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Biomedical subjects

R Wilkinson

Publications and source records attributed to R Wilkinson.

At least 145 records · Page 8Linked to original sources
PubMed1991

Erythrocyte sodium, potassium and sodium fluxes with cell and subject ageing.

In young subjects erythrocyte sodium was lower in females than in males. In males juvenile erythrocyte sodium decreased with subject age whereas in females aged erythrocyte sodium increased with subject age. Therefore, the difference in erythrocyte sodium between young male and female subjects was not observed in the elderly. These differences in erythrocyte sodium appeared to be mainly due to differences in the sodium pump rate constant. In juvenile cells from young subjects the sodium pump rate constant was related to the ouabain sensitive sodium flux rate, but not in elderly subjects, suggesting disturbed control of cell sodium in the latter group. Juvenile erythrocytes had a higher potassium content in elderly than young subjects but this was mainly in the 'frail' hospitalised elderly and it decreased more rapidly with cell ageing. This could indicate more active erythrocytes entering the blood in elderly subjects and then ageing more rapidly. Differences between young and elderly subjects in erythrocyte sodium, potassium and sodium pump rate constant were more marked in the 'frail' hospitalised elderly.

Adult↗
PubMed1991

The effects of two centrally-acting anti-hypertensive drugs on the quality of life.

The objectives of this study were to compare the effects of two centrally-acting antihypertensive drugs on measures of quality of life in a three-month double-blind trial of hypertensive patients randomized to methyldopa (n = 79) or rilmenidine (n = 78). We studied men and women aged over 21 y attending eight hospital out-patient clinics in the United Kingdom. They had average diastolic blood pressures between 95 and 110 mm Hg and systolic pressures below 210 mm Hg after a 4-week placebo run-in period. The doses ranged from 1 to 2 mg daily of rilmenidine and 500 mg to 1 g of methyldopa. Hydrochlorothiazide (25 mg daily) was added after 8 weeks when the diastolic blood pressure remained at 90 mm Hg or more in 29% of patients on rilmenidine and 35% of those on methyldopa. Quality of life was assessed from self-completed questionnaires using standardized instruments. Both drugs reduced blood pressure, but at the end of the trial the fall in the methyldopa group (19.3/13.0 mm Hg) was significantly greater than in the rilmenidine group (13.2/10.0 mm Hg). Ten patients in the methyldopa group withdrew from the trial compared with three in the rilmenidine group, primarily because of adverse effects. In both groups there was a significant increase in the overall reporting of adverse effects. Reports of dry mouth increased on both drugs, and sleepiness on rilmenidine but not methyldopa. There was no significant difference between the drugs in the overall reporting of adverse effects or of individual adverse effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1991

Lipid lowering therapy leads to a reduction in sodium-lithium countertransport activity.

Erythrocyte sodium-lithium countertransport (SLC) was measured in 17 patients with either combined hyperlipidaemia or hypercholesterolaemia before and after lipid lowering therapy. Before treatment SLC related to the serum triglyceride level and was increased in combined hyperlipidaemia. After treatment the SLC had returned to normal and the change in SLC was related to the change in serum triglyceride levels. Raised SLC is associated with essential hypertension but is not related to blood pressure. Therefore, the association of raised SLC with hyperlipidaemia and essential hypertension appears to have different underlying mechanisms.

Adult↗
PubMed1991

Purification and initial characterisation of koala immunoglobulins.

The production of koala immunoglobulins (Ig) was elicited by the immunisation of a koala (Phascolarctos cinereus) with bovine serum albumin. This Ig was then purified using the highly specific techniques of affinity chromatography. The purified protein was compared with a "potential" koala Ig protein which was subsequently purified by Protein G chromatography and both proteins were further characterised by agarose/SDS-PAGE and immunoelectrophoresis. Results indicate that koalas do produce Ig in response to antigen challenge, koala Ig has a higher net negative charge than that seen in most other mammals and possibly two subclasses of IgG and IgM are present in normal koala serum.

Animals↗
PubMed1991

Rapid inter-strain comparison by pyrolysis mass spectrometry of coagulase-negative staphylococci from persistent CAPD peritonitis.

Pyrolysis mass spectrometry (PyMS) was used as a method of rapid inter-strain comparison of 19 isolates of coagulase-negative staphylococci from episodes of CAPD peritonitis. Thirteen isolates were from multiple, but distinct, episodes of peritonitis in 6 patients and the remaining 6 isolates were from 6 patients with single episodes. The results, expressed in terms of identity/non-identity of strains, were compared with those obtained using an established typing system comprising an extended antibiogram, determination of biotype and plasmid profile analysis. The PyMS results for inter-strain comparison were in agreement with the reference typing scheme results. PyMS can be used in this setting to rapidly obtain evidence that persistent infection is/is not likely to be due to the same organism, although it cannot be used for formal typing. The results by both methods showed that serial, apparently distinct, episodes of peritonitis over periods as long as 120 days may be due to the same strain of coagulase-negative staphylococcus. Clinically based distinctions between recurrence of infection (same strain) and re-infection (different strains) may not always be supported by the microbiological evidence.

