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Biomedical subjects

B Robinson

Publications and source records attributed to B Robinson.

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

Inhibition of porcine reproductive and respiratory syndrome virus by interferon-gamma and recovery of virus replication with 2-aminopurine.

Porcine reproductive and respiratory syndrome virus (PRRSV) belongs to a group of RNA viruses that establish persistent infections. A proposed strategy for evading immunity during persistent PRRSV infection is by preventing the induction of IFN activity in pigs and/or by blocking the activation of antiviral proteins in permissive cells. IFN-gamma mRNA expression was observed in the lymph nodes and lungs of pigs infected with wild-type PRRSV strain SDSU-23983. Pretreatment of MARC-145 cells with IFN-gamma inhibited wild-type (SDSU-23983 P6) and culture-adapted (SDSU-23983 P136) PRRS viruses in a dose-dependent manner and at relatively low concentrations. The effect of IFN-gamma on virus replication included reductions in the number of infected cells, virus yield, and RNA content in single cells. Virus replication was partially restored by the addition of 2-aminopurine (2-AP), an inhibitor of dsRNA inducible protein kinase (PKR). The addition of 2-AP also restored the viral RNA content per cell to near normal levels, suggesting that inhibition of viral RNA synthesis was through PKR. The principal difference between P6 and P136 isolates was the recovery of P136 replication with lower concentrations of 2-AP. Immunostaining with anti-PKR antibody showed a redistribution of PKR from the cytoplasm into nucleoli of infected cells.

2-Aminopurine↗
PubMed2001

'Fast track' postoperative management protocol for patients with high co-morbidity undergoing complex abdominal and pelvic colorectal surgery.

BACKGROUND: A combination of factors has emphasized the need to reduce postoperative stay after surgery. Multimodal care plans may shorten hospital stay, but have been associated with high readmission rates and are generally reserved for straightforward, non-complicated colonic (not rectal) resections. This study evaluated a 'fast track' protocol in patients undergoing major colonic and rectal surgery. METHODS: Sixty consecutive patients (median age 44.5 (range 13-70) years) underwent major procedures over a 6-week period on one colorectal service. Nasogastric tubes and epidural anaesthesia were not used. Patients participated in a protocol of early diet and early ambulation, and were discharged after meeting defined criteria. RESULTS: Fifty-eight patients (97 per cent) were deemed suitable for the 'fast track' approach at the time of surgery and stayed for a mean(s.d.) of 4.3(1.6) days after operation. Patients in diagnosis-related group (DRG) 148 (colorectal resection with co-morbidity; n = 40) stayed for 4.6(1.7) days, which was longer than those in DRG 149 (without co-morbidity; n = 18) who stayed 3.5(0.8) days (P = 0.01). Three patients (5 per cent) required a nasogastric tube for vomiting. There were no readmissions directly attributable to 'fast track' failure, although four patients (7 per cent) were readmitted within 30 days of operation for other reasons. Eight poorly compliant patients stayed for 5.1(1.1) days (P = 0.02 versus compliant patients). 'Fast track' patients had a shorter length of stay than patients receiving traditional care on other colorectal services during the same time period (compared by DRG 148, DRG 149 and for all patients) (P < 0.0001). CONCLUSION: The 'fast track' protocol allows patients with high levels of co-morbidity undergoing complex colorectal and reoperative pelvic surgery to benefit from a rapid recovery and early discharge from hospital. The approach is safe and has low readmission rates.

Adolescent↗
PubMed2001

Intraoperative quick parathyroid hormone versus same-day parathyroid hormone testing for minimally invasive parathyroidectomy: a cost-effectiveness study.

BACKGROUND: Intraoperative quick parathyroid hormone (QPTH) measurement is claimed to eliminate failures during minimally invasive parathyroidectomy. The cost-effectiveness of QPTH (ie, true cost of avoiding a failed operation) needs careful evaluation. METHODS: In 92 consecutive patients who underwent minimally invasive parathyroidectomy via a small lateral incision, QPTH was estimated preoperatively and at 5, 10, and 15 minutes postparathyroidectomy. QPTH results were subsequently compared with the procedure outcome. Cost-effectiveness analysis was performed for 3 subsequent theoretical management strategies: QPTH not performed, QPTH results available intraoperatively, and parathyroid hormone and serum calcium levels measured routinely with results made available the same day. RESULTS: With criteria for cure being a decrease in the QPTH measurement to less than 50% of preoperative levels and to within normal range, QPTH predictions were true positive in 78 patients; false-negative in 7; false-positive in 1; and true negative in 2. The true cost of using QPTH measurement to avoid a failed operation was 19,801.19 US dollars, with 7 patients undergoing unnecessary conversion. Routine same-day parathyroid hormone and calcium measurements significantly reduced this to 624.73 dollars. Sensitivity analysis with varying cost assumptions demonstrated cost-effectiveness analysis to be robust. CONCLUSIONS: The fact that 97% of patients will be cured regardless of QPTH testing combined with its false-negative rates significantly reduces the cost-effectiveness of the test when compared with same-day parathyroid hormone testing.

