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Biomedical subjects

P Ng

Publications and source records attributed to P Ng.

At least 55 records · Page 3Linked to original sources

Random population-wide genetic damage induced in replicating cells treated with methotrexate.

Low lethality treatment of the NIH 3T3 mouse cell line with methotrexate (MTX) during exponential multiplication results in heterogeneous, heritable reduction in growth rate of most if not all the replicatively surviving cells. The effective concentrations of MTX are 10 to 100 times higher in molecular, cellular and developmental biology medium 402 (MCDB 402) than in Dulbecco's modification of Eagle's medium (DMEM) medium because of the folate-sparing presence of adenine, thymidine and, particularly, of folinic acid in MCDB 402 medium. The reduced growth rates are detectable during early passages of surviving populations before the faster growing cells dominate them. The heritable effect is most clearly demonstrated by sequestered cloning of many individual cells immediately after drug treatment, and repeatedly measuring the growth rates of the clones in serial passages. After 7-10 passages of the clones, there is an increase in growth rate of some of the slow growing clones presumably due to the generation and selection of faster growing cells. Evidence from mutagenic studies at a single genetic locus in other cell lines suggests that heritable reductions in growth rate arise from chromosome aberrations although point mutations may also contribute to the effect. Clastogenic changes can be induced by a wide variety of mutagens and carcinogens, many of which are used in chemotherapy of cancer and other chronic diseases. The population-wide, heritable damage to cells may be the source of, or may contribute to, late-occurring side effects of treatment in cancer and other chronic diseases.

3T3 Cells↗

Distinct molecular phenotypes in murine cardiac muscle development, growth, and hypertrophy.

The onset of cardiac hypertrophy is associated with characteristic changes in myocardial gene expression that are thought to recapitulate a developmental gene program. We report here the first gene expression profile of the murine myocardium, using a rapid method of quantitative expression analysis based on real-time analytical RT-PCR. This assay was used to measure expression levels of 29 genes in (1) late stage development as represented by day 1 neonatal ventricles, (2) normal cardiac growth in 3 and 18 month old mice, and (3) cardiac hypertrophy following pressure overload by aortic constriction. For males and females normal growth is not associated with differential expression although there is elevated expression of skeletal and smooth muscle actin mRNA's in males compared to females. Using normal adult ventricles as a reference, there are many qualitative and quantitative differences between the day 1 neonatal myocardium and experimental cardiac hypertrophy. These data suggest that the response to POL involves a subset of re-expressed developmental genes together with altered expression of genes not necessarily associated with cardiac development.

Animals↗

Environmental contamination and developmental abnormalities in eggs and hatchlings of the common snapping turtle (Chelydra serpentina serpentina) from the Great Lakes-St Lawrence River basin (1989-1991).

During 1989-1991, we assessed developmental abnormalities in embryos and hatchlings from eggs of the common snapping turtle (Chelydra serpentina serpentina). Eggs were collected and artificially incubated from eight sites in Ontario, Canada and Akwesasne/New York, USA. In eggs from the same clutches we measured 20 organochlorine pesticides, 48 polychlorinated biphenyl (PCBs) congeners including 6 non-ortho PCBs, 8 polychlorinated dibenzodioxins (PCDDs), 14 polychlorinated dibenzofurans (PCDFs) and total mercury. We found a significant increase in abnormal development with increasing polychlorinated aromatic hydrocarbon exposure in eggs, particularly PCDD and PCDF concentrations. In contrast, the risk of abnormality was not significantly higher as toxic equivalent concentrations increased in eggs. We also found significant 7-ethoxyresorufin O-deethylase and Cytochrome P4501A responses in livers of hatchling turtles from Lake Ontario relative to hatchlings from a clean, inland site whereas we did not find any evidence of porphyria in the hatchlings from either site.

Journal Article↗

Diffuse panbronchiolitis: case report and review of the literature.

Diffuse panbronchiolitis is an uncommon disease of unknown aetiology mainly occurring in Asian races. Treatment with erythromycin acting through unclarified mechanisms is promising and may improve the poor prognosis currently associated with the disease. A case is presented illustrating how the imaging features of the disease, particularly on high-resolution computed tomography, may be used to support a diagnosis suggested on clinical grounds.

Anti-Bacterial Agents↗

Ocular complications of heart, lung, and liver transplantation.

