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Biomedical subjects

A Poon

Publications and source records attributed to A Poon.

At least 19 recordsLinked to original sources

Somatostatin receptor expression, tumour response, and quality of life in patients with advanced hepatocellular carcinoma treated with long-acting octreotide.

Octreotide may extend survival in hepatocellular carcinoma (HCC). Forty-one per cent of HCCs have high-affinity somatostatin receptors. We aimed to determine the feasibility, safety, and activity of long-acting octreotide in advanced HCC; to identify the best method for assessing somatostatin receptor expression; to relate receptor expression to clinical outcomes; and to evaluate toxicity. Sixty-three patients with advanced HCC received intramuscular long-acting octreotide 20 mg monthly until progression or toxicity. Median age was 67 years (range 28-81 years), male 81%, Child-Pugh A 83%, and B 17%. The aetiologies of chronic liver disease were alcohol (22%), viral hepatitis (44%), and haemochromatosis (6%). Prior treatments for HCC included surgery (8%), chemotherapy (2%), local ablation (11%), and chemoembolisation (6%). One patient had an objective partial tumour response (2%, 95% CI 0-9%). Serum alpha-fetoprotein levels decreased more than 50% in four (6%). Median survival was 8 months. Thirty four of 61 patients (56%) had receptor expression detected by scintigraphy; no clear relationship with clinical outcomes was identified. There were few grade 3 or 4 toxicities: hyperglycaemia (8%), hypoglycaemia (2%), diarrhoea (5%), and anorexia (2%). Patients reported improvements in some symptoms, but no major changes in quality of life were detected. Long-acting octreotide is safe in advanced HCC. We found little evidence of anticancer activity. A definitive randomised trial would identify whether patients benefit from this treatment in other ways.

Adult↗

Estimating glomerular filtration rate in diabetes: a comparison of cystatin-C- and creatinine-based methods.

AIMS/HYPOTHESIS: We compared the predictive performance of a GFR based on serum cystatin C levels with commonly used creatinine-based methods in subjects with diabetes. SUBJECTS, MATERIALS AND METHODS: In a cross-sectional study of 251 consecutive clinic patients, the mean reference (plasma clearance of (99m)Tc-diethylene-triamine-penta-acetic acid) GFR (iGFR) was 88+/-2 ml min(-1) 1.73 m(-2). A regression equation describing the relationship between iGFR and 1/cystatin C levels was derived from a test population (n=125) to allow for the estimation of GFR by cystatin C (eGFR-cystatin C). The predictive performance of eGFR-cystatin C, the Modification of Diet in Renal Disease 4 variable formula (MDRD-4) and Cockcroft-Gault (C-G) formulas were then compared in a validation population (n=126). RESULTS: There was no difference in renal function (ml min(-1) 1.73 m(-2)) as measured by iGFR (89.2+/-3.0), eGFR-cystatin C (86.8+/-2.5), MDRD-4 (87.0+/-2.8) or C-G (92.3+/-3.5). All three estimates of renal function had similar precision and accuracy. CONCLUSIONS/INTERPRETATION: Estimates of GFR based solely on serum cystatin C levels had the same predictive potential when compared with the MDRD-4 and C-G formulas.

Adult↗

Tissue pH and temperature regulate pulpal nociceptors.

The TRPV1 receptor acts as a sensor for environmental changes in pH and temperature. Since many nociceptors express TRPV1, it is possible that local tissue-cooling may inhibit nociceptor activity via reduction of TRPV1 activation. The present study used isolated superfused rat dental pulp to test the hypothesis that capsaicin receptors are activated in inflamed tissue, as measured by alterations in neuropeptide release. We tested the hypothesis that alterations in the tissue temperature and pH of isolated superfused rat dental pulp regulate capsaicin-induced release of calcitonin gene-related peptide (CGRP). Application of capsaicin with increased proton concentration (i.e., lowered pH) produced a nearly two-fold increase in peak immunoreactive CGRP release, as compared with capsaicin applied at a pH of 7.4. Reduction in tissue temperature from 37 degrees C to 26 degrees C completely blocked the capsaicin effect. The study indicates that environmental stimuli regulate the activity of capsaicin-sensitive neurons innervating dental pulp, and these factors may be significant clinically in the development and amelioration of dental pain.

