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Biomedical subjects

R A Robson

Publications and source records attributed to R A Robson.

At least 37 records · Page 2Linked to original sources
PubMed1997

OKT3 for the treatment of steroid-resistant acute renal allograft rejection.

OKT3 (Orthoclone) was first used in this unit on February 25, 1987. Up until March 31, 1996, 153 patients had a total of 163 transplants. Fifty of these patients who received 53 transplants (28 male, mean age 37.5 years, 48 cadaveric donors), were treated with OKT3 for steroid-resistant acute rejection. Forty-nine graft biopsies were undertaken and 47 showed acute rejection. In the other 4 episodes a clear-cut clinical and laboratory diagnosis of severe rejection was made. OKT3 (5 mg i.v.) was started at a median of 19 days following transplantation and was successful in reversing 43 of 51 (84%) episodes of steroid-resistant acute rejection. Of those treated, the patient and graft survival at 1 year was 86 and 69%, at 3 years 82 and 64% and at 5 years 79 and 61%, respectively. Adverse effects were common. Four patients died from sepsis within the first 3 months after transplantation. OKT3 was effective in reversing 84% of steroid-resistant acute rejection episodes.

Adolescent↗
PubMed1997

Effect of lacidipine, a dihydropyridine calcium antagonist on renal function of hypertensive patients with renal insufficiency.

There are few studies on the use of dihydropyridine calcium antagonists in hypertensive patients with moderate renal insufficiency. We undertook an open study on the effects on renal function, albumin excretion and blood pressure of the slow-onset, long-acting dihydropyridine calcium antagonist, lacidipine, in 14 patients with stable, chronic renal insufficiency (mean assessed GFR 0.78 ml/s, range 0.50-1.17 ml/s) and moderate hypertension. Following a 2 week washout phase, lacidipine was administered for 24 weeks in a dose of 2 mg/day with the dose being titrated at 2 weekly intervals to a maximum of 6 mg/day in order to achieve adequate blood pressure control. Frusemide was introduced if blood pressure was not controlled on the maximum lacidipine dose. Blood pressure, creatinine clearance, 24 h urinary albumin excretion and plasma creatinine and albumin concentrations were measured at regular intervals throughout the study. Isotopic GFR was determined at the end of the washout period and at week 24. Lacidipine was not very effective in controlling blood pressure and had an adverse effect on renal function. In 3 patients with an incipient nephrotic syndrome this necessitated withdrawal from the study. Mean GFR of the 10 patients who completed the study decreased from 0.69 ml/s/1.73 m2 at baseline to 0.56 ml/s/1.73 m2 at week 24 (p = 0.006) with a decline in GFR being observed in 9 of these patients. The decrease in GFR was greatest in patients with poorly controlled blood pressure. An insignificant increase in mean urinary albumin excretion occurred during the study with this increase being observed only in patients with albuminuria > 1 g/24 h at baseline. These findings indicated that systemic hypertension altered glomerular hemodynamics and that the vasodilatation of pre-glomerular vessels which followed introduction of the calcium antagonist may have exacerbated this situation. The withdrawal of an angiotensin converting enzyme inhibitor during the washout period may have contributed to these changes. We suggest that renal function should be monitored closely in patients with renal insufficiency when a calcium antagonist is being used to control blood pressure, particularly in those with either marginal blood pressure control, significant albuminuria or an incipient nephrotic syndrome.

Adult↗
PubMed1996

Living related renal transplantation: the Christchurch experience.

AIM: To determine the outcome of renal transplants from living related donors. METHODS: Retrospective analysis of 33 living related donor renal transplants done between March 1976 and 31 December 1994 at Christchurch Hospital. RESULTS: One of the 33 renal transplants patients received an ABO incompatible kidney and was excluded from the statistical analysis. Twenty-one (66%) of 32 grafts continue to function. The 1, 5 and 10 year graft survival rates were 82%, 73% and 48%, respectively. The estimated 1 and 10 year patient survival rates were 96% and 94%, respectively. With the introduction of cyclosporin the 1 and 5 year graft survival rates increased to 90% and 80%, respectively. Three patients received donor specific transfusion preconditioning and one patient a skin graft from the prospective donor. Four patients (12.5%) had current and/or peak panel reactive antibody titres of more than 25%. Three of these grafts failed after 2, 95 and 463 days. Two grafts were lost due to catastrophic vascular complications. CONCLUSION: The overall outcome for patients who were not highly sensitised was excellent. The degree of sensitisation of the recipient, and the extent of atherosclerotic vascular disease in the recipient, were major predisposing factors for the graft loss due to rejection and vascular complications during the early post transplant period.

