Masaki Fujioka

Characterization of the isoenzymes of cyclic nucleotide phosphodiesterase in human platelets and the effects of E4021.

In extracts of human platelets, three isoenzymes of cyclic nucleotide phosphodiesterase (PDE), namely, PDE2, PDE3, and PDE5, were identified; activities of PDE1 and PDE4 were not detected. In human platelets, the cGMP-hydrolytic activity was about six times higher than the cAMP-hydrolytic activity, and PDE5 and PDE3 are the major phosphodiesterase isoenzymes that hydrolyze cGMP and cAMP, respectively. PDE5 exhibited organ-specific expression in humans, and platelets were among the tissues richest in PDE5. A novel inhibitor of PDE5, sodium 1-[6-chloro-4-(3,4-methylenedioxybenzyl)aminoquinazolin-2-yl ] piperidine-4-carboxylate sesquihydrate (E4021), was a potent and highly selective inhibitor of human platelet PDE5. However, E4021 (up to 10 microM) did not inhibit 9,11-epithio-11,12-methano-thromboxane A2-induced platelet aggregation, in vitro. E4021 plus SIN-1 (3-morpholino-sydnonimine), at concentrations that had little effect individually, inhibited aggregation. These results suggest the unique distribution of phosphodiesterase isoenzymes in human platelets and the PDE5 inhibitors might be useful as a new class of antiplatelet drugs.

Rectal pressure and rectal compliance in ulcerative colitis

Anorectal manometry, coupled with measurement of rectal compliance, was carried out on 11 healthy subjects and 9 patients with ulcerative colitis. Resting pressure profile of the anorectum but basal rhythmic contraction of the anal canal was normal in most of the patients and rectoanal reflex was positive in all. Rectal compliance was, however, significantly decreased in 7 of 9 patients. These results suggest that distensibility of the rectum may be decreased in cases of ulcerative colitis and that measurements of resting pressure profile, rectoanal reflex, and rectal compliance may be helpful in selecting patients suitable for elective surgery to preserve sphincter function.

Food poisoning associated with Kudoa septempunctata.

BACKGROUND Kudoa septempunctata is a recently identified cause of food poisoning. We report three cases of food poisoning due to ingestion of this parasite. CASE REPORTS Among the 358 people exposed during the same catered meal, 94 (including our 3 patients) developed vomiting and diarrhea within 1-9 h after ingestion of raw muscle from contaminated aquacultured olive flounders (Paralichthys olivaceus). These symptoms occurred frequently but were temporary; only 1 patient was hospitalized for dehydration and was discharged 2 days later. CONCLUSION In Japan, cases of food poisoning due to eating olive flounder have increased during recent years. This increase should prompt heightened awareness among clinicians diagnosing food poisoning.

A case of Strongyloides hyperinfection associated with tuberculosis.

Strongyloidiasis is a parasitic infection that occurs in tropical regions. Hyperinfection, which is an accelerated autoinfection, is often associated with an immunosuppressive state, such as HTLV-1 infection or steroid use. Immunosuppression can also lead to reactivation of tuberculosis infection. These infections may have interacted as a result of impaired cellular immunity. A 28-year-old Nepali male was referred to our hospital for slight abdominal pain and high fever. An abdominal CT scan showed ascites and intestinal swelling. He was admitted with suspected gastroenteritis. Results of stool microscopy on the third day of hospitalization revealed abundant strongylid larvae. We diagnosed a Strongyloides hyperinfection and prescribed ivermectin. Although the numbers of strongylid organisms in the patient’s stool soon diminished, his temperature remained high. After receiving a second dose of ivermectin on day 17, he was transferred to a nearby hospital for observation, where he was noted to have massive pleural effusion. He returned to our hospital where his pleural effusion was found to be positive for adenosine deaminase (ADA), and he was diagnosed with a tuberculosis infection. Strongyloides hyperinfection can occur in a non-endemic region. It can be associated with tuberculosis infection possibly due to impaired cellular immunity. It is important to consider other possible infections when treating a patient with an infection associated with impaired cellular immunity.

