Search PubMed⌕ Search

Biomedical subjects

M Wong

Publications and source records attributed to M Wong.

At least 145 records · Page 8Linked to original sources
PubMed1996

Phase I trial of extracellular adenosine 5'-triphosphate in patients with advanced cancer.

Adenosine 5'-triphosphate (ATP) has antineoplastic activity in vitro and in murine tumor systems, but there are no data in humans defining its potential use as an antineoplastic agent. We conducted a phase I study to determine the spectrum of toxicity, maximum safely tolerated dose (MTD), and pharmacokinetics of intravenous ATP. Fourteen men with advanced cancer received 96-hour infusions of ATP once monthly in doses ranging from 50 to 100 micrograms/kg/minute. Toxicity was assessed by standard National Cancer Institute (NCI) criteria, cardiac function was monitored serially by two-dimensional echocardiography, and whole blood ATP was measured serially in a subset of patients. ATP was generally well tolerated and no significant hematologic toxicity was noted. The dose-limiting toxicity was a cardiopulmonary reaction characterized by chest tightness and dyspnea that resolved within seconds of discontinuing ATP. Dose-limiting cardiopulmonary toxicity occurred in 3 of 3 patients at 100 micrograms/kg/minute, in 3 of 6 patients at 75 micrograms/kg/minute, and 4 of 11 patients at 50 micrograms/kg/minute. Whole blood ATP levels significantly increased with treatment, reaching a steady state by 24 hours and returning to or near baseline by 1 week after treatment. Plateau levels were 63%, 67%, and 116% above base-line at 50, 75, and 100 micrograms/kg/min, respectively. We conclude that prolonged infusions of ATP are feasible with acceptable toxicity and that 50 micrograms/kg/minute is both the MTD and the most appropriate dose rate for subsequent Phase II testing of 96-hour infusions of ATP in patients with advanced cancer.

Adenosine Triphosphate↗
PubMed1996

Zone-specific cell biosynthetic activity in mature bovine articular cartilage: a new method using confocal microscopic stereology and quantitative autoradiography.

A new methodology was developed to measure spatial variations in chondrocyte/matrix structural parameters and chondrocyte biosynthetic activity in articular cartilage. This technique is based on the use of a laser scanning confocal microscope that can "optically" section chemically fixed, unembedded tissue. The confocal images are used for morphometric measurement of stereologic parameters such as cell density (cells/mm3), cell volume fraction (%), surface density (l/cm), mean cell volume (micron3), and mean cell surface area (micron2). Adjacent pieces of tissue are simultaneously processed for conventional liquid emulsion autoradiography, and a semiautomated grain counting program is used to measure the silver grain density at regions corresponding to the same sites used for structural measurements. An estimate of chondrocyte biosynthetic activity in terms of grains per cell is obtained by dividing the value for grain density by that for cell density. In this paper, the newly developed methodology was applied to characterize the zone-specific behavior of adult articular cartilage in the free-swelling state. Cylinders of young adult bovine articular cartilage were labelled with either [3H]proline or [35S]sulfate, and chondrocyte biosynthesis and structural parameters were measured from the articular surface to the tidemark. The results showed that chondrocytes of the radial zone occupied twice the volume and surface area of the chondrocytes of the superficial zone but were 10 times more synthetically active. This efficient and unbiased technique may prove useful in studying the correlation between mechanically induced changes in cell form and biosynthetic activity within inhomogeneous tissue as well as metabolic changes in cartilage due to ageing and disease.

Animals↗
PubMed1996

Predictive utility of the CSQ in low back pain: individual vs. composite measures.

Researchers have typically used factor-analytic composite measures of coping, instead of individual scales, to predict rehabilitation outcome. There are, however, both advantages and disadvantages to using individual or composite scores. This study extended the findings of Jensen et al. (1992), by prospectively comparing the individual and composite scores of the Coping Strategies Questionnaire (CSQ) in the prediction of 4 types of adjustment to low back pain. Two-hundred patients completed the CSQ, the Oswestry Index, the SCL-90R, and 4 lifting tasks at admission and discharge from a multidisciplinary pain clinic. Return to work was determined at 9-month follow-up. The CSQ scales were factor-analyzed to devise composite indices, and the 3 resultant factors were compared to the individual scales in the prediction of pain and other outcomes. The results indicated that the relative predictive utility of the composite or individual scales depended on which outcome measure was used to define adjustment.

