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Biomedical subjects

F Wong

Publications and source records attributed to F Wong.

At least 127 records · Page 7Linked to original sources
PubMed1996

Assessing vocal function after chemoradiation for advanced laryngeal carcinoma.

OBJECTIVE: To identify objective parameters that could serve as valid indicators of vocal function in evaluating patients treated at multiple centers for head and neck cancer. DESIGN: Objective measures of voice were validated against functional outcome measures of voice and communication. SETTING: A multidisciplinary university-based ambulatory head and neck cancer clinic. SUBJECTS: Fifteen patients at varying posttreatment intervals after chemoradiation therapy for head and neck cancer and 5 volunteers with no cancer but with a history of heavy smoking and drinking. MAIN OUTCOME MEASURES: Acoustic and aerodynamic parameters were measured in patients with head and neck cancer after treatment with combined chemotherapy and irradiation and in control subjects. Communicative function was assessed by perceptual assessment of recorded voice samples, by a clinician-based communication score, and by patient self-rating of voice and communication. RESULTS: Both perceptual analysis and communication score were concordant with patient self-rating of voice and communication ability. Acoustic measures were abnormal in patients, and jitter scores correlated with listener ratings of perceived voice quality. However, acoustic measures did not relate to communication function, as assessed by either the patient or the clinician. Laryngeal resistance demonstrated a significant correlation with both patient and observer assessments of voice quality and communication function. Laryngeal resistance was on average twice as high in patients who complained of voice fatigue, but this difference was not statistically significant. CONCLUSIONS: Laryngeal resistance, determined during standardized phonation, is a reliable objective parameter of vocal function after chemoradiation therapy for head and neck cancer. A standardized clinician-based communication scale holds promise as a useful tool. Acoustic measures reflect the sound of the voice but not the ability to communicate effectively.

Acoustics↗
PubMed1996

Hyperinsulinemia in preascitic cirrhosis: effects on systemic and renal hemodynamics, sodium homeostasis, forearm blood flow, and sympathetic nervous activity.

Insulin has been shown to be vasodilatory and antinatriuretic and to stimulate sympathetic nervous activity independent of hypoglycemia in healthy normal subjects. It is hypothesized that hyperinsulinemia, which is commonly observed in cirrhosis, may in part be responsible for the systemic vasodilatation, sympathetic activation, and sodium retention in these patients. The aims of this study, in preascitic cirrhotics, were as follows: (1) to document baseline hyperinsulinemia and its effects on sodium handling, forearm and renal circulations, and sympathetic nervous activity; (2) to determine if pharmacological increases in plasma insulin levels would result in an exaggeration of these physiological effects. Seven male, nonobese, well-compensated, preascitic cirrhotic patients were studied, after being maintained on a 150 mmol sodium per day diet for 7 days, firstly at baseline level, followed by increasing doses of insulin from 10 to 1,200 mU/m2/min using the euglycemic clamp technique. Systemic and renal hemodynamics, urinary sodium excretion, plasma norepinephrine, and forearm blood flow (FBF) were measured at the end of baseline and each hyperinsulinemic period. Baseline measurements in the cirrhotics, when compared with our laboratory standards obtained from a comparable group of male healthy normals, showed significant hyperinsulinemia (P=.01), associated with significantly higher FBF (P=.02), and glomerular filtration rate (GFR) (P=.02), as well as significantly reduced urinary volume (P=.04) and fractional excretion of sodium (P=.04). Insulin infusions in the cirrhotics produced no further sodium retention, but further forearm vasodilatation occurred at doses > or = 10 mU/m2/min. In contrast, there was no further renal vasodilatation except at very high pharmacological levels of insulin together with an unchanged GFR, natriuresis, and diuresis. Hyperinsulinemia produced no significant effects on the sympathetic nervous activity. In conclusion, these results suggest that hyperinsulinemia may be implicated in the glomerular hyperfiltration and sodium retaining tendency of preascitic cirrhotic patients with glucose intolerance. The ability of the kidneys to escape from the sodium retaining effects may serve as an in-built physiological regulatory mechanism on sodium homeostasis.

Adult↗
PubMed1996

The effect of posture on central blood volume in patients with preascitic cirrhosis on a sodium-restricted diet.

