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Biomedical subjects

P C Lee

Publications and source records attributed to P C Lee.

At least 19 recordsLinked to original sources
PubMed2000

Attenuation of myocardial ischemia/reperfusion injury by superinduction of inducible nitric oxide synthase.

BACKGROUND: Nitric oxide (NO) has been implicated as a mediator in myocardial ischemia/reperfusion (I/R) injury, but its functional properties have been conflicting. We investigated whether NO has a protective role against I/R injury. METHODS AND RESULTS: Using endothelial NO synthase knockout (eNOS KO) mice, inducible NOS KO mice, the NO donor S-nitroso-N-acetylpenicillamine (SNAP), and the NOS inhibitor N-iminoethyl-L-ornithine (L-NIO), we performed studies of isolated perfused hearts subjected to 30 minutes of global ischemia followed by reperfusion. After 60 minutes of reperfusion, nitrite levels in the coronary effluent in the SNAP and eNOS KO groups were significantly elevated compared with other groups. Immunoblot and immunohistochemistry showed that iNOS was markedly induced in the eNOS KO hearts. Under spontaneous beating conditions during reperfusion, increased NO activity was correlated with a prevention of the hyperdynamic contractile response and enhanced myocardial protection, as evidenced by a reduction in myocardial injury and infarct size. During prolonged reperfusion, SNAP-treated hearts were able to preserve contractile functions for 180 minutes, whereas L-NIO-treated hearts showed a sustained deterioration in contractility. CONCLUSIONS: NO protects against I/R injury by preventing the hyperdynamic response of isolated perfused hearts during early reperfusion. In the eNOS KO hearts, a paradoxical increase in NO production was seen, accompanied by a superinduction of iNOS, possibly due to an adaptive mechanism.

Animals↗
PubMed2000

Endothelial nitric oxide synthase protects aortic allografts from the development of transplant arteriosclerosis.

BACKGROUND: Inducible nitric oxide synthase (iNOS) is up-regulated in rejecting allografts and is protective against allograft arteriosclerosis; it suppresses neointimal smooth muscle cell accumulation and inhibits adhesion of platelets and leukocytes to the endothelium. However, the functional importance of endothelial NOS (eNOS) in the rejecting allografts remains unclear. METHODS: We examined the effects of selective eNOS deficiency in aortic allografts in a murine chronic rejection model using grafts from eNOS knockout (KO) mice (C57BL/6 background; H2b) and normal C3H (H2K) as recipients. Grafts from wild-type C57BL/6 mice served as controls. Grafts from iNOS KO mice served as a second group of controls where the contribution from iNOS was eliminated but eNOS was preserved. Aortic grafts were harvested and analyzed at days 10-14, 18-22, and 26-30 after transplantation. RESULTS: Endothelial NOS-deficient grafts showed significantly increased intima/media ratios at days 26-30 compared to controls. Immunostaining demonstrated that in eNOS KO grafts, eNOS was not detectable whereas iNOS was expressed prominently in infiltrating recipient mononuclear cells. In control grafts, eNOS expression was preserved in the endothelium even by day 30, and associated with a decrease in intimal thickening. We further demonstrated that early overexpression of iNOS by ex vivo gene transfer completely prevented the development of arteriosclerosis associated with eNOS deficiency. CONCLUSIONS: We found that eNOS plays a protective role in allografts, and that in eNOS-deficient allografts, early overexpression of iNOS is capable of preventing the development of allograft arteriosclerosis. In allografts with dysfunctional vascular endothelium and impaired eNOS activity as a result of ischemia or native arteriosclerotic disease, iNOS gene therapy may serve to improve their long-term survival and function.

Animals↗
PubMed2000

Evaluation of linkage of markers on chromosome 6p with schizophrenia in Taiwanese families.

