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Biomedical subjects

L K Wong

Publications and source records attributed to L K Wong.

At least 19 recordsLinked to original sources

A randomized controlled trial of surgery vs steroid injection for carpal tunnel syndrome.

BACKGROUND: Decompressive surgery and steroid injection are widely used forms of treatment for carpal tunnel syndrome (CTS) but there is no consensus on their effectiveness in comparison to each other. The authors evaluated the efficacy of surgery vs steroid injection in relieving symptoms in patients with CTS. METHODS: The authors conducted a randomized, single blind, controlled trial. Fifty patients with electrophysiologically confirmed idiopathic CTS were randomized and assigned to open carpal tunnel release (25 patients) or to a single injection of steroid (25 patients). Patients were followed up at 6 and 20 weeks. The primary outcome was symptom relief in terms of the Global Symptom Score (GSS), which rates symptoms on a scale of 0 (no symptoms) to 50 (most severe). Nerve conduction studies and grip strength measurements were used as secondary outcome assessments. RESULTS: At 20 weeks after randomization, patients who underwent surgery had greater symptomatic improvement than those who were injected. The mean improvement in GSS after 20 weeks was 24.2 (SD 11.0) in the surgery group vs 8.7 (SD 13.0) in the injection group (p < 0.001); surgical decompression also resulted in greater improvement in median nerve distal motor latencies and sensory nerve conduction velocity. Mean grip strength in the surgical group was reduced by 1.7 kg (SD 5.1) compared with a gain of 2.4 kg (SD 5.5) in the injection group. CONCLUSION: Compared with steroid injection, open carpal tunnel release resulted in better symptomatic and neurophysiologic outcome but not grip strength in patients with idiopathic carpal tunnel syndrome over a 20-week period.

Adult↗

Triterpene antioxidants from ganoderma lucidum.

Ganoderma lucidum was studied for its antioxidative activity by bioassay guided isolation in conjunction with in vitro tests. The powdered crude drug was treated with boiling water and the aqueous extract (Ex1) was further separated to obtain terpene and polysaccharide fractions. The two fractions and Ex1 were screened for their antioxidative effect against pyrogallol induced erythrocyte membrane oxidation and Fe (II)-ascorbic acid induced lipid peroxidation. All tested samples showed antioxidative activities in a dose dependent manner and the terpene fraction was found to possess the highest effect compared with the others. Chemical isolation of the terpene fraction resulted in the detection of ganoderic acids A, B, C and D, lucidenic acid B and ganodermanontriol as major ingredients.

Animals↗

Chinese herbal medicine and acupuncture. How do patients who consult family physicians use these therapies?

OBJECTIVE: To determine how a population of Chinese patients consulting family physicians in Vancouver use traditional Chinese medicine (TCM), specifically Chinese herbal medicine and acupuncture. DESIGN: Bilingual survey (English and Chinese). SETTING: Four family practices with predominantly Chinese patients in metropolitan Vancouver. PARTICIPANTS: The 932 patients or family members who visited one of the practices. MAIN OUTCOME MEASURES: Demographic characteristics; frequency and reason for visiting a family physician, Chinese herbalist, or acupuncturist; choice of practitioner if affected by one of 16 common conditions. RESULTS: The study population was mostly Chinese and immigrant to Canada. Chinese herbal medicine was currently used by 28% (262/930) of respondents (more than one visit in the last year), and another 18% (172/930) were past users. Acupuncture was currently used by 7% (64/927) and had been used in the past by another 8% (71/927). Use of Chinese herbal medicine varied significantly (P < .01) according to age, sex, immigrant status, and ethnicity. Acupuncture use varied significantly only by age. The main reasons for consulting Chinese herbalists were infection (41%, 157/382), respiratory problems (11%, 42/382), and rheumatologic problems (10%, 38/382), whereas acupuncturists were consulted almost exclusively for rheumatologic problems (80%, 45/56). CONCLUSIONS: Using TCM in conjunction with visiting family physicians was very popular among this predominantly Chinese study population. Patients with acute conditions, such as influenza, consulted both their family physicians and Chinese herbalists in quick succession. On the other hand, those suffering from more chronic conditions, such as rheumatologic diseases, were more likely to start using TCM after repeated visits to their family physicians.

Acupuncture Therapy↗

Putaminal and thalamic hemorrhage in ethnic chinese living in Hong Kong.

