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Biomedical subjects

S Wong

Publications and source records attributed to S Wong.

At least 127 records · Page 7Linked to original sources
PubMed1997

Adjuvant therapy for stage III colon cancer after complete resection. Provincial Gastrointestinal Disease Site Group.

GUIDELINE QUESTIONS: Should patients with resected stage III colon cancer receive adjuvant therapy? If so, which therapy should be recommended? OBJECTIVE: To make recommendations regarding the use of adjuvant therapy in the treatment of resected stage III colon cancer. OUTCOMES: Overall survival is the primary outcome of interest. Secondary outcomes are disease-free survival and adverse effects of the treatment regimens. PERSPECTIVE (VALUES): Evidence was selected and reviewed by 4 members of the Gastrointestinal Disease Site Group (GI DSG) of the Ontario Cancer Treatment Practice Guidelines Initiative. Earlier drafts of the guideline were reviewed, discussed and approved by the GI DSG, which comprises medical and radiation oncologists, surgeons and epidemiologists. Community representatives did not participate in the development of this guideline but will participate in future guidelines development. QUALITY OF EVIDENCE: There are 3 meta-analyses, 33 published randomized controlled trials (RCTs) and 1 consensus statement. The GI DSG pooled data from 10 of the 33 RCTs that allowed for such an analysis. BENEFITS: Two of 3 RCTs reported improved survival rates with 5-fluorouracil (5-FU) plus semustine or mitomycin C (MMC) compared with no treatment (observation) after surgical resection. Three trials reported a benefit in both overall and disease-free survival with 5-FU plus levamisole compared with observation after surgery. In 2 trials, levamisole alone did not produce a survival benefit compared with observation. One trial reported improved disease-free, but not overall, survival rates with oral HCFU (1-hexylcarbamoyl-5-fluorouracil) compared with observation. In 3 trials of 5-FU plus leucovorin, disease-free and overall survival rates were improved compared with observation. Nine trials compared portal vein infusion (PVI) of 5-FU with observation after surgery. In 2 of the trials, for which data were available for stage III patients only, improved overall survival was reported. There was a trend in all studies favouring PVI. One trial reported a survival benefit for stage III and IV patients who received oral HCFU maintenance therapy for 1 year compared with no maintenance therapy. In a trial comparing MMC plus oral HCFU with MMC alone, a survival benefit was reported in the combined treatment group; however, the stages of cancer were unevenly distributed among the treatment groups. Only 1 study tested monoclonal antibody; a benefit was reported for both overall and disease-free survival. A meta-analysis of 10 trials comparing adjuvant therapy with observation in patients with stage III disease detected a significant reduction in the odds ratio (OR) for death (OR 0.69; 95% confidence interval [CI] 0.57 to 0.85), with an absolute improvement in survival of 4% to 13%. When trials were separated according to the type of treatment given, the significant ORs were for 5-FU plus either levamisole (OR 0.61; 95% CI 0.46 to 0.80) or leucovorin (OR 0.51; 95% CI 0.36 to 0.73). Three recently reported trials comparing various combinations of 5-FU plus leucovorin, with or without levamisole, showed similar improvements in disease-free and overall survival.

Chemotherapy, Adjuvant↗
PubMed1997

Adjuvant therapy for stage II colon cancer after complete resection. Provincial Gastrointestinal Disease Site Group.

