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Biomedical subjects

C Millar

Publications and source records attributed to C Millar.

At least 19 recordsLinked to original sources

MRSA pyomyositis complicating sickle cell anaemia.

A patient being treated for sickle cell crisis developed swollen, painful, indurated, discoloured thighs after several days in hospital. Imaging revealed the presence of multiple small abscesses in the muscle and methicillin resistant Staphylococcus aureus (MRSA) was cultured from aspirated fluid. Pyomyositis usually occurs in association with damaged muscle and impaired host defences. Staphylococcus is the most frequent organism involved. It is not a common complication of sickle cell disease, although it may be under diagnosed. Availability of advanced imaging techniques facilitates early diagnosis of pyomyositis.

Adult↗

Successful PCR amplification of genomic DNA from Cryptosporidium parvum oocysts extracted from a human faecal sample: a rapid and simple method suited for outbreak analysis.

A method to extract genomic DNA from oocysts of Cryptosporidium parvum in human faecal material was developed and consisted of a simple alkali wash, freeze/boil technique. This method was simple, quick, sensitive, inexpensive and resulted in the production of genomic DNA which was free of PCR inhibitors and as such was a suitable template for the detection of C. parvum by various PCR amplification targets.

Animals↗

CMV viral load measurements in whole blood and plasma--which is best following renal transplantation?

BACKGROUND: Quantitative commercial assays for cytomegalovirus (CMV) detection have recently been developed. Their role in the management of patients after transplantation needs to be evaluated. Widespread use of these assays will allow for comparison of results between centers and meaningful interpretation of the significance of viral load measurements. METHODS: Sequential samples from 52 patients after renal transplantation were tested in the murex hybrid capture assay (HCA) and the Roche Amplicor CMV DNA assay (QPCR) and correlated with the development of CMV disease. A comparison of viral loads in plasma and whole blood was also made. RESULTS: Both assays were sensitive and detected all cases of CMV disease. The specificity and positive predictive value increased from 0.34 and 0.36 to 0.85 and 0.96 for the HCA and 0.37, 0.37 to 0.72 and 0.63 for the QPCR following a receiver operator curve analysis. Higher viral loads were measured using the HCA compared to the QPCR. Response to ganciclovir was associated with a greater than 80% reduction in viral load by HCA or greater than 70% using the QPCR. CONCLUSIONS: Both assays were highly sensitive. By using a receiver operator curve analysis a cutoff viral load can be determined which maximizes the clinical utility of these assays.

Adult↗

ASW: a gene with conserved avian W-linkage and female specific expression in chick embryonic gonad.

Vertebrates exhibit a variety of sex determining mechanisms which fall broadly into two classes: environmental or genetic. In birds and mammals sex is determined by a genetic mechanism. In mammals males are the heterogametic sex (XY) with the Y chromosome acting as a dominant determiner of sex due to the action of the testis-determining factor, SRY. In birds females are the heterogametic sex (ZW); however, it is not known whether the W chromosome carries a dominant ovary-determining gene, or whether Z chromosome dosage determines sex. Using an experimental approach, which assumes only that the sex-determining event in birds is accompanied by sex-specific changes in gene expression, we have identified a novel gene, ASW (Avian Sex-specific W-linked). The putative protein for ASW is related to the HIT (histidine triad) family of proteins. ASW shows female-specific expression in genital ridges and maps to the chicken W chromosome. In addition, we show that, with the exception of ratites, ASW is linked to the W chromosome in each of 17 bird species from nine different families of the class Aves.

Amino Acid Sequence↗

The application of high permittivity piezoelectric ceramics to 2D array transducers for medical imaging.

Two-dimensional (2D) array transducers have become of great interest in the last few years, in view of real-time volumetric ultrasonic imaging. The electrical matching between the high electrical impedance of elements and the standard cables and electronics is one of the key issues in 2D array design. The use of high-permittivity ceramics such as PNNZT either in bulk configuration or in 1-3 piezocomposites decreases the electrical impedance. In this paper, bulk samples of PNNZT and PZT ceramics are characterised, and results are compared. 2D array elements are then manufactured and their electrical impedances measured. Theoretical predictions of homogenisation models for 1-3 piezocomposites allow the simulation of the electroacoustic behaviour of 2D array elements. Results for both piezocomposite and bulk materials can be obtained. Calculations of the input impedance, the sensitivity and the bandwidth of the different configurations are compared and discussed. These results demonstrate the advantages of the PNNZT compositions over standard PZT.

Acoustics↗

Perceptions of care and services by the clients and families: a personal experience.

