Telangiectatic pacemaker erythema.
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Aged↗
Biomedical subjects
H C Chiu
Publications and source records attributed to H C Chiu.
The phosphotidyl inositol 3-kinase/Akt signal pathway is involved in interleukin-6-mediated Mcl-1 upregulation and anti-apoptosis activity in basal cell carcinoma cells.
Dysregulation of interleukin-6 has been reported to be associated with various types of tumors, and interleukin-6 plays an important part in regulating apoptosis in many types of cells. Previously, Mcl-1 was shown to be significantly increased in interleukin-6-overexpressed basal cell carcinoma cells and conferred on them anti-apoptotic activity. The aim of this study was to investigate which signaling pathway is involved in the anti-apoptotic effect of interleukin-6 on basal cell carcinoma cells. Here we show that the addition of recombinant 100 ng per ml interleukin-6 to basal cell carcinoma cells induced a 2.3-fold increase in the level of Mcl-1 protein in basal cell carcinoma cells. Transfection with dominant-negative STAT3 (STAT3F) into inter-leukin-6-treated basal cell carcinoma cells caused a decrease of phosphotyrosyl STAT3 but did not alter Mcl-1 protein levels; however, AG490, a Janus tyrosine kinase inhibitor, was capable of inhibiting the interleukin-6-induced elevation of Mcl-1 protein. Next, interleukin-6 stimulation elicited extracellular signal-regulated kinase activation in basal cell carcinoma cells, and the mitogen-activated protein kinase inhibitor, PD98059, could affect this response without affecting the interleukin-6-medi-ated Mcl-1 upregulation. Use of the two phosphotidyl inositol 3-kinase inhibitors, LY294002 and wortmannin, to check whether this pathway is involved in Mcl-1 upregulation by interleukin-6, we found that the phosphotidyl inositol 3-kinase inhibitors completely attenuated the interleukin-6-induced Mcl-1 upregulation. Furthermore, in the interleukin-6-overexpressing basal cell carcinoma cell clone, dominant-negative Akt also significantly reduced the increased level of Mcl-1. Interestingly, Janus tyrosine kinase inhibitor, AG490, treatment strongly blocked the phosphotidyl inositol 3-kinase pathway activation, as evidenced by the decrease in phospho-Akt level. Blockage of phosphotidyl inositol 3-kinase/Akt pathway abolished the interleukin-6-mediated anti-apoptotic activity in ultraviolet B treated cells. Unexpectedly, without ultraviolet B irradiation, STAT3F transfection also induced a significant apoptosis in basal cell carcinoma/interleukin-6 cells. Taken together, our data suggest that both the phosphotidyl inositol 3-kinase/Akt and STAT3 pathways are potentially involved in interleukin-6-mediated cell survival activity in basal cell carcinoma cells; however, the upregulation of the anti-apoptotic Mcl-1 protein by interleukin-6 is mainly through the Janus tyrosine kinase/phosphotidyl inositol 3-kinase/Akt, but not the STAT3 pathway.
Apoptosis↗
Overexpression of interleukin-6 in human basal cell carcinoma cell lines increases anti-apoptotic activity and tumorigenic potency.
Interleukin-6 (IL-6) is a pleiotropic cytokine that is capable of modulating the diverse functions of cells such as acute phase responses and inflammation. Excessive or insufficient production of IL-6 may contribute to certain diseases of the skin. The aim of this study was to investigate the possible role of IL-6 in the tumorigenesis of basal cell carcinoma (BCC). Initially, we transfected IL-6 expression vector, under the control of a CMV promoter, into human BCC cells and successfully obtained IL-6-overexpressing clones (BCC/IL-6-c1 and BCC/IL-6-c2) and a mixture (BCC/IL-6). DNA synthesis assay determined using (3)H-thymidine pulse incorporation revealed that IL-6-expressing BCC cells exhibited a much higher DNA synthesis rate than the neo control or parental BCC cells. We also detected a greater abundance of IL-6-expressing cell colonies formed in soft agar than in the vector control cells. Furthermore, BCC/IL-6 cells, but not vector control cells, were resistant to UV and photodynamic therapy (PDT)-induced apoptosis, as confirmed using DNA fragmentation and morphologic change analyses. Immunoblot analysis showed that Mcl-1, an anti-apoptotic protein, was specifically up-regulated IL-6 transfectants but not in the control cells. Transient transfection of IL-6 transfectants with antisense mcl-1 greatly enhanced their apoptosis frequency by UV treatment. In tumorigenesis assay, IL-6 transfected clones formed tumors in nude mice more rapidly than the control cells. These tumors appeared to be highly vascularized using pathological examination. Supportive of this finding, we found that IL-6 transfected cells expressed elevated levels of two angiogenic factors, cyclooxygenase (Cox)-2 and vascular endothelial growth factor (VEGF). These results suggest that overexpression of IL-6 enhances the tumorigenic activity of BCC cells by both suppressing apoptosis and actively promoting angiogenesis.
