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Biomedical subjects

H Y Yu

Publications and source records attributed to H Y Yu.

At least 19 recordsLinked to original sources

Simultaneous heart and kidney transplantation for combined cardiac and renal failure.

Simultaneous heart and kidney transplantation (SHKT) is feasible for combined cardiac and renal failure. Herein we reviewed our 10-year experience in SHKT. Six patients underwent SHKT from June 1995 to December 2004. Their ages ranged from 13 to 63 years old with a mean of 45.5 +/- 15.8 years. They were all men except one girl, who was the youngest (aged 13) who suffered from dilated cardiomyopathy with congestive heart failure and chronic renal failure due to systemic lupus erythematosus. Because of aggravating heart failure, she changed from hemodialysis to peritoneal dialysis. Because of intractable heart failure, she underwent SHKT from a 24-year-old female donor. All received hemodialysis before SHKT. The indications for heart transplantation included dilated cardiomyopathy (n = 3), ischemic cardiomyopathy (n = 1), cardiac allograft vasculopathy (n = 1), and cardiac allograft failure (n = 1). The immunosuppressive protocol and rejection surveillance were these employed for heart transplantation. No operative mortality was noted in this study. The 1-year and 5-year survival rates were the same, 83%. The 10-year survival rate was 55%. No cardiac or renal allograft rejection was noted. No renal allograft loss was noted. There were two late mortalities: the one, who underwent redo heart transplantation for coronary artery vasculopathy died of cardiac allograft failure 1 year after SHKT. The other patient died of massive ischemic necrosis of the intestine at 6 years after SHKT. Our experience showed that SHKT had good short- and long-term results without increasing immunosuppressive doses. End-stage failure of either the heart or the kidney did not preclude heart plus kidney transplantation.

Adult↗

Sparing immunosuppression in heart transplant recipients with severe sepsis.

This study described an analysis of severe sepsis among heart transplantation recipients who were treated by sparing all immunosuppressants. Sepsis leading to multiple organ failure (MOF) in heart transplantation has a high mortality. This retrospective study of 190 patients who underwent heart transplantation from 1993 to 2004 included 12 who had severe sepsis with MOF who were treated by sparing all immunosuppressants. Half of them survived after sparing all immunosuppressants with intensive endomyocardial biopsy. Only one case needed pulse therapy for an acute rejection episode. The most common bacterial infectious episodes were caused by methicillin-resistant Staphylococcus aureus (n = 3). All sepsis episodes occurred in the first month after heart transplantation except in one case, which occurred 6 years after heart transplantation. There was a 50% survival rate of heart transplantation recipients who experienced MOF due to severe sepsis and were treated by sparing all immunosuppressants under a program of intensive endomyocardial biopsy.

Bacterial Infections↗

Successful treatment of hepatitis B virus infection with Lamivudine after heart transplantation.

Patients with hepatitis B virus (HBV) infection have a higher morbidity and mortality after heart transplantation (HT). HBV infection is endemic in Taiwan. We studied the effect of lamivudine treatment of HBV infection after HT. From July 1987 to July 2005, 252 patients underwent HT. All recipients and donors underwent routine screening of hepatitis B surface antigen (HBsAg), hepatitis B e antigen, antibody to hepatitis B surface antigen, antibody to hepatitis B core antigen, antibody to hepatitis B e antigen, and an alanine aminotransferase (ALT) level before HT. When ALT was two times greater than the upper limit of normal or serum bilirubin was higher than 3 mg/dL in HBsAg-positive patients, HBV-DNA were checked by a branched DNA assay or polymerase chain reaction. When HVB-DNA was greater than 100,000 copies/mL, lamivudine (100 mg per day) was prescribed indefinitely. There were 14 patients under lamivudine treatment after HT, among whom, none suffered severe adverse reactions from lamivudine. Four patients died: one due to end-stage cirrhosis while awaiting liver transplantation at 14 months after HT. Two died of sudden death at 54 months and 138 months after HT. Another died of diffuse B cell lymphoma at 62 months after HT. All the survivors have normal ALT and undetectable HBV-DNA after lamivudine treatment. But the YMDD mutant was detected in two patients. With successful treatment of HBV infection in HT, it is not necessary to exclude HBV infection patients from HT.

Adult↗

Extracorporeal membrane oxygenation hybrid with various ventricular assist devices as double bridge to heart transplantation.

