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Biomedical subjects

P G Kerr

Publications and source records attributed to P G Kerr.

At least 19 recordsLinked to original sources
PubMed2002

Development of a capture ELISA for the detection of antibodies to enteropathogenic Escherichia coli (EPEC) in rabbit flocks using intimin-specific monoclonal antibodies.

A capture enzyme-linked immunosorbent assay (cELISA) was developed using intimin-specific monoclonal antibodies to detect specific antibody in rabbits that have been in contact with enteropathogenic Escherichia coli (EPEC). Sera from 121 EPEC-negative, minimum-disease-level (MDL) rabbits were used for negative controls, and sera from 25 MDL rabbits, experimentally infected with EPEC of bio-/serotype 3-/O15, for positive controls. These were used to determine a cut-off value for a positive cELISA result. The value selected gave the test a sensitivity of 80.0% and a specificity of 98.4% on an individual level. At this value, a flock level sensitivity and specificity of 79.2 and 85.2%, respectively were calculated for a flock with a prevalence of seven per cent, if 40 animals were tested, and a minimum of two reactors were obtained. The test characteristics improve with increasing prevalence. To evaluate the diagnostic potential of the cELISA, sera from 40 to 50 slaughter rabbits per flock from 25 rabbit flocks with bacteriologically determined EPEC status were tested. The results demonstrated that this test can be a useful tool to determine the EPEC status of a rabbitry, provided that it is used at regular intervals.

Adhesins, Bacterial↗
PubMed2001

Women's health issues in haemodialysis patients.

OBJECTIVES: To describe reproductive health issues in women with end-stage renal disease (ESRD) treated with haemodialysis. STUDY DESIGN: Cross-sectional survey based on structured interviews. SETTING: Nephrology units of two major metropolitan tertiary referral hospitals in Victoria and their satellite dialysis centres between 1 November 1998 to 30 June 1999. METHODS: Women aged 20 years or over in haemodialysis programs. OUTCOME MEASURES: Menstrual status; prevalence of menstrual and climacteric symptoms; use of gynaecological screening; and prevalence of comorbidities that may benefit from hormone replacment therapy. RESULTS: 48 women completed the survey. They were similar to the 485 women undergoing haemodialysis in Victoria in age (mean age, 55.5 years; range, 20-84 years), years on dialysis (mean age, 3.9 years; range, 1 month-17 years) and primary diagnosis. Eleven of the 15 premenopausal women reported menstrual cycles of 22-35 days, 13 reported common premenstrual symptoms, and six reported dysmenorrhoea that interfered with daily activities. Average age at menopause was 47.7 years (95% CI, 45.6-49.9 years), and six of the 31 postmenopausal women underwent menopause before 45 years. Eight had ever been prescribed hormone replacement therapy (oral in all cases). Over half the women (26) had not had a Pap smear in the last two years, and 12 of those aged over 50 (38%) had not had a mammogram in the same period. CONCLUSION: Despite their risk of early menopause, cardiovascular disease and bone fracture, few women undergoing haemodialysis were offered hormone replacement therapy. Nor were they adequately screened for gynaecological cancers. Women's health issues seem to be neglected among haemodialysis patients.

Adult↗
PubMed2000

The antihypertensive hydralazine is an efficient scavenger of acrolein.