GUIDELINE QUESTION: Should patients with resected stage II colon cancer receive adjuvant therapy? OBJECTIVE: To make recommendations regarding the use of adjuvant therapy in the treatment of resected stage II colon cancer. OUTCOMES: Overall survival is the primary outcome of interest. Secondary outcomes are disease-free survival and adverse effects of the treatment regimens. PERSPECTIVE (VALUES): Evidence was selected and reviewed by 2 members of the Provincial Gastrointestinal Disease Site Group (GI DSG) of the Cancer Care Ontario Practice Guidelines Initiative. The recommendations resulting from this review have been approved by the GI DSG, which comprise medical and radiation oncologists, surgeons and epidemiologists. Community representatives did not participate in the development of this practice guideline but will do so in future guidelines development. QUALITY OF EVIDENCE: There are 25 published randomized controlled trials (RCTs) and 1 meta-analysis. The GI DSG pooled data from 11 of the 25 RCTs that provided adequate data. BENEFITS: The 25 RCTs are grouped according to the type of therapy and whether the control patients received no treatment (observation) or other adjuvant therapy after resection. Because the trials usually included patients with stage II and III cancer, the complete trial results and those for a subset of patients with stage II disease were analysed. Although the overall trial results showed a survival benefit for adjuvant treatments, the benefit was not significant for stage II patients. A meta-analysis of 11 trials comparing adjuvant treatment with observation in patients with stage II cancer indicated no significant reduction in the odds ratio (OR) for death (OR 0.83; 95% confidence interval [CI] 0.62 to 1.10). The OR for death among patients receiving chemotherapy by portal vein infusion (PVI) was 0.62 (95% CI 0.35 to 1.11). HARMS: The toxic effects of 5-fluorouracil (5-FU) with either levamisole or leucovorin, or both, were mild to moderate and consisted mostly of stomatitis, diarrhea and myelosuppression; 5% of patients required hospital admission. 5-FU plus levamisole was associated with transient neurotoxic effects in 18% of patients. Toxic effects associated with PVI were mild, rare and mostly consisted of leukopenia and diarrhea; 1% of patients experienced bowel perforation. PRACTICE GUIDELINE: Adjuvant therapy is not recommended at this time for the routine management of patients with resected stage II colon cancer. Patients with stage II disease and high-risk factors (bowel obstruction, tumour adhesion, invasion, perforation or aneuploidy) have a poorer prognosis, similar to that of patients with stage III colon cancer. For individual management, these patients should be made aware of their prognosis; treatment can be considered after the uncertainty of the value of adjuvant therapy has been explained to the patient. The enrolment of patients with high-risk stage II disease in clinical trials is encouraged. Trials comparing adjuvant therapy with observation are needed and are ethically acceptable in stage II colon cancer.

Chemotherapy, Adjuvant↗
PubMed1996

Photodynamic therapy-mediated oxidative stress can induce expression of heat shock proteins.

Photodynamic therapy (PDT) is an experimental cancer therapy inducing tumor tissue damage via photosensitizer-mediated oxidative cytotoxicity. A previous report indicates that oxidative stress induced by hydrogen peroxide or menadione activates the heat shock transcription factor in mouse cells but does not result in either increased transcription or translation of heat shock proteins (HSPs). Our study documents that photosensitizer-mediated oxidative stress can activate the heat shock factor as well as increase HSP-70 mRNA and protein levels in mouse RIF-1 cells. The cellular heat shock response after PDT varied for the different photosensitizers being examined. Treatments using either a chlorin (mono-L-aspartyl chlorin-e6)- or purpurin (tin etio-purpurin)-based sensitizer induced HSP-70 expression, whereas identical photosensitization conditions with a porphyrin (Photofrin)-based sensitizer failed to induce a cellular HSP response. These sensitizers, which generate singlet oxygen as the primary oxidant during photosensitization, were used in experiments under isoeffective treatment conditions. HSP-70 expression after photosensitization was associated with the concomitant induction of thermotolerance in PDT-treated cells. Interestingly, reverse transcription-PCR demonstrated that in vivo PDT treatments of RIF-1 tumors induce expression of HSP-70 for all photosensitizers including Photofrin. These results indicate that photosensitizer-generated singlet oxygen exposure can induce in vitro and in vivo HSP-70 expression, and that specific subcellular targets of PDT (which can differ for various sensitizers) are determinants for HSP-70 activation after oxidative stress.

Animals↗
PubMed1996

Constrictive pericarditis causing extrinsic mitral stenosis and a left heart mass.

