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Biomedical subjects

P M Leung

Publications and source records attributed to P M Leung.

At least 19 recordsLinked to original sources

Randomized study of brachytherapy in the initial management of patients with malignant astrocytoma.

PURPOSE: A randomized study was undertaken to assess the role of brachytherapy as a boost to external beam radiation therapy in the initial management of patients with malignant astrocytomas. METHODS AND MATERIALS: Inclusion criteria included the following: biopsy-proven supratentorial malignant astrocytoma of brain < or =6 cm in size, not crossing midline or involving corpus callosum, age 18-70, Karnofsky Performance Status (KPS) > or =70. Patients were randomized to external radiation therapy only delivering 50 Gray (Gy) in 25 fractions over 5 weeks or external radiation therapy plus a temporary stereotactic iodine-125 implants delivering a minimum peripheral tumor dose of 60 Gy. Patients were stratified to age < or =50 or >50, and KPS > or =90 or < or =80. RESULTS: There were 140 patients randomized between 1986 and 1996, 71 to the implant arm and 69 to external irradiation only. Pathologically 125 patients had necrosis noted in their tumor specimen. Factors associated with improved survival in univariate analysis were age < or =50, KPS > or =90, chemotherapy at recurrence, and reoperation at the original tumor site. The Cox proportional hazards model revealed the following significant factors: treatment at recurrence (chemotherapy or reoperation) with a relative risk (RR) of 0.6 (p = 0.004) and KPS > or =90 with a RR 0.6 (p = 0.007). Randomization to the implant arm was associated with a RR of 0.7 (p = 0.07). Median survival for patients randomized to brachytherapy or not were 13.8 vs. 13.2 months, respectively, p = 0.49. CONCLUSIONS: We conclude that stereotactic radiation implants have not demonstrated a statistically significant improvement in survival in the initial management of patients with malignant astrocytoma.

Adult↗

Re-irradiation for locally recurrent nasopharyngeal carcinoma.

Since 1989, 17 patients have undergone re-irradiation for locally recurrent nasopharyngeal cancer (NPC). The dose currently administered externally is 39.6 Gy in 36 fractions (BID) followed by an intracavitary boost (15-20 Gy). Disease persisted in five out of five patients treated palliatively. Eleven of 12 patients treated with curative intent achieved local control.

Adult↗

Disposal of therapeutic 131I waste using a multiple holding tank system.

Therapeutic application of 131I for the treatment of thyroid cancer generates a significant amount of liquid radioactive waste. Discharge of this waste into the public sewage system is governed by local regulations. In Canada, the permissible concentration is such that only a few patients can be treated in modern water-efficient buildings if this waste is discharged directly through the toilet to the public sewage system. If the toilet discharge is first collected into a holding tank for physical decay before it is released, a large patient load can be handled without exceeding the permissible concentration. In this paper, the principles of operation and the design parameters are discussed, and a multiple holding tank system installed in the Princess Margaret Hospital/Ontario Cancer Institute is described.

Equipment Design↗

Role of mitomycin C in the development of late bowel toxicity following chemoradiation for locally advanced carcinoma of the cervix.

PURPOSE: To determine if the inclusion of mitomycin C (MMC) in chemoradiation protocols for locally advanced cervical cancer (LACC) significantly enhances the development of serious (Grade 3) late bowel toxicity (SLBT). METHODS AND MATERIALS: The incidence of SLBT in 154 patients with LACC entered in six consecutive chemoradiotherapy protocols between February 1982 and June 1987 was determined. Fifty-four patients who were treated with MMC, 5-fluorouracil (5-FU), and radiation were compared to 100 patients who received similar treatment without MMC. Univariate and multivariate analyses assessed the effect of the following parameters on the development of SLBT: (a) external beam dose, (b) rectal and rectosigmoid dose, (c) paraaortic radiation, (d) intracavitary dose and dose rate, (e) volume of tissue irradiated to a total dose of 60 Gy, (f) International Federation of Gynecology and Obstetrics stage, (g) age, (h) number of courses of 5-FU, (i) previous abdominopelvic surgery, (j) split versus continuous radiation, and (k) administration of MMC. RESULTS: The overall incidence of SLBT was 15.6%: 14 of 54 (26%) versus 10 of 100 (10%) for patients who did or did not receive MMC, respectively (p = 0.009). Multivariate analysis revealed the administration of MMC as the only factor predictive for the development of SLBT (p = 0.012, odds ratio = 3.15; 95% confidence interval 1.3-7.7). A significant reduction in SLBT was observed with the elimination of MMC from the chemoradiation protocols despite dose escalation of both radiation and 5-FU. No increase in overall survival was observed in patients receiving MMC, 5-FU, and radiation compared with 5-FU and radiation alone. CONCLUSION: The inclusion of MMC in these chemoradiation protocols for LACC is associated with significant enhancement in serious late bowel toxicity.

