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F Wong

Publications and source records attributed to F Wong.

At least 37 records · Page 2Linked to original sources
PubMed2001

An allele-specific hammerhead ribozyme gene therapy for a porcine model of autosomal dominant retinitis pigmentosa.

PURPOSE: To develop a hammerhead ribozyme-based gene therapy for a porcine model of autosomal dominant retinitis pigmentosa (ADRP). METHODS: Hammerhead ribozymes were developed and assayed in vitro against RNA targets homologous to the opsin P347S mutants found in a transgenic porcine model and in humans. Both cloned and synthetic RNA oligonucleotide versions of ribozymes and targets were tested under multiple-turnover conditions using oligonucleotide RNA targets. Digestion of full-length P347S mRNA from porcine retina was performed. RESULTS: The porcine P347S hammerhead ribozyme was specific for the opsin P347S sequence. Multiple-turnover analysis yielded the following kinetic parameters: Vmax=7.3+/-0.5 nM/min, Km=2.1+/-0.6 mM, and kcat=1.5+/-0.4 min-1. The human P347S hammerhead ribozyme was substantially less active (~10,000 fold). CONCLUSIONS: We have developed a hammerhead ribozyme to use as a model for gene therapy of autosomal dominant retinitis pigmentosa in a transgenic porcine model. Based on kinetic characterization of this ribozyme compared to others used for gene therapy, this should be an effective reagent RNA. The allele specific ribozyme we tested for the human sequence, however, is not likely to be useful for gene therapy indicating that an alternative approach is necessary.

Alleles↗
PubMed2001

"What doesn't kill you makes you stronger": an ovarian cancer survivor survey.

OBJECTIVES: This survey was designed to learn more about the physical health and quality of life of ovarian cancer survivors without known active disease and not on treatment. METHODS: Women with ovarian cancer without evidence of active disease, and not on treatment for at least 2 years, were recruited in Canada and the United States from university cancer clinics, community ovarian support groups, and a cancer survivor network newsletter and asked to complete an anonymous mail-back survey on their physical, psychological, social, and spiritual well-being. RESULTS: Two-hundred (67.5%) women responded. Their mean age was 55.3 years, 72.5% had children, and they had been diagnosed with ovarian cancer a mean of 7.2 years previously. Eighty-nine percent regarded their health as good or excellent, but 53.5% had current pain or discomfort. They reported better mental health and equivalent energy levels to the general population. Although 57% reported that their sex lives had been negatively affected by cancer and its treatment, their overall sense of loss relating to sexual functioning was moderate to low. However, women under age 55 years reported a greater sense of loss about sexual function and fertility (P = 0.001). Most women reported that their ovarian cancer experience had changed their views on life and relationships in an overwhelmingly positive way. CONCLUSION: Most ovarian cancer survivors, despite some symptoms, enjoyed good physical, psychological, social, and spiritual health. Specific concerns emerged about sexuality which should be addressed in patient education. Having survived a life-threatening illness, ovarian cancer survivors appear to have put other life difficulties into perspective, altered their priorities, and felt enriched by the experience. In general, these women showed impressive and inspiring resilience and reported good physical health and energy, excellent psychological health, and feelings of greater pleasure in life and personal relationships.

Adult↗
PubMed2001

The hyperdynamic circulation in cirrhosis: an overview.

The hyperdynamic circulation begins in the portal venous bed as a consequence of portal hypertension due to the increased resistance to flow from altered hepatic vascular morphology of chronic liver disease. Dilatation of the portal vein is associated with increased blood flow, as well as the opening up or formation of veno-venous shunts and splenomegaly. At the same time, portal hypertension leads to subclinical sodium retention resulting in expansion of all body fluid compartments, including the systemic and central blood volumes. This blood volume expansion is associated with vasorelaxation, as manifested by suppression of the renin--angiotensin--aldosterone system, initially only when the patient is in the supine position. Acute volume depletion in such patients results in normalisation of the hyperdynamic circulation, whilst acute volume expansion results in exaggerated natriuresis. As liver disease progresses and liver function deteriorates, the systemic hyperdynamic circulation becomes more manifest with activation of the renin--angiotensin--aldosterone system. The presence of vasodilatation in the presence of highly elevated levels of circulating vasoconstrictors may be explained by vascular hyporesponsiveness due to increased levels of vasodilators such as nitric oxide, as well as the development of an autonomic neuropathy. However, vasodilatation is not generalised, but confined to certain vascular beds, such as the splanchnic and pulmonary beds. Even here, the status may change with the natural history of the disease, since even portal blood flow may decrease and become reversed with advanced disease. The failure of these changes to reverse following liver transplantation may be due to remodelling and angiogenesis.

