News Article | May 22, 2017
Liver cirrhosis is the 12th leading cause of mortality worldwide and approximately half of those deaths are due to alcohol abuse. Yet apart from alcohol abstinence, there are no specific treatments to reduce the severity of alcohol-associated liver disease. Researchers at University of California San Diego School of Medicine and J. Craig Venter Institute (JCVI) have linked intestinal fungi to increased risk of death for patients with alcohol-related liver disease. They also found that antifungal treatment protects mice from alcohol-related liver disease progression. The study is published May 22 in the Journal of Clinical Investigation. "Not only is this the first study to associate fungi and liver disease," said senior author Bernd Schnabl, MD, associate professor of gastroenterology at UC San Diego School of Medicine, "we might be able to to slow the progression of alcoholic liver disease by manipulating the balance of fungal species living in a patient's intestine." Alcoholism is associated with bacterial overgrowth in the intestines, as well as a shift in the types of bacteria found there, but little was known about the role of intestinal fungi in alcoholic liver disease. In this study, Schnabl and colleagues found that fungi flourished in the intestines of mice with chronic alcohol exposure. In turn, they noted, the fungal overgrowth exacerbated liver disease. Parts of the fungal cell wall, mainly a sugar called beta-glucan, moved through the mouse's intestinal wall into the surrounding body cavity and organs. Once relocated inside the liver, beta-glucan bound certain immune cells and triggered inflammation. Chronic inflammation kills liver cells and ultimately promotes alcoholic liver disease. But the researchers were able to protect mice from alcohol-induced liver disease by treating them with the antifungal compound amphotericin B. Compared to untreated mice, mice with alcohol-related liver disease that received amphotericin B had lower levels of liver injury and fat accumulation. These outcomes were determined by measuring plasma levels of a liver enzyme called alanine aminotransferase (reduced by approximately 55 percent) and levels of liver triglycerides (reduced by approximately 21 percent). In this study, the mice received a type of oral amphotericin B that is not absorbed into the bloodstream. The drug only acts locally in the intestine and thus did not cause systemic side effects. Because it has no effect on systemic fungal infections, oral amphotericin B is not FDA-approved for human use. Intravenous amphotericin B is FDA approved for the treatment of serious fungal infections and it can cause side effects such as stomach, bone, muscle or joint pain and shortness of breath. "This work demonstrates that alcoholic liver disease is exacerbated not only by bacteria, but also by fungi. Therefore, therapeutic strategies that target both need to be translated into clinical practice," said co-author Derrick Fouts, PhD, professor of genomic medicine at JCVI. "This study suggests a greater role of fungi in modulating the human microbiome than previously appreciated." The team also compared fungi in the stool of eight healthy people and 20 people with chronic alcohol abuse and various stages of liver disease. They found that the healthy people had a richer diversity of fungi living in their intestines, as compared to alcohol-dependent patients. Instead, alcohol-dependent patients at all stages of liver disease had dramatic overgrowths of one fungal type in particular -- Candida, which includes the species that causes yeast infections. In addition, Schnabl's team found a correlation between fungi and disease severity in a separate group of 27 patients with alcohol-related liver disease: The higher the exposure to fungi, as measured by a person's level of antibodies that recognize them, the higher the risk of death. Fourteen patients had high fungi levels and 13 were classified as low. After five years, 77 percent of the low-fungi group survived, compared to 36 percent of the high-fungi group. Schnabl cautioned that this human study is just proof-of-concept in a relatively small number of patients. In addition, he said it might not be the changes in fungal populations that cause progression of alcoholic liver disease. Rather, it could be the overgrowth of intestinal fungi in combination with leaky intestinal walls -- a known result of alcohol abuse -- that trigger chronic inflammatory responses in the liver. Further studies are needed to determine if a single fungal species contributes to liver disease progression more than others. "Since it was so effective in mice, we are interested in testing amphotericin B in patients with alcohol-related liver disease -- a population in urgent need of new therapeutics," Schnabl said. Co-authors of this study include: An-Ming Yang, UC San Diego and En Chu Kong Hospital, Taiwan; Tatsuo Inamine, UC San Diego and Nagasaki University; Katrin Hochrath, Peng Chen, Sena Bluemel, Phillipp Hartmann, Jun Xu, Yukinori Koyama, Tatiana Kisseleva, Hal M. Hoffman, UC San Diego; Lirui Wang, Cristina Llorente, Samuel B. Ho, UC San Diego and VA San Diego Healthcare System; Manolito G. Torralba, Kelvin Moncera, Karen Beeri, J. Craig Venter Institute; Chien-Sheng Chen, National Central University, Taiwan; Kim Freese, Claus Hellerbrand, Friedrich-Alexander University Erlangen- Nürnberg; Serene M.L. Lee, Hospital of the LMU Munich; Wajahat Z. Mehal, Guadalupe Garcia-Tsao, Yale University and VA-CT Healthcare System; Ece A. Mutlu, Ali Keshavarzian, Rush University Medical Center; Gordon D. Brown, University of Aberdeen; Ramon Bataller, University of North Carolina at Chapel Hill; and Peter Stärkel, St. Luc University Hospital, Université Catholique de Louvain, Brussels.
