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Biomedical subjects

J Walls

Publications and source records attributed to J Walls.

At least 19 recordsLinked to original sources
PubMed1992

Effect of cholesterol on the position of segmental lesions in unilaterally nephrectomized rats.

Different positions of segmental lesions within glomeruli may correspond to different pathogenetic mechanisms. The effect of a high cholesterol diet on the position of lesions had not previously been investigated. This was studied in rats following unilateral nephrectomy, as a change in position would suggest a different mechanism of damage. Thirty-two female WAG/ola rats had unilateral nephrectomy. Half the rats were given a diet supplemented with 4 per cent cholesterol and 1 per cent cholic acid. At death, six at 10 weeks after nephrectomy and the rest at 24 weeks, kidney sections were examined microscopically. There were significantly more segmental lesions in the cholesterol-fed rats than in the controls, and these lesions were almost entirely at the glomerular hilum in both groups. Significantly more glomeruli contained foamy cells in the cholesterol-fed group, both within lesions and away from them. These findings confirmed that in reduced renal mass, segmental lesions are mainly hilar. The diet increases the number of glomeruli affected by lesions, but these are still mainly hilar. Therefore one possibility is that hypercholesterolaemia worsens the hyperfiltration effect on glomeruli. The diet also produces foamy cells scattered throughout the glomeruli but these do not appear to develop into segmental lesions.

Animals↗
PubMed1992

The effects of dopamine and a low protein diet on glomerular filtration rate and renal plasma flow in the aged kidney.

The aims of this study were to determine the effects of dopamine and a low protein diet on glomerular filtration rate and effective renal plasma flow in the aged kidney. Effective renal plasma flow was measured using 125I-labelled hippuran and glomerular filtration rate using 51Cr-labelled EDTA. Low-dose continuous intravenous dopamine 3 micrograms.kg-1.min-1 in 10 healthy elderly volunteers caused a significant increase in effective renal plasma flow but not in the mean glomerular filtration rate when compared with baseline. However, glomerular filtration rate did increase substantially in 5 subjects (mean 14.4, SD 1.3). This implied that the elderly kidney was working maximally without reserve capacity in half the elderly. Since renal function is likely to be even more reduced in elderly patients with congestive cardiac failure, dopamine infusions may have little place in this condition in some older patients. A low protein diet (0.69 g.kg-1) in the same volunteers reduced glomerular filtration rate, suggesting that protein restriction may help to reduce the increased filtration rate in the remaining nephrons, thereby leading to structural and functional preservation in the aged kidney.

Age Factors↗
PubMed1992

Long-term outcome of a self-help very-low-calorie-diet weight-loss program.

This paper presents 90-wk data on five seriously overweight subjects originally brought together for 1-2 wk in simple residential accommodation to share the experience of beginning a program of very-low-calorie dieting. All subjects have remained well below their starting weight; four of the five subjects have continued to lose weight (weight losses 33.7-66.8 kg), now weighing less than at the end of the first 26 wk previously reported (1). It is proposed that this self-help group model, incorporating a very-low-calorie diet, is valuable for the long-term management of obesity.

Behavior Therapy↗
PubMed1992

Crossover comparison of intravenous and subcutaneous erythropoietin in haemodialysis patients.

To examine the suggestion that s.c. administration of recombinant human erythropoietin (rHuEpo) may be more effective than i.v. administration, we changed the route of administration in 11 patients, previously established on a stable dose of rHuEpo given twice or thrice weekly, from i.v. to s.c. administration without altering the dose. All patients were iron replete (serum ferritin greater than 100 micrograms/l). In one patient the haemoglobin concentration declined at the time of conversion due to poor compliance, and another patient died shortly after conversion. In the remainder there was a significant increase in haemoglobin concentration from 9.30 (SD 0.78) at the time of conversion to 9.84 (0.59) at 1 month, 10.35 (1.22) at 2 months, and 10.39 (1.42) at 3 months. The increase in haemoglobin concentration was greater than 1 g/dl at 3 months in only five of the patients. Serum ferritin prior to conversion was similar in 'responders' and 'non-responders', but all responders had a transferrin saturation of greater than 16%, whereas three of four non-responders had transferrin saturation of less than or equal to 16%. Subcutaneous administration of rHuEpo is more effective, dose for dose, than i.v. administration, but poor iron mobilization may limit the response.