Recent work indicates the highly toxic alpha,beta-unsaturated aldehyde acrolein is formed during the peroxidation of polyunsaturated lipids, raising the possibility that it functions as a 'toxicological second messenger' during oxidative cell injury. Acrolein reacts rapidly with proteins, forming adducts that retain carbonyl groups. Damage by this route may thus contribute to the burden of carbonylated proteins in tissues. This work evaluated several amine compounds with known aldehyde-scavenging properties for their ability to attenuate protein carbonylation by acrolein. The compounds tested were: (i) the glycoxidation inhibitors, aminoguanidine and carnosine; (ii) the antihypertensive, hydralazine; and (iii) the classic carbonyl reagent, methoxyamine. Each compound attenuated carbonylation of a model protein, bovine serum albumin, during reactions with acrolein at neutral pH and 37 degrees C. However, the most efficient agent was hydralazine, which strongly suppressed carbonylation under these conditions. Study of the rate of reaction between acrolein and the various amines in a protein-free buffered system buttressed these findings, since hydralazine reacted with acrolein at rates 2-3 times faster than its reaction with the other scavengers. Hydralazine also protected isolated mouse hepatocytes against cell killing by allyl alcohol, which undergoes in situ alcohol dehydrogenase-catalysed conversion to acrolein.

Acrolein↗
PubMed1999

Outcome of a screening program for vancomycin-resistant enterococci in a hospital in Victoria.

OBJECTIVE: To screen for faecal colonisation with vancomycin-resistant enterococci (VRE) among potentially at-risk patients. DESIGN: Infection control screening program. SETTING: Monash Medical Centre (a tertiary care hospital), Melbourne, Victoria, in the seven months from June 1997. PATIENTS: Patients in the Renal, Oncology and Intensive Care (ICU) Units. MAIN OUTCOME MEASURES: Presence of VRE in a rectal swab or faecal specimen taken at admission and at regular intervals during inpatient stay; presence of vancomycin-resistance genes (vanA, vanB and vanC) assessed by polymerase chain reaction (PCR); genetic clonality of isolates assessed by pulsed-field gel electrophoresis (PFGE). RESULTS: 574 patients (356 renal, 134 ICU and 84 oncology) were screened; 12 were colonised with VRE--nine renal inpatients, two having peritoneal dialysis or incentre haemodialysis, and one ICU patient. Nine isolates were Enterococcus faecalis (seven positive for vanB and two negative for all three resistance genes) and three were Enterococcus faecium (all positive for vanB). Eight were high-level gentamicin resistant. PFGE suggested genetic clonality between the index isolate and five other isolates from renal patients. No specific clinical practice was associated with VRE colonisation. Attempts to clear rectal carriage with oral ampicillin/amoxycillin or bacitracin were of limited success. Although antibiotic prescribing in the Renal Unit was generally consistent with defined protocols, use of vancomycin and third-generation cephalosporins has been further restricted. CONCLUSIONS: Renal inpatients in our institution appear most at risk of VRE colonisation (4.6% overall) and therefore of VRE infection. Routine screening, especially of potentially high-risk patients, should be considered in major Australian hospitals.

Adult↗
PubMed1999

Dialyzer performance in the clinic: comparison of six low-flux membranes.

The aim of this study is to assess the clinical performance of 6 different low-flux dialysis membranes under steady-state conditions in terms of urea and phosphate clearances. Ten stable hemodialysis patients were examined. The following dialyzers were studied, all in 1.5- to 1.6-m2 format: cuprammonium, cellulose acetate, cellulose diacetate, hemophane, polysulfone (low-flux), and polysynthane. The following parameters were examined: urea reduction ratio, phosphate reduction ratio, "instantaneous dialyzer clearance" for urea and phosphate, and total amount of urea and phosphate removed in the dialysate over a 1-week (three dialyses) period. Although there were differences between the membranes, all produced results within a narrow range. There was no one membrane that produced superior clearances in all categories. The cellulose acetate membrane was the least satisfactory membrane. Phosphate clearances were at best one third that of urea clearances. When choosing a low-flux dialysis membrane, urea and phosphate clearances are so similar amongst different membranes that other criteria are likely to have a greater influence on the choice of membrane.

Adult↗
PubMed1998

Granulomatous glomerulonephritis in intravenous drug users: a report of three cases in oxycodone addicts.