This study was initiated in response to a provincial mental health policy emphasizing the primacy of the person and the hospital's decision to adopt total quality management. The objective of the project was to learn more about how clients and families viewed the care and services received during a psychiatric admission. Their perceptions were elicited through seven focus groups including multiple admission (3) clients and families of single and multiple admission clients (2 each). Group sessions were tape-recorded, transcribed and analysed for themes. Three major themes were identified: quantity and quality of care, individuality and partnership. Both positive and negative comments were made within each of these themes, but two major areas for improvement were continuity of care and the environment. The findings are being used to change practices within the Department of Psychiatry.

Adult↗

Use of molecular assays in diagnosis and monitoring of cytomegalovirus disease following renal transplantation.

We compared two commercial molecular assays (the Murex Hybrid Capture CMV DNA assay [HCA], version 2, and the Roche Amplicor plasma PCR assay) with a standard shell vial assay in detecting and predicting cytomegalovirus (CMV) disease in a group of renal transplant patients and assessed the role of viral load measurements (using the HCA) in their management. The sensitivity of the HCA and Amplicor assay in terms of disease detection was 100%, compared to 71% for the shell vial assay. Both the HCA and the PCR assay detected all cases of disease, at medians of 11 and 12.5 days before the onset of symptoms, respectively. Significantly higher viral loads were detected in those patients with symptoms (7.9 x 10(5) copies/ml) than in patients without symptoms (7.9 x 10(4) copies/ml; P < 0.0001). There was also a trend towards higher viral loads in those patients with primary infections (7.8 x 10(5) copies/ml) than in those patients with reactivations of CMV disease or reinfections. Successful treatment with ganciclovir was associated with a >90% reduction in viral load. Both of these new assays are sensitive and easy to use. A comparison of accurate quantitation is also useful in monitoring responses to antiviral therapy.

Adult↗

Effects of H-7 on the iris and ciliary muscle in monkeys.

OBJECTIVES: To determine the effects of H-7 on (1) iris and ciliary muscles (CMs) in living monkeys; (2) isolated monkey CM strips; (3) actomyosin contractility in cultured Swiss 3T3 cells. METHODS: (1) Pupillary diameter (calipers) and accommodation (refractometer) in living monkeys were measured after topical, intracameral, or intravitreal administration of H-7 followed by systemic pilocarpine hydrochloride. (2) Pilocarpine-induced contraction of isolated monkey CM strips following administration of H-7 was measured in a perfusion chamber. (3) Actomyosin contractility in Swiss 3T3 cells cultured on thin silicone rubber film was determined by measuring cell-induced film wrinkles before and after administration of H-7. RESULTS: Topical H-7 prevented anesthesia-induced miosis but did not affect resting refraction. Intracameral or intravitreal H-7 dilated the pupil and inhibited miotic but not accommodative responses to pilocarpine. H-7 inhibited pilocarpine-induced contraction of isolated monkey CM strips and reduced Swiss 3T3 cell contraction. CONCLUSIONS: H-7 inhibits actin-based contractility in non-muscle cells and in monkey iris sphincter and CM. Under our in vivo experimental conditions, the effect on the iris predominates over that on the CM.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Bladder epithelial oxygen tension--a new means of monitoring regional perfusion? Preliminary study in a model of exsanguination/fluid repletion.

OBJECTIVE: To assess whether monitoring of bladder epithelial oxygen tension (BEOT) would provide an indication of regional (renal) organ perfusion in an exsanguination/fluid repletion animal model. DESIGN: Prospective non-randomized laboratory study. SETTING: Research laboratory. INTERVENTIONS: Eight anaesthetised, spontaneously breathing Sprague-Dawley male rats weighing approximately 200 g were instrumented. They received 1-ml aliquots of fluid until no further haemodynamic improvement was seen, followed by removal of 1-ml aliquots of blood until renal blood flow fell by 50%. The animal was then resuscitated with repeated 1 to 2-ml aliquots of fluid until no further improvement was achieved and, finally, progressively exsanguinated to cardiovascular collapse. MEASUREMENTS AND RESULTS: A continuous Clark-type oxygen electrode lying in contact with the inside wall of the bladder measured changes in BEOT during these exsanguination and fluid repletion manoeuvres. Changes in BEOT closely mirrored both systemic (blood pressure and aortic blood flow) and regional (renal blood flow) haemodynamic changes. A direct correlation existed between percentage change in BEOT and base deficit, and an indirect correlation was seen with arterial oxygen tension. CONCLUSIONS: Measurement of BEOT may be a useful and relatively non-invasive means of monitoring regional organ perfusion. Further studies are warranted.

Animals↗

Effects of timolol, terbutaline and forskolin on IOP, aqueous humour formation and ciliary cyclic AMP levels in the bovine eye.