Adult↗
PubMed1992

Case report: granulocyte colony-stimulating factor overcomes severe neutropenia of large granular lymphocytosis.

Large granular lymphocytosis (LGL) is characterized by enhanced proliferation of T lymphocytes that have antibody-dependent cell-mediated cytotoxicity or natural killer cell activity and that often produce severe cytopenias, including neutropenia. When a 68-year-old man with seropositive rheumatoid arthritis and severe neutropenia was examined, he was found to have LGL with a T cell gene rearrangement, indicating the presence of a clonal population of T lymphocytes. The patient was admitted with a fever of 102 degrees F and a nonhealing ulcer over the right tibia. When the infection did not respond to intravenous antibiotics, granulocyte colony-stimulating factor (GCSF) therapy was started at 5 micrograms/kg subcutaneously each day. The neutrophil count promptly increased and the patient subsequently defervesced and was able to have a skin graft placed, which healed without difficulty. GCSF, which is known to be an effective therapeutic agent for neutropenia associated with chemotherapy and bone marrow transplantation, also was a very valuable treatment for the life-threatening neutropenia of LGL.

Aged↗
PubMed1992

Deterioration in renal function associated with angiotensin converting enzyme inhibitor therapy is not always reversible.

Fifteen patients presented between January 1986 and January 1991 with deterioration in renal function coincident with the introduction of angiotensin converting enzyme inhibitors. There was evidence of extrarenal vascular disease in 12 patients and preexisting renal impairment in 13. Four patients remained dialysis-dependent and died within 4 weeks of presentation. Five patients required short-term dialysis. Serum creatinine remained above pre-treatment values in seven patients. Conventional explanations of the decline in renal function with ACE inhibition do not account for irreversible decrements in renal function. Possible mechanisms for this observation and clinical guidelines to identify patients at risk are suggested. We conclude that these agents should be used with great care in patients in whom atherosclerotic vascular disease is likely.

Acute Kidney Injury↗
PubMed1992

Comparison of subxiphoid and traditional approaches for ICD implantation.

We compared clinical and electrophysiological data in 18 patients undergoing ICD implantation via a traditional (median sternotomy or left lateral thoracotomy) with 29 patients with a subxiphoid approach. Both groups were similar in terms of age, sex, left ventricular ejection fraction, presence of coronary artery disease, and clinical indication for the device. Fifteen patients (83%) with the traditional approach had previous cardiac surgery compared with 6 patients (21%) who had a subxiphoid approach (P < 0.001). Both groups had similar patch R wave and sensing R wave measurements. Patients with the traditional approach had a lower energy for defibrillation than patients with a subxiphoid approach (13.6 +/- 6.8 J vs 17.9 +/- 4.1 J, P < 0.05). Postoperative hospital days were fewer in the subxiphoid group compared with the traditional approaches (9.8 +/- 5.3 vs 13.7 +/- 7.5 days) but the differences did not reach statistical significance, possibly due to small numbers. The subxiphoid approach appears to be a reasonable alternative approach to the traditional approach in selected patients undergoing ICD implantation.

Defibrillators, Implantable↗
PubMed1992

Clearance of iopamidol, a non-ionic contrast medium, by CAPD in patients with end-stage renal failure.

In normal healthy subjects radiographic contrast media are cleared by the kidneys with a half-life of approximately 2 h and a total body clearance of 8 l/h. The mechanism of contrast clearance has not been previously investigated in chronic renal failure patients undergoing continuous ambulatory peritoneal dialysis (CAPD). A study was undertaken to investigate the pharmacokinetics of a non-ionic water soluble radiographic contrast medium (iopamidol) in 10 patients stabilized on CAPD. All patients (eight male, two female) aged 22-68 years (median 53 years) had injection of 30 ml of iopamidol 300 via a forearm vein to investigate subclavian vein patency following previous cannulation for haemodialysis. Venous blood samples, CAPD dialysate and urine were collected for seven days post injection. The mean plasma half-life was 37.9 h (SD 10.6) (range 24.1-57.2 h) for the CAPD patients and was greatly prolonged in comparison to healthy subjects. The total body clearance of iopamidol was also greatly reduced (0.377 l/h). CAPD removed an average of 53.6% of the administered dose (range 36.3-80.8%) whilst an average of 26.9% was excreted in the urine (range 1.3-56.3%). The combined renal and dialysate clearance was up to 93% of the administered dose over the period of the study. There is therefore some evidence for a small extra renal clearance of iopamidol in end-stage renal failure patients. This study has shown for the first time that patients with end-stage renal failure undergoing CAPD have significantly delayed elimination of contrast medium. This should be taken into consideration when extensive or prolonged investigations using contrast medium are proposed.

