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Biomedical subjects

G M Clarke

Publications and source records attributed to G M Clarke.

At least 19 recordsLinked to original sources
PubMed2007

Whole-specimen histopathology: a method to produce whole-mount breast serial sections for 3-D digital histopathology imaging.

AIMS: To develop a method for preparing diagnostic-quality, whole-mount serial sections of breast specimens while preserving 3-D conformation. This required supporting the fresh specimen prior to breadloafing and refining the conventional tissue processing method. The overall goal is to use digital images of whole-specimen histopathology to improve the estimation of extent of disease. METHODS AND RESULTS: To maintain a 3-D conformation, the specimen is suspended in 3.5% agar at 55 degrees C. The block is sliced at 5-mm intervals. Sectioning is performed after extended fixation in 4% formaldehyde from paraformaldehyde in 0.1 m Millonig's buffer, followed by paraffin processing using a non-routine schedule and extended paraffin infiltration. Whole-mount serial breast sections are produced with features of equal or superior quality to that which can be achieved using conventional methods. The method is compatible with some immunohistochemical stains but requires further optimization for others. CONCLUSIONS: The technique is currently suitable for research applications. With the reduction in processing time achievable with microwave-assisted processing, there is the potential for its use as a routine clinical method. This tool may improve the accuracy of margin estimates and identification of multifocality in breast cancer; further evaluation is necessary.

Breast Neoplasms↗
PubMed2006

Tracing the geographic origin of the cosmopolitan parthenogenetic insect pest Liposcelis bostrychophila (Psocoptera: Liposcelididae).

The randomly amplified polymorphic DNA technique was used to trace the geographic origin of Liposcelis bostrychophila Badonnel populations in Australia from unknown geographic sources internationally. Haplotype (or clonal) diversity was high, with 474 unique haplotypes found from 616 individuals genotyped. Gene diversity estimates (0.10-0.28) and percent polymorphic loci (38.1-88.1%) were moderate to high for most populations. This resulted in genetic distance estimates that ranged from 0.04 to 0.26 and were significantly different for most pairwise population combinations. G ST values for all populations were also moderate (0.04-0.54) and again were significantly different for most pairwise population comparisons. Analysis of molecular variance revealed that the majority of variation was apportioned among individuals within populations regardless of the level at which they were grouped. Gene flow (Nm) was mostly low for all pairwise populations comparisons with an average Nm=1.8. A non-significant negative correlation between genetic distance and geographic distance was found for worldwide populations. In contrast, within Australian populations a significant positive correlation between genetic distance and geographic distance was detected. Genetic relationships explored using unweighted pair group method analysis and non-metric multidimensional scaling indicated a mixed pattern of genetic similarities among all populations. Multiple introductions, from a wide range of international source populations, have obscured the ability to accurately determine the geographic origin of L. bostrychophila in Australia.

Animals↗
PubMed2000

Wings and bristles: character specificity of the asymmetry phenotype in insecticide-resistant strains of Lucilia cuprina.

We investigated the hypothesis that observed higher levels of asymmetry displayed by insecticide-resistance genotypes of Lucilia cuprina are restricted to bristle characters, due to the action of resistance genes in bristle cell development, rather than through the disruption of genomic coadaptation. We compared the level of asymmetry of three bristle characters and three wing characters in non-modified and modified-resistance genotypes. Consistent with previous studies, resistance genotypes displayed greater levels of bristle asymmetry than either susceptible or modified genotypes. However, there were no differences among genotypes for any of the wing characters. To confirm that this result is attributable to the action of the resistance and modifier genes themselves, we also examined the responses of both bristle and wing characters to the more general developmental stress of extreme temperature. Sub-optimal temperature was shown to increase both bristle and wing asymmetry, suggesting that there are no underlying differences between the two character types which could, of themselves, explain the differential response observed in the resistance genotypes.

Animals↗
PubMed2000

Laboratory investigation of hemoglobinopathies and thalassemias: review and update.

