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Biomedical subjects

P Yuen

Publications and source records attributed to P Yuen.

At least 19 recordsLinked to original sources
PubMed2001

Transplacental chemical exposure and risk of infant leukemia with MLL gene fusion.

Infant acute leukemia (IAL) frequently involves breakage and recombination of the MLL gene with one of several potential partner genes. These gene fusions arise in utero and are similar to those found in leukemias secondary to chemotherapy with inhibitors of topoisomerase II (topo-II). This has led to the hypothesis that in utero exposures to chemicals may cause IAL via an effect on topo-II. We report a pilot case-control study of IAL across different countries and ethnic groups. Cases (n = 136) were population-based in most centers. Controls (n = 266) were selected from inpatients and outpatients at hospitals serving the same populations. MLL rearrangement status was derived by Southern blot analysis, and maternal exposure data were obtained by interviews using a structured questionnaire. Apart from the use of cigarettes and alcohol, very few mothers reported exposure to known topo-II inhibitors. Significant case-control differences were apparent for ingestion of several groups of drugs, including herbal medicines and drugs classified as "DNA-damaging," and for exposure to pesticides with the last two being largely attributable, respectively, to one nonsteroidal anti-inflammatory drug, dipyrone, and mosquitocidals (including Baygon). Elevated odds ratios were observed for MLL+ve (but not MLL-ve) leukemias (2.31 for DNA-damaging drugs, P = 0.03; 5.84 for dipyrone, P = 0.001; and 9.68 for mosquitocidals, P = 0.003). Although it is unclear at present whether these particular exposures operate via an effect on topo-II, the data suggest that specific chemical exposures of the fetus during pregnancy may cause MLL gene fusions. Given the widespread use of dipyrone, Baygon, and other carbamate-based insecticides in certain settings, confirmation of these apparent associations is urgently required.

Acute Disease↗
PubMed2001

Sézary syndrome in a Malay--case report and literature review.

Sézary syndrome is a rare form of primary cutaneous T cell lymphoma. It is a distinct systemic variant of mycosis fungoides, marked by erythroderma, lymphadenopathy and circulating cerebriform lymphocytes in the peripheral blood. We report a case of Sézary syndrome in a 61-year-old Malay man with a five-year history of indurated plaques, ulcers and tumours on the head and trunk, with characteristic findings on physical examination, skin biopsy, electron microscopy, immunophenotyping and peripheral blood film. A literature review on Sézary syndrome is presented.

Biopsy↗
PubMed1999

Synthesis and biological activity of substituted bis-(4-hydroxyphenyl)methanes as N-type calcium channel blockers.

Voltage activated calcium channel (VACC) blockers have been demonstrated to have utility in the treatment of stroke and pain. A series of aminomethyl substituted phenol derivatives has been identified with good functional activity and selectivity for N-type VACC's over sodium and potassium channels. The methods of synthesis and preliminary pharmacology are discussed herein.

Calcium Channel Blockers↗
PubMed1999

Bone marrow transplantation for chronic granulomatous disease: long-term follow-up and review of literature.

Chronic granulomatous disease (CGD) is a heterogeneous group of disorders with defective respiratory burst activity in phagocytes which results in recurrent pyogenic infections. We report an 8-year-old boy with X-linked CGD who received an HLA-identical BMT from his sister. The nitroblue tetrazolium test returned to normal 3 months post transplant. Neutrophil engraftment has been stable for 7 years post BMT. Our patient was the eighth case of CGD successfully treated by BMT. Conditioning regimens in these patients have consisted mainly of BU and CY. We suggest that BMT is a safe and effective method of cure for patients with CGD. BMT should be considered for patients with HLA-identical siblings.

Bone Marrow Transplantation↗
PubMed1999

Complications of surgical feeding jejunostomy in trauma patients.

