Home sleep study for patients with myasthenia gravis.

OBJECTIVES: The objective of the study was to examine predictors for sleep-disordered breathing (SDB) in patients with myasthenia gravis (MG) using Watch-PAT. MATERIALS AND METHODS: We prospectively studied 58 consecutive patients with MG without respiratory symptoms for a full-night Watch-PAT with concomitant recording of the MG score and acetylcholine receptor antibody concentration and analyzed potential risk factors of SDB. RESULTS: Twenty-four patients (41%) had definitive SDB, which was mild in 12 patients, moderate in six, and severe in six. Assessing risk factors with multivariate models, we found four significant predictors (BMI, age, male gender, and use of azathioprine); BMI was the most powerful predictor. The severity and prevalence of sleep-disordered breathing had no significant association with MG score, myasthenia stage, or seropositivity of acetylcholine receptor antibody. CONCLUSIONS: The prevalence of SDB in myasthenic patients with mild and moderate weakness was high when using the Watch-PAT. Both myasthenia-specific factors (use of azathioprine) and general predictors in terms of BMI, age, and male gender predisposed the development of SDB in patients with myasthenia gravis. Careful screening of patients with myasthenia gravis at risk of SDB using Watch-PAT might improve the quality of sleep and cardiovascular health through proper treatment of underlying SDB.

Risk of diabetes mellitus among patients with myasthenia gravis.

OBJECTIVES: To determine the risk of diabetes mellitus (DM) in patients with myasthenia gravis (MG) in a large cohort representing 99% of the Taiwan population. METHODS: Data from the Taiwan National Health Insurance Database were used to conduct retrospective cohort analyses. The study cohort comprised 1520 patients with MG who were four-fold frequency matched to those without MG by age and sex, and assigned the same index year. Cox proportional hazard regression analysis was conducted to estimate the risk of DM. RESULTS: The MG cohort had a 1.26-fold increased risk of developing DM compared with the comparison cohort (HR=1.26, 95% CI=1.04-1.53). MG patients without corticosteroids use had no increased risk of developing DM (HR=1.05, 95% CI=0.79-1.40), and MG patients with corticosteroids use had a 1.46-fold increased risk of developing DM (HR=1.46, 95%=1.15-1.86). In addition, patients with MG received aggressive treatment, associated thyroid diseases, and male patients had higher risk of DM. CONCLUSION: This population-based retrospective cohort study demonstrates that MG is associated with a high risk of DM, which might be related to the adverse effect of corticosteroid and aggressive therapy.

Curcumin attenuates renal ischemia and reperfusion injury-induced restrictive respiratory insufficiency.

OBJECTIVE: Pulmonary failure, instead of kidney failure, is one of the leading causes of acute kidney injury (AKI)-related death. Volume overload was previously regarded as the primary cause of lung injury, presumably by impaired renal fluid clearance. Recent evidence suggested that proinflammatory cytokines, chemokines, and free radicals released during AKI are playing a crucial role in the lung injury. We aimed to examine the protective efficacy of lung function with curcumin pretreatment. METHODS: AKI was induced by 45 minutes of kidney ischemia (bilateral occlusion of renal pedicles) followed by 3 hours of reperfusion. Rats were divided into 3 groups: sham-operated, kidney ischemia and reperfusion (I/R), and a group with 2 days of oral pretreatment with curcumin (12.5 mg/kg/d) before I/R injury. The pulmonary function test (PFT) was conducted at baseline and after 3 hours of reperfusion, yielding parameters of lung volumes, chord compliance (Cchord), inspiratory resistance (RI), and forced expiratory volume at the first 200 millisecond (FEV200). We also examined levels of protein concentration (PC), methylguanidine (MG), tumor necrosis factor-α (TNF-α), and malondialdehyde (MDA) in the bronchoalveolar lavage (BAL). RESULTS: Ischemic AKI-induced restrictive lung disease was demonstrated by the decreased Cchord, total lung capacitance (TLC), and FEV200, in addition to the increased lavage PCBAL, MG, TNF-α, and MDA level. Curcumin pretreatment ameliorated lung function impairment and alveolar vascular protein leak and attenuated lung inflammation. CONCLUSIONS: The protective effect of curcumin pretreatment against restrictive lung disease is most likely associated with decreasing hydroxyl radical, lipid peroxidation, and inflammation in the lungs and improving alveolar vascular permeability.

High-voltage thin-film GaN LEDs fabricated on ceramic substrates: the alleviated droop effect at 670 W/cm(2).