Wen L.-L.,En Chu Kong Hospital |
Lin L.-Y.,En Chu Kong Hospital |
Lin L.-Y.,National Taiwan University Hospital |
Su T.-C.,National Taiwan University Hospital |
And 4 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2013
Context: Perfluorinated chemicals (PFCs) have been widely used in a variety of products worldwide for years. The relationship between serum PFCs and thyroid function has never been addressed in a nationally representative survey. Objectives: The study examined the association between serum PFCs and thyroid function in the general U.S. population. Design and Participants: We selected 1181 subjects (aged 20 years) from a National Health and NutritionExaminationSurvey(NHANES) in2007through2008and2009through2010todeterminethe relationship between serum PFCs and thyroid function. Data were adjusted for confounding variables. Results: The geometricmeansand95%confidence interval (CI) concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate, perfluorononanoic acid, and perfluorohexane sulfonate (PFHxS) were 4.15 (4.02- 4.29), 14.2 (13.59 -14.86), 1.54 (1.48 -1.59), and 2.00 (1.89 -2.11) ng/mL, respectively. After weighting for sampling strategy, we determined a 1-U increase in natural log-serumPFOAincreased serum total T3 concentration by 6.628 ng/dL (95% CI0.545-12.712, P .035) in women. A 1-U increase in natural log-PFHxS was associated with an increase of total T4 by 0.26 g/mL (95% CI 0.108-0.413, P .002) and total T3 by 4.074 ng/dL (95% CI 2.232-5.916, P.001) inwomenanda decrease of natural log-free T4 by 0.016 (ng/dL)(95%CI0.029 to 0.003, P .019) in men. Conclusion: Higher serum concentrations of PFOA and PFHxS are associated with total T3, total T4, and free T4 in the U.S. general population. More studies are warranted to clarify the causal relationship between PFCs and thyroid function. Copyright © 2013 by The Endocrine Society.
Hsu C.-J.,En Chu Kong Hospital |
Weng W.-C.,National Taiwan University Hospital |
Peng S.S.-F.,National Taiwan University Hospital |
Lee W.-T.,National Taiwan University Hospital
Stroke | Year: 2014
BACKGROUND AND PURPOSE - : Early-onset seizures are common in children with arterial ischemic stroke, but the clinical features and effects on the outcome of early-onset seizures have been less studied in children. METHODS - : Children aged 1 month to 18 years presenting with first-time and image-confirmed arterial ischemic stroke were identified for analysis. RESULTS - : A total of 78 survivors of arterial ischemic stroke were enrolled. Twenty (25.6%) had early-onset seizures, and 90% were initial presentation. Younger children (mean, 3.4±3.9 versus 9.0±6.2 years; P<0.001) and cortical involvement (5% versus 63.8%; P=0.01) are more likely to have early-onset seizures. Thirteen of 20 survivors with early-onset seizures had late-onset seizures after the acute stage, and 12 of them were diagnosed as poststroke epilepsy. CONCLUSIONS - : Early-onset seizures occurred in 25.6% of children with arterial ischemic stroke. Younger age and cortical involvement were risk factors for early-onset seizures. Sixty-five percent of children with early-onset seizures had late-onset seizures after the acute stage. © 2014 American Heart Association, Inc.
