Primary lung sebaceous carcinoma successfully treated with radiotherapy and pembrolizumab: A case report.

Sebaceous carcinoma is a rare cutaneous malignant tumor, usually occurring on the eyelids, head, neck, and trunk. There have been few reports about sebaceous carcinoma with primary lung cancer, for which optimal therapy has not yet been established. A 70-year-old man presented with a mass in the left iliac bone and tumor of the lower left lung. The morphological characteristics of the iliac bone biopsy pathology and immunostaining results showed sebaceous gland differentiation. After systemic examination, we diagnosed a primary lung sebaceous carcinoma with intrapulmonary and bone metastases. PD-L1 was positive in 1%-24% of tumor cells, and microsatellites were stable. We detected protein kinase B (AKT1) mutations using the Oncomine Dx target test. Palliative radiotherapy (RT) of a total of 45 Gy was provided in 15 fractions to the left iliac region, which resulted in a 25% reduction in the tumor size. Subsequently, four courses of first-line pembrolizumab led to a 30% reduction in the total tumor count. RT and pembrolizumab may be treatment options for certain rare primary sebaceous carcinomas of the lungs. A synergistic effect from RT and subsequent administration of immune checkpoint inhibitors may have contributed to tumor reduction.

Learning and memory performance following acute intranasal insulin administration in abstinent smokers.

The highest incidence of relapse to smoking occurs within the first 2 weeks of a cessation attempt. In addition to enhanced nicotine craving, this phase of smoking cessation is also marked by learning and memory dysfunction. Many smokers are not able to overcome these symptoms, and they relapse to smoking shortly after trying to quit. In two clinical studies, we evaluated intranasal insulin for efficacy in improving learning and memory function during nicotine withdrawal. Our first study was a crossover evaluation (N = 19) following 20 hr of smoking abstinence. Study 2 was a parallel design study (N = 50) following 16 hr of abstinence. Intranasal insulin (60 IU) dose was administered in both studies and cognitive function was measured using California Verbal Learning Test-II. Intranasal insulin did not improve learning over the 5 verbal learning trials. In addition, intranasal insulin did not improve either short- or long-delay recall in either study. In summary, the one-time administration of intranasal insulin does not improve verbal learning and memory in smokers. Whether longer administration schedules may be of benefit should be evaluated in future studies.

[Nasopharyngeal Hib Carriage Among Healthy Children Attending Daycare Centers in Yokohama After One Year of a Publicly Funded Vaccine Program].

Yokohama city started a regular, free vaccine program for Haemophilus influenzae type b (Hib) from February of 2011. This study was completed to verify the effectiveness of the vaccine on the nasopharyngeal Hib carriage among healthy children attending daycare centers in the Isogo area. The research was conducted during the late spring (Jun--Jul) and fall (Oct-Nov) of 2012. There was a significant decrease in the Hib carriage rate (spring 8.8%, fall 1.6%). During this period there was no increase in the Hib vaccine coverage. The Hib carriage rate of each daycare center was 0-18.4% in spring and 0-4.9% in fall. There was no significant relationship between the rate of non immunized children and that of Hib carriage. This improvement in nasopharyngeal Hib carriage shows the impact of community immunity.

S-equol Partially Restored Endothelial Nitric Oxide Production in Isoflavone-deficient Ovariectomized Rats.

BACKGROUND: S-equol is known as an estrogenic substance, but its ability to restore vascular endothelial function is unknown. The aim of this study was to investigate the impact of S-equol on endothelial function and intimal thickening under isoflavone- and estrogen-deficient circumstances. METHODS: Twelve-week-old female Sprague-Dawley rats were bilaterally ovariectomized and assigned to one of the 3 groups: control, isoflavone-deficient (ID), or ID plus equol (n = 12, respectively). The control group received a normal diet containing isoflavones, while ID and ID plus equol groups received isoflavones-free diet. At 16th week, subcutaneous administration of S-equol (200 µg/d) started in the ID plus equol group. At 18th week, endothelial denudation of the left common carotid artery was performed in all groups, and thoracic and carotid arteries were collected at 20th week. RESULTS: In thoracic artery, endothelium-dependent relaxation, cyclic guanosine monophosphate levels in the tissue, and endothelial nitric oxide (NO) synthase expression and phosphorylation were significantly higher in the groups of ID plus equol and control than in the ID. The ratio of intima to media of the injured carotid artery in the control group was the lowest. CONCLUSIONS: Removal of dietary soy isoflavones decreased endothelium-derived NO level in ovariectomized rats. S-equol supplementation partially improved NO-related endothelial function.

Characterization of enterohemorrhagic Escherichia coli O111 and O157 strains isolated from outbreak patients in Japan.