Previous studies have indicated possible linkage of schizophrenia with chromosome 6p21-24. In an attempt to replicate these findings, we studied the linkage of schizophrenia with nine markers on chromosome 6p21-24 in 39 Taiwanese schizophrenic nuclear families with at least two affected siblings. Two diagnostic models (narrow: Diagnostic and Statistical Manual of Mental Disorders-IV schizophrenia only; and broad: including schizophrenia, schizoaffective, and other nonaffective psychotic disorders) were used to define the disease phenotypes. With the broad and narrow diagnostic models, the marker D6S296 produced maximum two-point lod scores of 1.46 (straight theta = 0.2) and 1.35 (straight theta = 0. 2), respectively, in the recessive inheritance model. Assuming locus heterogeneity, a multipoint lod score of 0.85 was obtained between markers D6S296 and D6S277 under the narrow/recessive model. Maximum nonparametric lod scores of 1.25 ( p= 0.09) and 1.36 (p = 0.08) were observed, but still not statistically significant, at D6S296 in the narrow and broad diagnostic models, respectively. Both two-point analysis of the dominant model (lod score 0.85) and nonparametric analysis (lod score 1.25) showed a mild peak lod score appeared at marker D6S 285 as well. The results add some support to the suggestive linkage of schizophrenia with markers in the regions of chromosome 6p22 and 6p24 in an ethnically distinct Taiwanese sample. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:74-78, 2000.

Adolescent↗
PubMed2000

Prevalence and risk factor analysis of TTV infection in prostitutes.

TTV, a DNA virus, has been isolated from patients with non-A to non-E post-transfusion hepatitis. In the past it was assumed that TTV was transmitted parenterally. It is unclear whether sexual contact leads to transmission of this virus. In this study, two sets of TTV-specific polymerase chain reaction primers were used to detect serum TTV DNA in 140 prostitutes and 136 controls. The prevalence of TTV DNA in prostitutes was significantly higher than in the control group (46/140 [32.9%] vs. 29/136 [21.3%]; P = 0.043). There was no significant difference in the prevalence of positive antibody to hepatitis A virus (anti-HAV) in either group (87.8% for prostitutes, 85.3% for controls). No particular risk factor was significantly associated with positive TTV DNA in prostitutes. In summary, TTV is highly prevalent in prostitutes. Transmission of TTV via sexual contact is not as efficient as transmission of hepatitis C and D viruses and GB virus-C hepatitis G virus. The high prevalence of TTV in controls indicates that there are diverse routes of transmission of this virus.

Adult↗
PubMed2000

Endothelial dysfunction in patients with heart failure: relationship to disease severity.

BACKGROUND: Heart failure is associated with abnormal endothelium-dependent vasodilation. However, the relationship of this abnormality to heart failure severity has not been well defined. METHODS AND RESULTS: We used strain-gauge plethysmography to assess forearm blood flow (FBF) responses to endothelium-dependent, endothelium-independent, and reactive hyperemic stimuli in normal subjects (n = 29) and in patients with mild (n = 26) and severe (n = 41) heart failure. FBF responses to intra-arterial methacholine (0.3, 1.5, 3.0 microg/min) were significantly (P < .005) and similarly reduced in patients with mild (2.8 +/- 0.4, 5.9 +/- 0.7, and 7.7 +/- 1.1 mL/min/dL) and severe (2.7 +/- 0.4, 5.4 +/- 0.7, and 6.9 +/- 0.9) heart failure compared with normal subjects (4.5 +/- 0.4, 9.4 +/- 1.0, and 12.0 +/- 1.1). FBF responses to nitroprusside (1, 5, 10 microg/min) were significantly reduced in mild (2.4 +/- 0.3, 6.7 +/- 1.1, and 11.9 +/- 2.0, P < .05) and severe (1.9 +/- 0.2, 5.1 +/- 0.5, and 7.3 +/- 0.9, P < .001) heart failure groups compared with normal subjects (3.8 +/- 0.5, 10.8 +/- 1.2, and 14.9 +/- 1.2). However, FBF responses were reduced to a greater extent (P < .001) in mild heart failure compared with severe heart failure. Peak reactive hyperemia was significantly impaired only in severe heart failure. There was no correlation between methacholine responses and ejection fraction, maximum oxygen consumption, wedge pressure, or serum norepinephrine. CONCLUSION: Impaired endothelium-dependent vasodilation is present and near maximum in mild heart failure. Endothelial dysfunction may be an early finding in human heart failure.

