Dynamic vocal cord behavior and stridor during emergence from general anesthesia in small children with supraglottic airway.

PURPOSE: Stridor during emergence from anesthesia is not rare in children managed with supraglottic airway (SGA). However, we know little about the mechanisms of stridor and behavior of the vocal cords (VC). This study aimed to clarify patterns of VC movement and laryngeal airway maintenance function during recovery from anesthesia in children with SGA. METHODS: This is a secondary analysis of data collected from an observational study involving 27 anesthetized children. Using a multi-panel recording system, endoscopic VC image, vital sign monitor, multi-channel tracings of respiratory variables and respiratory sound and patient's view were simultaneously captured in one monitor. Inspiratory and expiratory VC angles formed by lines connecting anterior and posterior commissures were measured at the first spontaneous breath and the breath one minute after the first breath. VC narrowing and dilation were assessed by differences of VC angles. RESULTS: Inspiratory VC narrowing (median (IQR): 5.3 (2.7, 9.1) degree at the first breath) and dilation (- 2.7 (- 3.8, - 1.7) degree at the first breath) were observed in 15 and 12 out of 27 children, respectively. The former group achieved greater tidal volume compared to the latter in one minute. Five children (19%) temporarily developed stridor-like sound from outside with inspiratory VC narrowing. The stridor-like sound was captured by microphones attached to the neck and anesthesia circuit, but was not evident from the chest. CONCLUSION: Laryngeal narrowing occurs in half of the children with SGA during emergence from anesthesia, and temporal stridor-like sound is relatively common. CLINICAL TRIAL REGISTRATION: UMIN (University Hospital Information Network) Clinical Registry: UMIN000025058 ( https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000028697 ).

Transition of rupture mode of strain crystallizing elastomers in tensile edge-crack tests.

We revisit the classical results that the fracture energy density (Wb) of strain crystallizing (SC) elastomers exhibits an abrupt change at a characteristic value () of initial notch length (c0) in tensile edge-crack tests. We elucidate that the abrupt change of Wb reflects the transition in rupture mode between the catastrophic crack growth without a significant SIC effect at c0 > and the crack growth like that under cyclic loading (dc/dn mode) at c0 < as a result of a pronounced SIC effect near the crack tip. At c0 < , the tearing energy (G) was considerably enhanced by hardening via SIC near the crack tip, preventing and postponing catastrophic crack growth. The fracture dominated by the dc/dn mode at c0 < was validated by the c0-dependent G characterized by G = (c0/B)1/2/2 and the specific striations on the fracture surface. As the theory expects, coefficient B quantitatively agreed with the result of a separate cyclic loading test using the same specimen. We propose the methodology to quantify the tearing energy enhanced via SIC (GSIC) and to evaluate the dependence of GSIC on ambient temperature (T) and strain rate (). The disappearance of the transition feature in the Wb-c0 relationships enables us to estimate definitely the upper limits of the SIC effects for T (T*) and  (*). Comparisons of the GSIC, T*, and * values between natural rubber (NR) and its synthetic analog reveal the superior reinforcement effect via SIC in NR.

Maoto, a traditional herbal medicine, for post-exposure prophylaxis for Japanese healthcare workers exposed to COVID-19: A single center study.

BACKGROUND: Little research has been done on post-exposure prophylaxis (PEP) for COVID-19. This study was done to determine if maoto, a traditional herbal medicine commonly used for diseases with symptoms similar to those of COVID-19, can be repurposed for post-exposure prophylaxis to prevent the spread of nosocomial infection with SARS-CoV-2. METHODS: A cohort analysis was done of the data of 55 health care workers (HCWs) whether to get infected with SARS-CoV-2 in a Japanese hospital experiencing a COVID-19 cluster in April of 2021. Of these subjects, maoto granules for medical use were prescribed for PEP to 42 HCWs and taken for three days in mid-April. Controls were 13 HCWs who rejected the use of maoto. Polymerase chain reaction was performed routinely once or twice a week or when a participant presented with symptoms of COVID-19. RESULT: There were no background differences between the maoto and control groups by profession, sex, or mean age. No severe adverse reactions were observed. During the observation period of 1 week, significantly fewer subjects were diagnosed with COVID-19 in the maoto group (N = 3, 7.1%) than in the control group (N = 6, 46.2%). The prophylactic effectiveness of maoto was 84.5%. CONCLUSION: Oral administration of maoto is suggested to be effective as PEP against nosocomial COVID-19 infection.

