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Biomedical subjects

P A Rutherford

Publications and source records attributed to P A Rutherford.

At least 19 recordsLinked to original sources
PubMed2003

Medical adjuvant treatment to increase patency of arteriovenous fistulae and grafts.

BACKGROUND: End Stage Renal Failure (ESRF) patients often require either the formation of an arteriovenous (A-V) fistula or an A-V interposition prosthetic shunt for haemodialysis. OBJECTIVES: To determine the effects of adjuvant drug treatment on the patency of fistulae and shunts in patients with ESRF undergoing haemodialysis by assessing the number of thrombotic episodes. SEARCH STRATEGY: Publications describing (or potentially describing), randomised controlled trials of medical adjuvant treatment of patients with ESRF on haemodialysis via A-V fistula or interposition prosthetic A-V shunt, were sought through electronic searches of the Cochrane Peripheral Vascular Diseases Specialised Trials Register (last searched October 2002), and the Cochrane Central Register of Controlled Trials (CENTRAL) database (last searched Issue 3, 2002). SELECTION CRITERIA: Randomised controlled trials of active drug versus placebo in patients with ESRF undergoing haemodialysis via an A-V fistula or prosthetic interposition A-V shunt. DATA COLLECTION AND ANALYSIS: Two reviewers (ADS, PAR), independently assessed trial quality and three (ADS, XE, PAR) extracted data. Information on adverse events was collected from the trials. The outcome measure analysed was the long term fistula, or shunt patency rate. MAIN RESULTS: The overall search identified three randomised controlled trials of aspirin versus placebo with a total number of 173 participants followed up to a maximum of 18 months. The aspirin dosage given was different in each of the trials (325 mg/once daily; 500 mg/once daily; and 160 mg/once daily). The overall result of the meta-analysis favoured treatment with aspirin (Odds Ratio (OR) 0.42, 95% Confidence Interval (CI) 0.20 to 0.86). The overall p-value for the three studies was 0.02. Three ticlopidine (a platelet aggregation inhibitor) versus placebo trials were also identified with a total number of 312 participants. All patients were followed up for one month, and the dose of ticlopidine given was the same for all three studies (250 mg/twice daily). The overall result of the meta-analysis also favoured treatment. (OR = 0.47, 95% CI 0.26 to 0.85). P-value for overall effect was 0.01. One trial in a parallel group design examined the effect of dipyridamole versus placebo, and dipyridamole plus aspirin versus placebo, and followed up patients for eighteen months. The overall result favoured treatment (OR 0.29, 95% CI 0.06 to 1.40) and (OR 0.77, CI 0.19 to 3.19) respectively. REVIEWER'S CONCLUSIONS: The meta-analysis confirmed the beneficial effect of antiplatelet treatment as an adjuvant to increase the patency of A-V fistulae and shunts in the short term.

Arteriovenous Shunt, Surgical↗
PubMed1999

Response to intradialytic parenteral nutrition.

Malnutrition is a major clinical problem in patients receiving maintenance hemodialysis and has adverse effects on survival. Nutritional intervention is indicated, and there is evidence that intradialytic parenteral nutrition can be beneficial. We describe the application of a formal policy regarding the use of intradialytic parenteral nutrition and the beneficial effects on nutrition in the first four patients managed in this fashion. However, the fifth patient did not respond to parenteral nutrition, despite adequate dialysis. This prompted further investigation, and the patient was shown to have extensive gastric malignancy. This report shows that establishing a protocol for intradialytic parenteral nutrition is possible in a medium-sized hemodialysis unit. In these circumstances, nonresponse to this intervention should always be investigated to determine if there is another underlying cause of malnutrition unrelated to renal failure.

Adult↗
PubMed1998

Erythrocyte membrane thiol proteins associated with changes in the kinetics of Na/Li countertransport: a possible molecular explanation of changes in disease.

BACKGROUND: Abnormal erythrocyte Na/Li countertransport is associated with diseases such as essential hypertension and diabetic renal disease. Although it seems unlikely that Na/Li countertransport contributes to any disease process, it may be abnormal because of a change in the cell membrane that is part of the disease process. METHODS: We have shown that Na/Li countertransport kinetics are modified by two types of thiol group. One of these, which we have called 'type 1', is rapidly alkylated by N-ethylmaleimide to give a kinetic pattern similar to that in the above diseases. RESULTS: AtpH 6 and 2 degrees C, both N-ethylmaleimide and iodoacetamide cause the K(m) of Na/Li countertransport to decrease to completion in 300s, with 78% (SEM 6%) of the decrease occurring in 30s. Using these reaction conditions, N-ethylmaleimide reacted with a unique thiol group on a 33-kD protein, blocking its subsequent reaction with biotin maleimide. This 33-kD protein was present in rabbit erythrocytes, which have high levels of Na/Li countertransport, but absent from rat erythrocytes, which have no Na/Li countertransport. Iodoacetyl biotin labelled a 60-kD protein that was specifically blocked by iodoacetamide. CONCLUSION: We suggest that these proteins are members of a cluster of membrane proteins that can modify Na/Li countertransport and may have a functional role in the disease processes.

