Oncologic emergencies associated with pancreatobiliary cancer

Clinically common oncologic emergencies associated with pancreatobiliary cancer are gastrointestinal bleeding caused by duodenal invasion of pancreatic carcinoma, severe duodenal obstruction due to pancreatic carcinoma, and acute cholangitis accompanied by obstructive jaundice in patients with biliary tract carcinoma. When a patient with gallbladder cancer presents with acute cholecysitis, emergency surgery is sometimes performed on the basis of the latter diagnosis. Emergency procedures can also be required in the perioperative management of pancreatobiliary cancer, for example, in biliary peritonitis caused by detachment of a percutaneous transhepatic biliary drainage (PTBD) tube and in ruptured pseudoaneurysm due to postoperative pancreatic or biliary leakage. Nonsurgical procedures are usually initially selected for oncologic emergencies associated with pancreatobiliary cancer, because patients are likely to develop severe organ dysfunction and it is difficult to access directly and remove the pancreas or biliary tract during emergency surgery. When systemic conditions improve, it is necessary to evaluate the degree of disease progression and systemic conditions, and if feasible, the primary lesion should be surgically resected. When performing emergency cholecystectomy in patients with acute cholecystitis, thorough intraoperative investigation of resected specimens is important, considering the possibility of concomitant gallbladder carcinoma, since thorough examination cannot be performed in such emergency settings. Furthermore, when cholangitis accompanies pancreatobiliary cancer, emergency drainage should be considered as sepsis can develop rapidly.     

Segment-selective absorption of lysozyme in the intestine

Absorption of fluorescein isothiocyanate-labeled lysozyme (FITC-lysozyme) was examined in rat small intestine. Messenger RNA of megalin, an endocytic receptor for lysozyme in the kidney, was expressed in the lower but not in the upper intestine. In in situ closed loop and recirculation methods, absorption of FITC-lysozyme from the upper intestine was much higher than from the lower intestine. The absorption rate of FITC-lysozyme in the upper intestine was significantly higher than FITC-dextran and was inhibited by unlabeled lysozyme in a concentration-dependent manner. The absorption of FITC-lysozyme was also inhibited by spermine and phenylarsine oxide. These results indicate that the intestinal absorption of lysozyme is segment-selective and occurs preferentially from the upper intestine. Megalin expressed in the lower intestine appears not to have a significant role in the absorption of lysozyme. In the upper intestine, lysozyme appears to be absorbed by an endocytic pathway, and cationic charge may be important for lysozyme absorption.     

Synthesis, in vitro pharmacology, structure-activity relationships, and pharmacokinetics of 3-alkoxy-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivatives as potent and selective group II metabotropic glutamate receptor antagonists

Novel group II metabotropic glutamate receptor (mGluR) antagonists, 3-alkoxy-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivatives 11 and 12, were discovered by the incorporation of a hydroxy or alkoxyl group onto the C-3 portion of selective and potent group II mGluR agonist 5, (1R,2S,5R,6R)-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid. Among these compounds, (1R,2R,3R,5R,6R)-2-amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (-)-11be (MGS0039) was a highly selective and potent group II mGluR antagonist with the best pharmacokinetic profile. Compound (-)-11be exhibited high affinities for mGlu 2 (Ki = 2.38 +/- 0.40 nM) and mGlu 3 (4.46 +/- 0.31 nM) but low affinity for mGluR 7 (Ki = 664 +/- 106 nM), and potent antagonist activities for mGlu 2 (IC50 = 20.0 +/- 3.67 nM) and mGluR 3 (IC50 = 24.0 +/- 3.54 nM) but much less potent antagonist activities for mGlu 4 (IC50 = 1740 +/- 1080 nM), mGlu 6 (IC50 = 2060 +/- 1270 nM), mGlu 1 (IC50 = 93300 +/- 14600 nM), and mGluR 5 (IC(50) = 117000 +/- 38600 nM). No significant agonist activities of (-)-11be were found for mGluRs 2, 3, 4, 6, 1, and 5 (EC50 > 100,000 nM). Furthermore, (-)-11be exhibited dose-dependent oral absorption (plasma C(max): 214 +/- 56.7, 932 +/- 235, and 2960 +/- 1150 ng/mL for 3 mg/kg, 10 mg/kg, and 30 mg/kg, po, respectively) and acceptable blood-brain barrier penetration (brain C(max): 13.2 ng/mL for 10 mg/kg, p.o. 6 h). In this paper, we report the synthesis, in vitro pharmacological profile, and structure-activity relationships (SARs) of 3-alkoxy-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivatives 11 and 12, and pharmacokinetic profiles of several typical compounds.     

