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Biomedical subjects

A M Davison

Publications and source records attributed to A M Davison.

At least 109 records · Page 6Linked to original sources

Effect of the direction of dialysate flow on the efficiency of continuous arteriovenous haemodialysis.

We have investigated the effect of the direction of the dialysate flow during continuous arteriovenous haemodialysis. Under similar conditions countercurrent flow was more efficient than concurrent flow in terms of both urea clearance (mean +/- SEM), 23.5 +/- 0.5 compared to 18.4 +/- 0.4 ml/min (p less than 0.001) and creatinine clearance, 21.1 +/- 0.5 compared to 15.6 +/- 0.4 ml/min (p less than 0.001). There was a greater drop in pressure along the blood compartment of the haemodiafilter during countercurrent flow, 16 +/- 0.8 compared to 13 +/- 0.3 mm Hg (p less than 0.05) during concurrent flow, and this was associated with a greater ultrafiltration rate, 7.2 +/- 0.6 compared to 6.0 +/- 0.5 ml/min. The differences in diffusion, back diffusion and convection between the two systems resulted in a net gain of lactate/bicarbonate and a net loss of chloride during countercurrent dialysate flow, and a net loss of lactate/bicarbonate with a gain of chloride during concurrent flow. These losses would have to be corrected in the clinical setting of patients who had been continuously treated by these systems for several days.

Adult↗

Urinary aluminium excretion following renal transplantation and the effect of pulse steroid therapy.

Urinary aluminium was measured in 48 patients with primary graft function for 14 days following renal transplantation. The plasma aluminium prior to transplantation was greater in those prescribed aluminium-containing phosphate binders (1.7 +/- 0.2 vs 0.6 +/- 0.2 mumol/L, P less than 0.05) and correlated with the duration of dialysis therapy (r = 0.42, P less than 0.008). After an initial reduction the plasma aluminium returned to pre-transplant values by the fifth day. The 24 h urinary aluminium excretion, aluminium clearance and fractional aluminium excretion all increased during the first week to a maximum around the sixth postoperative day, thereafter returning to values obtained during the first postoperative days, suggesting an early 'wash-out' of a readily accessible aluminium pool followed by a lower steady state determined by the rate of release of aluminium from tissue stores. For the whole group, aluminium excretion, at this steady state, was five times that of urinary aluminium excretion in normal subjects. Acute allograft rejection was diagnosed in 25 patients, who were treated with pulsed methyl prednisolone. Apart from improving graft function, no additional effect was observed on aluminium excretion, suggesting that the readily accessible aluminium pool does not come from lysosomal release, but probably from aluminium bound to small molecular weight protein.

Adolescent↗

Immunogold-silver staining of mesangial antigen in lowicryl K4M- and LR gold-embedded renal tissue using epipolarization microscopy.

We examined the localization of a glomerular mesangial antigen with a Thy-1.1 monoclonal antibody by epipolarization microscopy (EPI) of silver-enhanced, immunogold-stained renal tissue embedded in LR Gold and Lowicryl K4M, and compared the attributes of these hydrophilic resins. Antigen was well preserved in tissue embedded in both resins. LR Gold-embedded tissue demonstrated excellent immunostaining properties, sectioned more easily, and showed better durability during staining than K4M. Lowicryl K4M-embedded tissue, however, displayed a phenomenon of self-illumination when counterstained with eosin which was not seen with LR Gold. This enabled immunostaining to be precisely related to tissue morphology without the necessity of simultaneous transillumination, which can be problematic when used in combination with EPI because of reflection of incident illumination from sub-stage optical surfaces.

Animals↗

Late renal failure due to prostatic outflow obstruction: a preventable disease.