AIM: To document the nature and frequency of ocular complications in a large group of patients who underwent heart, lung, or liver transplantation. METHODS: A retrospective audit of the medical records of all patients undergoing heart, lung, or combined heart-lung transplantation at St Vincent's Hospital, Sydney, or liver transplantation at Royal Prince Alfred Hospital Sydney, was performed to detect patients with symptomatic ocular complications following transplantation. 19 of 860 patients were identified as having ocular complications. RESULTS: Ocular complications occurred in 2% of patients with 65% of these being opportunistic infections. Herpes group viral retinitis (77%) and fungal chorioretinitis (22%) were seen. Other complications included choroidal pseudolymphoma, central retinal vein occlusion, herpes zoster ophthalmicus, herpetic keratitis, dacryocystitis, cyclosporin retinopathy, and rifabutin associated uveitis. CONCLUSION: Herpes group viral retinitis was the most common ocular opportunistic infection and occurred most frequently during the second year after transplantation. Delayed diagnosis was associated with poor visual outcome.

Adult↗

Comparison of gas chromatography-electron capture and enzyme-linked immunosorbent assay for deoxynivalenol in milled fractions of naturally contaminated wheat.

An enzyme-linked immunosorbent assay (ELISA) for deoxynivalenol was compared with a gas chromatography-electron capture assay to determine deoxynivalenol levels in milled fractions of wheat. The milling provided eight fractions: first, second, and third break flours; first, second, and third reduction flours; brans; and shorts. The difference between levels of deoxynivalenol quantitated by ELISA or gas chromatography did not depend significantly on the wheat samples or milled wheat fractions. For none of the fractions or samples did the differences differ significantly (P=0.05) from zero. Based on these comparative tests, ELISAs for deoxynivalenol in milled wheat fractions should provide reliable results rapidly and economically in a commercial setting.

Chromatography, Gas↗

Quality-of-life information and clinical practice: the oncologist's perspective.

OBJECTIVE: To collect information from a group of Canadian oncologists about their perspectives on quality of life (QOL) and QOL information. DESIGN: A self-administered questionnaire (MD-QOL) containing 75 items with a 4-point Likert categorical response scale was administered by mail using Dillman survey methodology to all staff oncologists at a single institution. SETTING: A large Canadian cancer care centre (Princess Margaret Hospital, Toronto). MAIN OUTCOME MEASURES: Oncologists' knowledge, attitude, current behaviour and intended willingness to use QOL information. RESULTS: Of 67 eligible respondents 54 replied (80% response rate). In all, 74% felt that QOL can be quantified, and 95% felt that it gives information distinct from performance status measures. A total of 87% felt that published QOL data are useful for individual patient care, but 69% indicated that, at present, they would be more likely to base their recommendations on personal experience rather than on published literature. Of the respondents, 57% felt that decisions were made more difficult when QOL issues are considered. CONCLUSIONS: The surveyed oncologists support the relevance and importance of QOL information. Data from this study were used to develop a predictive model to assess oncologists' willingness to use QOL information; the model is being tested in other studies.

Adult↗

Bayer Immuno 1 PSA Assay: an automated, ultrasensitive method to quantitate total PSA in serum.

The Bayer Immuno 1 PSA Assay measures total PSA in human serum and demonstrates excellent performance with an interassay CV < or = 3.4% and a biological detection limit of 0.03 microgram/L. No significant interference from common hormonal and chemotherapeutic drugs, kallikrein, prostatic acid phosphatase, and trypsin, or elevated levels of total bilirubin, hemoglobin, triglycerides, and IgG was observed. The 95th percentile values for healthy individuals increased with age from 3.0 micrograms/L for males 50-59 years and 3.3 micrograms/L for males 60-69 years, to 4.6 micrograms/L for males > or = 70 years. Clinical studies with retrospective samples demonstrated correspondence between serial measurements of PSA and clinical outcome for 98% of 159 prostate cancer patients. Clinical sensitivity for patients with clinical evidence of disease, untreated at the time of specimen draw, increased with increasing stage from 77.5-100%. Specificity of 60-70% for BPH and other benign urogenital diseases was consistent with previous findings. Bayer Immuno 1 PSA Assay values for 2131 specimens from healthy subjects and patients with prostate cancer, BPH, and other malignant and nonmalignant diseases correlated well with the Abbott IMx PSA Assay over the range 0.0-6,238 micrograms/L (Y = 1.10 x + 0.02). The Bayer Immuno 1 PSA Assay provides automated ultrasensitive, precise, and equimolar measurement of total PSA in human serum.