We have studied the effects of terbutaline, timolol, forskolin and 8-bromo cyclic AMP on aqueous humour formation, intraocular pressure and on ciliary epithelial cyclic AMP levels, either in presence or in absence of IBMX, using the bovine isolated arterially perfused eye, excised ciliary processes and cultured ciliary epithelium. Both terbutaline, a beta-adrenoceptor agonist, and timolol, a beta-adrenoceptor antagonist, caused significant reduction in aqueous humour formation and intraocular pressure but produced no effect on ciliary epithelial cyclic AMP content in the absence of IBMX. Even a three times higher dose of terbutaline was entirely ineffective in producing any effect on ciliary cyclic AMP in the perfused eye. On the other hand, terbutaline at the IOP-reducing dose, produced a significant increase in cyclic AMP when injected after 30 min perfusion with IBMX. Incubation of excised ciliary processes or cultured ciliary epithelial cells with terbutaline (10(-6) to 10(-4) M) produced concentration-dependent increases in cyclic AMP, in both tissues, even in the absence of IBMX. Forskolin, which stimulates cyclic AMP synthesis without interacting with cell surface receptors, was found to produce highly significant increases in ciliary cyclic AMP content both in presence and in absence of IBMX but had no effect on aqueous humour formation in the isolated eye. IBMX perfused at concentrations of 1 mM or 10 microM had no effect on basal levels of ciliary cyclic AMP but the 1 mM concentration produced a marked and significant reduction in IOP. Direct application of 8-bromo cyclic AMP, a cell permeable analogue, more resistant to hydrolysis by phosphodiesterases, had also no effect on aqueous humour formation in the perfused eye. It is concluded that in the bovine arterially perfused eye, the correlation between the aqueous humour formation rate and ciliary epithelial cyclic AMP content is unclear.

1-Methyl-3-isobutylxanthine↗

Prostaglandin F2 alpha effects on isolated rhesus monkey ciliary muscle.

PURPOSE: The effects of prostaglandin (PG)F2 alpha on the contractile response in the longitudinal and coronal vectors of the isolated rhesus monkey ciliary muscle were studied. METHODS: Fresh rhesus monkey ciliary muscle strips from young and middle-aged animals were mounted in an apparatus capable of monitoring contractile force simultaneously in the two vectors. The responses to PGF2 alpha were measured and compared to those produced with 1 microM carbachol. RESULTS: PGF2 alpha consistently relaxed the carbachol precontracted ciliary muscle in a dose-dependent manner with equal potency and efficacy in both vectors, but it did not alter the tone of muscle strips at resting tension. CONCLUSIONS: The relaxation of precontracted ciliary muscle by PGF2 alpha may help explain how a single topical dose of this prostanoid increases uveoscleral outflow and antagonizes resting myopia in the living monkey.

Animals↗

Endothelin subtypes: effect on isolated rhesus monkey ciliary muscle.

The effects of endothelin (ET)-1, ET-2, ET-3 and sarafotoxin S6C on the contractile response in the longitudinal and coronal vectors of the isolated rhesus monkey ciliary muscle were studied. Fresh ciliary muscle strips from young and middleaged rhesus monkeys were mounted in an apparatus capable of monitoring contractile force simultaneously in the two vectors. The responses to the ET compounds were measured and compared to those produced with 1 microM carbachol. ET-1 produced contractions of up to 15% of the near-maximum response to carbachol in both vectors of 66% of ciliary muscle strips studied. In responsive strips, the maximal ET-1 induced contraction was approximately equal in both vectors, but the longitudinal vector was approximately 5-fold more sensitive than the circular. All ciliary muscle strips responded reproducibly to carbachol. None of the other ET compounds tested had any effect, suggesting that the ETA receptor may predominate in rhesus monkey ciliary muscle. Because ET-1 induces only weak and interindividually variable contraction in isolated rhesus monkey ciliary muscle strips, ET-1's enhancement of outflow facility with only minimal induction of accommodation in the living monkey may be due to effects directly on the trabecular meshwork. However, the 5-fold greater potency of ET-1 in the longitudinal compared to the circular contractile vector may indicate that selective contraction of the longitudinal portion of the ciliary muscle with consequent deformation of the trabecular meshwork but not the lens is also involved.

Animals↗

Awake intubation increases intracranial pressure without affecting cerebral blood flow velocity in infants.