Adult↗
PubMed1996

Audit of the outcome of patients with renal failure presenting to a regional nephrology service.

AIM: To assess the outcome of patients with renal failure presenting to a regional nephrology unit. METHODS: The records of patients with plasma creatinine concentration > or = 0.30 mmol/L who presented between 1 January 1988 and 31 December 1993, or were already under follow up, were studied. RESULTS: The outcome of 491 patients (293 males) aged from 4.8 to 88.8 years, 123 of whom had acute renal failure, was assessed at 30 June 1994. Thirty seven (30%) of the patients with acute renal failure had died. Of the 372 patients with chronic renal failure 139 had started regular dialysis treatment and 95 were dead, including 27 patients, with a mean age of 71 years, who died of untreated end-stage renal failure (ESRF). For 11 (40%) of these patients the patient and/or family made the decision not to start dialysis treatment. The rates of treatment of ESRF are lower in Canterbury and Westland than those in the Auckland region. The latter can be explained partly by the differences in the demography of the respective populations. CONCLUSION: Death from untreated ESRF is uncommon in Canterbury and Westland. The rates of treatment of ESRF with regular dialysis are lower than in the Auckland region.

Acute Kidney Injury↗
PubMed1996

DMSA renal scans in adults with acute pyelonephritis.

The 99mTc-DMSA scan is accepted as the most sensitive imaging modality for detecting areas of renal parenchymal scarring. More recently the DMSA scan has also been shown to be of value in imaging areas of renal parenchymal involvement in both children and adults with acute pyelonephritis. We assessed the acute DMSA scan findings in a consecutive series of 81 patients hospitalized with acute pyelonephritis. Acute pyelonephritis was diagnosed if the patient had a fever of > 37.8 degrees C, loin pain or tenderness and infected urine (99% Escherichia coli). Patients had a blood culture taken (8 positive), as well as a hematological (leukocytosis 75%) and biochemical screen, C-reactive protein (CRP) (increased in 57 of 66 [86%]) and urinary tract ultrasonography. If the initial DMSA scan was abnormal it was repeated after three months and in some instances again at six months. If persisting defects were noted an intravenous urogram was then undertaken. Of the 81 patients, 37 (46%) had an abnormality on the DMSA scan. Nineteen had a single defect, 12 multifocal defects, five features suggestive of pre-existing renal parenchymal scarring (all later shown to have reflux nephropathy) and one a shrunken kidney. Those patients with an abnormal scan had a higher CRP concentration than those with a normal scan. Of the 31 patients who had either a focal or multifocal defect on their initial DMSA scan there was adequate follow-up on 24 patients. In 18 of these the defects had resolved by six months (usually within three months), while of the remainder, three were shown to have reflux nephropathy, one had a large single renal cyst and another an area of parenchymal calcification. Fifty-three of 76 patients (70%) had normal ultrasonography. In adults with acute pyelonephritis, the DMSA scan may prove to be the most useful renal imaging procedure.

Acute Disease↗
PubMed1996

Prospective, randomized, controlled study comparing two dosing regimens of gentamicin/oral ciprofloxacin switch therapy for acute pyelonephritis.