Nineteen patients presenting with late renal failure due to prostatic outflow obstruction (mean age 68.7 years; mean serum creatinine concentration 1158 mumol/l) were identified from the admission records of two renal units. As late renal failure secondary to prostatic enlargement is preventable case records were analysed retrospectively in an attempt to identify aspects of management in which preventive efforts might be of value. Delays in referral were common, with a mean of 2.8 years between the onset of prostatic symptoms and time of referral, six patients being referred who had had symptoms for more than three years. Four of five patients who had had a prostatectomy were known to be in renal failure at the time of operation but were not referred until 2-13 years later, when prostatic symptoms had recurred and there was evidence of progressive nephropathy with dilatation of the upper urinary tract. Two patients died on admission and eight (47% of survivors) required long term dialysis, most patients (80%) requiring some dialysis support during the initial period. These findings suggest that progressive nephropathy caused by prostatic outflow obstruction might, in part, be averted by more adequate screening of renal function in men with untreated prostatism and closer follow up of patients with uraemia at the time of prostatectomy.

Aged↗

Quantitative bone scanning in the diagnosis of aluminium osteomalacia.

Skeletal uptake of diphosphonate was measured by emission tomography in 30 patients on chronic dialysis treatment. In 19 patients mean plasma aluminium concentrations, measured over the preceding 12 months, were 'high' (greater than 1.0 mumol/l, and in the other 11 were 'low' (less than 1.0 mumol/l). There was a strong correlation between serum alkaline phosphatase and skeletal uptake of diphosphonate in each group, but no difference in diphosphonate uptake between the groups. Additionally, when six patients with positive desferrioxamine tests were matched for serum alkaline phosphatase with six patients from the 'low' aluminium group there was no significant difference in uptake of diphosphonate (median and range 7.2; 5.2-16.5 and 5.9; 2.7-10.8 respectively). We conclude that skeletal uptake of diphosphonate is not suppressed in patients with moderate aluminium loading, but reflects bone turnover as indicated by serum alkaline phosphatase. Quantitative bone scintigraphy is not a useful discriminator for early aluminium osteomalacia.

Adult↗

Changes in intracranial pressure during haemofiltration in oliguric patients with grade IV hepatic encephalopathy.

Seven consecutive patients with grade IV hepatic encephalopathy, due to fulminant hepatic failure complicated by oliguric renal failure were allocated at random to treatment with daily machine haemofiltration (MHF) or continuous arteriovenous haemofiltration (CAVHF). Intracranial pressure (ICP) was continuously monitored using a subdural catheter. Four patients received 17 treatments by MHF, and ICP increased from 8.4 +/- 1.5 mm Hg (mean + SEM) prior to treatment to 12.6 +/- 1.8 mm Hg on completion (p less than 0.05). Active intervention was required on twenty occasions to treat sustained increases in ICP (greater than 25 mm Hg maintained for 5 min or longer). A total of 12 haemofilters were used in the treatment of 3 patients by CAVHF. The ICP showed greater stability during CAVHF therapy, the mean pressure prior to treatment was 15.6 +/- 5.2 mm Hg and fell to 11.7 +/- 2.3 mm Hg at 4 h. Sustained increases in ICP occurred in only 1 patient as a preterminal event. These findings suggest that CAVHF is the preferred method of treatment in patients with fulminant hepatic failure complicated by oliguric renal failure who are at risk of developing cerebral oedema.

Acute Kidney Injury↗

The effect of lactate-buffered solutions on the acid-base status of patients with renal failure.

We investigated the effect of an exogenous lactate load given during intermittent machine haemofiltration to three groups of patients with renal failure: those with dialysis-dependent end-stage renal failure (6 patients) and those with either acute renal (8 patients) and/or acute hepatorenal failure (6 patients). As expected, the hepatorenal group exhibited the greatest degree of hyperlactataemia, and this was associated with the development of a metabolic acidosis. There were correlations between the maximum blood lactate measured during treatment and the increase in arterial hydrogen ion concentration (r = 0.76, P less than 0.001), and between the decrease in serum bicarbonate (r = 0.89, P less than 0.001) and the mean arterial blood pressure prior to treatment (r = -0.57, P = 0.003). This suggests that hyperlactataemia is not as benign as previously thought and that lactate-buffered fluids should be used with care in patients with hepatorenal failure and cardiovascular instability.