High-voltage thin-film GaN LEDs with the emission wavelength of 455 nm were fabricated on ceramic substrates (230 W/m · K). The high-voltage operation was achieved by three cascaded sub-LEDs with dielectric passivation and metal bridges conformally deposited on the side walls. Under the driving power of 670 W/cm(2), the high-voltage LEDs exhibit much alleviated efficiency droop and the operative temperature below 80 °C. The excellent performances were attributed to the improved current spreading within each sub-LED and the superior heat sinking of the ceramic substrate.

Clinical features of myasthenia gravis patients with autoimmune thyroid disease in Taiwan.

OBJECTIVES: The aim of this study was to analyze the prevalence and clinical features of myasthenia gravis (MG) patients with and without autoimmune thyroid disease (ATD). MATERIALS AND METHODS: Between 1999 and 2009, we reviewed a total of 1482 patients with MG. On the basis of thyroid evaluations, as well as neurological, clinical, and serological findings, the patients were divided into group A (MG patients with ATD) or group B (MG patients without ATD). The patients were categorized as having ocular myasthenia when symptoms restricted to the ocular system were present for 2 years or more. RESULTS: Of the 1482 MG patients, 121 (8.2%) patients were classified into group A. Graves' disease was more predominant (5.7%) than Hashimoto's thyroiditis (1.1%) and antibody-positive thyroid disease (1.4%). MG patients with ATD were predominantly female, were younger at the onset of MG symptoms, had a higher frequency of mild MG (ocular and mild generalized MG) and thymic hyperplasia, and had lower levels of seropositive anti-acetylcholine receptor antibodies. Compared to patients without thyroid eye disease, ATD patients with thyroid eye disease had a higher frequency of ocular MG. CONCLUSIONS: This is the largest review of the clinical features of MG patients with and without ATD to date. We found that compared to ocular MG, mild MG is more commonly associated with ATD. Furthermore, we observed that thymic hyperplasia is more common in MG patients with ATD, while thymoma is more common in MG patients without ATD.

Liver reperfusion-induced decrease in dynamic compliance and increase in airway resistance are ameliorated by preischemic treatment with melatonin through scavenging hydroxyl radicals in rat lungs.

OBJECTIVES: Acute lung injury is frequently observed in patients subsequent to liver ischemia and reperfusion (I/R) injury. However, the changes in pulmonary function, eg, lung dynamic compliance (C(dyn)) and airway resistance (RI), are not well understood. We sought to study the alternations in pulmonary function during liver I/R and the protective effects of preischemic treatment with melatonin. METHODS: Animals were divided into 3 groups: sham-operated, liver I/R, and intraperitoneal (i.p.) pretreatment with melatonin (15 mg/kg). Liver I/R was performed by clamping the hepatic artery and portal vein for 30 minutes followed by releasing for 2 hours. The C(dyn) and RI were studied at baseline and at 2 hours of reperfusion. We assessed the level of pulmonary hydroxyl radicals by methylguanidine (MG) content in the bronchoalveolar lavage fluid (BALF) as well as the liver damage using plasma levels of lactate dehydrogenase (LDH), glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT). RESULTS: After 2 hours of liver reperfusion, C(dyn) was reduced by ∼25%, while RI increased by ∼16% (P < .05). The decreased C(dyn) and increased RI were markedly attenuated by melatonin pretreatment (P < .05). Melatonin pretreatment also protected the liver against I/R injury (P < .05), as seen by reduced LDH, GOT and GPT along with markedly reduced hydroxyl radicals (P < .05). CONCLUSIONS: Preischemic treatment with melatonin protected lung function against damage by liver I/R. The improvement in lung function was strongly associated with decreased hydroxyl radicals in the lungs.

Inhibition of peripheral blood natural killer cell cytotoxicity in patients with myasthenia gravis treated with plasmapheresis.

BACKGROUND AND PURPOSE: Myasthenia gravis (MG) is an autoimmune disorder that may involve natural killer (NK) cells. Although NK cells are part of the innate immune system, they also influence adaptive immune responses. Double-filtration plasmapheresis (DFP) is an effective therapy for MG crisis. Thus, we examined the effects of DFP on the cytotoxicity of NK cells. METHODS: A total of 20 patients with MG and 16 healthy controls were recruited for the study. Ficoll-Paque-isolated peripheral blood mononuclear cells (PBMCs) and K562 cells were used as the effector and target cells, respectively. NK cell cytotoxicity was analyzed using flow cytometry immediately before and after DFP and upon course completion. RESULTS: Double-filtration plasmapheresis treatment decreased significantly the NK cell cytotoxicity in patients with MG, especially in good responders, those who were positive for acetylcholine receptor (AChR) antibodies, and those receiving immunosuppressants. CONCLUSIONS: The decrease in NK cell cytotoxicity after DFP and the decline of AChR antibody titer were observed in good responders indicating that this could benefit patients with MG.