Blood Pressure↗
PubMed2000

Vascular ATP-dependent potassium channels, nitric oxide, and human forearm reactive hyperemia.

Vascular ATP-dependent potassium (K+ATP) channels open and contribute to reactive hyperemia (RH) in animals. The contribution of K+ATP channels to ischemic vasolidation during RH and interactions with endothelium-derived nitric oxide have not been well characterized in human subjects. RH blood flow responses (mL/dL) following 5 minutes of cuff occlusion were measured using strain-gauge plethysmography in 22 normal human subjects age 42 +/- 2 years. Measurements were obtained at baseline and following intra-arterial administration of the K+ATP channel closer glibenclamide, the nitric oxide synthase inhibitor L-N-monomethyl arginine (L-NMMA), or both drugs simultaneously. Glibenclamide (100 micrograms/min) did not change basal flow (2.7 +/- 0.3 to 2.7 +/- 0.3 mL/min/dL), but L-NMMA (8 mumol/min) and combined glibenclamide and L-NMMA significantly (p < 0.05) decreased basal flow (3.0 +/- 0.5 to 2.0 +/- 0.2 and 3.3 +/- 0.5 to 2.5 +/- 0.3, respectively). Glibenclamide significantly (p < 0.01) decreased RH flow (18.2 +/- 1.3 to 14.8 +/- 1.3) and excess flow (5.3 +/- 1.2 to 1.3 +/- 1.3). L-NMMA significantly (p < 0.05) decreased RH flow (21.2 +/- 1.8 to 18.9 +/- 1.9) and tended to decrease excess flow (6.1 +/- 2.2 to 3.9 +/- 2.5). Combined drug infusion significantly (p < 0.1) decreased RH flow (21.6 +/- 2.2 to 18.0 +/- 2.4) and excess flow (6.3 +/- 1.6 to 1.6 +/- 1.6), with reductions in RH and excess flow similar to those following glibenclamide infusion alone. We conclude that forearm vascular K+ATP channels are closed at baseline. They open and contribute to RH vasodilation. The addition of nitric oxide inhibition to K+ATP channel blockade does not result in additive or synergistic inhibition of RH.

Adenosine Triphosphate↗
PubMed2000

Complications of liner locking system in Micro-structured Omnifit acetabular components: a radiographic evaluation of 887 hips followed for 5-10 years.

We evaluated 887 hips in 672 patients with uncemented MicroStructured Omnifit acetabular components for liner locking complications. We found 2 types of radiographic signs of liner locking system complications in 7 hips, developing between 2 and 4 years postoperatively. The incidence of liner locking system complications was 0.8% using this modular acetabular component. We recommend that a patient who has received a total hip arthroplasty including a MicroStructured Omnifit acetabular component should be monitored frequently for radiographic signs of liner locking system complications, especially with a polyethylene thickness of less than 8 mm.

Adult↗
PubMed2000

Diabetes mellitus as a risk factor of liver cirrhosis in patients with chronic hepatitis B virus infection.

Liver cirrhosis may occur in chronic hepatitis B surface antigen (HBsAg) carriers. Diabetes mellitus (DM)-associated chronic hepatitis may also occasionally lead to cirrhosis; however, its role in the course of chronic HBsAg carriers has not been studied. A cohort of 500 HBsAg carriers (398 men; mean age at entry, 42 +/- 15 years) were followed up longitudinally. After a mean follow-up of 5.8 +/- 3.3 years, 71 (14.2%: 70 men) patients developed cirrhosis. Increased risks of cirrhosis were found among men and the elderly (p < 0.001). Fifteen (21.1%) cirrhotic patients were noted to have had DM for 2-15 years before the development of cirrhosis. By contrast, only eight (1.9%; p < 0.001 ) of the patients without cirrhosis developed DM. When cirrhotic patients were compared to 102 age- and sex-matched non-cirrhotic controls, DM and elevation of serum alanine transaminase levels were found to be independent factors associated with the advent of cirrhosis in multivariate analysis. Other factors, including acute exacerbation, bridging hepatic necrosis, and superinfection by hepatitis C or D viruses, were insignificant. Our results suggest that DM may play a role in the progression to liver cirrhosis in chronic HBsAg carriers. High-risk subjects should be closely monitored for late complications.

