Erratum to: Multicenter Prospective Study on the Safety of Upper Gastrointestinal Endoscopic Procedures in Antithrombotic Drug Users

Digestive Diseases and Sciences -     

Interstitial granulomatous dermatitis? An unusual presentation in the mucosa and periungual skin

Interstitial granulomatous dermatitis (IGD) is a reactive phenomenon accompanying disorders including autoimmune disease, lymphoproliferative disorders and drug reactions. Histologically, IGD shows a granulomatous infiltrate surrounding piecemeal fragmentation of collagen in the diffuse interstitium. IGD presents with linear cords, papules and plaques mainly on the trunk and extremities. Herein, we report a case with peculiar clinical features that were histopathologically consistent with IGD. A 74-year-old man presented with periungual painful erythema, nail deformity of all fingers and labial, penile and anal erosive erythema. Histopathological examination of the lesions showed interface dermatitis and a diffuse interstitial granulomatous infiltrate mainly composed of CD68-positive histiocytes and lymphocytes. Degenerative collagen bundles were also observed in granulomas. C-reactive protein and the white blood cell count were elevated, but further examinations did not reveal systemic inflammatory disorders such as autoimmune disease, lymphoproliferative disorder, inflammatory bowel disease or drug hypersensitivity. The lesions were successfully treated with oral and topical steroids.     

Cutaneous gene delivery

Over the past decade, many approaches to transferring genes into the skin have been investigated. However, most such approaches have been specifically aimed against genodermatosis, and have not produced sufficient results. The goal of such research is to develop a method in which genes are transferred easily, efficiently and stably into keratinocytes, especially into keratinocyte stem cells, and in which the transgene expression persists without a reaction from the host immune response. Although accidental development of cancer has occurred in trials of gene therapy for X-linked severe combined immunodeficiency (X-SCID), resulting in slowing of the progress of this research, the lessons of these setbacks have been applied to further research. Moreover, combined with the techniques acquired from tissue engineering, recent developments in our knowledge about stem cells will lead to new treatments for genodermatoses. The present review summarizes the methods by which therapeutic genes can be transferred into keratinocytes, with discussion of how gene transfer efficiency can be improved, with particular emphasis on disruption of the skin barrier function. It concludes with discussion of the challenges and prospects of keratinocyte gene therapy, in terms of achieving efficient and long-lasting therapeutic effects.     

Role of the Notch ligand Delta1 in embryonic and adult mouse epidermis

The Notch ligand Delta1 (Dll1) is expressed in human interfollicular epidermis (IFE) and regulates differentiation and adhesion of cultured human keratinocytes. However, the consequences of deleting Dll1 in mouse epidermis have not been examined. Here, we report that in embryonic mouse skin Dll1 is expressed by patches of keratinocytes in the basal layer of the IFE and in the dermal papilla and hair bulb. In a Dll1 hypomorph mutant that survives until birth, hair follicles formed normally but proliferation and thickness of the IFE were increased. Deletion of Dll1 using Cre recombinase expressed under the control of the keratin-5 (K5) promoter resulted in a delay in the first postnatal anagen, but subsequent hair cycles were normal. As in the hypomorph, IFE proliferation was stimulated and expression of K10 and K17 was disturbed. Older mice developed tumors with elements of IFE differentiation. Keratinocytes cultured from K5Cre x Dll1(flox/flox) epidermis showed a transient increase in proliferation, with a subsequent decrease in integrin expression and increased terminal differentiation. These results demonstrate that Dll1 contributes to the control of proliferation and differentiation in IFE, whereas Jagged1 regulates hair follicle differentiation.     

Utility of phase contrast MR imaging for assessment of pulmonary flow and pressure estimation in patients with pulmonary hypertension: Comparison with right heart catheterization and echocardiography

Purpose:

To compare the utility of phase contrast MR imaging (PC‐MRI) for assessment of pulmonary flow and pressure estimation with that of right heart catheterization and echocardiography (cardiac US) in patients with pulmonary arterial hypertension (PAH).

Materials and Methods:

Twenty consecutive patients with suspected PAH underwent PC‐MRI, cardiac US, and right heart catheterization. In each patient, PC‐MRI was acquired by cine 2D‐PC method on a 1.5 Tesla scanner, and stroke volume (SV) and pulmonary arterial systolic pressure (PASP) were assessed by using the modified Bernoulli's equation. To evaluate the agreements of SV and PASP among the three methods, correlations and limits of agreement among the three methods were statistically assessed by using the Bland‐Altman's analyses.