Aminolevulinic Acid↗
Hemodynamic effects of the different vascular accesses used for double-filtration plasmapheresis.
Systematic investigations of hemodynamic status during double filtration plasmapheresis (DFP) are rare in the literature. To investigate the hemodynamic effects of the vascular access chosen for DFP, variations in blood pressure (BP) and pulse rate (PR) induced acutely by DFP were prospectively analyzed in 46 myasthenia gravis (MG) patients a standard DFP protocol with isovolumetric saline fluid replacement. BP and PR were monitored at 30-min intervals (baseline, M30, M60, M90, and M120) during the procedures. The patients were randomized into central vein (CV) and peripheral vein (PV) groups based on the vascular access used. Systolic BP (SBP) dropped significantly at M60 (P < 0.05), M90 (P < 0.001), and M120 (P < 0.001) when compared to the baseline level. Symptomatic hypotension was not observed in any of the 46 sessions. SBP values during DFP in the CV group were significantly lower than the PV group's at M60 (93.1 vs. 101.0%, P < 0.05) and marginally lower at M90 (91.2 vs. 97.2%, P = 0.06). There was no significant difference in diastolic BP changes between the two groups. In the CV and PV groups, PR changes during plasmapheresis also differed at M90 (103.4 vs. 94.5%, P < 0.001) and M120 (101.3 vs. 95.0%, P < 0.05). The significantly lower SBP during DFP in the CV group at M60 may be due to the high central vein flow rate and resultant delay in volume replacement. In conclusion, the vascular access selected for DFP plays a role in the pathogenesis of plasmapheresis-related hypotension. Controlling flow rates may help to prevent hypotension.
Adolescent↗
Coagulation abnormalities in serial double-filtration plasmapheresis.
Intensive plasma exchange can transiently alter the hemostatic system. However, the effect of serial double filtration plasmapheresis (DFP) on the hemostatic system has not been adequately described. In this study, we sought to characterize the hemostatic effects of DFP in 32 myasthenia gravis patients who received one course of DFP treatment for five consecutive sessions within 10 days. Platelet count, prothrombin time (PT), partial thromboplastin time (PTT), and serum levels of albumin, globulin, cholesterol, and fibrinogen were measured before and after the course of DFP. Patients were divided into mild hypofibrinogenemia (MH) and severe hypofibrinogenemia (SH) groups based on post-plasmapheresis residual levels of fibrinogen above or below 70 mg/dl. The baseline fibrinogen level was significantly lower in the SH group (P < 0.01). After five sessions of DFP, the fibrinogen level was reduced to below 70 mg/dl in 14 patients (44%). The percentage of excessive prolongation of PT or PTT was significantly higher in the SH group. The SH group also had higher reduction rates of globulin and cholesterol (P < 0.05). Oozing in the punctured site of the central venous catheter occurred in 6 out of 26 patients, with four cases in the MH group and two in the SH group. There was no difference in the overall incidence of bleeding complications between the two groups. Only one episode of clinically overt bleeding occurred during the study after a large-bore femoral catheter was removed soon after the patient had received five consecutive daily treatments. The bleeding stopped after transfusion of 6 units of fresh frozen plasma. In conclusion, despite the obvious reduction of fibrinogen level and the modest decrease in platelet count after an intensive course of DFP treatment, the low incidence of clinically overt bleeding confirmed the safety of DFP.
