Novel endoscopic duodenal observation protocol based on Seven Pictures Rule for detecting duodenal neoplasms during esophagogastroduodenoscopy: Prospective observational study.

OBJECTIVES: No protocol for esophagogastroduodenoscopic examination of the duodenum has been established. We examined the feasibility and ability to detect neoplasms of a novel duodenal examination protocol. METHODS: This was a two-facility, prospective, observational study. Our protocol, the Seven Pictures Rule (7PR), requires pictures of the following seven locations: anterior and posterior to the bulb, area of and contralateral to the superior duodenal angle, area of and contralateral to the ampulla, and the transverse duodenum. The primary outcome was rate of completion of 7PR. Secondary outcomes were overall rates of detecting neoplasms, rates of detecting neoplasms for each location, examination time, and completion rates for standard or ultrathin endoscopes. RESULTS: There were 1549 participants. The 7PR completion rate was 81.1% and the detection rates of overall neoplasms, adenomas, and carcinomas were 0.84%, 0.71%, and 0.06%, respectively. The area in which most neoplasms was detected was contralateral to the ampulla (69.2%), and the fewest the transverse duodenum (0%). Mean duration of duodenal examination was 53.1 s. Completion rates for standard vs. ultrathin were 84.4% (1077/1276) vs. 65.6% (179/273) (P < 0.01), respectively. CONCLUSIONS: Seven Pictures Rule is acceptable for duodenal examination and a potential quality indicator.

Questionnaire survey on pharmacists' roles among non- and health care professionals in medium-sized cities in Japan.

Although the scope of pharmacists' work has expanded in Japan, people's perception of this is unclear. To contribute to medical care together with non- and health care professionals, clarifying the perceptions of these groups is important to best utilize pharmacist professionals. We conducted a cross-sectional questionnaire survey among non-health care professionals (n = 487) and nurses (n = 151), medical doctors (n = 133), and pharmacists (n = 204) regarding the work of pharmacists. The questionnaire comprised 56 items in four categories associated with the roles of pharmacists. For each questionnaire item, we performed logistic regression analysis to compare pharmacists' opinions with those of other professionals and non-health care professionals. Opinions were similar between pharmacists and nurses or medical doctors regarding "collecting patient information" and "providing drug information to patients." However, there were differences in perceptions regarding "medical collaboration" (nurses; 8/23 items, physicians; 11/23 items) and "community medicine" (nurses; 9/15 items, physicians; 11/15 items), and pharmacists themselves perceived greater roles related to health care collaboration and community health care. Perceptions of non-health care professionals were poorer than those of pharmacists in all categories (47/56 items). These results suggest that pharmacists must actively communicate to help others understand their specialty and build trusting relationships to improve patient care.

Sustained Surface ICAM-1 Expression and Transient PDGF-B Production by Phorbol Myristate Acetate-Activated THP-1 Cells Harboring Blau Syndrome-Associated NOD2 Mutations.

OBJECTIVES: Blau syndrome is a distinct class of autoinflammatory syndrome presenting with early-onset systemic granulomatosis. Blau syndrome-causing NOD2 mutations located in the central nucleotide-oligomerization domain induce ligand-independent basal NF-κB activation in an in vitro reporter assay. However, the precise role of this signaling on granuloma formation has not yet been clarified. METHODS: Blau syndrome-causing NOD2 mutations were introduced into human monocytic THP-1 cells, and their morphological and molecular changes from parental cells were analyzed. Identified molecules with altered expression were examined in the patient's lesional skin by immunostaining. RESULTS: Although the production of proinflammatory cytokines was not altered without stimulation, mutant NOD2-expressing THP-1 cells attached persistently to the culture plate after stimulation with phorbol myristate acetate. Sustained surface ICAM-1 expression was observed in association with this phenomenon, but neither persistent ICAM-1 mRNA expression nor impaired ADAM17 mRNA expression was revealed. However, the transient induction of PDGF-B mRNA expression was specifically observed in stimulated THP-1 derivatives. In the granulomatous skin lesion of a Blau syndrome patient, ICAM-1 and PDGF-B were positively immunostained in NOD2-expressing giant cells. CONCLUSIONS: Sustained surface ICAM-1 expression and transient PDGF-B production by newly differentiating macrophages harboring mutant NOD2 might play a role in granuloma formation in Blau syndrome.

Unusual endoscopic findings of gastric neuroendocrine tumor.