OBJECTIVE: To determine the complication rate of feeding jejunostomy (FJ) performed as an adjunct to trauma celiotomy. METHODS: Retrospective analysis of 222 patients from January of 1988 to May of 1998. RESULTS: Thirty-seven total FJ-related complications occurred in 22 patients (10%). Major FJ-related complications occurred in nine patients (4%): two small bowel perforations, two small bowel volvuli with infarction, two intraperitoneal leaks, and three small bowel necroses. Patients suffering major FJ-related complications were similar to those without complications, except for the FJ type. Patients with major FJ-related complications were more likely to have had a Witzel tube jejunostomy than a needle catheter jejunostomy (p = 0.03). Three deaths were related to major FJ complications, for a FJ-related mortality rate of 1.4%. CONCLUSIONS: FJ has a major complication rate of 4% in severely injured patients. Major complications occur more frequently with larger, Witzel-type tubes. Needle catheter jejunostomy appears to be a safer method of surgical jejunal access in trauma patients.

Abbreviated Injury Scale↗
PubMed1999

Mortality following laparoscopic surgery.

The rapid advance in laparoscopic surgery in different surgical specialities has raised concerns about its safety, especially when the procedures are now being performed by less-experienced surgeons. The use of electrosurgery further increases the possibility of unrecognized organ injury and requires a good understanding of the basic principles. Despite the fact that the use of electrosurgery is frequently emphasized and discussed in most of laparoscopic surgery conferences, this is seldom taught in in-house residence programs. We describe a case of death as a result of unrecognized thermal damage and would like to stress the importance of awareness of this potential lethal complication.

Electrosurgery↗
PubMed1997

Geographical variation in the standardized years of potential life lost ratio (SYPLR) in women dying from malignancies of the breast in England and Wales.

Geographical variation in the standardized years of potential life lost ratio (SYPLR) in women aged 20-74 dying from breast cancer has been mapped by local authority district in England and Wales and compared with the variation as described by the standardized mortality ratio (SMR). The geographical distribution of areas of low and high SMRs is similar to that observed some 15 years earlier, showing an increase from north to south. In contrast, the pattern of SYPLRs shows a less obvious trend. Years of life lost because of breast cancer mortality were particularly high in eight of the 401 county districts (SYPLR 1.22-1.48) and particularly low in nine (0.60-0.86). Mapping SYPLRs for breast cancer gives a different pattern from mapping SMRs, and one which is possibly more appropriate for targeting resources in circumstances in which death at younger age will have major social consequences. Care is required in interpreting maps indicating high and low rates in the presence of multiple comparisons. However, the range of values observed is suggestive of the need to investigate districts with contrasting values of SYPLR with respect to the inter-relationships between sociodemographic characteristics, duration of symptoms, clinical presentation and treatment efficacy.

Adult↗
PubMed1997

Clustering of childhood leukaemia in Hong Kong: association with the childhood peak and common acute lymphoblastic leukaemia and with population mixing.

Incidence data of childhood leukaemia (CL) in Hong Kong (1984-90) have been analysed for evidence of variation between small areas. All cases (n=261) were classified by morphological cell type, with the majority (n=205) being acute lymphoblastic leukaemia (ALL), and haematological review has permitted immunophenotypic classification for 73% of these. The data have been examined for evidence of spatial clustering within small census areas (TPUs) and for association with population mixing, with attention focused on those subgroups (especially the childhood peak of ALL--taken here to be diagnoses in children from 24 months up to the seventh birthday--and common ALL) which, it has been hypothesized, may be caused by unusual patterns of exposure and response to common infections. For the whole of Hong Kong, there was evidence of spatial clustering of ALL at ages 0-4 years (P = 0.09) and in the childhood peak (P<0.05). When these analyses were restricted to TPUs where extreme population mixing may have occurred, overall incidence was elevated and significant evidence of clustering was found for ALL (P<0.007) at these ages and for the common ALL in the childhood peak (P = 0.032). Replication of the analyses for subsets of leukaemia that were not dominated by the childhood peak of ALL found no evidence of clustering. This is the first investigation of an association between population mixing and childhood leukaemia in Asia and the first to include clustering and to consider particular subsets. The results are supportive of the 'infectious' aetiology hypothesis for subsets of childhood leukaemia, specifically common ALL in the childhood peak.

Adolescent↗
PubMed1996

Non-erythroid alpha-spectrin breakdown by calpain and interleukin 1 beta-converting-enzyme-like protease(s) in apoptotic cells: contributory roles of both protease families in neuronal apoptosis.

