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Biomedical subjects

K W Chan

Publications and source records attributed to K W Chan.

At least 109 records · Page 6Linked to original sources
PubMed1999

Immortalization of human prostate epithelial cells by HPV 16 E6/E7 open reading frames.

BACKGROUND: The exact pathogenesis for prostate cancer is not known. Progress made in prostate cancer research has been slow, largely due to the lack of suitable in vitro models. Here, we report our work on the immortalization of a human prostate epithelial cell line and show that it can be used as a model to study prostate tumorigenesis. METHODS: Replication-defective retrovirus harboring the human papillomavirus (HPV) type 16 E6 and E7 open reading frames was used to infect primary human prostate epithelial cells. Polymerase chain reaction, followed by Southern hybridization for the HPV 16 E6/E7, Western blot for prostatic acid phosphatase, telomeric repeat amplification protocol assay for telomerase activity, two-dimensional gels for cytokeratins, and cytogenetic analysis were undertaken to characterized the infected cells. RESULTS: The retrovirus-infected cell line, HPr-1, continued to grow in culture for more than 80 successive passages. Normal primary cells failed to proliferate after passage 6. HPr-1 cells bore close resemblance to normal primary prostate epithelial cells, both morphologically and biochemically. However, they possessed telomerase activity and proliferated indefinitely. Cytogenetic analysis of HPr-1 cells revealed a human male karyotype with clonal abnormalities and the appearance of multiple double minutes. CONCLUSIONS: The HPr-1 cells expressed prostatic acid phosphatase and cytokeratins K8 and K18, proving that they were prostate epithelial cells. They were benign in nude mice tumor formation and soft agar colony formation assay. The HPr-1 cell line is an in vitro representation of early prostate neoplastic progression.

Acid Phosphatase↗
PubMed1999

Outpatient treatment of fever and neutropenia for low risk pediatric cancer patients.

BACKGROUND: Fever and neutropenia (F&N) is a common complication of cancer chemotherapy. It is conveniently managed by hospitalization and empiric administration of parenteral antibiotics. This study attempted to determine whether pediatric cancer patients with F&N identified as low risk for morbidity and mortality by clinical criteria at the time of presentation could be treated safely as outpatients. METHODS: Seventy-three episodes of F&N in 41 patients were studied prospectively over 2 years. Eligibility criteria included age > or =2 years, reliable caretakers, and residence within 1 hour of the hospital. Exclusion criteria included hemodynamic instability, dehydration, severe mucositis, pneumonia, leukemia/lymphoma induction therapy, bone marrow transplantation, or other serious comorbidity. Patients were evaluated, received a single dose of intravenous ceftazidime, and were observed for 3-16 hours. They were randomized to receive either oral ciprofloxacin or intravenous ceftazidime as outpatients. Patients were seen daily until they had been afebrile for at least 48 hours and had a rising absolute phagocyte count of >500 cells/microL. RESULTS: Sixty-three of 73 episodes (86%) were successfully managed on an outpatient basis. For 31 of 33 episodes in the ceftazidime arm, the patients remained outpatients, compared with 32 of 40 in the ciprofloxacin arm; this difference was not statistically significant. On average, patients remained febrile for 2.7 days and were treated for 4.7 days. Seventy-seven percent of episodes required no modification of initial antibiotic therapy. Of the 10 patients who were hospitalized, 4 had prolonged fever and 3 had emesis. Protracted neutropenia was associated with the need for hospitalization. There were no deaths, intensive care unit transfers, or serious complications. CONCLUSIONS: Carefully selected low risk children with fever and neutropenia can be treated safely as outpatients. Close daily medical scrutiny is required.

Adolescent↗
PubMed1999

Transient monosomy 7: a case series in children and review of the literature.

BACKGROUND: Monosomy 7 and deletions of the long arm of chromosome 7 [del (7q)] are recurrent, nonrandom chromosomal abnormalities associated with both de novo and therapy-related myelodysplastic syndromes (MDS). The overall prognosis for children and adults with these chromosomal abnormalities is poor. In the current report, the authors present five children with MDS associated with monosomy 7/del(7q) who achieved spontaneous hematologic disease remission as well as a review of the literature. METHODS: Five children with either de novo or treatment-related MDS who achieved spontaneous hematologic disease remission are presented. Relevant clinical, cytogenetic, and fluorescent in situ hybridization data are included. RESULTS: All patients were boys. Three had de novo MDS whereas two others previously had received chemotherapy for another malignancy. Four patients achieved spontaneous and durable hematologic disease remission that was associated with cytogenetic disease remission in all three patients tested. The fifth patient developed a disease recurrence and died with evidence of clonal evolution after a long interval of hematologic and cytogenetic remission. CONCLUSIONS: A subset of children who develop MDS associated with monosomy 7 or del(7q) achieve spontaneous hematologic and cytogenetic improvement. Although this appears to be uncommon, further data are needed to determine the percentage of patients who improve without therapy and to define clinical characteristics that may predict this clinical outcome. These findings suggest that monosomy 7/del(7q) is insufficient to produce full leukemic transformation.

