Journal of the Formosan Medical Association

An antibody treats almost all refractory autoimmune diseases: Fact and beyond

Li-Yan Lin, Mei-Hsin Hsu, Kuender D. Yang — 2012-01-11

An antiCD20 monoclonal antibody (rituximab) has been shown to rescue almost all refractory autoimmune diseases. The chimeric antiCD20 antibody is one of the world’s most successfully therapeutic antibodies, with sales of approximately US$5.6 billion in 2009. Rituximab was first approved in 1997 by the US Food and Drug Administration (FDA) for treatment of B cell malignancies, and is now expanded to autoimmune indications, such as lupus nephritis, multiple sclerosis and vasculitis, particularly refractory autoimmune diseases that usually cause fatal outcomes. Autoimmunity is a complex process that involves the interaction of multiple immune cell types. B cells are thought to play a central role in the autoimmune disease serving as precursors to autoantibody-secreting plasma cells. In addition to producing antibodies, B cells are able to present antigen to T cells. Their depletion also results in the removal of antigen-presenting cells, reduced expression of molecules responsible for T cell costimulatory signals, and reduced levels of immune complexes formed between autoreactive antibodies and their antigen.

Rotavirus infection and the current status of rotavirus vaccines

Shou-Chien Chen, Lia-Beng Tan, Li-Min Huang, Kow-Tong Chen — 2012-03-30

Among children, rotaviruses are the most common cause of severe gastroenteritis worldwide and of diarrheal deaths in developing countries. Current vaccines (e.g., Rotarix, GlaxoSmithKline Biologicals; RotaTeq, Merck and Company) effectively reduce rotaviral gastroenteritis, emergency department visits, and hospitalizations. The tremendous burden of rotavirus-related diarrhea in children across the world continues to drive the remarkable pace of vaccine development. This review assesses the global epidemiological and economic burden of rotavirus diseases, summarizes the relevant principles of the development of rotavirus vaccines, and presents data on the efficacy and effectiveness of currently licensed vaccines in both developed and developing countries.

β-catenin expression in areca quid chewing-associated oral squamous cell carcinomas and upregulated by arecoline in human oral epithelial cells

2012-03-22

Background/Purpose: Nuclear localization of β-catenin is known to associate with malignant transformation of many squamous cell carcinomas. The aim of this study was to compare β-catenin expression in normal human oral epithelium and areca quid chewing associated oral squamous cell carcinomas (OSCCs) and further to explore the potential mechanisms that may lead to induce β-catenin expression.Methods: A total of 40 areca quid chewing-associated OSCCs and 10 normal oral tissue biopsy samples without areca quid chewing were analyzed by immunohistochemistry. The oral epithelial cell line GNM cells were challenged with arecoline, a major areca nut alkaloid, by using Western blot analysis. Furthermore, extracellular signal-regulated protein kinase inhibitor PD98059, glutathione precursor N-acetyl-l-cysteine (NAC), tyrosine kinase inhibitor herbimycin-A, p38 inhibitor SB203580, and phosphatidylinositaol 3-kinase inhibitor LY294002 were added to find the possible regulatory mechanisms.Results: β-catenin expression was significantly higher in OSCC specimens than that in normal oral epithelial specimens (p < 0.05). It was demonstrated that normal oral epithelium showed only membranous staining for β-catenin, and membranous staining was lost or reduced with an increase in cytoplasmic/nuclear staining in OSCCs. Arecoline was found to elevate β-catenin expression in a dose-dependent manner (p < 0.05). The addition of PD98059, NAC, herbimycin-A, SB203580, and LY294002 markedly inhibited the arecoline-induced β-catenin expression (p < 0.05).Conclusion: β-catenin expression is significantly upregulated in areca quid chewing-associated OSCC. The localization of β-catenin expression is correlated with the tumor size and clinical stage. In addition, β-catenin expression induced by arecoline is downregulated by PD98059, NAC, herbimycin-A, SB203580, and LY294002.

Impact of increasing alanine aminotransferase levels within normal range on incident diabetes

Chong-Shan Wang, Ting-Tsung Chang, Wei-Jen Yao, Shan-Tair Wang, Pesus Chou — 2012-03-26

