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Biomedical subjects

D Tan

Publications and source records attributed to D Tan.

At least 19 recordsLinked to original sources

Successful treatment of primary granulocytic sarcoma by non-myeloablative stem cell transplant.

Pre-leukemic granulocytic sarcoma (GS) may pose an initial diagnostic problem and its therapeutic approach has never been formally established. To our knowledge, non-myeloablative stem cell transplantation has been reported in cases of leukemic GS, but not in primary GS. We report a case of primary GS with extensive and aggressive presenting features and successfully treated with intensive chemotherapy followed by non-myeloablative allogeneic stem cell transplant. This resulted in complete remission with minimal complications. Our case demonstrates the potential of graft-vs.-tumour effect in the treatment of GS and suggests that non-myeloablative allogeneic stem cell transplant may be a feasible therapeutic approach for primary GS.

Antineoplastic Combined Chemotherapy Protocols↗

Is downregulation of MHC class I antigen expression in human non-small cell lung cancer associated with prolonged survival?

PURPOSE: To characterize HLA class I antigen expression in non-small cell lung cancer (NSCLC) lesions, and to assess the clinical significance of these molecules' downregulation. METHODS: One hundred and ninety primary formalin fixed, paraffin embedded NSCLC lesions were stained with HLA class I heavy chain-specific mAb HC-10. Results were scored as percentage of stained tumor cells and categorized into three groups: 0-24% (negative), 25-75% (heterogeneous) and >75% (positive). HLA class I antigen expression was correlated with clinical and pathologic predictors of time to progression and survival and analyzed using the chi-square test. Association between HLA class I antigen expression and survival was assessed using Cox regression models, while controlling for confounders. RESULTS: HLA class I antigen expression was negative, heterogeneous and positive in 153, 25 and 12 primary NSCLC lesions, respectively. Independent variables significantly associated with survival included tumor stage, PS and weight loss. The median survival times were 40.6, 44.0 and 17.9 months for patients with a HLA class I antigen expression scored as negative, heterogeneous and positive, respectively. CONCLUSION: HLA class I antigen defects were found with high frequency (93.6%) in NSCLC lesions. HLA class I antigen downregulation was associated with improved survival, although this association was not statistically significant. These results, which parallel similar findings in uveal melanoma and in breast carcinoma, raise the possibility that NK cells may play a role in the control of NSCLC tumors.

Adult↗

Vermicomposting of cattle and goat manures by Eisenia foetida and their growth and reproduction performance.

Vermicomposting is commonly adopted for the treatment of livestock organic wastes. In the present study, two types of livestock manure were used for culturing of the earthworm, Eisenia foetida. Each treatment group consisted of six replicates and worm vermicasts were examined after 5 weeks. The concentrations of total C, P and K in goat manure vermicasts were higher than those in cattle manure vermicasts. Cattle vermicasts had a higher N content than goat vermicasts but the C:N ratio of fresh manure was higher than that of vermicasts for both materials. Earthworm biomass and reproductive performance, in terms of number of worms after 5 weeks of experiment, were higher in cattle manure than in goat manure. The cocoon production per worm in cattle manure was higher than in goat manure. However, the hatchability of cocoons was not affected by manure treatments. In conclusion, cattle manure provided a more nutritious and friendly environment to the earthworms than goat manure.

Analysis of Variance↗

Geographic distribution, virologic and clinical characteristics of hepatitis B virus genotypes in China.

The significance of hepatitis B virus (HBV) genotypes for the heterogeneity of chronic HBV infection and severity of liver disease is not well understood. The aim of this study was to determine the distribution and virologic characteristics of HBV genotypes in China and possible association with the diversity of liver disease. The study includes 1096 chronic HBV carriers from nine provinces in China. We collected clinical and laboratory data and analysed the HBV strains in sera by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and nucleotide sequencing techniques. The most common HBV genotypes were B (41%) and C (53%), while genotypes A and D were also found. A North-South divide was identified in genotype B and C distribution - genotype C was predominant in northern China, while genotype B was more prevalent in southern provinces. Patients with genotype B were younger than those with genotype C, and had a lower prevalence of HBeAg - 65%vs 72%, respectively (P = 0.03). However, the severity of liver disease did not differ significantly between patients infected with genotype B or C - neither when comparing liver function tests (1024 patients), nor hepatic inflammation and fibrosis (264 patients). Amongst 47 patients with genotype D (by PCR-RFLP), 37 (79%) were infected with a new subtype (designated Dc), having a recombination fragment from genotype C precore/core region. This is the first large-scale HBV genotype study from China and convincing documentation of the North-to-South gradient of genotypes C vs B in this country. HBV DNA recombination over the surface and precore/core genes increases the diversity of HBV strains and may have diagnostic and clinical implications.