Adolescent↗
PubMed1999

Rapid drug metabolite profiling using fast liquid chromatography, automated multiple-stage mass spectrometry and receptor-binding.

Rapid drug metabolite profiling can be achieved using fast chromatographic separation and fast mass spectrometric scanning without compromising the separation efficiency. Fast chromatographic separations of drug and its metabolites can be achieved by eluting from a short narrow-bore guard cartridge column (20 x 2 mm I.D., 3 microns BDS Hypersil C8) at flow-rate of 1.0 ml/min and with a gradient volume greater than 90 column volumes. The need for chromatographic separation is important for automated data dependent multiple-stage mass spectrometry (MSn) experimentation. The total analysis time of 8 min permits profiling of metabolites in a 96-well plate in 13 h. The narrow chromatographic peaks resulting from the high flow-rate require the use of a mass spectrometer capable of fast scan speed due to the need to perform multiple MS experiments within the same chromatographic analysis. A method has been developed for screening potentially biologically active in vitro microsomal metabolites by affinity binding with a receptor. After separation by centrifugal ultrafiltration, the bound ligands are released and characterized by LC-MS. In vitro microsomal metabolites of tamoxifen, raloxifene and adatanserin were screened for potential biological activity using this method. The in vitro metabolites of tamoxifen captured by the receptor include N-demethyltamoxifen and three species of hydroxytamoxifen; these data are consistent with those from a conventional binding study and bioassay. In addition, both hydroxyraloxifene and dihydroxyraloxifene are also recognized by the receptor. The specificity of the molecular recognition process is illustrated by the absence of binding with control microsomal incubate and with adatanserin and its metabolites. Therefore, active metabolites can be rapidly profiled by fast LC, automated MSn, and receptor binding. This information can be obtained quickly and can add value to the drug discovery process.

Animals↗
PubMed1999

Cell block preparation on residual ThinPrep sample.

The liquid-based cytology system ThinPrep has overcome many of the deficiencies of the conventional Pap test. However, the cytologic appearances of the cells in the liquid-based medium are different and staffs of laboratories adopting the new system have to be specially trained. Even after the training sessions provided by the vendor, the cytology staff still face a sharp learning curve initially. One way to recognize the different appearances of cells in the liquid-based system is to look at paired split-sample cases from the same patient in laboratories offering the test as an adjunct to the conventional Pap test. Laboratories offering direct-to-vial testing may be able to overcome the difficulties with some cases by performing cell block sections of residual materials in the samples. The protocol for making cell blocks and its application in resolving difficulties with high-grade squamous and glandular epithelial lesions is illustrated in this report. Diagn. Cytopathol. 1999; 21:427-431.

Cytological Techniques↗
PubMed1999

Development of a rat head exposure system for simulating human exposure to RF fields from handheld wireless telephones.

The aim of this project was to develop an animal exposure system for the biological effect studies of radio frequency fields from handheld wireless telephones, with energy deposition in animal brains comparable to those in humans. The finite-difference time-domain (FDTD) method was initially used to compute specific absorption rate (SAR) in an ellipsoidal rat model exposed with various size loop antennas at different distances from the model. A 3 x 1 cm rectangular loop produced acceptable SAR patterns. A numerical rat model based on CT images was developed by curve-fitting Hounsfield Units of CT image pixels to tissue dielectric properties and densities. To design a loop for operating at high power levels, energy coupling and impedance matching were optimized using capacitively coupled feed lines embedded in a Teflon rod. Sprague Dawley rats were exposed with the 3 x 1 cm loop antennas, tuned to 837 or 1957 MHz for thermographically determined SAR distributions. Point SARs in brains of restrained rats were also determined thermometrically using fiberoptic probes. Calculated and measured SAR patterns and results from the various exposure configurations are in general agreement. The FDTD computed average brain SAR and ratio of head to whole body absorption were 23.8 W/kg/W and 62% at 837 MHz, and 22.6 W/kg/W and 89% at 1957 MHz. The average brain to whole body SAR ratio was 20 to 1 for both frequencies. At 837 MHz, the maximum measured SAR in the restrained rat brains was 51 W/kg/W in the cerebellum and 40 W/kg/W at the top of the cerebrum. An exposure system operating at 837 MHz is ready for in vivo biological effect studies of radio frequency fields from portable cellular telephones. Two-tenths of a watt input power to the loop antenna will produce 10 W/kg maximum SAR, and an estimated 4.8 W/kg average brain SAR in a 300 g medium size rat.

