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Biomedical subjects

D Churchill

Publications and source records attributed to D Churchill.

At least 55 records · Page 3Linked to original sources
PubMed1994

Hormone replacement therapy and blood pressure in hypertensive women.

There remains anxiety about the use of hormone replacement therapy (HRT) in postmenopausal women with hypertension. We therefore conducted a prospective open study of sequential changes in BP in 75 women referred to our hypertension clinic who required HRT for amelioration of menopausal symptoms. There were no significant differences in mean systolic or diastolic BPs following the introduction of HRT over a median follow-up time of 14 months (interquartile range 8-32 months), despite a significant rise in mean body weight for individual patients which was statistically significant at three, nine and 12 months following the introduction of HRT. No differences in BP were seen in relation to type of menopause, ethnic origin, history of previous pregnancy-induced hypertension or the type of HRT preparation used. Our data suggest that HRT is safe in hypertensive women who should not therefore be denied this therapy if they have menopausal symptoms, although careful supervision is necessary.

Blood Pressure↗
PubMed1993

Double whole-cell patch-clamp characterization of gap junctional channels in isolated insect epidermal cell pairs.

Double whole-cell patch-clamp methods were used to characterize junctional membrane conductances in epidermal cell pairs isolated from the prepupal integument of the flour beetle, Tenebrio molitor. The mean initial junctional conductance in 267 cell pairs was 9.5 +/- 1.0 nS (range 0-95 nS). Well-coupled cell pairs uncoupled spontaneously with a half-time of 7.6 min. Adding 5 mM ATP to the pipette solution stabilized coupling with less than a 50% drop occurring after 30 min. Nonjunctional membrane potential was the major determinant of junctional conductance with transjunctional potential playing a minor role. Junctional conductance approached 0 pA at nonjunctional membrane potentials greater than 0 mV and increased with hyperpolarization. The voltage at half-maximal conductance was -26 mV. The time course of the reversible changes in junctional conductance were slow (< or = 30 sec) with time-dependent decay occurring faster and recovery occurring slower with increasing depolarization. Single gap junctional channel activity was recorded in uncoupling cell pairs and in poorly coupled ATP-stabilized cell pairs. One main single channel conductance was observed in each cell pair. The mean single channel conductances from all cell pairs in this study ranged from 197-347 pS (mean 248 pS). Single channel conductance was linear over the +/- 60 mV transjunctional voltage range tested. A broad range of subconductance states of the main state representing 5% of the total open time of measurable main state events was observed. Single channel activity was strongly dependent on the nonjunctional membrane potential, increasing with hyperpolarization.

Adenosine Triphosphate↗
PubMed1992

The impact of recombinant human erythropoietin on medical care costs for hemodialysis patients in Canada.

Recombinant human erythropoietin (r-HuEPO) is an established and effective therapy for anemia related to end stage renal disease. In addition to its clinical effects, it has been associated with significant improvements in quality of life for anemic hemodialysis patients. The therapy's impact on overall medical care expenditures for these patients remains uncertain, however. In this study, we examine the costs of r-HuEPO as well as potential offsetting reductions in other medical care costs that might result from the therapy. We used data from a randomized clinical trial, a longitudinal study of hemodialysis patients and the clinical literature to estimate the impact of r-HuEPO on transfusion requirements, transfusion-related illness, hospitalization and transplant success for these patients. We estimate that for patients that otherwise would be transfused, the therapy would reduce blood requirements by nearly 10 units per patient annually and hospital use by 8 days per year. In addition, increased transplant success due to r-HuEPO might result in 150 fewer patient months of dialysis treatments each year. Comparing the dollar value of these reductions with the cost of therapy yields a base case net increase in medical care expenditures of $3425 per patient year. Under varying assumptions, the estimates range from a net cost of $8320 to a net saving of $1775 per patient year.

Anemia↗
PubMed1992

A prospective randomized trial of plasma exchange as additive therapy in idiopathic crescentic glomerulonephritis. The Canadian Apheresis Study Group.

Sixty-three patients with crescentic glomerulonephritis (cellular crescents in greater than 50% of glomeruli) were considered for a prospective randomized trial comparing intravenous methylprednisolone, prednisone, and azathioprine with and without plasma exchange. Of 32 patients who fulfilled the inclusion criteria for this study, 16 were randomly assigned to receive drug therapy (control) and 16 to receive plasma exchange as well. The randomization was stratified for initial need of dialysis, and the presence of oliguria and sclerosis. Renal pathology was similar in the two groups of patients. There was no significant difference in the number of patients initially on dialysis who were able to discontinue it during the study (2/7 control v 3/4 plasma exchange), whereas no control but two plasma exchange-treated patients started dialysis during the study. Serum creatinine at randomization was similar in the two groups: 769 +/- 486 mumol/L (8.7 +/- 5.5 mg/dL) in the control group versus 643 +/- 275 mumol/L (7.3 +/- 3.1 mg/dL) in the plasma exchange group. There was no significant difference between the two groups in mean serum creatinine, change in serum creatinine, change in reciprocal, or change in logarithm of serum creatinine at 1, 3, 6, or 12 months following randomization. Power calculation, assuming a 20% difference would be clinically relevant, was 0.94 at 12 months. There was significant morbidity in both groups; there were two deaths within 1 year of randomization, both of pulmonary infection and both in the plasma exchange group. We conclude that plasma exchange offers no additional therapeutic benefit to patients with idiopathic rapidly progressive glomerulonephritis (RPGN) who are not dialysis-dependent at presentation.

