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Biomedical subjects

J L Anderton

Publications and source records attributed to J L Anderton.

At least 19 recordsLinked to original sources
PubMed1995

Erythropoietin enhances vascular responsiveness to norepinephrine in renal failure.

The mechanism of hypertension induced by recombinant human erythropoietin (rHuEPO) is unclear but may include an increase in peripheral vascular resistance. We studied changes of arterial pressure and plasma endothelin in nine consecutive hemodialysis patients before, and 6 and 12 weeks after, starting rHuEPO. In six patients, changes in cardiac index (CI), stroke index (SI) and total peripheral resistance index (TPRI) were measured by bioimpedance, and forearm vascular responsiveness to intra-arterial norepinephrine (30 to 240 pmol/min) and endothelin-1 (5 pmol/min) were assessed. Six healthy age and sex matched subjects also underwent assessment of forearm vascular responsiveness to norepinephrine and endothelin-1. Treatment with rHuEPO significantly increased hemoglobin and mean arterial pressure (MAP). TPRI also increased by 35 +/- 11%. Plasma endothelin, although elevated basally, remained unchanged. Intra-arterial infusion of norepinephrine caused a maximal increase in forearm vascular resistance (FVR) of 17 +/- 9% before rHuEPO, significantly less than the 32 +/- 5% increase in healthy control subjects (P = 0.04). The response increased to 65 +/- 15% (P = 0.03) after 12 weeks rHuEPO treatment (P = 0.51 vs. controls). Endothelin-1 caused a maximal increase of FVR at 60 minutes of 45 +/- 24% before rHuEPO, which was not significantly different from controls, and tended to decrease with rHuEPO therapy. The response to endothelin-1, but not norepinephrine, correlated inversely with MAP (r = -0.52; P = 0.03) and TPRI (r = -0.51; P = 0.04). In conclusion, these studies show that anemia in chronic renal failure is associated with depressed vascular responsiveness to norepinephrine which is restored by rHuEPO therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

The effect of tenidap on the anti-hypertensive efficacy of thiazide diuretics in patients treated for mild to moderate hypertension.

1. This randomised, placebo-controlled, double-blind, parallel-group study was conducted to assess the effect of tenidap sodium 120 mg, a novel anti-arthritic cytokine modulating drug, on the hypotensive efficacy of the thiazide diuretics hydrochlorothiazide or bendrofluazide. 2. Twenty-three male and female patients, aged 41-78 years, with mild to moderate, uncomplicated, essential hypertension controlled with thiazide diuretic therapy, received either a single daily dose of tenidap sodium 120 mg or matched placebo for 22 days in addition to their diuretic therapy. Changes between baseline and endpoint in supine and standing systolic and diastolic pressures and pulse rate were compared between treatment groups. 3. Daily treatment with tenidap reduced the anti-hypertensive efficacy of the thiazide diuretics. Blood pressure tended to increase marginally and the increase in mean standing diastolic pressure observed with tenidap was significantly greater than the change in the placebo group. All pressures tended to decrease in the placebo group and all endpoint measurements were within 7 mm Hg of baseline in both groups. 4. Treatment-related side effects of mild to moderate severity were reported in two subjects receiving tenidap, but in neither case was treatment discontinued. Two subjects receiving placebo also experienced side effects considered to be treatment-related and both were withdrawn from the study. 5. The results of this study suggest that tenidap may be given to patients treated for mild to moderate essential hypertension controlled with thiazide therapy; however, the patient's blood pressure should be regularly monitored.

Adult↗
PubMed1995

The effect of tenidap on the anti-hypertensive efficacy of ACE inhibitors in patients treated for mild to moderate hypertension.