Adolescent↗
Involvement of nervous system in maternally inherited diabetes and deafness (MIDD) with the A3243G mutation of mitochondrial DNA.
OBJECTIVES: The A3243G mutation of mitochondrial DNA (mtDNA) has been associated with maternally inherited diabetes and deafness (MIDD) in a number of reports; however, the involvement of the nervous system has rarely been mentioned, prompting this exploration of the manifestation of neurological disorders in MIDD cases. MATERIAL AND METHODS: We investigated four generations of a large Taiwanese family in which MIDD is manifest. We conducted a series of clinical examinations, including computed tomography (CT) and magnetic resonance imaging (MRI) of the head, brain 99mTc-HMPAO single photon emission computed tomography (SPECT), cognitive function tests, and nerve conduction velocity (NCV) studies. Blood levels of creatine kinase (CK) and lactate, pathology of muscle biopsy samples and proportions of mutant mtDNA in blood cells, hair follicles, muscle and skin were also analyzed. Mean follow-up period was 4 years. RESULTS: The patients exhibited the clinical features of diabetes mellitus including sensorineural hearing loss, short stature, and/or histories of spontaneous abortion. No stroke-like episodes were reported. Analysis for mtDNA revealed that the A3243G mutation existed in 11 members (6 symptomatic and 5 asymptomatic members) of this MIDD-prone family, with the proportion of mutant mtDNA ranging from 21% to 47% in leukocytes. Head CT revealed diffuse brain atrophy for all 6 (100%) patients examined and bilateral basal ganglia calcification in 4 of 6 (67%) patients. Brain 99mTc-HMPAO SPECT revealed diminished uptake in the bilateral parieto-occipital or occipital regions for all 6 tested patients, cognitive function for these patients was normal. Results of head CT and SPECT were normal in one asymptomatic member of the family. One muscle biopsy revealed abundant ragged-red fibers with modified Gomori-trichrome stain. Muscle-enzyme activity and serum-lactate levels were normal. CONCLUSION: We have demonstrated that a wide spectrum of sub clinical pathologies of the central nervous system and muscle are present for this MIDD-prone family, none of whom developed typical MELAS during the 4-year period of follow-up study.
Adolescent↗
Double filtration plasmapheresis in the treatment of myasthenic crisis--analysis of prognostic factors and efficacy.
OBJECTIVES: To examine the prognostic factors and outcome of myasthenia gravis (MG) patients in crisis with double filtration plasmapheresis (DFP) treatment. MATERIAL AND METHODS: A total of 15 patients experienced 20 episodes of crisis during the study period. Plasmapheresis was carried out using a double filtration METHOD: Demographic information, clinical features of crisis, and associated complications were analyzed. RESULTS: The median duration of crisis was 9 days. Chest infection was the most common precipitant of crisis. Twelve out of the 20 episodes (60%) responded well to DFP and mechanical ventilation was discontinued after the third session of DFP in 8 of them. Three significant predictors for prolonged crisis were shorter intervals between the onset of MG and the first crisis (P=0.04), higher serum bicarbonate levels at baseline (P=0.03) and the thymic pathology of thymoma (P=0.03). CONCLUSION: DFP can ameliorate the profound weakness in crisis and seems to be a rational therapy for patients with myasthenic crisis.
Adolescent↗
Multiple minute parakeratotic keratoses of the hands in a patient with systemic lupus erythematosus.
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Adult↗
Comparison of transcranial color-coded sonography and magnetic resonance angiography in acute ischemic stroke.
