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Biomedical subjects

C Wong

Publications and source records attributed to C Wong.

At least 73 records · Page 4Linked to original sources
PubMed2000

Cocaine abusers show a blunted response to alcohol intoxication in limbic brain regions.

UNLABELLED: Cocaine and alcohol are frequently used simultaneously and this combination is associated with enhanced toxicity. We recently showed that active cocaine abusers have a markedly enhanced sensitivity to benzodiazepines. Because both benzodiazepines and alcohol facilitate GABAergic neurotransmission we questioned whether cocaine abusers would also have an enhanced sensitivity to alcohol that could contribute to the toxicity. In this study we compared the effects of alcohol (0.75 g/kg) on regional brain glucose metabolism between cocaine abusers (n = 9) and controls (n = 10) using PET and FDG. Alcohol significantly decreased whole brain metabolism and this effect was greater in controls (26+/-6%) than in abusers (17+/-10%) even though they had equivalent levels of alcohol in plasma. Analysis of the regional measures showed that cocaine abusers had a blunted response to alcohol in limbic regions, cingulate gyrus, medial frontal and orbitofrontal cortices. CONCLUSIONS: The blunted response to alcohol in cocaine abusers contrasts with their enhanced sensitivity to benzodiazepines suggesting that targets other than GABA-benzodiazepine receptors are involved in the blunted sensitivity to alcohol and that the toxicity from combined cocaine-alcohol use is not due to an enhanced sensitivity to alcohol in cocaine abusers. The blunted response to alcohol in limbic regions and in cortical regions connected to limbic areas could result from a decreased sensitivity of reward circuits in cocaine abusers.

Adult↗
PubMed2000

Development, dissemination, implementation and evaluation of a clinical pathway for oxygen therapy.

BACKGROUND: Oxygen is commonly administered to patients in hospital, but prescribing and monitoring of such therapy may be suboptimal. The objective of this study was to develop, disseminate, implement and evaluate a multidisciplinary clinical pathway for the administration of oxygen. METHODS: The authors developed a clinical pathway for the ordering, titration and discontinuation of oxygen, which was disseminated through teaching sessions, in-service training sessions and information posters in a medical clinical teaching unit (CTU). Implementation of the pathway was ensured by means of reminders and patient-centred audit and feedback to CTU nurses and house staff. During a 3-month intervention phase, consecutive patients requiring supplemental oxygen were treated according to the pathway. During a 1-month "wash-out" phase followed by a 3-month non-intervention phase, patients were treated at the discretion of the CTU team. Clinical and economic data were collected in both phases. RESULTS: In the 2 phases, patient characteristics, the concentration and duration of oxygen prescribed, the frequency of oxygen saturation monitoring, the frequency of arterial blood gas testing and the clinical outcomes were similar. However, there were more discontinuation orders in the intervention phase (p < 0.001). In the intervention phase, costs were higher for monitoring of oxygen saturation ($44.95/patient v. $36.17/patient, p = 0.048) and for order transcription ($2.71/patient v. $1.28/patient, p < 0.001); total costs, including those for personnel, were also higher in the intervention phase ($76.93/patient v. $56.67/patient, p = 0.02). The cost of education about the oxygen pathway was $45.71/patient. When the education cost was included, the total cost of oxygen therapy during the intervention phase was $122.64/patient; this was significantly higher than the total cost of oxygen therapy during the non-intervention phase ($56.67/patient) (p < 0.001). INTERPRETATION: This multidisciplinary, multimethod oxygen pathway led to changes in oxygen-prescribing behaviour, consumed more resources than standard management and was not associated with changes in patient outcome. Appropriate management of oxygen prescribing and monitoring by physicians and nurses take time and costs money.

Aged↗
PubMed2000

The yeast peptidyl proline isomerases FPR3 and FPR4, in high copy numbers, suppress defects resulting from the absence of the E3 ubiquitin ligase TOM1.

