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Biomedical subjects

C Wong

Publications and source records attributed to C Wong.

At least 235 records · Page 13Linked to original sources
PubMed1992

Comparison of subcutaneous and intravenous recombinant human erythropoietin for anemia in hemodialysis patients with significant comorbid disease.

While recombinant human erythropoietin (rHuEPO) is an effective therapy for anemia in renal failure, most published studies concern benefits in relatively healthy hemodialysis patients. The present study compares intravenous and subcutaneous administration of rHuEPO in an unselected group of 128 hemodialysis patients who were randomized to receive rHuEPO in an initial dose of 150 U/kg/week in three divided doses by subcutaneous or intravenous injection. Following a 4-week placebo run-in period, patients received rHuEPO until their hemoglobin was stable between 105 and 125 g/l for 4 weeks and then followed for a further 24 weeks. Eighty-three patients completed the study, 45 in the subcutaneous and 38 in the intravenous group. There was no difference in mean hemoglobin at any stage between subcutaneous and intravenous patients. Mean rHuEPO dose at the time of stabilization was significantly lower in the subcutaneous group compared to the intravenous (205.9 +/- 135.4 vs. 274.1 +/- 142.4 U/kg/week; p = 0.019), mean time to hemoglobin target was 9.9 +/- 4.5 weeks for the subcutaneous group and 11.9 +/- 4.9 weeks for the intravenous group (p = 0.037). Time to stabilization was 14.9 +/- 4.7 weeks for the subcutaneous compared to 17.3 +/- 3.9 weeks for the intravenous group (p = 0.006). Diabetic patients had higher dose requirements for rHuEPO at all time points and required a longer time to reach stabilization than nondiabetics (18.6 +/- 4.6 vs. 15.6 +/- 4.3 weeks; p = 0.016). Quality of life estimated by a disease-specific Kidney Disease Questionnaire improved significantly during rHuEPO therapy in both groups. There was no significant change in dialysis prescription throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

A disease-specific questionnaire for assessing quality of life in patients on hemodialysis.

A disease-specific questionnaire was developed for patients receiving chronic hemodialysis by interviewing patients to determine which aspects of their quality of life were adversely affected by their disease. The final questionnaire contained 26 questions in five dimensions (physical symptoms, fatigue, depression, relationships with others, frustration). The questionnaire demonstrated construct validity when compared with the Sickness Impact Profile, time trade-off technique and an exercise stress test. It was reproducible in stable, placebo-treated patients (correlation coefficient 0.85-0.98 for the 5 dimensions). It was more responsive than other measures in detecting an improvement with erythropoietin therapy in a randomized, placebo-controlled trial. This questionnaire should be useful for the assessment of the effect of various interventions upon the quality of life of hemodialysis patients.

Anemia↗
PubMed1992

Erythropoietin for anaemia in haemodialysis patients: results of a maintenance study (the Canadian Erythropoietin Study Group).

Most published studies of recombinant human erythropoietin (rHuEpo) have been of limited duration and in small patient populations. The present study examines the long-term effects of rHuEpo in 98 haemodialysis patients treated for up to 18 months. All patients had completed a 6 month placebo-controlled study of rHuEpo. Patients previously on placebo (group 1; n = 31) received rHuEpo at an initial dose of 50 U/kg thrice weekly with subsequent dose adjustments to maintain haemoglobin (Hb) in the range 105-120 g/l. Patients previously on rHuEpo (group 2; n = 67) continued on their usual dose with adjustments made to maintain Hb at 105-120 g/l. Haematological parameters were measured every 2 weeks. Quality of life, assessed by a disease-specific kidney disease questionnaire (KDQ), was measured every 6 months. Mean Hb in group 1 increased from 74.2 +/- 11.4 g/l at baseline to 112.9 +/- 12.6 g/l after 12 months of rHuEpo therapy. After 12 weeks of rHuEpo therapy Hb in groups 1 and 2 was indistinguishable. Hb remained constant in both groups throughout the period of follow-up. Mean rHuEpo dose requirements were similar in both groups. At the end of the study the mean intravenous rHuEpo dose in group 1 patients was 176.6 +/- 154.4 and in group 2 patients was 210.0 +/- 144.0 U/kg per week. Access failure was increased during rHuEpo therapy in patients with synthetic grafts (46% versus 7% failures compared to fistulae; P less than 0.001). Group 1 patients receiving rHuEpo had a significant increase in diastolic but not systolic blood pressure despite a 32% increase in overall antihypertensive prescriptions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Synthesis of putrescine under possible primitive Earth conditions.