Constrictive pericarditis is a fibrotic process involving both layers of the pericardium and is known to give rise to obstruction to blood flow in the right heart. We report a patient with constrictive pericarditis who had echocardiographic features of mitral stenosis caused by a fibrocalcific mass lesion involving the mitral annulus with infiltration into the base of the posterior mitral leaflet. To our knowledge, this has not been reported in the literature.

Biopsy, Needle↗
PubMed1996

A herpes simplex virus-1 vector containing the rat tyrosine hydroxylase promoter directs cell type-specific expression of beta-galactosidase in cultured rat peripheral neurons.

A defective herpes simplex virus-1 (HSV-1) vector system was used to study cell type-specific expression of the tyrosine hydroxylase (TH) gene. HSV-1 particles containing 663 bp (pTHlac 663), 278 bp (pTHlac 278), or 181 bp (pTHlac 181) of the rat TH promoter driving E. coli LacZ were used to infect superior cervical ganglia (SCG: TH-expressing tissue) and dorsal root ganglia (DRG:non-TH-expressing tissue) cultures. One day after infection, expression of beta-galactosidase was visualized by X-gal cytochemistry. Following viral transduction with pTHlac 663 at a multiplicity of infection of 0.2, 14.4% of the SCG neurons were X-gal positive whereas only about 0.9% of DRG neurons were X-gal positive. Infection with either pTHlac278 or 181 resulted in 3-fold more X-gal-positive DRG neurons. These results suggest that (i) the defective HSV-1 vector system may be useful in defining regulatory promoter motifs; (ii) 663 bp of the rat TH promoter contains sufficient information for cell type-specific expression in peripheral nervous system neurons; and (iii) sequences between -278 and -663 contain an element(s) that represses gene expression in non-catecholamingeric neurons.

Animals↗
PubMed1996

13C NMR of Nephila clavipes major ampullate silk gland.

The major ampullate glands of the spider Nephila clavipes contain approximately 0.2 microliter each of a highly concentrated (approximately 50%) solution of silk fibroin. Therefore, the reservoir of silk in these glands presents an ideal opportunity to observe prefolded conformations of a protein in its native state. To this end, the structure and conformation of major ampullate gland silk fibroin within the glands of the spider N. clavipes were examined by 13C NMR spectroscopy. These results were compared to those from silk protein first drawn from the spinneret and then denatured. The 13C NMR chemical shifts, along with infrared and circular dichroism data, suggest that the silk fibroin in the glands exists in dynamically averaged helical conformations. Furthermore, there is no evidence of proline residues in U-(13)C-D-glucose-labeled silk. This transient prefolded "molten fibril" state may correspond to the silk I form found in Bombyx mori silk. There is no evidence of the final beta-sheet structure in the ampullate gland silk fibroin before final silk processing. However, the conformation of silk in the glands appears to be in a highly metastable state, as plasticization with water produces the beta-sheet structure. Therefore, the ducts connecting the ampullate glands to the spinnerets play a larger role in silk processing than previously thought.

Alanine↗
PubMed1996

Drug-drug and drug-disease interactions in the ED: analysis of a high-risk population.

A study was undertaken to determine the potential for adverse drug interactions (ADIs) and drug-disease interactions (DDIs) in a high-risk population of emergency department (ED) patients and to characterize drug-drug and drug-disease interactions in terms of percentage of patients at risk from existing drug regimens, percentage of patients at risk from ED treatment, relation between number of drugs and potential for interactions, types of drugs and diseases posing greatest potential for interaction, and the differences in a general versus community hospital population with respect to these parameters. Records of 205 consecutive patients, 111 from a general hospital teaching facility ED (Facility 1) and 94 from a community hospital ED (Facility 2) were retrospectively reviewed. The records of all patients receiving three or more medications and all patients older than 50 years of age receiving two or more medications were analyzed by two computer programs for the presence of potential drug-drug and drug-disease interactions. A total of 226 potential ADIs were found in 89 patients (47%), with 50% of ADIs being related to ED treatment. A total of 94 potential DDIs were found in 44 patients (21%), with 34% of DDIs being related to ED treatment. The risk of an ADI rose from 13% for patients taking 2 medications to 82% for patients taking 7 or more medications. Eleven medications and four disease categories were identified as having particular potential for interactions. No significant differences were found between the general and the community hospital populations in these respects. ED patients taking three or more medications and patients older than 50 years of age taking two or more medications are at substantial risk for adverse drug-drug and drug-disease interactions. The risk is increased in patients taking particular drugs or having particular disease states.