Adult↗

Multifocal electroretinogram in children on atropine treatment for myopia.

AIM: To assess retinal function by multifocal electroretinogram (mfERG) in children on atropine eye drops for the treatment of myopia. METHODS: mfERGs were recorded in children receiving atropine eye drops (n = 48) once daily for 2 years and in those receiving placebo eye drops (n = 57) for a similar time. All recordings were performed between the second and third month of cessation of atropine/placebo treatment by a masked investigator. The amplitude and implicit time of the first order kernel (k1) and first slice of the second order kernel (k21) of mfERG responses were used to study the outer and inner retinal function, respectively. RESULTS: There was no significant reduction in k1 response amplitudes of the atropine group compared to that of the placebo group (N1, p = 0.181; P1, p = 0.150). No significant difference in the k1 response implicit times between the groups was found (N1, p = 0.767; P1, p = 0.849). The differences in the k21 amplitudes and implicit times between the groups were not statistically significant (k21 amplitude, p = 0.058; k21 implicit time, p = 0.156). CONCLUSIONS: Daily atropine usage over 2 years for the treatment of myopia has no significant effect on retinal function as demonstrated by recordings of mfERG.

Atropine↗

Use of lamotrigine to augment clozapine in patients with resistant schizophrenia and comorbid alcohol dependence: a potent anti-craving effect?

Comorbid alcohol dependence is common in patients with schizophrenia and is associated with a variety of serious adverse consequences. Although case reports exist concerning the positive impact of lamotrigine addition on clozapine treatment in resistant schizophrenia, a review of the literature fails to document any evidence regarding a combination of the two in the treatment of patients with schizophrenia and comorbid alcohol dependence. In the present study, we present three cases in which patients with resistant schizophrenia and comorbid alcohol use disorder were given lamotrigine to augment clozapine. Our findings suggest that clozapine plus lamotrigine may be helpful in reducing alcohol consumption and craving among patients with schizophrenia and comorbid alcohol dependence.

Adult↗

Therapeutic leukapheresis in hyperleukocytic leukaemias--the experience of a tertiary institution in Singapore.

INTRODUCTION: Hyperleukocytic leukaemias are associated with early mortality due to respiratory or neurological complications. They result from endothelial damage secondary to leukostasis. Leukapheresis, which aims to lower the white blood cell (WBC) count, has been used in certain patients to reduce the threat from leukostasis. However, there are very few published clinical investigations on the most appropriate use of leukapheresis in hyperleukocytosis. MATERIALS AND METHODS: We performed a retrospective analysis of 14 patients with hyperleukocytic leukaemia who presented to our institution and underwent therapeutic leukapheresis. We compare their clinical and biological characteristics and investigate the impact of leukapheresis on early mortality and long-term prognosis. RESULTS: The median presenting WBC count was 439 x 10(3)/mm(3). Although patients with acute myeloid leukaemia (AML) had the lowest median presenting WBC counts, they constituted the largest group of patients with symptomatic hyperleukocytosis. Leukapheresis was highly effective, with the mean absolute and percentage reduction in WBC after each cycle being 126 x 10(3)/mm(3) and 31.9% respectively. Four patients with AML died within 2 weeks of presentation despite prompt and effective leukapheresis. CONCLUSION: The interaction between the leukaemic cells and the vascular environment, a mechanism that none of the current therapies directly address, is probably more important in causing leukostasis than the absolute cell count itself.

Adolescent↗

Primary adenocarcinoma of cervical esophagus.

Most upper esophageal malignancies are squamous cell carcinomas, rarely adenocarcinomas arising from Barrett's esophagus and very rarely adenocarcinomas from heterotopic gastric mucosa without evidence of Barrett's especially in the cervical part of the esophagus. We report a case of adenocarcinoma of the polypoid type in the upper esophagus (cervical esophagus) arising from ectopic gastric mucosa, in a 60 year-old man who presented with progressive dysphagia. Accurate diagnosis by esophagogram revealed a large mass in the cervical esophagus; CAT scan showed intraluminal mass at the level of thoracic inlet, esophagogastroscopy showed a fleshy polyp (3.2cm x 3.0cm) at 20 cm from the incisors with a biopsy confirming moderately differentiated adenocarcinoma with no evidence of Barrett's esophagus. Through a left cervical approach and resection of medial third of clavicle, the tumor was removed by partial esophagectomy followed by lymph node dissection, and proved to be T1NOMO, stage I (AJCC staging 6th ed.). Post operatively, the patient received chemoradiation with no evidence of recurrence or metastasis in six years of follow up. It seems this tumor has a much better prognosis than adenocarcinomas arising from Barrett's. To our knowledge only 19 cases have been reported in literature so far.