Acid-Base Imbalance↗

Are changes in intracranial pressure during intermittent machine haemofiltration dependent upon membrane biocompatibility?

We measured the intracranial pressure, using a subdural catheter in three patients admitted with grade 4 hepatic encephalopathy following paracetamol (aminocetaphen) self poisoning. Acute oliguric renal failure was present in all cases and was treated with daily intermittent machine haemofiltration. Hypovolaemia prior to treatment was corrected and a total of 14 isovolaemic 17 litre exchanges carried out using either a Gambro FH77 (8) or Hospal 3600 (6) haemofilter. Intracranial pressure (ICP) increased during treatment with both types of filter, but the increase was greater in the Gambro FH77 treated group, mean ICP increased from 7.6 +/- 2 mmHg to 12 +/- 3 mmHg at 3 hours (p less than 0.05), this was associated with a greater fall in the percentage change from the pretreatment value of both arterial oxygen tension and total peripheral white blood cell count during the first hour of treatment compared to the Hospal 3600 treated group, 8 +/- 2% vs 1 +/- 2% (p less than 0.05) and 5 +/- 2% vs 3 +/- 2% (p less than 0.05). This suggests that membrane biocompatibility may also play a role in the development of increased intracranial pressure during intermittent machine haemofiltration.

Acetaminophen↗

Changes in intracranial pressure during machine and continuous haemofiltration.

Nine consecutive patients with both fulminant hepatic failure and acute oliguric renal failure were treated either by daily machine haemofiltration (MHF), or by continuous arterio-venous haemofiltration (CAVHF). Six patients received a total of twenty treatments by MHF and four CAVHF, mean duration of treatment 56 hours, range 24-160. Intracranial pressure (ICP) was measured using a subdural catheter. During treatment with MHF, the mean ICP increased from 8.9 +/- 1.4 mmHg at the start of filtration to 14.8 +/- 2.1 mmHg at the end of treatment (p less than 0.05), whereas there was no corresponding increase during the same period of time with CAVHF treatment, the mean ICP fell, but not significantly from 19.4 +/- 4.8 mmHg to 11.2 +/- 2.3 mmHg. The mean ICP increased to greater than 25 mmHg on eleven occasions during treatment with MHF, requiring treatment with bolus mannitol or propofol, during the same period of treatment with CAVHF no such surges in ICP were recorded. This suggests that continuous haemofiltration is to be preferred to intermittent machine haemofiltration in the management of patients with acute hepatorenal failure.

Adult↗

Fine-needle aspiration cytology monitoring of elective conversion from cyclosporin to azathioprine and prednisolone.

The elective conversion of renal allograft recipients from cyclosporin (CsA) to azathioprine and prednisolone has the advantage that the long-term risk of CsA nephrotoxicity is reduced, but it may precipitate a rejection episode. We have monitored this period by fine-needle aspiration cytology (FNAC) in 24 patients undergoing conversion of immunosuppression 6 months after transplantation. As expected the serum creatinine and alkaline phosphatase were significantly reduced and the mean creatinine clearance was significantly increased after conversion. FNAC exhibited increased mononuclear cellular infiltration in 13 of the 24 patients. In nine patients there was a transient infiltration of lymphocytes and monocytes without changes in the normal parameters of renal function. In four others 'blast' cell infiltration was evident in association with rejection episodes. All four responded to pulsed doses of methylprednisolone. However, two other patients had late rejection episodes (2 and 6 months after conversion) which were steroid resistant and required reintroduction of CsA. No grafts were lost (median follow-up 9 months). This study has shown that although overt rejection occurred in only 16.6% of patients, cellular infiltration was present in over 50% during conversion of immunosuppression. FNAC failed to identify clearly the patients at risk of rejection during conversion of therapy.

Adolescent↗

Spontaneous glomerular immunoglobulin deposition in young Sprague-Dawley rats.