Adult↗
PubMed1992

Effect of recombinant human erythropoietin on erythropoiesis in homozygous sickle-cell anaemia and renal failure.

The development of end-stage renal disease (ESRD) in patients with sickle-cell anaemia results in increased transfusion dependence, increasing the risk of iron overload. Correction of anaemia with recombinant human erythropoietin (rHuEpo) in dialysis patients might also result in stimulation of haemoglobin F production, which protects against sickling, although very high doses were required to achieve this effect in non-uraemic animals. rHuEpo was administered to three transfusion-dependent patients with ESRD and homozygous sickle-cell disease (initial dose 100 U/kg twice weekly, increasing to 125 U/kg at 6 weeks, and to 150 U/kg at 9 weeks in two patients). This resulted in reticulocytosis and increased circulating erythroid blast-forming units. Total haemoglobin was predominantly HbA (i.e. transfused blood) at the start of the study, reflecting transfusion dependence, but after 3 months' treatment was between 60 and 94% HbS. No sickling crises occurred. Haemoglobin F remained at less than 3% of total haemoglobin. One patient was withdrawn at 10 weeks with CAPD peritonitis. The other two patients completed 12 weeks' treatment without transfusion but final Hb concentrations were 4.5 and 5.5 g/dl. Whether larger doses of rHuEpo will be more successful in managing such patients remains unclear. No effect on HbF production can be expected.

Adult↗
PubMed1992

Carboplatin plus oral etoposide in the management of advanced, non-small cell lung cancer: preliminary results of a Vanderbilt trial.

Twenty-eight patients with unresectable, metastatic non-small cell lung cancer (NSCLC) were treated with carboplatin/oral etoposide. Carboplatin was administered intravenously on day 1 at a dose of 300 mg/m2 (12 patients) or 350 mg/m2 (16 patients); oral etoposide was administered at a dose of 50 mg/m2/d for 21 consecutive days. Treatment was repeated every 28 days. Patient characteristics included male:female ratio of 23:5, median age of 60 years, median Eastern Cooperative Oncology Group performance status of 1, weight loss of 5% or more in seven patients; stage IIIB disease in two patients and stage IV in 26. Twenty-five patients were evaluable for response and seven (28%) achieved a partial response (95% confidence interval, 14% to 48%). Median duration of response was 3+ months (range, 2+ to 6+) and median survival was 4+ months (range, 1+ to 10+). Myelosuppression was the predominate toxicity; leukocyte and platelet nadirs occurred between days 22 and 29, with median counts of 2,900/microL and 172,000/microL, respectively. The median interval between the start of cycle 1 and the start of cycle 2 was 33 days (range, 26 to 42). Carboplatin/oral etoposide is a moderately active regimen against advanced NSCLC that can be administered in an outpatient setting with manageable toxicity. Its impact on survival remains to be determined.

Administration, Oral↗
PubMed1992

Creatine and creatinine metabolism in uraemia.

Measurements of serum creatinine to monitor the progression of chronic renal failure may be misleading and influenced by factors other than GFR. Creatinine is produced by the degradation of creatine which is stored in muscle. The effect of biochemical changes observed in uraemia on the transport of [1-14C]creatine were examined in a cultured muscle model. In a Na-free medium flux of [1-14C]creatine was reduced (p < 0.001), however the addition of various uraemic toxins, insulin, parathyroid hormone and the alteration of pH had no effect on creatine influx. The variance of red cell creatine levels in uraemic patients was significantly different from controls (p < 0.02) and the plasma to red cell creatine gradient was low in some patients.

Animals↗
PubMed1991

Metabolic acidosis and skeletal muscle adaptation to low protein diets in chronic uremia.

