Association of the time to first epinephrine administration and outcomes in out-of-hospital cardiac arrest: SOS-KANTO 2012 study

Objective

This study assessed the association between the timing of first epinephrine administration (EA) and the neurological outcomes following out-of-hospital cardiac arrests (OHCAs) with both initial shockable and non-shockable rhythms.

Quality of life after single-incision laparoscopic cholecystectomy: A randomized,clinical trial

Background

Controversy continues as to whether single-incision laparoscopic cholecystectomy, with the somewhat larger incision at the umbilicus, may lead to a worse postoperative quality of life and more pain compared with the more classic 4-port laparoscopic cholecystectomy. The aim of this study was to compare single-incision and 4-port laparoscopic cholecystectomy from the perspective of quality of life.

Cibenzoline-induced respiratory muscular paralysis in a hemodialysis patient

A 69-year-old man was admitted to our kidney center with endstage renal failure. We started intermittent peritoneal dialysis immediately because of severe azotemia, hyperkalemia, and metabolic acidosis. Two weeks after admission, he developed uremic pericarditis with frequent ventricular premature contractions and supraventricular premature contractions. The intermittent peritoneal dialysis was then replaced by intensive hemodialysis, and oral administration of 300 mg/d of cibenzoline was started. Four days later, he developed thirst, weakness, and dyspnea due to respiratory muscular paralysis. We initiated respiratory support with a respirator because analysis of his blood gases revealed marked hypercapnia and hypoxia. He also developed hypoglycemia and prolonged PQ and QRS intervals on the electrocardiogram, which we believed were due to cibenzoline intoxication; we discontinued the cibenzoline immediately. All symptoms improved, and he was extubated 5 days later. After 2 months, his pericardial effusion disappeared. He now continues maintenance hemodialysis as an outpatient. We suspect that the cibenzoline induced the respiratory muscular paralysis for 2 reasons: 1) the patient experienced the respiratory muscular paralysis, at the same time he also experienced thirst, weakness, hypoglycemia, and prolonged PQ and QRS intervals on electrocardiogram, and all of these symptoms improved after the discontinuation of cibenzoline, and 2) his plasma concentration of cibenzoline became remarkably elevated, to 20 times above the standard therapeutic level. This patient's clinical course indicates that hemodialysis might be superior to intermittent peritoneal dialysis for treatment of cibenzoline intoxication.     

Characterization of peptide components in the venom of the scorpion Liocheles australasiae (Hemiscorpiidae).

Scorpion venoms are composed of a number of neurotoxic peptides. A variety of toxins have been isolated from the venoms of scorpions of the family Buthidae, however, little interest has been paid to non-Buthidae scorpions. In this study, we examined the toxicity of the venom of Liocheles australasiae (Hemiscorpiidae) to mice and crickets, and characterized the peptide components by HPLC and mass spectrometry. Over 200 components were detected in the L. australasiae venom by LC/MS analysis, with components of molecular masses ranging from 500 to 5000 Da being particularly abundant. A number of peptides contained two to four disulfide bridges, which was estimated based on the mass difference after derivatization of Cys residues. A peptide having a monoisotopic molecular mass of 7781.6 Da and four disulfide bridges was isolated from the venom. The peptide has a primary structure similar in terms of the position of eight Cys residues to those observed in several peptides found from scorpions, ticks and insects, although biological roles of these peptides are unknown.     

The study of the autopsies of six patients with progressive esophageal cancer to investigate complications caused by esophageal stents]

Endoscopic placement of metal stents are used widely for patients with esophageal obstruction and fistula due to progressive esophageal cancer, but cause high rate of severe complications associated with the immediate causes of death. To determine severe complications caused by stents, we studied clinical data and autopsy of six patients who had been treated with stents for inoperable progressive esophageal cancer. Occording to the clinical records only two patients had severe complications due to stents. But at autopsy, three patients had massive hemorrhage in the stent placement, one patient had mediastinitis, and one patient were in imminent danger of perforation whose stent had been incorporated into the adventitia of the wall. More severe complications were revealed than those expected clinically. Endoscopic placement of metal stents have a great deal for the improvement of quality of life. But we should carefully decide the indication because endoscopic placement of metal stents could cause severe complications associated with the immediate causes of death.     