Adult↗
PubMed2001

Anaesthesia for amiodarone-induced thyrotoxicosis: a case review.

Amiodarone-induced thyrotoxicosis is a life-threatening problem that is very effectively managed by total thyroidectomy, although often many of these patients are considered "too unfit" for anaesthesia. The aim of this study was to review the safety of anaesthesia for total thyroidectomy in the acute management of amiodarone-induced thyrotoxicosis. Information was obtained retrospectively from a prospective endocrine surgical database and from hospital records. Data, including outcomes and morbidity, are presented from 12 patients who underwent anaesthesia for total thyroidectomy as an urgent procedure for amiodarone-induced thyrotoxicosis. Despite the fact that these patients had uncontrolled thyrotoxicosis and marked cardiac failure at the time of anaesthesia, no anaesthetic or surgical mortality was seen. We conclude that a challenging patient with amiodarone-induced thyrotoxicosis that has not responded to conservative measures may be considered for total thyroidectomy early in their management. Total thyroidectomy can be performed under general or local anaesthesia with apparent relative safety.

Adult↗
PubMed2001

Osteoporosis with low dose corticosteroids: contribution of underlying disease effects and discriminatory ability of ultrasound versus bone densitometry.

OBJECTIVE: Corticosteroid use is associated with rapid bone loss, but the effect of low dose corticosteroids (CS) remains controversial and the extent to which increased fracture risk relates to quantitative effects, as reflected by change in bone mineral density (BMD), or to qualitative effects due to altered microarchitecture is unclear. Moreover the contribution of the underlying disease, for which CS are used, confounds the assessment of CS effects on bone. Our aim was to examine these effects of CS on bone. METHODS: We measured BMD, quantitative ultrasound (US), and clinical and radiological disease indices in 76 patients with rheumatoid arthritis (RA) treated with or without low dose CS. Disease effects were quantitated using the Health Assessment Questionnaire and radiological scores. RESULTS: BMD and US measures were significantly reduced in RA patients compared to age matched controls. Low dose CS use was associated with a further small but nonsignificant reduction in BMD, and US measures did not further discriminate CS effects on bone. Radiological score was an independent predictor of US measures, suggesting that in RA, calcaneal bone may reflect both systemic and local disease effects. CONCLUSION: US did not appear to discriminate effects of low dose CS on bone better than BMD. However, underlying RA disease effects on bone are detectable by US. Quantitative US should be investigated for its utility in assessing disease activity or progress in RA.

Absorptiometry, Photon↗
PubMed2000

In vivo cross-presentation of a soluble protein antigen: kinetics, distribution, and generation of effector CTL recognizing dominant and subdominant epitopes.

Cross-presentation of exogenous Ags via the MHC class I pathway is now recognized for its role in self-tolerance, tumor immunity, and vaccine development. However, little is known about the in vivo distribution and kinetics of cross-presented protein Ags, nor the subsequent development of CTL effector responses to dominant or subdominant epitopes. We examined the location and duration of cross-presented Ag by using 5,6-carboxy-succinimidyl-fluorescein ester-labeled T cells from class I-restricted Ag-specific TCR mice. Comparisons of results from an in vitro (51)Cr release CTL assay with an in vivo CTL assay provided physiologically relevant insights into the functional capacities of CTL specific for epitopes with differing affinities. These data demonstrate that efficient cross-presentation of a dominant class I-restricted Ag is dose related and remains largely localized, but not limited to the draining lymph nodes for up to 3 wk following a single injection of soluble protein. Within this period, dominant peptide-specific CTL are fully functional in vivo throughout the secondary lymphoid system. However, no in vivo responses are seen to a subdominant or cryptic epitope. Prolonging Ag cross-presentation via use of IFA promoted persisting in vivo dominant epitope-specific CTL activity and revealed dose-responsive precursor CTL to the subdominant, but not to a cryptic epitope. Analysis of functional in vivo CTL responses demonstrated that, in the presence of strong ongoing responses to the dominant peptide, lytic activity of CTL directed at weaker epitopes is undetectable.

Adjuvants, Immunologic↗
PubMed2000

Inhibition of HIV-1 protease by a boron-modified polypeptide.