Ventricular assist devices (VAD) have benefitted patients with end-stage heart failure as a bridge to heart transplantation (HTx). We present our experience with HTx after an extracorporeal membrane oxygenation (ECMO) hybrid with various ventricular assist devices (VAD). From May 1996 to December 2003, mechanical circulatory support with a Biopump VAD was performed in eight patients, HeartMate left VAD in eight patients, and Thoratec VAD in eight patients. Before VAD implantation, 19 patients maintained their circulation with ECMO. Half of the 24 patients were implanted with VAD to await a suitable donor for HTx. We observed that half of the patients supported by ECMO hybrid with various VAD awaited a suitable donor for HTx. In our experience, we recommend the application of ECMO for short-term support within 1 week and the Biopump VAD, Thoractec VAD, or HeartMate VAD for medium-term or long-term support as a bridge to HTx.

Adult↗

Heart retransplantation for heart allograft failure in Chinese heart transplant recipients: NTUH experience.

We investigated the short- and long-term results after heart retransplantation in terms of different causes of heart allograft failure. We sought to establish the data of heart retransplantation in Chinese compared with Western counterparts due to differences in heart allograft vasculopathy. From March 1995 to May 2005, eight heart transplantation recipients with allograft failure underwent retransplantation. Heart allograft failure was due to coronary vasculopathy (CAV) in six patients (75%) and acute rejection in two patients (25%). The mean interval to retransplantation was 32 to 84 months (mean 54.3 months). There were five patients who survived after heart retransplantation for CAV and no patient survived after an earlier diagnosis of acute rejection. Heart retransplantation is a feasible method with acceptable long-term survival rate for heart allograft failure. After careful pretransplant evaluation, retransplantation is acceptable. The survival after retransplantation for CAV is notably great than that after acute rejection. Heart retransplantation is the only way for patients who have cardiac allograft failure to achieve long-term survival.

Adult↗

Relationships among acylation stimulating protein, adiponectin and complement C3 in lean vs obese type 2 diabetes.

OBJECTIVE: The purpose of this study was to determine the relationships between adipocyte hormones acylation stimulating protein (ASP), adiponectin, complement C3 (C3) (ASP precursor) and insulin, C-reactive protein (CRP), lipid profiles and insulin resistance in lean vs obese type 2 diabetes subjects. SUBJECTS: Lean type 2 diabetes subjects (DL n = 27) vs obese type 2 diabetes subjects (DO n = 55) were compared to age-matched nondiabetic groups (Obese, OB n = 55 and control, CTL n = 50). RESULTS: The DO group demonstrated significant increases in plasma ASP and C3 with decreases in plasma adiponectin as compared to CTL. Interestingly, these increases in ASP and C3 were as high, or greater, in the DL group in spite of normal weight. By contrast adiponectin in the DL group was comparable to CTL, in spite of marked insulin resistance. C3 correlated with insulin, glucose and homeostasis model assessment of insulin resistance (HOMA-IR); ASP correlated with body mass index (BMI), glucose, insulin and plasma lipid parameters (non-esterified fatty acids (NEFA), triglyceride, cholesterol and apolipoprotein B). Adiponectin correlated with BMI, glucose, NEFA, triglyceride, high-density lipoprotein cholesterol and apolipoprotein A1 but not HOMA-IR, ASP or C3. CRP correlated only with HOMA-IR. CONCLUSION: Increased ASP and C3 are both associated with diabetes and related lipid factors but are not regulated coordinately. Adiponectin appears to be more closely related to body size (decreased in obese subjects) than insulin resistance in these subjects.

Adiponectin↗

Statin attenuates high glucose-induced and angiotensin II-induced MAP kinase activity through inhibition of NAD(P)H oxidase activity in cultured mesangial cells.

An increased oxidative stress may contribute to the development of diabetic nephropathy. We have recently reported that high glucose level stimulated superoxide production through protein kinase C (PKC)-dependent activation of NAD(P)H oxidase in cultured vascular cells. Here we show that 3-hydroxy-3-methylglutaryl CoA reductase inhibitor (statin) attenuates both high glucose level-induced and angiotensin II (Ang II)-induced activation of p42/44 mitogen-activated kinase (MAP kinase) in cultured human mesangial cells through inhibition of NAD(P)H oxidase activity. The intracellular oxidative stress in cultured mesangial cells was evaluated by electron spin resonance (ESR) measurement. MAP kinase activity was evaluated by western blot analysis using anti phospho-specific MAP kinase antibody and anti-ERK-1 antibody. Exposure of the cells to high glucose level (450 mg/dl) for 72 hrs significantly increased MAP kinase activity as compared to normal glucose level (100 mg/dl). This increase was completely blocked by the treatment of pitavastatin (5x10(-7) M) as well as a NAD(P)H oxidase inhibitor (diphenylene iodonium, 10(-5) M) in parallel with the attenuation of oxidative stress. Ang II-induced activation of MAP kinase was also completely blocked by pitavastatin as well as a diphenylene iodonium in parallel with the attenuation of oxidative stress. In conclusion, pitavastatin attenuated high glucose-induced and Ang II- induced MAP kinase activity in mesangial cells through inhibition of NAD(P)H oxidase. Thus, statins may have a potential as a therapeutic tool for early diabetic nephropathy.

