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Biomedical subjects

P G Kerr

Publications and source records attributed to P G Kerr.

At least 37 records · Page 2Linked to original sources
PubMed1994

Control of post-transplant erythrocytosis by enalapril.

OBJECTIVE: To assess the erythropoietin response in patients with erythrocytosis after renal transplantation who were treated with enalapril. PATIENTS: Fourteen patients with stable renal transplants (creatinine clearance, 74.4 +/- 24.6 mL/min) and a packed cell volume of 51% or more over six months and who had no other cause for their erythrocytosis. METHODS: Patients were treated with enalapril for six months. Serum erythropoietin levels, creatinine clearance and packed cell volume were measured before and during the study; patients were reviewed each month. RESULTS: All patients had erythropoietin levels inappropriate for their packed cell volume. After six months' therapy with enalapril their mean erythropoietin concentration of 21.3 +/- 5.0 U/L fell to 7.4 +/- 1.3 U/L (P < 0.02) although the concentration increased in two patients. The mean packed cell volume fell from 52.7% +/- 0.5% to 44.4% +/- 1.0% (P < 0.0001). There was no change in renal function. CONCLUSION: Low-dose enalapril controls post-transplant erythrocytosis, at least in part, by lowering serum erythropoietin levels.

Adult↗
PubMed1994

Deoxyspergualin suppresses local macrophage proliferation in rat renal allograft rejection.

Deoxyspergualin (DSP) is a potent immunosuppressive drug that is able to both prevent and reverse acute allograft rejection. Although there is good evidence that DSP can inhibit T and B lymphocyte responses, the effect of this drug upon monocyte function is controversial. In the current study, substantial local proliferation of inflammatory macrophages (41.6 +/- 5.5% of ED1+ cells) within acutely rejecting rat renal allografts was identified by expression of the proliferating cell nuclear antigen. Treatment of animals with DSP not only reduced macrophage accumulation within the tissue, but it also significantly inhibited local proliferation of macrophages within the graft (26.4 +/- 5.6% of ED1+ cells, P < 0.05 vs. untreated). This appeared to be, at least in part, a direct effect of DSP upon macrophages since the drug also inhibited growth of 2 monocytic cell lines (RC-2A and U937) in vitro. However, DSP treatment had no effect upon LPS-induced monocyte IL-1 beta, TNF alpha, and IL-6 mRNA and protein production, indicating that this drug is not a general inhibitor of monocyte function. In conclusion, this study has demonstrated that local proliferation of macrophages within the kidney is a prominent feature of acute allograft rejection and that inhibition of this response is one mechanism whereby DSP exerts its potent immunosuppressive actions.

Animals↗
PubMed1994

Cells surrounding haemodialysis-associated amyloid deposits are mainly macrophages.

Dialysis-related amyloidosis is a type of amyloidosis which had beta 2-microglobulin as the major protein constituent and occurs predominantly in haemodialysis patients. Its prevalence is very high with increasing time on dialysis treatment and its pathogenesis is not completely understood. While remarkable progress has been made in the identification of the components of the deposits, there are no reports characterizing the cells surrounding the amyloid fibrils. To characterize the cellular composition of the amyloid material, specimens from seven patients treated by maintenance haemodialysis were studied with immunoperoxidase labelling using monoclonal antibodies to leukocytes (CD3, CD14, CD68, CD4, CD8, CD45). The results were very reproducible for the seven deposits assessed: Of the 182 +/- 26 leukocytes/0.2 mm2 of amyloid tissue expressing the 71.5-CD45 marker (common leukocyte), 91 +/- 6% were CD68 (KP1) positive (monocyte macrophage). No CD3-positive cells (T-cell marker) were found in six of the seven patients, with only 1.6% in the remaining one. The present study shows that although amyloidosis has classically been considered as an acellular pathology, clearly there are cells surrounding amyloid fibrils. Strikingly, these cells are almost exclusively macrophages; there are no lymphocytes or granulocytes. The putative role of macrophages in the pathogenesis of beta 2-microglobulin amyloidosis remains to be established. However, the identification and quantitation of the cells surrounding the amyloid deposits may be important for subsequent studies to elucidate amyloid pathogenesis and particularly protein-cell interactions.