Recovery of lower oesophageal barrier function: a pilot study comparing a mixture of atropine and neostigmine and sugammadex: A randomised controlled pilot study.

BACKGROUND: The lower oesophageal sphincter (LOS) barrier serves to prevent regurgitation of gastric contents. Although general anaesthesia depresses its function, its recovery process during emergence from anaesthesia has not been systematically examined. OBJECTIVE: To explore whether recovery of lower oesophageal barrier function differed between patients receiving a mixture of 1 mg atropine and 2 mg neostigmine and those receiving 2 mg kg-1 sugammadex during emergence from anaesthesia. DESIGN: An unblinded randomised controlled pilot study. SETTING: A single university hospital from January 2016 to December 2018. PATIENTS: A total of 20 non-obese adult females undergoing minor surgery. INTERVENTION: The patients were randomly assigned to a group either receiving atropine and neostigmine or sugammadex for reversal of rocuronium. MAIN OUTCOME MEASURES: Through use of the high-resolution manometry technique, the lower oesophageal barrier pressure (PBAR: primary variable) defined as a pressure difference between pressures at the LOS and the stomach was measured at five distinguishable time points during emergence from total intravenous anaesthesia. A mixed effects model for repeated measures was used to test the hypothesis. RESULTS: In all patients baseline PBAR values were positive even under muscle paralysis and general anaesthesia before administration of reversal agents, and did not differ between the groups (P = 0.299). During recovery from muscle paralysis and general anaesthesia, PBAR (mean ±â€ŠSD) significantly increased (P = 0.004) from 17.0 ±â€Š2.9 to 21.0 ±â€Š5.0 mmHg in the atropine and neostigmine group (n = 8) and from 19.1 ±â€Š9.0 to 24.5 ±â€Š12.7 mmHg in the sugammadex group (n = 11). PBAR significantly increased immediately after return of consciousness in both groups, whereas return of muscle tone, lightening of anaesthesia and tracheal extubation did not change it. CONCLUSION: Recovery of the lower oesophageal barrier function does not differ between patients receiving either atropine and neostigmine or sugammadex and is completed after recovery of consciousness from general anaesthesia. TRIAL REGISTRATION: UMIN Clinical Trials Registry: UMIN000020500: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&recptno=R000023594&type=summary&language=E.

Hypercapnia versus normocapnia for emergence from desflurane anaesthesia: Single-blinded randomised controlled study.

BACKGROUND: Rapid emergence from general anaesthesia is desirable only if safety is not sacrificed. Mechanical hyperventilation during hypercapnia produced by carbon dioxide infusion into the inspired gas mixture or by rebreathing was reported to shorten emergence time from inhalation anaesthesia. OBJECTIVES: To test the hypothesis that hypercapnia produced by hypoventilation before desflurane cessation shortens emergence time from general anaesthesia (primary hypothesis) and reduces undesirable cardiorespiratory events. DESIGN: A single-blinded randomised controlled study. SETTING: A single university hospital. PATIENTS: Fifty adult patients undergoing elective abdominal surgery under general anaesthesia using desflurane inhalation and intra-operative epidural anaesthesia. INTERVENTION: The patients were randomly assigned to either the normocapnia or hypercapnia group. MAIN OUTCOME MEASURES: Emergence time from desflurane anaesthesia and comparison of the incidence of 11 predefined undesirable cardiorespiratory events during and after emergence from anaesthesia between the groups. RESULTS: Forty-six patients were included in the analysis. End-tidal carbon dioxide concentrations at cessation of desflurane were 35 ±â€Š6 mmHg (mean ±â€ŠSD) and 52 ±â€Š6 mmHg in normocapnia (n = 23) and hypercapnia groups (n = 23), respectively. Emergence time was significantly faster in the hypercapnia group than the normocapnia group: 9.4 ±â€Š2.4 min, hypercapnia: 5.5 ±â€Š2.6 min, (P < 0.001) with a difference of 3.8 min on average (95% CI: 2.4 to 5.3). Spontaneous breathing established before recovery of consciousness was more evident in hypercapnia patients (normocapnia: 13%, hypercapnia: 96%, P < 0.001). Hypercapnia patients had more episodes of bradypnoea and apnoea before emergence of consciousness. In contrast, after tracheal extubation, incidences of bradypnoea and hypopnoea were more common in the normocapnia group. Undesirable cardiovascular events were not common, and no group differences were observed during emergence and postextubation periods. CONCLUSION: Hypoventilation-induced hypercapnia before desflurane cessation shortens the emergence time without causing additional clinically significant undesirable events. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN000020143) https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&recptno=R000023266&language=E.

