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R Sinclair

Publications and source records attributed to R Sinclair.

At least 37 records · Page 2Linked to original sources
PubMed2001

Empirically supported ethical research practice: the costs and benefits of research from the participants' view.

Researchers and institutional review boards are routinely called upon to evaluate the cost-benefit status of proposed research protocols that involve human participants. Often these assessments are based on subjective judgments in the absence of empirical data. This reliance on subjective judgments is of particular concern for studies involving clinical samples where unfounded assumptions may adversely affect research progress or clinical outcomes. The Reactions to Research Participation Questionnaire (RRPQ) was designed to address this shortcoming and to help promote ethical decision making about research practice. The present study describes development of the RRPQ and presents a series of exploratory and confirmatory analyses investigating its structure. Based on these findings, a revised version of the instrument and suggestions for future research are presented. This approach provides a foundation for scientifically informed protection of human subjects.

Behavioral Research↗
PubMed2001

Review of management of purpura fulminans and two case reports.

Purpura fulminans (PF) is a haemorrhagic condition usually associated with sepsis or previous infection. Features include tissue necrosis, small vessel thrombosis and disseminated intravascular coagulation. Gram-negative organisms are the commonest cause of the acute infectious type, which is often associated with multi-organ failure. An idiopathic variety, however, is often confined to the skin. The mortality rate has decreased with better treatment of secondary infections, supportive care and new treatments, but it remains a disabling condition often requiring major amputations. We describe two cases and review the various treatments for this condition.

Acute Disease↗
PubMed2001

The incidence of biopsy-proven glomerulonephritis in Australia.

BACKGROUND: There is limited population-based epidemiological data on renal disease. An insight into the spectrum of clinically significant glomerulonephritis can be obtained from renal biopsy diagnoses. This is a descriptive report of biopsy-proven glomerulonephritis within a defined population. METHODS: A retrospective review of the pathology reports of all native renal biopsies performed in the Australian state of Victoria in 1995 and 1997 was undertaken. Trends in the average annual age- and sex-specific incidence rates for biopsy-proven glomerulonephritis were calculated. Comparisons were made with the incidence of end-stage renal disease due to glomerulonephritis confirmed on renal biopsy. RESULTS: The most common glomerulonephritides in adults are IgA disease, focal glomerulosclerosis, lupus nephritis and vasculitis, and in children are lupus nephritis, focal glomerulosclerosis, IgA disease and minimal change disease. A male predominance is seen for all glomerulonephritides, except lupus nephritis, in both adults and children. An increase in incidence of disease with age, particularly in males, is seen for vasculitis and focal glomerulosclerosis. The most common glomerulonephritides on renal biopsy are reflected in the most common causes of end-stage renal disease due to glomerulonephritis. CONCLUSIONS: This review has provided population-based descriptive epidemiological data on clinically significant glomerulonephritis. This data provides important clues for further studies relating to the identification of risk factors for the various types of glomerulonephritis.

Adult↗
PubMed2001

Three case reports of the use of haemodiafiltration in the treatment of salicylate overdose.

Aspirin (acetylsalicylic acid) is widely available without prescription. Although self-poisoning is rare, if severe it may be life threatening. Haemodialysis has been recommended in severe cases when salicylate levels exceed 7.3 mmol l(-1). We describe three cases of severe salicylate poisoning, which were treated with continuous veno-venous haemodiafiltration (CVVHDF). All patients survived. The first case had already undergone haemodialysis before transfer to the ICU, where CVVHDF was commenced because salicylism persisted at 3 mmol l(-1). A small reduction in serum salicylate was noted. In the second case, serum salicylate decreased from 8.5 to 3.5 mmol l(-1) after 3 h of CVVHDF even though only minimal urine was produced. Our third case is a chronic overdose in whom serum salicylate decreased from 6.2 to 4 mmol l(-1) after 4 h and to 1.4 mmol l(-1) after a further 7 h. No bicarbonate was administered to this patient and elimination can only be attributed to CVVHDF and urinary clearance, which is known to be slow. We discuss the pathogenesis of severe salicylate toxicity and postulate that CVVHDF, which is widely used in the intensive care setting, may be a useful therapy in severely poisoned patients who are unstable and cannot undergo haemodialysis or in situations where haemodialysis is unavailable.

Adult↗
PubMed2000

Development and evaluation of ELISA procedures to detect antibodies against the major envelope protein (G(L)) of equine arteritis virus.