Fan L.-Y.,En Chu Kong Hospital |
Fan L.-Y.,Graduate Institute of Brain and Mind science |
Chiu M.-J.,Graduate Institute of Brain and Mind science |
Chiu M.-J.,Graduate Institute of Psychology |
Chiu M.-J.,National Taiwan University Hospital
Neuropsychiatric Disease and Treatment | Year: 2014
It has been estimated that 35.6 million people globally had dementia in 2010 and the prevalence of dementia has been predicted to double every 20 years. Thus, 115.4 million people may be living with dementia in 2050. Alzheimer's disease (AD) is the leading cause of dementia and is present in 60%-70% of people with dementia. Unfortunately, there are few approved drugs that can alleviate the cognitive or behavioral symptoms of AD dementia. Recent studies have revealed that pathophysiological changes related to AD occur decades before the appearance of clinical symptoms of dementia. This extended preclinical phase of AD provides a critical chance for disease-modifying agents to halt or delay the relentless process of AD. Although several trials targeting various pathological processes are ongoing, the examination of the combined use of different approaches to combat AD seems warranted. In this article, we will review current therapies, future strategies, and ongoing clinical trials for the treatment of AD with a special focus on combination therapies. Furthermore, preventive strategies for cognitively normal subjects in the presymptomatic stages of AD will also be addressed. In this review, we discuss current hypotheses of the disease process. In the decades since the approval of cholinesterase inhibitors, no new drug has ultimately demonstrated clear success in clinical trials. Given the difficulties that have been encountered in attempts to identify a single drug that can treat AD, we must pursue effective multi-target strategies, ie, combination therapies. The combination of cholinesterase inhibitors and memantine is considered well tolerated and safe, and this combination benefits patients with moderate-to-severe AD. In contrast, with the exception of adjuvant therapies of conventional drugs, combinations of different disease-modifying agents with different mechanisms may have promising synergic effects and benefit cognition, behavior, and daily living function.
Sun Y.,En Chu Kong Hospital |
Chang Y.-H.,National Cheng Kung University |
Chen H.-F.,Far Eastern Memorial Hospital |
Chen H.-F.,Fu Jen Catholic University |
And 4 more authors.
Diabetes Care | Year: 2012
OBJECTIVE - We retrospectively assessed the age- and sex-specific incidence and relative risk of Parkinson disease (PD) in Taiwan's diabetic population. RESEARCH DESIGN AND METHODS - Study cohort included 603,416 diabetic patients and 472,188 nondiabetic control subjects. Incidence rate and relative risk of PD (ICD-9-CM 332.0) were evaluated. RESULTS - The incidence of PD was 3.59 and 2.15 per 10,000 person-years for the diabetic and control group, respectively, representing a covariate adjusted hazard ratio (HR) of 1.61 (95% CI 1.56-1.66), which was substantially reduced to 1.37 (1.32-1.41) after adjusting for medical visits. Diabetes was associated with a significantly elevated risk of PD in all sex and age stratifications except in young women, with the highest HR noted for young men aged 21-40 years (2.10 [1.01-4.42]), followed by women aged 41-60 (2.05 [1.82-2.30]) and >60 years (1.65 [1.58-1.73]). CONCLUSIONS - Diabetes is associated with an increased risk of PD onset in a Chinese population, and the relation is stronger in women and younger patients. © 2012 by the American Diabetes Association.
Lu C.-J.,En Chu Kong Hospital |
Sun Y.,En Chu Kong Hospital |
Muo C.-H.,Data Management |
Chen R.-C.,En Chu Kong Hospital |
And 2 more authors.
