Comparative analysis of methicillin-resistant Staphylococcus aureus isolated from outpatients of dermatology unit in hospitals and clinics.

Community-onset methicillin-resistant Staphylococcus aureus (CO-MRSA) is a causative agent of intractable skin infections. In general, clinical symptoms of hospital outpatients with skin infections are severer than those of clinic patients. Hence, molecular epidemiological features of the CO-MRSA strains from hospital outpatients are predicted to be different from those of clinic patients. Here, we conducted a comparative analysis for CO-MRSA isolates from outpatients with impetigo in hospitals and clinics located in the same district of Tokyo, Japan. Incidence of MRSA infection was higher in hospital outpatients (21.5%, 20/93 isolates) than in clinic patients (14.5%, 121/845 isolates). The resistance rate to clindamycin, which is a common topical antimicrobial agent in dermatology, in the isolates from hospital outpatients (60.0%) was higher than those from clinic patients (31.4%). Proportion of the staphylococcal cassette chromosome (SCC) mec type II, which is a representative type of hospital-acquired MRSA in Japan, in the isolates from hospital outpatients (65.0%) was significantly higher than those from clinic patients (30.6%) (P < 0.01). Multilocus sequence typing showed that the clonal complex 89-SCCmec type II (CC89-II) clone, which exhibits clindamycin resistance, was the most predominant (55.0%) in the isolates from hospital outpatients. On the other hand, all CC8-IV, CC121-V, and CC89-V clones accounted for 60% in clinic patients were susceptible to clindamycin. Our findings suggested that the clindamycin-resistant CC89-II CO-MRSA clone might be more related to skin infections in hospital outpatients than clinic patients.

[Multiple Spinal Intradural and Extradural Syphilis Granuloma Mimicking Lumbar Dumbbell Type Neurinoma:A Case Report].

Spinal intradural and extradural syphilis granuloma is extremely rare. Here, we report a patient with multiple spinal intradural and extradural syphilis granuloma mimicking dumbbell type neurinoma. The patient was a 68-year-old man, who presented with left femoral pain for a month. Magnetic resonance imaging(MRI)revealed a homogeneous enhanced dumbbell-shaped lesion occupying the spinal canal at the level of lumbar 3/4 and developing through the intervertebral foramen. Although initial blood tests revealed that he contracted with the syphilis, we diagnosed dumbbell type neurinoma preoperatively. He underwent partial tumor removal. The tumor adhered tightly to the cauda equina in intraoperative finding. Histopathological diagnosis of the lesion was granulomatous inflammation with the lymphocytic infiltration. Postoperatively, results of the Treponema pallidum hemagglutination(TPHA)test and the rapid plasma regain(RPR)test of cerebrospinal fluid were reactive, so we confirmed syphilis granuloma. He was treated with penicillin G for two weeks from 25 days after surgery. A follow-up MRI of the lumbar spine 51 days after surgery showed a reduction in size of the lumbar spinal tumor compared to the initial findings. Thus, syphilis granuloma should be considered in differential diagnosis of a spinal dumbbell shaped lesion. Penicillin G may be effective for the treatment of syphilis granuloma.

A case of idiopathic normal pressure hydrocephalus in an elder diabetic patient.