Adenocarcinoma↗

A survey of the long term outcome of elderly stroke survivors and the needs of their carers.

A survey was conducted to assess the long term outcome of 60 elderly stroke survivors (mean age, 81.7 years). Of these patients, 48% died within one year of discharge and 79% of the mortality occurred in the first six months. Patients discharged to institutions after the initial stroke had a significantly higher risk of death in one year (relative risk=1.47) compared with those who were discharged home. For those who survived for a mean period of 18.6months, 72% (21/29) were institutionalised. This group had significantly worse functional status and mobility compared with those who were living at home. The caring of elderly stroke patients was considered a heavy burden for most carers at home or in institutions and the need for medical and social support was great.

Journal Article↗

Laparoscopic ovarian transposition.

Preservation of ovarian function is both safe and feasible in many young women with pelvic malignancies. Techniques utilized to transpose the ovaries to date have uniformly required a laparotomy either at the time of surgical treatment or as a separate operation in patients about to undergo pelvic radiotherapy. We report our preliminary results in 3 patients who underwent laparoscopic ovarian transposition and pelvic lymphadenectomy as part of an experimental protocol using intracavitary radiation alone in patients with small node negative stage 1B cervical carcinoma desiring preservation of fertility. Dose calculations were performed to estimate the amount of radiation each transposed ovary received from the intracavitary radiation, as well as the dosage that would have been received had external pelvic (4500 cGy) with or without para-aortic nodal irradiation (4500 cGy) been required. The mean estimated distance each ovary was transposed was 14.4 cm for the right ovary and 14.3 cm for the left ovary. Operative times ranged from 2.75-4.0 hours, and the blood loss 100-300 mls. Post-operative hospital stays ranged from 1-2 days, and no complications were encountered. Two of the 3 patients are menstruating regularly 25-32 months after completion of treatment with serum FSH in the normal premenopausal range. Based on the above distances, the mean dose of radiation each transposed ovary received was estimated to be 126 cGy, whereas the range in dosage of radiation each ovary would have received had external pelvic +/- para-aortic nodal irradiation been required was 135-190 cGy, and 230-310 cGy respectively. One patient has become menopausal after her transposed ovaries slipped back into the pelvis. Laparoscopic ovarian transpositions can be performed. This procedure is technically easy to perform for those surgeons skilled in laparoscopic surgery and its preliminary morbidity appears to be low. More experience, longer followup, and refinement in the methods of ovarian transfixation are required.

Adult↗

Indirect stimulation of Ca(2+)-activated Cl- current by Na+/Ca2+ exchange in rabbit portal vein smooth muscle.

Macroscopic currents were recorded in freshly dissociated smooth muscle cells from the rabbit portal vein using the tight seal whole cell recording mode (22 degrees C). In some experiments, the indo 1 fluorescence technique was used to simultaneously monitor the changes in the concentration of free intracellular Ca2+ ([Ca2+]i; indo 1 ratio, 400/500 nm). In cells exposed to tetraethylammonium chloride (TEA) to inhibit K+ channels and 1-10 microM nifedipine or nicardipine to inhibit L-type Ca2+ channels, cell dialysis with 30 mM Na+ increased [Ca2+]i and induced membrane current consistent with the activation of Ca(2+)-activated Cl- channels [ICl(Ca)]. From holding potential (HP) of -60 mV, high intracellular Na+ concentration ([Na+]i)-mediated current was instantaneous in response to 0.5- to 10-s voltage clamp pulses from -80 to +20 mV; steps ranging from +20 to +80 mV evoked slow time-dependent outward current (I(t); superimposed on the instantaneous current) and voltage-dependent Ca2+ transient; on return to HP, slow inward tail current appeared that reflected deactivation of I(t). Both current components 1) exhibited outward rectifying properties, 2) reversed near the predicted equilibrium potential for Cl-, 3) were stimulated by elevation of extracellular Ca2+ concentration, 4) were abolished when the cells were dialyzed with 5 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, and 5) were inhibited by extracellular application of niflumic acid (50 microM). Complete replacement of extracellular Na+ concentration with tetramethylammonium increased both the instantaneous and time-dependent components of ICl(Ca), resting [Ca2+]i at -60 mV and Ca2+ transient at +40 mV. Cell dialysis with Na(+)-free pipette solution prevented these effects. Our results are consistent with an indirect mechanism of stimulation of ICl(Ca), which involves intracellular Ca2+ accumulation via reverse-mode electrogenic Na+/Ca2+ exchange activity.