Angiotensin II↗

Neuromagnetic separation of secondarily bilateral synchronized spike foci: report of three cases.

To demonstrate the high spatiotemporal resolution of magnetoencephalography (MEG), we report three cases with focal epilepsy that exhibited bilateral synchronized spikes on simultaneous scalp EEG and MEG recording. Constant time lags (19.4 +/- 3.0 ms and 20.0 +/- 5.5) between the leading and the following contralateral spikes were noted on MEG and the current dipole sources were localized in the bilateral homotopic regions symmetrically in Cases 1 and 3. In Case 2, MEG indicated leading spikes in the left frontal region, with a time lag of 42.3 +/- 8.4 ms to reach the contralateral frontal and bilateral temporal regions as well. Chronic subdural EEG recording in Cases 1 and 2 confirmed that the leading spike focus in MEG was close to the seizure onset zone in cortical EEG. Spatio-temporal analysis of MEG spikes may be useful to identify the primary epileptic region in patients with synchronized bilateral epileptiform discharges.

Adolescent↗

MEG localization of rolandic spikes with respect to SI and SII cortices in benign rolandic epilepsy.

The purpose of this study was to study the relationship between interictal spike sources and somatosensory cortices in benign rolandic epilepsy of childhood (BREC) using a whole-scalp neuromagnetometer. We recorded spontaneous magnetoencephalography (MEG) and EEG signals and cortical somatosensory-evoked magnetic fields (SEFs) to electric stimulation of the median nerve in 9 children with BREC. Interictal rolandic discharges (RDs) and SEFs were analyzed by equivalent current dipole (ECD) modeling. Based on the orientation and locations of corresponding ECDs, we compared generators of RDs with primary (SI) and second somatosensory cortices (SII). Our results showed that RDs and SII responses had similar ECD orientation on the magnetic field maps. The ECDs of RDs were localized 15.3 +/- 1.9 and 12.2 +/- 2.8 mm anterior to SI and SII, respectively. The spatial distance on average from the location of RDs to SII (21.9 +/- 1.6 mm) cortex was significantly shorter than to SI cortex (29.7 +/- 1.7 mm) (P<0.01, Wilcoxon signed-rank test). In conclusion, the cortical generators for RDs in patients with BREC are localized in the precentral motor cortex, closer to hand SII than to SI cortex.

Child↗

Magnetoencephalographic yield of interictal spikes in temporal lobe epilepsy. Comparison with scalp EEG recordings.

To compare magnetoencephalography (MEG) with scalp electroencephalography (EEG) in the detection of interictal spikes in temporal lobe epilepsy (TLE), we simultaneously recorded MEG and scalp EEG with a whole-scalp neuromagnetometer in 46 TLE patients. We visually searched interictal spikes on MEG and EEG channels and classified them into three types according to their presentation on MEG alone (M-spikes), EEG alone (E-spikes), or concomitantly on both modalities (M/E-spikes). The M-spikes and M/E-spikes were localized with MEG equivalent current dipole modeling. We analyzed the relative contribution of MEG and EEG in the overall yield of spike detection and also compared M-spikes with M/E-spikes in terms of dipole locations and strengths. During the 30- to 40-min MEG recordings, interictal spikes were obtained in 36 (78.3%) of the 46 patients. Among the 36 patients, most spikes were M/E-spikes (68.3%), some were M-spikes (22.1%), and some were E-spikes (9.7%). In comparison with EEG, MEG gave better spike yield in patients with lateral TLE. Sources of M/E- and M-spikes were situated in the same anatomical regions, whereas the average dipole strength was larger for M/E- than M-spikes. In conclusion, some interictal spikes appeared selectively on either MEG or EEG channels in TLE patients although more spikes were simultaneously identified on both modalities. Thus, simultaneous MEG and EEG recordings help to enhance spike detection. Identification of M-spikes would offer important localization of irritative foci, especially in patients with lateral TLE.