Background/Purpose: Abnormal alanine aminotransferase level (ALT) levels might be associated with type 2 diabetes, but whether higher ALT levels within the normal range predict the risk is unknown.Methods: We followed a community-based cohort of 3446 individuals who were ≥35 years old without diabetes and hepatitis B or C in southern Taiwan for 8 years (1997–2004) to study the risk for type 2 diabetes with different normal ALT levels.Results: Among the 337 incident diabetes cases, 16.0% were from those with ALT levels <10 IU/L, 44.5% with ALT levels 10–19 IU/L, 30.0% with ALT levels 20–39 IU/L, and only 9.5% with ALT levels ≥40 IU/L. A cumulative hazard function test showed that the higher the ALT levels, the greater the cumulative incidence rate of diabetes (p < 0.001, log-rank test). A multiple Cox proportional hazards analysis showed that increasing age, lower educational levels, higher body mass index levels (≥25 vs. <25), and higher ALT levels (vs. the reference group, ALT <10 IU/L), from hazard ratio (HR) = 1.8, for ALT = 10–19, HR = 3.7 for ALT = 20–39, to HR = 4.5 for ALT ≥40, were significant factors for developing diabetes (p < 0.001). The hazard ratios of higher ALT levels in the participants without alcohol consumption were similar to or higher than those in the total cohort.Conclusion: Higher ALT levels, even within the normal range, are strong predictors of type 2 diabetes independently of body mass index levels with a dose–response relationship.

Reduction of cystometric bladder capacity and bladder compliance with time in patients with end-stage renal disease

Jing-Liang Chen, Ming-Che Lee, Hann-Chorng Kuo — 2012-03-26

Background/Purpose: Reduced bladder capacity and compliance in patients with end-stage renal disease (ESRD) may affect storage and voiding function after kidney transplantation. This study evaluated the bladder capacity, compliance, and lower urinary tract dysfunction in ESRD patients with duration after dialysis and anuria.Materials and Methods: Adults with ESRD on kidney transplantation waiting list were consecutively enrolled. The survey items included videourodynamic study (VUDS), renal ultrasound, and cystoscopy. The analytical variables assessed included the duration of dialysis, the duration of anuria, cystometric bladder capacity and bladder compliance, voiding phases in VUDS, and cystoscopic findings.Results: A total of 62 patients with a mean dialysis duration of 58.9 ± 6.3 months were enrolled. The mean cystometric bladder capacity was 178 ± 14 mL and decreased significantly with duration of dialysis (p < 0.001). Anuria was diagnosed in 26 patients, and the mean cystometric bladder capacity decreased significantly with the duration of anuria (p = 0.002). Among the 26 patients with anuria, 16 had a poor bladder compliance. VUDS revealed abnormal storage function in 44 (71.0%) patients and bladder outlet obstruction due to bladder neck dysfunction or urethral narrowing in the voiding phase in 32 (51.6%). Abnormal cystoscopic findings were also noted in 30 (48.4%) patients.Conclusion: Cystometric bladder capacity and bladder compliance decreased with longer duration of dialysis, and the presence of anuria contributed to further decreases in cystometric bladder capacity and bladder compliance. More than two-thirds of patients with ESRD had abnormal findings on VUDS.

Comparison of oral health between inpatients with schizophrenia and disabled people or the general population

Kuan-Yu Chu, Nan-Ping Yang, Pesus Chou, Hsien-Jane Chiu, Lin-Yang Chi — 2012-03-19

Background/Purpose: There is little comparative research evidence to support the claim that there is disparity in dental care between inpatients with schizophrenia and the disabled people or the general population. This study aimed to investigate whether schizophrenia inpatients had poorer dental care and worse oral health than the disabled people and the general population, respectively.Methods: An oral health survey was conducted in a specific-psychiatric long-term care institution in Taiwan in 2006. The results of this survey were compared with the findings of oral health investigations of the disabled people or the general population in Taiwan using proportion test and t-test.Results: This study used decayed, missing, and filled teeth index (DMFT) to describe the condition of dental caries. Compared with the disabled people, schizophrenia inpatients aged 19 to 44 years had a lower subjects' filling rate of DMFT index (FI) and a higher caries experience, but schizophrenia inpatients aged 45 or more had a lower mean number of DMFT. Compared with the general population, schizophrenia inpatients had higher caries experience, mean number of DMFT, percentage edentulous, and community periodontal index and lower FI and number of remaining tooth among various gender or age groups.Conclusion: In Taiwan, inpatients with schizophrenia have a lower FI than the disabled people and a worse overall oral health status than the general population.

Clinical manifestations and outcomes of pediatric chronic neutropenia

2012-03-19

Background/Purpose: Neutropenia is a decrease in the number of circulating neutrophils. When neutropenia persists for more than 3 months, it becomes chronic. A heterogeneous group of diseases in children can cause chronic neutropenia. The aim of the present study was to categorize the diseases and present their clinical manifestations, treatment, and outcomes.Methods: Medical charts of patients with pediatric chronic neutropenia from the last 21 years (1988–2008) were reviewed in a tertiary referral center.Results: Twenty-nine patients were documented during the study period: seven with congenital neutropenia syndromes (CNSs), seven with autoimmune neutropenia (AIN), and 15 with chronic idiopathic neutropenia (CIN). Three CNS patients had severe chronic neutropenia, one had the Chediak–Higashi syndrome, one had the hyper-IgM syndrome, one had the glycogen storage disease type Ib, and one had the Barth syndrome. CNS patients had severe neutropenia early with frequent infections causing high morbidity and mortality. CNS patients usually required prophylactic antibiotics, granulocyte colony-stimulating factor therapies, or umbilical cord blood transplantations to improve or correct clinical conditions. However, most AIN and CIN patients later recovered spontaneously and did not require granulocyte colony-stimulating factor therapy. The mean absolute neutrophil count at onset, the mean onset age of neutropenia, and the mean duration of neutropenia of the two groups of patients did not significantly differ. Some AIN patients had anemia, and some CIN patients had anemia and/or thrombocytopenia.Conclusion: It is difficult and risky to draw any conclusion from such a small-scale study; however, we believe that promptly diagnosing underlying diseases and administering appropriate disease-oriented therapy would be crucial for the treatment of patients with chronic neutropenia, particularly with regard to CNSs.