BACKGROUND AND PURPOSE: This study was designed to assess the accuracy of transcranial color-coded sonography (TCCS) as compared to magnetic resonance angiography (MRA) for detecting intracranial arterial stenosis in patients with acute cerebral ischemia. METHODS: The authors prospectively identified 120 consecutive patients admitted with acute ischemic stroke and performed both TCCS and MRA with a mean interval of 1 day. TCCS data (sampling depth, peak systolic and end diastolic angle-corrected velocity, mean angle-corrected velocity, and pulsatility index) for middle cerebral arteries (MCAs) were compared to MRA data and classified into 4 grades: normal (grade 1): normal caliber and signal; mild stenosis (grade 2): irregular lumen with reduced signal; severe stenosis (grade 3): absent signal in the stenotic segment (flow gap) and reconstituted distal signal; and possible occlusion (grade 4): absent signal. The cutoffs were chosen to maximize diagnostic accuracy. RESULTS: Interobserver agreement for MRA grading resulted in a weighted-kappa value of 0.776. The rate of poor temporal window was 37% (89/240). Doppler signals were obtained in 135 vessels, and the angle-corrected velocities (peak systolic, end diastolic, mean) were significantly different (P = .001, P = .006, and P < .001) among the MRA grades: grade 1 (100, 47, 68 cm/s), grade 2 (171, 72, 110 cm/s), grade 3 (226, 79, 134 cm/s), grade 4 (61, 26, 39 cm/s). Additionally, an angle-corrected MCA peak systolic velocity > or = 120 cm/s correlates with intracranial stenosis on MRA (grade 2 or worse) with high specificity (90.5%; 95% confidence interval = 78.5%-96.8%) and positive predictive value (93.9%) but relatively low sensitivity (66.7%; 95% confidence interval = 61.2%-69.5%) and negative predictive value (55.1%). CONCLUSION: Elevated MCA velocities on TCCS correlate with intracranial stenosis detected on MRA. An angle-corrected peak systolic velocity > or = 120 cm/s is highly specific for detecting intracranial stenosis as defined by significant MRA abnormality.
Acute Disease↗
Plasmapheresis in the treatment of ataxic sensory neuropathy associated with Sjögren's syndrome.
Sjögren's syndrome (SS) is an important but poorly recognized cause of peripheral neuropathy. Several forms of peripheral nerve dysfunction occur, including trigeminal sensory neuropathy, mononeuropathy multiplex, distal sensorimotor polyneuropathy and pure sensory neuronopathy. The pathological findings vary and the definite treatment is not known. Here we present 4 cases of acute ataxic sensory polyneuropathy with SS, and the experience of treatment with plasmapheresis (PP). The 4 patients were all females; ages ranged from 30 to 58 years. All had prominent loss of kinesthetic and proprioceptive sensation. The course ranged from acute to subacute onset. Patients were treated with 5-9 sessions of PP. Two patients with initiation of treatment within 2 weeks of onset showed dramatic and sustained responses after PP, while the other 2 had no detectable effects. Our experience showed that PP should be considered in patients who present with sensory neuropathy associated with SS, and the treatment should be given as early as possible.
Adult↗
A novel mouse model of lipotoxic cardiomyopathy.
Inherited and acquired cardiomyopathies are associated with marked intracellular lipid accumulation in the heart. To test the hypothesis that mismatch between myocardial fatty acid uptake and utilization leads to the accumulation of cardiotoxic lipid species, and to establish a mouse model of metabolic cardiomyopathy, we generated transgenic mouse lines that overexpress long-chain acyl-CoA synthetase in the heart (MHC-ACS). This protein plays an important role in vectorial fatty acid transport across the plasma membrane. MHC-ACS mice demonstrate cardiac-restricted expression of the transgene and marked cardiac myocyte triglyceride accumulation. Lipid accumulation is associated with initial cardiac hypertrophy, followed by the development of left-ventricular dysfunction and premature death. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining and cytochrome c release in transgenic hearts suggest that cardiac myocyte death occurs, in part, by lipid-induced programmed cell death. Taken together, our data demonstrate that fatty acid uptake/utilization mismatch in the heart leads to accumulation of lipid species toxic to cardiac myocytes. This novel mouse model will provide insight into the role of perturbations in myocardial lipid metabolism in the pathogenesis of inherited and acquired forms of heart failure.
Animals↗
Organization and delivery of long-term care in Taiwan.
Taiwan reached the World Health Organization (WHO) benchmark of 7% aged 65 and over for defining an aging population only as recently as 1993. With this proportion projected to double to 14% by 2020, Taiwan faces a rapid increase in need for long-term care. This article presents an account of the current service delivery system, which is divided between health and social affairs administrations, with a substantial role also taken by the Veteran Administration, and growing provision of facilities that operate outside the government-registered system. While a basic level of both institutional and community care services has developed, they are not organized into an integrated service system. Problems arising from the divisions and overlaps in responsibility are identified in relation to competition for resources, differences in regulation and eligibility, funding arrangements and misallocation of resources, and divergent views about the philosophical basis of long-term care. Other aspects of services fall under each jurisdiction, but there is also some overlap. A case study of Taiwan's second largest city, Kaohsiung City, reports the outcomes of these divisions as a thin spread of a range of services rather than a coordinated service network. Several planning exercises have been undertaken in recent years to address these problems, and although at an early stage of implementation, the outcomes of these plans are seen as shaping the future directions of long-term care in Taiwan.