Giant suspensory lipoma with calcification

A seventy-four-year-old woman presented with a giant lipoma suspended from her left upper arm. The surgically removed tumor weighed 2,600 g and included calcified areas in its periphery. Our histologic observations suggested that the calcification was generated in association with degenerated fat.     

Duration of untreated psychosis and pathways to psychiatric services in first-episode schizophrenia

The aim of the present study was to examine the duration of untreated psychosis (DUP) in first-episode schizophrenia patients in Japan and to investigate the available pathways to psychiatric services. Eighty-three patients who visited Keio University Hospital (n = 54) or Oizumi Mental Hospital (n = 29) were evaluated retrospectively with regard to their DUP, living situation, social participation level, referral pathway, reason for seeking treatment, and their global assessment of functioning (GAF) score. The mean DUP was 13.7 months (median, 5.0 months) overall. No significant difference in DUP was found between subjects living alone and those living with others; however, employed patients had a significantly shorter DUP (8.1 months) than unemployed patients (18.7 months). Pathways to psychiatric services were totally different between the two institutions. Fifty-two subjects (62.7%) came to the services directly: 40 patients (74.1%) came to the university hospital and 12 patients (41.4%) came to the mental hospital. At the mental hospital, nine patients (31.0%) had been admitted because of a legal obligation, and six (20.7%) had been referred through public health centers. None of the patients had been referred to either of the services by general practitioners. The main reason for seeking treatment was psychiatric symptom aggravation (59.3%) at the university hospital and acting out (64.3%) at the mental hospital. Some universal psychosocial factors appear to influence the DUP but the characteristics of specific psychiatric services may also affect treatment delays.     

Airway management during the laryngoscopic surgery for the benign laryngeal obstructive disease

The airway management and anesthesia maintenance during the laryngoscopic surgery is essential for a safe operation. For the benign laryngeal obstructive disease such as a large mass or a foreign body of the upper airway, it is difficult to secure the airway. Sometimes they might be hazardous and potentially lethal. We present two cases of a large laryngeal polyp and a laryngeal foreign body of pressthrough-package (PTP). They were successfully operated on with laryngomicrosurgery under neuroleptanalgesia (NLA) without intubation. The choice of the operation and airway management were discussed.     

Rapid and sensitive diagnosis of adenoviral keratoconjunctivitis by loop-mediated isothermal amplification (LAMP) method

PURPOSE: To develop a new method to detect and type adenoviruses directly from conjunctival scrapings using loop-mediated isothermal amplification (LAMP) with adenovirus (ad) type specific primer. METHODS: Using primers specific for the gene of ad1, ad3, ad4, ad8, ad19 and ad37, heat denatured adenovirus DNA was amplified by the LAMP and polymerase chain reaction (PCR). Alkaline lysed adenovirus prototype and conjunctival scrapings were also used directly as templates. RESULTS: Type specific primers amplified ad genes of the corresponding ad prototype specifically. The specific amplification was observed in both heat denatured and alkaline lysed samples. The amplified product was first detected within 45 min. Ad genotypes of clinical samples determined by the LAMP method were almost identical to those determined using the PCR-sequencing method. CONCLUSIONS: LAMP based isothermal amplification of adenovirus genome for detection and typing of adenoviruses is faster than PCR based methods. This new method will be useful for rapid diagnosis and typing of adenoviral conjunctivitis.