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Biomedical subjects

K H Lee

Publications and source records attributed to K H Lee.

At least 37 records · Page 2Linked to original sources

MELD may not be the better system for organ allocation in liver transplantation patients in Singapore.

INTRODUCTION: The Model for End-Stage Liver Disease (MELD) score is a good predictor of mortality on the liver transplant waiting list and is the current system of organ allocation in the USA. However, a higher MELD may be associated with poorer outcome post-liver transplantation. The aim of this study was to determine if MELD should be implemented as the system for organ allocation for liver transplantation in Singapore. METHODS: There were 46 adult patients who underwent primary liver transplantation at the National University Hospital, Singapore from January 1996 to December 2002. We applied the MELD score to patients who were transplanted and looked for a correlation with survival post-transplant. Patients were followed-up until the most recent visit or death. Survival analysis was performed using Cox regression and Kaplan-Meier method. RESULTS: The mean age at transplant was 52.7 (SD 2.34) years. The majority of the patients transplanted had Hepatitis B (43 percent). The median MELD score at transplantation was 17 (7-42) and the median Child's score was 11 (6-15). There was a significant correlation between pre-transplant MELD and survival at six months (p-value is 0.037, 95 percent confidence interval [CI] is 1.004-1.13) but not at one year (p-value is 0.065, 95 percent CI is 0.99-1.12). There were no differences in the pre-transplant MELD (odds-ratio [OR] 1, 95 percent CI 0.9-1) as well as survival for patients with and without Hepatitis B (OR 0.72, 95 percent CI 0.22-2.35). CONCLUSION: MELD allows livers to be allocated to the patients with the greatest medical urgency but its influence on post-transplant survival should be further clarified so that post-transplant survival is not compromised.

Female↗

Referral patterns and waiting times for liver transplantation in Singapore.

INTRODUCTION: Referral patterns, waiting times, waiting list, and mortality provide information on how effectively a transplant programme deals with referred patients. This paper aims to review these parameters in the Singapore National Liver Transplant Programme. METHODS: Data of all patients referred to the Singapore National Liver Transplant Programme since its inception were captured and outcomes were retrieved and described. RESULTS: 562 patients were referred for liver transplant evaluation from 1990-2004, consisting of 457 adults and 105 children. The main indications for referral were hepatitis B liver disease and hepatocellular carcinoma in adults, and biliary atresia in children. Most patients were of United Network of Organ Sharing (UNOS) status 3 or 4 at the time of referral. 114 (20.28 percent) patients had transplants, consisting of 66 adults (14.44 percent) and 48 (45.71 percent) children. 138 adults and ten children were rejected for transplant, mainly for the reason of being "too early". The median waiting time for adults who had transplants was 3.3 months while adults still on the waiting list had been waiting for 16.2 months. The overall waiting list mortality was 44.3 percent, being 52.5 percent in adults and 23.2 percent in children. CONCLUSION: The overall transplantation rate is low and the waiting list mortality is high as a result of low availability of organs, particularly in adults. Paediatric liver transplant appears to have been better at dealing with referred patients but this is probably due to availability of living-related liver transplant. Improvement in these may result from the Human Organ Transplant Act.

Adult↗

Long-term post-liver transplant complications of renal impairment and diabetes mellitus: data from Singapore.

INTRODUCTION: Patients who survive the initial post-liver transplantation period face the development of chronic diseases in the long run. We studied two important complications of liver transplantation, namely: renal impairment and diabetes mellitus. METHODS: We analysed adult patients followed-up for more than one year using data from our liver transplant clinical records. Long-term post-transplant renal impairment (RI) was defined as glomerular filtration rate (GFR) less than 60 ml/min/1.73 square metres and long-term post-transplant diabetes mellitus (DM) was defined as fasting blood glucose more than 7.8 mmol/L, that existed at least one year after liver transplantation. Pre- and post-transplant factors that could be associated with these conditions were examined. RESULTS: Altogether, 35 patients were evaluated. Mean age at transplant was 50 years. Mean duration of follow-up was 58.4 months. There was 11.4 percent of pre-transplant RI and 17.0 percent of pre-transplant DM. Prevalence of post-transplant RI was 43.5 percent at one year and 45.0 percent at four years. Long-term post-transplant RI was associated with renal impairment at six months post-transplant (p-value is 0.033). Prevalence of severe post-transplant RI (GFR is less than 30 ml/min/1.73 square metres) at four years was 5.7 percent. Prevalence of post-transplant DM was 45.5 percent at two years but declined to 5.3 percent at four years. CONCLUSION: Post-transplant renal impairment appears to be a potential long-term problem while post-transplant diabetes mellitus appears to improve with time.