β2-glycoprotein I, anti-β2-glycoprotein I, and fibrinolysis

β₂-glycoprotein-I (β₂GPI) is a phospholipid-binding plasma protein that consists of five homologous domains. Domain V is distinguished from others by bearing a positively charged lysine cluster and hydrophobic extra C-terminal loop. β₂GPI has been known as a natural anticoagulant regulator. β₂GPI exerts anticoagulant activity by inhibition of phospholipid-dependent coagulation reactions such as prothrombinase, tenase, and factor XII activation. It also binds factor XI and inhibits its activation. On the other hand, β₂GPI inhibits anticoagulant activity of activated protein C. According to the data from knockout mice, β₂GPI may contribute to thrombin generation in vivo. Phospholipid-bound β₂GPI is one of the major target antigens for antiphospholipid antibodies present in patients with antiphospholipid syndrome (APS). Binding of pathogenic anti-β₂GPI antibodies increases the affinity of β₂GPI to the cell surface and disrupts the coagulation/fibrinolysis balance on the cell surface. These pathogenic antibodies activate endothelial cells via signal transduction events in the presence of β₂GPI. Impaired fibrinolysis has been reported in patients with APS. Using a newly developed chromogenic assay, we demonstrated lower activity of intrinsic fibrinolysis in euglobulin fractions from APS patients. Addition of monoclonal anti-β₂GPI antibodies with β₂GPI also decreased fibrinolytic activity in this assay system. β₂GPI is proteolytically cleaved by plasmin in domain V (nicked β₂GPI) and becomes unable to bind to phospholipids, reducing antigenicity against antiphospholipid antibodies. This cleavage occurs in patients with increased fibrinolysis turnover. Nicked β₂GPI binds to plasminogen and suppresses plasmin generation in the presence of fibrin, plasminogen, and tissue plasminogen activator (tPA). Thus, nicked β₂GPI plays a role in the extrinsic fibrinolysis via a negative feedback pathway loop.     

Identification of the metabolites of irinotecan, a new derivative of camptothecin, in rat bile and its biliary excretion.

1. To investigate the metabolites and biliary excretion of new camptothecin analogue, irinotecan, the drug was administered i.v. to rats (10 mg/kg) and bile, urine and faeces were collected. 2. In rat bile, unchanged irinotecan, the metabolite 7-ethyl-10-hydroxycamptothecin (EHCPT) and unknown metabolite M-1 were found by t.l.c. and h.p.l.c. From beta-glucuronidase hydrolysis, n.m.r. spectrometry and mass spectrometry, M-1 was identified as EHCPT-glucuronide (EHCPT Glu). Other metabolites in the bile were negligible. 3. The cumulative biliary and urinary excretion of radioactivity after dosage of rats with irinotecan were 62.2% and 33.3% dose, respectively, and 9.0% of the radioactivity was excreted in the faeces. 4. Approx. 55% of the biliary radioactivity excreted in 24 h was unchanged irinotecan, 22% was EHCPT Glu, and 9% was EHCPT. 5. Approx. 18% of the biliary radioactivity was reabsorbed from the intestine.     

A 62-year-old woman with early-onset Parkinson's disease associated with the PINKi gene deletion]

We report the first case of early-onset Parkinson's disease (EOP) with the PTEN-induced kinase 1 (PINK1) gene deletion in 62 years old Japanese female. The symptoms were started with unstable gait at the age 38. Parkinsonian symptoms became apparent in 45 years old. L-Dopa was markedly effective on her parkinsonian symptoms. However, equinovarus foot induced by L-Dopa intake appeared three months prior to the admission. On admission, she presented with mild cognitive impairment, severe depression, marked retropulsion, resting tremor in the left upper limb and mild hyperreflexia in the four limbs. Rigidity was not present. Mutational analysis revealed homozygous deletion from exon 6 to 8 in the PINK1 gene. An ethnic diversity in PINK1 mutation is suggested.