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Biomedical subjects

R Preston

Publications and source records attributed to R Preston.

At least 19 recordsLinked to original sources

Developing research capacity building for Aboriginal & Torres Strait Islander health workers in health service settings.

INTRODUCTION: Aboriginal and Torres Strait Islander health workers (hereafter called health workers) can play a major role in facilitating culturally appropriate health care delivery and program development through the acquisition of improved skills in the planning, monitoring and evaluation of these programs (RCB). However, many Aboriginal and Torres Strait Islander people and communities remain concerned about research and related activities. Health workers are well placed to assist communities to not only embrace research, but to be active players and promoters of relevant, appropriate and acceptable research. One means of achieving the twin goals of RCB and community acceptance and involvement in research, is through health workers undertaking research of health priority issues and evaluation of activities, such as program delivery, that are of direct relevance to their community's aim of improving or enhancing service delivery. This article outlines the development and content of a community-based RCB framework for health workers. The focus is on the major issues that enhance a proactive service delivery model using culturally appropriate research methods. Development process: The RCB framework described here was developed, over a period of time, through community workshops and consultations aimed at deriving general consensus on the key issues and components of a culturally-appropriate, community-based training process. The framework has subsequently been reviewed by Aboriginal and Torres Strait Islander community representatives from across Australia. The overall aim of the framework is to supplement current (institutionally-based) education and training resources for health workers with community-based research training modules. These modules can be tailored to provide research and evaluation skills relevant to health workers taking a more proactive role in facilitating health and wellbeing programs in their own communities. The use of collaborative consultation and participatory methods are intended to be a two-way education process. Course content: A visual pathway is used that encompasses the impact of health and practice in the community for health workers at a grass-roots level. This enables elements of the RCB process to be divided into a series of connected modules. These are: (i 'assessing' Existing Services; (ii) methods and measures for Identifying Need at various levels; (iii) important issues in Program Development; (iv) how the former contributes to Service Improvement; (v) resultant Outcomes that will impact on community and service provision; and (vi) Evaluation Methods and applying findings to service delivery. CONCLUSIONS: Active participation by the Aboriginal and Torres Strait Islander community is fundamental for effective research practices and outcomes. The aim is to provide health workers and community members with a working knowledge of research ethics and methods so that they can assist, monitor and steer the development of culturally appropriate research activities that will lead to provision of the highest quality services 'back' to the community. This RCB framework will enable health workers to be more proactive, self-reliant and self-sufficient within their community and healthcare settings.

Community Health Planning↗

Detection of Ki-ras mutations in tissue and plasma samples of patients with pancreatic cancer using PNA-mediated PCR clamping and hybridisation probes.

In the present study, we combined the PCR-clamping approach with melting curve analysis using mutant specific hybridisation probes and wild-type specific peptide nucleic acids (PNAs) to determine the genotypes of the most frequent point mutation in codon 12 of the proto-oncogene Ki-ras in tissue and plasma samples of patients with pancreatic cancer. The sensitivity of our assay was 1-5 x 10(-5). The melting curve analysis of tissue samples of four patients revealed two valine mutations, one none-valine mutation and one wild-type sequence. Ki-ras alterations were found in 28% of DNAs (18 out of 64) of nonrelated plasma samples of 10 patients with ductal adenocarcinoma of the pancreas. The valine mutation was the predominantly detected gene alteration (83%). Out of ten patients investigated, four patients (40%) became positive during clinical observation with respect to Ki-ras mutation. All four patients exhibited progressive disease and high levels of tumour marker CA 19-9. In conclusion, the one-step procedure discribed may be a useful clinical tool for analysing Ki-ras point mutations in tissue and plasmas samples. In addition, this method can be adapted for simultanous detection of multiple mutations and quantitation.

Carcinoma, Pancreatic Ductal↗

Acute radiation toxicity assessment of a 3-D conformal head and neck radiation treatment technique.

Patients undergoing radiation treatment for head and neck cancer have many critical structures within or adjacent to the treatment area. Avoiding these critical structures is more efficient and easier using 3-D conformal planning. At Sir Charles Gairdner Hospital an investigation into the acute radiation toxicity was undertaken when the head and neck treatment technique was changed from the conventional 2-D plan to the conformal 3-D plan. Although the primary target volume (PTV), fraction size and overall dose remain the same for the two techniques, differing beam configurations mean that treatment fields enter and exit through different parts of the head and neck. Ten patients were initially assessed to gain a baseline appearance of their head and neck region, and then graded weekly according to the toxicity criteria during treatment and at 4, 8 and 12 weeks after treatment. The results of the assessment indicate that there is no increase in toxicity as a result of treating using the conformal head and neck technique.

