Persistent Na+ influx drives L-type channel resting Ca2+ entry in rat melanotrophs.

Rat melanotrophs express several types of voltage-gated and ligand-gated calcium channels, although mechanisms involved in the maintenance of the resting intracellular Ca2+ concentration ([Ca2+]i) remain unknown. We analyzed mechanisms regulating resting [Ca2+]i in dissociated rat melanotrophs by Ca2+-imaging and patch-clamp techniques. Treatment with antagonists of L-type, but not N- or P/Q-type voltage-gated Ca2+ channels (VGCCs) as well as removal of extracellular Ca2+ resulted in a rapid and reversible decrease in [Ca2+]i, indicating constitutive Ca2+ influx through L-type VGCCs. Reduction of extracellular Na+ concentration (replacement with NMDG+) similarly decreased resting [Ca2+]i. When cells were champed at -80 mV, decrease in the extracellular Na+ resulted in a positive shift of the holding current. In cell-attached voltage-clamp and whole-cell current-clamp configurations, the reduction of extracellular Na+ caused hyperpolarisation. The holding current shifted in negative direction when extracellular K+ concentration was increased from 5 mM to 50 mM in the presence of K+ channel blockers, Ba2+ and TEA, indicating cation nature of persistent conductance. RT-PCR analyses of pars intermedia tissues detected mRNAs of TRPV1, TRPV4, TRPC6, and TRPM3-5. The TRPV channel blocker, ruthenium red, shifted the holding current in positive direction, and significantly decreased the resting [Ca2+]i. These results indicate operation of a constitutive cation conductance sensitive to ruthenium red, which regulates resting membrane potential and [Ca2+]i in rat melanotrophs.

Usefulness of Fibrinogen/Fibrin Degradation Products Value in Differential Diagnosis Between Acute Ischemic Stroke and Acute Aortic Dissection.

A post-marketing surveillance study reported fatalities following tissue plasminogen activator administration in acute aortic dissection (AAD) with the symptoms of acute ischemic stroke (AIS) patients. Therefore, it is important to discriminate AAD from AIS. The present study aimed to investigate whether fibrinogen/fibrin degradation products (FDP) value can be useful in differential diagnosis between AAD and AIS. The study group comprised 20 AAD patients (10 men and 10 women; age 63.9 ± 13.6 years) and 159 AIS patients (91 men and 68 women; age 74.2 ± 10.6 years) who were transported to our hospital from 2007 to 2012. The AAD cases were further divided into patent-type AAD and thrombosed-type AAD. FDP values were significantly higher in the AAD group than in the AIS group (18.15 [5.2 - 249.9] µg/ml vs. 2.3 [1.5 - 4.45] µg/ml ; P < 0.001). In AAD groups, FDP values were significantly higher in the patent-type AAD group (n = 9) than in the thrombosed type AAD group (n = 11) (293.2 µg/ml [63.1 - 419.6 µg/ml ] vs. 5.6 µg/ml [3.8 - 7.9 µg/ml ]. FDP values were significantly higher in patients with AAD than in those with AIS, especially those with patent-type AAD compared with AIS patients. High FDP values may be a useful marker for differential diagnosis between patent-type AAD and AIS.

A Case of Infectious Enterocolitis with Hyperammonemia.

Case reports of hyperammonemia due to urease-producing bacteria are found occasionally, but most of them are associated with urinary tract infections. We experienced a case of infectious enterocolitis with hyperammonemia in which the causative bacteria was speculated to be urease-producing bacteria. A Japanese woman in her 70s had been diagnosed with microscopic polyangiitis in a nearby hospital and was transferred to our hospital. Although the microscopic polyangiitis was relatively under control after treatment with steroids and rituximab, frequent diarrhea with hyperammonemia (324 µg/dl) appeared and she became comatose. Her blood ammonia decreased to 47 µg/dl and her consciousness recovered to a normal state after antibiotic treatment for infectious enterocolitis and ammonia detoxification therapy. Liver dysfunction, portosystemic shunt, excessive protein intake and constipation were not observed, and she took no medications that would cause hyperammonemia. Although culture results could not identify urease-producing bacteria, considering the clinical course, acute hyperammonemia was suspected to be due to urease-producing bacteria infection. It is necessary to consider the influence of urease-producing bacteria as a cause of acute hyperammonemia not only in urinary tract infections but also in infective enterocolitis.

The first fatal case of Corynebacterium ulcerans infection in Japan.