Gastric neuroendocrine tumor (NET) is sometimes found as a submucosal tumor on upper gastrointestinal endoscopy. Gastric NET with malignant profile and neuroendocrine carcinoma (NEC) show various forms which are difficult to distinguish from gastric cancer and other disease. We report a case of a cauliflower-shaped NET of the stomach. A 61-year-old man was referred to our hospital with a complaint of abdominal fullness. Upper gastrointestinal endoscopic examination revealed an unusual, whitish cauliflower-shaped tumor that belongs to Borrmann type I on the lesser curvature of the gastric antrum. Histological examination of the biopsy specimen revealed NET G2, because the tumor cells were CD56- and synaptophysin-positive by immunohistochemical analysis. A distal gastrectomy with D2 lymphadenectomy was performed. A recurrence in the liver was revealed by follow up computed tomography after 11 months from operation. Combined chemotherapy with irinotecan (CPT-11) plus cisplatin (CDDP) was treated. The patient achieved a partial response, but he died after 31 months from gastrectomy. There is no independent, large-scaled prospective study and no standard treatment for gastric NETs with distant metastases. Our case is reported with a literature review of the treatment of metastatic gastric NET G2.

Case of Paecilomyces lilacinus infection occurring in necrotizing fasciitis-associated skin ulcers on the face and surrounding a tracheotomy stoma.

A 28-year-old man undergoing treatment for hemophagocytic syndrome developed Paecilomyces lilacinus infection in skin ulcers on the face and in the tracheotomy stoma. While his bone marrow was suppressed by chemotherapy with dexamethasone, cyclosporin and etoposide for hemophagocytic syndrome, dental infection led to subacute necrotizing fasciitis caused by Pseudomonas aeruginosa on the right side of the face, resulting in a large area of soft tissue defects. Etoposide was discontinued, and prophylactic treatment with itraconazole was initiated. The ulcers resulting from necrotizing fasciitis were treated conservatively using trafermin and alprostadil alfadex ointment 0.003 %, and near-complete re-epithelialization occurred, except on the right lower eyelid, right buccal mucosa and perioral area. However, 6 weeks later, pustules/crusts started to form and break down repeatedly, leading to expansion of tissue defects on the face. Direct microscopic examination revealed fungal elements, and fungal culture identified Paecilomyces lilacinus suspicious twice some other day. Based on DNA extraction from the isolated fungus, this fungal strain was identified as Paecilomyces lilacinus. Cyclosporin and itraconazole were discontinued, and treatment with liposomal amphotericin B and a tapering dose of steroids was initiated. Cure was achieved in approximately 2.5 months after treatment initiation, and no relapse has been observed. The most important factor that ultimately contributed to the resolution of fungal infection might have been release of immunosuppression by discontinuing cyclosporin and tapering steroids.

miR-424 levels in hair shaft are increased in psoriatic patients.

Objective diagnostic markers have not been in clinical use for psoriasis. In this study, we investigated the levels of miR-424 in hair roots and hair shafts in psoriatic patients, and evaluated the possibility that miR-424 can be a biomarker of the disease. A single hair root and five pieces of hair shafts (~5 cm in length) were obtained from the non-lesional occiput of each individual of 26 psoriatic patients. Control hair samples were collected from nine normal subjects. Samples from 10 atopic dermatitis patients were also included as the disease control. miR-424 levels were determined by quantitative real-time polymerase chain reaction. Hair shaft miR-424 levels were significantly upregulated only in patients with psoriasis compared with normal controls and those with atopic dermatitis. By receiver-operator curve analysis of hair shaft miR-424 to distinguish psoriatic patients from normal subjects, the area under the curve was 0.77. However, relative miR-424 levels were not correlated with disease activity markers including disease duration, body surface area and Psoriasis Area and Severity Index. Hair root miR-424 was not useful for evaluating both diagnosis and severity of the disease. Our results indicated hair shaft miR-424 levels may be useful as a diagnostic marker of psoriasis.

A case of psoriasis accompanied by arthritis after delivery.

Psoriasis and psoriatic arthritis are chronic inflammatory diseases of the skin and joints, but the relationship between them has not been fully understood. Since the delay of treatment for psoriatic arthritis can result in the severe deformities, it is important to identify the pathological triggers of the arthritis. On the other hand, many reports suggest that the changes of immune balance during pre/postpartum period are associated with the state of autoimmune diseases. Here, we report a female case with psoriasis whose arthritis may be triggered by the delivery. Our report suggests that immune tolerance may diminish in the postpartum period, which may alter the susceptibility to arthritis. Female patients should be followed-up carefully during postpartum period against the development of arthritis.

Upregulation of miR-18a-5p contributes to epidermal necrolysis in severe drug eruptions.