Acute Disease↗

Impact of an ACE inhibitor and calcium antagonist on microalbuminuria and lipid subfractions in type 2 diabetes: a randomised, multi-centre pilot study.

BACKGROUND: Microalbuminuria (MA) is associated with increased cardiovascular risk and lipid abnormalities in people with type 2 diabetes. ACE inhibitors and calcium channel blockers (CCBs) reduce MA and are neutral on total cholesterol and triglycerides. The effect of ACE inhibitors and CCBs on lipid subfractions such as Lp(a), apolipoprotein (apo) A1, apo B, and others, however, is unclear. The current study tests the hypothesis that a fixed-dose combination of an ACE inhibitor, benazepril (B) with the dihydropyridine CCB, amlodipine (A), will further reduce arterial pressure and reduce atherogenic lipid fractions compared to either agent alone. DESIGN: A multicentre, randomised, open-label, parallel group design was used to study 27 participants with type 2 diabetes. Measurements for total cholesterol, high- and low-density lipoprotein (HDL and LDL), triglycerides, apo A1, apo B, Lp(a), MA, arterial pressure and creatinine clearance were obtained at baseline and at 12-week intervals during the 36 week study. RESULTS: Arterial pressure was significantly reduced at 36 weeks in all three groups (P = 0.0078 for A, P = 0.0039 for B, and P = 0.0313 for A+B). MA was lowered in all groups with relatively greater reductions in the B (P < 0.05) and A+B groups (P < 0.03) vs A. An increase in mean HDL-cholesterol from baseline was noted in the B and A+B groups; P < 0.05), but not in the A group. A trend was also observed between the rise in HDL-cholesterol and the reduction in MA in the B and A+B groups. Additionally, only the B group exhibited a decrease in the median value of Lp(a) (P < 0.05). CONCLUSION: These data support the concept that ACE inhibition with B reduces the atherogenic profile by decreasing Lp(a) and increasing HDL-cholesterol, the latter being correlated with reductions in MA. While A+B exhibited similar trends in lipid subfractions and MA as B, this group had the greatest reduction in systolic blood pressure of the three groups. Thus, use of A+B offers the benefits of a decreased atherogenic profile with a higher probably of achieving goal blood pressure as recommended by national guidelines.

Aged↗

Sequence and analysis of chromosome 5 of the plant Arabidopsis thaliana.

The genome of the model plant Arabidopsis thaliana has been sequenced by an international collaboration, The Arabidopsis Genome Initiative. Here we report the complete sequence of chromosome 5. This chromosome is 26 megabases long; it is the second largest Arabidopsis chromosome and represents 21% of the sequenced regions of the genome. The sequence of chromosomes 2 and 4 have been reported previously and that of chromosomes 1 and 3, together with an analysis of the complete genome sequence, are reported in this issue. Analysis of the sequence of chromosome 5 yields further insights into centromere structure and the sequence determinants of heterochromatin condensation. The 5,874 genes encoded on chromosome 5 reveal several new functions in plants, and the patterns of gene organization provide insights into the mechanisms and extent of genome evolution in plants.

Animals↗

IgG2 anti-Galalpha1-3Gal does not induce porcine aortic endothelial cell accommodation in vitro.