Animals↗
PubMed1999

Potential utility of MRI in the evaluation of children at risk of renal scarring.

BACKGROUND: Gadolinium-enhanced MRI has recently been employed in the diagnosis of acute pyelonephritis. Its potential utility in the diagnosis of renal scars in children is unknown. Objective. To evaluate the potential utility of MRI using fat-saturated T1-weighted (T1-W) and post-gadolinium, short-tau inversion-recovery (STIR) sequences in detecting renal scarring by comparison with technetium dimercaptosuccinic acid ((99 m)Tc-DMSA) renal scintigraphy in children at risk of renal scarring. MATERIALS AND METHODS: A group of 24 children with spina bifida and neurogenic bladder or anorectal anomaly was studied. No patient had a history of acute pyelonephritis. Documented urinary tract infection (UTI) was present in 10 children (42 %). The remaining 14 (58 %) children had a history of asymptomatic bacteriuria. None had clinical signs or symptoms of acute UTI at the time of the study. (99 m)Tc-DMSA and MRI were performed to detect renal scarring. (99 m)Tc-DMSA scans were supplemented with pinhole imaging. MRI of the kidneys employed a fat-saturated T1-W sequence and a post-gadolinium STIR sequence employing a short echo time. RESULTS: Of the kidneys studied, 33 % (n = 16) had evidence of a renal parenchymal defect suggestive of scarring on (99 m)Tc-DMSA. The concordance in the detection of a scarred kidney by post-gadolinium STIR sequence and (99 m)Tc-DMSA is 94 %; that by fat-saturated T1-W sequence and (99 m)Tc-DMSA is 82 %; that by both sequences (positive result on either sequence) and (99 m)Tc-DMSA is 100 %. Using (99 m)Tc-DMSA as the gold standard, MRI had a sensitivity of 100 % and a specificity of 78 % in the diagnosis of a scarred kidney. The concordance in the detection of a scarred zone by post-gadolinium STIR sequence and (99 m)Tc-DMSA is 68 %; that by fat-saturated T1-W sequence and DMSA is 44 %; that by both sequences (positive result on either sequence) and (99 m)Tc-DMSA is 84 %. MRI had a sensitivity of 84 % and a specificity of 86 % in the diagnosis of a scarred zone, using (99 m)Tc-DMSA as the gold standard. CONCLUSION: The detection rate for renal scarring on MRI using the fat-saturated T1-W and post-gadolinium STIR sequences is comparable to planar (99 m)Tc-DMSA. MRI is of potential utility in the evaluation of children at risk of renal scarring.

Anal Canal↗
PubMed1999

Depuration of metals from soft tissues of oysters (Crassostrea gigas) transplanted from a contaminated site to clean sites.

The present study aimed at studying the transplantation of oysters from a polluted site Lau Fau Shan (existing oyster culture zone) in Deep Bay to two clean sites mariculture zones at Yung Shue O and Kat O. The hydrological data, growth of oyster shell length, mortality and metal contents in whole soft tissue were monitored from February 1993 to February 1994. The high growth phase (increase in shell length) and gametogenesis (decrease in dry weight of whole soft tissue) were noted in winter (with low temperature and high salinity), and slow growth phase and spawning in summer (with high temperature and low salinity). Significant reductions (p<0.05) of Cd, Cr and Pb concentrations (dry wt basis) in soft tissue of transplanted oysters were observed at Kat O by 29, 55 and 29%, respectively, and at Yung Shue O by 34, 44 and 34%, respectively, with respect to the baseline values for the first batch of oysters and the concentrations in samples collected from Lau Fau Shan in the same months. Maximum reductions of total metal burden in whole soft tissue (microg per individual oyster) of the first oyster batch were found for Cd, Cr, Pb and Sb to be 62, 49, 60 and 25%, respectively, at Kat O, and to be 56, 47, 32 and 49%, respectively, at Yung Shue O. For the second batch of oysters transplanted to Yung Shue O in July 1993, significant reductions (p<0.05) of Cd concentration and total burden of Cd by 60 and 21%, respectively, were observed in February 1994. The high accumulated mortality and the significant (p<0.05) lower growth rate of the transplanted oysters illustrated that the best time for transplantation of oysters should be between the end of gametogenesis and the start of spawning (i.e. January and February), and the oysters should not be kept for longer than 3 months at the transplantation sites.

