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Biomedical subjects

A M Brownjohn

Publications and source records attributed to A M Brownjohn.

At least 19 recordsLinked to original sources

Immunocytochemical detection of a reduction in 1,25 dihyroxyvitamin D3 receptor expression in uraemic parathyroid tissue.

BACKGROUND: The vitamin D receptor is expressed in nuclei of parathyroid cells and plays an important role in the regulation of cell growth and parathyroid hormone secretion. A number of studies have shown reduced receptor expression in uraemic parathyroid glands but the relationship between receptor expression and renal function has not been identified. METHODS: This study used archive parathyroid tissue from patients with primary adenomas, dialysis patients with diffuse hyperplasia secondary to uraemia and normal parathyroid tissue. An immunocytochemical assay with a vitamin D receptor antibody was used to identify parathyroid cells expressing receptor in their nuclei. RESULTS: In patients with a serum creatinine < or = 110 mumol/l, 81.94% +/- 6.5 of parathyroid cells expressed vitamin D receptor. This fell to a mean of 49.3% in two patients with a serum creatinine between 110 and 300 mumol/l and to 40.17% +/- 8.6 in dialysis patients. CONCLUSION: Vitamin D receptor expression in parathyroid glands is reduced in renal failure.

Adenoma

Whole body and regional body composition in patients with chronic renal failure.

BACKGROUND: Nutritional state is a powerful prognostic factor in chronic renal failure (CRF). Techniques for the assessment of nutrition have limitations which are often most marked in the presence of renal disease. We have used techniques of body composition analysis to assess the nutritional state of groups of patients with CRF. METHODS: Body composition was measured in groups of patients with advanced CRF on conservative treatment, peritoneal dialysis, and haemodialysis and the results compared with a healthy control group. The selection criteria for the CRF patients ensured that they were "stable' with no recent intercurrent illness, and dialysis adequacy was satisfactory according to currently accepted targets. RESULTS: Whole body dual energy X-ray absorptiometry (DEXA) found significant reduction in lean tissue in haemodialysis patients and female peritoneal dialysis patients. Regional analysis with DEXA showed reduction in limb (especially arm), lean tissue in CRF patients, with arm lean tissue being reduced in all three CRF groups for females and both dialysis groups for males. Limb/trunk lean tissue ratios were significantly reduced for all CRF groups. Bioelectrical impedance showed reductions of fat-free mass in the same groups who had reduced whole body lean tissue with DEXA, but skinfold anthropometry failed to detect any significant reduction in fat-free mass. CONCLUSIONS: We conclude that even in "healthy' groups of CRF patients receiving adequate dialytic and dietary management, lean tissue depletion is a common problem. Regional analysis by DEXA, with measurement of limb lean tissue mass is a more sensitive method for the detection of lean tissue depletion than measurement of whole body lean tissue in patients with CRF.

Absorptiometry, Photon

The clinical and biochemical features of acute renal failure due to rhabdomyolysis.

Rhabdomyolysis caused 28 out of 903 (3.1%) of cases of severe acute renal failure (ARF) treated at Leeds General Infirmary over a 14-year period (1980-1993). The commonest cause of rhabdomyolysis was muscle compression, usually due to drug- or alcohol-induced coma. Other causes included fits, infection, acute limb ischemia, trauma, and heat stroke. Prognosis was relatively good, with a 78.6% survival rate and recovery of renal function to normal in all survivors who were followed up. The creatinine/urea ratio was higher in ARF due to rhabdomyolysis than in an unselected group of patients with other causes of ARF but not when the comparison was with sex- and age-matched controls with ARF. This suggests that this previously described feature of rhabdomyolysis simply reflects the increased muscle mass of a younger group of patients, rather than a specific effect of muscle damage. Clinical features of muscle damage were often absent and so the possibility of rhabdomyolysis should be considered in appropriate settings if the diagnosis is to be made early enough to administer treatment that may prevent ARF and the consequences of the compartment syndrome.

Acute Kidney Injury

Acute renal failure in patients with type 1 diabetes mellitus.