Blood Circulation↗
PubMed2001

The pathophysiologic basis for the treatment of cirrhotic ascites.

Advances in the understanding of the pathophysiology of sodium retention and ascites formation in cirrhosis has helped improve the treatment of ascites in these patients. It is likely that further unraveling of these pathophysiologic changes will lead to the development of novel and better treatment options. For example, the development of aquaretic agents for the management of hyponatremia in cirrhosis may allow more effective use of diuretic therapy. The ultimate challenge is to use the understanding of the pathophysiology to develop new strategies to prevent the development of ascites in cirrhosis.

Ascites↗
PubMed2001

New challenge of hepatorenal syndrome: prevention and treatment.

Hepatorenal syndrome (HRS) remains one of the major therapeutic challenges in hepatology today. The pathogenesis is complex, but the final common pathway seems to be that sinusoidal portal hypertension, in the presence of severe hepatic decompensation, leads to splanchnic and systemic vasodilatation and decreased effective arterial blood volume. Renal vasoconstriction increases concomitantly, renal hemodynamics worsens, and renal failure occurs. Renal failure was shown 15 years ago to be potentially reversible after liver transplantation. This potential reversibility together with increased understanding of the pathogenesis has led to successful preliminary attempts to reverse HRS nonsurgically with combinations of splanchnic vasoconstrictors and colloid volume expansion, insertion of transjugular intrahepatic portovenous shunt radiologically, and improved forms of dialysis. Recent classification of HRS into the acute onset or severe type 1 with virtually 100% mortality and the more insidious less severe type II promises to shed more light on the pathogenesis of HRS, especially on the currently unrecognized precipitating factors. It is hoped that this classification will be included in the necessary and carefully performed clinical trials, which should lead to clearer indications for the available therapies. The challenge now is to use all this information to improve our management of cirrhotic patients to prevent occurrence of HRS in the future.

Adrenergic alpha-Agonists↗
PubMed2001

Dispase facilitates posterior vitreous detachment during vitrectomy in young pigs.

PURPOSE: To evaluate the role of intravitreal dispase in conjunction with pars plana vitrectomy to facilitate the creation of a posterior vitreous detachment (PVD) in young pig eyes. METHODS: Twenty-four eyes of 24 animals were randomized to receive an intravitreal injection of dispase (50 microg/0.05 mL) or phosphate buffered saline (PBS) immediately after core vitrectomy and before attempted creation of a posterior cortical vitreous detachment. Following a 15-minute waiting period, surgical creation of a posterior vitreous separation was attempted by aspiration of the posterior vitreous immediately adjacent to the optic disk. Eyes were evaluated postoperatively by clinical examination (1, 4, and 8 weeks) and electroretinography (4 and 8 weeks), after which they were enucleated for light, scanning, and transmission electron microscopy. RESULTS: Based on intraoperative findings and postoperative scanning electron microscopy, eyes receiving intravitreal dispase exhibited a higher incidence of PVD compared to eyes receiving PBS (P = 0.029). Electroretinographic responses recorded at postoperative weeks 4 and 8 were similar in both dispase and PBS eyes compared to the unoperated fellow eyes. Clinical examinations, including indirect ophthalmoscopy, were indistinguishable between the PBS eyes and 11 of 12 eyes in the dispase group. Light and transmission electron microscopy demonstrated no differences in the retina between the dispase eyes and the PBS operated controls. CONCLUSION: Dispase is a useful adjunct in facilitating surgical creation of a PVDin young pig eyes.

Animals↗
PubMed2001

Factors influencing the choice of hysterectomy.