Adenocarcinoma↗

Successful treatment of idiopathic hypereosinophilic syndrome with imatinib mesylate: a case report.

Patients with idiopathic hypereosinophilic syndrome (HES) show persistent hypereosinophilia of unknown etiology that is associated with end-organ damage. Different treatments, including the use of corticosteroids and cytotoxics, have been investigated for HES with modest success. We describe a patient with HES who had significant end-organ damage from hypereosinophilia and remained refractory to conventional therapy. Therapy with imatinib mesylate, a selective tyrosine kinase inhibitor that is highly effective in treating patients with BCR-ABL-positive chronic myeloid leukemia, was tried with the patient. The result was impressive, with hematologic remission achieved after 12 days of administration. Our finding concurs with recent reports that imatinib mesylate may be a promising agent in the treatment of some cases of HES.

Adult↗

Molecular characterization and utilization of the CAK1 filamentous viruslike particle derived from Clostridium beijerinckii.

An examination of the replication origin and stability determinant associated with the CAK1 filamentous viruslike particle recovered from Clostridium beijerinckii NCIMB 6444 was carried out. Seven deletion derivatives, pCKE, pCEP1, pDT5, pCKP, pDTH102, pYL102E and pYL102, were constructed and transformed into C. beijerinckii NCIMB 8052. The successful transformation of pCKE, pDT5, pCKP, pDTH102, pYL102E and pYL102 into C. beijerinckii 8052, together with the corresponding recovery of single-stranded DNA from Escherichia coli indicated that the double- and single-stranded replication origins are located on a 0.4-kb CAK1 DNA fragment. Sequence analysis of the putative 0.4-kb replication origin region of CAK1 reveals a nick site containing 22 base pairs that has homology with plasmids pC194 and pUB110 and suggests the presence of a 2.0-kb DNA region involved in stability. The putative Rep protein of CAK1 contains three conserved motifs and three essential residues of the catalytic site in agreement with Rep proteins associated with the pC194 family. The utility of the developed CAK1-derived phagemid designated pYL102E was evaluated by using it to examine heterologous expression of: (1) the manA gene derived from Thermoanaerobacterium polysaccharolyticum in E. coli and C. beijerinckii NCIMB 8052 and (2) the sol operon derived from Clostridium acetobutylicum DSM 792 in C. beijerinckii SA-2.

Amino Acid Sequence↗

Vascular endothelial growth factor is elevated in ocular fluids of eyes harbouring uveal melanoma: identification of a potential therapeutic window.

BACKGROUND: Improved local treatment of uveal melanoma makes it possible for many patients to retain the affected eye, but a proportion will develop secondary complications such as neovascularisation of the iris (NVI) and require enucleation. Although vascular endothelial growth factor A (VEGF-A) is known to correlate with NVI and can cause NVI in experimental models, this pro-angiogenic cytokine is consistently reported to be absent in uveal melanoma. Novel anti-VEGF therapies are now in clinical trial, and the authors therefore wished to determine whether VEGF-A was indeed elevated in melanoma bearing eyes. METHODS: VEGF-A concentrations were measured in aqueous and vitreous from 19 and 30 enucleated eyes respectively. RESULTS: Elevated VEGF-A concentrations (up to 21.6 ng/ml) were found in melanoma bearing eyes compared with samples from patients undergoing routine cataract extraction (all had values below 0.96 ng/ml). Immunohistochemistry showed VEGF-A protein in the iris and/or ciliary body of 54% and basic fibroblast growth factor (bFGF) in 82% of the eyes examined. VEGF was found to a limited extent and at very low levels in only 9% of these tumours. Aqueous or vitreous VEGF levels showed no apparent correlation with retinal detachment, tumour size, vascularity, or immunohistochemistry. Though limited in number, the highest VEGF levels correlated with previous radiation therapy, and with the presence neovascularisation of the iris or optic nerve head. bFGF was not significantly elevated in ocular fluids: it is known to be a pro-angiogenic agent and was detected in the majority of primary uveal melanomas. CONCLUSION: Based on this study, though the source of VEGF within eyes harbouring uveal melanoma is not clear, these data suggest that anti-VEGF therapy might prove useful in the management of some patients with NVI secondary to uveal melanoma.

Adult↗

Severe lactic acidosis caused by a novel frame-shift mutation in mitochondrial-encoded cytochrome c oxidase subunit II.

