Apparently increased trough levels of tacrolimus caused by acute infantile diarrhea in two infants with biliary atresia after liver transplantation

Two infants with biliary atresia who exhibited three-fold increased trough levels of tacrolimus and required reduced doses during episodes of acute infantile diarrhea within 5 months of liver transplantation are described. The cause of the increase was not explained simply by hemoconcentration as a result of significant loss of extracellular fluid during these episodes. It does highlight an important issue: that of the continuing need to carefully monitor the trough levels of tacrolimus in such infants.     

Acute heart failure and acute renal failure in Kawasaki disease

Acute renal failure and acute heart failure are rare in Kawasaki disease. We experienced two patients with Kawasaki disease who presented acute renal failure and acute heart failure. These two patients gave us an important insight into the understanding of water balance and fluid therapy in Kawasaki disease. One patient showed acute prerenal failure due to fluid exudation from the intravascular to the extravascular space, and subsequent acute heart failure. The other patient showed acute heart failure caused by fluid infusion for the treatment of dehydration. It is suggested that acute renal failure could be caused by a fluid shift from the intravascular to the extravascular space in Kawasaki disease. It is also demonstrated that the reserve of cardiac function could be decreased in patients with Kawasaki disease due to myocarditis even with normal echocardiography and chest X-rays.     

Genetic analysis of hypophosphatasia

A review is presented of the recent advances in: (i) clinical features, (ii) biochemistry and molecular biology of alkaline phosphatase, (iii) genetic defect in hypophosphatasia, and (iv) prenatal diagnosis. Despite the recent progress, the pathogenesis of hypophosphatasia is far from being elucidated. More clinical cases and further characterization of the alkaline phosphatase gene mutations are needed for better understanding of the clinical spectrum of the entity.     

Prevalence of torus palatinus among a group of Japanese elderly

Summary The purpose of this study was to examine the prevalence of torus palatinus (TP) among Japanese elderly and to identify the factors associated with the formation of TP. The subjects were adults aged over 60, who lived independently in the community and attended lectures once a week at the Senior Citizens’ College in Osaka prefecture during 2007 and 2008. A total of 664 subjects, including 294 men and 370 women, were examined, and the mean age was 66·5 ± 4·2 (s.d.). After informed consent was obtained, participants responded to a questionnaire and underwent clinical examination consisting of dental status, temporomandibular symptoms and occlusal force. There were 113 (17·0%) subjects with TP. The prevalence of TP was more frequent in women than in men (24·6% versus 7·5%, P < 0·01). Moreover, there was a significant relationship between the presence of TP and the presence of Torus mandibularis (13·3% versus 25·9%). There was no significant relationship between the prevalence of TP and other factors; diurnal and nocturnal bruxism, occlusal force, occlusal support and temporomandibular diseases symptom. Logistic regression analysis, in which adjustment was made for age and occlusal force, revealed a significant relationship between the presence of TP and gender and the presence of torus mandibularis (TM) (P < 0·001 OR = 3·43, 95%CI = 2·00–5·86; P < 0·001, OR = 2·63, 95%CI = 1·64–4·24, respectively). This study suggests that genetic factors play a more significant role than factors related oromaxillofacial function in the aetiology of TP.     

Electron microscopic finding of eccrine sweat gland epithelial cells in a patient with Krabbe disease

A 13 month old boy was found to have severely reduced β-galactocerebrosidase activity suggesting infantile Krabbe disease. Clinically, the patient showed a progressive neurological deterioration with white-matter disease on radiological study. Axillary skin biopsy was performed to support the diagnosis. On electron microscopy, needle-like inclusions, which are the typical finding seen in the cytoplasm of astrocytes and Schwann cells in the classic infantile form, were present in eccrine sweat gland epithelial cells. This method is useful for diagnosis when nerve biopsy and biochemical analysis are not readily available.     

Genetic factors in lung disease Part II: Lung cancer and angiotensin converting enzyme gene

The recent progress in molecular biology has led to the elucidation of pathogenesis of lung cancer. The development of a lung cancer requires multiple genetic changes, consisting of the activation of oncogenes, including the K-ras and myc genes, and of inactivation of tumour suppressor genes, including the Rb, p53 and CDKN2 genes. Knowing the specific genes undergoing such changes should be useful as biomarkers for the early detection of cells destined to become malignant. Moreover, such genetic changes could be targets of newly designed drugs and gene-based therapy. Although the angiotensin I-converting enzyme was originally discovered in equine plasma, it has been recognized in various organs and cells other than vascular endothelial cells. This enzyme is also known to have wide substrate specificity to many peptides. The definite roles of angiotensin converting enzyme (ACE) in the respiratory system are largely unknown. Recent progress in molecular biology of the ACE, however, gives us a good chance to look over the significance of ACE in respiratory diseases as well as cardiovascular disorders. In this review, we show the recent advances in the basic studies of the ACE and refer to its clinical application.     

Cytomegalovirus infection during immunosuppressive therapy for diffuse parenchymal lung disease

Background and objective: Cytomegalovirus (CMV) infection is a life‐threatening condition in patients with diffuse parenchymal lung diseases (DPLDs), who are receiving immunosuppressive therapy. The aim of this study was to describe the clinical features of CMV infection and to propose a strategy for managing CMV infection in patients with DPLD who are receiving immunosuppressive therapy. Methods: A retrospective longitudinal observational study was performed on 69 patients with DPLDs (39 with acute/subacute onset, 30 with chronic onset) who were receiving immunosuppressive therapy and were positive for CMV pp65 antigen (CMV‐pp65Ag) in peripheral blood leukocytes (PBLs). Results: Clinical CMV disease and subclinical CMV antigenaemia developed in 23 and 46 patients, respectively. The cut‐off level of CMV‐pp65Ag indicating clinical CMV disease, as determined by receiver operator characteristic curve analysis, was 7.5 cells per 5 × 10⁴ PBLs. Multivariate analysis revealed that early CMV infection was associated with acute/subacute onset of underlying DPLD and with respiratory dysfunction at the commencement of immunosuppressive therapy. Multivariate analysis also suggested that the acute/subacute onset of underlying DPLD, a CMV‐pp65Ag titre of >7.5 cells per 5 × 10⁴ PBLs, and C‐reactive protein levels ≥10 mg/L indicated a poor prognosis. Conclusions: We recommend that CMV‐pp65Ag antigenaemia of >7.5 cells per 5 × 10⁴ PBLs in patients with DPLD should be treated with ganciclovir. Patients with lower levels of CMV‐pp65Ag antigenaemia should be closely monitored or treated with ganciclovir if the clinical findings suggest a poor prognosis.