The clinical entity idiopathic normal pressure hydrocephalus (iNPH) is characterized by dementia, urinary incontinence, gait ataxia. An 80-year old man with a past history of Type 2 diabetes mellitus admitted to our hospital. Combination of twice Aspart and Aspart premixed30/70 insulin were used. Although, he was unable to inject insulin by himself recently. On physical examination, he walked in a mildly wide based manner. According to his family, urinary incontinence was existed. Laboratory data were as follows: Postrandial blood glucose 243 mg/dl and glycated hemoglobin 8.0% (NGSP). Brain magnetic resonance imaging (MRI) scans showed thinning of the corpus callosum with enlargement of the lateral ventricles on a colonal image. Evan's ratio was 0.29. The revised version of Hasegawa's Dementia scale (HDS-R) was 10. The patient showed no evidence a related antecedent event, such as head trauma, intracerebral hemorrhage and meningitis. Thus, he was diagnosed as having possible Idiopathic normal pressure hydrocephalus (iNPH). The following several psychological tests and walking test were applied. Before and after the tap, he was evaluated using the HDS-R, Mini mental state examination (MMSE), Timed Up and Go test (TUG). Insulin was replaced by glargine, and Sitagliptin was added. On the 31 day, the patient underwent Ventriculo-perioneal shunt. Laboratoly data and memory impairment were also improved. 8 month's later, HbA1c was 7.5%. iNPH occurs in the elderly and is characterized by a clinical triad of gait disturbance, urinary incontinence and dementia. In the present case, thinning of the corpus callosum with enlargement of the lateral ventricles was detected by MRI. 49% of iNPH patients had Diabetes mellitus. However, we were unable to detect a relationship iNPH and Diabetes mellitus. Cognitive impairment may interfere with the insulin therapy. In the present case, failure of insulin self-injection was the first clinical sign to appear. We were able to reduce dose of insulin. We conclude that iNPH is a treatable disorder, especially when treatment is started early in the course of the disease.

Direct Carotid Cavernous Fistula Due to Rupture of a Cavernous Carotid Aneurysm Embedded Within a Prolactinoma After Cabergoline Administration.

BACKGROUND: A small number of reports have described subarachnoid hemorrhage resulting from a ruptured aneurysm embedded within a prolactinoma. To the best of our knowledge, no reports have described an embedded carotid cavernous fistula. We report a patient with carotid cavernous fistula secondary to a ruptured internal carotid artery aneurysm embedded within a prolactinoma. CASE DESCRIPTION: A 61-year-old woman was referred to our hospital with sudden headache, vomiting, and dizziness. Magnetic resonance imaging demonstrated a small acute subdural hematoma, recurrent prolactinoma, and left cavernous carotid aneurysm. Conservative therapy was initiated. Her serum prolactin level at hospitalization was 11,300 µg/L; therefore, we initiated cabergoline therapy. Twenty days after cabergoline administration, she suddenly presented with left conjunctival injection and pulsatile tinnitus. Angiography showed a left direct carotid cavernous fistula with a connection between the cavernous internal carotid artery and the cavernous sinus via the aneurysm and venous congestion. To prevent hemorrhagic stroke, we scheduled staged surgery. First, we urgently performed embolization of the cavernous sinus and fistula. One month later, to prevent aneurysm rerupture, we performed a radical operation with superficial temporal artery-middle cerebral artery double anastomosis with proximal occlusion of the left internal carotid artery at the cervical portion. The patient was discharged 2 weeks after surgery without neurological deficits. Follow-up angiography revealed complete occlusion of the aneurysm 2 months postoperatively. CONCLUSIONS: An aneurysm embedded within a prolactinoma should be closely observed when cabergoline administration is started.

Safety of selective cyclooxygenase-2 inhibitors and a basic non-steroidal anti-inflammatory drug (NSAID) in Japanese patients with NSAID-induced urticaria and/or angioedema: Comparison of meloxicam, etodolac and tiaramide.

The identification of a safe and reliable alternative for patients with non-steroidal anti-inflammatory drug (NSAID)-induced urticaria/angioedema is a frequent problem for dermatologists and other practitioners. Cyclooxygenase-2 (COX-2) inhibitors have been reported to be safe for NSAID-intolerant patients from the US and Europe but not all of them have yet been approved for use in Japan. It was our objective to investigate the clinical manifestations of oral NSAID challenges in Japanese patients with histories of urticaria and/or angioedema after the intake of NSAIDs and to find safe alternative drugs, including COX-2 inhibitors and a basic anti-inflammatory drug. Twenty subjects suspected NSAID-induced urticaria/angioedema from histories were included in a double-blind or single-blind, placebo-controlled oral challenge protocol using NSAIDs. Skin prick tests using NSAIDs, which were dissolved in saline, were conducted. The mean age of the patients was 37.3 years; 14 patients were female. The results of other challenge tests showed that the most frequently intolerated drugs was loxoprofen (100%), followed by acetyl salicylic (94.4%), etodolac (53.3%), dicrofenac (50%), acetaminophen (38.5%), meloxicam (33%), and tiaramide (21.4%). Urticaria and angioedema were induced after aspirin intake in 83.3% and 22.2% of patients, respectively, whereas an asthmatic response was seen in 5.6%. Skin prick tests with NSAIDs were 100% negative. This study showed that among the NSAIDs that are available in Japan and that were investigated in this study, tiaramide, which does not inhibit COX, is the relatively safe alternative drug for Japanese patients with NSAID-induced urtiacaria and/or angioedema. Furthermore, meloxicam seems to be better tolerated than etodolac between two selective COX-2 inhibitors.