Enzyme-linked immunosorbant assays (ELISAs) were developed for the detection of antibodies against the major envelope glycoprotein (G(L)) of equine arteritis virus (EAV). A 6-Histidine tagged recombinant protein expressing the complete G(L) ectodomain (G(L)-6His), a glutathione-S-transferase recombinant protein expressing amino acids 55-98 of G(L) (G(L)-GST) and an ovalbumin-conjugated synthetic peptide representing amino acids 81-106 of G(L) (G(L)-OVA) were used as diagnostic antigens. An ELISA procedure was developed and optimised for each antigen. The G(L)-OVA and G(L)-6His assays showed the greatest specificity while the G(L)-GST assay was slightly more sensitive that the G(L)-OVA and G(L)-6His assays; results based on the analysis of 50 virus neutralisation positive and 50 virus neutralisation negative sera. The G(L)-OVA ELISA was selected for further evaluation since it was simpler to use than ELISAs based on recombinant antigens and did not suffer from background reactivity. The final sensitivity and specificity of the G(L)-OVA ELISA were 96.75 and 95.6%, respectively, results based on the analysis of 400 virus neutralisation positive and 400 virus neutralisation negative sera. It also detected EAV antibody (100% efficiency) in seropositive shedding stallions and, in ponies infected experimentally with the UK93 isolate of EAV, the appearance of virus neutralising antibodies and G(L)-OVA ELISA-specific immunoglobulins coincided.

Animals↗
PubMed2000

Importance of nitric oxide in the regulation of burn oedema, proteinuria and urine output.

Burn injuries trigger a pronounced inflammatory response in the burned skin, resulting in oedema formation and impaired circulation. This response involves activation of the nitric oxide (NO) synthetic pathway, which could play a key role in the complex hemodynamic and hemostatic changes occurring as a result of a burn trauma. The results presented in full-thickness skin burns of rats show that the NO-precursor, L-arginine (n = 10), inhibit burn-induced plasma extravasation as compared to saline-treated burned controls (n = 10) (p<0.001) to a level not significantly different from nonburned animals. Administration of the NO-synthase inhibitor. NG-nitro-L-arginine (L-NNA) (n = 10), did not significantly influence burn extravasation compared to burned controls. Accumulated urine volume 90 min post-burn increased ten-fold in burned animals treated with L-arginine compared to saline-treated burned controls (p<0.001) and nonburned animals (p<0.001), while L-NNA had no significant effect on diuresis. A significantly increased proteinuria occurred in L-arginine treated burned animals as compared to burned controls and nonburned controls (p<0.001), whereas L-NNA did not significantly influence the leakage of protein in the urine. Activation of NO synthesis significantly suppresses burn edema and strongly increases diuresis along with increased proteinuria.

Albumins↗
PubMed2000

Role of nitric oxide in the control of burn perfusion.

Vascular changes following deep skin burns are characterised by vasoconstriction and progressive ischemia. Nitric oxide (NO) has been shown to be a potent regulator of vascular smooth muscle tone and tissue perfusion. We assessed the importance of NO on post-burn skin perfusion in rats using laser Doppler. The present results show that neither the NO-synthase inhibitor, NG-nitro-L-arginine (L-NNA) (n = 6) nor the NO precursor, L-arginine, significantly influenced skin perfusion in nonburned skin compared to saline-treated animals. In the area of full-thickness skin burn, neither L-arginine (n = 6) nor L-NNA (n = 6) had significant influence on post-burn perfusion compared to saline-treated controls (n = 6). Administration of L-NNA (n = 6) significantly impaired skin perfusion in the area adjacent to the contact burn representing a partial-thickness burn, while the NO precursor, L-arginine (n = 6) had no significant effect on burn perfusion as compared to saline-treated controls (n = 6). In conclusion, impairment of perfusion in a full thickness burn following administration of NO-synthase inhibitor suggests that nitric oxide is involved in the mechanisms responsible for maintaining adequate circulation post-burn. The lack of additional improvement of perfusion in response to L-arginine may suggest that NO synthesis in response to the thermal trauma is already at a peak.

Animals↗
PubMed2000

Getting ahead of head lice.

Dermatologists are the nominal experts in the management of head lice in Australia, yet many dermatologists infrequently treat patients with this condition. Most people are managed in the community by school nurses, local council health officers, pharmacists, paediatricians or general practitioners. Only a small number will present to the dermatologist and commonly these patients will have tried a variety of treatments and failed to respond. Resistance is reported to all of the currently available insecticide treatments and this makes management of this common community-acquired infestation more involved.

Adolescent↗
PubMed2000

Ultrastructural appearance of renal and other basement membranes in the Bull terrier model of autosomal dominant hereditary nephritis.