Introduction.Corynebacterium ulcerans (C. ulcerans) is a zoonotic pathogen that occasionally causes diphtheria-like symptoms in humans. Cases of C. ulcerans infection have been increasing in recent years, and C. ulcerans has been recognized as an emerging pathogen. Case presentation. Here we report a case of asphyxia death due to pseudomembrane caused by diphtheria toxin (DT)-producing C. ulcerans. This is, to our knowledge, the first fatal case of C. ulcerans infection in Japan. A strain of C. ulcerans was obtained from the patient's pet cat and was confirmed to be identical to the patient's isolate by sequencing of the 16S rRNA gene and the DT gene, by pulsed-field gel electrophoresis (PFGE) and by ribotyping. In the same way, it was revealed that the isolate in this case belonged to the same molecular type as the C. ulcerans 0102 isolated from the first case in Japan in a distant prefecture 15 years earlier, in 2001. Conclusion. DT-producing C. ulcerans can be contracted from a companion animal and causes human death if the appropriate treatment is delayed. The finding indicates that this molecular type of virulent C. ulcerans is currently widespread in Japan.

[Drug Therapy for Shock-Resistant Ventricular Fibrillation: Comparison of Nifekalant and Amiodarone].

Early direct current (DC) shock is the most important therapy for ventricular fibrillation. Following the increased availability of automated external defibrillators (AED), the survival rate of cardiopulmonary arrest patients with ventricular fibrillation has improved. Although patients with shock-resistant ventricular fibrillation require additional antiarrhythmic drug therapy, the optimal protocol has not been established. Nifekalant is a pure potassium channel blocker with a pyrimidinedione structure. Nifekalant was approved in Japan for the treatment of life-threatening ventricular tachyarrhythmias in 1999, and is widely used as a class III antiarrhythmic intravenous drug. Intravenous amiodarone was approved in Japan in 2007, and exhibits various effects on ion channels, receptors, sympathetic activity, and thyroid function. Nifekalant and amiodarone also exhibit many pharmacological and pharmacodynamic differences. As nifekalant has no negative inotropic effect and a rapid action and clearance with a short half-life, it has some advantages over amiodarone for use in cardiopulmonary resuscitation. Indeed, data from clinical and animal studies suggest that nifekalant is superior to amiodarone for resuscitation of cardiopulmonary arrest resulting from shock-resistant ventricular fibrillation. A 300-mg bolus intravenous injection of amiodarone is considered an overdose for resuscitation of shock-resistant ventricular fibrillation. Further clinical studies are required to evaluate the effects of nifekalant compared with amiodarone, and to determine the optimal dose of amiodaone, for resuscitation of shock-resistant ventricular fibrillation.

[A Case of Life-Threatening Angioedema Occurred During Prolonged Angiotensin-Converting Enzyme Inhibitor Treatment].

Although angiotensin-converting enzyme (ACE) inhibitors are widely used as the first choice drug for treating hypertension, we have only a superficial understanding of their relationship to angioedema. We report a case of life-threatening angioedema. The case was a 60-year-old man who had been taking an ACE inhibitor for hypertension for 11 years. He visited his home doctor for dyspnea, and tongue and neck swelling. He was transported to our hospital because of the possibility of airway obstruction. On admission, his tongue and neck swelling became more severe. We performed an intubation using an endoscope and started airway management. We also stopped his ACE inhibitor. The severe tongue and neck swelling improved gradually and he was extubated on day 3. On the fifth day he was discharged. We diagnosed angioedema caused by an ACE inhibitor. Although the risk of airway obstruction with ACE inhibitors is acknowledged, we have only a superficial understanding of how prolonged ACE inhibitor treatment induces angioedema. So we should consider angioedema in cases of taking ACE inhibitors, especially in cases of prolonged treatment.

Analysis of G-protein-activated inward rectifying K(+) (GIRK) channel currents upon GABAB receptor activation in rat supraoptic neurons.