The status of the central blood volume in cirrhosis is controversial. A combination of sodium restriction and upright posture, which redistributes intravascular volume to dependent parts of the body should further aggravate a contracted central blood volume reduction. The aim of this study was to determine the effect of upright posture and sodium restriction on central blood volume (CBV) in preascitic cirrhotic patients, compared with controls. Eight male, preascitic, alcoholic cirrhotic subjects and eight healthy male controls were studied while on a 20-mmol/d sodium diet. Measurements of CBV by radionuclide angiography, and neurohumoral factors were performed on day 7 in both supine and erect positions and cardiac output and systemic vascular resistance (SVR) was calculated. Sodium restriction resulted in less weight loss in the cirrhotic patients (P = .03), with significantly lower plasma renin activity (P = .001). Similar central blood volumes and systemic hemodynamics were observed in both groups in the supine posture. In contrast to the cirrhotic patients, in the control subjects, upright posture resulted in a significant reduction in cardiac output (P = .002) and increase in SVR (P = .005), associated with a decrease in all blood volumes which were significantly less than in the cirrhotic patients. Mean arterial pressure was maintained in both groups in both postures. In conclusion, with sodium restriction, preascitic cirrhotic patients have less intravascular volume contraction than control patients. Erect posture results in redistribution of this relatively expanded intravascular volume to the CBV. Therefore, a low-sodium diet can be safely administered in preascitic cirrhotic patients.

Adult↗
PubMed1996

Protease repertoires of cells adherent to membranes recovered after guided tissue regeneration.

Guided tissue regeneration is a clinical procedure used to restore mineralized tissue that has been lost to periodontal disease or after tooth extraction. The procedure makes use of Gore-tex membranes or Gore-tex augmentation membranes (GTAM) to prevent migration of keratinocytes and gingival fibroblasts into healing wounds. To begin to characterize the regenerative cells associated with these membranes, human cells have been rescued from membranes retrieved after bone-inductive procedures. Cell lines were established from tissue adherent to Gore-tex membranes used to regenerate bone around periodontally compromised teeth, and from tissue adherent to GTAM used in edentulous ridge augmentation procedures or in conjunction with implant placement. Cell lines were screened for mineralized nodule formation in vitro prior to their subsequent analysis. All but one of the lines selected for this study formed mineralized nodules in vitro with cells from GTAM tending to form nodules more quickly than cells from Gore-tex. Zymograms and Western blots were used to compare protease profiles of these cells with those of human gingival fibroblasts, keratinocytes and periodontal ligament (PDL) cells. All cell types except for keratinocytes produced a 72 kD protease. In contrast, keratinocytes were the only cells that produced 92 kD gelatinase. In some cell lines, notably those removed from patients after short periods of regeneration, collagenase was the major protease detected on gelatin substrate gels. Some of these cell lines also produced additional proteases including a low molecular weight protease (30 kD) not seen in gingival fibroblasts, PDL cells or keratinocytes.

Adult↗
PubMed1996

Overexpression of Bcl-2 and mutations in p53 and K-ras in resected human non-small cell lung cancers.

We investigated expression of Bcl-2, mutations in p53, and K-ras oncogene in 51 resected human non-small cell lung cancers. The studies were designed to test for the possibility of cooperativity between these oncogenes and p53 in the pathogenesis of lung cancer. An inverse relationship was found between expression of Bcl-2 and mutant p53 by immunohistochemistry (P < 0.01; Fisher exact test), suggesting that either Bcl-2 overexpression or mutations in p53 may fulfill a critical function in the pathogenesis of human non-small cell lung cancers. Tumors that harbored K-ras codon 12 mutations seldom had p53 mutations or overexpressed Bcl-2. Statistical analysis of these data showed that mutations in p53 and K-ras or overexpression of Bcl-2 and mutations in K-ras occurred at a frequency that could be explained only by chance [P > 0.1 in each case (Fisher exact tests)]. This suggests that cooperativity between mutant K-ras and mutant p53 or mutant K-ras and overexpressed Bcl-2 is not a common mechanism in the pathogenesis of human non-small cell lung cancers.

Adenocarcinoma↗
PubMed1996

The effect of varying sodium intake on blood volume, forearm blood flow and vascular responsiveness to sympathetic stimulation in pre-ascitic cirrhosis.