1. A randomised, placebo controlled, double-blind, parallel group study was conducted to assess the effect of tenidap sodium, a novel cytokine modulating drug, on the stable hypotensive response to the angiotension converting enzyme (ACE) inhibitor enalapril in subjects with mild to moderate, uncomplicated, essential hypertension. 2. Twenty-four male and female hypertensives, aged 33-77 years, received either 120 mg tenidap sodium or matched placebo daily for 22 days concomitantly with enalapril. 3. Mean endpoint supine and standing, systolic and diastolic pressures remained within 10% of baseline in each treatment group. However, the endpoint values were marginally above baseline during double-blind treatment with tenidap and marginally below baseline in the group receiving placebo. The increases in supine and standing systolic pressures in the tenidap group differed significantly from the changes in the placebo group. There were no significant differences between groups in changes in pulse rate. 4. Gastrointestinal side effects of mild to moderate severity attributed to treatment with tenidap were experienced by five subjects, one of whom was withdrawn during the third week of treatment. One subject receiving placebo was withdrawn because of a moderate headache attributed to study treatment. 5. The results of this study suggest that treatment with tenidap may interfere with the anti-hypertensive efficacy of ACE inhibitors. It is recommended that blood pressure should be monitored when tenidap is administered concomitantly with an ACE inhibitor.

Adult↗
PubMed1994

Cystometrography provides a previously unrecognized opportunity for successful management of urinary leaks after renal transplantation.

We report 3 cases of urinary leakage occurring in male kidney transplant recipients within 6 weeks of renal transplantation. Voiding cystometrography showed that high voiding detrusor pressure was the contributing factor. Endoscopic bladder outlet surgery restored normal detrusor voiding pressure and led to spontaneous resolution of urinary leakage without recurrence in all cases.

Adult↗
PubMed1994

Renal haemodynamic effects of bunazosin retard and prazosin in mild to moderately hypertensive patients with normal or moderately impaired renal function.

Effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) were measured in 53 hypertensive patients (26 renally impaired, 27 with normal renal function) before and after treatment with sufficient bunazosin retard or prazosin to control their high blood pressure. After a 3-week placebo run-in period, patients were classified as normal (creatinine clearance > 80 ml/min) or renally impaired (20-55 ml/min), and randomly assigned to bunazosin retard or prazosin. There followed a dose titration (T) phase of 6-7 weeks, and a maintenance (M) phase of 4 weeks. Blood pressure was satisfactorily controlled (sitting diastolic pressure < or = 90 mmHg or decreased by > or = 10 mmHg) by both drugs in both groups. Bunazosin Retard was associated with increases in GFR and ERPF in both normal and renally impaired groups; the increases were statistically significant in the renally impaired group (n = 14). Prazosin was associated with small decreases in both measures in both groups. One patient died of myocardial infarction during the placebo run-in. There were no other serious adverse events. Four patients reported dizziness (2 with each drug). We conclude that with appropriate dose titration, bunazosin retard is well tolerated and preserves renal blood flow when used to treat hypertension in patients with renal insufficiency.

Adolescent↗
PubMed1992

Renal transplant aspiration cytology. Role for simple morphological criteria.

Fine-needle aspiration (FNA) is a well-recognized technique for sampling solid organs. It is used in renal transplantation to clarify the cause of a poorly functioning graft. Differential scoring techniques with respect to peripheral blood cell populations, and immunocytochemistry have been employed in this context. We describe the use of simple morphological criteria alone in renal transplant FNA. We compare these with needle biopsy and clinical parameters and show their value in the detection of active cellular rejection. Their limitations are discussed within the framework of other patterns of transplant pathology.

Adolescent↗
PubMed1992

Oral herpes simplex virus type 1 infection following cadaveric renal transplantation in a young type 1 diabetic female. The role of acyclovir: a case report.

Oral infection with Herpes Simplex Virus (HSV) is a frequent and well documented complication in immunosuppressed individuals including patients on immunosuppressive medication. We report the development of severe oral infection with HSV type 1 in a 34 year old woman with type 1 diabetes mellitus and end stage renal disease (ESRD) following cadaveric renal transplantation at the Western General Hospital, Edinburgh. The role of acyclovir in therapy and chemoprophylaxis is discussed.

