carcinomas of the forestomach appeared from 122 days after the first treatment, reaching incidences of 81% in males, 94% in females, with invasion of the diaphragm in 3 male cases and the diaphragm, liver, pancreas, or adrenal in I I female cases. Glandular stomach tumors occurred in 12 males (52%), with 3 being signet ring cell carcinomas, and in 12 females (35%). In a sub-Group undergoing forestomach removal after MNU intubation esophagectasis appeared from 80 days after the operation at incidences of 63% in males and 74% in females. The glandular stomach tumors including 3 signet ring cell carcinomas were found in 17 of 46 (40%) males, 2 of 18 (11%) females demonstrated lesion, one being a signet ring cell carcinoma. In the Group receiving MNNG treatment, anemia appeared from the 5.5 month time point and no gastric tumors were observed. The present results do not support the conclusion that MNU induction of glandular stomach lesions in hypocatalasemic mice may provide a useful model of signet ring cell carcinomas

Prolyl endopeptidase-like immunoreactivity (PEP-LI) was detected and compared with amyloid beta-peptide-like immunoreactivity (A beta-LI) in the brains of senescence-accelerated mouse (SAM). Granular structures of PEP-LI in the hippocampus appeared progressively, and age- and strain-dependently to form deposits which distributed morphologically similar and closely to those of A beta-LI. These results suggest that PEP has functional relevance to amyloidgenesis in brains of SAM.

抗Porphyromonas gingivalis抗体の機能と, 本菌の歯周感染における主要抗原を調べる目的で, 初診時歯周炎患者および健常者の血清について, IgGサブクラス特異的モノクローナル抗体を用いて, 固相免疫測定法ELISA) による抗P. gingivalis抗体価の測定と, イムノブロット法による各IgGサブクラス抗体の対応抗原 の (解析を行った。凍結乾燥全菌体を抗原としたELISAの結果, 患者群では全てのサブクラスにおいて抗体価の有意な上昇が認められ, 大部分の患者では特定のサブクラスの抗体価が選択的に上昇していた。IgG2抗体価と各種臨床指数との問には有意な正の相関が認められた。しかし, IgG1, IgG3, IgG4および総IgG抗体価については, 各種臨床指数との間に, 相関は認められなかった。本菌の超音波破砕上清を使用したイムノブロット法による解析においては, IgG2サブクラスの抗体が患者に特徴的な染色像を最も頻繁に示し, IgG1サブクラスの抗体はすべての患者および健常者において反応が認められ, IgG3, IgG4のサブクラスに反応が認められた者は, 患者においても健常者においてもまれであった。P. gingivalis特異的IgG抗体の中でもIgG2サブクラスにおいて顕著な特徴が認められた事から, 本菌の糖抗原は歯周炎の免疫応答において重要な役割を演じているものと考えられる。

Gardenia yellow (GY) is a widely used natural yellow colorant for foods and clothing. In this study, we have examined the sub-chronic and chronic effects of GY in mice. Both sexes of C57BL/ HeN mice of six weeks old were used. GY was dissolved in distilled water and orally administered. In the sub-chronic study, 0, 0.05, 0.1, 0.2, 0.4, 0.8, and 1.6% of GY were given to mice and they were observed for 12 weeks. During this period, there were no abnormal changes detected in survivals, body weight increases or pathology of organs. It was concluded that GY had no toxicity up to 1.6% in drinking water. The concentrations of 0, 0.2 and 0.8% of GY were chosen for the further carcinogenicity study by observing for 95 weeks. In this chronic toxicity study, there was a 4.5 to 15.4% development of plasmacytoma in the mesenteric lymph nodes that has been known to occur spontaneously in C57BL mice. The pituitary and liver tumors were also noted regardless of the GY doses. The unique observation in this experimental series is the development of hepatosis that is characterized with enlarge-ments of liver, spleen, kidney, and lymph nodes, although they were not related to the doses of GY. These findings were rather systemic and this syndrome may be categorized as amyloidosis. The present study did not show any carcinogenicity or other chronic disorders by GY.