Analgesics, Non-Narcotic↗

18F-fluorodeoxyglucose positron emission tomography in evaluation of germ cell tumor after chemotherapy.

OBJECTIVES: To evaluate the role of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in the assessment of germ cell tumors after chemotherapy. METHODS: We reviewed patients' records for the histologic findings and clinical outcome. 18F-FDG PET results were correlated with tissue histologic features where available; and if not available, the correlation was with the clinical outcome. RESULTS: A total of 45 PET studies were performed on 38 patients (age range 19 to 64 years, median 31). All patients had received chemotherapy. In the nonseminomatous germ cell tumor (NSGCT) group, of the 31 patients with one scan, 18 PET scans were reported as positive, with only 2 not having active disease. Of the 12 negative scans, 6 showed teratoma, 1 tumor, and 5 did not show active disease. The equivocal scan revealed thyroid adenoma. In the seminoma group, the PET scans correlated well with the clinical and histologic outcomes. Four patients underwent salvage chemotherapy, and in this subgroup, the PET findings also correlated with the outcome. CONCLUSIONS: (18)F-FDG PET is a promising tool as an adjunct to current imaging techniques in detecting residual viable germ cell tumor after chemotherapy. In NSGCT, a positive PET scan was accurate in 16 of 18 patients, although negative PET studies did not exclude the presence of disease, mainly because of the presence of teratoma. In seminoma, a negative 18F-FDG PET study correlated with a favorable clinical outcome. PET was also predictive of the response to salvage chemotherapy and was highly specific for active tumor in both NSGCT and seminoma.

Adult↗

High-dose intrathecal diamorphine for analgesia after Caesarean section.

Forty women undergoing elective Caesarean section under spinal anaesthesia using hyperbaric 0.5% bupivacaine were randomly allocated to receive either 0.5 mg or 1 mg intrathecal diamorphine. All women received diclofenac 100 mg at the end of surgery and morphine via a patient-controlled analgesia system. Oral analgesics were not used. Postoperative analgesia was more prolonged and more reliable in the 1-mg group. Mean time to first analgesia was 10.2 h in the 1-mg group and 6.9 h in the 0.5-mg group, and 45% in the 1-mg group used no morphine, compared with 10% in the 0.5-mg group. Mean morphine consumption over 24 h was 5.2 mg in the 1-mg group and 10.6 mg in the 0.5-mg group. Pain scores all tended to be lower in the 1-mg group but this was only significant at 4 h. There were no serious side-effects. Minor side-effects were common but well tolerated, and the incidence did not differ between the groups. If intrathecal diamorphine is used in combination with rectal diclofenac and without oral analgesia, then 1 mg provides superior analgesia to 0.5 mg without any worsening of the side-effects.

Administration, Rectal↗

Safety of the Canadian blood supply in 1980-85: using a paediatric cohort for risk assessment of human immunodeficiency virus (HIV) infection.

The risk of HIV from transfusions in Canada in the period 1980-85 was estimated, using the information from a transfused paediatric cohort. Children who were transfused between January 1980 and November 1985 at a tertiary care paediatric hospital were contacted by letter. With this notification, HIV testing for recipients was recommended. HIV testing histories were obtained. The number tested for HIV was estimated from the questionnaire responses and from data matching with the HIV-testing laboratory. Cases of HIV infection were identified through multiple sources. In this cohort, 11,028 children were transfused a mean of 21 units. Of the 10,220 living recipients, the estimated proportion tested for HIV was 86% to 91%. Thirty-one cases of HIV infection were identified, representing 0.28% of the cohort but 0.34% of those expected to have been tested. The estimated HIV incidence per 1,000 units transfused ranged from 0.028 [95% CI 0.0007, 0.155] in 1980 to 0.445 [95% CI 0.2592, 0.712] in 1985. This suggests that the risk of HIV from transfusions in Canada continued to rise until the implementation of HIV testing of donors in November 1985.