Effects of Cardiac Surgery and Salvaged Blood Transfusion on Coagulation Function Assessed by Thromboelastometry.

OBJECTIVES: Coagulation function dynamically changes during cardiac surgery and is normalized after surgery. The authors investigated changes of coagulation function during cardiac surgery and after mimicked salvaged blood transfusion (SBT), and determined background risk factors for coagulation dysfunction by thromboelastmetry including maximum clot firmness of fibrinogen assay (FIBTEM-MCF: primary variable). DESIGN: Prospective observational study with ex vivo laboratory experiment. SETTING: University hospital. PARTICIPANTS: Consecutive 65 adult elective cardiac surgery patients being scheduled to use cell salvage technique. INTERVENTIONS: Arterial blood sampling (preoperative: after anesthesia induction, and postoperative: after reversal of heparin), and ex vivo dilution of postoperative blood with salvaged blood (7.4%: 2.5 mL + 0.2 mL and 18.5%: 2.2 mL + 0.5 mL). MEASUREMENTS AND MAIN RESULTS: Thromboelastometry was performed for the preoperative blood sample, and postoperative blood samples mixed with different amount of the salvaged blood. Preoperative FIBTEM-MCF significantly decreased after cardiac surgery (16.5 [95% confidence interval (15.4-17.6)] mm to 9.5 [8.4-10.6] mm, p < 0.0001). In vitro 7.4% and 18.5% salvaged blood addition dose-dependently reduced FIBTEM-MCF (9.1 [95% confidence interval (8.0-10.1)] mm, 7.9 [6.8-9.0] mm, respectively, p < 0.0001). Preoperative FIBTEM-MCF and changes of FIBTEM-MCF during cardiac surgery were independent risk factors for development of the FIBTEM-MCF 8 mm or less after in vitro salvaged blood addition. Furthermore, residual heparin within salvaged blood was indicated by significant increase of intrinsic assay-clotting time/ heparin assay-clotting time after 18.5% in vitro salvaged blood addition (p < 0.0001). CONCLUSIONS: Salvaged blood transfusion of more than 18.5% whole blood volume may impair coagulation function particularly in patients with lower FIBTEM-MCF before and after cardiac surgery.

Enhanced interleukin-8 production in mononuclear cells in severe pediatric obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is a risk factor for cardiovascular disease, metabolic disorders, and cognitive dysfunction. Current thinking links chronic intermittent hypoxia (CIH) with oxidative stress and systemic inflammation. However, the sequence of events leading to the morbidities associated with OSA is poorly understood in children. Monocytes are known to be altered by chronic hypoxia. Thus in this prospective study, we investigated inflammatory cytokine profiles from cultures of peripheral blood mononuclear cells (PBMC) obtained from children with severe OSA and sleep-related CIH. METHODS: Ten children with OSA (cases) and 5 age-matched children without OSA (controls) were recruited for study. Samples of plasma and PBMC were obtained before and after adenotonsillectomy. The levels of the inflammatory cytokines, interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-12p70, and tumor necrosis factor-α (TNFα), were measured in both plasma and ex vivo culture supernatants of PBMC incubated with lipopolysaccharide (LPS) using the cytometric bead assay. RESULTS: Upon activation of PBMC by LPS, the levels of IL-8 in the culture supernatants from cases were threefold higher than in controls. The levels of the other cytokines including IL-1ß, IL-6, and TNFα, in culture supernatant of PBMC from cases showed no difference from controls; nor were there significant differences in plasma cytokine levels. CONCLUSION: We speculate that in young children with sleep-related CIH, an enhanced production capacity of IL-8 precedes the development of systemic inflammatory markers. Future work should evaluate IL-8 production capacity as a potential biomarker for OSA severity.