Six boronated tetrapeptides with the carboxy moiety of phenylalanine replaced by dihydroxyboron were synthesized, and their activities against human immunodeficiency virus 1 (HIV-1) protease subsequently investigated. The sequences of these peptides were derived from HIV-1 protease substrates, which included the C-terminal part of the scissile bond (Phe-Pro) within the gag-pol polyprotein. Enzymatic studies showed that these compounds were competitive inhibitors of HIV-1 protease with K(i) values ranging from 5 to 18 microM when experiments were performed at high enzyme concentrations (above 5 x 10(-8) M); however, at low protease concentrations inhibition was due in part to an increase of the association constants of the protease subunits. Ac-Thr-Leu-Asn-PheB inhibited HIV-1 protease with a K(i) of 5 microM, whereas the non-boronated parental compound was inactive at concentrations up to 400 microM, which indicates the significance of boronation in enzyme inhibition. The boronated tetrapeptides were inhibitory to an HIV-1 protease variant that is resistant to several HIV-1 protease inhibitors. Finally, fluorescence analysis showed that the interactions between the boronated peptide Ac-Thr-Leu-Asn-PheB and HIV-1 protease resulted in a rapid decrease of fluorescence emission at 360 nm, which suggests the formation of a compound/enzyme complex. Boronated peptides may provide useful reagents for studying protease biochemistry and yield valuable information toward the development of protease dimerization inhibitors.

Boron Compounds↗
PubMed2000

Manganese superoxide dismutase levels are elevated in a proportion of amyotrophic lateral sclerosis patient cell lines.

The most frequent genetic causes of amyotrophic lateral sclerosis (ALS) determined so far are mutations occurring in the gene for copper/zinc superoxide dismutase (CuZnSOD). The mechanism may involve inappropriate formation of hyroxyl radicals, peroxynitrite or malfunctioning of the SOD protein. We hypothesized that undiscovered genetic causes of sporadically occurring amyotrophic lateral sclerosis might be found in the mechanisms that create and destroy oxygen free radicals within the cell. After determining that there were no CuZnSOD mutations present, we measured superoxide production from mitochondria and manganese superoxide dismutase (MnSOD), glutathione peroxidase, NFkappaB, Bcl-2 and Bax by immunoblot. Of the ten sporadic patients we tested we found three patients with significantly increased concentrations of MnSOD. These patients also had lower levels of superoxide production from mitochondria and decreased expression of Bcl-2. No mutations were found in the cDNA sequence of either MnSOD in any of the sporadic patients. A patient with a CuZnSOD mutation (G82R) used as a positive control showed none of these abnormalities. The patients displaying the MnSOD aberrations showed no specific distinguishing features. This result suggests that the cause of ALS in a subgroup of ALS patients (30%) is genetic in origin and can be identified by these markers. The alteration in MnSOD and Bcl-2 are likely epiphenomena resulting from the primary genetic defect. It suggests also that the oxygen free radicals are part of the cause in this subgroup and that dysregulation of MnSOD or increased endogenous superoxide production might be responsible.

Adult↗
PubMed2000

Mutations associated with microsatellite unstable colorectal carcinomas exhibit widespread intratumoral heterogeneity.

Although microsatellite instability (MSI) has been shown to be present in 15% of sporadic colorectal carcinomas, the genetic events underlying the development of these tumors have not been well described. By investigating intratumoral heterogeneity, this study attempts to elucidate whether MSI-positive colorectal carcinomas develop as the result of a random accumulation of mutations or as an ordered, stepwise sequence of genetic alterations. Eighty-six regions from 16 MSI-positive sporadic colorectal carcinomas were examined for mutations in repeat nucleotide sequences of the tumour suppressor genes transforming growth factor beta type II receptor (TGFBRII), insulin-like growth factor II receptor (IGFIIR), and BAX, and the mismatch repair genes MSH3 and MSH6. At least 2 and up to 5 of these genes were mutated in each tumour, and widespread intratumoral heterogeneity was observed for each gene. Regions of tumour with TGFBRII mutations were correlated with a poorly differentiated histology. Unlike the situation in microsatellite stable colorectal carcinomas, the findings of the present study did not suggest that a particular sequence of tumour suppressor and mismatch repair genes are mutated during colorectal tumorigenesis. It seems likely that a random accumulation of mutations, as a result of a defect in the mismatch repair pathway, drives tumour progression in this type of colorectal carcinoma.

Colorectal Neoplasms↗
PubMed2000

Calbindin-D28k immunoreactivity in the suprachiasmatic nucleus and the circadian response to constant light in the rat.