BACKGROUND: Toxic epidermal necrolysis (TEN) is a severe drug-induced cutaneous reaction. Although one of the primary histologic features of TEN is keratinocyte apoptosis, its exact mechanism remains unknown. OBJECTIVES: We investigated the role of microRNAs (miRNAs) in the pathogenesis of severe drug eruptions and evaluated the possibility that miRNA can be a disease marker. METHODS: miRNAs were extracted from tissues and sera of patients. PCR array analyses were performed to identify pathogenic miRNAs. The results were confirmed with quantitative real-time PCR, in situ hybridization, transient transfection of small interfering RNAs or miRNA mimics into cultured keratinocytes, flow cytometry, immunoblotting, luciferase assay, and immunohistochemistry. RESULTS: PCR array analysis and real-time PCR using tissue miRNAs demonstrated that the miR-18a-5p level was increased in the skin of patients with TEN in vivo. Transfection of the miR-18a-5p mimic into keratinocytes in vitro resulted in increased apoptotic cell numbers and caspase-9 activity, which were also increased in the skin of patients with TEN. The miR-18a-5p mimic also downregulated the expression of B-cell lymphoma/leukemia-2-like protein 10 (BCL2L10), an anti-intrinsic apoptotic molecule. A luciferase assay with the BCL2L10 3' untranslated region showed BCL2L10 is directly targeted by miR-18a-5p. The protein and mRNA expressions of BCL2L10 were decreased in the skin of patients with TEN. Transfection with BCL2L10 small interfering RNA induced keratinocyte apoptosis and caspase activity. Furthermore, serum miR-18a-5p levels tended to be increased in patients with TEN and were correlated with areas of skin erythema or erosion in patients with drug eruptions. CONCLUSIONS: Our results indicated that downregulated BCL2L10 caused by miR-18a-5p overexpression mediates intrinsic keratinocyte apoptosis in patients with TEN. Serum miR-18a-5p levels can be a useful disease marker for drug eruptions.

Detection of hair root miR-19a as a novel diagnostic marker for psoriasis.

BACKGROUND: Objective biomarkers that reflect the diagnosis and disease activity have not been in clinical use for psoriasis. OBJECTIVES: We investigated the hair root miR-19a levels, regulatory microRNA of TNF-α, and evaluated the possibility that miR-19a can be a biomarker of psoriasis. MATERIALS AND METHODS: microRNAs were extracted from hair roots of patients with psoriasis (n = 18) and healthy controls (n = 22). Samples from 10 atopic dermatitis patients and 4 dermatomyositis patients were also included as the disease controls. miR-19a levels were determined by quantitative real-time PCR. RESULTS: Hair root levels of miR-19a were significantly up-regulated only in psoriasis compared with normal controls. In characteristics (ROC) curve analysis for hair root miR-19a, to distinguish psoriasis patients from normal subjects, the areas under curve (AUC) was 0.87. Relative miR-19a levels were inversely and significantly correlated with duration between symptom onset and the first visit to the hospital in psoriasis patients. CONCLUSIONS: Our results indicated hair root miR-19a levels are effective as a disease marker.

Increased serum levels of miR-1266 in patients with psoriasis vulgaris.

MicroRNAs (miRNAs) are post-transcriptional regulators that bind to complementary sequences in the 3' UTRs of mRNAs, leading to gene silencing, and their serum levels can be useful biomarkers for diagnosis, prognosis and therapeutic value in various diseases. Although miRNAs are thought to be involved in the pathogenesis of human diseases, little is known about miRNAs in psoriasis. Recently, psoriasis has attracted attention for its characteristics as a Th17 disease; the expression of IL-17 is increased in lesional skin and serum. We hypothesized that miRNAs contribute to the mechanism underlying the overexpression of IL-17. Therefore, serum levels of miR-1266, a putative regulator of IL-17A, in psoriasis patients were determined with the expectation that miR-1266 levels may be decreased in these patients, which may result in induction of IL-17. However, real-time PCR demonstrated that serum miR-1266 levels were considerably higher in psoriasis patients than in healthy control subjects. Furthermore, miR-1266 levels showed weak inverse correlations with Psoriasis Area Severity Index scores and body surface areas of involved skin. Taken together, serum miR-1266 may have potential for a new disease marker. miR-1266 is not likely to regulate IL-17A expression directly, but may be involved in the pathogenesis of psoriasis by regulating other target molecules.

Ultraslow matched-pulse propagation in sodium vapor.

We have observed ultraslow propagation of matched pulses in a parametric amplifying hot sodium vapor. A fractional delay of more than 1 and a gain of 28 have been simultaneously achieved for a probe pulse of width 100 ns, accompanying a conjugate Stokes pulse with similar gain and delay under a strong coupling beam. The results are compared with the preceding work by Boyer et al. [Phys. Rev. Lett. 99, 143601 (2007)].

Parametric oscillation in sodium vapor by using an external cavity.

We report on parametric oscillation in sodium atomic vapor by using an external cavity. Output powers of approximately 56 mW are obtained for both the signal and idler waves with the input coupling power of 290 mW, resulting in a conversion efficiency of 39%. The signal and idler frequencies are either upshifted or downshifted from the coupling frequency by the amount of the Na hyperfine splitting frequency, and the two waves are found to be strongly temporally correlated.