Diabetes Mellitus↗

Reversed discrepancy between CT and diffusion-weighted MR imaging in acute ischemic stroke.

PURPOSE: We sought to determine whether an early CT ischemic lesion showing parenchymal hypoattenuation might be undetectable on diffusion-weighted imaging (DWI) in acute cerebral ischemia. MATERIALS AND METHODS: We retrospectively evaluated CT and MR images of 70 consecutive patients with acute middle cerebral artery (MCA) infarction. All patients underwent CT and MR imaging within 6 hours of symptom onset. We determined the presence of reversed discrepancy (RD), defined as an early ischemic lesion showing parenchymal hypoattenuation on CT but no hyperintensity on DWI. CT Hounsfield units (HU), apparent diffusion coefficients (ADCs), and perfusion parameters were calculated for RD lesions. RESULTS: RD was found in 9 (12.9%) patients and at basal ganglia (89%). The mean HU of RD lesion was lower than that of normal tissue (DeltaHU, 2.33 +/- 0.74, P < .001). RD lesions showed no significant decrease of ADC (ADC ratio, 0.97 +/- 0.07, P = .059) and cerebral blood flow (relative CBF, 0.87 +/- 0.20, P > 0.05). Delayed DWI hyperintensity occurred in 8 (88.8%) RD lesions, and all lesions progressed to infarction. In 6 (66%) of 9 patients with RD, Alberto Stroke Program Early CT scores of ischemic lesions were lower on CT than those on DWI. CONCLUSION: RD was uncommonly found mainly in basal ganglia, and all RD lesions progressed to infarction at follow-up. Early CT ischemic lesion showing parenchymal hypoattenuation may be undetectable on DWI, and DWI may underestimate extent of severe ischemic tissue in patients with acute MCA infarction.

Acute Disease↗

Genetic polymorphisms of OPG, RANK, and ESR1 and bone mineral density in Korean postmenopausal women.

To evaluate the effects of genetic polymorphisms of OPG, RANK, and ESR1, which regulate osteoclastogenesis, on bone mineral density (BMD), a cross-sectional study was conducted in 650 Korean postmenopausal women. BMDs of the distal radius and the calcaneus were measured by dual energy X-ray absorptiometry (DXA). Genetic polymorphisms of OPG 163 A > G, 1181 G > C; RANK 421 C > T, 575 T > C; and ESR1 1335 C > T, 2142 G > A were determined by matrix-assisted laser desorption/ionization-time of flight (MALDI-ToF) mass spectrometry. The differences between the BMDs of the genotypes of OPG, RANK, and ESR1 were analyzed by multiple linear regression model adjusted for age and body mass index. Women with the OPG 1181 CC genotype had higher BMDs at the distal radius (7%) and calcaneus (10%) than those with the GG genotype; and these differences were statistically significant (P = 0.001 and P = 0.007, respectively). A significant association was also observed between RANK 575 T > C and calcaneus BMD (P for trend = 0.017). No significant association was observed between BMDs and the polymorphisms of ESR1. The association between OPG 1181 G > C and BMD was profound in subjects with the RANK 575 TT or ESR1 2142 GG genotypes; women with OPG 1181 CC had higher BMDs at the distal radius (11%) and calcaneus (11%) than those with OPG 1181 GG only in women with RANK 575 TT genotype (P = 0.002 and P = 0.021, respectively). These results suggest that OPG genetic polymorphisms, especially with the RANK 575 TT or ESR1 2142 GG genotypes, are related to low BMD in postmenopausal Korean women.