AIDS Serodiagnosis↗

Establishment of a cytokine-producing anaplastic large-cell lymphoma cell line containing the t(2;5) translocation: potential role of cytokines in clinical manifestations.

A permanent cell line, HSC-M1, was established from a child with advanced CD30 (Ki-1)+ anaplastic large-cell lymphoma (ALCL). Clinical features included irritability, fever, weight loss, tender lymphadenopathy, pneumonitis, neutrophilia, and bone marrow erythrophagocytosis. While HSC-M1 cells exhibited an immunophenotype characteristic of ALCL of T-cell lineage, the cell line also demonstrated features of monocyte-macrophage lineage. Cytogenetic and polymerase chain reaction (PCR) analysis of the HSC-M1 cell line and involved bone marrow demonstrated the characteristic non-random chromosomal translocation t(2:5)(p23:q35). Reverse transcriptase PCR for mRNA expression of cytokines and cytokine receptors showed that HSC-M1 cells expressed the message for multiple cytokines and their receptors. Measurement of cytokine levels in serum samples using enzyme-linked immunosorbent assays showed increased concentrations of several cytokines. The increased levels of some cytokines correlated with disease activity and clinical symptoms. Although spontaneous production by HSC-M1 cells of some of these cytokines was demonstrated, the production of others was only detectable after stimulation with exogenous CD30 ligand. With few exceptions, there was good correlation between serum cytokine levels and cytokines produced by HSC-M1 cells. These findings indicate that cytokine production is a feature of ALCL cells and that some of the clinical manifestations in ALCL may result from cytokines produced by either the malignant or accessory cells.

Chromosomes, Human, Pair 2↗

Compensating for our load of mutations: freezing the meltdown of small populations.

We have investigated the reduction of fitness caused by the fixation of new deleterious mutations in small populations within the framework of Fisher's geometrical model of adaptation. In Fisher's model, a population evolves in an n-dimensional character space with an adaptive optimum at the origin. The model allows us to investigate compensatory mutations, which restore fitness losses incurred by other mutations, in a context-dependent manner. We have conducted a moment analysis of the model, supplemented by the numerical results of computer simulations. The mean reduction of fitness (i.e., expected load) scaled to one is approximately n/(n+2Ne), where Ne is the effective population size. The reciprocal relationship between the load and Ne implies that the fixation of deleterious mutations is unlikely to cause extinction when there is a broad scope for compensatory mutations, except in very small populations. Furthermore, the dependence of load on n implies that pleiotropy plays a large role in determining the extinction risk of small populations. Differences and similarities between our results and those of a previous study on the effects of Ne and n are explored. That the predictions of this model are qualitatively different from studies ignoring compensatory mutations implies that we must be cautious in predicting the evolutionary fate of small populations and that additional data on the nature of mutations is of critical importance.

Animals↗

Antinociceptive and anti-inflammatory properties of an adenosine kinase inhibitor and an adenosine deaminase inhibitor.

Spinal administration of an adenosine kinase inhibitor, alone or in combination with an adenosine deaminase inhibitor, produces antinociception in inflammatory pain tests. In the present study, we examined the antinociceptive and anti-inflammatory effects produced by the peripheral (intraplantar) administration of 5'-amino-5'-deoxyadenosine (an adenosine kinase inhibitor), 2'-deoxycoformycin (an adenosine deaminase inhibitor), and combinations of both agents in the carrageenan-induced thermal hyperalgesia and paw oedema model in the rat. When injected in the ipsilateral paw immediately prior to carrageenan injection, both agents produced antinociception only at the highest dose (1 micromol), whereas a reduction in paw swelling was evident at a lower dose (300 nmol). Significant augmentation in both the antinociceptive and anti-inflammatory effects was seen when 5'-amino-5'-deoxyadenosine and 2'-deoxycoformycin were co-administered in equimolar doses at all dose levels. Both effects were mediated via activation of adenosine receptors, as indicated by blockade by an adenosine receptor antagonist. When administered into the contralateral paw, 1 micromol 5'-amino-5'-deoxyadenosine+1 micromol 2'-deoxycoformycin produced prominent antinociception, indicating a systemic drug activity. There was only a modest reduction in paw oedema in the carrageenan-injected (ipsilateral) paw, suggesting that much of this activity was locally mediated. Reversal of systemic effects on thermal thresholds by an intrathecal adenosine receptor antagonist implicates a spinal site of action in this instance. An ipsilateral administration of 1 micromol 5'-amino-5'-deoxyadenosine, but not 1 micromol 2'-deoxycoformycin, reduced carrageenan-induced c-Fos expression in the spinal dorsal horn, and this was further reduced by the peripheral co-injection of the two agents. These results provide evidence for a predominantly spinal antinociceptive effect and a predominantly peripheral anti-inflammatory effect produced by inhibitors of adenosine kinase and adenosine deaminase.