Adaptation, Psychological↗
PubMed1996

Long-term results of electrophysiologically guided sotalol therapy for life-threatening ventricular arrhythmias.

The efficacy and safety of sotalol therapy for ventricular arrhythmias was evaluated in 133 patients with drug-refractory ventricular arrhythmias. All patients had baseline electrophysiologic studies before and after oral sotalol therapy. Sixty-six patients were discharged home, treated with sotalol (52 patients without inducible ventricular tachycardia or fibrillation and 14 patients with hemodynamically stable inducible ventricular tachycardia). The mean follow-up period was 41 +/- 27 months for the 14 patients with hemodynamically stable ventricular tachycardia. Sotalol was effective in 8 of these 14 patients. Recurrent nonlethal ventricular tachycardia occurred in 3 patients; 2 patients had sudden death; and 1 patient had adverse side effects. The 52 patients without inducible ventricular tachycardia were followed up for a mean period of 36 +/- 30 months. Thirty-five of 52 patients were successfully treated. Two patients had recurrent ventricular tachycardia; both of these episodes of ventricular tachycardia occurred within the first year. Four patients had sudden cardiac death; three of these deaths occurred within the first month, and the last episode of sudden death occurred after 8 years of sotalol therapy. The actuarial incidence of sotalol efficacy was 76% at 1 year, 72% at 2 years, 64% at 4 years, and 52% at 5 years. Approximately 46% of patients receiving long-term sotalol treatment reported side effects. Side effects severe enough to warrant withdrawal of sotalol occurred in 7 (11%) patients. The results of our study suggest that sotalol is effective for selected patients with drug refractory ventricular arrhythmias. Although the incidence of side effects are high, patients appear to tolerate long-term sotalol therapy well.

Adult↗
PubMed1996

Rifampicin antibiotic impregnation of the St. Jude Medical mechanical valve sewing ring: a weapon against endocarditis.

The Dacron sewing ring material of the St. Jude Medical mechanical heart valve (St. Jude Medical, Inc., St. Paul, Minn.) was passively impregnated with rifampicin (60 mg/ml) both in its unsealed state and after sealing by the methods of preclotting in blood, autoclaving in blood, and autoclaving in 20% albumin. Antistaphylococcal activity in the Dacron material was assessed immediately after rifampicin impregnation and at regular periods up to 5 days after implantation into the goat aorta. When the Dacron material had been sealed by autoclaving in blood and autoclaving in 20% albumin significant retention of antistaphylococcal activity was found after 5 days in vivo. Best results were obtained with the use of autoclaved blood (p < 0.05). We also compared these results with those obtained from impregnating commercially available gelatin-sealed (Gelseal) and collagen-sealed (Hemashield) Dacron material with rifampicin. Although antistaphylococcal activity was equivalent immediately after rifampicin impregnation, after 4 days in vivo the activity was negligible in Gelseal material (p < 0.05) and could not be demonstrated in Hemashield material. Rifampicin impregnation of the intact St. Jude Medical mechanical valve sewing ring may have an application in the prevention of prosthetic valve endocarditis and a clinical protocol is suggested.

Albumins↗
PubMed1996

Laparoscopic complications in markedly obese urologic patients (a multi-institutional review)

OBJECTIVES: Significant obesity is considered to be a relative contraindication to laparoscopic surgery. This study reviews the complications encountered in massively obese patients undergoing urologic laparoscopic surgery. METHODS: Body mass index (BMI) was used as an objective index to indicate massive obesity. Eleven institutions compiled retrospective data on 125 patients having a BMI greater than 30. Procedures performed included 76 pelvic lymph node dissections, 14 nephrectomies, 7 bladder neck suspensions, and 28 miscellaneous procedures. RESULTS: For the group as a whole, the mean BMI was 35.1 (range 30.1 to 57.2). Mean operative time was 202 minutes (range 60 to 480). Conversion to open surgery occurred in 15 of the 125 patients (12%). Complication rates (minor and major) were 22% (27 occurrences in 125 patients) intraoperatively and 26% (33 occurrences in 125 patients) postoperatively. The major complications included 2 trocar injuries to abdominal wall vessels, 1 bladder injury, 3 peripheral nerve injuries, 1 dysrhythmia, 1 deep vein thrombosis, 1 wound seroma, 1 nephrocutaneous fistula, 1 incisional hernia, and 1 death. CONCLUSIONS: In this review, complication rates for urologic laparoscopic surgery on massively obese patients were higher than in the general population undergoing laparoscopic surgery (0.3% to 21%).