OBJECTIVES: To assess, in patients with well-compensated pre-ascitic cirrhosis, (1) the extent of vasodilatation, if any, in the forearm circulation and (2) the effect of sodium status on its response to reflex sympathetic stimulation. DESIGN: Case-control study. SETTING: Clinical investigation unit of the Toronto Hospital, a tertiary referral hospital. PATIENTS: Eight male, alcoholic patients with pre-ascitic cirrhosis and 10 age- and sex-matched controls. INTERVENTIONS: Patients and controls were given a diet containing 20 mmol of sodium per day for 7 days, then a diet containing 200 mmol of sodium per day for the subsequent 7 days. On the seventh day of each diet, systemic hemodynamics, forearm circulation and effective arterial blood volume were assessed. A cold pressor test was performed after both diets to assess the response of the forearm circulation to reflex sympathetic stimulation. OUTCOME MEASURES: Heart rate, mean arterial pressure, forearm blood flow, forearm vascular resistance, central venous pressure, atrial natriuretic factor concentrations and neurohumoral pressor levels (plasma renin activity, aldosterone and plasma norepinephrine levels). RESULTS: No forearm vasodilatation was evident in the patients with pre-ascitic cirrhosis; their forearm blood flow and forearm vascular resistance were similar to those of the controls. Sodium loading did not influence baseline forearm blood flow. Cold pressor stimulus resulted in a significant decrease in forearm blood flow and a significant increase in forearm vascular resistance, mean arterial pressure, heart rate and plasma norepinephrine levels in both groups after the low-sodium diet. High sodium intake resulted in significantly greater reduction in forearm blood flow (-19%, standard error of the mean [SEM] 3% v. -8%, SEM 3%; p < 0.05) and significantly greater increase in forearm vascular resistance (+46%, SEM 7% v. +25%, SEM 8%; p < 0.05) in the patients with cirrhosis than in the controls. CONCLUSIONS: Well-compensated pre-ascitic cirrhotic patients do not have forearm vasodilatation. Sodium loading does not increase baseline forearm blood flow in these patients, but it does lead to a heightened response to reflex sympathetic stimulation. Sodium loading, with the associated sympathetic hyper-responsiveness, may therefore contribute to further sodium retention in these patients.

Adult↗
PubMed1995

Altered cAMP levels in retinas from transgenic mice expressing a rhodopsin mutant.

Transgenic mice expressing the rhodopsin mutant Pro347Ser (Serine 6) display retinal degeneration through apoptosis that is characteristic of the disease retinitis pigmentosa. By 5 weeks after birth, these mice have lost approximately 35% of their photoreceptor cells. Retinas from these mice showed higher levels of cAMP compared to the levels in retinas of normal mice. Our studies provide evidence that elevated cAMP is common to the apoptotic process that occurs in retinitis pigmentosa. In addition, in vitro studies demonstrate no differences in the ability of the mutant and the wild-type rhodopsin to activate transducin, the rod cell G protein, to be phosphorylated by rhodopsin kinase or to bind arrestin. Mutants of rhodopsin, including Pro347Ser, are mistargeted to the rod inner segment, raising the possibility that rhodopsin triggers apoptosis through activation of signaling pathways not normally under its control.

Animals↗
PubMed1995

Transjugular intrahepatic portosystemic stent shunt: effects on hemodynamics and sodium homeostasis in cirrhosis and refractory ascites.

OBJECTIVE: To assess the effects of transjugular intrahepatic portosystemic shunt (TIPS) on systemic and renal hemodynamics, neurohumoral factors, and sodium homeostasis in patients with cirrhosis and refractory ascites. DESIGN: Prospective study with 1-year follow-up. SETTING: Tertiary referral center and university-affiliated hospital. PATIENTS: 7 patients with cirrhosis and refractory ascites had metabolic studies done while receiving a 22 mmol/d sodium, 1 L/d fluid diet. INTERVENTION: TIPS insertion. MEASUREMENTS: Urinary sodium excretion, systemic and renal hemodynamics, hormonal profile, and central blood volume were measured before, at day 1 after, and at 1 month after TIPS insertion. RESULTS: Immediately after TIPS insertion, mean corrected sinusoid pressure decreased from 18.2 +/- 2.2 mm Hg to 7.7 +/- 1.3 mm Hg (P < 0.001); mean cardiac output increased from 6.83 +/- 0.68 L/min to 8.62 L/min (P = 0.005); and mean systemic vascular resistance decreased from 1018 +/- 103 dyne.s.cm-5 to 762 +/- 46 dyne.s.cm-5 (P = 0.011). Mean plasma renin activity, serum aldosterone levels, and 24-hour urinary sodium excretion (5.8 +/- 0.7 mmol/d before TIPS insertion compared with 6.0 +/- 1.8 mmol/d 1 day after insertion) were unchanged; mean elevated plasma norepinephrine levels significantly increased. By 1 month after insertion, mean proximal tubular reabsorption of sodium had decreased, and this had led to a mean natriuresis of 15.1 +/- 3.1 mmol/d (P = 0.02 compared with baseline), which was associated with a decrease in plasma renin activity and aldosterone levels to within the normal range. CONCLUSIONS: Our results suggest that natriuresis associated with TIPS is delayed and occurs in the presence of increased systemic vasodilatation at 1 month after insertion and that TIPS insertion should not be done in any patients with refractory ascites without careful attention to cardiac and renal status. However, in carefully selected patients, TIPS is a safe and effective means of managing refractory ascites.