Aminoglycosides are drugs of choice for severe gram-negative urinary tract sepsis. Recent evidence suggests that they are just as efficacious, but less nephrotoxic and ototoxic, if given as a single daily dose rather than in divided doses. We considered that a single, large dose of an aminoglycoside followed by oral therapy with a different antibiotic might be equally effective and possibly less toxic. This randomized, controlled study compared a single large i.v. dose (10 mg/kg) of gentamicin (S) with a standard multiple dose regimen (M) of gentamicin (2.5 mg/kg i.v. stat and then computer generated divided doses aiming for peak and trough concentrations of 8 and 1.5 mg/l respectively) for the treatment of patients with suspected acute pyelonephritis requiring hospitalization for parenteral antibiotic treatment. All patients were switched to oral ciprofloxacin either four hours after the S dose or when clinically appropriate in the M regimen. For all patients the total duration of treatment was five days. Fifty-three patients (48 women; mean age 32 yr) were enrolled. Clinical and bacteriological efficacy could be assessed in 41 patients. Thirteen of 16 in the S arm and 24 of 25 in the M arm were clinically cured and the other four clinically improved. Fifteen of 16 in the S arm and 23 of 25 in the M arm were cured bacteriologically (sterile urine 7-10 days after treatment). In 41 patients high tone audiometry was carried out before or very soon after the start of treatment, and again at the end of treatment. Ototoxicity (> or = 10 dB loss in > or = 2 frequencies in both ears) was observed in 3 of 18 in the S group (17%) and 7 of 23 in the M group (30%) (NS). Other side-effects and toxicity were mild and not different between groups. Substantial cost savings occurred in the S group. In summary, a large single dose of gentamicin was comparable in efficacy and toxicity to a standard regimen, but cheaper and more convenient to use.

Acute Disease↗
PubMed1995

Pregnancy in renal transplant recipients: the Christchurch experience.

AIM: Assess the pregnancies of our female renal transplant recipients and to document long term maternal and fetal outcome. METHODS: Between 7 June 1972 and 31 December 1992 112 females had at least one renal transplant. Sixty-four of these 112 women were in the reproductive age and had a functioning graft. RESULTS: Nine women had 16 pregnancies which resulted in 11 live births and three first trimester abortions. Two unplanned pregnancies were terminated. Mean age at transplantation was 17.2 yr [range 16-22.5 yr] and mean interval from transplant to pregnancy was 6.8 yr [range 1.8-9.0 yr]. Prednisone and azathioprine were used in all patients and cyclosporin in five. For seven of the successful pregnancies plasma creatinine remained < or = 0.10 mmol/L. One of these women developed allograft nephropathy 5 years after delivery and returned to dialysis 9 years later. For the other four successful pregnancies the preconception plasma creatinine was 0.12-0.14 mmol/L. The woman with two successful pregnancies had a halving of glomerular filtration rate during the second pregnancy, but it has remained stable for 15 years; one was poorly compliant with her immunosuppressive regimen and reached endstage renal failure two years after delivery; one developed cyclosporin nephrotoxicity, but 18 months later renal function was stable after a dosage reduction. Ten infants were delivered by caesarean section, four of them urgently. Three babies were preterm and five growth retarded. One died of sudden infant death syndrome at four months. All other infants developed normally. CONCLUSION: There is no contraindication to pregnancy in female transplant recipients who have stable graft function and controlled blood pressure. Management of such pregnancies should be by shared obstetrical/nephrological/paediatric care.

Adolescent↗
PubMed1995

Short-term response of nonurea organic osmolytes in human kidney to a water load and water deprivation.

The cells of the inner medulla of the mammalian kidney accumulate high concentrations of nonurea organic osmolytes. The organic osmolytes found in the kidney include glycine betaine and sorbitol. This study was designed to measure changes in the urinary excretion of glycine betaine and sorbitol and the plasma concentration of glycine betaine in response to an acute water load (20 ml/kg) or acute water deprivation in young healthy males. In response to a water load the urinary excretion of glycine betaine and sorbitol increased parallel with or shortly after urinary urea excretion. The increase in urinary urea and sorbitol excretions preceded maximum minute volume, whereas peak glycine betaine excretion was closely related to maximum urine minute volume. Subsequently, urea, sorbitol, and glycine betaine excretion rates returned to baseline. In contrast, during water deprivation no change in glycine betaine, sorbitol, and urea urinary excretions occurred during the study period. Plasma glycine betaine concentration was stable during both diuresis and antidiuresis. We conclude that the organic osmolytes glycine betaine and sorbitol are components of a physiological and dynamic system in response to an acute water diuresis.

Adult↗
PubMed1995

Effect of enalapril on erythrocytosis in hypertensive patients with renal disease.