Displacement of the hyoid bone by muscle paralysis and lung volume increase: the effects of obesity and obstructive sleep apnea.

Study Objectives: Animal studies suggest a pivotal role of the hyoid bone in obstructive sleep apnea (OSA). We aimed to explore the role of the hyoid bone in humans by testing the hypotheses that muscle paralysis and lung volume (LV) changes displace the hyoid bone position particularly in people with obesity and/or OSA. Methods: Fifty patients undergoing general anesthesia participated in this study (20 participants with nonobese, non-OSA; 8 people with nonobese OSA; and 22 people with obese OSA). Three lateral neck radiographs to assess the hyoid position (primary variable) and craniofacial structures were taken during wakefulness, complete muscle paralysis under general anesthesia, and LV increase under general anesthesia. LV was increased by negative extrathoracic pressure application and LV changes were measured with a spirometer. Analysis of covariance was used to identify statistical significance. Results: Muscle paralysis under general anesthesia significantly displaced the hyoid bone posteriorly (95% CI: 1.7 to 4.6, 1.5 to 5.2, and 1.1 to 4.0 mm in nonobese non-OSA, nonobese OSA, and obese OSA groups, respectively), and this was more prominent in people with central obesity. LV increase significantly displaced the hyoid bone caudally in all groups (95% CI: 0.2 to 0.7, 0.02 to 0.6, and 0.2 to 0.6 mm/0.1 liter LV increase in nonobese non-OSA, nonobese OSA, and obese OSA groups, respectively). Waist-hip ratio was directly associated with the caudal displacement during LV increase. Conclusions: The hyoid bone plays an important role in the pathophysiology of pharyngeal airway obstruction due to muscle paralysis and LV reduction, particularly in people with obesity. Clinical Trial: UMIN Clinical Trial Registry, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=cR000022635&language=E, UMIN000019578.

Differences of Recovery from Rocuronium-induced Deep Paralysis in Response to Small Doses of Sugammadex between Elderly and Nonelderly Patients.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Complete recovery from rocuronium-induced muscle paralysis with sugammadex is reported to be delayed in elderly patients. The authors tested a hypothesis that recovery from deep neuromuscular block with low-dose sugammadex is slower (primary hypothesis) and incidence of recurarization is higher (secondary hypothesis) in elderly patients than in nonelderly patients. METHODS: In anesthetized elderly (n = 20; 76.9 ± 5.0 yr of age) and nonelderly patients (n = 20; 53.7 ± 12.8 yr of age) under deep paralysis with rocuronium, change of train-of-four ratio per minute (primary outcome variable) was measured with an acceleromyograph neuromuscular monitor during spontaneous recovery from rocuronium-induced muscle paralysis (0.6 mg/kg) and after infusion of low-dose sugammadex (50 µg · kg · min). Recurarization was defined as the negative change of train-of-four ratio. RESULTS: Spontaneous train-of-four ratio recovery rate was significantly slower in the elderly group (median [25th percentile, 75th percentile]: 1.89 [1.22, 2.90] %/min) than in the nonelderly group (3.45 [1.96, 4.25] %/min, P = 0.024). Train-of-four ratio change rate in response to low-dose sugammadex was significantly slower in elderly (0.55 [-0.29, 1.54] %/min) than in the nonelderly group (1.68 [0.73, 3.13] %/min, P = 0.024). Incidence of recurarization was significantly higher in the elderly group than in the nonelderly group (35% vs. 5%, P = 0.044). Multiple linear regression analyses indicate that slower spontaneous train-of-four ratio recovery rate and impaired renal function are two major contributing factors that decrease train-of-four ratio change rate in response to low-dose sugammadex. CONCLUSIONS: Elderly patients are at greater risk for recurarization and residual muscle paralysis when low-dose sugammadex is administered.