The cytoskeletal protein non-erythroid alpha-spectrin is well documented as an endogenous calpain substrate, especially under pathophysiological conditions. In cell necrosis (e.g. maitotoxin-treated neuroblastoma SH-SY5Y cells), alpha-spectrin breakdown products (SBDPs) of 150 kDa and 145 kDa were produced by cellular calpains. In contrast, in neuronal cells undergoing apoptosis (cerebellar granule neurons subjected to low potassium and SH-SY5Y cells treated with staurosporine), an additional SBDP of 120 kDa was also observed. The formation of the 120 kDa SBDP was insensitive to calpain inhibitors but was completely blocked by an interleukin 1 beta-converting-enzyme (ICE)-like protease inhibitor, Z-Asp-CH2OC(O)-2,6-dichlorobenzene. Autolytic activation of both calpain and the ICE homologue CPP32 was also observed in apoptotic cells. alpha-Spectrin can also be cleaved in vitro by purified calpains to produce the SBDP doublet of 150/145 kDa and by ICE and ICE homologues [ICH-1, ICH-2 and CPP32(beta)] to produce a 150 kDa SBDP. In addition, CPP32 and ICE also produced a 120 kDa SBDP. Furthermore inhibition of either ICE-like protease(s) or calpain protects both granule neurons and SH-SY5Y cells against apoptosis. Our results suggest that both protease families participate in the expression of neuronal apoptosis.

Amino Acid Sequence↗
PubMed1996

An alpha-mercaptoacrylic acid derivative is a selective nonpeptide cell-permeable calpain inhibitor and is neuroprotective.

Overactivation of calcium-activated neutral protease (calpain) has been implicated in the pathophysiology of several degenerative conditions, including stroke, myocardial ischemia, neuromuscular degeneration, and cataract formation. Alpha-mercaptoacrylate derivatives (exemplified by PD150606), with potent and selective inhibitory actions against calpain, have been identified. PD150606 exhibits the following characteristics: (i) Ki values for mu- and m-calpains of 0.21 microM and 0.37 microM, respectively, (ii) high specificity for calpains relative to other proteases, (iii) uncompetitive inhibition with respect to substrate, and (iv) it does not shield calpain against inactivation by the active-site inhibitor trans-(epoxysuccinyl)-L-leucyl-amido-3-methylbutane, suggesting a nonactive site action for PD150606. The recombinant calcium-binding domain from each of the large or small subunits of mu-calpain was found to interact with PD150606. In low micromolar range, PD15O6O6 inhibited calpain activity in two intact cell systems. The neuroprotective effects of this class of compound were also demonstrated by the ability of PD150606 to attenuate hypoxic/hypoglycemic injury to cerebrocortical neurons in culture and excitotoxic injury to Purkinje cells in cerebellar slices.

Acrylates↗
PubMed1995

Prostatic non-Hodgkin's lymphoma causing acute urinary retention in childhood.

An 8-year-old boy presented with dysuria and acute retention of urine. Rectal examination showed a hard mass arising from the prostate. CT scan of the pelvis confirmed the presence of a large prostatic tumor causing bladder outflow obstruction. A provisional diagnosis of pelvic sarcoma was initially made. Biopsy of the tumor mass however, revealed non-Hodgkin's lymphoma of T-cell type. The tumor showed very good response to chemotherapy and the urinary obstruction significantly improved with a week after starting therapy.

Acute Disease↗
PubMed1995

Stereoselective metabolism of enflurane by human liver cytochrome P450 2E1.