Adolescent↗
PubMed1996

Anomalous perceptual asymmetries for negative emotional stimuli in the psychopath.

This study tested the hypothesis that when processing negative emotional material, psychopaths, compared with nonpsychopaths, would rely less on connotative-emotional processes based in the right hemisphere and more on denotative-linguistic processes based in the left hemisphere. Psychopathic and nonpsychopathic inmate groups, defined by their scores on the Psychopathy Checklist--Revised (R. D. Hare 1985), completed 2 analogous tachistoscopic tasks (words and faces). Accuracy and reaction times of inmates' responses in identifying which of 2 bilaterally presented stimuli (1 neutral and 1 emotional) was the emotional stimulus were measured. Significant lateral processing differences between the 2 groups emerged on the word task but not on the face task, providing partial support for the experimental hypothesis. Psychopaths also showed lower generalized emotional responsivity than nonpsychopaths on the Affect Intensity Measure.

Adult↗
PubMed1996

Cellular targets and molecular responses associated with photodynamic therapy.

The positive clinical results associated with photodynamic therapy (PDT) have led to an expanded need to identify the cellular targets and molecular responses associated with this treatment. Increased knowledge regarding the mechanisms of action associated with PDT-mediated cytotoxicity should contribute to the continued advancement of this therapy. This report focuses on recent studies analyzing PDT resistance and examining stress protein and early response gene activation induced by photosensitizer mediated oxidative stress. Recurring observations from these studies indicate that subcellular targets and cellular responses associated with PDT can vary significantly for different photosensitizers.

Animals↗
PubMed1996

Diagnosis of disseminated microsporidian Encephalitozoon hellem infection by PCR-Southern analysis and successful treatment with albendazole and fumagillin.

A 37-year old AIDS patient presented with foreign body sensation. Microsporidia were detected in smears from a conjunctival swab and urine sediment stained with calcofluor and a modified trichrome blue stain and by indirect fluorescent-antibody staining with murine polyclonal antiserum raised against Encephalitozoon hellem. This antiserum cross-reacted with other Encephalitozoon species, so PCR was performed to amplify the microsporidian ribosomal DNA (rDNA) with pan-Encephalitozoon primers. The PCR DNA products from the urine and conjunctival clinical specimens, along with the tissue culture-derived microsporidian controls, were assayed by Southern analysis with oligonucleotide probes specific for Encephalitozoon cuniculi, E. hellem, and Encephalitozoon (Septata) intestinalis. The PCR product amplified from the urine specimen hybridized with the E. hellem probe only, while insufficient DNA was amplified from the conjunctiva specimen for detection by Southern analysis. For corroboration of the PCR-Southern analysis results, aliquots of the urine and conjunctiva specimens were seeded onto RK-13 cell monolayers. The rDNA extracts of the cultured microsporidia were amplified by PCR with pan-Encephalitozoon primers, and the PCR DNA products were subjected to digestion with restriction endonuclease FokI. The amplified rDNA of both the urine and conjunctiva isolates generated digestion patterns that were identified to the E. hellem PCR rDNA digestion pattern. In addition, double-stranded heteroduplex mobility shift analysis with these PCR products indicated that the urine and conjunctiva isolates were identical to each other and to E. hellem. The patient was treated with albendazole and topical fumagillin and responded rapidly, with no recurrence of ophthalmologic signs. The results of this study demonstrate that PCR-Southern analysis provides a basis for distinguishing E. cuniculi, E. hellem, and E. intestinalis in clinical specimens.

AIDS-Related Opportunistic Infections↗
PubMed1996

Regulation of type I adenylyl cyclase by calmodulin kinase IV in vivo.