Adolescent↗
PubMed1996

Repeated prevalence surveys of paediatric hospital-acquired infection.

Hospital-acquired infection (HAI) results in an enormous burden of excess morbidity, mortality and cost in both adults and children. Monitoring HAI is difficult, especially with limited resources, but it is vital if infection control measures are to be appropriately implemented and assessed. Cross-sectional prevalence surveys, repeated every six months, have been used effectively to monitor HAI in adults, but this technique has not been previously employed in the paediatric population. We performed prevalence surveys of HAI on a single day once every six months for five years, using a standardized questionnaire. Of the 1623 inpatients surveyed, 125 (7.7%) had HAI and 352 (21%) had community-acquired infection. In those with HAI, central-line infections, pneumonia, and wound infections predominated. A hospital stay of greater than seven days was associated with a sixfold increase in the risk of HAI. In addition, admission to a paediatric or neonatal intensive care unit, the presence of a urinary or vascular catheter, the presence of an endotracheal tube, immunosuppression and recent surgery were all associated with a significantly increased risk of HAI. In contrast to other studies, younger children were not at increased risk of HAI; admission to the neonatal unit, rather than age per se, was associated with increased risk. We conclude that repeated prevalence surveys enable simple and cost-effective assessment of HAI, facilitating appropriate infection control interventions. They should be used more widely in the paediatric setting.

Age Factors↗
PubMed1996

Comorbidity of depression with chronic facial pain and temporomandibular disorders.

OBJECTIVE: The objective of this study was to examine the comorbidity of depressive disorders in patients with chronic facial pain presenting to a multidisciplinary facial pain clinic. STUDY DESIGN: Data were collected from 72 consecutive patients with chronic facial pain who had received a maltidisciplinary evaluation including a psychiatric examination for the presence of depressive disorders. RESULTS: Twenty-eight percent of patients met criteria of the latest Diagnostic and Statistical Manual of Mental Disorders for major depression, and 25% met the criteria for minor depression. A further 22% reported subsyndromal depressive symptoms. Temporomandibular disorders were demonstrable in 71% of these patients, but the remaining 29% had no objective physical findings. There was no statistical difference in comorbidity of depressive disorders in patients with temporomandibular disorders compared with patients without temporomandibular disorders. CONCLUSION: Screening for symptoms of depression should be an integral part of the evaluation of all patients with chronic facial pain, even when masticatory muscle or temporomandibular joint disorders are identified.

Adolescent↗
PubMed1996

Expression of steroidogenic factor-1 (SF-1) mRNA and protein in the human placenta.

Steroidogenic factor-1 (SF-1), also known as adrenal-4-binding protein (Ad4BP), is a recently-described transcription factor, which has been shown to be important for the differentiation of steroidogenic tissues. In addition, SF-1 has been implicated in regulating the glycoprotein hormone alpha-subunit gene in a pituitary gonadotroph cell line. Considering that the human placenta produces both steroids and human chorionic gonadotrophin (HCG), we studied the expression of SF-1 in this tissue. Human first trimester and term placentas were collected at the time of therapeutic abortion and birth respectively. Messenger RNA was extracted, reverse transcribed, and used for polymerase chain reaction (PCR) amplification with primers specific for the human SF-1 cDNA sequence. A band of the expected size was obtained from both first and third trimester samples, indicating that SF-1 expression in the human placenta starts early in pregnancy and is maintained until birth. In addition to normal placental samples, JEG3 and JAR choriocarcinoma cells were also analysed and found to express SF-1 mRNA. The identity of the amplified products was confirmed by diagnostic restriction digest and Southern hybridization. SF-1 protein was localized mainly to the nuclei of the cyto- and syncytiotrophoblast and to some mesenchymal villous nuclei by immunocytochemistry using a specific antibody. We conclude that SF-1 is expressed in human first trimester and term placenta, where it could be implicated in the regulation of HCG production, in steroidogenesis, or both.