Various well-documented renal lesions are associated with intravenous drug use; however, intraglomerular mesangial granulomas have not been previously described. We report three patients who developed an unusual granulomatous glomerulonephritis and interstitial nephritis after intravenous injection of oxycodone, derived from suppositories. Granulomas were seen in an intraglomerular mesangial and also interstitial location. In both sites, the granulomas were associated with filamentous material, presumably derived from a component of the suppositories. This material was periodic acid-Schiff-positive, but negative with Congo red and silver stains. Ultrastructurally, the filamentous material was seen within the mesangial granulomas and also in a subendothelial location, suggesting derivation from the circulation with subsequent transport across the basement membrane and accumulation in the mesangium, where a granulomatous reaction was elicited. All patients developed a degree of renal failure; two of the patients require hemodialysis 20 and 30 months after presentation.

Adult↗
PubMed1998

Total body nitrogen predicts long-term mortality in haemodialysis patients--a single-centre experience.

BACKGROUND: It has been estimated that 30-50% of adult haemodialysis patients have moderate to severe malnutrition. We have previously shown that estimation of total body nitrogen, expressed as a nitrogen index (NI) by in vivo neutron activation analysis (IVNAA) is an accurate tool for estimating total body protein in dialysis patients. It is not clear whether the nitrogen index is predictive of mortality and morbidity in dialysis patients. METHODS: We studied the long-term predictive value of nutritional assessment by IVNAA and serum albumin on mortality and morbidity (including infection episodes requiring hospital admission, ischaemic heart disease (IHD), cerebrovascular or peripheral vascular disease (PVD). Seventy-six chronic haemodialysis patients were initially studied between 1989 and 1991, with a minimum follow-up of 5 years. The mean age of the patients was 48.3 years (range 21-76). Patients were divided into two groups, group I, n = 22, had a NI < or = 0.8 (NI < or = 0.8 represents protein malnutrition) and group II, n = 54, had a NI > 0.8. RESULTS: Fifteen patients in group II died in the follow-up period compared to nine from group I (P < 0.05), but NI < or = 0.8 did not predict vascular or infective morbidity. Serum albumins < or = 35 g/day did predict over all mortality (P < 0.05) as well as infection episodes (P < 0.001). When patients above the age of 50 years were analysed, NI did predict mortality (P < 0.05) but serum albumin did not, while the age of> 50 itself was a strong predictor of mortality (P < 0.001). CONCLUSION: We conclude that NI < or = 0.8 is predictive of long-term mortality. This reinforces the view that low body protein stores are predictive of increased mortality in dialysis patients and that the serum albumin is predictive of mortality because of its reflection of protein stores.

Adult↗
PubMed1997

Precise quantification of dialysis using continuous sampling of spent dialysate and total dialysate volume measurement.