Aged↗

Fallopian tube carcinoma--a review.

Although a common site of metastases, primary fallopian tube carcinoma comprises only 0.3% of all gynaecological malignancies. Presenting symptoms are variable and non-specific, with preoperative diagnosis rarely entertained. The FIGO system assigns nearly two-thirds of patients to stage I or II and is based on surgical staging criteria similar to those for ovarian cancer. Likewise, management is based on that for ovarian cancer-radical debulking followed by platinum-based combination chemotherapy. Five-year survival for patients with disease confined to the tube at diagnosis (stage I) is only about 60% and only 10% of patients with advanced disease will be cured.

Adenocarcinoma, Papillary↗

A preliminary survey of oncologists' perceptions of quality of life information.

Quality of life (QOL) of cancer patients has become the focus of increasing research in oncology, and a frequently measured endpoint in clinical trials. Very little attention has been paid to the perspective of physicians on quality of life information, and its role in clinical decision-making. This report describes the findings of research focused on exploring the perspectives of physicians about quality of life information that is available for cancer patients. On the basis of qualitative data gathered through in-depth interviews with 60 oncologists in the first phase of this project, we have developed a self-administered questionnaire (MD-QOL survey) designed to assess oncologists' views on QOL. This survey was administered to an international group of gynecologic oncologists. The objectives of this study were to assess the face validity of the initial items in the MD-QOL, to expand the pool of items, and to assess the feasibility of utilizing a self-administered questionnaire to assess physicians' perspectives on QOL information. Twenty-eight oncologists responded to the questionnaire. The majority of respondents felt that QOL can be measured and that it should be measured from the patient's own perspective. Half of the physicians felt that currently available QOL information is useful in clinical practice. Ninety-three percent of respondents felt that the greatest benefit of QOL information is 'being able to treat the whole patient'. Forty one percent of respondents felt that length of survival is more important to patients than quality of life. However, only 7% of the respondents felt that the primary job of physicians is to save lives, and that QOL should not be a predominant concern for physicians. The inclusion of QOL in randomized trials was perceived as encouraging both patient and physician participation. The results of this survey are being used to further explore these critical issues.

Adult↗

Death substrates come alive.

Interleukin 1 beta-converting enzyme (ICE)-like proteases (caspases) play an important role in programmed cell death (apoptosis), and elucidating the consequences of their proteolytic activity is central to our understanding of the molecular mechanisms of cell death. Diverse structural and regulatory proteins and enzymes, including protein kinase C delta, the retinoblastoma protein (a protein involved in cell survival), the DNA repair enzyme DNA-dependent protein kinase and the nuclear lamins, undergo specific and limited endoproteolytic cleavage by various caspases during apoptosis. Since individual caspases can cleave multiple substrates, the consequences of cleavage of only a single substrate are still poorly understood. Nevertheless, proteolytic activation of protein kinase C delta may be an important early step in the cell death pathway, and cleavage of the retinoblastoma protein could suppress its cell survival function, whereas proteolytic inactivation of DNA repair enzymes might compromise the ability of the cell to reverse DNA fragmentation. On the other hand, cleavages of nuclear and cytoplasmic structural proteins (e.g. the lamins and Gas2) appear to be required for or contribute to the dramatic rearrangements in cellular architecture that are necessary for the completion of the cell death process. An emerging theme is that parallel and sequential proteolytic activation and inactivation of key protein substrates occurs during the multiple steps of apoptosis.

Animals↗

Lymphomatoid granulomatosis: case report and review of the literature.

Lymphomatoid granulomatosis (LG) is an uncommon disease now regarded by most authors as an unusual form of lymphoma with the ability to affect any bodily system. The disease and its complications may result in a spectrum of radiological appearances. A case illustrating how cerebral lesions may mimic demyelinating plaque, neoplasm or infection and how pulmonary lesions may lead to pneumopericardium is presented. The difficulty in establishing a definitive diagnosis, due to the non-specificity of symptoms, pathological investigations and radiological appearances of the disease, is emphasized. Clinicians must therefore consider LG in their differential diagnoses, as delayed treatment may affect prognosis.

Adult↗

Arachnoiditis ossificans of the cauda equina demonstrated on computed tomography scanogram. A case report.