Coagulase↗
PubMed1991

Osmoregulation of thirst and vasopressin release in severe chronic renal failure.

Subjects with severe chronic renal failure (CRF) have higher plasma concentrations of arginine vasopressin (AVP) than normal subjects, and some develop severe thirst. Eight patients with CRF and seven matched controls underwent hypertonic saline infusion to explore the relationship of thirst and plasma AVP with plasma osmolality. Differences in urea concentration between the two groups were controlled for by correcting measured osmolality to a urea of zero. Linear regression analysis of the relationships between plasma AVP and thirst with plasma osmolality (corrected for urea) was performed. Mean results were: control, pAVP = 0.26 (pOsmc - 283.7) versus CRF, pAVP = 0.72 (pOsmc - 282.0); and control, thirst = 4.0 (pOsmc - 279.4) versus CRF, thirst = 3.5 (pOsmc - 281.8). The apparent sensitivity (slope) of AVP release was greater in severe CRF than in normal controls (P = 0.04). There was no significant difference between the groups in thirst sensitivity, threshold for thirst onset and threshold for AVP release. Osmoregulated thirst was normal in severe CRF, but increasing osmolality leads to higher concentrations of AVP than would be expected.

Adult↗
PubMed1991

Captopril renography in the diagnosis of renovascular disease.

Several investigators have reported methods for the use of renal scintigraphy in the diagnosis of renal artery stenosis. We report the experience of Duke University Medical Center, and offer some suggestions for standardizing and optimizing the use of this potential screening tool. We evaluated 140 clinically selected hypertensive adults with postcaptopril renal scintigraphy (renography), pre- and postcaptopril peripheral renin activity, and conventional renal arteriography. Postcaptopril renography (using 99mTc-diethylenetriaminepentaacetic acid (DTPA) to measure glomerular filtration and [131I]iodohippurate to measure renal plasma flow) was considered abnormal if one kidney contributed 47% or less of total activity. Postcaptopril renin was considered elevated if it was at least 4 ng/mL/h. Renovascular disease was defined as 50% or greater main renal artery stenosis. Of 140 subjects, 31 (22%) had significant renovascular disease. Captopril-stimulated DTPA renography suggested asymmetric function in 24 (74%) of these, but was also abnormal in 61 of 109 (56%) with normal renal arteries. Captopril-stimulated hippuran renography performed in a similar manner. Captopril-stimulated renin activity was elevated in only 58% of subjects with renal artery stenosis, and had a false positive rate of 24%. These data differ from reports from other centers, perhaps due to differences in renography methods, criteria for interpretation of renography, and/or patient selection criteria.

Adult↗
PubMed1991

Haemodialysis: effects on white and red blood cell sodium content and transport.

A circulating sodium pump inhibitor, released in response to volume expansion, may, by increasing intracellular sodium concentrations, be responsible for some of the features of the uraemic state. Haemodialysis, by correcting volume overload, would be expected to be associated with a decrease in intracellular sodium towards normal. The effects of a haemodialysis session on leukocyte (WBC) sodium content and transport have not been described and there are conflicting reports of the effects of haemodialysis on erythrocyte (RBC) sodium content and transport. We have measured sodium (NaWBC/RBC) and potassium content (KWBC/RBC), net ouabain-sensitive sodium flux rate (FR) and sodium flux rate constant (RC) before and after a standard haemodialysis session in 20 stable hospital haemodialysis patients. In leukocytes (n = 18), sodium (P = 0.078), FR (P = 0.006), and RC (P = 0.071) decreased over dialysis, whereas in erythrocytes sodium increased (P less than 0.001, n = 19) and RC declined (P = 0.002, n = 18). Although in opposite directions in RBC and WBC, the changes in sodium were toward normal in both cell types. Changes in intracellular sodium content and transport did not correlate with changes in measures of ECF volume or biochemical efficiency of dialysis. We conclude that haemodialysis does affect cell sodium content and transport, but in different ways in different cell types. There was no evidence that haemodialysis removed a sodium pump inhibitor. The use of RBC or WBC as 'model' cells to study sodium transport in uraemia is of questionable validity.

Adult↗
PubMed1991

Differentiation of regional perfusion and fatty acid uptake in zones of myocardial injury.