The "gold standard" method to evaluate the mass balances achieved during dialysis for a given solute remains total dialysate collection (TDC). However, since handling over 100 liter volumes is unfeasible in our current dialysis units, alternative methods have been proposed, including urea kinetic modeling, partial dialysate collection (PDC) and more recently, monitoring of dialysate urea by on-line devices. Concerned by the complexity and costs generated by these devices, we aimed to adapt the simple "gold standard" TDC method to clinical practice by diminishing the total volumes to be handled. We describe a new system based on partial dialysate collection, the continuous spent sampling of dialysate (CSSD), and present its technical validation. Further, and for the first time, we report a long-term assessment of dialysis dosage in a dialysis clinic using both the classical PDC and the new CSSD system in a group of six stable dialysis patients who were followed for a period of three years. For the CSSD technique, spent dialysate was continuously sampled by a reversed automatic infusion pump at a rate of 10 ml/hr. The piston was automatically driven by the dialysis machine: switched on when dialysis started, off when dialysis terminated and held during the by pass periods. At the same time the number of production cycles of dialysate was monitored and the total volume of dialysate was calculated by multiplying the volume of the production chamber by the number of cycles. Urea and creatinine concentrations were measured in the syringe and the masses were obtained by multiplying this concentration by the total volume. CSSD and TDC were simultaneously performed in 20 dialysis sessions. The total mass of urea removed was calculated as 58038 and 60442 mmol/session (CSSD and TDC respectively; 3.1 +/- 1.2% variation; r = 0.99; y = 0.92x -28.9; P < 0.001). The total mass of creatinine removed was 146,941,143 and 150,071,195 mumol/session (2.2 +/- 0.9% variation; r = 0.99; y = 0.99x + 263; P < 0.001). To determine the long-term clinical use of PDC and CSSD, all the dialysis sessions monitored during three consecutive summers with PDC (during 1993 and 1994) and with CSSD (1995) in six stable dialysis patients were included. The clinical study comparing PDC and CSSD showed similar urea removal: 510 +/- 59 during the first year with PDC and 516 +/- 46 mmol/dialysis session during the third year, using CSSD. Protein catabolic rate (PCR) could be calculated from total urea removal and was 1.05 +/- 0.11 and 1.05 +/- 0.09 g/kg/day with PDC and CSSD for the same periods. PCR values were clearly more stable when calculated from the daily dialysate collections than when obtained with urea kinetic modeling performed once monthly. We found that CSSD is a simple and accurate method to monitor mass balances of urea or any other solute of clinical interest. With CSSD, dialysis efficacy can be monitored at every dialysis session without the need for bleeding a patient. As it is external to the dialysis machine, it can be attached to any type of machine with a very low cost. The sample of dialysate is easy to handle, since it is already taken in a syringe that is sent directly to the laboratory. The CSSD system is currently in routine use in our unit and has demonstrated its feasibility, low cost and high clinical interest in monitoring dialysis patients.

Creatinine↗
PubMed1996

Dialyzer reuse: interaction between dialyzer membrane, disinfectant (formalin), and blood during dialyzer reprocessing.

The growing practice of dialyzer reuse in recent years is mainly based on medical and economic considerations. However, adverse reactions such as immunohemolytic anemia due to anti-Nform antibody associated with dialyzer reuse have been reported. In this study, scanning electron microscopy and cytologic staining were used to evaluate the interaction between blood components and the reprocessed synthetic dialyzer membrane (polysulfone) after disinfectant (formaldehyde) treatment. The results showed that various blood components such as fibrin and blood cells still adhered to the dialyzer membrane after reprocessing. The study also demonstrated that the adhered denatured blood components could be detached by sonication and/or simulated hemodialysis and then gain access into the circulation. The re-entry of the denatured blood components to the patients exposed to reused dialyzers may result in an enhanced immunological response which may contribute to antibody formation (such as anti-Nform antibody) with a reused hemodialyzer.

Anemia, Hemolytic↗
PubMed1996

Assessment of the nutritional state of dialysis patients.

The importance of the nutritional state of our dialysis patients has been stressed for many years. Although the calculation of the protein catabolic rate has become common practice in many dialysis units, there are several problems with this measurement. In addition, the serum albumin level is subject to multiple influences making its interpretation in individual patients difficult. This paper examines a different approach to nutritional assessment-that of using longer term measures of nutrition. Several techniques for measuring body composition are explored and their use in end-stage renal disease (ESRD) examined. Total body nitrogen measurement is a gold standard technique which has been validated in renal patients, unfortunately it is not widely available. Of the alternatives, dual energy X-ray absorptiometry scanning for assessment of fat-free mass appears to be the best technique with the narrowest limits of agreement compared to gold standard techniques. Whilst bioelectrical impedance is reasonable for body water assessment, it is not reliable in ESRD patients for lean-body mass estimation.

Absorptiometry, Photon↗
PubMed1996

Total body protein status assessed by different estimates of fat-free mass in adult peritoneal dialysis patients.

