JPN Guidelines for the management of acute pancreatitis: medical management of acute pancreatitis

The basic principles of the initial management of acute pancreatitis are adequate monitoring of vital signs, fluid replacement, correction of any electrolyte imbalance, nutritional support, and the prevention of local and systemic complications. Patients with severe acute pancreatitis should be transferred to a medical facility where adequate monitoring and intensive medical care are available. Strict cardiovascular and respiratory monitoring is mandatory for maintaining the cardiopulmonary system in patients with severe acute pancreatitis. Maximum fluid replacement is needed to stabilize the cardiovascular system. Prophylactic antibiotic administration is recommended to prevent infectious complications in patients with necrotizing pancreatitis. Although the efficacy of the intravenous administration of protease inhibitors is still a matter of controversy, there is a consensus in Japan that a large dose of a synthetic protease inhibitor should be given to patients with severe acute pancreatitis in order to prevent organ failure and other complications. Enteral feeding is superior to parenteral nutrition when it comes to the nutritional support of patients with severe acute pancreatitis. The JPN Guidelines recommend, as optional measures, blood purification therapy and continuous regional arterial infusion of a protease inhibitor and antibiotics, depending on the patient’s condition.     

Plasma noradrenaline as an indicator of functional state in hearts with mitral stenosis: The influence of acutely reduced left atrial pressure by balloon mitral commissurotomy

Summary To investigate the mechanism in which plasma noradrenaline concentration (pNA) is elevated in heart failure, the effect of balloon mitral valvulo-plasty was used as a model of acute manipulation of the left atrial pressure reduction in ten patients with mitral stenosis. Gorlin mitral valve area and pNA were correlated with New York Heart Association functional class and found to have a significant exponential inverse relationship with each other ([pNA, pg/ml] = 198.9 × [mitral valve area, cm²]^–0.696;P = 0.003). Elevated pNA could be partially explained by a reduced cardiac index (CI) ([pNA, pg/ml] = 403.4 × [CI, l/min/m²]^–0.889;P = 0.027;r = 0.495), especially in severely failed hearts, but not by pulmonary capillary wedge pressure (PCWP). However, the percent changes (%) of variables early after balloon valvulo-plasty exhibited aparadoxical contrast; % pNA showing a clear negative exponential correlation with % PCWP ([% pNA] = 436.0 × [% PCWP + 80]^–0.679 – 80;P = 0.021), but not with % CI. These results suggest that pNA should be considered an indicator of cardiac functional class in mitral stenosis. PNA is modulated by both cardiac index and pulmonary capillary pressure, but in different ways.     

A new organotypic culture of adipose tissue fragments maintains viable mature adipocytes for a long term, together with development of immature adipocytes and mesenchymal stem cell-like cells

Adipose tissue that consists of mature and immature adipocytes is suggested to contain mesenchymal stem cells (MSCs), but a culture system for analyzing their cell types within the tissue has not been established. Here we show that three-dimensional collagen gel culture of rat sc adipose tissue fragments maintained viable mature adipocytes for a long term, producing immature adipocytes and MSC-like cells from the fragments, using immunohistochemistry, ELISA, and real time RT-PCR. Bromodeoxyuridine uptake of mature adipocytes was detected. Adiponectin and leptin, and adipocyte-specific genes of adiponectin, leptin, and PPAR-gamma were detected in culture assembly, whereas the lipogenesis factor insulin (20 mU/ml) and inflammation-related agent TNF-alpha (2 nm) increased and decreased, respectively, all of their displays. Both spindle-shaped cell types with oil red O-positive lipid droplets and those with expression of MSC markers (CD105 and CD44) developed around the fragments. The data indicate that adipose tissue-organotypic culture retains unilocular structure, proliferative ability, and some functions of mature adipocytes, generating both immature adipocytes and CD105+/CD44+ MSC-like cells. This suggests that our method will open up a new way for studying both multiple cell types within adipose tissue and the cell-based mechanisms of obesity and metabolic syndrome.     

Association of a genetic polymorphism in ectonucleotide pyrophosphatase/phosphodiesterase 1 with hepatitis C virus infection and hepatitis C virus core antigen levels in subjects in a hyperendemic area of Japan

Background  The clinical course of chronic hepatitis C virus (HCV) infection is strongly associated with insulin resistance and obesity. The K121Q polymorphism in the ectonucleotide pyrophosphatase/phosphodiesterase (ENPP)-1 gene and the rs7566605 genotype located near insulin-induced gene 2 have been shown to be associated with insulin resistance and obesity. This study examined whether the K121Q polymorphism in ENPP1 or the rs7566605 genotype is associated with the clinical course of HCV infection. Methods  The relationships between the clinical characteristics of 469 anti-HCV antibody-seropositive subjects (353 were positive for HCV core antigen or RNA, whereas 116 were negative for HCV RNA) and the polymorphisms were analyzed. Results  No significant differences in body mass index, plasma glucose level, serum insulin level, and other biochemical markers were observed between subgroups of subjects with different genotypes at the K121Q polymorphism or rs7566605. The frequency of the homozygous wild-type genotype at K121Q in HCV carriers, however, was significantly higher than that in subjects who were negative for HCV RNA (84.5% vs. 75.9%; P < 0.05). Moreover, in HCV carriers, HCV core antigen levels in subjects homozygous for the wild-type genotype at K121Q were significantly higher than in heterozygous carriers of K121Q (5358 fmol/l vs. 4002 fmol/l; P = 0.04). In contrast, the rs7566605 genotype was not associated with hepatitis C viremia or with the HCV core antigen level. Conclusions  The K121Q variant of ENPP1 may be associated with hepatitis C viremia and core antigen levels in HCV carriers.     