Acyclovir↗
PubMed1990

The prevalence of skin disorders in renal allograft recipients receiving cyclosporin A compared with those receiving azathioprine.

Ninety-four renal allograft recipients receiving cyclosporin A (CsA) immunosuppression for up to 4 years were examined for the presence of viral warts, keratoses, and skin cancers. They were compared with a group of 68 recipients on azathioprine who had been matched for duration of immunosuppression and other factors that might influence the occurrence of these lesions. No difference in prevalence of these tumours was found. Viral, bacterial, and fungal infections and other disorders of the skin related to immunosuppression were also noted. Apart from hypertrichosis, which occurred more frequently in the CsA group, no differences were observed. In view of the importance of duration of immunosuppression, the relative effects on the skin of the two drugs will not become apparent until CsA has been in general use for a much longer period of time. In the early stages, however, there appear to be no differences in the dermatological side-effects between CsA- and azathioprine-treated patients.

Adolescent↗
PubMed1990

An evaluation of the efficacy and safety of doxazosin in the treatment of hypertension associated with renal insufficiency.

The efficacy, safety and potential effect on renal function of doxazosin were studied in hypertensive patients with renal impairment. Thirty adult patients with moderate hypertension (DBP between 95-114 mmHg and SBP less than 210 mmHg) and moderately impaired renal function of varying underlying pathology (serum creatinine between 220-640 mumol/l) were given doxazosin, either as monotherapy or part of polytherapy, in an open study. Their average duration of doxazosin therapy was 75 days and the median dose was 2 mg. With doxazosin treatment, the mean supine and standing SBPs were reduced by 15 mmHg and 13 mmHg, respectively. These changes were highly significant (P less than 0.0001). Supine and standing DBPs were also significantly reduced by 16 mmHg and 17 mmHg, respectively (P less than 0.0001). Heart rate was increased by 4 beats/min (mean maximum change); this was statistically, but not clinically, significant. There was a small but significant rise in serum creatinine (mean value, 35 mumol/l) in the group as a whole over a mean period of 75 days. This was considered to be compatible with the natural progression of the underlying renal pathology. Retrospective plotting of the reciprocal of available serum creatinine values against time during the months before doxazosin therapy yielded a linear relationship which supported this hypothesis. One patient withdrew from the study because of a rapid rise in serum creatinine concentration during the placebo run-in phase. Overall, side effects were minimal and did not necessitate reducing the dosage or discontinuing active therapy. The results of this study indicate that doxazosin is effective and well-tolerated in the treatment of hypertension with concomitant renal insufficiency and does not appear to compromise renal function.

Acute Kidney Injury↗
PubMed1989

Effect of pindolol versus atenolol on lipid profile in hypertensive patients.

The effect of pindolol (a beta-blocker with intrinsic sympathomimetic activity, ISA) on fasting plasma lipid profile in 30 hypertensive patients was compared with atenolol (without ISA) in a crossover single blind study. Both drugs lowered blood pressure. HDL-cholesterol increased significantly with pindolol (from 1.15 +/- 0.05 to 1.34 +/- 0.05 mmol/l at 12 weeks, P less than 0.001), but not with atenolol. VLDL-cholesterol increased with atenolol (from 0.57 +/- 0.09 to 0.86 +/- 0.14 mmol/l at 12 weeks, P less than 0.002), while there was no change with pindolol. These changes in lipoprotein profile suggest a more favourable effect of pindolol than of atenolol on lipid profile.

Adult↗
PubMed1989

Value of the gamma camera renogram in the differential diagnosis of acute tubular necrosis and rejection in the early post-transplant period. Comparison with biopsy findings.