Cerebrovascular Diseases | Year: 2013
Background: Thiazolidinediones (TZDs) - rosiglitazone and pioglitazone - a class of insulin sensitizer for treating type 2 diabetes, have been reported to exhibit neuroprotective effects in preclinical studies and have good effects in the control of blood sugar for diabetic patients with insulin resistance. However, clinical trials and observational studies have raised the possibility of higher stroke risk in patients treated with rosiglitazone. Whether pioglitazone poses similar stroke risk remains uncertain. Most of the studies on cardiovascular effects of TZDs were based on studies in the USA and Europe. The present study aimed to compare the stroke risk among diabetic patients on TZD to those on non-TZD medications in an Asian population. Methods: The study cohort included 15,981 patients with a diagnosis of diabetes without prior stroke, acute myocardial infarction (AMI) or heart failure who were followed from 2001 to 2010. Patients were classified by their prescriptions into rosiglitazone, pioglitazone and non-TZD groups. The study end points included ischemic and hemorrhagic stroke. In view of the reported association of heart failure and AMI with rosiglitazone, these 2 end points were also included in the present study. Cox hazard proportional models were used to estimate the risk of developing the end points. Likelihood ratio test was used to examine the age-drug interactions. Dose-response effects were evaluated by comparing the incidence rates among patients with different cumulative exposures to TZD. Results: During the 10-year follow-up, the rosiglitazone group showed significantly higher risk of ischemic stroke (multivariate adjusted hazard ratio, HR = 1.39; 95% confidence interval, CI = 1.16-1.66) and heart failure (HR = 1.59; 95% CI = 1.18-2.14) than the non-TZD group. The pioglitazone group did not show significant difference from the non-TZD group in ischemic stroke (HR = 0.97; 95% CI = 0.75-1.26) and heart failure (HR = 0.94; 95% CI = 0.59-1.50). The results also showed a significant dose-dependent effect of higher risk of ischemic stroke with increasing dosage of rosiglitazone, while there was no increased risk at any level of pioglitazone dosage. Conclusions: This population-based cohort study shows that rosiglitazone imposes a higher risk of developing stroke or heart failure in this Asian patient population, suggesting the adverse side effects of rosiglitazone across ethnic boundaries. Pioglitazone, on the other hand, does not increase cardiovascular or stroke risk compared to the non-TZD group among diabetic patients without a history of macrovascular disease. Copyright © 2013 S. Karger AG, Basel.
Chung S.-D.,Far Eastern Memorial Hospital |
Chung S.-D.,Tzu Chi University |
Wang C.-C.,En Chu Kong Hospital |
Kuo H.-C.,Tzu Chi University
Neurourology and Urodynamics | Year: 2014
Aims: To report our early results of augmentation enterocystoplasty (AE) for severe bladder pain associated with chronic ketamine cystitis (KC). Methods: We performed AE for 14 patients with refractory KC-related bladder pain, which is based on the criteria including severe bladder pain, urgency and frequency and/or upper urinary tract damage such as bilateral hydronephrosis, and contracted bladder. Every patient had been treated conservatively with medication or cystoscopic hydrodistention for at least 1 year before they had received surgical intervention. Video-urodynamic studies were obtained before AE and 3-6 months after surgery. Outcome measurements included visual analogue score (VAS) for pain, cystometric bladder capacity (CBC), maximum urinary flow rate (Qmax), post-void residual, and maximal detrusor pressure (Pdet). The patients' general satisfaction with regard to treatment outcome was also assessed by the Patient Perception of Bladder Condition (PPBC). Results: Atotal of 4 men and 10 women underwent this procedure as indicated. The mean age was 26.7 (ranged 20-38) years old and the duration of ketamine abuse was 3.82 years (ranged 2-7). Contracted bladder was noted in all patients, hydronephrosis in nine and vesicoureteral reflux (VUR) in eight. At 3-6 months after AE, VAS was remarkably improved from baseline to the end-point (8.29 ± 1.54 vs. 2.14 ± 1.51, P < 0.0001), CBC increased from 50.9 ± 15.7 to 309.2 ± 58.0 ml (P < 0.0001), Qmax increased from 6.94 ± 3.60 to 15.2 ± 5.51 ml/sec (P < 0.0001) and Pdet reduced from 29.7 ± 16.0 to 17.9 ± 8.2 cmH2O (P = 0.008). All patients reported marked improvement in PPBC from 6.0 to 1.4 ± 0.89 (P < 0.0001). All hydronephrosis disappeared and VUR was resolved in five patients after AE with ureteral reimplantation. Conclusions: This pilot study demonstrated that AE is effective in relieving refractory ketamine-related bladder pain and lower urinary tract symptoms. © 2013 Wiley Periodicals, Inc.