Colonization pattern of Pasteurella pneumotropica (P. pneumotropica) in mice with latent pasteurellosis was examined with the original selective media, NKBT medium and TGN broth. In the mice of 0 to 15 weeks old, the organism was mainly isolated from the upper respiratory tract, lower intestinal tract, feces and vagina, with the highest isolation rate in the pharyngolarynx. In the pregnant and lactating mice, the organism was isolated from the same sites, but not from the uterus, fetus or mammary gland. In the neonates, the organism was isolated from the respiratory and intestinal tracts within 24hr after birth. The organism was constantly detected in the feces of the 0- to 20-week-old mice, with the highest viable count one week after birth. Through the monitoring of mouse colonies, the pharyngolarynx always showed higher isolation rate than the feces in several mouse strains. These results reveal that the pharyngolarynx is the primary colonization site of P. pneumotropica in mice, and the lower intestinal tract and vagina are also the main sites. Further, frequent isolation of the organism from the feces and vagina, and the results in neonates suggest the mode of the transmission to newborn mice in the colony, i.e., intravaginal infection at the partition, and oro-nasal infection through the maternal feces and saliva.

Brugada syndrome is characterized by an electrocardiograph pattern of right bundle-branch block and has an increased risk for cardiac arrest due to malignant arrhythmia. We describe the successful anesthetic management for electroconvulsive therapy in a patient with Brugada electrocardiograph pattern. Patients with Brugada ECG pattern are not recommended to use neostigmine which augments ST elevation. Sugammadex was administered as a neuromuscular reversal agent in this case. Sugammadex provides rapid reversal of profound rocuronium-induced neuromuscular blockade under propofol anesthesia.

Hepatitis C virus RNA as detected by reverse transcription and nested polymerase chain reaction was monitored in 16 patients with chronic hepatitis C treated with interferon. Hepatitis C virus RNA became undetectable after 4 to 8 wk of interferon administration in 13 of the 16 patients. During 6 mo of follow-up, 5 of the 13 patients who became negative for hepatitis C virus RNA after interferon administration remained negative, and all five continued to have normal ALT levels. Repeat liver biopsy in these five patients revealed histological improvement. Antibody to hepatitis C virus, which was initially positive in all treated patients, fell to undetectable levels in three of the five patients. In contrast, aminotransferase levels rose again in all eight patients who had become hepatitis C virus RNA negative but had again exhibited hepatitis C virus RNA after completion of therapy. In 16 untreated patients, hepatitis C virus RNA remained detectable. These results indicate that detection of hepatitis C virus RNA may be useful as a marker of viral replication in chronic hepatitis C; they also suggest that interferon should again be administered to patients who become hepatitis C virus RNA negative on treatment but again exhibit this marker of viral replication when treatment is stopped. (HEPATOLOGY 1991;13:1040–1043.)

Obstructive sleep apnea syndrome (OSAS) is defined as intermittent complete or partial upper airway obstruction during sleep, causing mental and physical effects. Both the local and systemic inflammation observed in OSAS induce certain potent pro-inflammatory mediators, which may contribute to the development of cardiovascular consequences. The present study was designed to evaluate the plasma levels of TNF-alpha, which is one of the known pro-inflammatory cytokines, in patients with OSAS and to assess the effect of surgical treatment on the levels of TNF-alpha levels. Twenty seven patients diagnosed to have OSAS, 7 non-apneic patients with chronic tonsillitis (non-OSAS patients), and 4 healthy subjects were enrolled in this study. Blood samples were collected one week preoperatively and postoperatively, and the plasma TNF-alpha levels were measured using high-sensitivity ELISA. The plasma TNF-alpha levels in patients with OSAS were significantly elevated in comparison to normal healthy subjects. In contrast, there was no difference between the patients with non-OSAS and healthy subjects. Moreover, the surgical treatment to enlarge the upper airway in patients with OSAS significantly decreased the levels of TNF-alpha levels. Surgical treatment of patients with OSAS reduces the plasma TNF-alpha levels, thereby ameliorating the systemic inflammation and preventing the development of cardiovascular consequences.

Drug-induced mammary hyperplasias have been reported as rare complications of D-penicillamine and Neothetazone. The authors report the first case of bucillamine-induced giant mammary hyperplasia. Bucillamine is used as an antirheumatic drug that is structurally analogous to D-penicillamine. A 25-year-old woman with rheumatoid arthritis for the past 5 years started to develop gradual enlargement of her breasts 15 months before presentation. She had been on a combined treatment of steroid and lobenzarit disodium for the first 3 years, and then continued with a combined treatment of steroid and bucillamine for the following years until she was found to have pulmonary tuberculosis, at which time the steroid was suspended 10 months before she visited the authors' clinic. An almost total breast reduction was performed; 5 kg of right breast tissue and 7 kg of left breast tissue were excised. Retrospectively, bucillamine was believed to be the cause of the giant hypertrophy because of its structural similarity to D-penicillamine, which was the subject of an abundance of reports of mammary hyperplasia.