BACKGROUND: Hemorrhagic stroke is very common in the Chinese population, and it is one of the leading causes of mortality in Chinese communities. The risk factors to explain this high incidence are unknown. It is the purpose of this study to look into the features of hemorrhagic stroke in the Hong Kong Chinese. METHODS: We conducted a prospective hospital-based study in which 60 consecutive Chinese patients with computed tomography diagnosis of putaminal or thalamic hemorrhage were included. Their demographic and clinical data were collected and analyzed. RESULTS: Two major findings evolved from the present study. (1) Unlike the Western studies, the majority of our patients were about a decade younger; (2) 50% of the patients had previously diagnosed hypertension, but only 20% of these patients were compliant with their antihypertensive medication. Our results also suggested that low admission Glasgow Coma Scale scores, large hematoma size, and the presence of intraventricular blood were associated with poor outcomes. CONCLUSIONS: This study concludes that hemorrhagic stroke is indeed a serious health problem in Hong Kong. Simple measures, such as improvement of health education and the primary care system in the management of hypertension, would help to reduce the incidence of hemorrhagic stroke.

Adult↗

Use of low-dose low molecular weight heparin in hemodialysis.

We investigated the lowest effective dosage of low molecular weight (LMW) heparin for hemodialysis in comparison to unfractionated (UF) heparin. Initial hemodialysis sessions were undertaken in 10 uremic patients with UF heparin of the dose habitually required for each patient. Four-hour hemodialysis sessions were then undertaken with LMW heparin (nadroparin) in a single bolus (200 anti-Xa unit Institut Choay/kg [aXaU IC/kg], 175 aXaU IC/kg, 150 aXaU IC/kg, or 125 aXaU IC/kg; two sessions for each dosage). Anti-Xa levels and activated partial thromboplastin time (APTT) were monitored hourly during dialysis. Fiber bundle volume of dialyzer was measured before and after dialysis. Urea clearance was determined at the onset and completion of dialysis. There were no episodes of excessive bleeding, clotting of dialyzers, or clots in air traps with UF heparin or LMW heparin. A 35% increase in APTT above baseline was observed in all dialysis sessions 1 hour after LMW heparin bolus, but the APTT decreased rapidly thereafter. The anti-Xa levels exceeded 0.5 U/mL for all sessions using LMW heparin irrespective of the dosage. No significant reduction of urea clearance was found in dialysis with either UF or LMW heparin. No reduction of fiber bundle volume of dialyzer was observed in dialysis with either UF or LMW heparin, although a small reduction (3%) was observed in dialysis with LMW heparin at 125 aXaU IC/kg. We concluded that the use of LMW heparin for hemodialysis is safe and effective as compared with UF heparin. The lowest effective dosage can be reduced to 125 aXaU IC/kg in high-risk patients to reduce hemorrhagic complications.

Adult↗

Synthesis, antiinflammatory, and cytotoxic activities of 2-alkyl and 2-benzyl-2-dimethylaminomethyl-5-(E)-arylidene cyclopentanone hydrochlorides.

PURPOSE: A series of 2-substituted-2-dimethylaminomethyl-5-(E)-arylidene cyclopentanones, 4 were synthesized. The main objective of this investigation was to explore the structural parameters necessary for antiinflammatory activity in this series of compounds, while keeping cytotoxic action to a minimum. METHODS: The target compounds were synthesized in two steps commencing with 2-alkyl-cyclopentanones. Antiinflammatory, analgesic and cytotoxic activities were determined in rats. Cytotoxic results were examined in human cell lines. RESULTS: Eight of the eighteen synthetic substances possessed significant antiinflammatory activity and twelve showed appreciable analgesic action. Cytotoxicity was minimal or non-existent for most of the compounds. The stability of one of the compounds, 4b in both aqueous and non-aqueous media, and an amine exchange reaction with aniline were used to explain the observed antiinflammatory and cytotoxic activities. CONCLUSIONS: Unlike monosubstituted aminomethyl groups (Mannich bases) at the 2-position of 5-arylidene-2-cyclopentanones, a second substituent at the 2-position increases stability of the Mannich base and significantly decreases cytotoxic activity. Antiinflammatory and analgesic action is retained in many of the compounds, thus strongly indicating that these desired pharmacological results can be obtained without untoward damage to cells.

Analgesics↗

Synthesis and cytotoxic activities of the amine-exchange products of 2-dimethylaminomethyl-5-(E)-substituted arylidene cyclopentanones with anilines: 2-arylaminomethyl-5-(E)-arylidene cyclopentanones.

A series of 2-arylaminomethyl, and 2-(4-morpholinylmethyl)-5-(E)-arylidene cyclopentanones have been synthesized via an amine-exchange reaction. Most of the compounds showed significant cytotoxic activities, in vitro, on various human cancer cell lines. Generally, compounds with a para-chloroanilino moiety were more active than those of other aniline derivatives. No apparent changes were observed by altering the substituents on the arylidene portion. For the majority of active compounds, leukemia is one of the most sensitive subpanels at both GI50 and TGI levels but the least sensitive one at the LC50 level. Colon cancer is one of the most sensitive subpanels in all three levels. COMPARE results indicated that the characteristics, and possibly the mechanism of the cytotoxic properties of the 2-arylaminomethyl derivatives might be different from that of the 2-dialkylaminomethyl derivatives previously reported.