Adult↗
PubMed2000

Comparison of 201Tl SPET and treadmill exercise testing in patients with Kawasaki disease.

About 4% of children with Kawasaki disease ultimately develop ischaemic heart disease. Therefore, the early detection, non-invasive monitoring and long-term follow-up of myocardial ischaemia are essential. We compared the sensitivity and specificity of 201Tl single photon emission tomography (SPET) and treadmill exercise in the detection of myocardial ischaemia in 23 patients (19 boys, 4 girls) with Kawasaki disease. They were divided into two groups according to the results of coronary angiography. Group I consisted of 11 patients with coronary abnormalities; Group II consisted of 12 patients with no coronary abnormalities. The sensitivity, specificity, false-positive and false-negative rates for detecting coronary arterial lesions were 72.7% (8/11), 58.3% (7/12), 38.5% (5/13) and 30% (3/10) for 201Tl SPET, and 45.5% (5/11), 100% (12/12), 0% (0/5) and 33.3% (6/18) for treadmill exercise, respectively. We conclude that 201Tl SPET is more sensitive than treadmill exercise for the detection of coronary arterial abnormalities, but that the specificity of treadmill exercise is better than that of 201Tl scintigraphy. Coronary artery lesions detected by coronary angiography have good concordance of ischaemic areas with perfusion defects detected by 201Tl SPET. When ischaemic findings on 201Tl SPET and/or positive treadmill exercise testing are noted, coronary angiography is strongly indicated to detect possible stenotic lesions in the coronary arteries.

Adolescent↗
PubMed2000

Factors predictive of liver cirrhosis in patients with chronic hepatitis B: a multivariate analysis in a longitudinal study.

OBJECTIVE AND DESIGN: Chronic hepatitis B virus (HBV) infection may lead to liver cirrhosis; however, factors associated with the development of cirrhosis have been incompletely studied. A total of 516 patients with chronic hepatitis B were followed up longitudinally to determine their outcome. METHODS: The clinical and pathological features were compared between those with and without cirrhosis occurrence. The risk factors were analysed, and the probability of the development of cirrhosis was estimated. RESULTS: During a mean follow-up period of 5.7 +/- 3.4 years (range 1-17 years), cirrhosis occurred in 71 patients, with a calculated annual incidence of 2.4%. Older age (> 45 years) at entry, male gender, persistent hepatitis (> 1.5-fold rise of serum alanine aminotransferase levels for at least one year) and diabetes mellitus were identified as independent risk factors of cirrhosis in a multivariate analysis (odds ratios 8.0, 19.3, 2.0 and 5.2, respectively; P values all < 0.05). A logistic regression equation was used to predict the probability of cirrhosis occurrence, which was as high as 76.6% when all risk factors were present. Acute exacerbation or super-infection by hepatitis C or D viruses were not significant predictors. Patients with subsequent cirrhosis had higher initial hepatic histological necro-inflammatory activities when compared to age- and sex-matched non-cirrhotic controls (Knodell's scores: 8.2 +/- 2.4 versus 6.0 +/- 4.1, P< 0.05). CONCLUSIONS: Patients who were elderly, male, diabetic or had a history of persistent and histologically severe hepatitis were at increased risks of liver cirrhosis. Aggressive anti-viral therapy may be needed for these patients and they should be closely monitored for HBV-related late complications.

Adult↗
PubMed2000

Potent and selective activity of a combination of thymidine and 1843U89, a folate-based thymidylate synthase inhibitor, against Plasmodium falciparum.