Base Sequence↗
PubMed1996

Late-onset infections of infants in neonatal units.

OBJECTIVE: To examine regional variations in the incidence of late-onset neonatal infections in Australian and New Zealand neonatal units. METHODOLOGY: A longitudinal, prospective surveillance study of systemic sepsis (septicaemia or meningitis) in 11 neonatal units: 10 in the Australian States of the Northern Territory, New South Wales, Queensland, Victoria and Western Australia, and 1 in Christchurch, New Zealand. The results are reported of late-onset neonatal infection (defined as sepsis after 48 h) for the second year of prospective surveillance, data being collected from 1 October 1992 to 30 September 1993. RESULTS: Data were available on 24535 live births in Australia, representing approximately 10% of all live births in the country. There were 320 episodes of sepsis in Australian units affecting 294 babies. One hundred of these episodes (31%) were early-onset; 3.0% of babies admitted to six tertiary care neonatal units attached to maternity hospitals developed late sepsis, and this rate did not differ between units. The proportion of babies infected was inversely related to birthweight: 22.6% of babies under 1OOOg, but 0.6% over 2000g. Coagulase negative staphylococci were the commonest cause of late-onset sepsis. There were 26 episodes of S. aureus septicaemia, of which only one was due to MRSA. Meningitis occurred in 13 babies (5.9%) with late-onset sepsis. The mortality from late-onset sepsis was 7.7%. CONCLUSIONS: Coagulase-negative staphylococci are the commonest cause of late-onset sepsis of babies in neonatal units. There were no major regional differences in the incidence of, or the organisms causing, late sepsis.

Australia↗
PubMed1996

Comparison of randomly cloned and whole genomic DNA probes for the detection of Porphyromonas gingivalis and Bacteroides forsythus.

Whole genomic and randomly-cloned DNA probes for two fastidious periodontal pathogens, Porphyromonas gingivalis and Bacteroides forsythus were labeled with digoxigenin and detected by a colorimetric method. The specificity and sensitivity of the whole genomic and cloned probes were compared. The cloned probes were highly specific compared to the whole genomic probes. A significant degree of cross-reactivity with Bacteroides species, Capnocytophaga sp. and Prevotella sp. was observed with the whole genomic probes. The cloned probes were less sensitive than the whole genomic probes and required at least 10(6) target cells or a minimum of 10 ng of target DNA to be detected during hybridization. Although a ten-fold increase in sensitivity was obtained with the whole genomic probes, cross-hybridization to closely related species limits their reliability in identifying target bacteria in subgingival plaque samples.

Bacterial Typing Techniques↗
PubMed1996

Mycobacterium genavense infections in pet animals.

Mycobacterium genavense, a recently reported cause of a wasting illness in patients with AIDS, was isolated from a cervical lymph mode from a dog with severe hind limb weakness and from trachael tissue from a parrot with acute onset respiratory distress. Physicians caring for immunocompromised patients should consider birds and dogs potential sources of M. genavense infection and submit appropriate specimens for culture.

AIDS-Related Opportunistic Infections↗
PubMed1996

One-year prevalence of psychiatric disorder in Ontarians 15 to 64 years of age.

OBJECTIVE: To present the one-year prevalence of 14 psychiatric disorders in a community sample of Ontarians aged 15 to 64 years. METHOD: Data on psychiatric disorders were collected on 9953 respondents using the University of Michigan revision of the Composite International Diagnostic Interview (UM-CIDI). DSM-III-R criteria were used to define the psychiatric disorders. RESULTS: Almost 1 in 5 Ontarians (18.6%) had one or more of the disorders measured in the survey. Among 15-to 24-year-olds, 1 in 4 was affected. The distribution of individual disorders varied by sex and age. CONCLUSION: Because of the immense burden of suffering associated with psychiatric disorders, clinical and research efforts in this area should receive high priority within the health budget.