Structural hemoglobin (Hb) variants typically are based on a point mutation in a globin gene that produce a single amino acid substitution in a globin chain. Although most are of limited clinical significance, a few important subtypes have been identified with some frequency. Homozygous Hb C and Hb S (sickle cell disease) produce significant clinical manifestations, whereas Hb E and Hb D homozygotes may be mildly symptomatic. Although heterozygotes for these variants are typically asymptomatic, diagnosis may be important for genetic counseling. Thalassemia, in contrast, results from quantitative reductions in globin chain synthesis. Those with diminished beta-globin chains are termed beta-thalassemias, whereas those with decreased alpha-chain production are called alpha-thalassemias. Severity of clinical manifestations in these disorders relates to the amount of globin chain produced and the stability of residual chains present in excess. The thalassemia minor syndromes are characterized clinically by mild anemia with persistent microcytosis. Thalassemia intermedia (i.e., Hb H disease) is typified by a moderate, variably compensated hemolytic anemia that may present with clinical symptoms during a period of physiologic stress such as infection, pregnancy, or surgery. The thalassemia major syndromes produce severe, life-threatening anemia. alpha-Thalassemia major usually is incompatible with extrauterine life; beta-thalassemia major presents in infancy and requires life-long transfusion therapy and/or bone marrow transplantation for successful control of the disease. Double heterozygosity for certain structural variants and/or thalassemia syndromes may also lead to severe clinical disease. Several guidelines have been published that outline the required steps for hemoglobinopathy and thalassemia investigation. The availability of HPLC has streamlined many of these requirements, allowing an efficient stepwise diagnostic strategy for these complex disorders.

Chromatography, High Pressure Liquid↗
PubMed1996

Proximally delivered dilute heparin does not improve circuit life in continuous venovenous haemodiafiltration.

OBJECTIVE: To assess the effect on circuit life in continuous venovenous haemodiafiltration (CVVHD) by manipulating heparin dilution and point of administration. DESIGN: Repeated crossover design. Cases were randomised for first circuit and heparin dilution, after which crossovers occurred until treatment was stopped. SETTING: A 24-bed combined general and surgical intensive care unit admitting 1900 patients a year. On average, 54 cases a year receive CVVHD. PATIENTS: 26 critically ill adult patients requiring CVVHD were enrolled, 18 of whom used at least one standard circuit and one modified circuit. INTERVENTIONS: Two circuit configurations and heparin dilutions were compared. In combination A, standard CVVHD blood lines and heparin concentration (100 units/ml) were used. In combination B, heparin was delivered in a more dilute volume (10 units/ml) via a modified circuit design with an administration port immediately adjacent to the venous access. MEASUREMENTS AND RESULTS: 18 randomised crossovers of circuits A and B occurred. Mean/median circuit life for the standard heparin/circuit combination A was 20.1/17.5 (SD 14.6) and for the modified combination B 21.4/15.4 (SD 19.2). There was no significant difference between circuits (paired t-test, p = 0.8175). To identify other factors which could have influenced circuit life (platelet count, heparin dose and pre- and post-filter activated partial thromboplastin time, APTT) all circuits terminated for the reasons identified (n = 105) were analysed using linear modelling. Survival analysis was used to determine the survival function of the circuit. Pre-heparin APTT was the only factor associated with an increase in filter life (p = 0.035). The hazard rate for filter failure was 0.049/h (95% confidence interval 0.04 to 0.06), the range of time until filters failed was 1.8 to 78.5 h. CONCLUSIONS: Proximally administered dilute heparin is not associated with a significant increase in circuit life.

Acute Kidney Injury↗
PubMed1996

Acute renal failure in cardiac surgical patients, potentiated by gentamicin and calcium.

A retrospective study in coronary artery bypass graft patients was undertaken to assess the effect of gentamicin and a bypass prime with a high calcium on the incidence of renal failure. Patients who received both Haemaccel (polygeline, Hoechst Marion Roussel) (calcium concentration 6.25 mmol/l) in the bypass prime and gentamicin perioperatively had a higher incidence of renal failure compared with those who received only Haemaccel (P = 0.005), only gentamicin (P = 0.002) or neither (P = 0.0001). We suggest that the combination be avoided in this group of patients.

Acute Kidney Injury↗
PubMed1993

Fluctuating asymmetry of invertebrate populations as a biological indicator of environmental quality.

Fluctuating asymmetry (FA) of populations of the shrimp, Palaemon elegans, and the blood worm, Chironomus salinarius, was used to assess the environmental impact of a fertilizer manufacturing facility on the surrounding marine and freshwater ecosystems, respectively. Populations of both species were found to have elevated levels of asymmetry compared with control populations, indicating that the facility was having a significant impact on organism development. The use of FA of invertebrate populations as a simple, sensitive and cost-effective biomonitoring system for the detection of environmental stress is discussed.

Journal Article↗
PubMed1993

The Training/Examination Programme in Intensive Care, Australian and New Zealand College of Anaesthetists. 1. Training.

Unlike training for programmes in other countries which have published details of training programmes for Intensive Care Medicine, the training programme of the Australian and New Zealand College of Anaesthetists does not require certification in a primary specialty, although it is possible to combine training in Intensive Care and Anaesthetics. The lynchpin of the programme is the requirement that training can be undertaken in recognised posts in intensive care units which are approved by the College. Approval of the Unit requires evidence of appropriate supervision and teaching of trainees, sufficient number of admissions with a casemix suitable for the trainees' learning needs and an adequate level of staff and equipment. The Units are assessed by physical inspection by assessors appointed by the College. The programme includes a Final Examination in Intensive Care.