Tom1p is a 3268-amino acid protein with extensive homology to the hect-domain class of E3 ubiquitin ligases. Disruption of the TOMI gene results in temperature sensitivity for growth. Genes encoding the peptidyl proline isomerases Fpr3p and Fpr4p, when present on multicopy plasmids, will suppress this temperature-sensitive growth phenotype. FPR3 can also suppress the mating defect seen in tom1 strains. Suppression is specific for disruption of TOM1, since FPR3 does not restore wild-type growth to strains lacking the E2 ubiquitin-conjugating enzyme Rad6p or the transcriptional regulator Ngglp. Interestingly, the peptidyl proline isomerase domains of Fpr3p and Fpr4p are not required for suppression; rather the essential sequences include about 170 highly conserved residues at the proteins' N-termini. Previously we found that Tomlp plays a role in gene regulation. Since overexpression of FPR4 does not suppress the reduced expression of the ARG1 promoter found in tom1 deletion strains, Tom1p probably has one or more functions beyond its involvement in gene expression.

Amino Acid Sequence↗
PubMed2000

Difficult problems and their solutions in patients with cancer pain of the head and neck areas.

Pain management can be especially difficult in patients with head and neck cancer due to the erosive nature of the neoplasms that invade the region, the rich innervation of the head and neck, and other factors. Consequently, diagnosis is a complex process that cannot be dealt with in a cursory fashion. Furthermore, tumor pain can mimic noncancer conditions, nonmalignant orofacial disorders can be suggestive of tumor growth, and antineoplastic treatment-related conditions can be difficult to distinguish from tumor recurrence. A series of case reports illustrates key elements of diagnosis and pain management in patients with head and neck cancer. These elements include 1) detailed assessment of pain intensity and characteristics; 2) appropriate use of analgesic adjuvant medications; 3) use of diagnostic and therapeutic nerve blocks and myofascial trigger point injections; and 4) a high index of suspicion regarding tumor recurrence pain.

Adult↗
PubMed2000

Retrograde perfusion and true reverse brain blood flow in humans.

OBJECTIVE: Reversal of brain blood flow is necessary for retrograde cerebral perfusion (RCP) to have any metabolic benefit, but RCP is commonly used with little clinical evidence of the true incidence of reverse brain blood flow and impact. S-100B is exclusive to the brain and spinal cord and released during hypothermic circulatory arrest (HCA). True reverse brain blood flow (tRBBF) during RCP may be determined by demonstrating an excess of S-100B in the effluent blood from the common carotid artery compared to blood entering the brain. METHODS: Simultaneous blood samples were drawn from the jugular bulb and left common carotid artery during RCP at 5 min intervals in ten patients undergoing aortic surgery, utilizing HCA and subjected to blood gas, glucose and S-100B quantification. RCP was instituted at maximum pressure of 25 mmHg. Trans-cranial Doppler (TCD) continuously monitored the middle cerebral artery velocity (MCAV). RESULTS: The mean HCA and RCP durations were 31 min (20-50 min). Reversal of MCAV was demonstrated in only 6/10 cases (mean, 6 cm/s). Veno-arterial (V-A) extraction of oxygen and glucose occurred in all cases (P<0.001), with the mean effluent pO(2) falling to 14 mmHg. V-A S-100 gradients greater than 5% were demonstrated in 8/10 cases and correlated with higher oxygen extraction (P<0.01). In patients with and without MCAV reversal, the S-100 gradients were 1. 7 and 0.3 micromol/l, respectively (P<0.01). CONCLUSIONS: tRBBF occurred in nearly all patients. MCAV reversal appears to be a specific but insensitive guide to reverse perfusion. The de-saturation of effluent blood is not a reliable guide to true brain perfusion, and despite RCP, the brain remains ischaemic.

Biomarkers↗
PubMed2000

Directed evolution of D-2-keto-3-deoxy-6-phosphogluconate aldolase to new variants for the efficient synthesis of D- and L-sugars.

BACKGROUND: Exploitation and improvement of enzymes as catalysts for organic synthesis is of current interest in biocatalysis. A representative enzyme for investigation is the Escherichia coli D-2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolase, which catalyzes the highly specific reversible aldol reaction using the D-configurated KDPG as substrate. RESULTS: Using in vitro evolution, the aldolase has been converted into aldolases with improved catalytic efficiency, altered substrate specificity and stereoselectivity. In particular, some evolved aldolases capable of accepting both D- and L- glyceraldehyde in the non-phosphorylated form as substrates for reversible aldol reaction have been obtained, providing a new direction to the enzymatic synthesis of both D- and L-sugars. CONCLUSIONS: This research has demonstrated the effectiveness of using in vitro evolution to rapidly alter the properties of an aldolase to improve its utility in asymmetric synthesis. The evolved aldolases, differing from the native enzyme which is highly phosphate- and D-sugar-dependent, catalyze the efficient synthesis of both D- and L-sugars from non-phosphorylated aldehydes and pyruvate. The principles and strategies described in this study should be applicable to other aldolases to further expand the scope of their synthetic utility.