We report the first frame-shift truncation mutation in a mitochondrial DNA (mtDNA)-encoded subunit II of cytochrome c oxidase (COXII). The mutation was identified by temporal temperature gradient gel electrophoresis (TTGE) followed by direct DNA sequencing in an infant who died at 12 days of age following a course of apnea, bradycardia, and severe lactic acidosis. The patient had a twin brother who died at two days of age of similar course. The mutation, 8042delAT, produced a truncated protein that was 72 amino acids shorter than the wild type protein. The mutant protein, missing one third of the amino acid residues at the C-terminal essential for hydrophilic interaction with cytochrome c, ligand binding to CuA and Mg, and the formation of proton and water channels, apparently has devastating effects on mitochondrial respiratory function.

Acidosis, Lactic↗

POE-PEG-POE triblock copolymeric microspheres containing protein. II. Polymer erosion and protein release mechanism.

The first paper of this series presented the fabrication and characterization of POE-PEG-POE triblock copolymeric microspheres containing protein. In this paper, we focus on the polymer erosion and the mechanism of protein release. Fourteen-week in vitro behaviors of POE-PEG-POE microspheres loaded with bovine serum albumin (BSA) have been monitored. SEM micrographs reveal that after 14-week incubation in PBS buffer, pH 7.4, 37 degrees C, the polymeric particles remain spherical despite mass loss of almost 90%. On the other hand, molecular weight undergoes a high initial loss of 38% and 44% during the first 2-week incubation for POE-PEG(5%)-POE and POE-PEG(10%)-POE, respectively. Then, it keeps relatively unchanged over 12 weeks. However, POE-PEG(20%)-POE copolymer provides a better compatibility between the POE and PEG blocks. Hydrolysis is homogeneous through the polymer backbone. Thus, its molecular weight remains relatively constant and mass loss shows quite sustained over the 14-week in vitro release. The similar phenomena are observed in the polydispersity index of the degrading copolymers. SDS-PAGE of the encapsulated BSA within the POE-PEG(5%)-POE microspheres displays that the structural integrity of BSA is intact for at least 8 weeks due to a mild environment provided by the copolymer. In addition, XPS and FTIR are utilized to investigate protein behaviors in the degrading microspheres. Protein release from the POE-PEG-POE microspheres shows a biphasic pattern, characterized by an initial stage followed by a non-detectable release. The non-release phase is dominated by either slow polymer degradation or dense microsphere matrix structures. The microsphere formulation is optimized and a sustained protein release over 2 weeks is achieved by using POE-PEG(20%)-POE at a high protein loading.

Animals↗

Differential amplification of hypervariable region 1 of hepatitis C virus by partially mismatched primers.

The quasispecies nature of hepatitis C virus (HCV) has been well documented over its whole genome and the most variable domain is located at the 5' end of the second envelope region, the so-called hypervariable region 1 (HVR1). HVR1 has therefore been extensively used as the target for characterizing HCV quasispecies profiles. In this study, we reported our finding that partially mismatched primers preferentially amplify different HVR1 sequences in a heterogeneous virus population. This finding suggests a possible mechanism of bias during the amplification of HVR1 sequences and may be responsible for some conflicting data regarding evolutionary or clinical implications of HCV quasispecies.

Amino Acid Sequence↗

Quantitation of mitomycin C in human ocular tissues by high-performance liquid chromatography-photo-diode array detection.

A chromatographic method, which can quantitate mitomycin C (MMC) along with two antiglaucoma drugs, is described. The separation of MMC, alphagan and timolol was performed on a reversed-phase C18 column with water-methanol-trifluoroacetic acid (65:35:0.01, v/v) as the mobile phase. By monitoring at 360, 248 and 296 nm, the lower limits of detection for MMC, alphagan and timolol are, respectively, 1.0, 2.0 and 5.0 ng (injection amount) at three-time S/N ratio. The dynamic ranges of quantitation for the three drugs are, respectively, 1.0 ng-10.0 microg, 2.0 ng-10.0 microg and 5.0 ng-10.0 microg with linearity being larger than 0.9960. This method was applied to the determination of MMC levels in Tenon's and trabeculum tissues of 10 glaucoma patients. MMC levels in these tissues, which were obtained from glaucoma filtering surgery, were determined following a multiple extraction with methanol. The recovery of MMC for a two-batch extraction was better than 91.2%. The reproducibility of measurement for the MMC levels in these tissues is 2.5-6.0% RSD for triplicate injections. The intra-day variation of retention times for the MMC peaks was less than 1.6% RSD (n=3). The inter-day variation of retention times for the MMC peaks was less than 4.8% RSD (n=3). MMC was detectable in three trabeculum tissues out of 10 cases (ranging from 0.8 to 25.5 ng/mg specimen), while MMC was detected in nine Tenon's tissues out of 10 cases (ranging from 0.3 to 21.1 ng/mg specimen). The results obtained show that the method is sensitive and selective for the quantitation of MMC.

Antihypertensive Agents↗