Journal Article↗
PubMed1999

Acute renal failure after immersion in seawater polluted by diesel oil.

Acute renal failure after exposure to toxic doses of hydrocarbon has been uniformly associated with multiorgan failure. We report a case of isolated acute renal failure in a patient after immersion in seawater polluted by diesel oil. The sites of absorption were likely to be skin, gastrointestinal tract, and lung. Investigations showed renal impairment as the only consequence from the exposure. The patient recovered uneventfully and did not require dialysis. This case highlighted the unusual consequence of isolated renal involvement resulting from hydrocarbon toxicity.

Acute Kidney Injury↗
PubMed1999

Amyloidosis complicating idiopathic myelofibrosis.

An 84-year-old man presented with ankle edema, significant proteinuria, and mild impairment of renal function soon after treatment was started for idiopathic myelofibrosis. Renal amyloidosis was found on biopsy. The amyloid deposit was resistant to potassium permanganate treatment and showed no immunoreactivity to immunoglobulin light chains, beta-amyloid protein, or amyloid A component. A review of the literature showed that the occurrence of amyloidosis in idiopathic myelofibrosis is very rare, and the chemical nature of the amyloid involved remains unclear.

Aged↗
PubMed1999

Focal segmental glomerulosclerosis and mesangial sclerosis associated with myeloproliferative disorders.

The myeloproliferative disorders (MPDs) are clonal disorders of the hematopoietic stem cell and classified as polycythemia vera (PV), essential thrombocythemia (ET), or agnogenic myeloid metaplasia (AMM), depending on the main hematopoietic lineage involved. Primary renal parenchymal lesions are not commonly reported in these cases. We conducted a retrospective analysis of 138 consecutive patients with MPD to determine the frequency of renal parenchymal complications. Five patients (3.6%) (two PV, two ET, one AMM) were found to have focal segmental glomerulosclerosis (FSGS) and diffuse mesangial sclerosis, presenting as proteinuria in all the cases and progressing to chronic renal failure in two cases. A possible common risk factor was a high platelet count, because abnormal platelet activation in MPD has been shown to contribute to the development of glomerulosclerosis. The pathophysiologic basis of our observations and the implications in management of MPD patients remain to be studied.

Adult↗
PubMed1999

Substance use disorders among adolescents in Taiwan: prevalence, sociodemographic correlates and psychiatric co-morbidity.

BACKGROUND: This paper reports prevalences, sociodemographic correlates and psychiatric co-morbidity of substance use disorders (SUDs) among adolescents in Taiwan. METHODS: A random sample of ninth grade students (N = 774) was selected from an urban, a suburban and a rural community. Two-stage case identification was employed with a brief screening tool and a modified Chinese version of the Kiddie-SADS conducted by child psychiatrists. RESULTS: The overall prevalence of any SUD was 11.0%, with nicotine (96.0%) as the most prevalent substance. The prevalences of SUDs were significantly higher in boys, rural community and classes with poor academic performance. Sixty-two per cent of all SUD cases suffered from other concurrent psychiatric disorders. The most common co-morbid conditions were conduct disorder, attention deficit hyperactivity disorder and mood disorders. CONCLUSIONS: High prevalences of SUDs were found among adolescent school children in Taiwan. Effects of urbanization, selective migration and the availability of substances are possible explanations for the urban-rural difference on the risk for SUDs. Psychiatric co-morbid conditions for SUD among adolescents in Taiwan were similar to those in Western societies.

Adolescent↗
PubMed1999

Fludarabine-based preparative protocol for unrelated donor cord blood transplantation in children: successful engraftment with minimal toxicity.