Adult↗
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↗
PubMed1990

Early diagnosis of acute myocardial infarction based on assay for subforms of creatine kinase-MB.

Thrombolytic therapy for patients with acute myocardial infarction (AMI) has produced the need for an accurate early diagnostic marker. We previously developed and assessed an assay for the creatine kinase (CK)-MB subforms; assay time is 25 minutes. Plasma MB2 (tissue subform) activity, MB1 (plasma-modified subform) activity, and MB2/MB1 ratio in 56 healthy individuals were 0.61 +/- 0.33 units/l, 0.63 +/- 0.33 units/l, and 0.94 +/- 0.39, respectively. Only one individual had both an MB2 activity greater than 1.0 units/l and an MB2/MB1 ratio of more than 1.5. Similar results were obtained in 50 hospitalized patients without cardiac disease; two of these patients had both an MB2 activity and an MB2/MB1 ratio greater than the cutoff values. Among 49 patients with AMI, MB2 activity and the MB2/MB1 ratio began to increase 2 hours after AMI; the ratio reached a plateau of 3.1 by 4-6 hours. The first available plasma sample was abnormal by the subform assay in 67% of patients and by a conventional MB assay in 27% of patients. Assay sensitivities in samples collected at 2-4, 4-6, and 6-8 hours after AMI were 59%, 92%, and 100% for the subform assay and 23%, 50%, and 71% for the conventional assay (p less than 0.03 versus subform assay at each time interval). False-negative results were obtained by the subform and conventional assays in 15 and 45 samples at a mean of 2.3 and 5.8 hours, respectively. Subform assay provides rapid and reliable diagnosis of AMI within 4-6 hours after the onset of symptoms, which is 6 hours before conventional CK-MB assays are accurate.

Creatine Kinase↗
PubMed1989

Effect of catecholamine-induced cardiac hypertrophy on the force-interval relationship.

Cardiac hypertrophy was induced in adult female Wistar rats following 12 days of daily subcutaneous injections of isoproterenol (ISO). The left atria responded with a 13-14% increase in tissue growth, while the ventricles achieved a 34-39% increased tissue mass. Maximum force generation and twitch characteristics in 1.0 mM external Ca2+ for the left atria or the right papillary muscle were unchanged in the ISO-treated animals. The force-interval relation was determined at 26 degrees C between 0.5 and 120 s. The development of maximum force clearly passed through two phases identified as alpha and beta. To characterize these two processes the data were fitted to a two-term linear combination of exponentials (two-compartment model). The time constant and capacity of each process to contribute to the whole force-interval curve was determined by a four-parameter least square fit method. In control atrial muscle the time constants for the alpha and beta processes were 0.47 and 11.23 s, respectively. The contribution of each process to the total force curve in control atrial muscle was approximately 50% alpha and 50% beta. Following ISO-induced growth the time constants were 0.38 and 13.33 s with a shift of contributions towards 60% alpha and 40% beta. Control papillary muscle from the right ventricle had a similar alpha time constant of 0.49 s compared with atrial muscle but possessed a considerably slower beta time constant of 26.17 s. The contribution of each process to interval-dependent force development was 44.5 and 55.5%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

The variation of sonic plesio-velocity in dose dependent lathyritic rabbit femurs.

It has been hypothesized that the origin of the increased elastic modulus of mineralized bone compared with the demineralized bone matrix is in the higher crosslinking density of the collagen in bone. Osteolathyrism is ascribed to an inhibition of crosslinking of the collagen by the lathyrogen and should be accompanied by a decrease in the elastic modulus of the bone. Dose dependent osteolathyrism was induced by varying the amount of BAPN ingested per day by young New Zealand white rabbits until they were mature. The femurs exhibited dose dependent properties, including wet bone density and sonic plesio-velocity in the radial direction. It was found that there is no minimum critical dose. Even though no overt osteolathyritic stigmata could be observed, both the sonic properties and the wet bone density could be affected at any dose level. The sonic plesio-velocity and the longitudinal elastic modulus decreased with BAPN dose level, most rapidly at the lower dose levels and then less so at higher dosages. Since BAPN acts to inhibit the crosslinking density, it appears that the elastic moduli of bone are dependent on the crosslinking density.