The frequency, age-onset and distribution of spontaneously deposited immunoglobulins (Igs) in glomeruli of Sprague-Dawley rats has been investigated. Groups of rats (n = 10) were examined at 4-7 day intervals from birth (presuckling) until 30 days of age. Findings were compared with circulating immunoglobulin concentrations in each age group. Immunoglobulins were undetectable in immature kidneys of newborn rats. However, as early as 5 days, scanty IgA and IgM deposits were observed predominantly in mesangial areas of mature glomeruli, corresponding to low circulating concentrations of these immunoglobulins. By contrast, glomerular IgG deposits were not observed until 21 days, despite relatively high concentrations of circulating maternal IgG from birth. Mesangial deposition of immunoglobulins increased with age. Absence of complement C3c or electron dense deposits associated with this mesangial localization suggests that immunoglobulins were not deposited as immune complexes. Accumulation of non-phlogogenic immunoglobulins in the mesangium of normal rats supports the concept that the mesangium is constantly perfused by circulating macromolecules and filtration residues. The results indicate problems of interpretation of the significance of endogenous immunoglobulin deposition in models of experimental glomerulonephritis, even in studies involving weanling rats.

Animals↗

Glomerular inflammation: a consequence of sequential challenge of the rat mesangium with particulate macromolecules.

Imposil pretreatment (50 mg/100 g bodyweight) of male Sprague-Dawley rate (100-150 g), 24-48 h before an albumin-coated latex challenge resulted 24 h later in markedly reduced mesangial endocytosis of latex, compared with control animals receiving latex-albumin alone. This reduced capacity to ingest latex was associated with increased glomerular infiltration by Ia+ macrophages and mesangial localisation if immunoglobulins and complement C3c. In sharp contrast, pretreatment with albumin-coated latex had little effect on the subsequent mesangial uptake of Imposil. In this reverse situation macrophage infiltration was minimal, immunoglobulin deposition was similar to that in untreated control animals, and C3c was not detectable. Similarly, extending the interval between Imposil pretreatment and albumin-coated latex challenge up to 144h resulted in only minor infiltration by Ia+ macrophages and immunoglobulin localisation without accompanying C3c deposition, even though mesangial latex uptake was still limited. These observations demonstrate the consequences of secondary challenge following mesangial impairment due to a predisposing insult. Glomerular inflammation was dependent upon the timing and nature of the sequential challenge. The results support the concept that mesangial impairment following an initial insult may be a major factor in the predisposition to some forms of human glomerular inflammation.

Animals↗

Combination fine-needle aspiration cytology and intrarenal manometry at the onset of renal dysfunction.

Twenty-three consecutive cadaveric renal allograft recipients immunosuppressed with cyclosporin have been monitored three times a week by fine-needle aspiration cytology and intrarenal manometry until discharge from hospital or until 30 days post-transplant. Standard criteria were used to determine the cause of allograft dysfunction. The onset of allograft rejection was marked by an elevation of the total corrected increment score by fine-needle aspiration cytology in 80 per cent of rejection episodes whereas intrarenal pressure was raised in only 46.6 per cent. However, intrarenal pressure was greater than 40 mmHg on a single occasion in 16 measurements performed on allografts showing evidence of cyclosporin nephrotoxicity. By combining fine-needle aspiration cytology and intrarenal manometry the sensitivity of these tests for allograft rejection was increased to 93.3 per cent at the onset of renal dysfunction. Our results demonstrate that fine-needle aspiration cytology is more sensitive than intrarenal manometry as a single investigation. However, the combined test may have an important role in the differentiation of allograft rejection and cyclosporin nephrotoxicity in the early management of renal allograft recipients.

Biopsy, Needle↗

Preparation, purification and analysis of BSA-coated latex particles for in vivo studies. Non-ionic adsorbance of unbound protein ligand.

A procedure for the preparation, purification and analysis of small, BSA-coated carboxylate-modified latex (CML) particles, suitable for use in in vivo studies has been developed. Following conjugation, uptake of unbound BSA by Amberlite XAD-8 non-ionic adsorbent beads has been shown to be an effective method by which unbound protein ligands may be removed from coated latex preparations.

Adsorption↗