Changes in serum cytokine levels during plasmapheresis in patients with myasthenia gravis.

BACKGROUND: The effect of plasmapheresis on cytokine levels in patients with myasthenia gravis (MG) has not been well established. METHODS: Cytokine levels were measured in 19 patients with MG before and after treatment with one course of double-filtration plasmapheresis (DFP). The control group comprised 6 age- and sex-matched healthy volunteers. RESULTS: At baseline, patients with MG had higher levels of IL-10 than normal controls. The levels of IL-2, IL-4, IL-5, and tumor necrosis factor-alpha were almost undetectable in MG patients. After a single session of DFP treatment, IL-10 levels were significantly increased. After three sessions, IL-10 levels were still higher than those at baseline. Elevated IL-10 level was significantly associated with use of immunosuppressant drugs, thymectomy, and good response to DFP treatment. CONCLUSIONS: Interleukin-10 might play a crucial role in the pathogenesis and perpetuation of MG.

Lower urinary tract symptoms in female patients with rheumatoid arthritis.

OBJECTIVE: Patients with autoimmune diseases such as systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) are associated with an increased severity of lower urinary tract symptoms (LUTS). Recent surveys also reveal that rheumatoid arthritis (RA) is prevalent in patients with interstitial cystitis (IC). Therefore, we have investigated LUTS in patients with RA. METHODS: A total of 198 female patients with RA, aged 40 years or older, from the rheumatology outpatient clinic completed this prospective study. The American Urological Association Symptom Index (AUASI) score was used to assess the severity of LUTS and the O'Leary-Sant Symptom Index (ICSI) was used to evaluate IC-like urinary symptoms in these patients, which were compared to those of 679 age-matched controls. The possible associations of clinical parameters with LUTS were also explored. RESULTS: The Mean AUASI score and the percentage of individuals reporting severe LUTS (AUASI score > or = 20) or IC-like urinary symptoms (ICSI score > or = 12) showed no significant differences between the RA and control groups. However, in the RA group multivariate regression analyses identified patients with secondary SS (n = 21) to be associated with a significantly higher AUASI score (p = 0.007) and a higher percentage of severe LUTS (p = 0.02); these were also significantly higher than those of the control group (p = 0.02 and p = 0.01, respectively). CONCLUSION: Patients with RA have similar urinary complaints when compared to controls. However, those with secondary SS have a greater severity of LUTS, a finding similar to that observed in patients with primary SS.

Predicting the course of myasthenic weakness following double filtration plasmapheresis.

OBJECTIVE: To evaluate the clinical course of patients with myasthenia gravis (MG) up to 3 months after double filtration plasmapheresis (DFP). MATERIAL AND METHODS: We recorded the MG score and measured the level of acetylcholine receptor antibody (AchRAb) at baseline and day 1 (D1), week 1 (W1), 1 month (M1), 2 (M2) and 3 months (M3) after DFP in 16 MG patients. Based on the difference in score during follow-up, we divided our patients into clinical improvement (CI) and clinical worsening (CW) groups. RESULTS: The MG score decreased in all courses from a mean of 8.1 at baseline to 5.6 at D1, and to 4.7, 4.0, 3.8, and 3.7 at W1, M1, M2, and M3, respectively. In the CW group, AchRAb levels were significantly higher at M1 (P = 0.022). The AchRAb level at W1 correlated significantly with the MG score at M3 (P = 0.027) and the changes of MG score from W1 to M1 (P = 0.029). The ratio of AchRAb levels of M1 to W1 correlated well with MG score at W1 (P = 0.032), at M3 (P = 0.001), and the changes of MG score from W1 to M1 (P = 0.004). CONCLUSION: Excessive rebounds of AchRAb level at W1 may suggest clinical worsening and further increases in AchRAb level at M1 predict poorer outcome after DFP.

Removal of arsenic from groundwater using point-of-use reverse osmosis and distilling devices.

Ground water in both the northeastern and southwestern coast areas of Taiwan may contain high concentrations of arsenic. Since no central water supply system is available in some of those areas, point-of-use (POU) water purification devices are considered as an option for providing safe drinking water. In this study, removal of arsenic, using two types of POU purification devices, reverse osmosis (RO) systems and distillers, was investigated. Three commercially available RO systems and two distillers were selected to test their removal efficiency of arsenic from synthetic and real ground water. Experimental results of the three RO systems using synthetic ground water showed that only one system had good removal efficiency for arsenic. In subsequent experiments using real ground water with 0.7 mg l(-1) arsenic, only one RO system was able to meet the drinking water standard after producing about 1,000 l of treated water. For the distilling systems, 99% of the arsenic was removed from both synthetic and real groundwater. The arsenic concentrations in the finished water of both distillers were all below the standard for drinking water. Although systems with higher arsenic removal efficiency seemed to have better removal of total dissolved solids (TDS), no correlation could be found after analysis.