Treatment of hypertension with an angiotensin converting enzyme inhibitor (ACEI) may be associated with a decrease in haemoglobin concentration especially in patients with renal insufficiency. This open study in 19 patients with a variety of renal diseases with complicating hypertension investigated the effects of the ACEI, enalapril, on haemoglobin and plasma erythropoietin (EPO) concentrations. Blood samples were obtained at baseline and 2, 60 and 120 days after starting treatment with enalapril. By day 60 there was a significant decrease in mean haemoglobin concentration (mean decrease 7.4 g/l) that was sustained until day 120. Apart from a small, but significant, reduction by day 2, mean plasma EPO concentration remained constant throughout the study. The magnitude of the decrease in haemoglobin concentration was, however, significantly correlated with the baseline plasma creatinine concentration and creatinine clearance. These results suggested that the degree of renal insufficiency was important in determining the haematological response to ACE inhibition. While the mechanism of these changes remains unclear, our findings suggest that inhibition of the renin-angiotensin system, rather than decreasing EPO production, may reduce the erythropoietic activity of the hormone.

Adult↗
PubMed1995

Effect of enalapril on hemorheology in hypertensive patients with renal disease.

An open, prospective study was undertaken to investigate the effects of enalapril on hemorheology in patients with renal disease and complicating hypertension. Cellular and plasma determinants of blood viscosity and renal function were measured in 19 patients at baseline and 2, 60 and 120 days after treatment with enalapril (mean dose 5.4; range 2.5-20 mg/day). Within 2 days of starting enalapril there was a significant decrease in apparent blood viscosity measured at high shear rate (-0.15 mPa.s; p < 0.05) which fell further by day 60. The decrease in blood viscosity was primarily the result of hemodilution, as evidenced by a concurrent fall in plasma albumin concentration and plasma viscosity. A small, but significant decrease, in hemoglobin concentration (-7.4g/l; p = 0.03), and a trend of improved red blood cell (RBC) and white blood cell (WBC) rheological properties may have also contributed to the decrease in blood viscosity. We conclude that enalapril had a beneficial effect on hemorheology in patients with renal disease. The mechanism of the rheological changes appeared to be multifactorial and would be expected to decrease vascular resistance to blood flow.

Adult↗
PubMed1994

Abnormal glycine betaine content of the blood and urine of diabetic and renal patients.

In normal human plasma the concentrations of the renal osmolyte, glycine betaine, are usually between 20 and 70 mumol/l, in adult males (median 44 mumol/l) higher than in females (34 mumol/l). Concentrations are lower in renal disease (median 28 mumol/l) and normal in diabetes. Urinary excretion of glycine betaine shows no sex difference and is frequently elevated both in renal disease and in diabetes (medians: normal, 6.2, renal 12.3 and diabetes, 39.7 mmol/mol creatinine). The elevation in diabetes does not strongly correlate with known renal disease, nor with either urinary microalbumin or plasma creatinine. There is no correlation with glycated haemoglobin. The positive correlation with the excretions of another renal osmolyte, sorbitol, was highly significant in diabetic subjects. In the diabetic group there was also a significant negative correlation between plasma glycine betaine and urine microalbumin.

Adult↗
PubMed1994

Long term follow up of patients with IgA nephropathy.

AIM: To assess the long term outcome of patients with IgA nephropathy. METHOD: The outcome of 151 patients (120 male; mean age 32.5, median age 29.6, SD 15.4 years; 146 Caucasian) with biopsy-proven IgA nephropathy. The patients were enrolled between 30 April 1973 and 21 August 1992. RESULTS: Ninety-five (63%) of the patients presented with microscopic haematuria, with or without proteinuria and/or renal insufficiency. At presentation renal insufficiency was present in 34% and hypertension in 48% of patients. During a mean follow up period of 63.3 months (range 0-233 months) 12 patients have reached end stage renal failure, five have died of a nonrenal cause and 25 were lost to follow up. The actuarial renal survival rate was 92.6% at five years and 91.1% at both 10 and 15 years. A significantly poorer renal survival rate was seen in those patients with a plasma creatinine > or = 0.12 mmol/L, hypertension, a serum albumin of < 35 g/L, or a 24 hour urinary albumin excretion > or = 1.0 g at presentation, and this became apparent within the first few years of follow up. CONCLUSIONS: The long term outcome of IgA nephropathy is better than previously reported. Those patients with a poor prognosis can be identified with considerable certainty at presentation.