OBJECTIVE: To assess the usefulness of fat-free mass (FFM) as an index of total body protein (TBPr) status in continuous ambulatory peritoneal dialysis (CAPD) patients. DESIGN: TBPr was measured by in vivo neutron activation analysis (IVNAA) and expressed as a standardised protein index (PI). FFM was estimated by dual energy X-ray absorptiometry (DXA), whole body counting of total body potassium (TBK), and creatinine kinetics (CK), and expressed as a standardised FFM index (FFMI). FFM was also determined by a criterion method based on four compartment model (4CM) which is defined as the sum of total body water determined by D2O dilution, TBPr determined by IVNAA, bone mineral determined by DXA, and glycogen estimated to be 4.4% of TBPr. Each patient was measured within a four hour period by all methods. SETTING: Body Composition Laboratory, Monash Medical Centre. SUBJECTS: Six male and twelve female CAPD patients (33-77 years). RESULTS: FFMI assessed by DXA and by TBK agreed with measurements of PI on identifying the mean TBPr status of the CAPD group as significantly below a comparable normal reference population (mean Z score: PI = -1.01 (P < 0.05); FFMI by DXA = -0.50 (P < 0.05); FFMI by TBK = -1.24 (P < 0.05)). In contrast, FFMI assessed by CK did not reveal a significantly reduced TBPr status (mean Z score: -0.70 (NS)). Furthermore, significant linear correlations were noted between PI and FFMI estimated by DXA and by TBK (r = 0.57 (P < 0.05) vs r = 0.69 (P < 0.05)) however no significant correlation was observed between PI and FFMI estimated by CK (r = 0.36 (NS)). Moderate variation in FFM hydration did not compromise the ability of DXA, TBK or CK to differentiate between protein deleted, normal and enriched patients. Comparison of FFM estimates between the criterion method and either DXA, TBK or CK revealed no significant bias (+ 1.8 kg vs -2.0 kg vs +0.8 kg) and respective SEE values of 3.8 kg (8.3%), 5.9 kg (14.3%) and 9.6 kg (21.7%). CONCLUSION: The findings of this study indicate that FFM estimated by either DXA or the whole body counting of TBK is a useful index of TBPr status in CAPD patients. However, FFM assessed by CK does not appear to be an appropriate index of TBPr status in CAPD patients.

Absorptiometry, Photon↗
PubMed1995

Kt/V in CAPD by different estimations of V.

This study compared the measurements of total body water (TBW) by 58% body weight (TBW58%), the Watson equation (TBWWV) and bioelectric impedance (TBWBIA) with the gold standard, Deuterium oxide (TBWD2O) dilution method in twenty continuous ambulatory peritoneal dialysis (CAPD) patients. TBW volumes were highest when calculated as TBW58% (42.6 +/- 9.4 liter) and lowest when calculated from TBWWV (34.6 +/- 6.8 liter). TBWBIA underestimated TBW when compared to TBWD2O, although the difference was not statistically significant (37.1 +/- 9.8 liter and 38.8 +/- 9.3 liter, respectively). In fact, TBWBIA correlated strongly with TBWD2O (r = 0.8, P < 0.0001). These discrepancies resulted in significant differences when Kt/V week-1 derived from the four methods were compared. To determine the effect of percent fat mass on the estimation of TBW by each method, we compared TBW and Kt/V week-1 derived from the four methods in nine CAPD patients who had normal percent fat mass (Non-Obese) and 11 CAPD patients who had greater than normal % fat mass (Obese). In the Non-Obese group, there was close correlation of TBWBIA, TBWWV and TBW58% when compared with TBWD2O (r = 0.93, P < 0.001, r = 0.89, P < 0.01 and R = 0.86, P < 0.01, respectively. Also, Kt/V week-1 derived from TBWBIA, TBWWV and TBW58% correlated strongly with Kt/V week-1 from TBWD2O (r = 0.93, P < 0.0005, r = 0.83, P < 0.01 and r = 0.8, P < 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Body Composition↗
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↗