Adult↗
PubMed1994

Suppression of pulmonary injury in experimental 'Goodpasture's syndrome' by deoxyspergualin (DSP).

DSP is a potent immunosuppressive drug which can prevent allograft rejection and suppress acute rejection episodes. In this study, the ability of DSP to suppress pulmonary injury in experimental Goodpasture's syndrome was investigated. Passive accelerated anti-glomerular basement membrane (GBM) disease was induced in rats by priming with rabbit IgG, followed 5 days later by injection of rabbit anti-GBM serum (day 0). Groups of five animals were treated with DSP (5 mg/kg intraperitoneally per day) or saline (untreated) from day 0 until being killed on days 1, 7, 14 or 21. At day 1, both DSP-treated and untreated animals exhibited similar pulmonary haemorrhage, oedema, and prominent perivascular leucocyte infiltration. Untreated animals subsequently developed severe widespread pulmonary damage including granulomatous lesions and extensive fibrosis, which correlated with infiltration of macrophages and immune-activated (IL-2R+) mononuclear cells (P < 0.01). Tumour necrosis factor-alpha (TNF-alpha), a known mediator of acute lung damage, was produced by pulmonary mononuclear cells throughout the experimental course. In contrast, DSP treatment resolved pulmonary haemorrhage, prevented the appearance of granulomatous lesions, and resulted in a histologically normal lung structure by day 21. This improvement was associated with a marked suppression of macrophage infiltration (P < 0.001 versus untreated), accumulation of immune activated (IL-2R+) mononuclear cells (P < 0.01 versus untreated), and TNF-alpha production (P < 0.05 versus untreated). DSP treatment also suppressed the deposition of rat anti-rabbit IgG immunoglobulin and C3 along the alveolar basement membrane (P < 0.05 versus untreated). In conclusion, DSP suppressed pulmonary injury in accelerated anti-GBM disease by acting on the local cellular immune response and the systemic humoral immune response. Further studies are warranted to determine whether this could be a useful drug for the treatment of Goodpasture's syndrome in humans.

Animals↗
PubMed1994

The adequacy of fragmin as a single bolus dose with reused dialyzers.

Thirty-four hemodialysis patients were studied in a crossover fashion to compare the effectiveness of bolus-dose Fragmin (a low molecular weight heparin) with regular heparin usage in hemodialysis. For each anticoagulant, 3 dialyzes were studied for each patient; the first sessions involved a new dialyzer, and the subsequent sessions involved dialyzers reprocessed with peracetic acid. To assess the effectiveness of the anticoagulation regimens, the following were measured: the dialyzer fiber bundle volume and the instantaneous dialyzer clearances for urea (1 h into the second session). In addition, factor Xa levels were measured in 5 patients during the first and second sessions at 0 min, 30 min, and 4 h. Fiber bundle volumes were (in ml) 75.4 +/- 8.8, 73.0 +/- 8.9, and 73.5 +/- 7.6 on first, second, and third uses with Fragmin (p = ns); and 77.8 +/- 9.0, 73.4 +/- 8.1, and 73.8 +/- 8.1 with heparin (p < 0.001 second and third vs. first). Thus, there were no significant differences between Fragmin and heparin. Instantaneous dialyzer clearances were 165.8 +/- 12.6 ml/min with Fragmin and 163.8 +/- 9.8 with heparin (p = ns). Factor Xa levels were 0 predialysis, 0.81 +/- 0.17 U/ml at 30 min on first use, and 0.92 +/- 0.09 U/ml on second use (p = ns); they were 0.51 +/- 0.21 U/ml at 4 h on first use and 0.61 +/- 0.16 U/ml on second use (p = ns). Thus, bolus-dose Fragmin provided similar results to constant infusion heparin and is not deleteriously influenced by reprocessing dialyzers with peracetic acid.