Animals↗

Description and evaluation of a new 3-D computerized treatment planning dose compensator system.

Evaluation has been performed of compensators generated by means of a computerized three-dimensional treatment planning system that can utilize either digitized slice profiles or CT scans. Two methods of calculating compensator thickness are used: the modified Batho power law (dSAR) method for digitized profiles and the equivalent TAR (eqTAR) method for CT scans. This system not only compensates for patient surface contours but also compensates for internal inhomogeneities. In addition, any required wedging will be incorporated in the compensator generation. This system has been tested for a number of extreme cases with inhomogeneities and sloping contours. Good agreement was obtained between the measured and computer calculated dose profiles especially along the central axis of the beam. A "Profile Uniformity Index" was defined to quantify the goodness of dose compensation in three dimensions. Compensation using this system can achieve good dose uniformity within the target volume in all clinical cases and is definitely an improvement over systems based solely on tissue deficit.

Algorithms↗

Physiological role of Ca(2+)-activated and voltage-dependent K+ currents in rabbit coronary myocytes.

The properties and function of Ca(2+)-activated K+ (KCa) and voltage-dependent K+ (IK) currents of rabbit coronary myocytes were studied under whole cell voltage-clamp conditions (22 degrees C). Inhibition of KCa by tetraethylammonium chloride (1-10 mM) or charybdotoxin (50-100 nM) suppressed noisy outward rectifying current elicited by 5-s voltage steps or ramp at potentials > 0 mV, reduced the hump of the biphasic ramp current-voltage relation, and shifted by less than +5 mV the potential at which no net steady-state current is recorded (Enet; index of resting membrane potential). Inhibition of steady-state inward Ca2+ currents [ICa(L)] by nifedipine (1 microM) displaced Enet by -11 mV. Analysis of steady-state voltage dependence of IK supported the existence of a "window" current between -50 and 0 mV. 4-Aminopyridine (2 mM) blocked a noninactivating component of IK evoked between -30 and -40 mV, abolished the hump current during ramps, and shifted Enet by more than +15 mV; hump current persisted during 2-min ramp depolarizations and peaked near the maximum overlap of the steady-state activation and inactivation curves of IK (about -22 mV). A threefold rise in extracellular Ca2+ concentration (1.8-5.4 mM) enhanced time-dependent outward K+ current (6.7-fold at +40 mV) and shifted Enet by -30 mV. It is concluded that, under steady-state conditions, IK and ICa(L) play a major role in regulating resting membrane potential at a physiological level of intracellular Ca2+ concentration, with a minor contribution from KCa. However, elevation of intracellular Ca2+ concentration enhances KCa and hyperpolarizes the myocyte to limit Ca2+ entry through ICa(L).

Animals↗

Changes in cerebrospinal fluid and plasma amino acid concentrations with elevated dietary protein concentration in dogs with portacaval shunts.

Effects of dietary protein concentration on plasma and cerebrospinal fluid (CSF) amino acids (AA) in dogs with portacaval shunts (PCS) were examined. An 18% protein purified diet (18P) was fed to 4 PCS dogs and 2 controls; at week 10, 2 of the PCS dogs were switched to 36% protein (36P) until week 28. Effects of the diet switch on plasma and CSF AA in 8 normal dogs were determined in another experiment. Neither surgery nor protein level significantly affected average food intake (weeks 10-28). Plasma amino acid patterns typical of PCS animals were observed: phenylalanine and tyrosine increased and branched chain AA decreased with shunting (p less than 0.05). Plasma phenylalanine increased further with 36P in PCS dogs (p less than 0.05), but was not affected by dietary protein concentration in controls. With 36P: CSF arginine, serine, histidine, tryptophan, phenylalanine, glutamate and glutamine increased in PCS dogs; but only arginine decreased in CSF of controls (p less than 0.05). In PCS dogs, significant CSF AA changes with elevated dietary protein were unrelated to plasma AA changes.

Amino Acids↗

Shielding effects of Selectron applicator and pellets on isodose distributions.