Aminopropionitrile↗
PubMed1984

Study of alleles of the second complement component (C2) on Canadian HLA haplotypes.

Typing for genetic variation in the second complement component C2 was performed on sera from HLA haplotyped Canadian families. Part of the data has been studied and analysed as a population; in addition there is a further random collection of haplotypes bearing the C2*2 allele. In the population data there were 444 separate haplotypes from unrelated parents or other founders: 4.7% of the haplotypes carried the uncommon allele C2*2; one haplotype carried the rare C2*3. Study of C2 2-1 heterozygotes in the population data revealed 59 haplotypes which carried the common C2*1 allele and one which carried a deficiency allele C2*0. The remaining haplotypes carried either C2*1 or else an undetectable C2*0 allele. In the entire data there were 281 meioses informative for C2. The only recombinant between HLA-B and C2 showed the C2 locus to be on the DR side of the B locus. Strong allelic association between C2 *2 and Bw22 and less strong association between C2 *2 and B15 suggested the possibility of two ancestral C2 mutants. Examination of other markers on these and subsequently collected haplotypes do not conflict with this idea since the B15 haplotypes mostly carry C4A *4, C4B *2 whilst the Bw22 haplotypes mostly carry C4A *4, C4B *4. The alternative idea, that there was one original mutant which crossed over from a B15 to a Bw22 haplotype or vice versa is not excluded, however. Since approximate equilibrium has been reached between Bw22 and the HLA-A locus alleles on these C2 *2 bearing haplotypes, we conclude that this mutation is at least 5000 years old. Other haplotypes carrying C2 *2 are assumed to be ancestral recombinants; if this is true, the C2 locus map position between HLA-B and HLA-DR is confirmed. Study of C2 mutation may provide a model for understanding the genetics of some disease susceptibility genes in the HLA region.

Alleles↗
PubMed1980

Comparison of infrared and wet chemical analysis of urinary tract calculi.

Infrared analysis of urinary tract calculi using the system of interpretation of spectra of Oliver and Sweet [1] was compared with qualitative wet chemical analysis. This method of interpretation could be learned quickly and gave reproducible results, but had some limitations. Advantages of the infrared procedure include greater reproducibility. 1-mg sample size, greater sensitivity for oxalate and more uniform sensitivities. Minimum detectable amounts of reference standards varied roughly within 1 order of magnitude, compared with a range of 10(5) for wet chemical procedures. The comparable sensitivity for oxalate and phosphate permits a semi-quantitative approach for infrared. The main problems relate to the detection of magnesium ammonium phosphate and carbonate apatite, and wet chemical tests are recommended in addition, when these compounds are suggested. Calculi from 308 patients were analyzed by infrared. With this system of interpretation of spectra, infrared is considered to be a major advance in methodology for analysis of urinary tract calculi in the clinical laboratory, compared with qualitative wet chemical procedures.

Calcium↗
PubMed1980

Diagnosis of perilymph fistula using ENG and impedance.

The presence of perilymph fistula has been difficult to determine because of the lack of efficient and reliable testing methods. The condition is suspected on the basis of history alone and confirmed by surgery. This paper details a quick, reliable procedure called the ENG fistula test, using impedance bridge for pressure change and electronystagmography to aid the establishment of nystagmus and dizziness. To evaluate this procedure, a combination of tests were performed, including Valsalva maneuver, tragal compression, and pneumatic otoscopy, which were previously considered helpful in the diagnosis of fistula. Of them, Valsalva maneuver and tragal compression proved inconclusive; pneumatic otoscopy proved to be helpful. In comparison, however, the ENG fistula test proved most valuable, with results surgically confirmed in 90.8% of cases in this series. This study involved 74 patients whose primary complaint was dizziness. Only some patients simultaneously experienced hearing lows. Included are 5 patients whose positive ENG fistula test results and 15 whose negative test results were confirmed by surgery. Selected case histories are presented.

Acoustic Impedance Tests↗
PubMed1978

Hemodialysis for methanol intoxication.

We describe nine patients with methyl alcohol poisoning who were treated with hemodialysis. The time from ingestion to dialysis varied from 4 to 100 hours. Predialysis blood methanol levels ranged from 3 to 570 mg/dl. All patients were acidotic and had an increased anion gap. Two patients died, seven recovered, but three had permanent visual impairment. There was little correlation between the blood methanol level or anion gap and visual outcome. The interval from ingestion to treatment appears to be more important than the initial biochemical status. We recommend prompt hemodialysis if the blood methanol level is above 50 mg/dl, when an amount of methanol exceeding the minimal lethal dose (30 ml) is known to have been ingested, when there is evidence of acidosis or when an abnormality has developed in vision, funduscopic examination or mental state. Concurrent therapy with alkali and ethanol is vital.

Adolescent↗