The toxicity of the chiral fluorinated volatile anesthetics halothane, enflurane, and isoflurane is closely related to their metabolism by hepatic cytochrome P450. Although individual anesthetic enantiomers have been shown to exhibit a difference in anesthetic efficacy, metabolism of anesthetic enantiomers has not been reported. Human liver enflurane metabolism to difluoromethoxydifluoroacetic acid (DFMDFA) and inorganic fluoride is catalyzed in vivo and in vitro by cytochrome P450 2E1. The purpose of this investigation was to characterize enflurane racemate and enantiomer metabolism to test the hypothesis that fluorinated ether anesthetic metabolism by cytochrome P450 2E1 exhibits substrate stereoselectivity. Enflurane metabolism by microsomes from three human livers and by microsomes containing cDNA-expressed human P450 2E1 was measured at saturating enflurane concentrations. DFMDFA was quantitated with gas chromatography-mass spectrometry by detection of the ethanolamide derivative. In microsomes from all three livers, (R)-enflurane metabolism was significantly greater than that of (S)-enflurane, whereas rates of racemic enflurane metabolism were generally between those seen for the R- and S-enantiomers. The ratio of (R)-enflurane to (S)-enflurane metabolism in the three livers studied was 2.1:1, 1.9:1, and 1.4:1. (R)-, (S)-, and racemic enflurane were all metabolized by expressed P450 2E1. The ratio of (R)-enflurane to (S)-enflurane metabolism was 1.9:1. The metabolic enantiomeric selectivity of human liver P450 2E1 for (R)-enflurane suggests that enflurane metabolism by P450 2E1 occurs by direct substrate oxidation, rather than indirectly through the generation of a P450-dependent reactive oxygen species, and supports the hypothesis that the P450 2E1 active site is somewhat restrictive and capable of stereochemical discrimination.

Anesthetics, Inhalation↗
PubMed1994

On the development of the Medical Research Council trial of alpha-interferon in metastatic renal carcinoma. Urological Working Party Renal Carcinoma Subgroup.

This paper describes the steps taken by the British Medical Research Council (MRC) in developing the MRC RE01 trial, a randomized clinical trial for patients with metastatic renal cancer; we discuss the reasons for adopting a triangular sequential design and the impact that this has upon the monitoring of the trial. It had been suggested to the MRC that a trial of biological agents for metastatic renal carcinoma should be initiated. The Cancer Therapy Committee (CTC) of the MRC, through its associated site specific working parties, is responsible for designing and co-ordinating randomized trials of alternative treatments in cancer in solid tumours. Since no MRC working party for renal carcinoma existed at that time, development began by the formation of an ad hoc group set up under the auspices of the CTC. They assessed, by means of a postal questionnaire, U.K. interest in the trials of, and modalities utilized for, treatment of renal cancer. The responses focused attention on the important questions to ask and indicated the level of potential collaboration. These responses and related clinical and statistical issues suggested a protocol to compare medroxy-progesterone acetate (MPA) against alpha-interferon (alpha-IFN). In view of the special problems of comparing an expensive and potentially toxic therapy with an inexpensive and non-toxic standard, a sequential design was used rather than a fixed sample size design. Statistical issues raised and solutions provided are described. The method of establishing the trial data monitoring committee and a brief review of mortality from renal carcinoma in England and Wales are also included. The trial opened to patient recruitment on 1 January 1992. The formal statements regarding statistical issues that appear in the formal trial protocol (RE01) are set out in the Appendix.

Aged↗
PubMed1994

Monte Carlo calculations of monoenergetic electron depth dose distributions in LiF chips: skin dose correction factors for beta rays.

Monte Carlo calculations have been carried out for monoenergetic electrons from 0.1 to 4 MeV irradiating LiF chips in both perpendicular and isotropic geometry. This enabled the calculation of skin dose correction factors (beta factors) for typical beta energy spectra as measured with a beta-ray spectrometer at CANDU nuclear generating stations. The correction factors were estimated by averaging the depth dose distributions for the monoenergetic electrons over the experimentally measured beta-ray spectra. The calculations illustrate the large uncertainty in beta factors arising from the unknown angular distribution of the beta-ray radiation field and uncertainties in the shape of the beta-ray spectra below 500 keV.

Fluorides↗
PubMed1994

Bone marrow transplantation in Hong Kong.

Comprehensive programmes for BMT started in Hong Kong in 1990. As of September 1993, there are a total of 13 BMT beds in Government-funded University Hospitals performing about 110 transplants per year or 18 transplants per million population per year. So far, 194 transplants were performed: allogeneic BMT (72.2%), autologous BMT (11.8%), matched unrelated donor BMT (8.8%), identical twin BMT (1.5%), mismatched BMT (2.1%) and second BMT (3.6%). The major indication was haematological malignancy (84%). About 40% of the patients were prepared by chemotherapy alone. A combination of CsA and short MTX was the commonest GVHD prophylaxis. The incidence of GVHD was the same as in the Caucasians. Results of transplant outcome were comparable to those reported by the International Bone Marrow Transplant Registry.

Bone Marrow Transplantation↗