Results:

The correlations and limits of agreement for SV and PASP between PC‐MRI and catheterization (r = 0.96, r² = 0.94, 1.1 ± 6.9 mL and r = 0.94, r² = 0.88, ?3.2 ± 14.5 mmHg, respectively) were better than between cardiac US and catheterization (r = 0.01, r² < 0.01, 8.9 ± 42.1 mL and r = 0.86, r² = 0.72, ?5.9 ± 27.7 mmHg, respectively).

Conclusion:

PC‐MRI is more compatible with right heart catheterization than cardiac US in pulmonary flow and pressure estimation. J. Magn. Reson. Imaging 2009;30:973–980. © 2009 Wiley‐Liss, Inc.

     

Advances in the treatment of hepatocellular carcinoma and concomitant esophageal varices

Twenty-four patients with hepatocellular carcinoma (HCC) concomitant with esophageal and/or cardial varices concurrently underwent hepatic resection for HCC and various treatments for varices. All patients had cirrhosis of the liver, and had either blue or white varices with "red color signs" endoscopically. These patients were assigned to two groups. Group A patients simultaneously underwent partial hepatectomy and selective shunt or direct interruption procedures (n = 13). Group B patients underwent hepatic resection and devascularization of the upper half of the stomach and/or preoperative or postoperative endoscopic injection sclerotherapy (n = 11). Seven patients in Group A had a tumor recurrence 4 to 58 months postoperatively, while in Group B, one of 11 patients had a tumor recurrence in the remnant liver. There was one patient in Group A with postoperative rebleeding from esophageal varices, and there was neither variceal bleeding nor variceal recurrence after treatment in Group B. Liver failure was the immediate cause of death in five, including three in-hospital deaths in Group A. Survival rates during the first 5 years in Group A were 75%, 67%, 31%, 21% and 10%, while the four-year survival rate in group B was 100%. In the light of this evidence, the treatment given to Group B is to be preferred.     

An antagonist of platelet-activating factor suppresses endotoxin-induced tumor necrosis factor and mortality in mice pretreated with carrageenan.

We found that carrageenan (CAR), that is, sulfated polygalactose, can enhance both lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF) production and the rate of lethality in mice (M. Ogata, S. Yoshida, M. Kamochi, A. Shigematsu, and Y. Mizuguchi, Infect. Immun. 59:679-683, 1991). It has been reported that platelet-activating factor (PAF) antagonists reduce the rate of mortality from endotoxin shock. However, there are few reports regarding the effect of PAF antagonists on TNF production. The aim of the present study is to examine the effect of TCV-309, a new PAF antagonist, on LPS-induced TNF production and mortality in mice pretreated with CAR. ddY mice (6 to 7 weeks old) were injected intraperitoneally with CAR (5 mg per mouse) and were then divided into two groups: mice treated with a PAF antagonist (TCV-309; Takeda Pharmaceutical Co.) and control mice. The mice treated with PAF antagonist received indicated doses of TCV-309 subcutaneously (s.c.) at 30 min before LPS injection, while the control mice received 1 ml of saline s.c. at the same time. All mice were stimulated by intravenous injection of LPS (50 micrograms per mouse) at 24 h after pretreatment with CAR. At intervals after injection of LPS, serum samples were obtained for a TNF assay in which cytotoxicity to L929 cells was measured. TCV-309 both significantly suppressed LPS-induced TNF production and reduced mortality in a dose-dependent manner. When TCV-309 was administered at 30 min before injection of LPS, the effect of TCV-309 on the suppression of TNF activity was at its peak. Treatment with TCV-309 (990 micrograms per mouse) s.c. significantly improved the survival rate after challenge with LPS compared with the survival rate of control mice. Although the 50% lethal dose of LPS was 15 micrograms per mouse for control mice, it increased to 102 micrograms per mouse for mice that were treated s.c. with TCV-309 (990 micrograms per mouse). Even in vitro, TCV-309 also inhibited LPS-induced TNF production in thioglycolate-elicited macrophages. It was concluded that PAF plays an important role in endotoxin-induced TNF production and mortality.