Aged↗
Does nifedipine aggravate cyclosporin--induced gingival overgrowth? An experiment in rats.
BACKGROUND: Nifedipine (NIF) may aggravate cyclosporin A (CsA)-induced gingival overgrowth because the potentiated gingival overgrowth has been observed in the patients treated with CsA and NIF. The purpose of this study was to evaluate whether NIF could aggravate the CsA-induced gingival overgrowth in a rat model. METHODS: Ninety male Sprague-Dawley rats were divided into 6 groups: the first group received 8 mg/kg of CsA daily by gastric feeding for 6 weeks; the second and third groups received NIF daily at a dosage of 10 or 50 mg/kg; the fourth and fifth groups received CsA (8 mg/kg) and NIF (10 or 50 mg/kg); and the sixth group received solvents as a negative control. Gingival dimensions (including bucco-lingual depth, mesio-distal width, and vertical height) were assessed bi-weekly from impressed stone models of the mandibular incisal region. At the end of the experiment, the animals were sacrificed. Following histopathological procedures, serial horizontal sections were obtained at the base of the central incisal papilla. Two tissue levels were selected for histometric analysis. Level 1 was defined as the point where the lingual gingiva embraced the bucco-lingual midpoint of the roots and the level 2 as the point where the lingual gingiva at the enamel-dentinal junction approximated the bucco-proximal angle of the roots. The bucco-lingual depth and the mesio-distal width of the papilla were recorded on 5 consecutive sections at the 2 levels, respectively. RESULTS: At the 6-week observations, the gingival dimensions (including the depth, width, and height) significantly increased after CsA therapy and the increasing treatment duration; however, only the mesio-distal width increased after NIF therapy. For NIF therapy alone, a positive linear relation was noted by increased NIF treatment dosages in all gingival dimensions at week 6. But, this relationship was not found in the combined therapies. By histometry, tissue dimensions increased following single drug therapy, either CsA or NIF, at both levels. In animals with the combined therapies, the tissue dimensions decreased if the animals received 10 mg NIF, while they rebounded to control levels with the 50 mg dosage. A dose-dependent positive pattern by NIF was noted in tissue dimensions, but the pattern did not occur in animals that received combined therapy. CONCLUSIONS: The gingival dimensions increased after CsA or NIF therapy, although they were more prevalent with CsA. But the augmenting pattern in gingival morphology observed with CsA therapy decreased when the animals received additional NIF. Therefore, we question whether NIF is a critical factor in aggravating the CsA-induced gingival overgrowth.
Animals↗
Summary from the International Society for Apheresis 3rd World Congress Taipei, Taiwan, January 11-14, 2001.
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Blood Component Removal↗
Comparison of official coders versus physician panel in assignment of underlying cause of death.
BACKGROUND AND PURPOSE: In outcome analyses of clinical trials and mortality follow-up studies, the underlying cause of death (UCOD) is commonly assigned either by official coders or by a panel of physicians. We evaluated the validity of UCOD assigned by official coders by comparison with the assignments of a panel of physicians who reviewed the available medical records of the deceased. METHODS: The comparisons focused on deaths occurring from October 1995 through June 1998 in a series of residents in a veterans home. Because of limited resources, only the first 104 deaths that occurred during the study period were included. Agreement rate, sensitivity, specificity, and kappa statistics were calculated to assess the consistency of coder versus physician panel assignment of UCOD by selected main causes of death. For 32 of the 104 deaths, the panel concluded that the information obtained from medical records was insufficient to determine the UCOD, and the following analyses were confined to the other 72 deaths. RESULTS: For the 72 deaths considered by the panel to have sufficient information to determine UCOD, all four physicians agreed on a single UCOD in 50 (69%) cases, while three or four agreed in 66 (92%) cases. A consensus was reached in cases with disagreement. The two procedures completely agreed in 40 (56%) of the deaths. For general category UCOD, the kappa value was high for cancer (0.83) and cardiovascular disease (CVD, 0.73) but only moderate for pulmonary disease (PD, 0.60). When the UCOD assigned by the panel was used as the gold standard, official coders showed relatively low sensitivity for correct determination of UCOD in cases of CVD (0.76) compared with cancer (0.86) and PD (0.80). CONCLUSIONS: Given the high inter-physician consistency and the relatively low sensitivity of official coders in assigning CVD as the UCOD, we conclude that the use of clinical review panels would provide more accurate UCOD assignments for use in outcome analyses in mortality follow-up studies and clinical trials in Taiwan.