Bull terrier hereditary nephritis may represent a model for autosomal dominant Alport's syndrome because affected dogs have the typically lamellated glomerular basement membrane (GBM) and father-to-son disease transmission occurs. This study examined the ultrastructural appearance of the renal and extrarenal basement membranes and their composition in affected Bull terriers. Affected stillborn animals and puppies had subepithelial frilling and vacuolation of the GBM. In adult dogs, lamellation was common, and subepithelial frilling and vacuolation were less prominent. Foot-process effacement and mesangial matrix expansion occurred frequently. Basement membranes in the glomeruli, tubules, and Bowman's capsule were significantly thickened and often mineralized. Immunohistochemical examination showed alpha 1(IV) and alpha 2(IV) collagen chains in all renal basement membranes; alpha 3(IV), alpha 4(IV), and alpha 5(IV) chains in the GBM, distal tubular basement membrane, and Bowman's capsule; and the alpha 6(IV) chain in Bowman's capsule. Conversely, the basement membranes from the affected Bull terrier cornea, lens capsule, retina, skin, lung, and muscle had a normal ultrastructural appearance and were not thickened compared with membranes in normal age-matched dogs. The distribution of basement membrane abnormalities in Bull terrier hereditary nephritis may occur because the defective protein is present exclusively or more abundantly in the kidney and is structurally more important in the kidney or because of local intrarenal stresses.

Age Factors↗
PubMed2000

Immunity to equine influenza: relationship of vaccine-induced antibody in young Thoroughbred racehorses to protection against field infection with influenza A/equine-2 viruses (H3N8).

Field outbreaks of influenza that occurred in vaccinated Thoroughbred racehorses in Newmarket in 1995 and 1996 were investigated by nucleoprotein ELISA and serology. Investigations showed that serum levels of vaccine-induced single radial haemolysis (SRH) antibody correlated closely with protective immunity against equine influenza and were consistent with observations made in previous experimental studies using nebulised aerosol challenge. In the second part of this study, antibody levels stimulated by vaccination were investigated to examine probable protection in high risk groups, such as yearlings and horses in training. Results for yearlings correlated closely with experimentally derived antibody profiles described for several equine influenza vaccines. The horses in training had levels of antibody immediately prior to revaccination, which were higher than those measured in the yearlings. In conclusion, SRH antibody, used in the investigation of outbreaks and surveillance of post vaccination responses, was shown to correlate with and validate experimental vaccination and challenge models currently used in ponies in the licensing of modern vaccines. There may be benefit from serological monitoring of horses following vaccination through identification of susceptible periods to infection and demonstration of poor vaccine responders. This would allow appropriate and timely amendment of vaccination strategies to maximise protective immunity against influenza.

Animals↗
PubMed1999

Comparative histopathology of radial artery versus internal thoracic artery and risk factors for development of intimal hyperplasia and atherosclerosis.

BACKGROUND: In this study, we examined the comparative histopathology, morphometry, and risk factors for the development of intimal hyperplasia and atherosclerosis in the radial artery (RA) and the internal thoracic artery (ITA). METHODS AND RESULTS: Paired specimens of RAs and ITAs, obtained from 150 patients who underwent CABG, were evaluated with histopathology; 110 pairs of arteries were suitable for morphometric analysis. The severity of disease was evaluated on the basis of percentage of luminal narrowing, intimal thickness index, and intima-to-media ratio. Risk factors were determined with stepwise linear regression. Intimal hyperplasia was seen in 141 RAs (94%) and 103 ITAs (69%) (P<0.001). Atherosclerosis was seen in 5% of RAs and 0.7% of ITAs (P=0.04). Medial calcification was found only in RAs (20 of 150, 13.3%) (P<0.001). Morphometric analysis showed that compared with ITAs, RAs had a significantly higher intimal area, medial area, percentage of luminal narrowing, intimal thickness index, and intima-to-media ratio (all P<0.001) Factors found to be significant (P<0.05) predictors of the 3 severity indices of intimal hyperplasia, including atherosclerosis, in RAs were peripheral vascular disease, smoking, age, and diabetes. Risk factors for intimal hyperplasia in ITAs were age and smoking. CONCLUSIONS: The RA is more likely to have atherosclerosis, intimal hyperplasia, and medial calcification than the ITA. Morphometric analysis indices showed marked differences between the RA and the ITA. Care should be taken when selecting the RA as a conduit in CABG, particularly in patients who are elderly, diabetic, smoke, or have peripheral vascular disease.