Numerical determination of entropy associated with excess heat in steady-state thermodynamics.

We numerically determine the global entropy for heat-conducting states, which is connected to the so-called excess heat considered as a basic quantity for steady-state thermodynamics in nonequilibrium. We adopt an efficient method to estimate the global entropy from the bare heat current and find that the obtained entropy agrees with the familiar local equilibrium hypothesis well. Our method possesses a wider applicability than local equilibrium and opens a possibility to compare thermodynamic properties of complex systems in nonequilibrium with those in the local equilibrium. We further investigate the global entropy for heat-conducting states and find that it exhibits both extensive and additive properties; however, the two properties do not degenerate each other differently from those at equilibrium. The separation of the extensivity and additivity makes it difficult to apply powerful thermodynamic methods to the nonequilibrium steady states.

Extramammary Paget's disease: analysis of growth signal pathway from the human epidermal growth factor receptor 2 protein.

Paget's disease is a skin cancer characterized by characteristic (Paget) cells scattered in the epidermis. Although its prognosis is generally favorable with surgical resection, the clinical outcome turns unfavorable in cases with recurrence and metastasis. Therefore, establishment of effective therapeutic regimens is required for advanced Paget's disease. The human epidermal growth factor receptor 2 (HER2) protein, a transmembrane growth factor receptor, is frequently overexpressed in malignancies, causing activation of the phosphatidylinositol 3 kinase (PI3K) and extracellular signal-regulated kinase (ERK) signal pathways. Recently, HER2-targeting molecular therapy using trastuzumab (Herceptin; Genentech, Inc, South San Francisco, Calif) was revealed to be effective in advanced breast cancers overexpressing HER2 protein. Here, we analyzed the correlation between activation of the HER2 signal pathways and clinicopathologic parameters of 36 extramammary Paget's disease samples from 34 Japanese patients, using immunohistochemical analyses for HER2, phosphorylated HER2, phosphorylated AKT, and phosphorylated ERK proteins. We found overexpression of the HER2 protein in 19.4% (7) of the lesions, 3 of which showed HER2 amplification by chromogenic in situ hybridization. Phosphorylated HER2 protein was detected in 12 lesions (33.3%), including 2 of the 7 HER2-overexpressing lesions. Phosphorylated AKT was detected in approximately 75.0% (27/36) and phosphorylated ERK in 38.9% (14/36). Both HER2 and AKT were simultaneously phosphorylated in 9 cases (25.0%) and HER2 and ERK in 9 cases (25.0%), but all 3 molecules were phosphorylated in only 1 sample. Phosphorylated ERK correlated with the maximum diameter of the tumors (P < .025), but other immunohistochemical parameters failed to show any correlation with clinicopathologic features. These results suggest the contribution of the HER2 signaling pathway to the pathogenesis and progression of some cases of extramammary Paget's disease, for which clinical use of molecular target therapy against the HER2 pathway is warranted.

The novel VEGF receptor antagonist, VGA1155, reduces edema, decreases infarct and improves neurological function after stroke in rats.

Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis and also a strong vascular permeability factor. Blockade of VEGF may have a potential to treat cerebral edema after brain injury. We evaluated the effect of VGA1155 (5- [N-Methyl-N-(4-octadecyloxyphenyl)acetyl]amino-2- methylthiobenzoic acid), a novel binding antagonist of VEGF, on cerebral edema after transient focal cerebral ischemia. Focal cerebral ischemia was induced with the suture occlusion method for 2 h. In the treatment group, a single dose of VGA1155 (1 ~ 50 mg/kg i.p.) was administrated 30 min before the induction of focal ischemia, and the vehicle group received phosphate buffer only. The brain water content, Evans blue extravasation, infarct volumes and neurological score were determined. Physiological parameters were not influenced by the administration of VGA1155. The brain water content at 24 h after cerebral ischemia was significantly reduced by intraperitoneal administration of VGA1155 and the dose of 10 mg/kg showed the maximum effect on brain water content (81.8 ± 0.5% in non treated group vs. 80.2 ± 0.6% in treated group). With this dose, VGA1155 also reduced vascular permeability from 2.2 ± 0.8 µg/g to 1.2 ± 0.5 µg/g studied at 6 h after the ischemia by intravenous injection of Evans blue. VGA1155 administration significantly reduced infarct volume and improved neurological scores at 1 week after ischemic injury. The data suggested that VGA1155 has antiedematous effect in acute phase after transient focal cerebral ischemia and improves neurological and histological outcomes 1 week after ischemic injury.

Anti-VEGF receptor antagonist (VGA1155) reduces infarction in rat permanent focal brain ischemia.

BACKGROUND AND PURPOSE: Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis and a strong vascular permeability factor. VEGF is known to open the blood-brain barrier (BBB) and induce cerebral edema. Experimental studies of VEGF antagonism have shown it reduces cerebral edema after ischemia, indicating its potential for prevention of secondary brain damage. We examined the therapeutic effect of VGA1155 (5- [N-Methyl-N- (4-octadecyloxyphenyl) acetyl] amino-2-methyl-thiobenzoic acid), a novel small molecule antagonist of VEGF, on rat permanent focal cerebral ischemia. METHODS: Permanent middle cerebral artery occlusion (MCAO) was induced with the suture occlusion method. A single dose of VGA1155 (10mg/kg, i.p.) was administered 30 minutes before the induction of MCAO after which brain water content, Evans blue extravasation, neurological score, infarct volumes and VEGF expression determined by means of ELISA were compared with corresponding values for vehicle injected control rats. RESULTS: Brain water content and Evans Blue extravasation 24 hours after ischemia were not significantly reduced, but, compared with control group, VGA1155 significantly reduced infarct volume (32.0% for VGA1155 vs. 46.7% for control; % volume of hemisphere volume) and improved neurological function 7 days after ischemia, when tissue content of the VEGF group markedly increased to nine times that of the vehicle-treated animals. CONCLUSION: VGA1155 was found to protect against secondary ischemic brain damage after permanent focal cerebral ischemia, although it did not reduce vasogenic edema at 24 hours. Changes in endogenous VEGF may be related to the therapeutic effect of VGA1155.

Docosahexaenoic acid and eicosapentaenoic acid induce changes in the physical properties of a lipid bilayer model membrane.

We investigated the effect of fatty acids such as stearic acid (SA, 18:0), oleic acid (OA, 18:1), eicosapentaenoic acid (EPA, 20:5), and docosahexaenoic acid (DHA, 22:6) on a dipalmitoylphosphatidylcholine (DPPC) bilayer by determining the phase transition temperature, fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH), and detergent insolubility. Treatment with unsaturated fatty acid broadened and shifted the phase transitions of the DPPC bilayer to a lower temperature. The phase transition temperature and the value of fluorescence anisotropy of DPH at 37 degrees C decreased progressively with increasing treatment amounts of unsaturated fatty acid. A large amount of the DPPC bilayer treated with unsaturated fatty acid was dissolved in Triton X-100, obtaining a low level of detergent insolubility. These modifications of the bilayer physical properties were most pronounced with DHA and EPA treatment. These data show that unsaturated fatty acids, particularly DHA and EPA, induce a marked change in the lipid bilayer structure. The composition of fatty acids in the DPPC bilayer was similar after treatment with various unsaturated fatty acids, suggesting that the different actions of unsaturated fatty acids are attributed to change in the molecular structure (e.g., kinked conformation by double bonds). We further explored the change in physical properties induced by fatty acids dispersed in a water-in-oil-in-water multiple emulsion and found that unsaturated fatty acids acted efficiently on the DPPC bilayer, even when incorporated in emulsion form.