Adult↗
PubMed1995

Small cell carcinoma of the cervix treated with concurrent radiotherapy, cisplatin, and etoposide.

A multimodality regimen of four cycles of cisplatin and etoposide with concurrent locoregional radiotherapy (XRT) has been, since May 1988, the standard therapy for women with small cell carcinoma of the cervix (SCCC). Prophylactic cranial irradiation was to be used in all but primary progressors. All 11 patients (median age 47; 4 with pure SCCC and 7 with mixed histology) seen by us were treated with this regimen. Only 1 patient progressed while on treatment. The 3-year overall and failure-free survivals were 28%. Four patients remain alive in first remission; the remaining 7 died (2 from toxicity, 5 from cancer). Although not statistically significant due to the small numbers, it appeared that the chance of long-term survival depended both on the amount of the cancer as indicated by the FIGO stage and size of the primary and also the performance status. The toxicity was significant with 70% experiencing severe neutropenia and 40% being admitted for control of emesis. This regimen is only appropriate for those women in whom all of the apparent tumor can be encompassed within a radiation field and who, in addition, have a performance status of 0 or 1. For the remainder it does not offer any chance of long-term survival and its toxicity renders it antipalliative.

Adult↗
PubMed1995

Pattern of sodium handling and its consequences in patients with preascitic cirrhosis.

BACKGROUND/AIMS: The initial abnormalities in the renal sodium handling in patients with cirrhosis before developing ascites remain unknown. The aim of this study is to further characterize sodium metabolism and the effects of sodium loading in preascitic cirrhosis. METHODS: Eight male, preascitic patients with cirrhosis and 6 volunteers had their daily urinary sodium excretion level measured while on a strictly metabolically controlled diet, first consisting of 20 mmol then of 200 mmol sodium per day each for 7 days. Central blood volume, plasma norepinephrine, and atrial natriuretic factor levels were measured during each diet. RESULTS: Preascitic patients with cirrhosis had significantly less daily urinary sodium excretion on both diets. Volume expansion in the patients with cirrhosis was indicated by significantly greater weight gain and higher atrial natriuretic factor levels for each diet. Patients with cirrhosis had central blood volume expansion (1725 +/- 54 mL/m2) compared with controls (1495 +/- 81 mL/m2; P = 0.03) on a low-sodium diet. This increased significantly in the controls (1864 +/- 164 mL/m2; P = 0.04) on a high-sodium diet, associated with suppression of plasma norepinephrine, but not in the patients with cirrhosis (1679 +/- 107 mL/m2; P > 0.05). CONCLUSIONS: Failure of further central blood volume expansion in the patients with cirrhosis on high-sodium diet in the presence of significant weight gain suggests maldistribution away from the effective arterial blood volume. This study provides further reasons why preascitic patients with cirrhosis might benefit from sodium restriction.

Adult↗
PubMed1995

The effect of misoprostol on indomethacin-induced renal dysfunction in well-compensated cirrhosis.

BACKGROUND/AIMS: Indomethacin has been shown to have adverse effects on renal function in patients with well-compensated alcoholic cirrhosis. The aim of this study was to determine whether an oral prostaglandin E1 analogue, misoprostol, could prevent this indomethacin-induced renal dysfunction. METHODS: Six patients with well-compensated alcoholic cirrhosis were studied. Renal hemodynamics and tubular function were assessed by clearance techniques before and after an oral dose of (i) 50 mg of indomethacin alone (I50), and (ii) a combination of I50 and 200 micrograms of misoprostol. RESULTS: I50 produced a significant reduction in glomerular filtration rate, a fall in effective renal plasma flow and an increase in renal vascular resistance. Two hundred micrograms of misoprostol was able to abolish the deleterious renal effects of indomethacin totally, yielding an increase in glomerular filtration rate and effective renal plasma flow and a decrease in renal vascular resistance as well as an increase in urinary volume and urinary sodium excretion. These beneficial effects were maximal in the hour immediately following medication, but were only transient, and this may be a limiting factor in its clinical use. CONCLUSIONS: If the beneficial renal effects of misoprostol could be confirmed after chronic administration, then the vasodilatory, natriuretic and diuretic potential of 200 micrograms of misoprostol could be of potential therapeutic value in patients with well-compensated alcoholic cirrhosis who require non-steroidal anti-inflammatory drug therapy.