The synthesis of putrescine was accomplished by decarboxylation of L-ornithine when this amino acid was heated in aqueous solution and in the absence of oxygen. Chromatographic, radioisotopic, and enzymatic techniques were used to demonstrate that one mole of non-radioactive putrescine and one mole of 14CO2 was formed during the heating of L-(l-14C)-ornithine. This work indicates that the synthesis of putrescine can occur starting with ornithine and in conditions that are presumed could have existed on the primitive Earth. The possible significance of these results in the prebiotic molecular evolution is briefly discussed.

Decarboxylation↗
PubMed1991

The use of generic and specific quality-of-life measures in hemodialysis patients treated with erythropoietin. The Canadian Erythropoietin Study Group.

The effect of recombinant human erythropoietin (EPO) on the quality of life and exercise capacity of 118 hemodialysis patients was assessed in a randomized, double-masked placebo-controlled trial. Patients were randomized into three groups: 1) placebo, 2) EPO to achieve a hemoglobin of 95-110 g/L and 3) EPO to achieve a hemoglobin of 115-130 g/L. Patients were followed for six months. Quality of life was assessed using a disease-specific measure [the Kidney Disease Questionnaire (KDQ)] and two generic measures [Sickness Impact Profile (SIP) and the Time Trade OFF (TTO)]. The KDQ contains five dimensions. Functional capacity was assessed with a Six-Minute Walk test (SMW) and an Exercise Stress Test (EST). The mean hemoglobin at six months was 74, 102, and 117 gm/l in groups one, two and three, respectively. There was a marked improvement in quality of life with EPO therapy, but no difference between groups 2 and 3. The outcome measure that was the most responsive to change was the KDQ (P less than .001 for the fatigue and physical symptoms dimensions). The aggregate global (P less than .02) and physical (P = .005) scores of the SIP improved with EPO therapy, the psychosocial score did not. There was no improvement in the TTO. There was an improvement in the EST (P = .02) but not in the SMW. The reproducibility of the outcome measures in placebo-treated patients varied between 0.80 and 0.98 (intra-class correlation coefficient). The correlation among the outcome measures at six months was statistically significant in most cases, as was the correlation of change scores between baseline and six months.

Adult↗
PubMed1991

Effects of visual stimulation on the redistribution of iodine-123-IMP in the brain using SPECT imaging.

A study was performed to validate the assumption that redistribution and clearance of [123I]IMP localization in the brain are unaffected by changes in ambient light levels and visual stimulation occurring after radiopharmaceutical is administered and deposited in the brain. Serial SPECT and planar imaging studies were performed on six healthy, volunteer, adult male subjects under resting, nonactivation conditions. Studies were repeated 7 days later with each subject exposed to strobe light stimulation prior to delayed SPECT procedures at 3 hr. Redistribution and clearance of 123I-IMP in the brain were examined in cortical, subcortical, and cerebellar regions on transaxial slices for the two sets of serial procedures in each subject. Visual stimulation following the initial uptake of [123I]IMP did not affect the distribution or clearance of [123I]IMP in the brain, including the visual cortex, and therefore should not influence the interpretation of delayed SPECT images.

Adult↗
PubMed1990

Quantitative electroencephalographic correlates of cognitive decline in normal elderly subjects.

We obtained a topographic computer analysis of the electroencephalogram in 53 normal elderly subjects. Normal aging was not associated with an increase in slow (delta) activity. However, cognitive performance correlated positively with fast (beta) activity particularly in frontal leads, even after controlling for age, education, occupation, and medication. Five subjects who showed early signs of cognitive decline, had all a marked reduction in beta activity suggesting that this may be an early indication of intellectual loss.

Aged↗
PubMed1990

NMR studies in experimental allergic encephalomyelitis: factors which contribute to T1 and T2 values.

To determine the factors which may alter NMR relaxation times in multiple sclerosis (MS) lesions we measured the proton T1 and T2, specific gravity (SG), and histology in the central nervous system (CNS; 13-19 levels per animal) in the myelin basic protein (MBP) and CNS-induced acute and relapsing EAE models in 44 juvenile Hartley guinea pigs. In the MBP model, T1 is unchanged but T2 is prolonged before symptoms and pathological changes occur. T2 remains prolonged during the acute phase of MBP-induced EAE. In the acute CNS model, T1 and T2 were not different from control despite advanced pathological changes of inflammation and demyelination and changes in specific gravity, indicating a marked change in tissue water content. No single variable, pathological or SG, could predict T1 or T2 values in the CNS-induced model. In active disease in the MBP model, when edema occurs in the presence or absence of parenchymal infiltration, T2 values are increased. However, as the factors which influence tissue NMR characteristics are complex in these MS models, it is likely difficult to infer specific pathological events from MRI findings in patients with MS.