A retrospective review of women undergoing hysterectomy between May 1998 and April 2000 was performed. Multiple logistic regression analysis was used to identify factors influencing the choice of hysterectomy performed. Two independent factors, the surgeons' expertise and the concomitant adnexal surgery, had a strong influence on the decision-making process regarding type of hysterectomy Generalist gynaecologists tended to perform either an abdominal hysterectomy (AH) or a vaginal hysterectomy (VH) while non-generalist gynaecologists were more likely to perform laparoscopic hysterectomy (LH). Patients undergoing a hysterectomy along with adnexal surgery had a far greater chance of undergoing either an AH or a LH as opposed to a VH. In addition, patients who had bigger uterus were more likely to undergo an AH versus a VH as compared to those with a small uterus. Patients aged 50 or older had more chance of undergoing a VH than a LH.

Adnexal Diseases↗
PubMed2001

Effects of ascites resolution after successful TIPS on nutrition in cirrhotic patients with refractory ascites.

OBJECTIVE: Malnutrition is common in patients with decompensated cirrhosis and refractory ascites. The use of transjugular intrahepatic portosystemic stent shunt (TIPS) is effective in eliminating ascites. The purpose of this study was to investigate the effect of TIPS and resolution of refractory ascites on the nutritional status of patients with decompensated cirrhosis. METHODS: Fourteen consecutive patients with refractory ascites and a Pugh score of 9.0+/-0.5 had a TIPS insertion. Biochemical data, resting energy expenditure (REE), total body nitrogen (TBN), body potassium (TBK), body fat (TBF), muscle force (MF), and food intake were recorded before TIPS, and at 3 and 12 months after the procedure. RESULTS: Ten patients completed the study. Baseline values for REE, TBN, TBF, MF, and energy intake were below normal at baseline. There was a significant increase in dry weight, TBN, and REE at 3 and 12 months compared with baseline. TBF improved significantly at 12 months. There was a trend toward an increase in energy intake (p = 0.072). There was no change in protein intake, TBK, MF, and Pugh score. CONCLUSION: In cirrhotic patients with refractory ascites, resolution of the ascites after TIPS placement resulted in improvement of several nutritional parameters, especially for body composition.

Absorptiometry, Photon↗
PubMed2001

The cardiac response to exercise in cirrhosis.

BACKGROUND: Impaired exercise capacity and oxygen consumption are common in cirrhosis. AIM: To explore the relationship between possible myocardial dysfunction and exercise tolerance in cirrhosis. METHODS: Cardiac responses to exercise, using radionuclide angiography and graded upright cycle ergometry with oxygen consumption, were assessed before and after exercise in 39 cirrhotics patients and compared with 12 age and sex matched healthy volunteers. Baseline cardiac chamber dimensions and wall thickness, ejection fraction, and diastolic function were measured using two dimensional echocardiography is all subjects. RESULTS: Baseline diastolic dysfunction with prolonged isovolumic relaxation times (p=0.02), left atrial enlargement, and left ventricular wall thickening were present in all cirrhotics (p=0.02), despite increased mean ejection fraction. With graded exercise, cirrhotics achieved 71 (4)% (p=0.03) (pre-ascitics) and 46 (3)% (p<0.001) (ascitics) of predicted work loads, respectively, without significant increases in ejection fraction. The smaller absolute and percentage increases in cardiac output (p=0.003) in the cirrhotics were associated with significantly reduced oxygen consumption (p=0.003) and anaerobic threshold (p<0.001), and correlated significantly with work and metabolic parameters. CONCLUSIONS: Impaired exercise capacity in cirrhosis is associated with myocardial thickening and ventricular stiffness leading to decreased diastolic function, inotropic and chronotropic incompetence under conditions of stress, with metabolic consequences. This picture is compatible with the condition now known as cirrhotic cardiomyopathy.

Analysis of Variance↗
PubMed2001

Sodium homeostasis with chronic sodium loading in preascitic cirrhosis.