Aniline Compounds↗

Characterization and kinetic analysis of the intracellular domain of human protein tyrosine phosphatase beta (HPTP beta) using synthetic phosphopeptides.

The intracellular domain of human protein tyrosine phosphatase beta (HPTP beta) (44 kDa) was expressed in bacteria, purified using epitope 'tagging' immunoaffinity chromatography, and characterized with respect to kinetic profile, substrate specificity and potential modulators of enzyme activity. A chromogenic assay based on the Malachite Green method was employed for the detection of inorganic phosphate (Pi) released from phosphopeptides by HPTP beta. This assay, modified so as to improve its sensitivity, was adapted to a 96-well microtitre plate format, and provided linear detection between 50 and 1000 pmol of Pi. The cytoplasmic domain of HPTP beta was strongly inhibited by vanadate, molybdate, heparin, poly(Glu, Tyr) (4:1) and zinc ions. In order to explore the substrate preferences of this PTPase, we generated 13-residue synthetic phosphotyrosine-containing peptides that corresponded to sites of physiological tyrosine phosphorylation. HPTP beta demonstrated kcat. values between 76 and 258 s-1 using four different phosphopeptides. The substrate preference of HPTP beta was in the order srcTyr-527 > PDGF-RTyr-740 > ERK1Tyr-204 >> CSF-1RTyr-708 with Km values ranging from 140 microM to greater than 10 mM. The variations in affinity were probably due to differences among the four phosphopeptides compared, particularly with respect to the character of the charged amino acids flanking the phosphotyrosine residue.

Amino Acid Sequence↗

Synthesis and anti-cancer activity of 2-alkylaminomethyl-5-(E)-alkylidene cyclopentanone hydrochlorides.

A series of 2-alkylaminomethyl-5-(E)-alkylidene cyclopentanone hydrochlorides (2), have been synthesized and evaluated as anti-cancer agents. These compounds were designed as masked alpha-methylenecyclopentanones, which appear in many cytotoxic or anti-cancer natural products. Most of the synthesized compounds were found to be active towards various human cancer cell lines and many showed significant subpanel selectivity. For compounds containing the same alkylidene moiety (from C3 to C9), the dimethylaminomethyl analogs were more active than structures possessing morpholino-, pyrrolidino-, or piperidino-methyl groups. Alteration of the alkylidene moiety had little effect on anti-cancer potency. The mass spectrum of a glutathione adduct of 2h indicated that the mechanism of action for these anti-cancer agents may be related to the attack at the aminomethyl carbon atom by biological nucleophilic thiols.

Antineoplastic Agents↗

Synthesis and biological evaluation of novel potent antagonists of the bombesin/gastrin releasing peptide receptor.

This paper reports the synthesis and antagonist activity of 20 C-terminal analogues of gastrin releasing peptide (GRP). The ability of each analogue to inhibit bombesin (BN) stimulated amylase release from rat pancreatic acini was determined, and those showing antagonist activity were further evaluated for their ability to inhibit BN-stimulated [3H]thymidine uptake in serum-starved 3T3 cells. The assays also included two known peptide antagonists, C (Leu14,psi 13,14]BN) and H (N-pivaloyl-GRP20-25-(R)-2-methyl-4-nonylamide) as positive controls. On the basis of these assays we suggest that a des-Met27,Leu26-psi[CH2NHCOCH3]GRP C-terminal octapeptide imparts antagonist activity. The two most active compounds are peptides 14 ([D-Phe19,Leu26-psi(CH2NHCOCH3)]GRP19-26) and 18 ([D-Phe19,Gln20,Leu26-psi(CH2NHCOCH3)]GRP19++ +-26). In their ability to inhibit BN-stimulated [3H]thymidine uptake, the IC50 of peptides C, H, 14, and 18 were 43.2, 31.2, 2.7, and 32.5 nM, respectively. In conclusion, the novel C-terminal psi[CH2NHCOCH3] bond promises to be a useful peptide backbone modification for imparting antagonism in GRP/BN analogues.

Amino Acid Sequence↗

Kinetics of the multi-step catalytic degradation of a polymer to its constituent subunits.