Adult↗
PubMed1993

Calcium kinetics and the long-term effects of lowering dialysate calcium concentration.

The optimal dialysate calcium (Ca) content for hemodialysis has been classically fixed at 1.75 mM. However, this dialysate Ca concentration (dCa) with its positive intradialytic Ca balance combined with the use of CaCO3 as a phosphate binder may result in hypercalcemia. To prevent or treat hypercalcemia, a decrease in dCa has been proposed. In the present study both the acute and the long-term effects of lowering dCa were assessed. Additionally, given the results obtained after one year with low dCa the effectiveness of i.v. 1 alpha vitamin D3 in lowering PTH serum levels in two groups of patients dialyzed with different dCa was also studied. (a) Ca kinetics during hemodialysis (HD) and on line hemodiafiltration (HDF) were studied in a group of nine stable patients who were sequentially treated with 1.75, 1.5 and 1.25 mM dCa. Dialysate was the same but for the dCa which was lowered stepwise. Na, K, tCa, ionized Ca (iCa), proteins, phosphate and pH were measured from blood inlet and outlet and dialysate outlet at the start, one hour, two hours and after the treatments. At the same time weight, blood pressure and heart rate were recorded. The sieving of iCa was significantly different in HDF versus HD (F = 6.73; P < 0.01); intravenous infusion of 18 liters of filtered ultrapure dialysate compensated the Ca loss due to the convective component of HDF, as iCa was similar at the blood inlet in HD and HDF in the three dCa tested (F = 2.59; NS). Intradialytic iCa kinetics measured in the blood inlet were significantly different with different dCa (P < 0.001 for 1.75 mM vs. 1.5 mm and P < 0.001 for 1.5 mM vs. 1.25 mM). A significant increase in post-dialysis iCa was observed with dCa of 1.75 and 1.5 while no modification was observed with 1.25 mM dCa. (b) Regarding long-term effects of lowering dCa, seven of the nine patients acutely studied were followed for a one year period after changing from dCa = 1.5 to dCa = 1.25 mM. A control group of six patients was maintained with dCa = 1.5 for the same period of time and with the same treatment schedule but for dCa. Total Ca, phosphate and alkaline phosphatase were assessed monthly, and phosphate binders and oral vitamin D derivative doses were adapted accordingly. Intact PTH was determined quarterly. CaCO3 oral intake was more than doubled in the low dCa group. Total Ca, phosphate and ALP were similar in both groups over the assessed year.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Suppression of experimental crescentic glomerulonephritis by deoxyspergualin.

Deoxyspergualin is an immunosuppressive drug which is effective in both preventing allograft rejection and suppressing steroid-resistant acute rejection. This study was designed to determine whether deoxyspergualin could suppress the development of rapidly progressive crescentic glomerulonephritis in antigen-primed animals. Accelerated anti-glomerular basement membrane (GBM) glomerulonephritis was induced by priming rats with rabbit immunoglobulin G (IgG), followed 5 days later by an injection of rabbit anti-rat GBM serum (day 0). Groups of five animals were treated with deoxyspergualin (5 mg/kg.day) or saline by daily ip injection from day 0 until euthanasia on days 1, 7, 14, or 21. Deoxyspergualin treatment resulted in a significant suppression of renal disease. Compared with saline-treated controls, deoxyspergualin treatment reduced proteinuria, resolved hematuria, and completely prevented a fall in creatinine clearance. Deposition of rabbit IgG along the GBM was unaffected by deoxyspergualin treatment, but glomerular deposition of rat IgG and C3 was significantly reduced from day 14 onwards, which was associated with a significant reduction of circulating rat anti-rabbit IgG. Deoxyspergualin treatment also produced a dramatic improvement in renal histology. Glomerular necrosis, fibrosis, and crescent formation were markedly suppressed, whereas tubulointerstitial lesions were completely prevented. This was associated with a marked suppression of mononuclear cell infiltration and activation. In the glomerulus, macrophage infiltration was suppressed by approximately 50%, whereas accumulation of macrophages and immune-activated (interleukin-2 receptor) T cells within the interstitium was almost completely abrogated by deoxyspergualin treatment. In conclusion, deoxyspergualin was found to be effective in suppressing the development of experimental crescentic glomerulonephritis in antigen-primed animals by acting on both the local cell-mediated response within the kidney and the systemic humoral immune response. Further work is warranted to determine whether this could be a useful drug for the treatment of human proliferative glomerulonephritis.