BACKGROUND: Preascitic cirrhotic patients receiving 200 mmol of sodium daily for seven days remain in positive sodium balance. Thereafter, sodium handling is unknown. AIM: To assess renal sodium handling in preascitic cirrhosis on a high sodium diet for five weeks. METHODS: Sixteen biopsy proven preascitic cirrhotics were assessed at weekly intervals for five weeks on a diet of 200 mmol sodium/day using a daily weight diary and weekly 24 hour urinary sodium estimations. Fasting supine neurohormone levels were measured at baseline and weekly for five weeks while haemodynamics were measured at baseline and at five weeks. RESULTS: The daily diet of 200 mmol of sodium resulted in weight gain and a positive sodium balance for three weeks, associated with significant suppression of plasma renin activity and aldosterone levels, and a significant rise in plasma atrial natriuretic peptide levels (p<0.05). Patients' weights plateaued during week 4, associated with complete sodium balance and significant suppression of plasma noradrenaline levels (p<0.05). This was followed by a negative sodium balance and weight loss, and finally complete sodium balance, again despite a mean net gain of 2.3 (0.3) kg, associated with a return of plasma renin activity and aldosterone levels to within normal ranges. The lack of increase in central blood volume in addition to the persistent increase in plasma atrial natriuretic peptide levels indicated that residual volume expansion, consequent to persistent weight gain, was distributed on the venous side of the circulation. No free fluid was seen on repeat abdominal ultrasound after five weeks. CONCLUSION: Preascitic cirrhotics have a natriuretic "escape" after three weeks on high sodium dietary intake, associated with elevated plasma atrial natriuretic peptide levels and suppression of the renin-angiotensin-aldosterone system. With continued suppressed sympathetic activity, preascitics re-establish complete sodium balance but with a net weight gain and presumed increased intravascular volume, but without ascites. This further elucidates the compensated sodium retaining abnormality that characterises preascitic cirrhosis.

Aldosterone↗
PubMed2001

The views of ovarian cancer survivors on its cause, prevention, and recurrence.

METHODS: Women who had survived ovarian cancer without further treatment, active disease, or recurrence for at least 2 years were surveyed by mail. RESULTS: Two hundred (67.8%) ovarian cancer survivors, who had been recurrence free for a mean of 7.2 +/- 4.9 years, responded. The cause of ovarian cancer was attributed to stress (63.5%), diet (39.0%), genes (36.5%), environment (32.5%), hormones (30.0%), sex life (11.0%), and smoking (9.5%). They attributed their lack of cancer recurrence to positive attitude (82.5%), close medical follow-up (82.0%), healthy lifestyle (69.0%), prayer (68.0%), stress reduction (66.5%), diet (63.0%), and exercise (58.5%). Overall, 45% of women thought their recurrence risk was below average, 28.5% average, 23% above average, and 3.5% reported that they did not know their particular risk. Although 35.5% of women reported that they hardly ever thought of cancer recurrence, 28% thought of it at least monthly, 24.5% at least weekly, and 12% at least daily. Almost half (43.5%) of the women had bad dreams related to their cancer experience, and 25% of these women reported the dreams had a negative effect on their sense of well-being. Over half (62.5%) reported high to extreme anxiety at the time of cancer check-ups, but 47% were not afraid of what their futures held for them. However, 12% were very afraid of dying of ovarian cancer, and 5% were "constantly afraid of dying." Most women reported healthy behaviors with respect to not smoking (95.5%), balanced diet (92.0%), and regular exercise (65.0%). Of note was that 82% took vitamins or other supplements. CONCLUSION: Healthcare providers should be aware that the personal beliefs held by ovarian cancer patients and survivors about cancer cause and recurrence prevention may be at variance with scientific evidence. This may assist in framing the ongoing management of patients in personally meaningful ways, which may increase adherence to a healthy lifestyle, engender a sense of control, and improve quality of life.

Adult↗
PubMed2001

Brain natriuretic peptide: is it a predictor of cardiomyopathy in cirrhosis?