Adolescent↗
PubMed1996

The transcription activator steroidogenic factor-1 is preferentially expressed in the human pituitary gonadotroph.

Steroidogenic factor-1 (SF-1), also known as adrenal-4-binding protein, is a transcription factor that is important for the differentiation of steroidogenic tissues. We investigated whether SF-1 is expressed in specific hormone-producing cell types in the human pituitary and its adenomas. Pituitary adenomas (n = 35) were collected at the time of surgery, and normal adenohypophyses were obtained from autopsies; 3 corticotroph adenomas were excluded because pit-1 messenger ribonucleic acid (mRNA) expression indicated contamination by nontumorous elements. Expression of SF-1 mRNA was determined by reverse transcription-PCR. SF-1 protein was localized with immunocytochemistry. By reverse transcription-PCR, SF-1 mRNA was found in the nontumorous pituitary and in pituitary adenomas expressing gonadotropins. All 8 gonadotroph adenomas had a strong signal for SF-1. SF-1 mRNA was also detected in 2 of 3 corticotroph adenomas, 2 of 13 somatotroph/mammosomatotroph adenomas, 1 of 6 lactotroph adenomas, and 2 silent subtype 3 adenomas; however, in most of the positive tumors there was also positivity for FSH beta and/or LH beta mRNA, suggesting that contaminating nontumorous gonadotrophs may be the source of SF-1 mRNA signal. SF-1 protein was localized by immunocytochemistry in the nuclei of scattered cells of the nontumorous adenohypophysis that were shown to be gonadotrophs with double immunostaining and in gonadotroph adenomas; nuclear staining was not found in other adenoma types, except in areas shown to contain trapped nontumorous tissue. We conclude that SF-1 expression correlates with the expression of gonadotropins. These findings implicate SF-1 as a cell-specific transcription factor that may regulate gonadotroph differentiation in the pituitary.

Adenoma↗
PubMed1996

Nongenomic actions of estrogen in the brain: physiological significance and cellular mechanisms.

Estrogen regulates neuroendocrine, reproductive, and behavioral functions of the brain by utilizing a number of diverse cellular mechanisms. In the classical genomic mechanism of steroids, estrogen induces relatively long-term actions on neurons by activating specific intracellular receptors that modulate transcription and protein synthesis. In addition, estrogen can also exert very rapid effects in the brain that cannot be attributed to genomic mechanisms. These nongenomic actions of estrogen influence a variety of neuronal properties, including electrical excitability, synaptic functioning, and morphological features, and are involved in many of the physiological functions and clinical effects of estrogen in the brain. Recently the specific cellular and molecular mechanisms underlying the nongenomic actions of estrogen have begun to be elucidated. Estrogen may utilize direct membrane mechanisms, such as activation of ligand-gated ion channels and G-protein-coupled second messenger systems and regulation of neurotransmitter transporters. Additionally the membrane and genomic actions of estrogen have the potential to interact, producing synergistic effects and dependence between the two types of mechanisms. The combination of nongenomic and genomic mechanisms endows estrogen with considerable diversity, range, and power in regulating neural function.

Animals↗
PubMed1996

Cloning and sequence analysis of the human gene encoding steroidogenic factor 1.

The orphan nuclear receptor steroidogenic factor 1 (SF-1) plays key roles in endocrine development and function. Initially identified as a positive regulator of the cytochrome P450 steroid hydroxylases, analyses of knockout mice deficient in SF-1 revealed that SF-1 is essential for adrenal and gonadal development, pituitary gonadotropin expression and formation of the ventromedial hypothalamic nucleus. Although more limited in scope, analyses of SF-1 in humans similarly have suggested that SF-1 is important for differentiated function in adrenocortical and gonadotrope adenomas. In the hope of extending our understanding of SF-1 function by identifying possible roles of SF-1 in clinical endocrine disorders, we isolated the FTZ-F1 gene encoding human SF-1 and mapped it to chromosome 9q33. In this report, we characterize the sequence and structural organization of the human cDNA and gene encoding SF-1, providing new insights into comparative aspects of SF-1 structure that will facilitate efforts to study the role of this transcription factor in human endocrine disorders.

Amino Acid Sequence↗