Unlike mammalian cells, malarial parasites are completely dependent on the de novo pyrimidine pathway and lack the enzymes to salvage preformed pyrimidines. In the present study, first, it is shown that 1843U89, even without polyglutamylation, is a potent folate-based inhibitor of purified malarial parasite thymidylate synthase. The binding was noncompetitive with respect to methylenetetrahydrofolate, and 1843U89 had a K(i) of 1 nM. The compound also had potent antimalarial activity in vitro. Plasmodium falciparum cells in culture were inhibited by 1843U89, with a 50% inhibitory concentration of about 70 nM. The compound was effective against drug-sensitive as well as drug-resistant clones of P. falciparum. As predicted by the biochemistry of the parasite, the potent inhibition of parasite proliferation by 1843U89 could not be reversed with 10 microM thymidine. In contrast, in the presence of 10 microM thymidine, mammalian cells were unaffected by 1843U89 even at concentrations as high as 0.1 mM, thus offering a selectivity window of more than 1,000-fold. On this basis, folate-based thymidylate synthase inhibitors may represent a powerful additional tool that can be used to combat drug-resistant malaria.

Animals↗
PubMed2000

Adult monteggia fracture with ipsilateral distal radius fracture: case report.

Although the adult Monteggia fracture is a well-known injury, the combination of a Monteggia fracture and an ipsilateral distal radius fracture is extremely rare. It is important for the treating physician to recognize that this injury involves not only the bone elements but also their articulations. The distortion of the integrity of both the elbow and the wrist results in the potential for functional compromise, if inadequately treated. The case report presented here describes a 21-year-old woman with this complex injury resulting from a fall. The injury included a Monteggia type II fracture and an ipsilateral distal radius intra-articular fracture in the left forearm. An excellent result was obtained by surgical intervention in both the radial and ulnar bones. The factors we believe contributed to the excellent result were early diagnosis, anatomic reduction, stable fixation, and early physical exercise. The mechanism of injury giving rise to this rare combination of fractures is discussed, as well as a review of the literature.

Adult↗
PubMed2000

Effectiveness of an organ-sharing program in providing zero HLA-A,B,DR mismatched kidneys for transplantation in Taiwan.

PURPOSE: This study evaluated the effects of organ sharing on the allocation of kidneys from cadaveric donors to uremic patients from National Cheng Kung University Hospital (CKUH) and National Taiwan University Hospital (NTUH) who were waiting for kidney transplantation. METHODS: Standard complement-dependent microcytotoxicity assays were used. Human leukocyte antigen (HLA)-A,B,C typing was performed on nylon-wool-enriched T lymphocytes. HLA-DR typing was performed on either nylon-wool-separated B cells or Dynabeads. Isolation of class II-positive cells was performed with commercial typing trays. RESULTS: Organs were allocated from a total of 88 cadaveric donors to 320 patients treated at CKUH and 179 patients treated at NTUH. Cadaveric kidneys could be allocated with an A,B,DR mismatch to 6.9% of CKUH patients and to 4.7% of NTUH patients. When CKUH and NTUH patients were pooled, the total number of kidneys that could be allocated with 0-A,B,DR mismatch increased to 13.3% (p < 0.004). However, when allocation was assessed using 10,000 potential bone marrow donors instead of the 88 cadaveric donors, kidneys could have been allocated with 0-A,B,DR mismatch to 12% (p = 0.64) of patients. No significant benefit was found when allocation estimates from the 10,000 potential bone marrow donors were compared with those for the 88 cadaveric donors. Use of epitope matching resulted in a 0-A,B cross-reactive epitope group, and a 0-DR mismatch allocation rate of 36.4% in CKUH patients and 31.8% in NTUH patients. This rate increased to 54.6% (p < 0.001) when the patients from these hospitals were pooled. CONCLUSION: The results of this study demonstrate that the pooling of patients among regional transplant centers in Taiwan can significantly enhance the benefits of an organ donation program through better HLA matching.

HLA-A Antigens↗
PubMed1999

Comparisons of a proposed five-seed assay method with the single-seed and batch assay methods for I-125 seeds in ultrasound-guided prostate implants.