Adenosine Deaminase↗

Nutricel as an additive solution for neonatal transfusion.

Red cell concentrates stored in additive solutions have limitations for use in the pediatric population. Our survey of 10 pediatric institutions found that Nutricel supernatant was often removed prior to infusion. Examination of packed red cells showed a potassium concentration in excess of 15 mmol/l by day 7 in AS-3 and 40 mmol/l by day 35. Comparison with cells stored in CP2D and CPDA1 showed that the total mass of potassium was highest in AS-3 (5.6 mmol/l) as was the phosphate. The total mass of citrate and glucose was considerably increased in the AS-3 system at 1.73 mmoles and 3.23 mmoles. All had a pH less than 6.6 at day 35. The high concentration of potassium in AS-3 raises concern for the potential for hyperkalemic dysrhythmias during massive transfusion while the citrate load has clinical implications for divalent cation homeostasis during rapid infusion or exchange; the glucose may induce hyperglycemic sequelae.

Erythrocyte Transfusion↗

Eye injuries in patients with major trauma.

BACKGROUND: A study was performed to determine the type and frequency of ocular injuries in patients with major trauma. METHODS: All patients with ocular and adnexal injuries (n = 178) among 1,119 patients admitted with major trauma (Injury Severity Score >15) to the Royal Prince Alfred Hospital from July 1990 to December 1997 were analyzed. RESULTS: Sixteen percent of the major trauma cohort had ocular or orbital trauma. Fifty-five percent of patients with injuries involving the face had ocular or orbital injuries. A range of ocular injuries was seen. Analysis of the major trauma cohort showed that motor vehicle drivers, orbital and base of skull fractures, eyelid lacerations, and superficial eye injuries were strongly associated with vision-threatening injury. CONCLUSION: Patients with major trauma and facial injuries have a high risk of vision-threatening injury. Patients with orbital fractures, base of skull fracture, eyelid lacerations, and superficial eye injuries should be assessed by an ophthalmologist as part of the early management of their trauma to determine whether an ocular injury is present.

Accidents, Traffic↗

Is bone marrow aspiration needed in acute childhood idiopathic thrombocytopenic purpura to rule out leukemia?

OBJECTIVE: To assess the prevalence of leukemia in a series of bone marrow aspiration (BMA) samples collected to confirm provisional diagnoses of acute idiopathic thrombocytopenic purpura (ITP) in children. DESIGN: A retrospective cohort. SETTING: All BMA reports at The Hospital for Sick Children, Toronto, Ontario (a tertiary care pediatric hospital), from January 1, 1984, to May 31, 1996, were reviewed. PATIENTS: Included were BMAs performed to confirm provisional diagnoses of ITP in children (6 months to 18 years of age) with "typical" contemporaneous hematologic features of ITP (platelet count, < or =50 x 10(9)/L; hemoglobin level, > or =100 g/L [6-12 months of age] or > or =110 g/L [> 1 year of age]; white blood cell count, > or =5 x 10(9)/L [6 months to 6 years of age] or > or =4 x 10(9)/L [> 6 years of age]; and neutrophil count, > or =1.5 x 10(9)/L [6 months to 6 years of age] or > or =2 x 10(9)/L [> 6 years of age]). Children with chronic ITP, thrombocytopenia-related chronic conditions, or leukemic blasts on peripheral smears were excluded. MAIN OUTCOME MEASURE: The finding of leukemia in the BMA report was chosen a priori as the primary outcome for the yield of BMA. RESULTS: Four hundred eighty-four BMAs were performed to confirm provisional diagnoses of acute childhood ITP. No diagnoses of leukemia were revealed in the 332 children with typical hematologic features of ITP. The risk of missing the diagnosis of leukemia in this setting is less than 1%. CONCLUSIONS: The yield of BMA for leukemia in this setting is low. Routine BMA is not necessary for children with typical acute ITP.