Acute Disease↗
PubMed1990

Intrinsic potential for high fetal hemoglobin production in a Druz family with beta-thalassemia is due to an unlinked genetic determinant.

The mechanism for elevated production of fetal hemoglobin (Hb F) in a Druze patient with beta zero-thalassemia intermedia was investigated. Heterozygous family members exhibited normal Hb F levels, suggesting that the increase in gamma-gene expression in the propositus may be partly due to anemic stress. Erythroid progenitors of these family members cultured in vitro [burst forming units (erythroid); (BFUe)] showed elevated synthesis of Hb F, indicating the existence of a genetically determined intrinsic capacity for high Hb F production in this family. The propositus was found to be homozygous for a IVS2-position 1 mutation, on the background of Mediterranean haplotype I, which is not known to be linked to high Hb F production. Moreover, extensive molecular studies of the beta-globin gene cluster, including sequence analysis of the promoter regions of the gamma-globin genes, did not reveal any cis- actin mechanism that could account for the high Hb F production in the propositus. A young niece of the propositus with beta zero-thalassemia major was recently discovered, who was homozygous for the same beta-globin allele and haplotype as the propositus. However, unlike her uncle, she does not have a high Hb F level and presents with a severe clinical course. Her inability to produce high Hb F suggests that the genetic determinant for increased gamma-gene expression in the propositus is unlinked to the beta-globin gene cluster.

Adolescent↗
PubMed1990

Diffusion of Mn2+ ions into liposomes mediated by phosphatidate and monitored by the activation of an encapsulated enzymatic system.

Transbilayer diffusion of Mn2+ ions occurred in liposomes formed from dipalmitoyl-phosphatidylcholine or egg-yolk phosphatidylcholine and egg-yolk phosphatidate (molar ratio 2:1) containing DNA and DNase I within their aqueous compartments. Cation diffusion was demonstrated by the hydrolytic activity of DNase I, activated by the Mn2+ ions that diffused into the vesicles, and this was confirmed by light scattering. Phosphatidate, a cone-shaped lipid which has been synthesized under simulated prebiotic conditions, was necessary for cation diffusion across the liposome membranes. Such liposomes represent a simple precellular system that interchanges cations with the surroundings and provides a microenvironment for enzymatic reactions, as evidenced by the hydrolysis of DNA by DNase I inside these closed lipid compartments.

Cations↗
PubMed1990

The salt-induced dissociation and inactivation of a mammalian enolase: evidence for the formation of active monomers.

The gamma gamma isozyme of rabbit enolase was labeled with fluorescein and the effects of NaClO4 on both enzymatic activity and fluorescence polarization were studied. NaClO4, but not NaCl, dissociates and partially inactivates the enzyme. If dissociation is prevented, either by the addition of substrate or by covalently crosslinking the enzyme, inactivation is also prevented. Analysis of the time and concentration dependence of inactivation and dissociation shows that the decrease in activity is a two-step process: D in equilibrium 2M in equilibrium 2M*. Both monomeric forms of the enzyme are catalytically active.

Animals↗
PubMed1990

Developmental changes in the clustering pattern of sleep rapid eye movement activity during the first year of life: a Markov-process approach.

Findings are presented in support of the hypothesis that the tendency of sleep rapid eye movement (REM) activity to group into burst structures changes with age during the first year of life in normal infants. Specifically, by assuming a markovian model for the generation of 1 sec long units of REM activity, it is shown that the propensity of those units to develop a sustained clustering pattern may increase during the first 2 months, possibly reaching a plateau at about 4 months. On the other hand, the overall density of REM activity units may continue to increase beyond that point in time.

Age Factors↗
PubMed1990

Characterization of mutations in the factor VIII gene by direct sequencing of amplified genomic DNA.

In order to search for mutations resulting in hemophilia A that are not detectable by restriction analysis, three regions of the factor VIII gene were chosen for direct sequence analysis. Short segments of genomic DNA of 127 unrelated patients with hemophilia A were amplified by polymerase chain reaction. A total of 136,017 nucleotides were sequenced, and four mutations leading to the disease were found: a frameshift at codon 360 due to deletion of two nucleotides (GA), a nonsense codon 1705 due to a C----T transition, and two missense codons at positions 1699 and 1708. The first missense mutation (A----T) results in a Tyr----Phe substitution at a putative von Willebrand factor binding site. The second results in an Arg----Cys substitution at a thrombin cleavage site. In addition, we identified three rare sequence variants: a silent C----T transition at codon 34 which does not result in an amino acid change, a G----C change at codon 345 (Val----Leu), and an A----G change at the third nucleotide of intron 14. Direct sequence analysis of amplified DNA is a powerful but labor-intensive method of identifying mutations in large genes such as the human factor VIII gene.