Animals↗
PubMed1993

Serum alpha 2-macroglobulin in haemodialysis patients: baseline and kinetic studies.

The pathogenesis of dialysis related amyloidosis remains unresolved despite the identification of beta 2-microglobulin (beta 2M) as the major protein constituent, as well as other proteins being present in the deposits. Among the latter we have assessed the serum concentrations of alpha 2-macroglobulin (alpha 2M) both in the baseline stage and during the haemodialysis (HD) procedure. We have also assessed the influence of the membrane on alpha 2M kinetics. Fifteen HD patients with histologically proven dialysis-related amyloidosis (DRA group) and 15 HD patients clinically and radiologically considered dialysis-related amyloidosis free (control group) were included in the baseline study. Blood was sampled the day before the second dialysis of the week and alpha 2M, beta 2M and alpha 1 antitrypsin were determined along with the routine biological analysis of these patients. Serum alpha 2M was greater in dialysis-related amyloidosis than in control patients (t = 2.35; P < 0.026). Serum beta 2M was similar in both groups. The serum alpha 2M and beta 2M correlated in patients with dialysis-related amyloidosis (r = 0.64; P < 0.01), while no correlation was found in controls (r = 0.17; NS). Stepwise analysis taking the presence of dialysis-related amyloidosis as the dependent variable retained the serum alpha 2M concentration as the first variable in the model (F = 4.4; partial r = 0.38; P < 0.046).(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloidosis↗
PubMed1993

Accuracy of Kt/V estimations in high-flux haemodiafiltration using per cent reduction of urea: incorporation of urea rebound.

The estimation of Kt/V by utilization of the pre- and postdialysis urea concentrations (per cent reduction in urea and In(Upre/Upost)) provides a simple, quick technique that can be applied at the bedside. However, the accuracy of such techniques has been questioned. One possible reason for this inaccuracy may be the frequently observed postdialysis rebound in serum urea. We assessed the urea rebound at 30 min postdialysis in 34 haemodiafiltered patients and compared the calculation of Kt/V using this urea concentration with that using the immediate postdialysis concentration. These results were then compared to the Kt/V calculated by urea kinetic modelling (UKM), also utilizing the delayed serum urea concentration. The degree of urea rebound observed was large, 21.4%, being a reflection of the short-duration, rapid-flux dialysis. The formulae for calculation of Kt/V all significantly correlated with Kt/V by UKM but all gave results significantly different from Kt/V by UKM (P < 0.001 by paired t test). For assessment of Kt/V by these formulae or by UKM, the urea rebound is too large to ignore in the setting of short-duration, rapid-flux dialysis.

Blood Proteins↗
PubMed1992

The effects of reprocessing high-flux polysulfone dialyzers with peroxyacetic acid on beta 2-microglobulin removal in hemodiafiltration.

The reuse of dialyzers is widely practiced, especially in the United States. Despite this, the effects of reuse on the efficacy of removal of solutes and more recently proteins such as beta 2-microglobulin (beta 2M) are the subject of much debate. There is considerable evidence to suggest that reuse after cleansing and sterilizing with formalin, with or without bleach, maintains dialyzer performance. In this study, we have examined peroxyacetic acid use as the cleansing and sterilizing agent using Renatron machines. We analyzed reuse in 24 patients using polysulfone membranes in a hemodiafiltration (HDF) unit over a 2-year period. The mean maximum number of uses achieved was 20.1 +/- 0.5. Several factors considered clinically to influence the number of reuses achievable (hemoglobin, white blood cell, and platelet levels, erythrocyte sedimentation rate [ESR], and fibrinogen and total protein levels) were found not to influence the maximum number of uses obtainable. We then assessed prospectively the performance of 26 polysulfone dialyzers after peroxyacetic acid reprocessing up to 20 times, particularly with regard to their ability to remove beta 2M. We report that this combination of polysulfone membranes reprocessed with peroxyacetic acid used for HDF up to 20 times exhibits a maintained high level removal of compounds beyond a molecular weight (MW) of 12,000. Any secondary membrane formation that occurs appears not to influence the subsequent removal of beta 2M. Thus, we would recommend the use of peroxyacetic acid for reprocessing dialyzers in a safe and efficacious manner.