Adolescent↗

Antinociception by adenosine analogs and inhibitors of adenosine metabolism in an inflammatory thermal hyperalgesia model in the rat.

The present study examined the spinal antinociceptive effects of adenosine analogs and inhibitors of adenosine kinase and adenosine deaminase in the carrageenan-induced thermal hyperalgesia model in the rat. The possible enhancement of the antinociceptive effects of adenosine kinase inhibitors by an adenosine deaminase inhibitor also was investigated. Unilateral hindpaw inflammation was induced by an intraplantar injection of lambda carrageenan (2 mg/100 microl), which consistently produced significant paw swelling and thermal hyperalgesia. Drugs were administered intrathecally, either by acute percutaneous lumbar puncture (individual agents and combinations) or via an intrathecal catheter surgically implanted 7-10 days prior to drug testing (antagonist experiments). N6-cyclohexyladenosine (CHA; adenosine A1 receptor agonist; 0.01-1 nmol), 2-[p-(2-carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadenos ine (CGS21680; adenosine A2A receptor agonist; 0.1-10 nmol), 5'-amino-5'-deoxyadenosine (NH2dAdo; adenosine kinase inhibitor: 10-300 nmol), and 5-iodotubercidin (ITU; adenosine kinase inhibitor; 0.1-100 nmol) produced, to varying extents, dose-dependent antinociception. No analgesia was seen following injection of 2'-deoxycoformycin (dCF; an adenosine deaminase inhibitor; 100-300 nmol). Reversal of drug effects by caffeine (non-selective adenosine A1/A2 receptor antagonist; 515 nmol) confirmed the involvement of the adenosine receptor, while antagonism by 8-cyclopentyl-1,3-dimethylxanthine (CPT; adenosine A1 receptor antagonist; 242 nmol), but not 3,7-dimethyl-1-propargylxanthine (DMPX; adenosine A2A receptor antagonist; 242 nmol), evidenced an adenosine A1 receptor mediated spinal antinociception by NH2dAdo. dCF (100 nmol), which was inactive by itself, enhanced the effects of 10 nmol and 30 nmol NH2dAdo. Enhancement of the antinociceptive effect of ITU by dCF was less pronounced. None of the antinociceptive drug regimens had any effect on paw swelling. These results demonstrate that both directly and indirectly acting adenosine agents, when administered spinally, produce antinociception through activation of spinal adenosine A1 receptors in an inflammatory model of thermal hyperalgesia. The spinal antinociceptive effects of selected adenosine kinase inhibitors can be significantly augmented when administered simultaneously with an adenosine deaminase inhibitor.

Adenosine↗

Recurrent scleritis in lepromatous leprosy.

BACKGROUND: Recurrent immune-mediated scleritis after adequate treatment of leprosy is not well documented in the literature. We describe an Australian resident with unilateral intra-ocular lepromatous leprosy who had persistent non-infectious scleritis. METHODS: A man of Anglo-Indian ancestry initially presented with lepromatous leprosy and unilateral ocular involvement. The affected eye had an interstitial keratitis and a granulomatous anterior uveitis that responded to antileprotics and anti-inflammatory agents. Despite systemic cure with triple antileprotic therapy, he developed recurrent scleritis that required multiple scleral patch grafts for scleral thinning and, subsequently, an enucleation. Histology failed to demonstrate persistent infection, rather a chronic non-granulomatous scleritis, which was probably immune mediated. RESULTS/CONCLUSIONS: This case demonstrates an ocular complication of leprosy that is infrequently reported. Patients with ocular involvement by leprosy are at risk of developing recurrent scleritis despite systemic cure with antileprotics.