To maintain nitrogen equilibrium when prescribed a low protein diet (LPD), metabolic adaptations occur involving a reduction protein turnover, principally decreased muscle protein degradation. Studies suggest that in patients with chronic renal failure (CRF) uncomplicated by metabolic acidosis (MA), these adaptive responses are intact. Because MA stimulates muscle proteolysis, this study examined the hypothesis that in CRF complicated by MA, the adaptation to LPD may be impaired, inducing a nitrogen wasting state. Six adults with CRF (mean GFR: 12.8 +/- 1.5 ml/min) and MA (mean serum bicarbonate: 17.0 +/- 1.0 mM/liter) receiving an unrestricted diet (protein intake: 1.2 g/kg body wt/day) were converted to an isocaloric LPD (protein: 0.6 g/kg body wt/day). Two weeks later total urinary nitrogen losses decreased, but skeletal muscle protein catabolism (SMPC), assessed from the urinary 3-methyl histidine:creatinine ratio, increased, demonstrating impairment in the adaptive down-regulation of SMPC. The LPD was continued for a further two weeks and MA was corrected with oral sodium bicarbonate (mean serum bicarbonate: 24.3 +/- 1.2 mM/liter). Correcting MA decreased SMPC to a level below that measured prior to protein restriction. The decreased SMPC was paralleled by further decreases in urinary nitrogen losses, confirming that MA impaired nitrogen utilization. It is concluded that MA can override the expected metabolic adaptive response to a LPD. The associated impairment of nitrogen utilization not only diminishes the efficacy of the diet, but also accelerates the loss of lean body mass.

Acidosis↗
PubMed1991

Skeletal muscle degradation and nitrogen wasting in rats with chronic metabolic acidosis.

1. Chronic metabolic acidosis is associated with impaired growth and negative nitrogen balance, suggesting that it promotes endogenous protein catabolism. 2. Skeletal muscle is the major repository of body protein and is a potential target for stimuli of protein catabolism. 3. This study in vivo examines the effects of chronic metabolic acidosis on the relationship between growth, nitrogen disposal and skeletal muscle catabolism in the rat. 4. Growth, nitrogen utilization and acquisition of body mass were significantly impaired in acidotic animals compared with pair-fed controls. 5. Total nitrogen excretion was significantly increased in acidotic rats despite decreased urea production. The time course of this response to acidosis was synchronous with that of accelerated protein catabolism in skeletal muscle. 6. It is proposed that metabolic acidosis impairs growth by stimulating skeletal muscle protein catabolism. It is suggested that this forms part of a co-ordinated multi-organ homoeostatic response to acidosis, skeletal muscle and down-regulated urea production supplying the nitrogen required for renal ammoniagenesis.

Acidosis↗
PubMed1991

Influence of nifedipine on cyclosporin A nephrotoxicity after unilateral nephrectomy in the spontaneously hypertensive rat.

1. Nifedipine ameliorates cyclosporin A-induced renal impairment in surgically intact (two-kidney) rats. This study investigates the effect of nifedipine on cyclosporin A nephrotoxicity in spontaneously hypertensive rats after either uninephrectomy or uninephrectomy with contralateral renal denervation. 2. Fourteen days after uninephrectomy pair-fed rats were injected for 14 days with cyclosporin A (25 mg/kg body weight) via the subcutaneous route and with nifedipine (0.1 mg/kg body weight) via the intraperitoneal route. Renal and systemic haemodynamics were measured in conscious unrestrained rats. 3. Whole-blood levels of cyclosporin A did not differ between groups (overall 352 +/- 22 ng/ml, means +/- SEM). After uninephrectomy, cyclosporin A decreased the glomerular filtration rate (olive oil versus cyclosporin A: 0.96 +/- 0.04 versus 0.70 +/- 0.06 ml min-1 100 g body weight, P less than 0.02) and effective renal plasma flow (1.94 +/- 0.10 versus 1.38 +/- 0.13, P less than 0.01), and increased renal vascular resistance [(20.2 +/- 1.8) x 10(4) versus (31.6 +/- 3.3) x 10(4) kPa l-1 s [(20.2 +/- 1.8) x 10(3) versus (31.6 +/- 3.3) x 10(3) dyn s cm-5], P less than 0.02] and mean arterial pressure (146.7 +/- 6.7 versus 167.3 +/- 2.9 mmHg, P less than 0.05). Neither renal denervation nor nifedipine prevented the reduction in glomerular filtration rate or effective renal plasma flow induced by cyclosporin A. 4. This study infers that the sympathetic nervous system does not play an active role in cyclosporin A nephrotoxicity and demonstrates that the concomitant administration of nifedipine to rats with reduced renal mass does not ameliorate cyclosporin A-induced renal impairment.

Animals↗