The stepwise catalytic degradation of a polymer to its constituent subunits results in many molecules of polymers of shorter chain length. Using the Law of Mass Action, ordinary differential equations for each species can be obtained from the set of elementary reactions and these can be integrated to obtain species concentrations as a function of time. A special case of catalytic degradation of polymers, in which one subunit is released at each step, is examined. A mathematical dissertation on the kinetics of the series of reactions involved is presented. The solution of the set of differential equations involve tedious computations and cannot be easily adapted to the analysis of experimental data. Two additional methods of analysis are described. The first one makes use of the property that for any intermediary polymer whose initial and final concentrations are zero, the integral of its concentration with respect to time is inversely proportional to the degradation rate constant. Stepwise calculation of the rate constants can thus be obtained by determining the area under the concentration-time trajectories while the degradation rate constant of the first polymer is known. The second method makes use of the property that the maximum concentration attained by any individual intermediary polymer is inversely proportional to its degradation constant. These methods have the advantage of being simple since the degradation constants can be obtained stepwise from experimental data.

Catalysis↗

Effect of recombinant alpha 2 interferon with or without prednisone in Chinese HBsAg carrier children.

Ninety Chinese hepatitis B surface antigen (HBsAg) carrier children, aged 2-17 years, positive for hepatitis B e antigen (HBeAg) and hepatitis B virus DNA on at least three occasions in 6 months, were randomized into 3 groups. Thirty children received syrup vitamin B complex as control, 29 received 6 weeks of placebo syrup followed by 16 weeks of recombinant alpha 2b-interferon [intron A (rIFN2b)], 5 x 10(6) u/m2 subcutaneously thrice weekly; and 31 received 6 weeks of syrup prednisone (0.6 mg/kg tailed to 0.2 mg/kg) followed by 16 weeks of recombinant alpha 2b-interferon as above. The placebo/prednisone syrup was given on a double-blind basis. At 24 months of follow-up, persistent loss of hepatitis B virus DNA occurred in none of the children in the control group, in one child receiving recombinant alpha 2b-interferon alone, who also seroconverted to anti-HBe and anti-HBs and in five children receiving interferon with steroid priming (p = 0.0571 compared with controls), with four seroconverting to anti-HBe and one also seroconverting to anti-HBs. A rise of transaminases to above twice the upper limit of normal levels during the first 7 months of follow-up occurred in one subject in the control group, four in the group receiving alpha 2b-interferon alone and nine in the group receiving recombinant alpha 2b-interferon with steroid priming (p = 0.0144 compared with controls). Side effects of the steroid were negligible; those of recombinant alpha 2b-interferon were transient and acceptable. We conclude that 6 weeks of prednisone followed by 16 weeks of recombinant alpha 2b-interferon is of use in inducing persistent loss of hepatitis B virus DNA (16.1 per cent) and e-seroconversion (12.9 per cent) in a proportion of Chinese HBsAg carrier children: the prednisone probably enhances the immunomodulatory effect of recombinant alpha 2b-interferon.

Adolescent↗

Peptidyl aminosteroids as potential new antiarrhythmic agents.

The synthesis of peptidyl derivatives of the aminosteroid, amafalone (Am), is described. Six analogs were synthesized: the hydrochloride salts of Gly-Am (2) Ala-Gly-Am (3), D-Ala-Gly-Am (4), Pro-Am (6), Pro-Pro-Am (7), and D-Ala-Pro-Am (8). The peptide bonds were formed by the polymeric reagent method using polymeric hydroxybenzotriazole as the activating polymer. Peptidyl aminosteroids 2, 6, 7, and 8, when administered to rats intravenously, had protective antiarrhythmic effects similar to those of amafalone. By the oral route, less marked protection, in comparison to amafalone, was observed with 6, while 7 and 8 were disappointingly inactive.

Administration, Oral↗

Effects of scopolamine on antipredator defense reactions in wild and laboratory rats.

Two experiments were designed to investigate the effects of scopolamine hydrobromide (0.25-1.0 mg/kg), and its methyl derivative, on the defensive reactions of rats to nonpainful threat stimuli. In the first experiment, over the dose range studied neither compound significantly altered avoidance, freezing, defensive threat or attack in wild Rattus rattus confronted by the experimenter and other predator-related stimuli. Scopolamine hydrobromide did, however, produce a dose-dependent increase in flight distance; this effect was not seen with the methyl compound, confirming central cholinergic mediation. In the second experiment, no dose of either compound significantly altered the behaviour of Long-Evans rats prior to cat exposure. During cat exposure, however, scopolamine hydrobromide (but not methyl scopolamine) increased the amount of time spent in the vicinity of the cat, increased scanning and rearing, and reduced grooming behaviour. Although reliable, the latter effects were not pronounced. Together, these data do not support a major involvement of central muscarinic receptor mechanisms in the regulation of defensive patterns in wild or laboratory rats.

Aggression↗