Adult↗
PubMed1999

Topical wound anaesthesia in children--a temporary postoperative pain relief.

BACKGROUND: Administration of local anaesthetics into the surgical wound may modulate pain at the peripheral level. A previous study in adults has shown good analgesic effects of topical lidocaine in wounds after herniorrhaphy. METHODS: Postoperative pain relief after topical administration of 10% lidocaine aerosol in the surgical wound was investigated in a randomised, double-blind study in children undergoing inguinal hernia repair. Forty-four patients aged between 9 months and 11 years were randomised into three groups. One group received active treatment with a lidocaine aerosol 2.5-4.7 mg kg-1, one group received a placebo aerosol and one control group was untreated. Postoperative pain was evaluated by nurse assessment, self-assessment and wound palpation 0, 1, 4 and 12 h after arrival in the recovery room. RESULTS: After 1 h the incidence of pain, as estimated by behavioural assessment and self-assessment, was significantly reduced in the lidocaine group in comparison to the placebo group, but not in comparison to the control group. The reaction on wound palpation was significantly reduced in the lidocaine group compared to both the placebo and control groups. At 0, 4 and 12 h no significant differences between the groups were observed. Plasma lidocaine concentrations were measured in six patients. Maximum individual concentrations were low, ranging from 0.17 to 0.86 microgram ml-1. CONCLUSION: A very short and clinically insignificant pain relief is obtained following the administration of a lidocaine aerosol in the surgical wound. A low pain level in this model may limit the possibility to detect an effect of lidocaine.

Administration, Topical↗
PubMed1999

Effects of amide local anaesthetics on eicosanoid formation in burned skin.

BACKGROUND: Previous studies have demonstrated potent inhibition of burn oedema and progressive ischaemia by local anaesthetics. Since eicosanoids have been suggested to play an important role in the pathophysiology of burns, we compared in the present ex vivo study the effects of topical lidocaine/prilocaine cream (EMLA, ASTRA, Sweden) and intravenous lidocaine with that of saline on eicosanoid formation by normal and burned rat skin. METHODS: A full-thickness burn trauma was induced in the abdominal skin. All the agents were given 5 min postburn until 2 h after the trauma. The experimental skin was subsequently removed and incubated in Krebs solution for 1 h. Eicosanoid concentrations in the solution were analysed by radioimmunoassay. RESULTS: EMLA cream induced a significant inhibition of TXB2 (P<0.05) and 6-Keto-PGF1alpha (P<0.01) but not of PGE release from burned skin as compared to saline treatment. Intravenous lidocaine infusions did not significantly influence the release of any of the measured eicosanoids versus saline. CONCLUSION: In conclusion, the lack of effect of intravenous lidocaine could relate to the severe burn trauma inducing rapid ischaemia which may have interfered with the delivery of the agent to the burned tissues or to insufficient concentrations achieved in the burn area. Topical treatment of burned skin with a local anaesthetic cream significantly reduced the release of TXB2 and 6-Keto-PGF1alpha, suggesting a possible mechanism of action in progressive burn ischaemia.

6-Ketoprostaglandin F1 alpha↗
PubMed1999

Digital image analysis of erythema development after experimental thermal injury to human skin: effect of postburn topical local anesthetics (EMLA).

UNLABELLED: Local anesthetics inhibit edema and improve circulation in experimental burns. We evaluated the effect of topical local anesthetics on human skin burns in volunteers using computerized color analysis that allowed repeated noninvasive quantitative measurements. A standardized partial-thickness burn (1 cm2) was induced in one forearm of 10 healthy volunteers and in the opposite forearm a week later. The burned areas were treated with lidocaine/prilocaine cream (EMLA; Astra, Sweden) or a placebo cream for 1 h. The experimental skin area was photographed before and 1, 2, 4, and 12 h postburn. Digitized images were evaluated using normalized red-green-blue and Hue-Saturation-Intensity. Differences in erythema between skin treated with EMLA and placebo were not significant during the first 4 h postburn. However, 12 h postburn, a pronounced decrease in the degree of erythema was observed in EMLA-treated skin compared with placebo-treated skin. We conclude that topical local anesthetics administered for 1 h postburn significantly reduces the duration of erythema after a mild thermal injury, which suggests a potential use in clinical practice in the treatment of minor skin burns. IMPLICATIONS: Burn injury constitutes a serious type of tissue damage that activates inflammatory mechanisms, often causing pain, disfiguration, or malfunction. We treated burns using an anesthetic cream and demonstrated a reduction in burn-induced inflammation by using computer-based color image analysis.

Administration, Topical↗