A group of 128 consecutive patients was identified on whom renal isotope studies had been performed during the first 2 months after renal transplantation and within 7 days of transplant biopsy. The prospective renogram and biopsy reports were reviewed and graded into 4 categories: severe rejection, predominant rejection, predominant acute tubular necrosis (ATN) and pure ATN. Two extreme patterns of renogram were identified: a sharp rise with a fast decline in the first min, attributed to ATN, and a slowly rising curve with no early peak occurring in severe rejection although not specific to this condition. There was a continuous intermediate spectrum. There was no inter-observer variation in gradings at the 2 ends of the spectrum. In the middle part the difference between 2 independent observers never exceeded more than 1 grade. There was good correlation between the biopsy and renogram gradings, with a discrepancy of more than 1 grade in only 5 patients; 2 of these, with severe rejection on the renogram, showed predominant ATN on biopsy, but the final clinical diagnosis was severe rejection (false positive biopsies). Two patients with biopsies showing severe rejection had a sharp initial up-slope in the renograms but a slower down-slope (over 4 min compared with 1 min in true ATN). With better definition of the criteria these renograms would not have been graded as ATN. There was 1 patient in whom no satisfactory explanation for the discrepancy was found (presumed false positive renogram). When properly defined criteria are used to interpret renograms, this simple test is at least as reliable as renal biopsy in differentiating ATN from rejection in the early post-transplant period, especially in the presence of anuria or severe oligurea.

Acute Kidney Injury↗
PubMed1989

A comparison of cyclosporin versus azathioprine treatment in renal transplants in Edinburgh.

Three year graft survival rates were calculated for 66 patients on cyclosporin and prednisolone immuno-suppression and compared to survival rates for 73 patients on azathioprine and prednisolone. There was a temporary early advantage for the cyclosporin treatment group up to four months post transplant. There was no further significant difference between the two treatment groups with graft survival rate of 81.4% in cyclosporin and 76.7% in azathioprine group at three years post transplant. Fewer of the patients on cyclosporin had acute episodes of rejection. There was no significant difference in serum creatinine or urea at one year, but the haemoglobin level was higher in cyclosporin treated patients. Cyclosporin does not appear to have increased the survival rate significantly in our centre where there is already a high graft survival with azathioprine.

Azathioprine↗
PubMed1988

Radioimmunoassay of beta-thromboglobulin. False high values from frozen plasma samples.

Aliquots of plasma samples assayed after storage at -26 degrees C can show a significantly higher level of measured beta-thromboglobulin (beta-TG) than the corresponding unstored aliquots. Blood spun at the recommended speed of 1,800 X g still contains platelets that will release beta-TG on freezing to yield false results--a point that has not been stressed in the literature. Aliquots of blood plasma spun at either 1,800 X g (low speed [LS]) or 20,000 X g (high speed [HS]) were assayed by radioimmunoassay fresh and after storage at 4 degrees C or -26 degrees C. Storage at -26 degrees C increased mean beta-TG values of fresh or 4 degrees C stored LS samples from 0.78 to 1.94 nmol/L (28-70 ng/mL), whereas all HS mean values were +/- 0.51 nmol/L (between 18 and 19 ng/mL). The authors believe that in addition to the accepted precautions regarding blood sampling and handling, it is essential to stress that for accurate measurement of beta-TG in plasma, samples should be centrifuged at HS or, if this is not feasible, that they be assayed as soon as possible without prior freezing.

Blood Preservation↗
PubMed1988

Effect of nifedipine and mefruside on renal reserve in hypertensive patients.

Changes in glomerular filtration rate and effective renal plasma flow following a protein meal were measured in seven patients with essential hypertension on no treatment and after 6 weeks' treatment with nifedipine and mefruside. Glomerular filtration rate and effective renal plasma flow increased significantly following a protein meal in patients on no treatment (P less than 0.01 and P less than 0.05 respectively). The response to a protein meal was lost following antihypertensive treatment (P less than 0.5 and P less than 0.1 respectively). Although there was some increase in the fasting values of glomerular filtration rate and effective renal plasma flow this was less pronounced and more difficult to demonstrate when only fasting values were compared. We propose that the loss of response to a protein meal is due to recruitment of renal reserve function and that protein meal challenge is a sensitive test for detecting changes in renal function.

Adult↗