Guo J.-L.,National Taiwan Normal University |
Tsai Y.-Y.,National Taiwan Normal University |
Liao J.-Y.,National Taiwan Normal University |
Tu H.-M.,En Chu Kong Hospital |
Huang C.-M.,National Yang Ming University
International Journal of Geriatric Psychiatry | Year: 2014
ObjectiveThis exploratory meta-analysis aimed to examine and compare the effective interventions to prevent falls among institutionalized/non- institutionalized older adults without cognitive impairment with interventions to prevent falls for older adults with cognitive impairment. DesignA database search identified 111 trials published between January 1992 and August 2012 that evaluated fall-prevention interventions among institutionalized/non- institutionalized older adults with and without cognitive impairment as measured by valid cognition scales. ResultsExercise alone intervention was similar effective on reducing the numbers of falls among older adults without cognitive impairment regardless of setting (non-institutionalized: OR = 0.783, 95% confidence interval (CI) = 0.656-0.936; p = 0.007 institutionalized: OR = 0.799, 95% CI = 0.646-0.988, p = 0.038). Vitamin D/calcium supplementation had a positive effect on the reduction of numbers of falls among non-institutionalized older adults without cognitive impairment (OR = 0.789, 95% CI = 0.631-0.985, p = 0.036), as did home visits and environment modification (OR = 0.751, 95% CI = 0.565-0.998, p = 0.048). Exercise alone, exercise-related multiple interventions, and multifactorial interventions were associated with positive outcomes among both institutionalized and non-institutionalized older adults with cognitive impairment, but studies are limited. ConclusionsSingle exercise interventions can significantly reduce numbers of falls among older adults with and without cognitive impairment in institutional or non-institutional settings. Vitamin D and calcium supplementation, home visits, and environment modification can reduce the risk of falls among older adults in non-institutional settings. Exercise-related multiple interventions and multifactorial interventions may only be effective for preventing falls in older adults with cognitive impairment. Copyright © 2013 John Wiley & Sons, Ltd.
Chen R.-C.,En Chu Kong Hospital
Journal of Nursing | Year: 2015
The duty of medical personnel is to save lives, cure diseases, relieve suffering, and promote health. Medical personnel care for their patients from birth to death. At the end of terminal care, medical personnel should maintain a religious / holistic commitment to their patients to "remove their suffering and provide happiness" as much as possible. Mackay Hospital opened the first hospice in Taiwan in 1990. Financial coverage of hospice care by the National Health Insurance, the enactment of the Hospice Palliative Act, the attention of Hospital Accreditation to hospice care, and the establishment of the system of clinical chaplaincy have all contributed to the development of hospice palliative care in Taiwan. Application of the Taiwan Coma Scale has been shown to decrease the use of futile life sustaining treatments in the ICU. The author hopes that nurses may further expand community hospice care services to help facilitate the peaceful dying of terminal patients at home.
Hsu C.-L.,En Chu Kong Hospital |
Chen C.-W.,En Chu Kong Hospital
American Journal of Otolaryngology - Head and Neck Medicine and Surgery | Year: 2011
Most migrated foreign bodies in the neck were removed immediately in patients with persistent symptoms. It is a rare condition that a fish bone was buried for a prolonged time in the tongue with little discomfort. We report a unique case of an ingested fish bone lodged in the tongue for 16 months until infection ensued. Ludwig angina was considered first because the patient had fever, odynophagia, swelling of the tongue, and mouth floor. The fish bone buried in the tongue was incidentally found on the computed tomography scan and successfully removed by surgical exploration. Although dental infection is the most common underlying cause in Ludwig angina, embedded foreign body should be considered as one of the pathogenesis. On the other hand, computed tomography scan can be useful in identifying extraluminal migration of fish bones in the neck. © 2011 Elsevier Inc.