Type I adenylyl cyclase is a neurospecific enzyme that is stimulated by Ca2+ and calmodulin (CaM). This enzyme couples the Ca2+ and cyclic AMP (cAMP) regulatory systems in neurons, and it may play an important role for some forms of synaptic plasticity. Mutant mice lacking type I adenylyl cyclase show deficiencies in spatial memory and altered long-term potentiation (Z. Wu, S. A. Thomas, Z. Xia, E. C. Villacres, R. D. Palmiter, and D. R. Storm, Proc. Natl. Acad. Sci. USA 92:220-224, 1995). Although type I adenylyl cyclase is synergistically stimulated by Ca2+ and G-protein-coupled receptors in vivo, very little is known about mechanisms for inhibition of the enzyme. Here, we report that type I adenylyl cyclase is inhibited by CaM kinase IV in vivo. Expression of constitutively active or wild-type CaM kinase IV inhibited Ca2+ stimulation of adenylyl cyclase activity without affecting basal or forskolin-stimulated activity. Type I adenylyl cyclase has two CaM kinase IV consensus phosphorylation sequences near its CaM binding domain at Ser-545 and Ser-552. Conversion of either serine to alanine by mutagenesis abolished CaM kinase IV inhibition of adenylyl cyclase. This suggests that the activity of this enzyme may be directly inhibited by CaM kinase IV phosphorylation. Type VIII adenylyl cyclase, another enzyme stimulated by CaM, was not inhibited by CaM kinase II or IV. We propose that CaM kinase IV may function as a negative feedback regulator of type I adenylyl cyclase and that CaM kinases may regulate cAMP levels in some cells.

Adenylyl Cyclases↗
PubMed1996

Screening African-American elderly for the presence of depressive symptoms: a preliminary investigation.

Several authors have reported that older African-Americans with multiple medical problems and decreased activities of daily living are at an increased risk of reporting symptoms of depression. African-Americans were more likely to report symptoms of anger, irritability, denial of illness, and to spontaneously report symptoms that did not reflect a change in mood, but rather forbearance of a difficult time or somatic complaints. This paper describes the results of a study to assess the presence of depressive symptoms in older African-American community residents. A new instrument, the Baker Belief Scale, is compared with the Center for Epidemiologic Studies-Depression Scale (CES-D) and the association of medical illnesses, social network, and level of physical function in activities of daily living (ADL). Ninety-six African-American men and women, aged 60 years or older, with equal representation from urban and rural counties in western Tennessee comprised the sample. The sample was stratified, in each of the two counties, into three age categories; 60-69, 70-79, and 80 years and older. A screening battery consisting of the Short Portable Mental Status Questionnaire, the CES-D, the Lubben Social Network Scale, and the Katz ADL were administered to the sample. Current medical illnesses were recorded with demographic data. There was a significant association between the CES-D score and the BBS score for those who screened positive for symptoms of depression. In addition there was a significant relationship between CES-D score and specific medical illnesses, social network, physical function in ADL, and residence (urban vs. rural). Residents who screened positive (N = 19) for depressive symptomatology with CES-D scores of 16 or higher exhibited a higher frequency of hypertension, arteriosclerosis, and circulatory problems than those who tested negative (N = 77). More urban residents (N = 13) than rural residents (N = 6) screened positive for symptoms of depression. Approximately 21% (N = 20) of the 96 respondents had scores of 20 or less on the Lubben Social Network Scale, suggesting a group of "at risk" for social isolation.

Black or African American↗
PubMed1996

Relationships among sex steroids, oxytocin, and their receptors in the rat uterus during late gestation and at parturition.