Aged↗
Bethlem myopathy in a Taiwanese family.
We report three cases of Bethlem myopathy from three consecutive generations of a Taiwanese family, including one woman aged 70, one man aged 40, and a boy aged 8. The clinical features of the patients included autosomal dominant inheritance, childhood or adolescent onset, mainly proximal and extensor involvement, early diffuse joint contractures, and absence of cardiac involvement. These features fulfilled the diagnostic criteria for Bethlem myopathy. Though the clinical course of the disease was once thought to be benign, our female patient became wheelchair-bound at the age of 53. This suggests that the disease process in Bethlem myopathy is slow but ongoing.
Adult↗
Postoperative 6-month and 1-year evaluation of health-related quality of life in total hip replacement patients.
BACKGROUND AND PURPOSE: During the last decade, health-related quality of life (HRQOL) has been recognized as a principal outcome measure for total hip replacement (THR). However, most THR outcome studies in Taiwan have limited their assessments to the areas of pain relief and physical function. This study examined the effects of THR on quality of life. METHODS: A longitudinal prospective study design was adopted. A total of 76 THR patients were enrolled. Disease specific (Harris Hip Score) and generic measures (SF-36) were determined before and after surgery. Postoperative evaluations were completed at 6 months and 1 year. Patient characteristics and related medical information were derived from chart data. RESULTS: Significant improvement was found in HRQOL. This improvement was maintained at both 6-month and 1-year follow-up. Specifically, the mean Harris Hip Score improved from 44.7 to 88.9 at the 6-month postoperative evaluation, and further improved to 91.3 at the 1-year evaluation. In the SF-36, each domain of health status showed a significant improvement at 6-month and 1-year evaluations (p < 0.05 or p < 0.01). CONCLUSIONS: The results of the Harris Hip Score and the SF-36 showed that THR not only relieved physical pain but also enhanced all aspects of quality of life. In addition to pain relief and improved physical function, improvements in role limitations due to physical or emotional problems were also significant. These findings indicate that a general health survey should be combined with a disease-specific scoring system to assess THR outcome.
Adult↗
Therapeutic apheresis in Taiwan.
From July 1, 1999, to June 30, 2000, the Formosan Blood Purification Society conducted a survey on the current status of therapeutic apheresis (TA) treatments in Taiwan. There were 13 centers with a total of 437 patients, 498 courses, and 2,086 procedures. The most common indication was for neurological disorders (58.4%), which included mainly myasthenia gravis (34.9%) and Guillain-Barré syndrome (18.2%). The other indications were hematological disorders (19.3%), hepatic-pancreatic disorders (12.3%), and rheumatic disorders (7.1%). Seventy-one percent of TA treatments were reported to be effective. Plasma exchange (PE) performed by either centrifugation or the filtration method constituted 55.4% of TA treatments, the double-filtration (DF) method constituted 39.3% of treatments, and cytapheresis constituted 5.3% of treatments. The most common machines used for TA were the Plasauto iQ, the KM 8800, the Hemonetics series, and the Fenwal CS-3000. The overall frequency of complications was 42.2% per course and 12.9% per procedure. Among them, fever, urticaria, and hypotension were the major complications. As compared with the trends of TA treatment in the world, PE still represents the major TA treatment in Taiwan, which should be replaced by DF or more selective adsorptive methods to reduce the PE-related adverse effects.
Blood Component Removal↗