Adult↗

Glucose metabolism in early onset versus late onset Alzheimer's disease: an SPM analysis of 120 patients.

The aims of this cross-sectional study were (i) to compare the overall glucose metabolism between early onset and late onset Alzheimer's disease in a large sample of patients; and (ii) to investigate the pattern of glucose metabolism as a function of dementia severity in early onset versus late onset Alzheimer's disease, using a statistical parametric mapping (SPM) analysis. Subjects consisted of four groups: 74 patients with early onset Alzheimer's disease, 46 patients with late onset of the disease, and two control groups age matched to each patient group. All the subjects underwent 2-[(18)F]fluoro-2-deoxy-d-glucose (FDG)-PET under the same scanning conditions. Severity of dementia was rated with the Clincial Dementia Rating (CDR). Voxel-based SPM99 was used for statistical analyses. Overall glucose hypometabolism of early onset Alzheimer's disease patients was much greater in magnitude and extent than that of late onset patients, though both groups were similar in dementia severity: the early onset group showed more severe hypometabolism in parietal, frontal and subcortical (basal ganglia and thalamus) areas. When the decline of glucose metabolism was compared as a function of CDR stage, the slope was steeper in early onset than in late onset Alzheimer's disease. The rapid decline occurred at CDR 0.5-1 in the early onset group, whereas similar changes occurred at CDR 2-3 in the late onset group. The greater hypometabolism in early onset than in late onset patients is required to reach the same severity of dementia, probably reflecting greater functional reserve in younger than in older subjects. Alternatively, the metabolic decline curve suggests that the early onset patients may take a more rapid course in the reduction of glucose metabolism than the late onset patients.

Age of Onset↗

Mechanism of action and resistant profile of anti-HIV-1 coumarin derivatives.

Dicamphanoyl khellactone (DCK) is a coumarin derivative that can potently inhibit HIV-1 replication. DCK does not inhibit RNA-dependent DNA synthesis. However, an HIV reverse transcriptase (RT) inhibitor-resistant strain, HIV-1/RTMDR1, is resistant to DCK. Thus, it is possible that HIV-1 RT is the target of DCK. To test this possibility, DCK-resistant viruses were selected in the presence of DCK. Our results indicate that a single amino acid mutation, E138K in HIV-1 RT, is sufficient to confer DCK resistance. Interestingly, a DCK derivative, 3'R,4'R-Di-O-(-)-camphanoyl-2-ethyl-2',2'-dimethyldihydropyrano[2,3-f]chromone (DCP8), is effective against HIV-1/RTMDR1. However, the DCK-escape virus carrying the E138K mutation remains resistant to DCP8. Since DCK did not inhibit the RNA-dependent DNA polymerase activity of HIV-1 RT when using poly-rA or poly-rC as template, we evaluated the effect of DCK on the DNA-dependent DNA polymerase activity of HIV-1 RT. Our results indicate that DCK can inhibit the DNA-dependent DNA polymerase activity of HIV-1 RT. In conclusion, DCK is a unique HIV-1 RT inhibitor that inhibits the DNA-dependent DNA polymerase activity. In contrast, DCK did not significantly affect the RNA-dependent DNA polymerase activity when poly-rA or poly-rC was used as templates. An E138K mutation in the non-nucleoside RT inhibitors (NNRTIs) binding pocket of HIV-1 RT confers resistance to DCK and its chromone derivative, DCP8.

Animals↗

The pattern of distribution of pectin, peroxidase and lignin in the middle lamella of secondary xylem fibres in alfalfa (Medicago sativa).