Direct activation of GABAA receptors by substances in the organic acid fraction of Japanese sake.

We investigated the effect of substances present in Japanese sake on the response of ionotropic γ-aminobutyric acid (GABA)A receptors expressed in Xenopus oocytes. Sake was fractionated by ion-exchange chromatography. The fraction containing organic acids (OA fraction) showed agonist activities on the GABAA receptor. OA fractions from sake were analyzed by capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). Of the 64 compounds identified, 13 compounds showed GABAA receptor agonist activities. Especially, l-lactic acid showed high agonist activity and its EC50 value was 37µM. Intraperitoneal injections of l-lactic acid, gluconic acid, and pyruvic acid (10, 10, and 5mg/kg BW, respectively), which showed agonistic activity on the GABAA receptor, led to significant anxiolytic effects during an elevated plus-maze test in mice.

Mask Ventilation during Induction of General Anesthesia: Influences of Obstructive Sleep Apnea.

BACKGROUND: Depending on upper airway patency during anesthesia induction, tidal volume achieved by mask ventilation may vary. In 80 adult patients undergoing general anesthesia, the authors tested a hypothesis that tidal volume during mask ventilation is smaller in patients with sleep-disordered breathing priorly defined as apnea hypopnea index greater than 5 per hour. METHODS: One-hand mask ventilation with a constant ventilator setting (pressure-controlled ventilation) was started 20 s after injection of rocuronium and maintained for 1 min during anesthesia induction. Mask ventilation efficiency was assessed by the breath number needed to initially exceed 5 ml/kg ideal body weight of expiratory tidal volume (primary outcome) and tidal volumes (secondary outcomes) during initial 15 breaths (UMIN000012494). RESULTS: Tidal volume progressively increased by more than 70% in 1 min and did not differ between sleep-disordered breathing (n = 42) and non-sleep-disordered breathing (n = 38) patients. In post hoc subgroup analyses, the primary outcome breath number (mean [95% CI], 5.7 [4.1 to 7.3] vs. 1.7 [0.2 to 3.2] breath; P = 0.001) and mean tidal volume (6.5 [4.6 to 8.3] vs. 9.6 [7.7 to 11.4] ml/kg ideal body weight; P = 0.032) were significantly smaller in 20 sleep-disordered breathing patients with higher apnea hypopnea index (median [25th to 75th percentile]: 21.7 [17.6 to 31] per hour) than in 20 non-sleep disordered breathing subjects with lower apnea hypopnea index (1.0 [0.3 to 1.5] per hour). Obesity and occurrence of expiratory flow limitation during one-hand mask ventilation independently explained the reduction of efficiency of mask ventilation, while the use of two hands effectively normalized inefficient mask ventilation during one-hand mask ventilation. CONCLUSIONS: One-hand mask ventilation is difficult in patients with obesity and severe sleep-disordered breathing particularly when expiratory flow limitation occurs during mask ventilation.

Non-response to daclatasvir and asunaprevir therapy in patients co-infected with hepatitis C virus genotypes 1 and 2.

Direct-acting antiviral agents for hepatitis C virus (HCV) have been developed such as combined daclatasvir (DCV) and asunaprevir (ASV) treatment. This typically enables HCV serotype 1 patients to achieve a high sustained virological response rate, but a small number of such patients fail to respond to therapy. We investigated three HCV patients who showed no response to DCV and ASV therapy. Hepatitis C genotyping was undertaken in the three patients using nested polymerase chain reaction and polymerase chain reaction direct sequencing in the core region of the HCV genome. All three patients possessed HCV serotype 1, and no mutations were identified in either the non-structural protein 3 or 5A region. The three patients were shown to be co-infected with HCV genotypes 1 and 2 because genotypes 2a and 2b were also identified. This is the first report into failed response to DCV and ASV therapy in patients co-infected with HCV genotypes 1 and 2.