Anterior Chamber↗

Genetic characterization and heterologous expression of brochocin-C, an antibotulinal, two-peptide bacteriocin produced by Brochothrix campestris ATCC 43754.

Brochocin-C, produced by Brochothrix campestris ATCC 43754, is active against many strains of the closely related meat spoilage organism Brochothrix thermosphacta and a wide range of other gram-positive bacteria, including spores of Clostridium botulinum. Purification of the active compound and genetic characterization of brochocin-C revealed that it is a chromosomally encoded, two-peptide nonlantibiotic bacteriocin. Both peptides of brochocin-C are ribosomally synthesized as prepeptides that are typical of class II bacteriocins. They are cleaved following Gly-Gly cleavage sites to yield the mature peptides, BrcA and BrcB, containing 59 and 43 amino acids, respectively. Fusion of the nucleotides encoding the signal peptide of the bacteriocin divergicin A in front of the structural genes for either BrcA or BrcB allowed independent expression of each component by the general protein secretion pathway. This revealed the two-component nature of brochocin-C and the necessity for both peptides for activity. A 53-amino-acid peptide encoded downstream of brcB functions as the immunity protein (BrcI) for brochocin-C. In addition, the cloned chromosomal fragment revealed open reading frames downstream of brcI, designated brcT and brcD, that encode proteins with homology to ATP-binding cassette translocator and accessory proteins, respectively, involved in the secretion of Gly-Gly-type bacteriocins.

Amino Acid Sequence↗

Regional cancer cytogenetics: a report on 1,143 diagnostic cases.

The results of studies from a regional cancer cytogenetics diagnostic service are reported. In a 10-year period, 1,143 marrow samples from patients with newly diagnosed leukemia and myelodysplastic syndrome were referred. Successful studies were completed on 992 cases (87%). Among all referred cases, the rates of detection of cytogenetically abnormal clones were 95% for chronic myelogenous leukemia (CML), 54% for acute lymphoblastic leukemia (ALL), 51% for acute myeloid leukemia (ANLL), and 43% for myelodysplastic syndrome (MDS). Of 169 cases of CML studied, 90.5% bore the standard Philadelphia chromosome (Ph), 3.55% had an unusual Ph, and 5.33% were Ph-negative. Among the 59 cases of cytogenetically abnormal MDS, common abnormalities observed were trisomy 8 and changes resulting in loss of material from the long arm of chromosomes 5 and 7, and 20q-. Of the 168 abnormal ANLL, there was a strikingly non-random pattern of aneuploidy, with monosomy 7 and trisomy 8 predominating. Common structural changes observed were changes resulting in loss of material from the long arm of chromosomes 5 and 7, trisomy 8, rearrangements of 11q23, t(15;17), t(8;21), rearrangements of 12q13 and 3q, inversion 16, trisomy 11, Ph, trisomy 21, t(6;9) and t(1;22). The differences between adult and pediatric findings were minor, with the exception of chromosome 5 abnormalities, which were common among adults with ANLL but rare in the pediatric cases. There were 273 ALLs with abnormal cytogenetic findings. There was preferential gain of chromosomes 21, X, 14, 6, 4, 18, 17, and 10 (in decreasing order of frequency) in leukemic clones. Of the 193 ALLs with structural changes, many fell into-well-defined categories with established correlations to FAB subtypes. Common changes in ALL were rearrangements of 9p, 12p, 6q, TCR loci, 11q23, Ig loci, and 8q24, and duplication of 1q, Ph, i(17q), t(1;19), i(9q) and dic(9;12). The detailed documentation of the cytogenetic findings in this relatively large, single-institution study will likely facilitate the further characterization of rare, primary cytogenetic changes associated with leukemias and MDS. From a managed health care perspective, regional cancer cytogenetic services may be cost-effective alternatives to single-institution laboratories.

Adult↗