BACKGROUND: Xenografts that have been protected from hyperacute rejection (HAR) are termed accommodated if they are not then rejected despite the presence of xenoantibody. It has been proposed that IgG may confer resistance to complement dependent cytotoxicity (CDC), a conventional in vitro marker of accommodation. We hypothesized that noncytotoxic IgG2 anti-Galalpha1-3Gal was responsible for this effect. METHODS AND RESULTS: We purified IgG anti-Galalpha1-3Gal from pooled human normal immunoglobulin and three sera, by elution from protein G and Galalpha1-3Gal-R immunoadsorbents. The eluates were IgM free and > or =95% IgG2. They bound to Galalpha1-3Gal, porcine aortic endothelial cells (PAEC) and lymphocytes. It was not possible to block IgM binding to PAEC or lymphocytes using IgG anti-Galalpha1-3Gal (200 microg/ml). The eluates were noncytotoxic in micro-CDC assays. To investigate accommodation, PAEC were cultured with subsaturating doses of the four IgG eluates for up to 144 hr. Resistance of nontrypsinized PAEC to CDC by human serum was measured in a cell viability assay. PAEC were not rendered resistant to CDC in any of the experiments. To investigate the possibility that accommodation might be induced by non-Galalpha1-3Gal IgG, the experiments were repeated using HNIg, again with no protection demonstrated. CONCLUSIONS: Using primary PAEC monolayers, we were unable to induce resistance to CDC with human normal immunoglobulin and its IgG2 anti-Gabeta1-3Gal subset. This contradicts previous experiments using trypsinized, immortalized cells. Although resistance to CDC is not an ideal marker of accommodation, the detrimental effects of IgG make it unlikely that it will become a useful clinical means of inducing accommodation.

Acute Disease↗

Sclerosing mesenteritis involving the pancreas: two cases of a rare cause of abdominal mass mimicking malignancy.

Two patients presented with abdominal pain and weight loss and each was found to have an abdominal mass involving the pancreas and small bowel mesentery. In both cases a malignant process was suspected clinically, radiologically and surgically. Multiple biopsy specimens in both patients showed dense fibrosis, chronic inflammation and fat necrosis with pancreatic infiltration. Histological opinions included the differential diagnosis of retroperitoneal fibrosis but, with the knowledge of the presence of localized masses, these cases were eventually considered to be due to sclerosing mesenteritis. Direct involvement of the pancreas has not previously been highlighted and led to diagnostic difficulty. Both patients have responded to treatment with corticosteroids. Interestingly, one of the patients subsequently developed a tubulo-interstitial nephritis, which has not previously been reported as associated with sclerosing mesenteritis. This has also responded to corticosteroid treatment.

Adult↗

Polymorphism in the human anti-pig natural antibody repertoire: implications for antigen-specific immunoadsorption.

BACKGROUND: Anti-Galalpha1-3Gal antibodies cause hyperacute rejection (HAR) in pig-to-primate xenotransplantation. Long-term graft survival has not been achieved despite abrogation of HAR using transgenic pigs. IgG and IgM anti-Galalpha1-3Gal also play a role in the events following abrogation of HAR. Characterizing these antibodies and developing a system for their removal is therefore crucial to future success in xenotransplantation. METHODS AND RESULTS: We have developed a neoglycoprotein enzyme-linked immunosorbent assay to probe the precise antigenic requirements for the binding of anti-Galalpha1-3Gal and have analyzed 77 normal sera. Sixty-six percent of individuals have IgG that recognizes the Galalpha1-3Gal di-, tri-, and pentasaccharides (D, T, and P, respectively), termed DTP phenotype. The frequency of other phenotypes was - -P, 13%; -TP, 12%; D-P, 8%; and DT-, 1%. The IgG subclasses found were IgG2 (95%), IgG3 (34%), IgG1 (31%), and IgG4 (17%). IgM in 91% of individuals recognized all three antigens. Further antibody heterogeneity was demonstrated when immunoadsorbents derived from Galalpha1-3Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc (PENTA) were tested. Galalpha1-3Galbeta1-4Glc (TRI 6) or PENTA agarose were effective for IgG removal in all individuals. For IgM removal, two deoxy derivatives were completely successful in 73% of individuals. Combining the Galalpha1-3Gal (DI) and TRI 6 agarose produced an adsorbent that completely removed anti-Galalpha1-3Gal IgG and IgM in all individuals tested. CONCLUSIONS: Although the polymorphism in the anti-Galalpha1-3Gal repertoire, which we have demonstrated, represents a major obstacle to the development of an effective immunoadsorbent, the combination of DI and TRI 6 agarose appears sufficient for pig-to-human xenotransplantation.

Animals↗

Obstetrical anaesthesia for a parturient with preeclampsia, HELLP syndrome and acute cortical blindness.