Adolescent↗

A possible target of antioxidative therapy for diabetic vascular complications-vascular NAD(P)H oxidase.

A growing body of evidence has shown that oxidative stress may be involved in the development of vascular complications associated with diabetes. However, the molecular mechanism for increased reactive oxygen species (ROS) production in diabetes remains uncertain. Among various possible mechanisms, attention have increasingly been paid to NAD(P)H oxidase as the most important source of ROS production in vascular cells. High glucose level stimulates ROS production through protein kinase C (PKC)-dependent activation of vascular NAD(P)H oxidase. Furthermore, the expression of NAD(P)H oxidase components is increased in micro- and macrovascular tissues of diabetic animals in association with various functional disorders and histochemical abnormalities. These results suggest that vascular NAD(P)H oxidase-driven ROS production may contribute to the onset or development of diabetic micro- or macrovascular complications. In this point of view, the possible new strategy of antioxidative therapy for diabetic vascular complications is discussed in this review.

Animals↗

Saturated non-esterified fatty acids stimulate de novo diacylglycerol synthesis and protein kinase c activity in cultured aortic smooth muscle cells.

AIMS/HYPOTHESIS: Insulin resistance is linked with a cluster of multiple risk factors and excessive acceleration of atherosclerosis. The underlying mechanism is not, however, fully understood. METHODS: To determine the link between insulin resistance and altered vascular function, we focused on the effect of various non-esterified fatty acids on diacylglycerol-protein kinase C pathway and mitogen-activated protein kinase activity in cultured aortic smooth muscle cells. RESULTS: Incubation of the cells with saturated non-esterified fatty acids (200 micromol/l) for 24 h, such as palmitate or stearate, induced a significant increase in diacylglycerol concentrations by about fivefold or eightfold, respectively, whereas oleate induced a slight increase in diacylglycerol concentrations by 1.8-fold and arachidonate induced none. In addition, the increased diacylglycerol concentrations induced by palmitate were completely restored to control concentrations by triacsin C, acyl-CoA synthetase inhibitor. These results suggest that saturated non-esterified fatty acids may increase diacylglycerol concentrations through de novo pathway by stepwise acylation. In parallel with the increased diacylglycerol, incubation of the cells with saturated non-esterified fatty acids significantly induced the activation of protein kinase C and mitogen-activated protein kinase. The palmitate-induced increase in mitogen-activated protein kinase activity was restored to control concentrations by GF109203X (5 x 10(-7) mol/l), a specific protein kinase C inhibitor, suggesting a protein kinase C-dependent activation of mitogen-activated protein kinase. CONCLUSION/INTERPRETATION: Saturated non-esterified fatty acids induced an increase in de novo diacylglycerol synthesis and subsequent activation of protein kinase C and mitogen-activated protein kinase in cultured aortic smooth muscle cells. This could contribute to the altered vascular functions in the insulin resistant state.

Animals↗

Altered gap junction activity in cardiovascular tissues of diabetes.

Hyperglycemia appears to be an important etiologic factor in the development of micro- and macrovascular complications in diabetic patients. However, its detailed molecular mechanism remains unclear. Among various possible mechanisms, it is widely accepted that high glucose level and a diabetic state induce protein kinase C (PKC) activation in vascular cells in cultured and vascular tissues of diabetic animals. Gap junctions are clusters of membrane channels that permit the intercellular exchange of ions and second messengers between adjacent cells. Gap junctional intercellular communication (GJIC) plays an important role in cardiovascular tissue homeostasis. Here we report that GJIC in cultured vascular cells such as endothelial cells and smooth muscle cells is inhibited by high glucose level. Furthermore, we show that it is mediated by PKC-dependent excessive phosphorylation of connexin-43 which is the main functional component of gap junction in vascular cells. In addition, we also show that in diabetic rats, PKC-dependent excessive phosphorylation of connexin-43 induces the impairment of ventricular conduction in the heart. These results suggest that PKC-dependent impairment of GJIC may lead to various disorders of cardiovascular homeostasis and contribute to cardiovascular dysfunctions associated with diabetes.

Animals↗

Antiepileptic drug withdrawal in patients with temporal lobe epilepsy undergoing presurgical video-EEG monitoring.