Aldehyde-Lyases↗
PubMed2000

Bowel dysfunction following spinal cord injury: a description of bowel function in a spinal cord-injured population and comparison with age and gender matched controls.

STUDY DESIGN: A controlled, descriptive and comparative, questionnaire based study. OBJECTIVES: To describe the bowel function of spinal cord injured (SCI) patients and compare this with a general community control group. SETTING: Christchurch, New Zealand. METHODOLOGY: A postal questionnaire was sent out to past SCI patients of the Burwood Spinal Injuries Unit, Christchurch, New Zealand, and age/gender matched with controls randomly selected from the electoral roll. Permission was obtained from SCI participants to retrieve data relating to their injury from hospital case notes. The questionnaire detailed general bowel function, influence of bowel problems on everyday life, incidence of incontinence and methods of defecation. A Faecal Incontinence Score was generated according to an established incontinence grading scheme. RESULTS: Questionnaires were sent out to 1200 SCI patients and 1200 control subjects. Of these, 467 completed questionnaires were returned from SCI patients and age/gender matched from the 668 returned control questionnaires. Mean Faecal Incontinence Score was higher for SCI patients than controls (P<0.0001), and for complete compared with incomplete injury (P=0.0023). Age or time from injury did not affect Faecal Incontinence Score. Incontinence affected quality of life for 62% of SCI patients, compared with 8% of controls. Faecal urgency and time spent at the toilet were also significantly higher for the SCI group (39% of SCI patients use laxatives, compared with 4% of controls (P<0.0001)). Haemorrhoidectomy was more common (P<0.001) in the SCI population (9% vs 1.5%), particularly among those requiring manual evacuations. CONCLUSION: SCI has a significant effect on bowel function in terms of faecal incontinence, urgency, and toileting methods. This results in a marked impact on quality of life. While bowel function may deteriorate with time, most patients with poor function can be identified early implying a role for early intervention in those with potential bowel problems, such as colostomy or ACE procedure.

Activities of Daily Living↗
PubMed2000

Use of tamoxifen in hepatocellular carcinoma: a review and paradigm shift.

Hepatocellular carcinoma is often diagnosed at a late, inoperable stage for which there are no uniformly efficacious treatment available presently. The oral anti-oestrogen drug, tamoxifen, has been used in such patients, based on the belief that the growth of hepatocellular carcinoma is promoted by endogenous oestrogen via a receptor-mediated process. In this review, we examine the trials reported in the literature using tamoxifen in hepatocellular carcinoma. Randomized controlled trials with tamoxifen have so far revealed mixed results. We propose that this may be due to the fact that the mechanism of action of tamoxifen in hepatocellular carcinoma is via an oestrogen-receptor independent pathway that requires much higher doses of tamoxifen for activation than those used in the trials so far. Thus there must be a paradigm shift to dissociate the action of tamoxifen from oestrogen receptors in hepatocellular carcinoma. This means that future trials with tamoxifen in hepatocellular carcinoma should use higher doses of tamoxifen, at least four to eight-fold that of the dose that is efficacious in an oestrogen-receptor dependent mechanism.

Antineoplastic Agents, Hormonal↗
PubMed2000

Increased risk of hip fracture among patients with end-stage renal disease.

