Long-term intermittent pulse therapy with mizoribine attenuates histologic progression in young patients with severe lupus nephritis: report of two patients

Mizoribine (MZR), a novel selective inhibitor of inosine monophosphate dehydrogenase in the de novo pathway, whose mode of action is very similar to that of mycophenolate mofetil, has been successfully applied without serious adverse effects for the treatment of renal diseases. We have previously reported the efficacy and safety of a new MZR treatment regimen, namely, oral MZR intermittent pulse therapy, which we examined based on the observation that it might show superior efficacy to the conventional daily low-dose MZR regimen on account of the higher peak serum MZR levels, in selected patients with lupus nephritis. Two Japanese patients with severe lupus nephritis (WHO class IV-G) who were administered long-term intermittent MZR pulse therapy, and in whom pre- and post-treatment renal biopsies were reported. Post-treatment renal biopsy confirmed the marked attenuation of histologic progression by the treatment. These clinical observations may lend further support, from the histologic standpoint, to the efficacy of long-term MZR intermittent pulse therapy for selected patients with active lupus nephritis.     

A case of Paenibacillus polymyxa bacteremia in a patient with cerebral infarction

We report a case of Paenibacillus polymyxa bacteremia in a patient with cerebral infarction. The patient was a 93-year-old female who was admitted to our hospital. On the 4 day after admitted, she had a fever 38.2 degrees C. The result of the blood culture showed a gram positive spore bacillus in the blood culture bottle. As a result of performing 16SrDNA sequence analysis (500bp), it was a close relationship most by 99.26% P. polymlxa of coincidence was found. With a result using api 20E and api 50CH, this bacillus turned out to be P. polymyxa. The patient had a habit of weeding around her house daily. So we had to take her habit into consideration. We thought she could to get her hands injured. We assumed probably her habit might put her into high risk state of infection of this bacillus. We have supposed this bacillus might be infected with her through her blood.     

Initial experiences in management of blunt aortic injury taking associated brain injury into consideration.

BACKGROUND: Although endovascular stent-grafting (SG) has become acceptable for blunt aortic injury (BAI), open surgical repair (OR) does provide reliable, good long-term results. A current surgical strategy for BAI, taking account of associated brain injury, is presented and preferable initial management for BAI is proposed. METHODS AND RESULTS: The surgical strategy for BAI was established in 2001: SG is performed for patients with obvious brain injuries, but OR is performed for patients without brain injury, and conservative treatment should be used initially for patients with critical non-aortic injuries. Between 2001 and 2004 20 patients with BAI were admitted to hospital: 16 blunt aortic ruptures and 4 blunt aortic dissections. Of them 15 patients underwent surgery (SG, 9; OR, 6) and 5 patients were treated conservatively. One patient died from associated lung injury after SG, all patients treated conservatively died because of associated brain injuries or another rupture of BAI, and 2 elderly patients treated by OR died within 1 year from postoperative respiratory failure. CONCLUSION: This brain-injury conscious surgical strategy for BAI provided acceptable early results. OR should be chosen for young patients without brain injury, but endovascular SG seems to be a better initial treatment for elderly patients or patients with other comorbidities.     

Outcome from severe accidental hypothermia with cardiac arrest resuscitated with extracorporeal cardiopulmonary resuscitation

Purpose

This study aimed to identify factors of neurologic prognosis in severe accidental hypothermic patients with cardiac arrest.

Basic procedures

This retrospective observational study was performed in a tertiary care university hospital in Sapporo, Japan (January 1994 to December 2012). We investigated 26 patients with accidental hypothermic cardiac arrest resuscitated with extracorporeal cardiopulmonary resuscitation (ECPR). We evaluated the neurologic outcome in patients who were resuscitated with ECPR at discharge from hospital.

Main findings

In those 26 patients, their median age was 50.5 years; and 69.2% were male. The cause of hypothermia was exposure to cold air in 46.1%, submersion in 46.1%, and avalanche in 7.8%. Ten (38.5%) of these patients survived to favorable neurological outcome at discharge. Factors associated with favorable neurological outcome were a cardiac rhythm other than asystole (P = .009), nonasphyxial hypothermia (P = .006), higher pH (P = .01), and lower serum lactate (P = .01). In subgroup analyses, the patients with hypothermic cardiac arrest due to submersion or avalanche (asphyxia group) showed no factors associated with good neurological outcome, whereas the nonasphyxia group showed a significantly lower core temperature (P = .02) and a trend towards a lower serum lactate (P = .09).