Characterization of Major Phosphoproteins in the cGMP-Mediated Protein Phosphorylation System of Vascular Smooth Muscle Membranes

G₀ (215–250 kD) and G₁ (120–140 kD), the unidentified major phosphoproteins in the cGMP-mediated protein phosphorylation system of vascular smooth muscle membranes, were compared for biochemical and immunological properties with the type 1 inositol 1,4,5-trisphosphate receptor (InsP₃R, 240 kD) and the myosin-binding subunit (MBS, 138 kD) of myosin phosphatase, both of them substrates for cGMP-dependent protein kinase. Two microsomal proteins that were immunoreactive with antibodies to InsP₃R and MBS were detected, and comigrated with G₀ and G₁, respectively, on SDS-PAGE. When thiophosphorylated G₀ and G₁ were subjected to immunoprecipitation, MBS antibody induced the precipitation of a 138-kD phosphoprotein, but did not significantly affect the amount of G₁ remaining in the supernatant, while InsP₃R antibody precipitated G₀ almost completely. Unexpectedly, InsP₃R antibody coprecipitated a large portion of G₁, which did not cross-react with either antibody to MBS or InsP₃R. Just like InsP₃R, G₀ bound to the calmodulin column in a Ca²⁺-dependent manner, and, again, a large portion of G₁ was copurified with G₀. These results suggest that G₀ is identical to InsP₃R, while G₁ consists of several phosphoproteins, including the 138-kD protein associated with InsP₃R as a major component. MBS is not G₁ or may represent only a minor component of it.

Use and effectiveness of prothrombin complex concentrate in an emergency department: a review of 15 cases

Hemostatic management of patients on oral anticoagulant therapy with critical bleeding continues to be a major challenge. The present study aimed to validate the efficacy, safety, and optimal dosage of prothrombin complex concentrate for rapidly normalizing elevated international normalized ratio (INR) values and achieving control of hemorrhage at an emergency department in Japan.

Case Series of Iliopsoas Abscesses Treated at a University Hospital in Japan: Epidemiology, Clinical Manifestations, Diagnosis and Treatment

OBJECTIVE The incidence of iliopsoas abscesses has been increasing due to advances in diagnostic imaging techniques and the increased number of elderly individuals and immunodeficient patients with co-morbidities. Our aim was to investigate the management and treatment of iliopsoas abscesses, particularly the effectiveness of computed tomography (CT)-guided drainage in the era of interventional radiology. METHODS A retrospective analysis was performed at a university hospital between January 2009 and March 2014. Patients There were 15 patients (eight men, seven women) 50-85 years of age (average: 70 years) diagnosed with an iliopsoas abscess. RESULTS The etiology of the disease was investigated in 14 of the 15 patients, each of whom had a secondary iliopsoas abscess. The primary condition in nine of these patients (64.3%) was an orthopedic infection (spondylodiscitis); the most common symptom was fever (12 patients, 80%). Altogether, 10 patients (66.7%) had a multilocular abscess and five (33.3%) had bilateral abscesses. The most common pathogen was Staphylococcus aureus (seven patients, 50%). All 14 patients underwent drainage: 11 received CT-guided drainage, two underwent postdrainage surgery and one received ultrasonography-guided drainage. Poor drainage was overcome by inserting multiple drainage tubes (six patients) or performing transmembrane drainage with a guidewire. All but one patient survived. CONCLUSION Based on the high success rate of CT-guided drainage in this study, this technique is expected to continue to play a major role in cases requiring drainage, even in patients with bilateral or multilocular abscesses. However, this modality cannot be used in cases of gastrointestinal perforation.

Respiratory failure with hydrothorax due to acute onset pleuroperitoneal communication after upper endoscopy