BACKGROUND: Although patients with end-stage renal disease (ESRD) are at increased risk for bone loss, the risk of hip fracture in this population is not known. We compared the risk of hip fracture among dialysis patients with the general population. METHODS: We used data from the United States Renal Data System (USRDS) to identify all new Caucasian dialysis patients who began dialysis between January 1, 1989, and December 31, 1996. All hip fractures occurring during this time period were ascertained. The observed number of hip fractures was compared with the expected number based on the experience of residents of Olmstead County (MN, USA). Standardized incidence ratios were calculated as the ratio between observed and expected. The risk attributable to ESRD was calculated as the difference between the observed and expected rate of hip fracture per 1000 person-years. RESULTS: The number of dialysis patients was 326,464 (55.9% male and 44.1% female). There were 6542 hip fractures observed during the follow-up period of 643, 831 patient years. The overall incidence of hip fracture was 7.45 per 1000 person years for males and 13.63 per 1000 person years for females. The overall relative risk for hip fracture was 4.44 (95% CI, 4.16 to 4.75) for male dialysis patients and 4.40 (95% CI, 4.17 to 4.64) for female dialysis patients compared with people of the same sex in the general population. While the age-specific relative risk of hip fracture was highest in the youngest age groups, the added risks of fracture associated with dialysis rose steadily with increasing age. The relative risk of hip fracture increased as time since first dialysis increased. CONCLUSIONS: The overall risk of hip fracture among Caucasian patients with ESRD is considerably higher than in the general population, independent of age and gender.

Age Distribution↗
PubMed2000

Applying the quit & win contest model in the Vietnamese community in Santa Clara county.

OBJECTIVE: To evaluate the effectiveness of modifying and applying a Quit & Win contest model to Vietnamese Americans. DESIGN: Uncontrolled trial, multicomponent program, including two Quit & Win incentive contests, smoking cessation classes, videotape broadcasts, and newspaper articles. SUBJECTS AND SETTING: Vietnamese smokers living in Santa Clara County, California. MAIN OUTCOME MEASURES: Contest participation rates and quit rates at six month follow up; saliva cotinine validation of quitting. RESULTS: There were 57 eligible contest entrants to the 1995 contest, approximately 0.9% of the potential pool of smokers, and 32 entrants to the 1996 contest, approximately 0.5% of the potential pool. Overall, 48 of 49 (98%) individuals who said that they had quit smoking had validation of that fact by saliva cotinine testing. At six months, telephone follow up of 76 individuals revealed a self reported continued abstinence rate of 84.2%. CONCLUSION: Modification and application of the Quit & Win contest model for Vietnamese resulted not only in reasonable participation by Vietnamese male smokers, but also good success in initial quitting and an unexpectedly high abstinence rate at six month follow up.

Adult↗
PubMed2000

Association between age-related decline in brain dopamine activity and impairment in frontal and cingulate metabolism.

OBJECTIVE: Despite the well-documented loss of brain dopamine activity with age, little is known about its functional consequences in healthy individuals. This study investigates the relationship between measures of brain dopamine D(2) receptors (molecules that transmit dopamine signals) and regional brain glucose metabolism (a marker of brain function) in healthy individuals. METHOD: Thirty-seven healthy volunteers aged 24-86 years underwent positron emission tomography scans after injection of [(11)C]raclopride to assess dopamine D(2) receptors and [(18)]fluorodeoxyglucose to assess regional brain glucose metabolism. Two methods used to assess the correlations between metabolism and dopamine D(2) receptors-pixel-by-pixel correlations and correlations in preselected regions of interest-were then compared. RESULTS: D(2) receptors as well as frontal and cingulate metabolism declined with age. Regardless of the method used, significant correlations between metabolism and D(2) receptors were found in the frontal cortex (Brodmann's areas 6, 7, 8, 9, 10, 11, 44, 45, 47), anterior cingulate gyrus (areas 24, 32), temporal cortex (area 21), and caudate. These correlations remained significant after removing age effects (partial correlation). CONCLUSIONS: These results provide the first link between age-related declines in brain dopamine activity and frontal and cingulate metabolism, which supports the need to investigate the therapeutic utility of interventions that enhance dopamine function in the elderly. The fact that correlations remained significant after removing age effects suggests that dopamine may influence frontal, cingulate, and temporal metabolism regardless of age.

Adult↗
PubMed2000

Hepatitis B immunization coverage among Vietnamese-American children 3 to 18 years old.