BACKGROUNDS AND AIMS: Information on the micro-distribution of lignin within the middle lamella is only just beginning to emerge. This paper provides evidence of marked heterogeneity in the micro-distribution of lignin, pectin, peroxidase and hydrogen peroxide in the middle lamella of alfalfa (Medicago sativa). METHODS: Specimens from alfalfa stems were collected and processed for transmission electron microscopy. The middle lamella architecture was examined prior to and during lignification, using transmission electron microscopy in combination with pectin- and lignin-specific staining. In addition, immuno-gold labelling of peroxidase and cytochemical localization of hydrogen peroxide (H2O2) were undertaken. KEY RESULTS: Lignin showed inhomogeneity in its distribution in the middle lamella. It was found that the distribution of pectin was irregular and corresponded to the pattern of deposited lignin. Additionally, a similarity in the pattern of the deposited lignin to the pattern of distribution of peroxidase and H2O2 was also observed. CONCLUSIONS: Irregular distribution of pectin in the middle lamella may be related to subsequent inhomegeneity in lignin in this region.

Cell Wall↗

Decision-related factors and attitudes toward donation in living related liver transplantation: ten-year experience.

INTRODUCTION: Living related liver transplantation (LRLT) has been performed since 1994 in Korea; more than 600 donors have contributed to our successful LRLT program for 10 years. Although the decision to donate is difficult and the donors need a formal psychosocial assessment, no system has been available to us for the assessment. This survey was performed as a presurveillance for the development of a psychosocial assessment protocol. METHODS: A survey questionnaire included 31 questions on general and medical characteristics, factors, and processes related to the decision for donation. Donors of partial livers at least 6 months ago during the period from December 1994 to August 2003 and whose address could be confirmed by telephone were enrolled in the study. RESULTS: A questionnaire was sent by mail to 441 contactable donors of whom 209 (47.4%) responded. Male-to-female ratio was 2:1 and mean age was 32.8 years (range: 16 to 60 years). The number of spousal donors was 120 (57.4%) and 164 (78.5%) donors were employed at the time of donation. Protestants, Buddhists, and Catholics were 29.2%, 19.1%, and 14.8%, respectively. Parents were the most common recipients (33.0%), followed by siblings (17.2%), extended family members (17.2%), and children (15.8%); one hundred eighty nine (90.4%) donors had decided by themselves, the major reason for donation in 192 (91.9%) donors was "to save the lives of family members and relatives." The first person who suggested donation was the donor (64.1%), followed by family members (23.9%) or the attending physicians (8.6%). Although 70.8% of donors answered that they were not hesitant to donate at the time of decision, 44.5% were uneasy at the possibility of being unable to sustain a normal life after donation, at their lack of knowledge on organ donation, and about the pain and fear of surgery. Family members and relatives (53.3%), medical personnel (46.7%), and previous donors (35.4%) were the preferable counselors compared to transplantation institutions and clergymen. The large majority (80.8%) of donors would encourage others to donate. CONCLUSIONS: Although the decision to donate was made by the donors themselves in most cases and they appeared firm and determined about their decision, a significant number of donors felt uneasy about possible complications of organ donation and effects on their lives after donation. A precise and formal psychosocial assessment protocol is needed to support and secure their decision before and after donation.

Adolescent↗

Treatment of steroid-resistant acute liver transplant rejection with basiliximab.

Current rescue therapies for acute steroid-resistant rejection, such as OKT3 and high-dose tacrolimus, are not uncommonly associated with side effects that contribute to significant morbidity of the patient. Basiliximab is a chimeric monoclonal antibody that acts as an interleukin-2 receptor antagonist on the surface of activated T lymphocytes. It has until now only been used as immunoprophylaxis in adult liver transplant patients. In this report, we describe the use of Basiliximab as rescue therapy in a case of acute steroid-resistant rejection in an adult living related liver transplant recipient.

Adrenal Cortex Hormones↗

Complete sequence and structure of the mitochondrial genome of the human tapeworm, Taenia asiatica (Platyhelminthes; Cestoda).