Acute renal failure (ARF) is a serious condition which still carries a mortality of around 50%. People with diabetes may be at increased risk of developing ARF, either as a complication of diabetic ketoacidosis or hyperosmolar coma, increased incidence of cardiovascular disease, or due to increased susceptibility of the kidney to adverse effects in the presence of underlying diabetic renal disease. During the period 1956-1992, 1,661 cases of ARF have been treated at Leeds General Infirmary. Of these, we have identified 26 patients also having type 1 diabetes. ARF due to diabetic ketoacidosis is surprisingly uncommon (14 cases out of 23 patients whose notes were reviewed). All cases of ARF complicating ketoacidosis in the last decade have been associated with particularly severe illness requiring intensive care unit support, rather than otherwise 'uncomplicated' ketoacidosis. We discuss the conditions that may result in ARF in patients with diabetes and the particular difficulties that may be encountered in management.

Acute Kidney Injury

Nocturnal intermittent peritoneal dialysis.

Automated methods of peritoneal dialysis have developed as alternative methods of treatment to CAPD. We review our experience of 47 patients treated with nocturnal intermittent peritoneal dialysis (NIPD). Patients receive a nocturnal exchange of 15-25 litres of dialysate with the peritoneum left dry during the day. If biochemical control is inadequate, 1 litre of dialysate is left in during the day. Indications for NIPD included social reasons and CAPD failure due to poor ultrafiltration or problems related to raised intra-abdominal pressure. Some features of biochemical control were less good with NIPD compared with CAPD with higher phosphate (2.18 mmol/l versus 1.83 mmol/l, P < 0.001); creatinine (1256 mumol/l versus 1085 mumol/l, P < 0.001); and potassium (4.92 mmol/l versus 4.64 mmol/l, P = 0.056) in patients changing between CAPD and NIPD. Overall peritonitis rate on NIPD was one episode per 47.1 months compared with a rate of one episode per 17.5 months for patients commencing CAPD over the same period. Conversion from CAPD to NIPD was successful in all six cases for problems related to raised intra-abdominal pressure on CAPD and in six of nine patients transferred due to poor ultrafiltration. NIPD is a useful form of treatment and we believe that the increased cost is offset by the reduced peritonitis rate.

Adult

Complement activation during CAPD.

Complement activation was monitored in 20 CAPD patients and 20 normal individuals using markers of the alternative (Bb fragment), classical (C4d fragment), common (iC3b) and terminal pathways (SC5b-9, the soluble form of the membrane attack complex, MAC), together with C3, C4 and factor B. CAPD plasma SC5b-9 was higher than normal although this was not due to increased complement activation in the plasma. The calculated cleavage for C3, C4 and factor B to iC3b, C4d and Bb respectively, due to spontaneous activation, was similar in both groups. C3, C4 and factor B in dialysate were less than 1% of plasma concentration, consistent with vascular leakage, whereas iC3b, Bb and SC5b-9 were at higher concentrations, suggesting generation in the peritoneum by the alternative pathway. 2.4% C4d is consistent with leakage of this small molecule but may indicate slight classical activation. It is concluded that complement activation occurs in the peritoneum during CAPD. MAC and the anaphylatoxins which are also generated may contribute to an increased risk of infection and other inflammatory complications.

Blood

Infarction of the tongue in Wegener's granulomatosis.

Wegener's granulomatosis is a form of systemic vasculitis. Untreated, it has a 90% two year mortality, but complete remission can be obtained in 93% of patients following treatment with cyclophosphamide (usually in combination with steroids). There is early and major involvement of the respiratory tract. Renal involvement adversely affects prognosis.

Acute Kidney Injury

Erythropoietin deficiency in acute renal failure.

Erythropoietin (Epo) was sequentially measured by radioimmunoassay in 11 patients with acute renal failure (ARF) of varied aetiology. Epo rapidly decreased to a level inappropriately low for the haemoglobin, the reduced Epo value persisting throughout the oliguric phase and for up to 2 weeks after the restoration of apparently normal renal function. Epo values found in ARF were: at referral 18.2 +/- 9.5, mid-oliguria 14.4 +/- 6.8, diuresis 15.6 +/- 5.8, and recovery 25.1 +/- 15.8 mU/ml. Results are compared with 34 patients with end-stage chronic renal failure, 42 with non-renal anaemia, and 96 normal subjects. Epo deficiency alone is an inadequate explanation of the rapid reduction in haemoglobin at the onset of ARF, but would appear to be an important factor in the maintenance of anaemia in prolonged ARF and accounts for the slow increase in haemoglobin following recovery.