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.

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.

Acute oxalate nephropathy induced by star fruit in rats.

In this study, we intend to establish a connection between star fruit and acute oxalate nephropathy and also investigate predisposing factors for its development. Male Sprague-Dawley rats of 180 to 200 g were assigned to four groups; namely, control, experimental, fasting, and water-deprivation groups. The former two groups were subjected to both fasting and water deprivation, whereas the latter two groups were subjected to either fasting or water deprivation, respectively. Except for tap water for controls, the remaining groups were administered 4 mL/100 g of body weight of sour star fruit juice with an oxalate concentration of 2.46 g/dL. After these procedures, serial measurement of serum creatinine levels and kidney pathological examination were performed. Peak serum creatinine levels in the control, experimental, fasting, and water-deprivation groups were 0.50 +/- 0.04, 1.46 +/- 0.26, 0.68 +/- 0.20, and 0.52 +/- 0.08 mg/dL, respectively. The experimental group had a greater peak serum creatinine level (P < 0.05). Mean serum creatinine levels of the experimental group days 0, 1, 2, 3, 4, and 5 were 0.43 +/- 0.03, 1.11 +/- 0.18, 1.31 +/- 0.27, 1.16 +/- 0.28, 0.8 +/- 0.26, and 0.82 +/- 0.28 mg/dL, respectively. Mean serum creatinine levels days 1 to 3 were greater than that day 0 (P < 0.05). Pearson's correlation analysis of peak serum creatinine level and kidney weight for the experimental group showed a significant correlation (R = 0.75; P < 0.05; n = 9). In addition to typical changes of oxalate nephropathy, kidney pathological examination showed many refractile oxalate crystals with all rainbow colors under polarized light microscopy in the experimental group. In conclusion, sour star fruit with abundant oxalate contents could cause acute oxalate nephropathy in rats under the conditions of fasting and water deprivation.

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.

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.

Novel CD28-responsive enhancer activated by CREB/ATF and AP-1 families in the human interleukin-2 receptor alpha-chain locus.

The interaction of interleukin-2 (IL-2) with its receptor (IL-2R) critically regulates the T-cell immune response, and the alpha chain CD25/IL-2Ralpha is required for the formation of the high-affinity receptor. Tissue-specific, inducible expression of the IL-2Ralpha gene is regulated by at least three positive regulatory regions (PRRI, PRRII, and PRRIII), but none responded to CD28 engagement in gene reporter assays although CD28 costimulation strongly amplifies IL-2Ralpha gene transcription. By DNase I hypersensitivity analysis, we have identified a novel TCR-CD3- and CD28-responsive enhancer (CD28rE) located 8.5 kb 5' of the IL-2Ralpha gene. PRRIV/CD28rE contains a functional CRE/TRE element required for CD28 signaling. The T-cell-specific, CD28-responsive expression of the IL-2Ralpha gene appears controlled through PRRIV/CD28rE by cooperation of CREB/ATF and AP-1 family transcription factors.

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.

Comparison between double-filtration plasmapheresis and immunoadsorption plasmapheresis in the treatment of patients with myasthenia gravis.

Two techniques for plasmapheresis are used in the treatment of myasthenia gravis (MG): immunoadsorption (IA) and double filtration (DF). This controlled study evaluated the differences between these techniques in clinical effects and serological changes. Five patients with generalized MG (clinical states IIb and III) were enrolled; each patient received IA and DF plasmapheresis on separate occasions. Immunosorba TR-350 with an affinity to acetylcholine receptor antibodies (AchRAb) was used for IA, while Evaflux 4A was used as the plasma fractionator for DF. Each course of treatment consisted of five sessions of apheresis. MG score, titers of AchRAb, immunoglobulins (Ig), and plasma biochemistry were assessed by blinded examiners before and immediately after the entire course of treatment. Both treatments effectively ameliorated symptoms of MG. There were no significant changes in MG score between the two groups (IA vs. DF: 2.2 vs. 2.6, P> 0.5). IA had a higher clearance rate of AchRAb than DF (66 % vs. 54 %, P< 0.05), while DF removed more IgA (72% vs. 21%, P< 0.05) and IgM (89% vs. 57%, P< 0.01) than did IA. Although IA removed AchRAb more effectively than DF, the clinical effects between these two treatments were similar. The titers of AchRAb cannot reflect the clinical severity. Some circulating factors other than AchRAb may contribute to the pathogenesis of MG.