While magnocellular neurons in the supraoptic nucleus (SON) possess rich Gi/o-mediated mechanisms, molecular and cellular properties of G-protein-activated inwardly rectifying K(+) (GIRK) channels have been controversial. Here, properties of GIRK channels are examined by RT-PCR and whole-cell patch-clamp techniques in rat SON neurons. Patch clamp experiments showed that the selective GABAB agonist, baclofen, enhanced currents in a high K(+) condition. The baclofen-enhanced currents exhibited evident inward rectification and were blocked by the selective GABAB antagonist, CGP55845A, the IRK channel blocker, Ba(2+), and the selective GIRK channel blocker, tertiapin, indicating that baclofen activates GIRK channels via GABAB receptors. The GIRK currents were abolished by N-ethylmaleimide pretreatment, and prolonged by GTPγS inclusion in the patch pipette, suggesting that Gi/o proteins are involved. RT-PCR analysis revealed mRNAs for all four GIRK 1-4 channels and for both GABABR1 and GABABR2 receptors in rat SON. However, the concentration-dependency of the baclofen-induced activation of GIRK currents had an EC50 of 110 µM, which is about 100 times higher than that of baclofen-induced inhibition of voltage-dependent Ca(2+) channels. Moreover, baclofen caused no significant changes in the membrane potential and the firing rate. These results suggest that although GIRK channels can be activated by GABAB receptors via the Gi/o pathway, this occurs at high agonist concentrations, and thus may not be a physiological mechanism regulating the function of SON neurons. This property that the membrane potential receives little influence from GIRK currents seems to be uncommon for CNS neurons possessing rich Gi/o-coupled receptors, and could be a special feature of rat SON neurons.

A rare case of acquired methemoglobinemia associated with alkaptonuria.

We herein present a rare case of acquired methemoglobinemia associated with alkaptonuria. Alkaptonuria is a congenital error of metabolism caused by the deficiency of homogentisic acid oxidase, which subsequently results in the accumulation of homogentisic acid (HGA) in body tissues. As renal dysfunction progresses, the level of HGA excretion in the urine decreases and the blood concentration of HGA increases. HGA oxidizes oxyhemoglobin to methemoglobin, which can induce multiple organ failure accompanied by tissue hypoxia, intravascular hemolysis and metabolic acidosis. The mortality of this disease is high when alkaptonuria is associated with the presence of methemoglobinemia; therefore, treatment should be carefully planned in such cases.

[Examination of relationship between lactate clearance and neurologic outcome in cardiac arrest induced by ventricular fibrillation].

A significant relationship between lactate clearance and mortality rates in cardiac arrest cases has been reported. However, the relationship between lactate clearance and neurologic outcomes in cardiac arrest cases is not clear. We examined lactate clearance in cardiac arrest cases induced by ventricular fibrillation. We investigated 13 patients with cardiac arrest induced by ventricular fibrillation from April, 2006 to March, 2012 in which therapeutic hypothermia was performed. Patients were classified into two groups: those with a favorable neurologic outcome (n=7) and those with a poor outcome (n=6). We compared lactate clearance levels between the two groups. There was no significant difference in lactate concentrations at admission and 8 or 24 hours lactate clearance between the two groups 8 or 24 hours after admission. This result suggests we may not predict the neurologic outcome of cardiac arrest cases induced by ventricular fibrillation using lactate clearance.

Comparison of nifekalant and amiodarone for resuscitation of out-of-hospital cardiopulmonary arrest resulting from shock-resistant ventricular fibrillation.

PURPOSE: Nifekalant is a pure potassium channel blocker that has been used to treat ventricular tachyarrhythmias since 1999 in Japan. Intravenous amiodarone was approved later than nifekalant in Japan, and it is still unclear which of the two agents is superior. The aim of this study was to compare the efficacy of nifekalant and amiodarone for resuscitation of out-of-hospital cardiopulmonary arrest caused by shock-resistant ventricular fibrillation. METHODS: From December 2005 to January 2011, ambulance services transported 283 out-of-hospital cardiopulmonary arrest patients to our hospital. Of these, 25 patients were treated with nifekalant or amiodarone in response to ventricular fibrillation that was resistant to two or more shocks. We undertook a retrospective analysis of these 25 patients. RESULTS: We enrolled 20 men and 5 women with a mean age (± standard deviation) of 61.1 ± 16.4 years. All 25 patients were treated with tracheal intubation and intravenous epinephrine. Fourteen patients received nifekalant and 11 patients received amiodarone. The rates of return of spontaneous circulation (ROSC) (nifekalant, 5/14, versus amiodarone, 4/11; P = 0.97) and survival to discharge (nifekalant, 4/14, versus amiodarone, 2/11; P = 0.89) were not significantly different between the two groups. The time from nifekalant or amiodarone administration to ROSC was 6.0 ± 6.6 and 20.3 ± 10.0 min, respectively, which was significantly different (P < 0.05). CONCLUSION: In this small sample size study, nifekalant, compared with amiodarone, is equally effective for ROSC and survival to discharge after shock-resistant ventricular fibrillation and can achieve ROSC more quickly. Further prospective studies are needed to confirm our results.

[A case of accidental hypothermia caused by cervical spinal cord injury].