Adult↗
PubMed1992

Whole blood serotonin levels are markedly elevated in patients on dialytic therapy.

The normal range for whole blood serotonin levels in chronic renal failure patients has not been defined. As serotonin may be implicated in platelet abnormalities, hypo- and hypertension and itch in dialysis patients, serotonin whole blood levels were measured in a group of patients with chronic renal failure and/or who were dialysis dependent. The levels were elevated in 12 patients with moderate (mean serum creatinine 335 +/- 54 mumol/l) chronic renal failure (270 +/- 46 micrograms/l) compared to 11 normals (163 +/- 17 micrograms/l, p less than 0.05; quoted normal range less than 300 micrograms/l) but did not correlate with serum creatinine levels. There was a marked elevation in serotonin levels in dialyzed patients, including those on hemodialysis (polysulfone, n = 6, 747 +/- 234 micrograms/l; cuprophane membranes, n = 6, 708 +/- 198 micrograms/l), hemodiafiltration (n = 12, 695 +/- 130 micrograms/l) and especially peritoneal dialysis (n = 6, 1,148 +/- 162 micrograms/l). All results were significant (p less than 0.01) compared to normals and compared to the nondialyzed group (p less than 0.05). The level of serotonin decreased during hemodialysis regardless of the membrane used. There was no positive correlation of serotonin levels with pruritus or hypertension, although there was a negative correlation with systolic blood pressure. The reference range for serotonin whole blood levels needs to be broadened when considering dialyzed patients.

Adult↗
PubMed1992

Measurement of vascular access recirculation without contralateral venous puncture.

The rate of recirculation is an important variable in calculating the correct dose of dialysis delivered to a patient. Traditionally it is calculated using blood results obtained from the arterial and venous lines and from venous puncture of the opposite arm. To avoid this venipuncture, cessation of the blood pump for 1 or 2 min was attempted to mimic the systemic circulation. This technique underestimated recirculation but was statistically correlated with the result obtained by the classical method, thus it is possible to derive a formula to obtain the recirculation value without contralateral venipuncture.

Adult↗
PubMed1992

Two new anti-rat macrophage monoclonal antibodies.

There are relatively few monoclonal antibodies (MAbs) to rat monocyte/macrophages available. We describe here 2 new such antibodies. The first, 109.2, recognizes most rat monocyte/macrophages and all polymorphs. The antigen recognized by this antibody is upregulated by 15 mins exposure to PMA (Phorbol myristate acetate) but down regulated by overnight exposure to LPS (lipopolysaccharide). It is probably an adhesion molecule and is likely to represent the rat equivalent of CD11b. The second antibody, 112.1, recognizes lysozyme in rat macrophages, particularly alveolar macrophages. In addition it also recognizes lysozyme in hen, rabbit and human macrophages. It also recognizes lysozyme in other tissues such as Paneth cells and proximal renal tubular cells.

Animals↗
PubMed1992

A call to the international nursing community: put AIDS in developing countries on the agenda.

In some African countries 10%-15% of the middle class may due during the 1990s and at the present time the human infrastructure is being eroded by HIV. Over 90% of home and community care is being supervised by nursing and midwifery personnel in some developing countries. What will happen if these carers become ill or die? Peter Kerr provided a micro view of HIV disease in developing countries in 'Health care crisis in Africa', August ANJ. In this article he discusses the macro implications for developing countries as they encounter the consequences of what is likely to be the most devastating epidemic of this century.

Acquired Immunodeficiency Syndrome↗