The Selectron is a mobile remote afterloading device which was developed specifically to reduce the radiation exposure to hospital personnel during intracavitary brachytherapy. Applicators for these devices contain source trains of 48 spherical pellets per channel, composed of both active and inactive pellets which have an external diameter of 2.5 mm. The configuration of pellets is chosen to optimize the dose distribution in accordance with the patient's geometry. A new dose calculation model has been proposed based on the separation of radiation into primary and secondary components. This model takes into account the attenuation of the primary radiation by the pellets. Isodose distributions around a Selectron standard applicator containing a typical patient loading of active pellets were measured and compared with those calculated by program SEEDS of the Atomic Energy of Canada Ltd. (AECL) Theraplan computer planning system. The shielding effects of the stainless steel applicator tubes, the ovoids, screws, inactive and active pellets will be considered. The effects of scatter and attenuation by the pellets will be illustrated by measured isodose distributions around a single applicator tube.

Brachytherapy↗

Developing professional responsibility in maternity care in Hong Kong.

A simple questionnaire was used to document basic information surrounding all perinatal deaths in Hong Kong. Coordinators were appointed for every maternity unit. Replies were sent by mail to the Obstetrical and Gynaecological Society. Using volunteer time and minimum budget, the data were collated and analyzed. The main causes of death were congenital anomalies, intrauterine death of unknown cause and prematurity. There was significant difference in performance when the University units were compared with the private and Government units. Changes in resource allocation and modification of clinical practice may be recommended as a result of such audit.

Cause of Death↗

Dietary amino acid imbalance and neurochemical changes in three hypothalamic areas.

The impact of feeding imbalanced amino acid diets on monoamine, metabolite and amino acid concentrations was measured in the ventromedial hypothalamus (VMH), lateral hypothalamus (LH) and paraventricular nucleus (PVN). After rats were fed either an isoleucine imbalanced diet, a threonine imbalanced diet, or the appropriate basal or corrected control diets, regional differences were found in neurochemical concentrations. Contrary to our expectations, the limiting amino acid was unchanged in the imbalanced groups, tending to be decreased only in the isoleucine imbalanced-diet group in the PVN. This is the first report that the limiting amino acid was not reduced uniformly in the brain after imbalanced amino acid feeding. In the VMH, norepinephrine (NE) was increased by 22% and 63% in the threonine and isoleucine imbalanced-diet groups, respectively. Since the concentration of NE was affected even before the decrease in feeding, both in the VMH, and, as previously reported, in the prepyriform cortex, the NE system may be involved in very early responses to imbalanced amino acid diets.

Amino Acids↗

Plasma and brain ammonia and amino acids in rats measured after feeding 75% casein or 28% egg white.

Male rats were trained to consume their daily food intake in 3 h. When rats were fed 6% casein for 14 d and were then fed either the 6 or 75% casein diet for 1 d, the plasma and brain ammonia concentrations of rats fed 75% casein were higher (P less than 0.05) at 23 h after test meal initiation compared to those of rats fed 6% casein. When rats were fed 6% casein for 13 d and then fed the same 6% casein diet with or without an additional 15% ammonium acetate for an additional 7 d before feeding 75% casein for 1 d, the plasma ammonia concentration of each group was not different, but plasma and brain amino acid concentrations were lower in rats prefed 15% ammonium acetate before the 75% casein diet. When rats were fed 6.8% egg white for 9 d and then fed 27.9% egg white for an additional 7 d, food intake of rats fed the 27.9% egg white diet was lower (P less than 0.05, paired t-test) for 4 d compared with that during the 3-d pretest period. When rats were meal-fed the 6.8% egg white diet for 13 d and then fed either the same 6.8% egg white diet or the 27.9% egg white diet for 1 d, plasma ammonia and plasma and brain amino acid concentrations were higher at 5 h after test meal initiation (P less than 0.05) in rats fed 27.9% egg white compared to those of rats fed 6.8% egg white. At 23 h after test meal initiation, plasma ammonia, plasma amino acid and most brain amino acid concentrations were lower than they were at 5 h after test meal initiation in rats fed 27.9% egg white.

Amino Acids↗

Plasma ammonia, plasma, brain and liver amino acids and urea cycle enzyme activities in rats fed ammonium acetate.