Adjusting the starting dose of telaprevir according to renal function decreases adverse effects and affects the sustained virological response rate.

BACKGROUND: Telaprevir (TVR) plays a major role in renal damage and anemia associated with TVR/pegylated interferon/ribavirin therapy for chronic hepatitis C. Adjusting the TVR starting dose may reduce these adverse effects. We aimed to determine whether adjusting the starting dose according to renal function reduces TVR-associated renal damage and anemia and affects the sustained virological response (SVR). PATIENTS AND METHODS: Our study included 112 patients infected with hepatitis C genotype 1 treated with pegylated interferon/ribavirin/TVR triple therapy. The TVR starting dose adjusted according to renal function was calculated as TVR/unadjusted estimated glomerular filtration rate (eGFR) ratio=TVR/(eGFR×body surface area/1.73). RESULTS: A TVR/unadjusted eGFR ratio of 32 or greater was a predictor of renal impairment and anemia in multivariate analysis (odds ratio 12.09, P<0.001, and OR 4.14, P<0.001, respectively). Patients with a TVR/unadjusted eGFR ratio of 32 or greater developed significant renal impairment and anemia (P<0.001 and P=0.002, respectively). SVR was significantly reduced in patients with a TVR/unadjusted eGFR ratio less than 23 versus 23 or greater (66.7 and 87.2%, respectively, P=0.045). SVR tended to increase stepwise [<23.0 (66.7%), ≥23 to <32 (84.8%), and ≥32 (89.6%), respectively]. The TVR/unadjusted eGFR ratio was correlated significantly with the serum TVR concentration (r=0.541, P<0.001). CONCLUSION: Adjusting the TVR starting dose according to the TVR/unadjusted eGFR ratio decreased adverse effects and affected the SVR rate. The TVR starting dose should be adjusted by a TVR/unadjusted eGFR ratio of 23 or greater to less than 32 to safely achieve SVR.

Malignant Hyperthermia during Thoracoscopic Pulmorrhaphy in a 70-Year-Old Man.

Malignant hyperthermia (MH) is a rare but potentially fatal complication that may develop under general anesthesia (GA) and is rarely reported in elderly patients. We encountered a case of mild-onset MH in a 70-year-old patient who was receiving an elective thoracoscopic pulmorrhaphy and had a history of several GA procedures. Anesthesia was induced with propofol, fentanyl, and rocuronium and maintained with sevoflurane and remifentanil. His body temperature (BT) was 37.9°C after induction. During the procedure, the end-tidal CO2 (ETCO2) increased steadily to 47-50 mmHg, presumably in response to the single lung ventilation. At the end, BT was 38.1°C and ETCO2 was 47 mmHg under spontaneous breathing. After extubation, the patient wheezed on inspiration and expiration, and his trachea was reintubated. Sixty minutes after surgery, BT increased to 40.5°C and the arterial blood gas analysis showed severe metabolic acidosis. Based on these findings, MH was suspected and a bolus dose of dantrolene was administered. He responded to the dantrolene, and no complications or recurrence of MH was observed postoperatively. In this patient, the initial signs of MH were so subtle that making the diagnosis of MH was difficult. A high degree of suspicion is necessary to prevent a fulminant MH crisis.

Late-evening snack with branched-chain amino acids improves liver function after radiofrequency ablation for hepatocellular carcinoma.