OBJECTIVE: Persons with chronic hepatitis B virus (HBV) infection are at increased risk of chronic hepatitis, cirrhosis, and liver cancer. Although HBV infection is relatively uncommon in the United States, the disease is endemic in persons born in Southeast Asia, including Vietnamese-Americans. Current US infant immunization recommendations and state-mandated school-entry programs have left many nontargeted age-cohorts unvaccinated and at risk of infection. To assess the need for catch-up hepatitis B immunizations, this study reports the hepatitis B immunization rates of Vietnamese-American children 3 to 18 years old living in the metropolitan areas of Houston and Dallas, Texas, and the Washington, DC, area. DESIGN: We conducted 1508 telephone interviews with random samples of Vietnamese households in each of the 3 study sites. We asked for hepatitis B immunization dates for a randomly selected child in each household. Attempts were made to verify immunization dates through direct contact with each child's providers. Low and high estimates of coverage were calculated using reports from providers when reached (n = 720) and for the entire sample (n = 1508). RESULTS: Rates of having 3 hepatitis B vaccinations ranged from 13.6% (entire sample) to 24.1% (provider reports, Dallas), 10. 3% to 26.4% (Houston), and 18.1% to 37.8% (Washington, DC). Children living in the Texas sites, older children, children whose families had lived in the United States for a longer time, and children whose provider was Vietnamese or who had an institutional provider were less likely to have been immunized. The odds of being immunized were greater, however, for children who had had at least 1 diphtheria, tetanus toxoid, and pertussis shot, and whose parents had heard about HBV infection, and were married. CONCLUSIONS: The low rates of hepatitis B vaccine coverage among children and adolescents portend a generation which, too old to benefit from infant programs and school entry laws, will grow into adulthood without the protection of immunization. Increased efforts are needed to design successful catch-up campaigns for this population.

Adolescent↗
PubMed2000

General practitioners' beliefs, attitudes and reported actions towards chronic fatigue syndrome.

OBJECTIVE: To undertake a survey of Australian general practitioners (GPs) to explore their beliefs, attitudes and reported actions with respect to chronic fatigue syndrome (CFS). METHOD: A random sample of 2090 Australian GPs, stratified by state, was surveyed in May-August 1995. RESULTS: A 77% response rate was obtained. For the majority of practitioners who pursue a diagnosis of CFS, six symptoms were considered to be of significance: chronic unremitting fatigue for over 6 months; failure to recover energy after rest; reduced exercise tolerance; prostration for several days after exercise; generalised myalgia and poor concentration. Individual counselling was the most frequently used treatment. Thirty-one percent of practitioners reported that they did not believe that CFS is a distinct syndrome. Of these, 70% reported that the most likely cause of chronic fatigue was depression. CONCLUSION: There is considerable diversity of opinion between practitioners about CFS. The diversity extends from questioning whether the syndrome even exists to different strategies for diagnosis and management.

Adult↗
PubMed2000

Comparison of CA 125 after three courses of chemotherapy and results of second-look surgery.

OBJECTIVE: To compare CA 125 levels after three courses of cisplatin-based chemotherapy and the results of second-look surgery. METHODS AND MATERIALS: From January 1990 to December 1996, the medical records of 72 patients diagnosed with epithelial ovarian cancer were reviewed. After initial staging surgery, all patients received cisplatin-based chemotherapy. Prior to each course of chemotherapy, patients underwent physical exams and serum CA 125 was obtained. After 6 courses of chemotherapy, if CA 125 levels were normal (< or = 35 IU/ml) and there was no clinical evidence of disease, the patient was offered second-look surgery. The sensitivity, specificity, and negative predicative value of CA 125 levels after 3 courses of chemotherapy and results of second-look surgery were calculated. Survival curves were constructed using Kaplan-Meier actuarial methods. RESULTS: Seventy-two patients were enrolled in the study. After completing 3 courses of chemotherapy, 43 out of 72 patients were reported to have normal CA 125 levels and were offered second-look surgery. Forty-six out of 72 patients underwent second-look surgery, 28 patients (60%) were reported to have positive second-look surgery. Of the patients with normal CA 125 levels after 3 courses of chemotherapy, 23 patients (57.5%) had a positive second-look surgery. The sensitivity and specificity of CA 125 values after 3 courses of chemotherapy were 17.9% and 94.7%, respectively and the negative predicative value was 43.9%. Patients with normal CA 125 values after 3 courses of chemotherapy had a significantly improved survival compared to those who failed to normalized their CA 125 levels after three courses of chemotherapy. CONCLUSION: Normalization of CA 125 after 3 courses of chemotherapy is a poor predicator of findings at second-look surgery.

Antineoplastic Agents↗