Accidental hypothermia is the state in which body temperature falls due for exposure to a chilly environment. In accidental hypothermia, the mortality rate is higher the lower the body temperature. We report a case of a consciousness disorder and severe hypothermia, with a body temperature below 28 degrees C, in which it later became clear that a cervical spinal cord injury had been caused by a small external force. A 70-year-old woman was transported to our hospital in an ambulance for consciousness disturbance and severe hypothermia. At the time of arrival, her rectal temperature was 26.2 degrees C. We promptly performed rewarming. Her consciousness level became clear, but paralysis and diminished sensation were observed below the C5 domain. We suspected cervical spinal cord injury and performed cervical magnetic resonance imaging. She was diagnosed as having C5 cervical spinal cord injury. When there is a consciousness disorder due to accidental hypothermia, it might not be possible to evaluate the neurological value of the cervical spinal cord injury correctly. The presence of cervical spinal cord injury should be considered when patients have a decreased consciousness level due to hypothermia.

[Relationship between occupational health and emergency medicine].

The primary aim for occupational health care is to appropriately control risks related to health problems arising in workplace environments which are caused by work methods. Lowering risks might not always prevent accidents or illnesses; but initial treatment after an accident or of ill workers is crucial work for occupational health care staff. By implementing appropriate initial treatment, it is possible to increase the survival rate of workplace accidents and decrease the rate of illness. Crisis management at the time of an accident is a very important function of occupational health. Thus there is a close relationship between occupational health care and emergency medicine.

[A case of acalcuous cholecystitis developed after cardiopulmonary resuscitation].

A 47-year-old man was found at his home in a state of cardiopulmonary arrest. His family performed cardiopulmonary resuscitation on him. He was brought to our hospital by ambulance. On arrival, his pupils were dilated and his heart was in a state of ventricular fibrillation. After returning to spontaneous circulation by the cardiopulmonary resuscitation, the electrocardiogram revealed ST elevation at V2-V5. Cardiac catheterizatin revealed a left anterior descending coronary obstruction. Percutaneous coronary angioplasty was performed. On the 26th day after admission, acalculous cholecystitis was found. It was difficult to perform emergent surgery, because the patient was taking an anticoagulant drug. We performed PTGBA (percutaneous transhepatic gallbladder aspiration) on the same day, and the gallbladder inflammation was improved. We consider that PTGBA is an effective treatment for difficult cases of acalcuous cholecystitis.

[A case of multiple trauma with sinking skull, whose life was saved by consistent team medical treatment].

A 54 year old man was brought to our hospital by ambulance. He had been injured by falling heavy steel. An examination was performed, and he was diag nosed as having sinking skull, acute extradural hematoma, trauma of the righ eye, right eye laceration, injury of the optic canal (right blind), and multipl fractures. Open fractures were observed in the right ring finger and little finger Simple fractures were observed in the zygomatic bone nasal bone and maxillary bone. An emergency operation (external skeletal fixation, taxis of the skull and maxillary bone, extradural hematoma depletion, suture of right eyelid) was performed. His life was saved by consistent team treatment from preoperation t postoperation. He was discharged from our hospital on foot at 45 days after th operation.

Late onset of Wolff-Parkinson-White syndrome in a 72-year-old man.

We encountered a case of wide QRS tachycardia with chronic atrial fibrillation in Wolff-Parkinson-White syndrome. Unique features were late onset of syncope attacks associated with this tachycardia at an advanced age of 72 years old without previous documentation of Wolff-Parkinson-White syndrome on electrocardiogram. He had a high likelihood of sudden cardiac death. Catheter ablation using CARTO system easily led to a successful ablation of the accessory pathway. The mechanism of late onset of the wide QRS tachycardia was attributed to possible changes of electrophysiologic properties including the atrio-ventricular node and/or the accessory pathway, and the unique location of the accessory pathway.

Successful treatment of severe orthostatic hypotension with erythropoietin.

A 71-year-old man, who was diagnosed with familial amyloidosis type I, was admitted for treatment of severe orthostatic hypotension associated with recurrent syncopal attacks. Head-up tilt testing demonstrated severe orthostatic hypotension (114/72 mmHg in the supine position and 62/34 mmHg in the upright position) with syncope or presyncope. Oral midodorine and fludrocortisone therapies failed to prevent his symptoms. After administration of subcutaneous erythropoietin, his blood pressure drop in the upright position was decreased and symptoms disappeared unassociated with improvement of anemia. Although previous reports have shown that the mechanism by which erythropoietin improves orthostatic hypotension is related to improvement in anemia, other mechanisms may also play a role.