Principal conclusions

Patients with hypothermic cardiac arrest due to nonasphyxial hypothermia have improved neurologic outcomes when treated with ECPR compared to patients with asphyxial hypothermic cardiac arrest. Further investigation is needed to develop a prediction rule for patients with nonasphyxial hypothermic cardiac arrest to determine which patients would benefit from treatment with ECPR.     

Pharmacokinetics and clinical evaluation of imipenem/cilastatin sodium in pediatric surgery

Pharmacokinetic and clinical studies on imipenem/cilastatin sodium (IPM/CS) in pediatric surgery were performed and the results obtained are summarized below. 1. Plasma and urinary levels of IPM/CS were measured in 9 neonate patients following drip-infusion for 1 hour of IPM/CS (dose of IPM 10 mg/kg for 5 patients, 20 mg/kg for 4 patients). In the 10 mg/kg group, peak plasma levels were observed at the end of infusion or after 1 hour of it. IPM 9.95-14.2 micrograms/ml, CS 7.7-30.1 micrograms/ml. In the 20 mg/kg group, peak levels were found at the end of the infusion, IPM 39.2-41.7 micrograms/ml, CS 48.1-58.8 micrograms/ml. In both groups, plasma levels of IPM/CS decreased rapidly, and plasma half-lives (T 1/2) in the 20 mg/kg group were 0.9-1.2 hours (IPM) and 0.8-1.1 hours (CS). Urinary recovery rates were 17.7-28.7% (10 mg/kg), 21.1-36.9% (20 mg/kg) for IPM and 27.1-43.8% (10 mg/kg) and 21.5-76.5% (20 mg/kg) for CS. 2. Bile levels of IPM/CS were measured in 3 patients with congenital biliary atresia and 1 patient with neonatal hepatitis. Peak levels of IPM/CS in bile were noted 1 hour after the end of infusion, and they were 3.01-12.3 micrograms/ml for IPM, and 2.5-13.1 micrograms/ml for CS. Recovery rates in bile in 7 hours after the end of infusion were 0.03-0.12% (IPM), 0.01-0.12% (CS). 3. IPM/CS was administered to 9 patients as prophylaxis against postoperative infections and to 2 patients with postoperative cholangitis. No infectious complications were observed in patients after the prophylactic use. In 1 patient with cholangitis, clinical effect was good and organisms were eradicated. No clinical or laboratory adverse reactions due to the administration of IPM/CS were noted. It is concluded that IPM/CS is an effective and safe antibiotic in pediatric surgery.     

Immunoelectron Microscopic Study of Podoplanin Localization in Mouse Salivary Gland Myoepithelium

We have recently reported that salivary gland cells express the lymphatic endothelial cell marker podoplanin. The present study was aimed to immunohistochemically investigate the expression of the myoepithelial cell marker α-smooth muscle actin (SMA) on podoplanin-positive cells in mouse parotid and sublingual glands, and to elucidate podoplanin localization in salivary gland myoepithelial cells by immunoelectron microscopic study. The distribution of myoepithelial cells expressing podoplanin and α-SMA was examined by immunofluorescent staining, and the localization of reaction products of anti-podoplanin antibody was investigated by pre-embedded immunoelectron microscopic method. In immunohistochemistry, the surfaces of both the mucous acini terminal portion and ducts were covered by a number of extensive myoepithelial cellular processes expressing podoplanin, and the immunostaining level with anti-podoplanin antibody to myoepithelial cells completely coincided with the immunostaining level with anti-α-SMA antibody. These findings suggest that podoplanin is a salivary gland myoepithelial cell antigen, and that the detection level directly reflects the myoepithelial cell distribution. In immunoelectron microscopic study, a number of reaction products with anti-podoplanin antibody were found at the Golgi apparatus binding to the endoplasmic reticulum in the cytoplasm of myoepithelial cells between sublingual gland acinar cells, and were also found at the myoepithelial cell membrane. These findings suggest that salivary gland myoepithelial cells constantly produce podoplanin and glycosylate at the Golgi apparatus, and transport them to the cell membrane. Podoplanin may be involved in maintaining the homeostasis of myoepithelial cells through its characteristic as a mucin-type transmembrane glycoprotein.