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Biomedical subjects

P E Hickman

Publications and source records attributed to P E Hickman.

At least 19 recordsLinked to original sources
PubMed2000

Automated measurement of unsaturated iron binding capacity is an effective screening strategy for C282Y homozygous haemochromatosis.

BACKGROUND: C282Y hereditary haemochromatosis is an appropriate condition for population screening. Transferrin saturation, the best screening test to date, is relatively expensive, labour intensive, and cannot be automated. Unsaturated iron binding capacity is a surrogate marker of transferrin saturation and its measurement can be automated. AIMS: To evaluate a screening strategy for C282Y hereditary haemochromatosis in a tertiary hospital environment based on unsaturated iron binding capacity as the initial screening test. METHODS: Measurement of unsaturated iron binding capacity was adapted to the main laboratory analyser. An unsaturated iron binding capacity of less than 30 micromol/l was identified as an appropriate decision point and 5182 consecutive subjects were screened over 28 consecutive days. RESULTS: Of those screened, 697 had an unsaturated iron binding capacity less than 30 micromol/l. Of these, transferrin saturation was greater than 40% in 294. A total of 227 were able to be genotyped for the C282Y mutation. Nine subjects homozygous for C282Y were identified. Based on full cost recovery, affected persons were identified at a cost of Aus$2268.77 per case (approximately US$1496). CONCLUSION: Automated measurement of unsaturated iron binding capacity enables a cost effective, large scale population screening programme for C282Y hereditary haemochromatosis to be developed.

Adult↗
PubMed1999

The lack of standardization of cardiac troponin I assay systems.

The lack of standardization of cardiac troponin I (cTnI) assay systems has meant an inability to compare absolute values between methods, and non-traceability of cTnI measurement in clinical laboratories. The present study tested whether a common calibrator for cTnI would harmonize values between different methods. Twenty fresh-frozen plasma samples and a common calibrator were analyzed in duplicate using the Dade Behring Stratus II, Chiron ACS:180, Abbott AxSYM, and Beckman Coulter Access immunoassay systems. Uncorrected cTnI values varied up to 60-fold between systems, and when correlated to the Stratus, linear regression slopes were 0.97 (ACS:180), 4.86 (AxSYM), and 0.03 (Access), verifying the differences in calibration. After correction for calibration differences by reference to the common calibrator, among-assay CV ranged from 2.7% to 55%, and was >25% for eight samples. However, the exclusion of Access results reduced the CV to 32% with only four outliers. The results show that comparable cTnI values between methods are possible by the use of a common calibrator. The lack of method harmonization for some samples may be due to non-equal antibody immunoreactivity of different plasma cTnI forms. The complete standardization of cTnI measurement requires both a secondary reference material and standardization of manufacturers' cTnI antibodies.

Clinical Chemistry Tests↗
PubMed1999

Plasma homocysteine levels in indigenous Australians.

OBJECTIVES: To determine plasma homocysteine levels in indigenous Australians living in urban areas, and the relationship of these levels with other risk factors in this population. DESIGN: Cross-sectional study. SUBJECTS AND SETTING: 365 urban indigenous Australian subjects, 153 men and 212 women, mean (SE) age 42 (1) years, ascertained without regard to history of atherosclerotic disease, in collaboration with community-based health centres in five indigenous communities in south-east Queensland, 1997-1998. MAIN OUTCOME MEASURES: Plasma homocysteine levels, age, sex, smoking history, metformin therapy, history of atherosclerotic vascular disease, serum creatinine level, red cell folate and serum vitamin B12 levels. RESULTS: 89 subjects (24%) had plasma homocysteine levels 15 mumol/L or above. Homocysteine levels were higher in men than in women (men: 14.4 mumol/L; 95% confidence interval [CI], 13.6-15.2; women: 11.9 mumol/L; 95% CI, 11.4-12.5) (P < 0.001); correlated with age (P < 0.001); higher in current smokers (P = 0.02); higher in subjects taking metformin therapy (P = 0.007); and higher in subjects with a history of atherosclerotic vascular disease (P < 0.001). Homocysteine levels were also correlated with serum levels of creatinine (P < 0.001), red cell folate (P < 0.001), and vitamin B12 (P < 0.001). CONCLUSIONS: These data indicate that the high plasma levels of homocysteine of Australian indigenous subjects are associated with a history of vascular disease, and correlated with, among other things, smoking, and folate and vitamin B12 nutritional deficiency. These are potentially reversible risk factors, and our data suggest that focusing public health initiatives on these issues may reduce the high prevalence of cardiovascular disease in the Australian indigenous population.

Adult↗
PubMed1998

Functional and structural characterization of isolated perfused stingray liver including effects of ischaemia/reperfusion.

The morphological and functional characteristics of stingray liver were studied, including the effect of ischaemia/reperfusion. With an isolated perfused model, it was shown that the stingray liver was more resistant than the rat liver to ischaemia/reperfusion injury; this was consistent with the differing partial oxygen tensions usually present in the two species. This study confirmed that whereas stingray hepatocytes form tubules with central bile canaliculi as in other fish, the stingray liver has portal triads and a lobular architecture as in mammals. Apoptosis of hepatocytes, demonstrated in the normal liver, was only marginally enhanced by ischaemia/reperfusion. Resulting apoptotic bodies were phagocytized by macrophage-like cells in hepatocyte tubules. In contrast to rat liver, the stingray liver showed no necrosis after ischaemia-reperfusion.