Base Sequence↗
PubMed1990

Molecular cloning of a human macrophage lectin specific for galactose.

The murine Mac-2 protein is a galactose- and IgE-binding lectin secreted by inflammatory macrophages. We describe here the cloning and characterization of a cDNA representing the human homolog of Mac-2 (hMac-2). The amino acid sequence derived from the hMac-2 cDNA indicates that the protein is evolutionarily highly conserved, with 85% of its amino acid residues being similar to those in the murine homolog. This conservation is especially marked in the carboxyl-terminal lectin domain. The amino-terminal half of the protein is less conserved but still contains the repetitive proline-glycine-rich motif seen in the mouse protein. hMac-2 synthesized in vitro is recognized by the M3/38 monoclonal antibody to Mac-2 and binds to the desialylated glycoprotein asialofetuin and to laminin, a major component of basement membranes. These findings are discussed in the context of the potential functions of hMac-2.

Amino Acid Sequence↗
PubMed1990

Metals and the liver in Alzheimer's disease. An investigation of hepatic zinc, copper, cadmium, and metallothionein.

Significant alterations of tissue metal levels have been reported in Alzheimer's disease (AD). Because the liver is intimately involved in metabolism and storage of metals, it may provide a useful site for study of these metals in AD. This study compares livers in AD and controls in their concentrations of zinc, copper, cadmium, and metallothionein, a metal-binding protein important in regulation of metal metabolism. Liver tissue was obtained from 17 patients with AD and 17 age- and sex-matched controls within 12 hours of death and stored at -70 degrees C. Neuropathologic confirmation of diagnosis was available in all cases. Liver homogenates (20%) were used for metal analysis by atomic absorption spectroscopy after wet digestion. Cytosolic metallothionein levels were quantitated by the cadmium or silver saturation method. A significant decline in body and liver weight was found in patients with AD, with no significant change in liver protein or DNA concentration. Total hepatic cadmium (P less than .001) and zinc (P less than .030) concentrations were significantly elevated in AD. The Sephadex G75 chromatographic profile was altered in AD with reduction in zinc bound to metallothionein fractions and increased binding to high molecular weight fractions. These data suggest that the metabolism of cadmium and zinc is altered in AD.

Aged↗
PubMed1990

Size and subdomain architecture of the glucan-binding domain of sucrose:3-alpha-D-glucosyltransferase from Streptococcus sobrinus.

Mild trypsin proteolysis of Streptococcus sobrinus sucrose:3-alpha-D-glucosyltransferase (GTF-I) reduced most of the enzyme to small products but left a few large fragments undigested. The digest had no glucosyl transfer activity, but several digestion products had an affinity for glucan equivalent to that of the native enzyme. The glucan-binding fragments ranged in size from 17 to 60 kilodaltons (kDa), with a particularly prominent 42-kDa fragment. The largest of these (60 kDa) appears to be the full extent of the domain since it increases in abundance when the enzyme is protected with glucan during proteolysis. The presence of smaller fragments with glucan-binding function and intact tertiary structure indicates that the full domain must be built on glucan-binding subdomains. Among the range of glucan-binding fragments, only the 42-kDa segment could be satisfactorily purified. It was subjected to N-terminal sequence analysis and, because of some ambiguity, was also subjected to chymotrypsin digestion and sequence of several chymotryptic peptides. The sequence data established that the 42-kDa domain fragment is initiated approximately two-thirds into the 170-kDa enzyme in a region previously identified as a segment of the gene that includes the glucan-binding domain (J. J. Ferretti, M. L. Gilpin, and R. R. B. Russell, J. Bacteriol. 169:4271-4278, 1987). The site is approximately 60 kDa from the C terminus and covers a region characterized by extensive amino acid sequence repeats. The data are discussed in the context of the size range of the glucan-binding fragments and subdomain architecture of the full glucan-binding domain.

Amino Acid Sequence↗
PubMed1990

Evidence for involvement of a Robertsonian translocation 13 chromosome in formation of a ring chromosome 13.

We have used molecular and cytogenetic methods to study the derivation of a ring chromosome 13 in the fetus of a woman mosaic for a translocation chromosome 13. DNA analysis showed that the translocation chromosome was a Robertsonian translocation, not an isochromosome. We suggest that the ring is derived from the translocation chromosome by breaks in both long arms and subsequent reunion, r(13) (q12q14).

Abnormalities, Multiple↗