PURPOSE: To investigate antiepileptic drug (AED) withdrawal during video-EEG monitoring in adult patients with temporal lobe epilepsy (TLE). METHODS: Between 1995 and 1997, 102 consecutive patients with refractory TLE were admitted to the epilepsy monitoring unit for presurgical evaluation. Patients were monitored with ongoing AEDs being rapidly decreased and discontinued in 4-6 days. The monitoring was continued until sufficient numbers of seizures were recorded. Serum AED levels were checked at admission and after the first complex partial seizure (CPS). RESULTS: In all, 89 patients had 429 CPSs (mean, 4.8 per patient), including 156 (36.4%) secondarily generalized. A mean of 153.8 h (16-451 h) was required for completing the monitoring in each patient. Forty-three (48.3%) patients experienced seizure clusters, and eight (9.0%) had generalized seizures that had never occurred or had been absent for years. However, none evolved to status epilepticus. Carbamazepine was the most commonly used AED in 71.9% of patients, followed by valproate and phenytoin. When the first CPS occurred, mean 77.2 h since the beginning of the monitoring, serum levels of these three AEDs were mostly subtherapeutic rather than minimal. CONCLUSIONS: Acute AED withdrawal effectively provoked seizures in TLE patients undergoing presurgical video-EEG monitoring. However, nearly 50% of patients had seizure clusters or secondarily generalized seizures. Serum AED levels were mostly subtherapeutic when the first CPS occurred.

Adolescent↗

Lateralizing value of early head turning and ictal dystonia in temporal lobe seizures: a video-EEG study.

To investigate early head turning, we retrospectively studied videotapes of 262 seizures from 82 patients who were seizure free after temporal lobectomy. Early head movements were arbitrarily classified into non-tonic turning, tonic turning, and absence of turning. Among the 222 seizures which showed early head turning, 168 (75.7%) had non-tonic turning and 54 (24.3%) had tonic turning. The direction of the first head turning was ipsilateral to the epileptogenic foci in 132 (78.6%) seizures with non-tonic turning and in 35 (64.8%) seizures showing tonic head turning. The proportion of seizures with turning towards the ipsilateral side in the presence of tonic and non-tonic head turning were significantly different (P= 0.04). Seventy-four seizures (28.2%) evolved to secondary generalization, more frequently found in seizures with early head turning (P= 0.0015) and especially those showing tonic turning (P< 0.0001). The direction of head turning immediately preceding secondary generalization was contralateral to the lesion side in 53 seizures (82.8%). Dystonic upper limb posturing occurred in 86 seizures (32.8%), exclusively contralateral to the seizure focus, whereas 65 (75.6%) were associated with initial head turning ipsilateral to the focus. In summary, temporal lobe seizures with tonic head turning tends to secondarily generalize and the direction of head turning before secondarily generalized was contralateral to the seizure foci. Earlier in the seizures the direction of non-tonic head turning tends to be towards the epileptogenic hemisphere. In addition, dystonic posturing of the extremities is a significant lateralizing sign to the contralateral hemisphere in temporal lobe seizures.

Adult↗

Accelerated apoptosis in the Timp-3-deficient mammary gland.

The proapoptotic proteinase inhibitor TIMP-3 is the only molecule of this family thought to influence cell death. We examined epithelial apoptosis in TIMP-3-deficient mice during mammary gland involution. Lactation was not affected by the absence of TIMP-3, but glandular function, as measured by gland-to-body weight ratio and production of beta-casein, was suppressed earlier during post-lactational involution than in controls. Histological examination revealed accelerated lumen collapse, alveolar-epithelial loss, and adipose reconstitution in Timp-3(-/-) females. Epithelial apoptosis peaked on the first day of involution in Timp-3-null glands but at day 3 in wild-type littermates. Unscheduled activation of gelatinase-A was evident by zymography and correlated with earlier fragmentation of fibronectin in Timp-3(-/-) mammary. To obtain independent evidence of the proapoptotic effects of TIMP-3 deficiency, we introduced recombinant TIMP-3-releasing pellets into regressing Timp-3(-/-) mammary tissue and showed that this treatment rescued lumen collapse and epithelial apoptosis. Ex vivo, involuting Timp-3(-/-) mammary tissue demonstrated accelerated epithelial apoptosis that could be reduced by metalloproteinase inhibition. The physiological relevance of TIMP-3 became apparent as Timp-3(-/-) dams failed to reestablish lactation after brief cessation of suckling. Thus, TIMP-3 is a critical epithelial survival factor during mammary gland involution.

Adipose Tissue↗