Acute Kidney Injury

Plasma and dialysate immunoglobulin G in continuous ambulatory peritoneal dialysis patients: a multicenter study.

Peritoneal dialysate immunoglobulin (Ig)G concentrations were measured in 120 continuous ambulatory peritoneal dialysis (CAPD) patients evaluated at four dialysis centers in different countries to assess the normal range for dialysate IgG and to investigate the relationships of this protein levels with peritoneal episodes, For 65 of these patients, plasma IgG levels were determined, and IgG clearances were calculated. The mean dialysate concentration of IgG was 6.9 +/- 4.2 mg/dl, and there was no difference between men and women or between patients who had or had not previously undergone hemodialysis. Dialysate IgG concentrations were significantly related to residual renal creatinine clearance and negatively correlated with dialysate volume, plasma albumin and total protein. There were no significant correlations between IgG levels in the dialysate and age, protein losses in the dialysate, time on CAPD or time from the last peritonitis episode. Plasma and dialysate IgG were unrelated to the incidence of peritonitis, statistical analysis being performed with different methods. These results suggest that IgG levels in the dialysate or plasma are not a major factor in the prevention of CAPD peritonitis.

Ascitic Fluid

Amino-acid-based continuous ambulatory peritoneal dialysis (CAPD) fluid over twelve weeks: effects on carbohydrate and lipid metabolism.

Aspects of lipid and carbohydrate metabolism were studied in 8 patients established on continuous ambulatory peritoneal dialysis (CAPD) with plasma albumin less than 35 g/L, before, during, and after substitution of 1 of the daily glucose exchanges by a commercial 1% amino acid dialysis fluid for 12 weeks. The amount of glucose absorbed from the dialysis fluid was consequently reduced by about 25%, hence total energy intake decreased by about 100 Kcal/day, but peritoneal glucose transfer kinetics were unaffected. Glucose was lost into amino acid dialysate as expected (2 g/day). Excluding 1 patient with a large rise in calorie intake, total and LDL cholesterol fell at 8 and 12 weeks (LDL cholesterol week 0, 5.26 +/- 1.13; week 8, 4.32 +/- 0.74; week 12, 4.30 +/- 1.22; mean +/- SD, p less than 0.01 for both), but returned to baseline 2 weeks after the restoration of glucose fluid (LDL 4.91 +/- 1.22, p less than 0.05 vs. week 12). Apolipoprotein B concentration also fell at 12 weeks (p less than 0.01). No changes were seen in body weight, body fat, arm muscle circumference, fasting plasma glucose, insulin, growth hormone, triglyceride, nonesterified fatty acids, or HDL cholesterol. The response of these biochemical indices to single 8-h glucose and amino acid morning exchanges at 0 and 12 weeks were studied. After 12 week's use of amino acid dialysis fluid, plasma cholesterol and apolipoprotein B were significantly lower throughout the exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids

Longitudinal study of proteins in plasma and dialysate during continuous ambulatory peritoneal dialysis (CAPD).

The aim was to evaluate plasma proteins during continuous ambulatory peritoneal dialysis (CAPD) in relation to dialysis losses, membrane permeability, renal insufficiency, and time on CAPD. Ten male patients, established on CAPD for at least 14 months, were studied every 8 weeks for 56 weeks. Blood and dialysate from the morning exchange were analysed for urea, creatinine, and 7 proteins, and used to calculate dialysate to plasma concentration ratios (D/P). These ratios were not significantly changed suggesting that permeability remained constant. However, there was a trend for beta 2-microglobulin, creatinine, and urea to increase progressively. After 56 weeks, beta 2-microglobulin had increased from 27.9 to 31.3 mg/L (p less than 0.05) and creatinine 1006 to 1099 mumoL/L (p less than 0.05) and both correlated with time on CAPD (p less than 0.001). Plasma alpha 1-acid glycoprotein, albumin, transferrin, IgG, IgA, and complement C3 were not significantly changed, although IgA and complement C3 were each negatively correlated with time on CAPD (r = -0.70 and -0.67, respectively), creatinine (r = 0.51 and -0.54), and urea (r = -0.61 and -0.61) (p less than 0.001 for all). It is concluded that increases in beta 2-microglobulin, creatinine, and urea are not due to loss of membrane permeability but reflect a slight increase in uraemia. Long-term decreases in immunological proteins may be caused by uraemia or progressive depletion.

Adult