Actuarial Analysis↗
PubMed1994

The pharmacokinetics of quinapril and quinaprilat in patients with congestive heart failure.

The pharmacokinetics of quinapril and its active metabolite quinaprilat were studied in 12 patients with congestive heart failure (CHF) after multiple oral doses of 10 mg quinapril twice daily. Six patients had an ejection fraction of < 35% and six had an ejection fraction between 35%-50%. Increases in the apparent elimination half-life and in AUC(0, 12h) values of quinaprilat were associated with smaller ejection fractions, decreased creatinine clearance, and increased patient age. Comparison with data from age-matched controls having comparable renal function suggests that creatinine clearance is the major determinant of quinaprilat clearance. CHF per se appears to have minimal effect. Dosing of quinapril in patients with CHF should be based on their renal function.

Administration, Oral↗
PubMed1994

End-stage reflux nephropathy.

Forty-two of 371 patients (11.3%) entering a dialysis-transplant program had end-stage reflux nephropathy. Thirteen of these 371 patients were under 16 years of age, with 6 of them having reflux nephropathy. Most patients presented with severely impaired renal function, hypertension, and proteinuria. Documented urinary tract infections occurred in only 4 of the 18 male and 14 of the 24 female patients. Thirty-five patients had hypertension, which in 22 had not been detected before presentation. Five presented with accelerated hypertension. Eight of the 24 women presented during a pregnancy. Twenty-nine patients are still alive, 20 with a functioning renal transplant. Reflux nephropathy is an important cause of end-stage renal failure, particularly in younger people. All patients presenting with renal insufficiency and proteinuria, with or without urinary tract infections or hypertension, should have reflux nephropathy excluded.

Adolescent↗
PubMed1994

Effect of hemodialysis and recombinant human erythropoietin on determinants of blood viscosity.

Blood viscosity (hemorheology) is a major determinant of the rate of blood flow, and increases in viscosity are known to be involved in the etiology of vascular diseases. This placebo-controlled study investigated the independent and combined effects of hemodialysis and recombinant human erythropoietin (rHuEpo) on determinants of blood viscosity in patients with chronic renal failure and related any changes to the normal physiological range. Hemodialysis patients were shown to have a high incidence of rheological abnormalities although the degree of anemia associated with chronic renal failure compensated for these changes. The main effect of both hemodialysis and rHuEPO treatment was an increase in hematocrit associated with a rise in blood viscosity and inconsistent changes in red blood cell (RBC) deformability. The rise in viscosity was significant only following rHuEPO treatment. Hemodialysis-induced increases in blood and plasma viscosity correlated strongly with the degree of hemoconcentration. Although hemodialysis patients have inherent hemorheological abnormalities, correction of renal anemia with rHuEPO to a hematocrit level of < 0.35 in conjunction with dialysis-induced hemoconcentration did not result in adversely high blood viscosity levels in any patient.

Anemia↗
PubMed1993

Organic osmolytes in human and other mammalian kidneys.

Osmotically-active organic solutes, or osmolytes, have been found in high concentration in the renal inner medulla of a wide variety of mammalian species, but their existence in human kidneys has not yet been shown. The aim of this study was to demonstrate the presence of osmolytes in the human kidney. Human tissues were obtained from kidneys removed surgically for diseases which involved only one pole of the kidney; in most cases this was a tumor. Animal kidneys analyzed were from dogs, pigs and rabbits. Inner medulla and cortex tissue samples were analyzed and found to contain the organic osmolytes glycine betaine, myo-inositol, sorbitol and glycerophosphorylcholine. The levels were much higher in the medulla than in the cortex. Further dissection of the human kidneys showed that sorbitol, glycerophosphorylcholine and glycine betaine were maximally concentrated at the papillary tip, while myo-inositol was found in highest concentration at the papillary base. Osmolytes were in low concentrations or undetectable in rabbit skeletal muscle, ureter and bladder. The organic osmolytes detected are likely to be physiologically important in humans. Studies in other mammals can be used as models for the investigation of the osmolyte system in human kidney function.

Animals↗