Unrelated umbilical cord blood (UCB) is a new source of hematopoietic stem cell (HSC) for allogeneic transplantation. The optimal conditioning for UCB transplant has not been defined. Intensive immunosuppression is frequently employed because of the higher risk of graft failure. Fludarabine monophosphate is shown to be an effective agent for facilitating allogeneic HSC engraftment. We have recently encountered three children who were not ideal candidates for 'conventional' conditioning protocols. TBI followed by fludarabine and melphalan were used for transplant preparation. The UCB units were one HLA-antigen (n = 1) and two HLA-antigen mismatched with the recipients. All three patients engrafted successfully. There was mild extramedullary toxicity. Two patients are alive with complete chimerism 8 and 20 months after transplant. A fludarabine-based protocol may be considered for selected cases of UCB transplants.

Adolescent↗
PubMed1999

Tacrolimus for prevention of graft-versus-host disease after mismatched unrelated donor cord blood transplantation.

Ten children with hematologic malignancies or a storage disease underwent transplantation using cord blood cells from an unrelated donor mismatched for 1 (n = 7) or 2 (n = 3) HLA antigens. The median total nucleated cell dose was 4.0 (range, 2.2-7.1) x 10(7)/kg. GVHD prophylaxis consisted of tacrolimus dose-adjusted to maintain a whole blood level of 5-15 ng/ml with or without methotrexate 5 mg/m2 i.v. on days 1, 3, 6 and 11. Corticosteroids were not administered prophylactically. Median follow-up is 12 months (range, 5-28 months). One patient had autologous recovery and subsequently relapsed 153 days post transplant. For the remainder of the patients, the median time to an ANC >0.5 x 10(9)/l was 21 days (range, 19-38 days), and the median time to platelets >20 x 10(9)/l was 39 days (range, 21-97 days). The actuarial risk of grade 2 GVHD was 77% (95% CI, 49-100%), and no patient had grades 3-4 GVHD. Two patients developed chronic GVHD. The survival rate is 90% (95% CI, 81-100%). The combination of tacrolimus and minidose methotrexate is active for the prevention of severe but not moderate acute GVHD after mismatched unrelated donor cord blood transplantation.

Antimetabolites, Antineoplastic↗
PubMed1999

Tacrolimus and minidose methotrexate for prevention of acute graft-versus-host disease after HLA-mismatched marrow or blood stem cell transplantation.

Thirty adults with leukemia or lymphoma transplanted with marrow or blood stem cells from 1-antigen mismatched related donors received tacrolimus and minidose methotrexate to prevent acute graft-versus-host disease (GVHD). The group had a median age of 42 years (range 18-56 years). Twenty-seven patients had advanced disease, and 13 were resistant to conventional therapy. Tacrolimus was administered at 0.03 mg/kg/day i.v. by continuous infusion from day -2, converted to oral at four times the i.v. dose following engraftment, and continued to day 180 post-transplant. Methotrexate 5 mg/m2 was given i.v. on days 1, 3, 6 and 11. Mild nephrotoxicity was common before day 100; 69% of patients had a doubling of creatinine, 56% had a peak creatinine greater than 2 mg/dl, and two patients were dialyzed. Other toxicities prior to day 100 thought to be related to tacrolimus included hypertension (45%), hyperkalemia (17%), hyperglycemia (14%), seizures (13%), headache (3%) and hemolytic uremic syndrome (3%). Grades 2-4 GVHD occurred in 59% (95% CI, 38-70%), and grades 3-4 GVHD in 17% (95% CI, 1-32%). Overall survival at 1 year was 29% (95% CI, 12-45%). We conclude that tacrolimus and minidose methotrexate is active post-transplant immunosuppression for patients with 1-antigen mismatched donors.

Acute Disease↗
PubMed1999

Acquired pseudocholinesterase deficiency after high-dose cyclophosphamide.

Succinylcholine, a depolarizing neuromuscular blocking agent used in anesthesia is hydrolyzed in the plasma by the enzyme pseudocholinesterase (PSC). Conditions associated with reduced PSC activity lead to sustained action of succinylcholine and result in prolonged apnea. Cyclophosphamide is an inhibitor of PSC and its suppressive effect may be dose-dependent. We report a case of severe PSC deficiency after high-dose cyclophosphamide at 7 g/m2. The patient received succinylcholine during anesthesia 9 h after chemotherapy and developed prolonged apnea. This case highlights the potential risk of drug-induced PSC deficiency and cautions the use of depolarizing muscular relaxants soon after high-dose cyclophosphamide.

Adrenal Gland Neoplasms↗