Sex steroids and oxytocin (OT) produced within intrauterine tissues have been implicated in the regulation of parturition. The purpose of these studies was 1) to determine the relationships among estradiol (E2), progesterone (P4), OT, and their receptors in uterine tissues during late gestation and parturition in the rat; 2) to observe the effects of the estrogen antagonist tamoxifen (TAM) on these factors; and 3) to evaluate the rat as a potential model for events at human parturition. Concentrations of E2, P4, PGE2, and OT were measured by RIA. E2 receptor (ER) was measured by enzyme immunoassay, and P4 receptor (PR) and OT receptor (OTR) were measured by binding assays. OT messenger RNA (mRNA) was measured by ribonuclease protection assay. Groups (n = 5) of pregnant rats (normal gestation = 22 days) were treated with TAM (200 mg/day) or vehicle and killed on gestation day 19, 21, 21.5, or 22 or after delivery of the first pup. Serum E2 increased throughout late gestation accompanied by an increase in uterine OT mRNA and ER. Serum P4 declined after day 19, and uterine PR did not change significantly. Uterine PGE2 increased progressively, reaching peak levels the evening before delivery. Uterine OTR did not increase until the morning of delivery, and uterine OT peptide concentrations increased only during parturition. Parturition was significantly delayed by 24 h in the TAM-treated group. TAM inhibited the increase in serum E2, uterine ER, and OT mRNA and peptide, but had no effect on serum P4 or uterine PR levels. With TAM, the responses of uterine OTR and PGE2 were significantly delayed, but still underwent a significant increase before the delayed parturition. These results support the hypothesis that E2 stimulates the synthesis of ER, OT, and OTR within the rat uterus and is essential for normal parturition. P4 withdrawal may be more important to the increases in OTR and PGE2, but these are delayed in the absence of estrogen. These data also suggest that the rat may be a relevant model for human parturition.

Animals↗
PubMed1996

Recognizing glaucoma. A guide for the primary care physician. .

Glaucoma is a group of diseases leading to characteristic cupping and damage of the optic nerve head associated with progressive visual loss. The exact mechanism of damage is unknown, but current research is pointing toward a multifactorial disease process, in which elevated intraocular pressure is just one of the factors. Early detection and proper management are imperative because of the disease's prevalence, progressive and often insidious nature, and significant associated morbidity.

Acute Disease↗
PubMed1995

Carbohydrate recognition by a natural killer cell receptor, Ly-49C.

Ly-49 represents a family of type II transmembrane proteins containing C-type lectin domains. At least two members of the Ly-49 family, namely Ly-49A and Ly-49C, are expressed by distinct subsets of natural killer cells and bind to class I major histocompatibility complex antigens on the surface of target cells. In this report we have established that Ly-49C mediates carbohydrate recognition. The sulfated glycans fucoidan, lambda-carrageenan, and dextran sulfate were found to be potent inhibitors of Ly-49C-mediated cell adhesion, whereas other polysaccharides of similar size, charge, or sulfate content were noninhibitory. All of the polysaccharides which inhibited Ly-49C adhesion also blocked the binding of the antibody 5E6 to Ly-49C-expressing COS cells, confirming the direct protein-carbohydrate interaction. The enzymatic removal of specific carbohydrates from the target cell surface has shown that Ly-49C-mediated adhesion is not sialic acid-dependent, but is significantly decreased following fucosidase treatment. These results suggest an important role for carbohydrate recognition by natural killer cell receptors.

Animals↗
PubMed1995

An asymmetric half-wedged field technique for the treatment of inferiorly extended head and neck cancers.

Adequate dose coverage of the target volume of head and neck cancer patients can be difficult to achieve with lateral opposing fields when the patient's neck is short and the disease involves the lower cervical region. Rotation of the couch away from the side of the gantry, such that the beams are angled towards the inferior aspect of the patient, can result in a better dose distribution. However, if the neck separation is large, unacceptable dose inhomogeneities will still exist. The conventional approach in these situations is to treat with parallel opposed lateral fields junctioned with anterior/posterior opposed low neck fields. We present a variation on the couch rotation technique as an alternative. Asymmetric jaws and half-wedged fields are used to obtain a homogeneous dose within an inferiorly extended target volume. The advantages of this technique are a simple set up and the capability of adding spinal cord shielding without shielding midline primary tumour.

Film Dosimetry↗