The relative myocardial distribution of 201Tl and modified fatty acid (123I-labelled 3-methyl-p-[iodo]-phenyl pentadecanoic acid, MFA) was determined in eight patients with unstable angina (UA) and six patients with acute myocardial infarction treated with reperfusion therapy within 4.1 h (MI). The results of radionuclide imaging were correlated with coronary angiography and quantitative left ventriculography performed within 10 days of the radionuclide procedures. Zones of injury were identified as areas with diminished 201Tl uptake distal to sites of coronary narrowing. A nearly parallel reduction in regional fatty acid concentration was observed in these areas. Comparison of the regional distributions of the two agents revealed subtle differences in their distributions in the ischaemic zones. Three patterns were recognized: (a) MFA uptake greater than Tl (MFA greater than Tl), (b) matched decrease of MFA and Tl (MFA = Tl), (c) MFA uptake less than Tl (MFA less than Tl). Seven of eight patients with UA had normokinesis or hypokinesis on quantitative left ventriculography. Five of the seven showed the MFA greater than Tl pattern, while one had the MFA less than Tl pattern and one had the MFA = Tl pattern. The eighth patient with UA had akinesis and the MFA = Tl pattern. All six patients with acute infarction had akinesis on ventriculography. One of these patients had the MFA greater than Tl pattern, two had the MFA = Tl pattern and three had the MFA less than Tl pattern. These results suggest that fatty acid and thallium have grossly similar distributions in areas of acute myocardial ischaemia. On careful inspection, zones of slight relative excess fatty acid concentration are observed more often in areas of acute ischaemia with normal wall motion.

Adult↗
PubMed1991

Disturbance of osmoregulated thirst and vasopressin secretion in thyrotoxicosis.

OBJECTIVE: To assess the effect of untreated thyrotoxicosis on osmoregulated thirst sensation and AVP secretion. DESIGN: Measurements were made at 30-minute intervals while untreated thyrotoxic patients were given sodium chloride 855 mmol/l intravenously for 2 hours followed by water drinking ad libitum for 2 hours. The protocol was repeated when the patients were euthyroid. PATIENTS: Eight newly diagnosed thyrotoxic patients were studied. MEASUREMENTS: Thirst sensation (visual analogue scale), plasma osmolality, AVP and plasma renin activity were measured. RESULTS: Prior to osmotic stimulation and after plasma osmolality had been returned to normal by drinking water, thirst sensation was increased in the thyrotoxic state. Plasma AVP showed an exaggerated response to hypertonic saline in the patients when they were thyrotoxic. Increasing plasma osmolality produced a linear increase in thirst sensation and log linear increase in plasma AVP. However, in the thyrotoxic state both these relations were altered. The apparent osmolar thresholds for onset of thirst sensation and AVP release were similar (281 and 280 mosm/kg respectively) and were reduced similarly in the thyrotoxic state (269 and 274 mosm/kg respectively). CONCLUSIONS: The osmostat mechanisms which regulate thirst sensation and AVP release are reset in the thyrotoxic state. The responses of thirst sensation and of plasma AVP to increasing plasma osmolality are altered similarly, suggesting that thyrotoxicosis affects both homeostatic functions by a common mechanism.

Adult↗
PubMed1991

Erythrocyte hydration in normal human pregnancy.

OBJECTIVE: To determine whether the fall in plasma osmolality in normal human pregnancy resulted in cellular overhydration. DESIGN: The changes in erythrocyte hydration, potassium and total osmoles in response to a decrease in osmolality in vitro and associated with the fall in plasma osmolality in normal pregnancy were determined. SUBJECTS: Fifty-one women were studied serially during pregnancy and again 20 weeks after delivery. RESULTS: Erythrocytes from pregnant women exposed in vitro to a 29.9% osmolality decrement had a 28.5% increase in cell hydration. At 14 weeks gestation although plasma osmolality was lower than after delivery (281.1 vs 291.6 mosmol/kg; P less than 0.001) both erythrocyte hydration (1.83 l/kg dry weight cells) and potassium (264 mmol/kg) contents were reduced from the nonpregnant values (1.88 l/kg; P less than 0.01; 272 mmol/kg; P less than 0.001). For the remainder of pregnancy plasma osmolality remained at this lower level but cell hydration and potassium both increased to values at 38 weeks gestation that were greater than in the nonpregnant state (1.92 vs 1.88 l/kg; 287 vs 272 mmol/kg). CONCLUSIONS: These findings suggest that a loss of cell osmoles may be a primary event affecting cell hydration in pregnancy and plasma osmolality is then reduced to maintain normal cell hydration. Subsequent changes in cell hydration were led by changes in intracellular osmole content.

Erythrocytes↗
PubMed1991

Polyclonal human immunoglobulin G labeled with polymeric iron oxide: antibody MR imaging.