Male Sprague-Dawley rats were trained to eat a 6% casein diet within a 3-h period each day. They were then fed a 6% casein diet for 10-16 d before they were fed either the same 6% casein diet or the 6% casein diet supplemented with 15% ammonium acetate for 1 or 7 d. During the absorptive period, plasma ammonia, plasma amino acids and brain amino acids were measured on d 1 and d 7 after feeding ammonium acetate. Food intake of rats fed 15% ammonium acetate was depressed on d 1 and increased to approximately 75% of the intake of the 6% casein-fed group by d 7. On d 1 plasma ammonia of the rats fed 5% ammonium acetate was 101 microM as compared to 56 microM for the rats fed 6% casein (P less than 0.05). On d 7, plasma ammonia of the rats fed 15% ammonium acetate was 240 microM (P less than 0.05) as compared to 44 microM for the rats fed 6% casein. In rats fed 15% ammonium acetate, after 7 d ornithine transcarbamylase and arginase activities were higher and argininosuccinate synthetase activity was lower (P less than 0.05) while carbamyl phosphate synthetase activity tended to be higher than that of rats fed 6% casein. The results suggest that rats adapt to ingestion of 15% ammonium acetate by some unknown neural mechanism rather than by increases in all urea cycle enzyme activities. Feeding ammonium acetate causes changes in plasma, brain and liver amino acid concentrations.

Acetates↗

Congenital cardiovascular malformations in Chinese children with Down's syndrome.

149 Chinese children (70 boys, 79 girls) with Down's syndrome and congenital heart disease were studied. Diagnosis of the cardiac abnormality was made by cardiac catheterisation in 119, two-dimensional echocardiography in 23 and autopsy in 7. The commonest lesion was ventricular septal defect which was present in 43.6%, a higher frequency than that reported in Caucasians. Other common lesions included atrioventricular septal defect (15.4%), atrial septal defect (13.4%), tetralogy in Fallot (13.4%) and patent ductus arteriosus (12.1%). Multiple lesions occurred in 36% of the cases, with patent ductus arteriosus, the most frequent coexisting lesion. Other cyanotic congenital heart conditions were very rare and coarctation of aorta was not seen. An aberrant right subclavian artery arising from the descending aorta was present in 16.5% and abnormalities of the radial artery at the wrist were found in 19%. The literature on patterns of congenital heart diseases seen in Down's syndrome was reviewed.

Asian People↗

Effect of pre-feeding ammonium acetate on food intake of rats fed high protein diets.

The effect on intake of a 75% casein diet after prefeeding for one week a 6% casein basal diet with additional 0%, 2%, 5%, 8% or 15% ammonium acetate was examined in rats trained to eat in three hours per day. Food intake was measured from 0-15, 15-30, 30-90, and 90-180 minutes for the first two days that the ammonium acetate diets were presented. Rats eating 5% and 8% or 15% ammonium acetate diet depressed their intake significantly for one day and for four days respectively. Rats eating 2%, 5%, 8%, or 15% ammonium acetate diets depressed their intake significantly from 0-30 minutes. When presented with the 75% casein diet, rats prefed 0% to 5% and 8% and 15% ammonium acetate diets ate 55% to 58% and 72% and 94% of their respective baseline intakes. It is suggested that prefeeding 15% ammonium acetate apparently induces sufficient metabolic adaptation to ammonia intake so that the rat is able to offset the metabolic consequences of intake of the 75% casein diet, thus preventing the usual food intake depressing effect of the high protein diet.

Acetates↗

Increase in plasma ammonia and amino acids when rats are fed a 44% casein diet.

Rats were trained to eat a 6% casein basal diet during a 3-hour period per day. They were then fed either the same 6% casein diet or a 44% casein diet for 3 hours. No food intake depression was observed in the rats eating 44% casein diet during the 3-hour period. Plasma ammonia and amino acids and brain amino acids were measured at 0, 4, 12 and 24 hours after presentation of the 6% or 44% casein diets. Plasma ammonia rose to 134 (p less than 0.01) and 110 micromolar (p less than 0.05) in the 44% casein fed rats at 4 and 12 hours, respectively, as compared to 67 and 53 micromolar, respectively, for the 6% casein fed rats. All plasma amino acid concentrations except methionine and glutamate were elevated (p less than 0.05) at 4 hours. In the brain, threonine, glutamine and tyrosine concentrations were elevated (p less than 0.05) at 4 hours after diet presentation. At 24 hours, valine, isoleucine, leucine, phenylalanine, and methionine concentrations were also elevated (p less than 0.05). Because intake of the 44% casein diet decreases the second day of its presentation, as noted in an earlier experiment, the increases in plasma ammonia and its possible entry into the brain as reflected by increased brain glutamine together with changes in amino acid concentrations should be considered collectively among possible metabolic signals affecting intake of high protein diets.

Amino Acids↗