PURPOSE: To report the management of a multigravida presenting with preeclampsia, HELLP syndrome and acute cortical blindness for Caesarean section. CLINICAL FEATURES: A 39-yr-old woman, with three past uncomplicated pregnancies presented at 33 wk with acute cortical blindness. Based on clinical and laboratory assessment, a diagnosis of preeclampsia with HELLP syndrome was made. A CT scan of her head demonstrated ischaemic lesions of her basal ganglia, extending superiorly to involve both posterior parietal and occipital regions. Infusions of magnesium sulphate and hydralazine were started and an urgent Caesarean section was performed under subarachnoid anaesthesia after insertion of an arterial line and intravenous hydration. The course of anaesthesia and surgery was uneventful and she delivered a live 1540 g female infant. By the following morning, she had recovered some vision and visual recovery was complete by 72 hr postpartum. She underwent an MRI with angiography on the first postpartum day. Ischaemic lesions were confirmed in the same sites identified on CT scan but all major cerebral vessels were patent and no significant vascular abnormality was noted. Her postoperative course was uneventful and she was discharged home seven days postpartum after being prescribed labetalol for continued hypertension. CONCLUSION: The anaesthetic management of a parturient with acute cortical blindness and HELLP syndrome is modeled on the underlying preeclamptic condition. Invasive monitoring is not routinely indicated but is specifically indicated in some cases. Provided that it is not contraindicated because of prohibitive risk to the mother, regional anaesthesia has particular advantage in these patients. In particular, the use of spinal anaesthesia, which has been discouraged by some for this patient population, should be re-evaluated.

Acute Disease↗

Perinatal methanol exposure in the rat. II. Behavioral effects in neonates and adults.

The use of methanol as a component of automobile fuel will increase perinatal exposures in the general population. Few studies have addressed questions concerning neurotoxicity stemming from such exposures. In the current study, four cohorts of pregnant Long-Evans rats, each cohort consisting of an exposure and a control group, were exposed to 4500 ppm methanol vapor in Rochester-type inhalation chambers for 6 hr daily beginning on Gestation Day 6. Exposure continued for both dams and pups through Postnatal Day 21 (PND 21) to model gestational and neonatal toxicity in humans. Several behavioral procedures were used to assess exposure effects in the offspring. Male-female littermates were studied whenever possible to examine sex differences, with one pair from a litter for each procedure. Exposure to methanol did not affect suckling latency and nipple attachment on PND 5 or performance on an aversive olfactory conditioning procedure on PND 10. Exposure to methanol did alter performances in a motor activity procedure. Methanol-exposed neonates were less active on PND 18, but more active on PND 25 than the equivalent control group pups. Two operant conditioning procedures, not used previously in this context, assayed other littermates as adults. A fixed ratio schedule required the rat to rotate a running wheel a specified number of revolutions to obtain food-pellet reinforcers. When the fixed ratio requirement changed, number of responses (revolutions) per 1-hr session displayed a complex interaction with treatment. Changes in performance over the course of training differed between males and females depending on exposure to methanol. Compared to initial baseline performances, methanol-exposed males showed decreases, and methanol-exposed females increases, in the rate of running. A stochastic spatial discrimination procedure permitted subjects to respond on any three levers, with the probabilities of food-pellet delivery determined by the location of the preceding response. A reinforcement matrix defined the response sequence required to maximize reinforcements. When the matrix was changed, the methanol-exposed subjects responded less efficiently at asymptotic levels of performance than controls. Across procedures, developmental exposure to 4500 ppm methanol vapor was associated with subtle behavioral changes in both neonates and adults.

Administration, Inhalation↗

Epidural morphine vs hydromorphone in post-caesarean section patients.

PURPOSE: The purpose of this randomized controlled double blind study was to compare the efficacy of pain relief and the side effects of epidural hydromorphone and morphine in post-Caesarean patients. METHODS: In all patients, epidural anaesthesia was induced using carbonated lidocaine 2% with 1:200,000 epinephrine and 50 micrograms fentanyl, given in incremental doses. Patients in Group 1 (n = 24) received 0.6 mg hydromorphone and patients in Group 2 (n = 22) received 3 mg morphine after delivery of the infant. Pain, pruritus and nausea were measured using a visual analog scale (at times: baseline, on admission to the recovery room, 3, 6, 12, 18 and 24 hr postoperatively), by the number of requests for additional medications and by an overall satisfaction score. RESULTS: There was no difference between the groups in pain relief of in the incidence and severity of side effects. Pruritus was more pronounced within the first six hours in Group 1 and at 18 hr in Group 2. CONCLUSION: Hydromorphone provides no clinical benefit over epidural morphine for post operative analgesia following Caesarean section.

Adult↗