In April and May 2011, there was a serious food-poisoning outbreak in Japan caused by enterohemorrhagic Escherichia coli (EHEC) strains O111:H8 and O157:H7 from raw beef dishes at branches of a barbecue restaurant. This outbreak involved 181 infected patients, including 34 hemolytic-uremic syndrome (HUS) cases (19%). Among the 34 HUS patients, 21 developed acute encephalopathy (AE) and 5 died. Patient stool specimens yielded E. coli O111 and O157 strains. We also detected both EHEC O111 stx2 and stx-negative E. coli O111 strains in a stock of meat block from the restaurant. Pulsed-field gel electrophoresis (PFGE) and multilocus variable-number tandem-repeat analysis (MLVA) showed that the stx-negative E. coli O111 isolates were closely related to EHEC O111 stx2 isolates. Although the EHEC O157 strains had diverse stx gene profiles (stx1, stx2, and stx1 stx2), the PFGE and MLVA analyses indicated that these isolates originated from a single clone. Deletion of the Stx2-converting prophage from the EHEC O111 stx2 isolates was frequently observed during in vitro growth, suggesting that strain conversion from an EHEC O111 stx2 to an stx-negative strain may have occurred during infection.

Ezogabine: an evaluation of its efficacy and safety as adjunctive therapy for partial-onset seizures in adults.

OBJECTIVE: To evaluate the safety, efficacy, pharmacokinetics, pharmacodynamic properties, and clinical application of ezogabine (retigabine, INN), an antiepileptic drug approved in 2011. DATA SOURCES: Published data from in vitro, animal, and clinical studies were obtained from PubMed and CINAHL searches, from January 1980 to March 31, 2012. Other relevant data regarding the safety and efficacy of ezogabine were obtained from the Food and Drug Administration and the European Medication Agency Web sites. STUDY SELECTION AND DATA EXTRACTION: Selected articles were prospective in vitro, animal, and controlled clinical studies of ezogabine. Non-English-language articles were excluded. DATA SYNTHESIS: In vitro and animal studies show that ezogabine activates voltagegated potassium channels, leading to reduction of seizure frequency by inhibiting hyperexcitability activity in the central nervous system. Additionally, ezogabine enhances γ-aminobutyric acid (GABA) activity and de novo GABA synthesis. Eight clinical studies of ezogabine have been published, 5 being Phase 1 clinical trials in healthy subjects and 3 being Phase 3 clinical trials in patients with pharmaco-resistant partial-onset seizures. Phase 3 clinical trials demonstrated the safety and efficacy of ezogabine in patients with partial-onset seizures. CONCLUSIONS: Clinical trials have shown that ezogabine is efficacious as an adjunctive agent in patients with pharmacoresistant partial seizures. Careful monitoring of drug interactions and adverse reactions is necessary. While ezogabine is efficacious for partial seizures, its precise role in the management of patients with epilepsy is yet to be determined.

Salmonella enterica serovar Ohio septic arthritis and bone abscess in an immunocompetent patient: a case report.

INTRODUCTION: Non-typhi Salmonella species cause severe extra-intestinal focal infection after occult bacteremia. Although the number of cases of non-typhi salmonellosis is increasing worldwide among patients with immunocompromising conditions such as human immunodeficiency virus infection, infection is uncommon in immunocompetent subjects. We report a case of septic arthritis and bone abscess due to a rare non-typhi Salmonella organism that developed after a prolonged asymptomatic period. CASE PRESENTATION: A 44-year-old Japanese immunocompetent man presented with acute-onset left knee pain and swelling. He had no history of food poisoning, and his most recent travel to an endemic area was 19 years ago. Salmonella enterica serovar Ohio was identified from samples of bone abscess and joint tissue. Arthrotomy and necrotic tissue debridement followed by intravenous ceftriaxone was successful. CONCLUSIONS: Non-typhi Salmonella species only rarely cause extra-intestinal focal infections in immunocompetent patients. Our case suggests that non-typhi Salmonella species can cause severe focal infections many years after the occult bacteremia associated with food poisoning.

Generic substitution of antiepileptic drugs: a systematic review of prospective and retrospective studies.