Hepatosplenic actinomycosis in an immunocompetent patient

2012-04-09

Hepatosplenic abscess caused by Actinomyces is rare and often misdiagnosed as malignancy. Herein, we report a case of hepatosplenic actinomycosis in a 37-year-old immunocompetent man with a 2-month clinical history of intermittent fever and upper left abdominal pain. Physical examination revealed a mildly ill-appearing man with a low-grade fever (38°C) and upper left quadrant abdominal tenderness. Abdominal sonographic examination showed the presence of a 6.3 cm × 6.5 cm heterogeneous abscess with a hypoechoic center and honeycomb appearance in an enlarged spleen (8 cm × 5 cm). Computerized tomography of the abdomen revealed a multiloculated splenic lesion, and laparotomy showed multiple hepatic nodules and a splenic abscess. Histopathological examination of the biopsy revealed filamentous branching bacilli and sulfur granules in the hepatosplenic abscess. The patient successfully underwent splenectomy accompanied by intravenous and oral penicillin treatment. Proper and prompt diagnosis of hepatosplenic actinomycosis is important because the therapeutic plan and prognosis of this pathogen are quite different from other microorganisms and malignancies.

Congenital toxoplasmosis in a neonate with significant neurologic manifestations

Ya-Cheng Chuang, Jia-Yuh Chen, Dar-Der Ji, Pen-Hua Su — 2012-03-05

Congenital toxoplasmosis is a major cause of premature delivery and neonatal illness. Here we report a rare case of congenital toxoplasmosis with significant brain tissue loss to highlight the potential threat of congenital toxoplasmosis to neonates.

Infections due to different genospecies of the Acinetobacter calcoaceticus-A baumannii complex

Chih-Cheng Lai, Yi-Chieh Lee, Po-Ren Hsueh — 2012-03-19

We read with great interest the article by Chang et al in the December issue of the Journal of the Formosan Medical Association. In that report, the authors retrospectively investigated 180 adults with ventilator-associated pneumonia (VAP) caused by Acinetobacter baumannii. Of the 180 A baumannii isolates, 87 (48.3%) were susceptible to imipenem. The authors also reported several significant differences in terms of score on the Charlson Comorbidity Index, site of infection, white blood cell count, and in-hospital mortality rate between patients with VAP caused by imipenem-resistant A baumannii and patients with VAP caused by imipenem-susceptible A baumannii. Their findings are interesting, however, no molecular methods were used to identify isolates of Acinetobacter at the genospecies level. In addition, the authors did not investigate the clinical association between different A baumannii genospecies and the development of VAP.

Corrigendum to “Immune defects in active mycobacterial diseases in patients with primary immunodeficiency diseases (PIDs)”

2012-04-01

The section on page 753 under the heading “Narrow predisposition to mycobacterial diseases” is corrected as follows: Here, we use the comprehensive definition of MSMD as described by Filipe-Santos et al, and with their permission:10 MSMD (MIM 209950)56 is a rare congenital syndrome that was probably first described in 1951 in an otherwise healthy child with disseminated disease caused by BCG vaccine.57 It is defined by severe clinical disease, either disseminated or localized and recurrent, caused by weakly virulent mycobacterial species, such as BCG vaccines and nontuberculous, environmental mycobacteria (EM) in otherwise healthy individuals.2,3,58–60 Understandably, patients with MSMD are also susceptible to the more virulent species, Mycobacterium tuberculosis.5,61–64 Severe disease caused by nontyphoidal and, to a lesser extent, typhoidal Salmonella serotypes is also common, observed in nearly half of the reported cases, including patients who did not have any mycobacterial disease before the diagnosis of salmonellosis, or even at last follow-up.2,3,65 The title “Mendelian susceptibility to mycobacterial disease” is therefore misleading, and it may be more accurate to refer to the underlying genetic defects, namely inborn errors of the IL-12/23-IFN-γ circuit. Other infectious diseases have rarely been reported in these patients, and have mostly involved pathogens phylogenetically (e.g., Nocardia) or pathologically (e.g., Paracoccidioidomyces) related to mycobacteria, suggesting that these infections were not coincidental.