Five subtypes of hepatitis C virus (Pt[I], K1[II], K2a[III], K2b[IV] and Tr[V]) have been suggested based on the nucleotide sequence of the non-structural five region. To assess the susceptibility of each subtype to interferon therapy, we developed a one-step method which allows quick determination of subtype using polymerase chain reaction with a mixed primer set deduced from the sequence of each subtype. We were able to determine the subtype of 69 of 80 (86.3%) Japanese patients who received natural alfa-interferon treatment. The incidence of each subtype was K1: 53 (76.8%), K2a: 14 (20.3%), K2b: 3 (4.3%) and Tr: 1 (1.4%). Interferon was administered to these patients and found to be effective in 28 of 51 (54.9%) patients with K1 subtype and in 16 of 18 (88.9%) patients with other subtypes (P< 0.01). These data show that K1 is a major subtype in Japan and relatively resistant to interferon treatment.

Corticotropin-releasing hormone (CRH)–deficient (KO) mice provide a unique system to define the role of CRH in regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Despite several manifestations of chronic glucocorticoid insufficiency, basal pituitary proopiomelanocortin (POMC) mRNA, adrenocorticotrophic hormone (ACTH) peptide content within the pituitary, and plasma ACTH concentrations are not elevated in CRH KO mice. The normal POMC mRNA content in KO mice is dependent upon residual glucocorticoid secretion, as it increases in both KO and WT mice after adrenalectomy; this increase is reversed by glucocorticoid, but not aldosterone, replacement. However, the normal plasma levels of ACTH in CRH KO mice are not dependent upon residual glucocorticoid secretion, because, after adrenalectomy, these levels do not undergo the normal increase seen in KO mice despite the increase in POMC mRNA content. Administration of CRH restores ACTH secretion to its expected high level in adrenalectomized CRH KO mice. Thus, in adrenal insufficiency, loss of glucocorticoid feedback by itself can increase POMC gene expression in the pituitary; but CRH action is essential for this to result in increased secretion of ACTH. This may explain why, after withdrawal of chronic glucocorticoid treatment, reactivation of CRH secretion is a necessary prerequisite for recovery from suppression of the HPA axis.

Estrogen receptor (ER) levels were evaluated in thyroid tumors induced by N-methyl-N-nitrosourea (MNU) and low iodine diet (LID) or propylthiouracil (PTU) in intact and estrogen (E2) loaded Long-Evans (LE) rats. MNU at 40 mg/kg body wt was injected in 50 day-old LE rats of both sexes. The animals were killed 17-22 weeks later and the thyroid tissues were subjected to ER assay. In LID-treated groups, cytosolic ER (cER) levels were 6.7 +/- 5.8 (fmol/mg protein, mean +/- SE) in females and 0.7 +/- 1.4 in males, E2 increased the ER levels. In E2-loaded LID groups, cER levels were 12.9 +/- 3.7 in females and 1.7 +/- 1.7 in males. PTU treatment produced almost comparable ER levels as LID treatment. PTU treatment as well as LID treatment increased the serum TSH levels with E2 treatment producing additional elevation. In evaluating ER levels by histological type of thyroid tumors, the level in cER plus nER showed the lowest value of 6 +/- 6.4 (fmol/mg DNA, mean +/- SE) in hyperplasia, followed by 129 +/- 52.3 in adenoma and 289 +/- 51.7 in carcinoma. The rates of BrdU incorporation in thyroid follicles indicated higher proliferation activity in the area of adenoma and carcinoma rather than in the hyperplastic area. These data suggested that E2 treatment increases the ER levels in MNU and LID/PTU-induced thyroid tumors. The level of ER was correlated to the histological type of thyroid tumors.

Background Barber-Say syndrome (BSS) is a very rare congenital disorder characterized by macrostomia, cutis laxa, and other features. We report our experience of performing general anesthesia on a Japanese child with BSS. Case presentation A bilateral repair of the corners of the mouth under general anesthesia was planned for an 18-month-old male with macrostomia; the child was 75 cm in height and weighed 9.9 kg. As insertion of the peripheral intravenous catheter was difficult, it was inserted before the surgery by a pediatrician. The patient wore a mask and was ventilated manually after loss of consciousness with intravenous anesthesia. A mask for adults provided a superior fit and was effective in preventing air leakage from the corners of the mouth. After rocuronium was administered, the larynx was spread with a Macintosh laryngoscope. There was no laryngeal anatomical abnormality, and tracheal intubation was readily possible. The operation was completed without incident. Stiffening of both arms occurred for several seconds one hour after the operation ended, but the patient did not develop other complications. Conclusions Mask ventilation and the insertion of an intravenous catheter may be difficult in the general anesthesia of patients with BSS, and anesthetic management requires caution.