Administration, Oral↗
PubMed1995

Effects of sodium status on the venous response to noradrenaline infusion in pre-ascitic cirrhosis.

1. This study assesses the effects of sodium status on venous responsiveness to noradrenaline and the neurohumoral profile in pre-ascitic cirrhotic patients. Eight cirrhotic patients and ten control subjects were studied after both a low (20 mmol/day) and a high (200 mmol/day) sodium diet. Venous responsiveness to increasing doses of noradrenaline in a dorsal hand vein and various plasma hormone levels were measured. Maximal response (Rmax.) and the dose of noradrenaline that yielded 50% of Rmax. (ED50) were then calculated. 2. A significantly smaller dorsal hand vein diameter was observed in the control subjects on a low sodium (2.23 +/- 0.14 mm) compared with a high sodium (2.57 +/- 0.15 mm; P = 0.04) diet, but not in the cirrhotic patients. Rmax. was not significantly different in either group on both diets. With low sodium intake, ED50 was similar in the two groups. However, on high sodium intake, control subjects had a significantly higher ED50 (34.4 +/- 7.4 ng/min) than the cirrhotic patients (5.03 +/- 0.86 ng/min; P < 0.003). Plasma noradrenaline in the control subjects fell significantly with the change from a low (1.29 +/- 0.11 nmol/l) to a high (0.68 +/- 0.09 nmol/l; P < 0.001) sodium diet, but remained elevated in the cirrhotic patients. Cirrhotic patients had significantly higher atrial natriuretic factor levels and lower plasma renin activity than the control subjects on both diets. 3. In conclusion, pre-ascitic cirrhotic patients show no evidence of venodilatation. Their sympathetic nervous activity is not suppressible by volume expansion. Relative hyper-responsiveness of the peripheral venous circulation to adrenergic stimulation with high sodium intake is present.

Adult↗
PubMed1995

Randomized trial of epirubicin and cisplatin chemotherapy followed by pelvic radiation in locally advanced cervical cancer. Cervical Cancer Study Group of the Asian Oceanian Clinical Oncology Association.

PURPOSE: Pelvic radiation is standard treatment for women with stage IIb to IVa cervical cancer, but treatment results are disappointing, particularly for women with bulky tumors. We investigated the role of primary chemotherapy followed by pelvic radiotherapy in a randomized trial. PATIENTS AND METHODS: Two hundred sixty patients with stage IIb and IVa cervical cancer received either standard pelvic radiotherapy or primary chemotherapy with cisplatin 60 mg/m2 and epirubicin 110 mg/m2 administered at 3-week intervals for three cycles, followed by pelvic radiotherapy. RESULTS: Ninety-nine patients have relapsed with a median follow-up duration of 1.3 years; in 62 patients, the first site of progressive disease was the pelvis. Patients who received primary chemotherapy had a significantly higher pelvic failure rate than those who received radiotherapy alone (P < .003). Seventy-six patients have died, and those who received primary chemotherapy had significantly inferior survival compared with those who received radiotherapy alone (P = .02). Tumor response following chemotherapy was observed in 63%. After radiotherapy, tumor response occurred in 72% of those who received combined modality treatment, compared with 92% of those who received radiotherapy alone. CONCLUSION: Primary chemotherapy with epirubicin and cisplatin, although resulting in tumor response in a significant proportion of patients, is accompanied by an inferior local control rate and survival compared with standard pelvic radiotherapy alone.

Adenocarcinoma↗
PubMed1995

Site-directed mutagenesis using thermostable enzymes.

The two-primer method for site-directed mutagenesis facilitates the mutation of targets in double-stranded DNA. We have encountered difficulties using the original method for the mutagenesis of DNA cloned into pBluescript vectors, which is possibly due to the presence of regions of secondary structure that cannot be efficiently copied by the enzymes used. We report a modification of the two-primer method using the thermostable VentR DNA polymerase and Thermus aquaticus ligase, allowing an increase in reaction temperatures. The modified method is functional with the pBluescript family of vectors.

Base Sequence↗