Tracheal intubation is frequently required in neonatal anaesthetic practice. Awake intubation is one method of securing the airway and in certain circumstances, for many anaesthetists, can be preferable to intubation following induction of anaesthesia. Previous studies have inferred that the elevation in anterior fontanelle pressure observed during tracheal intubation in neonates was caused by an increase in cerebral blood flow although it was never measured. In this study, direct methods were used to observe changes in the cerebral circulation. Thirteen neonates, ASA I to III (E), aged from 1 to 34 days of age were studied. Patients were randomized to receive either tracheal intubation awake or following induction of anaesthesia with thiopentone 5 mg.kg-1 and succinylcholine 2 mg.kg-1. Heart rate, systolic arterial blood pressure, anterior fontanelle pressure, cerebral blood flow velocity (using transcranial Doppler sonography) and oxygen saturation were recorded at the following intervals: baseline (not crying), after intravenous atropine 0.02 mg.kg-1, during laryngoscopy, immediately after insertion of the endotracheal tube, one and five minutes later. The use of atropine masked the cardiovascular responses to intubation. Whereas the change in anterior fontanelle pressure from baseline was different between the groups (P < 0.05), the cerebral blood flow velocity variables were not. The rise in anterior fontanelle pressure seen in the awake group may be attributed to a reduction of the venous outflow from the cranium thereby increasing cerebral blood volume and subsequently the intracranial pressure.

Cerebrovascular Circulation↗

Cerebral arteriovenous malformations in children.

The treatment of cerebral arteriovenous malformations (AVM) or vascular anomalies are challenging neurosurgical procedures for an anaesthetist. Large AVMs are uncommon in children. Only 18% of AVMs become symptomatic before the age of 15 yr. This series reviews the experience at this institution during the period of 1982 to 1992. The symptoms at the time of presentation are varied and include haemorrhage (50%), seizures and hydrocephalus (36%) or congestive cardiac failure (18%). Symptoms of congestive heart failure predominate in the newborn whilst neurological symptoms, such as stroke, seizures or hydrocephalus occur more commonly in infants and older children. Approximately one third of AVMs in childhood present acutely. Radiological investigations, e.g., CT scan, MRI and cerebral angiography are essential to identify the precise location of the lesion. Therapeutic intervention in the acute presentation may involve craniotomy for evacuation of haematoma and treatment of increased intracranial pressure (ICP). Control of seizures and congestive heart failure may take priority and allow time to plan the elective procedures of embolization and surgical excision of the AVM. Operative intervention is hazardous and peroperative complications can be expected in more than 50% of patients. The morbidity and mortality associated with cerebral AVM are high, especially in infants who present in the neonatal period with congestive cardiac failure. The overall mortality in this series was 20%. Children presenting with intracranial arteriovenous malformations require a multidisciplinary approach. The successful management of anaesthesia either for embolization or surgical resection necessitates an understanding of the disciplines of paediatric and neuroanaesthesia. Special care and specific attention to detail may contribute to reduce the high morbidity and mortality encountered in these compromised children.

Adolescent↗

The bovine arterially-perfused eye: an in vitro method for the study of drug mechanisms on IOP, aqueous humour formation and uveal vasculature.

A method is reported in which the isolated bovine eye is perfused through a long posterior ciliary artery with buffered physiological saline, to provide simultaneous monitoring of drug effects on intraocular pressure (IOP), vascular resistance and the condition of the blood-aqueous barrier. With perfusion under constant pressure of 45 mm Hg, perfusate flows at 1.64 +/- 0.12 ml.min-1 (mean +/- SEM) and IOP is 7.26 +/- 0.16 mm Hg. Applying a constant flow rate of 2.25 ml.min-1, IOP averages 10.19 +/- 0.32 mm Hg and in both cases this can be maintained for around 2h. Increasing the perfusion flow rate from 1.5 to 3.5 ml.min-1 produces a 76% rise in perfusion pressure but IOP increases only insignificantly (< 10%). The inclusion in the perfusion fluid of dextran and albumin to maintain oncotic pressure similar to that of plasma makes no difference to the IOP achieved and does not affect the leakiness of the barrier. The preparation shows a net consumption of oxygen, supporting the hypothesis that the aqueous humour formed is secreted by active transport processes. Timolol (in bolus doses of 1-300 nmol) injected into the perfusing fluid is shown to induce a dose-dependent fall in IOP within 5 min, reaching a steady state within 40 min. Timolol, however, causes no significant change in vascular resistance, whether this is measured as perfusion flow rate under constant pressure or as perfusion pressure at constant flow rate, nor does it alter the permeability of the barrier. Other beta-blockers such as oxprenolol and betaxolol also induce dose-dependent decreases in IOP. By applying a fluorescein dilution technique, it is found that the aqueous formation rate (K(out) = 0.0046 min-1, or 12.9 microliters.min-1) is also reduced by timolol and, in a dose-dependent manner, by the new carbonic anhydrase inhibitor, MK-927. The bovine perfused eye offers a useful method for studying the mechanisms of action of drugs on IOP and aqueous humour formation, in isolation from the complicating influences of the CNS and the cardiovascular system and without the necessity to kill animals for experimental purposes.

Adrenergic beta-Antagonists↗