AIM: This prospective study was designed to examine whether consumption of a branched-chain amino acid (BCAA)-enriched nutrient mixture as a late-evening snack (LES) helps maintain and/or improve liver functioning in liver cirrhosis (LC) patients who have undergone radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). METHODS: An equal number (10) of 30 LC patients who had undergone RFA for HCC was randomly assigned to a standard diet group (control) group, a morning BCAA (M-BCAA) administration group, or a LES with BCAA (LES-BCAA) administration group. Liver function testing was performed and Child-Pugh scores (CPS) calculated for each group to assess the improvement at 1, 4 and 12 weeks post-RFA. RESULTS: Compared to the control and M-BCAA groups, the LES-BCAA group experienced a rapid and significant improvement in albumin and total serum bilirubin levels and in CPS that began during the initial post-RFA period. These results indicate that LES with BCAA supplementation significantly improved the CPS of the LES-BCAA group at 4 and 12 weeks post-RFA. Although no patients experienced serious adverse effects, two patients who had been diagnosed with diabetes mellitus before undergoing RFA required blood sugar management to improve glycemic control and one subject withdrew due to supplement-induced vomiting. CONCLUSION: LES with BCAA supplementation significantly and rapidly improves liver functioning and CPS in LC patients who have undergone RFA for HCC. Control of blood sugar levels is necessary when calorie-containing BCAA is administrated to LC patients with impaired glucose tolerance.

Clinical features of Wilson disease: Analysis of 10 cases.

AIM: The diagnosis of Wilson disease is based on the results of several clinical and biochemical tests. This study aimed to clarify the clinical features and spectrum of Wilson disease, including severe Wilson disease. METHODS: Between 1985 and 2009, 10 patients with clinical, biochemical or histological evidence of Wilson disease were either diagnosed or had a previously established diagnosis confirmed at Fukuoka University Hospital. Severe Wilson disease was defined by a serum prothrombin time ratio of more than 1.5 or serum prothrombin activity of less than 50%. The 10 Wilson disease patients were divided into two groups, one containing three non-severe patients and the other containing seven severe patients, and the biochemical features of the patients in these two groups were compared. RESULTS: The mean age at diagnosis was 21.5 ± 11.7 years (range, 7-39). Decreased serum ceruloplasmin, enhanced 24-h urinary copper excretion, presence of Kayser-Fleischer rings and histological signs of chronic liver damage were confirmed in 100%, 100%, 66.7% and 100% of patients, respectively. Severe Wilson disease patients had higher levels of serum ceruloplasmin and serum copper (P < 0.05, P < 0.05, respectively) than non-severe patients. CONCLUSION: In severe Wilson disease patients, the serum ceruloplasmin and serum copper levels were higher than those in non-severe Wilson disease patients.

Reduced expression of low-density lipoprotein receptor in hepatocellular carcinoma with paraneoplastic hypercholesterolemia.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is frequently associated with paraneoplastic hypercholesterolemia. In familial hypercholesterolemia, genetic mutation of the low-density lipoprotein (LDL) receptor gene has been recognized as being a pathogenesis of the disease. We investigate the expression of a LDL receptor protein and gene abnormalities of a LDL receptor in HCC cells in cases with paraneoplastic hypercholesterolemia. METHODS: Eleven patients with HCC associated with paraneoplastic hypercholesterolemia and seven patients with HCC who did not have hypercholesterolemia were studied. Paraffin-embedded tissues were obtained at operative resection, autopsy, or biopsy. Immunohistochemistry was performed using a monoclonal antibody against human LDL receptors. Confocal laser-scanning microscopy was used to observe the FITC-labeled LDL receptor. DNA samples were extracted from paraffin-embedded tissues. Since a LDL receptor gene is located on chromosome 19p13.2, a microsatellite marker, D19S413, was used to analyze the chromosomes. RESULTS: Immunoreactive LDL receptors were observed all over the surface of non-tumorous hepatocytes. However, expression of the LDL receptor was significantly decreased in all HCC cells derived from the 11 patients with hypercholesterolemia. In contrast, the expression was retained in the HCC cells of all patients without hypercholesterolemia. In two patients with hypercholesterolemia, DNA analysis revealed a loss of heterozygosity on chromosome 19p13.2. CONCLUSION: We demonstrated reduced expression of the LDL receptor in HCC cases with paraneoplastic hypercholesterolemia. LDL receptor genes with genomic disorders may cause decreased expression of the LDL receptor protein, leading to feed-back failure of the cholesterol regulation system, as seen in familial hypercholesterolemia. This is the first report considering the mechanism behind the development of paraneoplastic hypercholesterolemia in HCC.