A simple five-seed assay method was proposed and investigated. A commercial well ion chamber system with an NIST-traceable single-seed calibration constant was used for the single-seed assays. A batch seed holder was used for batch assays. For the five-seed assays, a second single-seed holder was modified such that all five seeds were loaded in a central region of the well ion chamber. Compared with the same seed in the standard single-seed holder, the relative chamber responses for the five seed positions were 0.993, 0.993, 1.000, 1.001, and 0.977, respectively, indicating little or no position-dependent chamber response and no self-attenuation among seeds. Subsequent comparison of assays with the single-seed and five-seed methods indicated only 0.4% difference in charge collection. The five-seed calibration constant was therefore taken to be the same as the single-seed calibration constant. The reproducibility of the five-seed assay method was found to be better than 0.8%. When a dummy seed replaced an active seed, a nearly 20% reduction in charge was found, indicating that the proposed five-seed assay method can detect a dead seed. Clinical comparison of all three assay methods showed that they produced qualitatively the same assay results when the batch assay method was performed with extra care. Compared with the single-seed assay method, the five-seed method is equally simple, rigid, and reproducible, but it demands much less assay time. Compared with the batch assay method, the five-seed method is much more reproducible and reliable because of its rigid assay geometry; it only demands a moderate amount of assay time and can detect dead seeds. The American Association of Physicists in Medicine Task Group 40 (AAPM TG40) states that, for brachytherapy, ideally every (i.e., 100%) loose seed should be calibrated. For procedures involving large number of loose seeds, it then recommends that 10% of seeds be calibrated. The proposed five-seed assay is very simple to implement. It will facilitate the compliance of the "10%" recommendation from the AAPM TG40; it will make the "ideally 100%" statement from AAPM TG40 a more realistic and practical QA procedure in seed assaying.

Brachytherapy↗
PubMed1999

Early polyethylene wear and osteolysis in cementless total hip arthroplasty: the influence of femoral head size and polyethylene thickness.

We examined initial polyethylene thickness, early polyethylene liner wear, and osteolysis in 350 primary, cementless total hip arthroplasties (THAs). All of the prostheses were of identical design and used Omnifit components. In the 32-mm head group, the mean liner wear correlated significantly with polyethylene thickness (P<.001) and increased rapidly with initial thinner polyethylene following a logarithmic model, although this increase was not statistically significant (r = -.633). Inadequate polyethylene thickness in the 32-mm head group was implicated as the major cause of higher liner wear. A minimal polyethylene thickness of 7 mm is recommended in cementless metal-backed THAs. The use of a large head combined with poor prosthetic design appeared to be responsible for the unacceptably high incidence of femoral osteolysis.

Acetabulum↗
PubMed1999

Early results and long-term follow-up after corrective surgery for total anomalous pulmonary venous return.

OBJECTIVE: An ever increasing number of patients with an operated congenital cardiac anomaly is reaching adulthood. Insight in the long-term characteristics of these patients is steadily growing for the more common anomalies, but is still scarce for the less frequent entities. In this regard we report our results and long-term follow-up of surgically treated total anomalous pulmonary venous return (TAPVR). METHODS: Since 1973 44 patients with TAPVR were treated with surgery. There were 23 girls and 21 boys. Hospital mortality concerned six patients and additionally one patient died 2.5 months after surgery. Follow-up data could be collected from all the surviving patients at last outpatient visit or by phone contact. The mean duration of the follow-up was 12 years (range 1 month to 24 years). RESULTS: The Kaplan-Meier estimate of survival at 15 years was 84% (95% CI 73-95%). Reoperations were performed for five patients at 7 days to 4.5 years after surgery. In one patient this involved obstruction of pulmonary venous return, in four complications of the primary repair. The reoperation-free survival at 15 years was 74% (95% CI 61-87%). At the end of follow-up all survivors were in NYHA functional class I and, at appropriate age, normally attended school or were employed. None of the patients was using cardiac medication. CONCLUSIONS: We conclude that, despite a possible hectic initial postoperative course of surgery for TAPVR, only a limited number of reoperations is necessary relatively short after initial surgery. The long-term perspective for those surviving surgical treatment is good.

Cardiopulmonary Bypass↗