Animals↗
PubMed1998

Longitudinal study of bone turnover after acute spinal cord injury.

Increased bone turnover is a sequel of spinal cord injury (SCI) and predisposes to a number of clinically relevant complications, including osteoporosis and fractures. There are limited data available regarding the changes in modern markers of bone metabolism after SCI. We report a 6-month longitudinal follow-up of biochemical markers of bone metabolism (free and total deoxypyridinoline, total pyridinoline, N-telopeptide, osteocalcin, and total alkaline phosphatase) and bone mineral densitometry in 30 subjects with acute SCI. Markers of bone formation showed only a minor rise, remaining within the reference range. In contrast, markers of bone resorption showed a significant rise after acute SCI, peaking around weeks 10-16, with values up to 10 times the upper limit of normal. Paired bone mineral densities (n = 11; on the average, determined 14 weeks apart) showed no change at the hip, lumbar spine, or radius, but demonstrated a decrement in the entire lower limbs. changes in biochemical markers of bone formation and resorption were comparable in patients with quadriplegia and paraplegia, except for a greater increase in quadriplegics in pyridinoline, expressed as a percentage of baseline. In conclusion, a marked increase in bone resorption and modest changes in bone formation occur after SCI, and possibly increased bone resorption occurs in quadriplegia.

Adolescent↗
PubMed1997

Heterophilic antibodies remain a problem for the immunoassay laboratory.

The prevalence of heterophilic antibody interference in a modern immunochemiluminometric assay containing blocking agents was determined using thyrotropin as an illustrative example. Serum samples were obtained from 295 consecutive patients who underwent routine thyroid function testing. The following versions of the thyrotropin assay were used: protocol A (zero blocker), protocol B (routine blocker concentration), and protocol C (extra blocker). Ten patients (prevalence 3.4%) had significant levels of heterophilic antibodies (protocol A value greater than 9 SD from the protocol B value). The observed thyrotropin levels for protocols B and C were the same for all patients, consistent with the reagent blockers in routine assays adequately eliminating heterophilic antibody interference. However, seven more patients (0.03%) in series of 21,000 assessed by routine thyroid function testing had discordant results because of a concentration of heterophilic antibodies so high as to overwhelm the added blocking agents.

Analysis of Variance↗
PubMed1997

Clinical chemistry and post-liver-transplant monitoring.

Liver transplantation is an accepted therapy for end-stage liver disease. After allografting, a variety of clinical problems may require laboratory involvement for accurate and timely diagnosis and intervention. Critical factors in the choice of a laboratory test menu to support a transplant program include turnaround times that support clinical decisionmaking, real diagnostic value, and real value for money. Particular clinical problems, whose early presentation must be anticipated, include graft ischemia, primary nonfunction, and hepatic artery thrombosis. Acute rejection is common at 5-10 days posttransplantation, the principal target being the biliary tree. Longer-term problems are associated with the therapeutic drug measurement of cyclosporin A and, increasingly, tacrolimus (FK506); the side effects of immunosuppressant therapy also require monitoring. A successful liver transplant program can be adequately supported with a simple battery of automated tests that are cheap, fast, and available at all times.

Biomarkers↗
PubMed1996

An optimized model for rat liver perfusion studies.

Conditions which influence the viability, integrity, and extraction efficiency of the isolated perfused rat liver were examined to establish optimal conditions for subsequent work in reperfusion injury studies including the choice of buffer, use of oncotic agents, hematocrit, perfusion flow rate, and pressure. Rat livers were perfused with MOPS-buffered Ringer solution with or without erythrocytes. Perfusates were collected and analyzed for blood gases, electrolytes, enzymes, radioactivity in MID studies, and lignocaine in extraction studies. Liver tissue was sampled for histological examinations, and wet:dry weight of the liver was also determined. MOPS-buffered Ringer solution was found to be superior to Krebs bicarbonate buffer, in terms of pH control and buffering capacity, especially during any prolonged period of liver perfusion. A pH of 7. 2 is chosen for perfusion since this is the physiological pH of the portal blood. The presence of albumin was important as an oncotic agent, particularly when erythrocytes were used in the perfusate. Perfusion pressure, resistance, and vascular volume are flow-dependent and the inclusion of erythrocytes in the perfusate substantially altered the flow characteristics for perfusion pressure and resistance but not vascular volume. Lignocaine extraction was relatively flow-independent. Perfusion injury as defined by enzyme release and tissue fine structure was closely related to the supply of O2. The optimal conditions for liver perfusion depend upon an adequate supply of oxygen. This can be achieved by using either erythrocyte-free perfusate at a flow rate greater than 6 ml/min/g liver or a 20% erythrocyte-containing perfusate at 2 ml/min/g.

Animals↗
PubMed1996

The use of the lidocaine-monoethylglycinexylidide test in the liver transplant recipient.