Human polyclonal immunoglobulin (Ig) G was attached to a monocrystalline iron oxide nanocompound (MION), a small superparamagnetic probe developed for receptor and antibody magnetic resonance (MR) imaging. The resulting complex, MION-IgG, had a slightly negative surface charge, a molecular weight of 150-180 kDa, and 0.36 microgram of IgG attached per milligram of iron. After intravenous administration of MION-IgG to normal rats, most of the compound localized in liver, spleen, and bone marrow. In an animal model of myositis, MION-IgG caused reduced signal intensity (most apparent on T2-weighted spin-echo and gradient-echo images) at the site of inflammation. No change in signal intensity existed after an injection of unlabeled MION. Site-specific localization of MION-IgG was corroborated with scintigraphic imaging with indium-111 IgG and MION-In-111-IgG and was confirmed histologically with iron staining. These results indicate that antibody MR imaging is feasible in vivo. Target-specific and antibody MR imaging could be easily extended to other applications, including detection of cancer, infarction, and degenerative diseases.

Animals↗
PubMed1991

A comparison of induction and maintenance therapy for acute nonlymphocytic leukemia in childhood: results of a Pediatric Oncology Group study.

Two hundred fifty-six children with previously untreated acute nonlymphocytic leukemia (ANLL) were evaluated on a Pediatric Oncology Group (POG) phase III randomized trial of both induction and continuation chemotherapies. Induction therapy compared vincristine, cytarabine, and dexamethasone (VADx) with daunorubicin, cytarabine, and thioguanine (DAT). The complete remission (CR) rate using DAT was superior (82% v 61%, P = .02). Postremission therapy consisted of either "standard" two-cycle therapy or a more intensive four-cycle regimen given for 2 years. Overall, there was no difference in outcome for patients randomized to either continuation regimen. The overall complete continuous remission rate (CCR) for the "best" induction/continuation therapy combination at 2 years was .50 (SE = .06), at 3 years was .35 (.04), and at 4 years was .34 (.05). Analysis of selected clinical and laboratory parameters demonstrated differences in induction responses favoring DAT induction but did not impact eventual disease-free survival. There were two subgroups of patients who responded better to four-cycle continuation therapy. These were patients with French-American-British (FAB) M1/M2 (2-year CCR was .20 v .44, P = .01) and patients older than 10 years at diagnosis (.32 v .62, P = .004).

Agranulocytosis↗
PubMed1991

Variation in applied force during insertion of cemented femoral prostheses.

Information is presented on forces applied to cemented prostheses during insertion. An instrumented femoral pusher was used to collect information during simulated operations on cadavers while using a laboratory test rig and during live surgery. Surgeons using flanged or collared prostheses tend to apply more force than those using collarless prostheses. There is a tendency for abrupt changes in applied force to occur when: 1) clearing cement; 2) easing hand discomfort; and 3) testing cement consistency. Tests showed that an overall impression of the force applied could be obtained from a laboratory simulation, but that clearing cement and testing cement were not modelled by this method. We discuss the implications of our observations in terms of prosthesis fixation and training of staff.

Biomechanical Phenomena↗
PubMed1991

Imaging focal sites of bacterial infection in rats with indium-111-labeled chemotactic peptide analogs.

Four DTPA-derivatized chemotactic peptide analogs: ForNleLFNleYK-DTPA (P1), ForMLFNH(CH2)6NH-DTPA (P2), ForNleLFK(NH2)-DTPA (P3), and ForNleLFK-DTPA (P4), were synthesized and evaluated for in vitro bioactivity and receptor binding. The peptides were radiolabeled with 111In by transchelation and their biodistribution determined in rats at 5, 30, 60 and 120 min after injection. Localization at sites of infection was determined by scintillation camera imaging in animals with deep-thigh infection due to Escherichia coli. Images were recorded from 5 min to 2 hr after injection. All peptides maintained biologic activity (EC50 for O2-production by human PMN's: 3-150 nM) and the ability to bind to the oligopeptide chemoattractant receptor on human PMN's (EC50 for binding: 7.5-50 nM); biologic activity and receptor binding were highly correlated (r = 0.99). For all the peptides, blood clearance was rapid (half-lives: 21.5, 33.1, 31.6, and 28.7 min for P1, P2, P3, and P4, respectively). Biodistributions of the individual peptides were similar with low levels of accumulation in the heart, lung, liver, spleen, and gastrointestinal tract. In the kidney, P1 had much greater accumulation than other organs. All peptides yielded high quality images of the infection sites within 1 hr of injection. This study demonstrates that 111In-labeled chemotactic peptide analogs were effective agents for the external imaging of focal sites of infection.

Animals↗