STUDY DESIGN: This case report illustrates a patient with arachnoiditis ossificans of the cauda equina of sufficient severity to be demonstrable on a computed tomography scout view. OBJECTIVES: The diagnosis of extensive arachnoiditis ossificans by computed tomography does not necessitate surgical intervention. The authors patient had only mild, chronic symptoms when treated expectantly. SUMMARY OF BACKGROUND DATA: The value of axial computed tomography in visualizing and characterizing the lesions of arachnoiditis ossificans has been well documented. Arachnoiditis ossificans involving the cauda equina is uncommon. To the authors' knowledge, this report represents the first case of arachnoiditis ossificans of the cauda equina in which the arachnoid calcifications were of sufficient density to be obvious on a computed tomography scan. METHODS: The patient was reviewed by a neurologist for paraesthesia in his right foot, occasional backaches, and urinary frequency. Physical examination revealed only a mild loss of lumber lordosis and an area of hypoesthesia in the right foot. He then was investigated with computed tomography, which showed extensive arachnoiditis ossificans. Because his symptoms were mild, surgery was not contemplated. RESULTS: The patient's symptoms remained minimal despite being treated conservatively. CONCLUSIONS: The value of computed tomography in delineating the lesions of arachnoiditis ossificans and the outcome of surgery for resection of its compressive osseous plaques have been well described. Despite extensive arachnoid calcification caused by arachnoiditis ossificans involving the cauda equina that was visible on a computed tomography scan, this patient continued to have only low-grade symptoms when treated conservatively.

Aged↗

Temporal and geographic variation of organochlorine residues in eggs of the common snapping turtle (Chelydra serpentina serpentina) (1981-1991) and comparisons to trends in the herring gull (Larus argentatus) in the Great Lakes basin in Ontario, Canada.

Common snapping turtle (Chelydra serpentina serpentina) eggs from five sites within the Great Lakes basin, and from a reference site in north-central Ontario were collected during 1981-1991 and analyzed for four organochlorine pesticides, polychlorinated biphenyls (PCBs) including six non-ortho PCBs, polychlorinated dibenzodioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs). The pattern of geographic variation was consistent over time in eggs with Cootes Paradise/ Hamilton Harbour and Lynde Creek eggs on Lake Ontario containing the highest concentrations and most PCDD and PCDF congeners among all sites. Eggs from Cranberry Marsh on Lake Ontario contained organochlorine concentrations similar to those from Big Creek Marsh and Rondeau Provincial Park on Lake Erie except PCDDs and PCDFs which occurred at higher concentrations and more congeners were detectable in Cranberry Marsh eggs. Concentrations of most contaminants in turtle eggs from Algonquin Park, the reference site, have significantly decreased in the past decade. Dieldrin concentrations, however, increased in Algonquin Park eggs from 1981 to 1989. Significant decreases in concentrations of hexachlorobenzene, mirex and PCBs occurred between turtle eggs collected in 1981/84 and 1989 at Big Creek Marsh and Rondeau Provincial Park, whereas there was no significant change in concentrations of p,p'-DDE and dieldrin. In Lake Ontario eggs, concentrations of PCBs, p,p'-DDE and dieldrin increased significantly between 1984 and 1991. Differences were also found in patterns of temporal variation in contamination between herring gulls (Larus argentatus) and snapping turtles which were attributed to differences in diet. Elevated and continued contamination in turtle eggs from Lake. Ontario is probably due to a combination of local sources of chemicals and consumption of large migratory fish that spawn in wetlands inhabited by these turtles.

Animals↗

Physicians' perspective on quality of life: an exploratory study of oncologists.

There is an implicit assumption that physicians incorporate quality of life (QOL) information in clinical decision-making. However, very limited data exists on how physicians view QOL information and how they actually use it. To explore this issue, an in-depth study was conducted using a semi-structured interview guide, with 60 oncologists in Canada and the USA. While the majority of respondents perceived QOL as important they reported a tendency to use it informally and not in all situations. Key findings include the belief expressed by 88% of respondents that the term QOL could be defined, although they differed in their definitions. Although 85% stated that QOL can be formally measured, only a third perceived that the current instruments provide valid and reliable data. Respondents noted a number of significant benefits and drawbacks of using QOL data in their clinical practice that had not been previously noted in the literature. For example, its use as an endpoint in clinical trials was generally perceived to enhance both physician and patient participation. A drawback noted was that including QOL might adversely affect the decision-making process. These findings have been used to develop a self-administered questionnaire (MD-QOL) which will test the generalizability of these findings.

Adult↗