The complete Taenia asiatica mitochondrial genome was amplified by long extension polymerase chain reaction (long PCR) to yield overlapping fragments that were then completely sequenced. The whole mitochondrial genome was 13 703 bp long and contained 12 protein-encoding, 2 ribosomal RNA (small and large subunits), 22 transfer RNA genes and a short non-coding region. Thus, its gene contents are like those typically found in metazoan animal mitochondrial genomes (apart from the absence of atp8). All the genes were transcribed from the same strand. The 3' end 34 bp region of nad4L overlapped with the 5' end portion of nad4. The tRNA genes were 61-69 bp long, and the secondary structures of 18 tRNAs had typical clover-leaf shapes with paired DHU arms. However, trnC, trnS1, trnS2 and trnR had unpaired DHU arms that were 7-12 bp in length. The tRNAs that transferred serine lacked a DHU arm, as is also observed in a number of parasitic platyhelminths and metazoans. However, the trematode trnRs have paired DHU arms. The T. asiatica mtDNA non-coding region was like that in other cestodes since it was composed of a short non-coding region of 72 nucleotides and a long non-coding region of 176 nucleotides separated by a trnL1/, trnS2/, trnL2/, trnR/, nad5 gene cluster. The sequences of the cox1 genes between T. asiatica and T. saginata differ by 4.6%, while the T. asiatica cob gene differs by 4.1% and 12.9% from the cob genes of T. saginata and T. solium, respectively. In conclusion, the T. asiatica mitocondrial genome should provide a resource for comparative mitochondrial genomics and systematic studies of parasitic cestodes.

Animals↗

Different subsets of primary chronic myeloid leukemia stem cells engraft immunodeficient mice and produce a model of the human disease.

Xenograft models of chronic phase human chronic myeloid leukemia (CML) have been difficult to develop because of the persistence of normal hematopoietic stem cells in most chronic phase CML patients and the lack of methods to selectively isolate the rarer CML stem cells. To circumvent this problem, we first identified nine patients' samples in which the long-term culture-initiating cells were predominantly leukemic and then transplanted cells from these samples into sublethally irradiated NOD/SCID and NOD/SCID-beta2microglobulin-/- mice. This resulted in the consistent and durable (>5 months) repopulation of both host genotypes with similar numbers of BCR-ABL+/Ph+ cells. The regenerated leukemic cells included an initial, transient population derived from CD34+CD38+ cells as well as more sustained populations derived from CD34+CD38- progenitors, indicative of a hierarchy of transplantable leukemic cells. Analysis of the phenotypes produced revealed a reduced output of B-lineage cells, enhanced myelopoiesis with excessive production of erythroid and megakaropoietic cells and the generation of primitive (CD34+) leukemic cells displaying an autocrine IL-3 and G-CSF phenotype, all characteristics of primary CML cells. These findings demonstrate the validity of this xenograft model of chronic phase human CML, which should enable future investigation of disease pathogenesis and new approaches to therapy.

Animals↗

Role of combined modality treatment of buccal mucosa squamous cell carcinoma.

BACKGROUND: Squamous cell carcinoma of the buccal mucosa is an oral cancer reported as having a poor prognosis. In many patients combined modality treatment incorporating surgery and adjuvant radiotherapy should be considered best practice. METHODS: Patients treated for buccal mucosa squamous cell carcinoma were identified through the computer database in the Department of Radiation Oncology, Westmead Hospital, Sydney. All eligible patients were treated with curative intent. Survival was calculated using the Kaplan-Meier product limit method. RESULTS: A total of 32 eligible patients were identified. There were 20 males and 12 females. Median age at diagnosis was 67 years (range 44-82 years). Median duration of follow-up was 42 months (6-205 months). More than half (59 per cent) presented with early stage disease (stage I/II) with 35 per cent presenting with advanced (stage III/IV) disease. Most patients (28/32; 88 per cent) underwent surgery with eight patients also undergoing adjuvant radiotherapy. Four patients underwent definitive radiotherapy alone. A total of 15/32 (47 per cent) patients developed recurrence: four locally, eight regionally and three with locoregional recurrence. Patients treated with surgery and adjuvant radiotherapy had the lowest rate of recurrence. Median time to recurrence was five months. The three-year overall and disease free survival was 55 and 47 per cent, respectively. CONCLUSION: Buccal mucosa squamous cell carcinoma is an aggressive squamous cell carcinoma of the oral cavity. Despite treatment patients remain at risk of locoregional recurrence especially in the untreated ipsilateral neck. In many cases patients will benefit from multimodality treatment.