Anesthesiology↗
PubMed1993

The Training/Examination Programme in Intensive Care, Australian and New Zealand College of Anaesthetists: 2. Examination.

The structure of the Final Examination in Intensive Care for the award of Diploma of Fellow of the Australian and New Zealand College of Anaesthetists is based on a model explicated in the College's Objectives of Training in Intensive Care. There are five sections in the examination: short answer questions, essay questions, investigations, orals and a clinical. The first examination was held in October 1979. Up to and including the examination of October 1992, 94 of the 136 attempts by 107 candidates had been successful. Eighty-three per cent of the candidates passed at the first attempt. The failure rate has been highest in the clinical section. The examination is regarded as a hard examination but one which is helpful in training and subsequent practice.

Anesthesiology↗
PubMed1992

Efficacy of flecainide for the reversion of acute onset atrial fibrillation.

The efficacy and safety of intravenous flecainide to convert recent-onset atrial fibrillation (AF) (present for greater than or equal to 30 minutes and less than or equal to 72 hours and a ventricular response greater than or equal to 120 beats/min) was investigated. A total of 102 patients without severe heart or circulatory failure were randomized to receive either intravenous flecainide (2 mg/kg, maximum dose 150 mg; 51 patients) or placebo (51 patients) in a double-blind trial. Digoxin (500 micrograms intravenously) was administered to all patients who had not previously been receiving digoxin. The electrocardiogram was monitored continuously during the study. In 29 (57%) patients stable sinus rhythm was restored within 1 hour after flecainide and in only 7 (14%) given placebo (chi square 18.9; p = 0.000013; odds ratio 8.3; 95% confidence interval 2.9-24.8). Reversion to sinus rhythm within 1 hour after starting the trial medication was considered a pretrial end point and likely to be due to a drug effect. At the end of the 6-hour monitoring period, 34 patients (67%) in the flecainide group were in sinus rhythm whereas only 18 (35%) in the placebo group had reverted (chi square 8.83, p = 0.003; odds ratio 3.67; 95% confidence interval 1.5-9.1). Significant hypotension, although short lived, was more common in the flecainide group. One patient given flecainide developed torsades de pointes and was successfully electrically cardioverted. Flecainide is useful for the management of recent-onset AF both for control of the ventricular response and conversion to sinus rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1991

Reversion of recent-onset atrial fibrillation to sinus rhythm by intravenous flecainide.

Spontaneous reversion to sinus rhythm is a frequent occurrence in recent-onset atrial fibrillation (AF). In a randomized, double-blind, controlled study, intravenous flecainide (2 mg/kg, maximum dose 150 mg) was compared with placebo in the treatment of recent-onset AF (present for greater than or equal to 30 minutes and less than or equal to 72 hours' duration and a ventricular response greater than or equal to 120 beats/min). Intravenous digoxin (500 micrograms) was administered concurrently to all patients in both groups who had not previously taken digoxin. The trial medication was administered over 30 minutes. Exclusion criteria included hemodynamic instability, severe heart failure, recent antiarrhythmic therapy, hypokalemia and pacemaker dependence. One hundred two consecutive patients with recent-onset AF were enrolled in the study. All patients underwent continuous electrocardiographic monitoring in the intensive care or coronary care unit. Twenty-nine (57%) patients given flecainide and digoxin, but only 7 (14%) given placebo and digoxin, reverted to sinus rhythm in less than or equal to 1 hour after starting the trial medication infusion and remained in stable sinus rhythm (chi-square 18.9, p = 0.000013; odds ratio 8.3, 95% confidence interval 2.9 to 24.8). At the end of the 6-hour monitoring period, 34 patients (67%) in the flecainide-digoxin group were in stable sinus rhythm, whereas only 18 patients (35%) in the placebo-digoxin group had reverted (chi-square 8.83, p = 0.003; odds ratio 3.67, 95% confidence interval 1.5 to 9.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Fibrillation↗
PubMed1991

Male crossing over and genetic sexing systems in the Australian sheep blowfly Lucilia cuprina.

Field-female killing (FK) systems based on deleterious mutations and Y-autosome translocations are being evaluated for genetic control of the Australian sheep blowfly, Lucilia cuprina. Experience during field trials has shown that mass-reared colonies of FK strains are subject to genetic deterioration, caused mainly by genetic recombination in males. A previous study found higher male recombination frequencies in two Y-linked translocation strains than in chromosomally normal males. However, the results of the present study indicate that breakage of the Y chromosome is neither sufficient nor necessary for increased levels of male recombination. The frequency of male recombination appears to be unrelated to the presence of specific chromosome rearrangements.

Animals↗