The lidocaine-monoethylglycinexylidide (MEGX) test is used to monitor liver function in liver transplant recipients. Serial studies have been undertaken after 155 allografts. The initial MEGX concentration is significantly correlated with the donor MEGX concentration. It is also influenced by the recipient's pretransplant bilirubin concentration, being lowest among patients with very high bilirubin levels. Use of segmental grafts is also accompanied by low MEGX concentrations. The flow-dependent clearance of lidocaine makes it a sensitive indicator of disturbed liver blood flow, with decreased MEGX concentrations occurring in hepatic artery thrombosis and rejection and as a result of cardiac failure and pulmonary effusions. Significant hepatic ischemia resulting in delayed initial function or cholestasis also is associated with low MEGX concentrations. The initial median MEGX concentrations were lowest among patients who required retransplantation or who died within 2 months of allografting.

Adolescent↗
PubMed1995

Glutaraldehyde concentration in the sterilization of endoscopes.

Controversy over appropriate disinfection of endoscopes continues with the most commonly utilized solution in Australian hospitals, despite concern over its efficacy, being 1% glutaraldehyde (AIDAL). Review of the in-use concentrations of glutaraldehyde at Princess Alexandra Hospital has documented a significant dilutional effect in 1% glutaraldehyde by gastrointestinal endoscopes. Each hospital should determine the minimum in-use concentration acceptable for any given disinfecting solution and any given range of endoscopes. Once this level is reached, a solution change should routinely occur. Such decisions can only be made by regularly monitoring in-use concentrations of disinfectants.

Disinfectants↗
PubMed1995

Altered endogenous growth hormone secretory kinetics and diurnal GH-binding protein profiles in adults with chronic liver disease.

OBJECTIVE: Increased serum GH concentrations and GH responses to a variety of stimuli have been reported in patients with chronic liver disease (CLD). We investigated the pulsatile pattern of endogenous GH release and GH-binding protein (GHBP) and insulin-like growth factor-I (IGF-I) diurnal profiles in adults with cirrhosis, in comparison with healthy, matched control subjects. DESIGN: Case-control, cross-sectional. PATIENTS: Seven patients with biopsy proven cirrhosis, and sex, age, height, weight and oestrogen status matched controls. MEASUREMENTS: Serum immunoreactive GH concentrations in samples collected at 20-minute intervals for 24 hours were analysed using a multi-parameter deconvolution method to simultaneously resolve endogenous GH secretory and disappearance rates. Diurnal patterns of GHBP (specific immunoprecipitation method) and serum IGF-I (RIA after acid-ethanol extraction) were assessed. RESULTS: The mean daily GH secretion rate in patients with CLD was increased (210 +/- 93 vs 100 +/- 55 mU/I/day; P = 0.025), and GH disappearance half-time was prolonged (43 +/- 10 vs 24 +/- 9 min; P = 0.006) compared to controls. Detectable GH secretory bursts were more frequent in patients with CLD (10 +/- 1 vs 6 +/- 3/day; P = 0.038), but of similar mean mass (21 +/- 10 vs 17 +/- 8 mU/I) compared to controls. In patients with CLD, mean serum GHBP was slightly lower (63 +/- 36 vs 71 +/- 14% pooled control; P > 0.1). Fasting serum IGF-I concentrations (after size-exclusion HPLC) were lower in the patients with CLD (13 +/- 5 vs 21 +/- 2 nmol/l; P < 0.0001). Multiple regression analysis showed that GH secretion rate was increased in patients with CLD with higher Child's classifications (R2 = 0.86; P = 0.002) and with lower serum IGF-I concentrations measured after HPLC (R2 = 0.11; P = 0.044). CONCLUSIONS: Adults with chronic liver disease have (1) increased total daily GH secretion rates, which appear to be influenced by disease severity and diminished serum IGF-I-mediated negative feedback; (2) markedly impaired endogenous GH clearance, possibly reflecting changes in hepatic GH-receptor status; and (3) GHBP levels which do not correlate with GH kinetics or serum IGF-I concentrations.

Adult↗
PubMed1994

Simple procedures can markedly enhance automated immunoassay performance.

Theoretically, optimal performance for an immunoassay system is achieved when both the interassay and within-run precisions are identical. Using the Ciba Corning ACS:180 automated immunoassay system, the authors made two simple changes to the operating procedures that allowed near-optimal analytic performance (as assessed with the interassay coefficient of variation determined by the protocol of the National Committee for Clinical Laboratory Standards) for four of six hormones: thyroid-stimulating hormone, luteinizing hormone, prolactin, and human chorionic gonadotropin. At low hormone concentrations, the 20% interassay coefficients of variation for the hormones assayed were as follows: free tetraiodothyronine, 1.74 pM; thyroid-stimulating hormone, .033 mIU/L; luteinizing hormone, .21 U/L; follicle-stimulating hormone, .69 U/L; prolactin, 5.03 mU/L; and human chorionic gonadotropin, 1.52 mU/L. The operational enhancements improved the analytic performance of the assay for all hormones assessed compared with the performance of previously used isotopic immunoassays.

Autoanalysis↗