A case of primary small cell carcinoma of the liver that was treated with chemotherapy

Primary small cell carcinoma (SSC) of the liver is very rare in Japan and only ten cases have been reported worldwide. We report herein the case of a 77-year-old man with primary SCC of the liver. He had a tumor over 10 cm in diameter which was localized in the right lobe of the liver and had invaded the right diaphragm. In laboratory tests, high serum levels of lactate dehydrase and neuron-specific enolase were observed. A biopsy specimen showed that the tumor cells were similar in cytology to a pulmonary SCC. The patient was first treated with carboplatin and etoposide according to the therapy protocol for pulmonary SCC and then with a regimen using etoposid and cisplatinum, resulting in an unfavorable outcome. We discuss the clinical course and therapy of extra-pulmonary SCC and review the literature of the cases previously reported.     

A case of squamous cell carcinoma of the lung with a high titer of proteinase 3 antineutrophil cytoplasmic antibody]

A 57-year-old man who had a history of sinusitis was admitted to Ryugasaki-Saiseikai hospital in April 2002 because of productive cough and bloody sputum. Chest radiographs and CT scans showed mediastinal lymphadenopathy and a solitary mass lesion with an irregular margin and cavity in the left lower lung field. Proteinase 3 antineutrophil cytoplasmic antibody (PR3 ANCA) was positive, and this is a sensitive and specific indicator of Wegener's granulomatosis. The pathological findings from transbronchial biopsy revealed squamous cell carcinoma of the lung, without the presence of vasculitis, accompanied by Wegener's granulomatosis. A partial response was finally obtained after three courses of paclitaxel and carboplatin. The serum level of PR3 ANCA decreased from 142 EU to 16 EU. This case appears to have had parallel time courses of progression of squamous cell carcinoma of the lung and changes in serum PR3 ANCA level. This is of importance in considering the relationship of lung cancer and paraneoplastic vasculitis.     

Radioimmunoimaging of tumors with radioactive antibody against a glycoprotein (GP68) found in developing mouse brain

Summary The in vivo localization of a polyclonal antibody (pAb) against a glycoprotein with a molecular mass of 68 kDa (GP68), which was found in developing mouse brain, was studied in murine tumor models to evaluate potential applications of this antibody for in vivo radioimmunodetection and/or therapy of cancer. The tissue distribution of¹²⁵I-labeled GP68 pAb 3 days after i.V. injection into mice bearing four different kinds of solid tumor revealed a high uptake ratio by adenocarcinoma 755 and Lewis 3LL lung cancer. In contrast, the uptake ratio was low in mice bearing Ehrlich solid tumor and sarcoma-180 (S-180). These uptake ratios accorded well with the in vitro binding activity of this antibody with the tumor cells. In an immunoscintigraphic study, adenocarcinoma 755 was successfully visualized with⁶⁷Ga-labeled GP68 pAb. The results of these biodistribution and in vivo radioimmunoscintigraphic studies suggest that GP68 antibody may be applicable to the diagnosis and/or therapy of cancer.Abbreviations pAb polyclonal antibody - AFP -fetoprotein - GP68 68-kDa glycoprotein     

A case of the limited from of Wegener's granulomatosis without c-ANCA]

A 46-year-old woman was admitted to our hospital because of fever, cough and headache in December 2001. Although she had been treated for nasal obstruction and epistaxis by an otorhinolaryngologist in our hospital since 1996, no accurate diagnosis had been made despite repeated biopsies of the nasal mucosa. A chest CT taken in 1999 showed ground-glass opacities in both upper lobes. On admission, chest radiography and CT showed mass shadows without cavitation, corresponding to the lesions causing the ground-glass opacities. In addition, paranasal sinus MRI showed a deformity of the nasal septum accompanied by a space-occupying lesion, suggesting Wegener's granulomatosis. However, the cytoplasmic-antineutrophil cytoplasmic antibody (c-ANCA) test was negative. To achieve a definitive diagnosis, we performed an open lung biopsy. The specimen, obtained from the right upper lobe, showed the typical findings of a Wegener's granulomatosis including necrotizing vasculitis. Oral prednisolone treatment initiated at 20 mg daily, combined with oral cyclophosphamide at 50 mg daily markedly improved not only the clinical symptoms, but also the mass shadows in the left upper lobe. Patients with the limited form of Wegener's granulomatosis are occasionally seronegative and respond well to therapy. However, the natural course and the changes in chest radiographs are not understood well in such cases. In this paper, we report a case of the limited form of Wegener's granulomatosis that progressed slowly over a period of 6 years.