OBJECTIVE: To systematically review the literature on generic antiepileptic drugs (AEDs), evaluate the efficacy and safety of generic AED substitution, and perform pharmacokinetic (PK) analysis using the American Academy of Neurology (AAN) scheme to classify evidence. DATA SOURCES: PubMed and Cumulative Index to Nursing and Allied Health Literature searches from January 1, 1980, to October 15, 2010, were performed using the search terms anticonvulsant, antiepileptic drug, carbamazepine, divalproex, ethosuximide, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pheno-barbital, phenytoin, primidone, topiramate, valproate, valproic acid, and zonisamide; bioavailability, bioequivalence, bioequivalency, bioequivalent, and substitution; and generic. STUDY SELECTION AND DATA EXTRACTION: Retrospective and prospective controlled studies of generic substitution of AEDs were included in the review. Non-English-language articles and uncontrolled clinical studies were excluded. Published articles were categorized using the AAN criteria for systematic reviews. DATA SYNTHESIS: We identified 156 articles. Of these, 20 met our inclusion criteria; 7 were retrospective studies, 6 were prospective studies in patients with epilepsy, and 7 were prospective studies in healthy subjects. All articles were rated Class I to Class III, using AAN criteria. The retrospective studies were categorized as Class III and showed a significant relationship between generic substitution and increased use of health care resources because of seizures or AED toxicity. Prospective studies were categorized as Class I, II, and III. Prospective studies in patients showed no differences between brand and generic drugs in PK parameters of bioequivalence. Three prospective studies in healthy subjects reported significant differences in maximum drug concentrations. Comparison of brand and generic drugs revealed no significant difference in seizure frequency; however, some prospective studies showed significant differences in PK parameters, primarily those not used for bioequivalence determinations. CONCLUSIONS: There is inconsistency between retrospective and prospective studies of generic AED substitution. The highest levels of evidence indicate that there should not be a problem with generic substitution, although some patients are more prone to problems with the generic products. Some evidence suggests that switches between multiple generic AED products in certain individuals may be problematic.

Electrophysiological characterization of tight junctional pathway of rabbit cornea treated with ophthalmic ingredients.

The purpose of this study was to investigate the continuous and real-time influence of ophthalmic ingredients on rabbit cornea by monitoring electrophysiological characteristics. The tight junctional permeabilities of FITC-dextran 4,400 (FD-4) was also determined through the cornea in the presence of ophthalmic ingredients. Intact cornea showed approximately one k-ohmxcm(2) of transepithelial electrical resistance (TEER) and extremely low permeability of FD-4. The ophthalmic ingredients used in the present study were benzalkonium chloride (BK; 0.002%, 0.01%, 0.05%), ethylenediaminetetraacetic acid (EDTA; 0.5%), capric acid (C10; 0.25%), saponin (SP; 0.1%), taurocholic acid (TA; 1.0%) and sodium dodecyl sulfate (SDS; 0.01%). They were previously reported to be effective on corneal penetrations of various drugs at those concentrations without severe toxicity. These ingredients decreased TEER and increased corneal permeability of FD-4. BK reduced TEER in a concentration-dependent manner. There was a significant correlation (gamma=0.860) between the permeability coefficient (Papp) of FD-4 and conductance (Gm), which is the reciprocal value of TEER. It was also indicated that Papp and Gm have a relationship with the corneal cytotoxicity of the ingredients. In conclusion, an electrophysiological method using isolated cornea was very useful to determine the continuous and real-time influence of ophthalmic ingredients on the cornea. In this method, electrophysiological conductance must be able to predict corneal tight junction permeability and the corneal cytotoxicity of ingredients.

[An epidemiological study of outbreaks of Salmonella enterica serovar paratyphi A occurred in two Chinese families after traveled to different areas of China].

We reported two familial clusters of paratyphoid fever after travel to China occurring in the same Yokohama ward from September to October 2002. Six Salmonella enterica serovar Paratyphi A (S. Paratyphi A) strains, 3 each from 2 clusters, were isolated and their characteristics analyzed using phage typing, susceptibility to antibiotics, and patterns of restriction endonuclease-digested DNA fragments in agarose gel following pulsed-field gel electrophoresis (PFGE). Mutations in genes for gyrA and parC, which determine sensitivity to fluoroquinolones, were also investigated. All isolates showed the same characteristics, i.e. "untypable", employing bacteriophages, resistant to antibiotics nalidixic acid and fosfomysin, and decreased susceptibility to fluoroquinolones. No difference was observed in PFGE patterns after digesting with 4 restriction enzymes, Xba I, Bin I, Spe I, and Xho I. We also found that the gyrA gene, which is one of the quinolone-resistance-determining regions (QRDR), was mutated at position 83 from serine to phenylalanine (from TTC to TCC) in all 6 strains. Other QRDR's, parC were not mutated commonly in them. Hearing from patients and family members, it was apparent that these 2 families had been contacted neither in Japan nor in China during ill or incubation period of paratyphoid fever, although a member of one cluster had a familial relationship with one of another family. It was also reported by them that typhoid fever is endemic in both of the areas of their visits. From these results, it was suggested that these 2 cluster cases were infected separately in China with the progeny of the same clone which is endemic in these regions.