Adult↗
PubMed1998

Sodium-lithium countertransport: physiology and function.

Current opinions on the relationships between erythrocyte sodium-lithium countertransport kinetics and primary hypertension, hyperlipidaemia and diabetic nephropathy are reviewed. Problems associated with the assay are analysed. Some possible mechanisms that could modify the kinetics of ion exchange are examined. The question of what catalyses sodium-lithium countertransport is discussed, but not answered. Some models are put forward showing how a study of sodium-lithium countertransport kinetics could further our understanding of important disease processes.

Animals↗
PubMed1997

Na-Li countertransport kinetics in the relatives of hypertensive patients with abnormal Na-Li countertransport activity.

Familial factors are believed to be important in determining the high sodium-lithium countertransport activity (defined as >0.40 mmol Li/(h x l cell) at external sodium concentration of 140 mmol/L (Nae 140)) which is observed in a proportion of patients with essential hypertension. However, environmental factors such as pregnancy and dyslipidemia also affect activity. High sodium-lithium countertransport activity (Nae 140) in essential hypertension is mainly due to a low Michaelis constant (Km) and is associated with a high Vmax/Km ratio. In contrast, dyslipidemias affect Vmax. This study aimed to determine if there was evidence that Km and Vmax/Km ratios are influenced by familial factors. Sodium-lithium countertransport kinetics were measured in the 47 first degree relatives of 12 hypertensive probands with abnormal sodium-lithium countertransport kinetics and 35 normotensive control subjects. Sodium-lithium countertransport was measured as Na-stimulated Li efflux from lithium loaded erythrocytes. The relatives had significantly reduced Km and increased Vmax/Km compared to normal subjects. Eleven relatives had high sodium-lithium countertransport activity (Nae 140), associated with low Km and high Vmax/Km. The 14 relatives that were hypertensive had abnormalities of sodium-lithium countertransport kinetics. The results of this study suggest that familial factors are important in determining the Km and Vmax/Km of sodium-lithium countertransport activity. Studies aimed at determining the inheritance of sodium-lithium countertransport and its use as an intermediate phenotype of essential hypertension must measure its kinetic determinants to reduce the risk of confounding effects from other variables.

Adult↗
PubMed1997

Impact of a short stay unit on asthma patients admitted to a tertiary pediatric hospital.

A short stay unit (SSU) was opened at the Children's Hospital, Boston, with the aim of better fulfilling the needs of pediatric patients with straightforward diagnoses. Using historical and simultaneous comparison groups and controlling for disease severity, the opening of the SSU led to a decrease of between 16.5 and 28.4 percent in the mean length of stay for asthma patients without any increase in the rate of hospital readmission.

Acute Disease↗
PubMed1997

Monoclonal antibodies for high-resolution localization of NHE3 in adult and neonatal rat kidney.

Previous immunochemical studies have shown that NHE3 is an apical Na+/H+ exchanger in some renal epithelia. The purpose of the present study was to develop high-affinity, isoform-specific monoclonal antibodies (MAbs) that would be useful for carrying out high-resolution immunocytochemical studies of NHE3 in the adult and neonatal mammalian kidney. Three MAbs were developed to a fusion protein containing amino acids 702-832 of rabbit NHE3. Specificity was established by immunoblotting membranes from NHE-deficient LAP cells that had been transfected with either NHE1,-2, -3, or -4. With the use of high-resolution immunocytochemical techniques, NHE3 was found in vesicles in the apical cytoplasm of proximal tubule cells, as well as in the apical plasma membrane of the proximal tubule, and in both the thin and thick limbs of the loop of Henle. When localized in the 1-day-old rat kidney, NHE3 was first detected in the late stages of the S-shaped body. In later stages of nephron development, the pattern of NHE3 staining was similar to that seen in the adult. This study demonstrates 1) the specificity of three MAbs for Na+/H+ exchanger isoform NHE3; 2) NHE3 is present in an intracellular vesicular compartment in cells of the proximal tubule, consistent with possible regulation by membrane recycling; and 3) NHE3 is expressed on the apical membrane in early stages of the developing nephron.

Aging↗
PubMed1996

Abnormal sodium-lithium countertransport kinetics in immunoglobulin A nephropathy patients and the families: association with hypertension.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. There is an increased prevalence of hypertension, which is an important risk factor for progressive renal impairment, in patients with IgAN. Changes in sodium-lithium countertransport (Na/Li CT) kinetics, particularly high Vmax/Km, have been shown in familial essential hypertension. In this study a high Vmax/Km was observed in IgA probands with hypertension and/or progressive renal impairment. Mean blood pressure was higher in the first-degree relatives of patients with IgAN compared with relatives of normotensive IgAN probands. These hypertensive relatives had an increased Vmax/Vm ratio and a low Km of Na/Li CT. There is a strong correlation of Vmax/Vm (r = 0.82) between the IgA probands and their first degree relatives, suggesting strong familial factors contributing to this Na/Li CT kinetic parameter. An increased Vmax/Km ratio of Na/Li CT seems to be a better marker for familial hypertension than Km alone and may be useful in identifying those patients who are at a greater risk of developing hypertension.