Dear Editor, Pleural effusion that results from pleuroperitoneal communication occurs in 1.6–10% of patients on continuous ambulatory peritoneal dialysis, but is also infrequently observed in relation to liver cirrhosis. We report an educational case of respiratory distress with hydrothorax due to acute onset of pleuroperitoneal communication after upper endoscopy. A 67-year-old man with end-stage renal disease (on hemodialysis three times a week for over 7 years), hypertension, and liver cirrhosis (Child–Pugh B), was transferred to our hospital due to respiratory distress. He was in his usual state of health until 1 day prior to admission for routine upper endoscopic examination, which revealed no major disease and was completed without any acute complication. On admission, his vital signs were stable except for slight tachypnea (respiratory rate 24 breaths/min) with desaturation (oxygen saturation 95% on 2 L/min oxygen administered by nasal cannula). Breath sounds had disappeared on the right side, but he was not edematous. Laboratory examination revealed significant changes reflecting underlying disease: platelet count, 6.8 9 10/lL; albumin, 2.3 mg/dL; and creatinine, 5.49 mg/dL. Chest radiographs showed a large right unilateral pleural effusion, which had changed drastically compared with 1 week prior (Fig. 1A,B). Computed tomography scan showed previously known mild ascites (Fig. 1C). Transthoracic echocardiogram showed normal cardiac function. The patient’s history was indicative of iatrogenic esophageal perforation, however, this was

Usefulness of prothrombin complex concentrate for cardiac injury in patients receiving oral anticoagulant therapy

Dear Editor, Intravascular procedures such as radiofrequency catheter ablation and pacemaker implantation for patients with atrial fibrillation (AF) receiving oral anticoagulant therapy (OAT), warfarin, and novel anticoagulation therapy (NOAC) are now widely employed. Recently, these procedures are increasingly performed without OAT discontinuation and, although such procedures are generally considered safe, devastating bleeding complication may occur. Rapid reversal of OAT is crucial in such cases, however, no consensus has yet been established for optimal management. Here we report three experiences of cardiac injury treated with prothrombin complex concentrate (PCC) (PPSB-HT Nichiyaku; Nihon Pharmaceutical, Tokyo, Japan) (Table 1). The administration of PCC as an off-label agent was approved by the ethics committees of our hospital. Case 1 (77-year-old woman) and case 2 (70-year-old man) with paroxysmal AF, both receiving OAT (warfarin in case 1 and apixaban in case 2), developed shock during their catheter ablation. Because ultrasonography showed pericardial effusion, and percutaneous cardiocentesis was performed with the diagnosis of cardiac tamponade, these patients received 500 IU PCC immediately concomitant with protamine for reversal of heparin. Fresh frozen plasma was then given in case 1. Both patients achieved satisfactory hemostasis without surgical repair. Case 3 (70-year-old woman), having chronic AF with bradycardia receiving warfarin, developed dyspnea. She had undergone pacemaker implantation 3 days prior to the onset of symptoms. The chest X-ray showed hemopneumothorax of the left side, and the chest computed tomography scan suggested that a pacemaker lead had staved in her right ventricle. The diagnosis of delayed onset cardiac injury accompanying hemopneumothorax was made. She immediately received i.v. vitamin K; however, optimization of international prothrombin ratio (PT-INR) was not achieved in the next 2 h. After the additional administration of 500 IU PCC, her PT-INR level was optimized within 40 min. She received emergency thoracotomy and patch repair safely. Currently, the evidence to support the use of PCC in the management of cardiac injury is limited; however, our experiences showed that PCC administration for acute reversal of OAT, including NOAC, yielded a satisfactory level of efficacy. However, the most effective dosing regimen for PCC in cardiac injury is still uncertain. According to our recent report, PCC provide rapid (within 30 min) reversal of warfarin-related coagulopathy, but fixed dose of 500 IU may be insufficient for normalization of prolonged INR value. Moreover, the effectiveness of PCC for NOAC has not been confirmed. Although it may be an overtreatment, in the view of potentially fatal complications and the difficulty in predicting the amount of bleeding, we believe that it is acceptable to administer PCC as soon as cardiac injury is diagnosed. Based on these experiences, we believe following a strategy of: (i) early administration of PCC for acute reversal of OAT in patients with cardiac injury, (ii) determination of the dose of PCC by INR values in patients receiving warfarin (e.g., 500 IU for INR value below <2.5 and 1,000 IU for those >2.5) will be promising. However, the possibility of thromboembolic complications after PCC administration should always be considered.

Postmortem diagnosis of massive gastrointestinal bleeding in a patient with aberrant right subclavian artery–esophageal fistula

Aberrant right subclavian artery–esophageal fistula is a rare, but fatal, complication. A 55‐year‐old febrile man with a nasogastric feeding tube developed sudden massive hematemesis and shock.