Adult↗

Tuberculosis post-liver transplantation: a rare but complicated disease.

INTRODUCTION: Tuberculosis is a rare but serious complication after transplantation. We report a case and discuss its presentation and management. CLINICAL PICTURE: A 60-year-old Indonesian male presented initially with fever, acute confusion and rapidly progressive right upper lobe pneumonia 3.5 months post-liver transplant, and was diagnosed with pulmonary tuberculosis by positive sputum smear for acid-fast bacilli and tuberculosis culture. TREATMENT/OUTCOME: Standard anti-tuberculosis therapy was administered but was complicated by interaction with cyclosporine and drug-induced cholestasis. CONCLUSION: A high level of suspicion, prompt antituberculosis treatment and close follow-up are essential in management of post-transplant tuberculosis.

Antibiotics, Antitubercular↗

Use of fouling resistant nanofiltration and reverse osmosis membranes for dyeing wastewater effluent treatment.

Dyeing wastewater was post-treated by using nanofiltration (NF) and reverse osmosis (RO) membranes. To reduce membrane fouling, poly (vinyl alcohol) (PVA) with a neutral charge was coated on NF and RO membranes. The effect of surface charge and surface roughness on membrane fouling was investigated. Dyeing wastewater was pre-treated by using coagulation, activated sludge process, and MF process to investigate the effect of the pre-treatment on the membrane fouling. It is demonstrated that the extent of fouling is significantly influenced by the surface roughness and the surface charge on the NF and RO membranes. A membrane with a smooth and neutral surface was fouled less. The pre-treatment was essential for avoiding NF and RO membranes fouling. The quality of the final permeate was acceptable for water reuse.

Bioreactors↗

Calcified Klatskin tumor mimicking intrahepatic stone: case report.

Calcification is a relatively uncommon manifestation of malignant liver neoplasm. Calcifications in peripheral cholangiocarcinomas but not in Klatskin tumor have been reported. We present a rare case of Klatskin tumor that had dystrophic calcification mimicking a intrahepatic stone in a 65-year-old man.

Aged↗

Complete nonvisualization of basilar artery on MR angiography in patients with vertebrobasilar ischemic stroke: favorable outcome factors.

BACKGROUND: In vertebrobasilar ischemic stroke, magnetic resonance angiography (MRA) occasionally fails to visualize the basilar artery, but in these patients, little attention has been given to establishing correlations between the clinical and the radiological findings. Our aim was to identify clinical or radiological measures that could assist in predicting a favorable clinical outcome. METHODS: Risk factors, clinicoradiological features, and functional outcomes were assessed in 40 patients with vertebrobasilar ischemic stroke whose basilar arteries were absent on MRA. The presence of potential feeding arteries to the posterior circulation was recorded from a review of the MRA data. To permit quantitative analysis of the images, a potential feeding artery score (PFAS; range: 0-8) was established. One point was assigned when a signal was seen from an intracranial vertebral artery, a posterior inferior cerebellar artery, a superior cerebellar artery, or a posterior cerebral artery. On MRI, the location of the infarction was classified as involving the proximal, middle, and distal territories of the intracranial posterior circulation. The infarctions were also categorized as single- or multi-sector infarctions, and according to whether more than one penetrating or branch artery was involved. Clinical outcomes were classified as favorable (modified Rankin Scale = 0-2) or poor (modified Rankin Scale = 3-6). RESULTS: The clinical outcome was favorable in 30% (n = 12) of patients, and poor in 70% (n = 28). A transient ischemic attack preceded the stroke in 48% of patients, especially those with a favorable outcome (67%). Patients with a favorable outcome had a higher PFAS (p = 0.036) and an increased incidence of single-sector infarction (p = 0.049). CONCLUSIONS: Our study suggests that a higher PFAS, accompanied by a single-sector infarction, is a predictor of improved clinical outcome in patients with vertebrobasilar ischemic stroke in which the basilar artery was absent on MRA.

Adult↗