Adult↗
PubMed1996

Thiol group control of sodium-lithium countertransport kinetics in uraemia: evidence of a membrane abnormality affected by haemodialysis.

Uraemia affects erythrocyte metabolism and membrane function but no consistent effect on Na/Li countertransport (CT) has been reported. We report only small differences in Na/Li CT at 150 mmol/l Na over haemodialysis, but major differences in other properties of Na/Li CT. The Km for external sodium and Vmax both increased during haemodialysis but the Vmax/Km ratio, which was greater than normal, was not affected. The thiol reagent, N-ethylmaleimide (NEM), which causes a decrease in Km and Vmax in normal subjects, had no effect on Km in the predialysis erythrocytes. After haemodialysis, the sensitivity of Na/Li CT to NEM was improved. The changes in Na/Li CT kinetics were not related to changes in membrane lipid fluidity or plasma lipids. These observations suggest that uraemia affects a thiol group that controls Na/Li CT kinetics and that haemodialysis temporarily improves this aspect of membrane function.

Aged↗
PubMed1995

Sulphydryl group control of sodium-lithium countertransport kinetics: a membrane protein control abnormality in essential hypertension.

Erythrocyte sodium-lithium countertransport (SLC) is an obligatorily coupled equimolar exchange of intracellular sodium or lithium with extracellular sodium or lithium. SLC is partially inhibited by N-ethylmaleimide (NEM) but only when a transported ion (sodium of lithium) is present in the extracellular medium. In essential hypertensive patients with a strong family history of hypertension the Km of SLC for extracellular sodium was lower and Vmax tended to be higher than in normal controls, but the ratio Vmax/Km gave a much clearer distinction between the two groups. After NEM treatment, the remaining SLC activity in normal individuals had a lower Vmax and Km for sodium but Vmax/Km was not affected. In essential hypertensives the remaining SLC activity after NEM again had lowered Vmax and Km but in these patients the Vmax/Km was much lower than in untreated erythrocytes and was then the same as in normal controls. On the assumption that NEM reacts with a -SH group on a membrane protein that regulates SLC, and that the ratio Vmax/Km reflects a rate constant for binding extracellular sodium to the unloaded carrier, the results suggest that (a) essential hypertensives have an increased rate of sodium binding to the transporter and (b) this is due to abnormal behaviour of a membrane -SH group.

Adolescent↗
PubMed1995

Sodium-lithium countertransport kinetics in IgA nephropathy: relation to plasma lipids and renal impairment.

We have investigated the activity and kinetics of sodium-lithium countertransport (SLC) in patients with IgA nephropathy and their relationship to plasma lipids. Standard SLC activity, the Michaelis constant (Km) and maximum velocity (Vmax) were measured in patients who had IgA nephropathy with either normal serum creatinine (IgA-NRF), or raised serum creatinine (IgA-IRF), and normal subjects (NC). The standard SLC activity was raised in hypertensive patients with IgA-NRF due to a raised Vmax in association with hyperlipidaemia. The Km was significantly lower and Vmax also tended to be lower in IgA-IRF. Km and Vmax were not different in IgA-NRF compared with the NC. There was no difference in the mean standard SLC activity between all three groups. The low Km and low Vmax resulted in a normal standard SLC activity being observed in IgA-IRF which is similar to the situation we have observed in a proportion of diabetic patients with nephropathy. The low Km in patients with IgA nephropathy may be due to inheritance associated with familial essential hypertension or to an acquired change of the kinetics related to a change in the environment of the plasma membrane during the development of renal impairment.

Adult↗
PubMed1994

Nephropathy and changes in sodium-lithium countertransport kinetics in type 2 (non-insulin-dependent) diabetes mellitus.

Previous studies of erythrocyte sodium-lithium countertransport activity, a putative genetic marker of essential hypertension, in Type I and Type II diabetic patients with nephropathy have given conflicting results. We have found changes in the maximum velocity (Vmax) and sodium-affinity constant (Km) of sodium-lithium countertransport in Type I diabetic patients with diabetic nephropathy. In this study, sodium-lithium countertransport kinetics were measured in Type II diabetic patients with established diabetic nephropathy, matched uncomplicated Type II diabetic patients, non-diabetic patients with nephropathy and healthy control subjects. Mean standard sodium-lithium countertransport activity was not significantly increased in either of the groups of diabetic patients compared with the non-diabetic control groups. The Type II diabetic patients with nephropathy had a significantly reduced km and Vmax compared with the uncomplicated diabetic patients and non-diabetic control group. These kinetic changes are identical to those observed in Type I diabetic nephropathy patients. There are similar underlying changes in the erythrocyte plasma membrane with the development of nephropathy in both Type I and Type II diabetes.

Antiporters↗