Subtle cardiac abnormalities have been described in patients with cirrhosis. Natriuretic peptide hormones have been reported to be sensitive markers of early cardiac disease. We postulate that plasma levels of N-terminal pro-atrial natriuretic peptide and brain natriuretic peptide could be used as markers of cardiac dysfunction in cirrhosis. The aim of the study was to evaluate the levels of N-terminal pro-atrial natriuretic peptide and brain natriuretic peptide and their relationship with cardiac structure and function in patients with cirrhosis. The study population comprised 36 patients with cirrhosis of mixed aetiologies, but with no cardiac symptoms; 19 of the patients had ascites and 17 did not. The subjects underwent (i) trans-thoracic two-dimensional echocardiography, and (ii) radionuclide angiography for measurements of cardiac structural parameters, diastolic and systolic function. Levels of N-terminal pro-atrial natriuretic peptide and brain natriuretic peptide were also measured. The results were compared with those from eight age- and sex-matched healthy volunteers. Compared with the controls, the baseline mean ejection fraction was increased significantly in both patient groups (P=0.02), together with prolonged deceleration times (P=0.03), left atrial enlargement (P=0.03) and interventricular septal thickening (P=0.02), findings that are compatible with diastolic dysfunction. Levels of N-terminal pro-atrial natriuretic peptide and brain natriuretic peptide were significantly higher in all patients with cirrhosis with ascites (P=0.01 and P=0.05 respectively), but in only some of the pre-ascitic cirrhotic patients, compared with controls. All high levels of brain natriuretic peptide were correlated significantly with septal thickness (P<0.01), left ventricular diameter at the end of diastole (P=0.02) and deceleration time (P<0.01). We conclude that elevated levels of brain natriuretic peptide are related to interventricular septal thickness and the impairment of diastolic function in asymptomatic patients with cirrhosis. Levels of brain natriuretic peptide may prove to be useful as a marker for screening patients with cirrhosis for the presence of cirrhotic cardiomyopathy, and thereby identifying such patients for further investigations.

Adult↗
PubMed2001

Incidence of deep venous thrombosis after gynaecological laparoscopy.

OBJECTIVE: To evaluate the incidence of deep venous thrombosis (DVT) after gynaecological laparoscopy. METHODS: The incidence of DVT was studied in 72 consecutive patients who underwent gynaecological laparoscopy in the Liverpool Health Service between May and September 1997. B-mode ultrasound supplemented by Doppler was used to examine venous patency and intraluminal echoes to diagnose DVT. Sixty-one patients who had pneumoperitoneum less than 60 minutes were classified a minor procedure and 11 who had pneumoperitoneum more than 60 minutes were classified as major procedure. Two Doppler ultrasound scans were planned for every patient. The first one was done within 24 hours and the second was performed on day 7 post-surgery. All 72 patients had the first scan and 40 out of 61 in the minor procedure group and 9 out of 11 in the major procedure had the second scan. Twenty-three patients who did not come for the second scan were followed up by phone. RESULTS: No DVT was found in our study. CONCLUSION: This study confirms an impression that gynaecological laparoscopic procedure has a very low incidence of DVT. If it occurs, the diagnosis and treatment must be made as soon as possible so that the fatal complications such as pulmonary embolus can be avoided.

Adult↗
PubMed2000

Early loss of synaptic protein PSD-95 from rod terminals of rhodopsin P347L transgenic porcine retina.

Retinitis pigmentosa (RP), a type of retinal degeneration involving first rod and then slow cone photoreceptor degeneration, can be caused by any of a number of mutations in different genes. In the cases of mutations affecting rod-specific genes such as rhodopsin, it is unclear how the mutations may cause degeneration of cones. We have used the porcine retina, which is rod-dominated and has an abundance of cones, to study the mutation-induced changes in both rod and cone photoreceptors. Like patients with the same mutation, rhodopsin P347L transgenic swine manifest rod-cone degeneration. In addition, the rod bipolar cells fail to form synaptic connections with rods; instead, they form ectopic synapses with cones. The mechanisms that prevent the formation of the rod-rod bipolar cell synaptic connection are not known. We used specific antibodies and immunocytochemistry to show that the synaptic protein, PSD-95, is present in both normal and transgenic porcine retinas. During neonatal development, however, PSD-95 is lost from rod terminals in the transgenic swine. This loss is virtually complete (90%) by postnatal day 5, at a time when greater than 80% of rod cell bodies still remain. Furthermore, the remaining rods retain their outer segments and their gross morphology appears relatively normal. In contrast, PSD-95 expression continues in cone terminals, even in 10-month-old transgenic swine, where the rods have all disappeared and the cones show signs of severe degeneration. These results suggest that loss of PSD-95 may not be a general consequence of the deteriorating cell. Rather, the very early and selective loss of PSD-95 from the rod terminals may be causally related to the absence of rod-rod bipolar cell synapses in the rhodopsin P347L transgenic retina.

Animals↗