Coexistence of pemphigus vulgaris and bullous pemphigoid in the upper aerodigestive tract

Pemphigus vulgaris and bullous pemphigoid are autoimmune blistering diseases of the skin and the mucosa characterized by circulating autoantibodies. Coexistence of these lesions is extremely uncommon. We report herein a case of both pemphigus vulgaris and bullous pemphigoid which occurred in the upper aerodigestive tract. The diagnosis was made based on the circulating autoantibodies and direct immunofluorescent studies. The literature on this subject is reviewed.     

Successful Plasmapheresis in the Not-So-Benign Bickerstaff s Brain Stem Encephalitis Associated with Anti-GQ1b Antibody

Abstract: A patient with Bickerstaff s brain stem encephalitis (BBE) associated with anti-GQ_1b antibody developed coma, severe weakness, and respiratory distress. The patient required ventilatory support. After having failed to improve on steroids, she was treated with plasmapheresis. She improved concomitantly with the plasmapheresis treatment and made a complete recovery. BBE associated with anti-GQ_lb antibody is generally considered to be benign, and specific treatments have not been established. The results with this patient suggest that the condition is not always benign, and plasmapheresis may be beneficial in this disorder.     

Long-term oral administration of dipyridamole improves both cardiac and physical status in patients with mild to moderate chronic heart failure: a prospective open-randomized study.

Adenosine is known as an endogenous cardioprotectant. We previously reported that plasma adenosine levels increase in patients with chronic heart failure (CHF), and that a treatment that further elevates plasma adenosine levels may improve the pathophysiology of CHF. Therefore, we performed a prospective, open-randomized clinical trial to determine whether or not exposure to dipyridamole for 1 year improves CHF pathophysiology compared with conventional treatments. The study enrolled 28 patients (mean+/-SEM: 66+/-4 years of age) attending specialized CHF outpatient clinics with New York Heart Association (NYHA) class II or III, no major complications, and stable CHF status during the most recent 6 months under fixed medications. They were randomized into three groups with or without dipyridamole (Control: n=9; 75 mg/day: n=9; 300 mg/day: n=10) in addition to their original medications and were followed up for 1 year. The other drugs were not altered. Among the enrolled patients, 100%, 4%, 100%, and 79% received angiotensin-converting enzyme inhibitors, aldosterone analogue, loop diuretics, and beta-adrenoceptor blocker, respectively. Fifteen patients suffered from dilated cardiomyopathy, and 7/3/3 patients suffered from ischemic/valvular/hypertensive heart diseases, respectively. Mean blood pressure was comparable among the groups. While the baseline conditions were comparable, we found that echocardiographic ejection fraction (p<0.01 vs. baseline, p<0.01 vs. Control), left ventricular systolic diameter (p<0.05, p<0.05), Specific Activity Scale (SAS) score (p<0.05, p<0.01), maximal oxygen consumption (p<0.05, p<0.05) and plasma B-type natriuretic peptide level (p<0.01, p<0.01) were significantly improved in patients with dipyridamole after 1 year, generally in a dose-dependent manner. Therefore, we suggest that an additional administration of dipyridamole further improves CHF pathophysiology.     

A patient with primary biliary cirrhosis complicated with slowly progressive insulin-dependent diabetes mellitus

We report a case of primary biliary cirrhosis (PBC) complicated by slowly progressive insulin-dependent diabetes mellitus (SPIDDM). A 67-year-old woman was diagnosed as having PBC based on clinical manifestations and a positive result of anti-mitochondrial antibody. Furthermore, SPIDDM was diagnosed by her clinical course and a positive result of anti-glutamic acid decarboxylase antibody. Both PBC and SPIDDM are considered to be autoimmune diseases. However, the coexistence of PBC and SPIDDM is extremely rare. Liver cirrhosis sometimes accompanies hyperglycemia. When the etiology of liver cirrhosis is an autoimmune disorder such as PBC, SPIDDM should be considered as a cause of hyperglycemia.     

Autophagic cell death of pancreatic acinar cells in serine protease inhibitor Kazal type 3-deficient mice

BACKGROUND & AIMS: Serine protease inhibitor Kazal type 1 (SPINK1), which is structurally similar to epidermal growth factor, is thought to inhibit trypsin activity and to prevent pancreatitis. Point mutations in the SPINK1 gene seem to predispose humans to pancreatitis; however, the clinical significance of SPINK1 mutations remains controversial. This study aimed to elucidate the role of SPINK1. METHODS: We generated Spink3-deficient (Spink3(-/-)) mice by gene targeting in mouse embryonic stem cells. Embryonic and neonatal pancreases were analyzed morphologically and molecularly. Specific probes were used to show the typical autophagy that occurs during acinar cell death. RESULTS: In Spink3(-/-) mice, the pancreas developed normally up to 15.5 days after coitus. However, autophagic degeneration of acinar cells, but not ductal or islet cells, started from day 16.5 after coitus. Rapid onset of cell death occurred in the pancreas and duodenum within a few days after birth and resulted in death by 14.5 days after birth. There was limited inflammatory cell infiltration and no sign of apoptosis. At 7.5 days after birth, residual ductlike cells in the tubular complexes strongly expressed pancreatic duodenal homeodomain-containing protein 1, a marker of pancreatic stem cells, without any sign of acinar cell regeneration. CONCLUSIONS: The progressive disappearance of acinar cells in Spink3(-/-) mice was due to autophagic cell death and impaired regeneration. Thus, Spink3 has essential roles in the maintenance of integrity and regeneration of acinar cells.