Recent studies in the hamster have led to the discovery that the expression of the calcium binding protein, calbindin-D28k, is a defining feature of neurons in the suprachiasmatic nucleus involved in the regulation of circadian rhythms by environmental light.(2,18, 19,32) To study further the involvement of calbindin-D28k, we examined the effect of exposure to constant light on calbindin-D28k immunoreactivity in the suprachiasmatic nucleus of intact rats and of rats treated neonatally with the retinal neurotoxin, monosodium glutamate. Exposure to constant light is known to disrupt circadian rhythms in rodents and we found previously that treatment with monosodium glutamate selectively prevents the disruptive effect of constant light on circadian rhythms in rats.(7,9) In the present study we found that exposure to light suppresses calbindin-D28k expression in the ventrolateral retinorecipient region of the suprachiasmatic nucleus of rats and that neonatal treatment with monosodium glutamate blocks the suppressive effect of constant light on calbindin-D28k expression. These findings are consistent with the proposed role of calbindin-D28k in photic signaling in the suprachiasmatic nucleus,(32) and point to the possibility that suppression of calbindin-D28k expression is linked to the mechanism by which constant light disrupts circadian rhythms.

Animals↗
PubMed2000

Personal theories, intellectual ability, and epistemological beliefs: adult age differences in everyday reasoning biases.

Age-related differences in everyday reasoning biases were explored. In each of 2 social domains, examination of theoretical beliefs and biases along 2 dimensions of scientific reasoning, involving the law of large numbers and the evaluation of experimental evidence, revealed that, across age groups, scientific reasoning was used to reject evidence that contradicted prior beliefs; relatively cursory reasoning was used to accept belief-consistent evidence. Biased reasoning was more common among middle-aged and older adults than among young adults. Dispositions to engage in analytic processing were negatively related to biases, but intellectual abilities and bias were not related. The findings support a 2-process view of adult cognitive development and suggest that the tendency to rely on heuristic information processing increases with age.

Adult↗
PubMed2000

Replication-restricted vaccinia as a cytokine gene therapy vector in cancer: persistent transgene expression despite antibody generation.

BACKGROUND: As antitumoral immunity requires the generation of local immunity directed against tissue proteins, we attempted to recreate within tumors the same environment found within tissues affected by autoimmune diseases (i.e., prolonged cytokine expression). Vaccinia virus (VV) has not been widely used as a cytokine gene therapy vector because of presumed high immunogenicity that would likely make repeated injections impossible; therefore, we modified it by inserting the cytokine gene into the thymidine kinase region, rendering it replication-restricted. The cytokine chosen was human interleukin-2 (IL-2); a molecule with powerful antitumoral effects. METHODS: Six patients with the treatment-resistant tumor malignant mesothelioma received intratumoral (i.t.) VV-IL-2 therapy for 12 weeks by injection of 10(7) plaque-forming units of VV-IL-2 per dose. Serial tumor biopsies, sputum, urine, and blood samples were tested for VV-IL-2 mRNA expression; VV culture and T-cell infiltrates were evaluated by immunohistochemistry. Patients and contacts of patients were monitored for changes in VV immunoglobulin G (IgG) levels and clinical evidence of VV infection. RESULTS: VV-IL-2 was not excreted and was only cultured in one patient from tumor biopsies. A T-cell infiltrate was detected in 50% of tumor biopsies. VV-IL-2 mRNA expression was highest on days 1-3 postinjection and was detected for up to 3 weeks after each injection even though VV IgG levels rose in all patients. No significant toxicities, infection of patient contacts, or tumor regressions were observed. CONCLUSIONS: I.t. VV-IL-2 administration is safe, is associated with minimal toxicity, and results in i.t. expression of VV-IL-2 for up to 3 weeks postinjection regardless of the level of anti-VV IgG titers generated. This suggests that VV may be a good vector for repeated cytokine gene therapy of solid human cancer.

Adult↗
PubMed2000

Loss of heterozygosity in sporadic parathyroid tumours: involvement of chromosome 1 and the MEN1 gene locus in 11q13.

OBJECTIVE: Hyperparathyroidism (HPT) is a common endocrine disorder. Several loci of genetic interest have been identified in parathyroid tumours, including the MEN1 gene locus at 11q13; the HPT-JT region at 1q21-q32; and a putative tumour suppressor gene on 1p. We analysed these intervals, which harbour known genes or putative loci associated with familial hyperparathyroidism, in order to clarify the involvement of the respective regions in parathyroid tumourigenesis. DESIGN: We performed loss of heterozygosity (LOH) studies on 33 sporadic parathyroid tumours using a PCR based technique. A total of 22 microsatellite markers were used to analyse loci at 11q13, 1q21-q32 and 1p. Ten markers located distal on 1p, eight markers encompassed the HPT-JT region at 1q21-q32 and four markers surrounded the MEN1 gene locus at 11q13. MEN1 mutations were screened for using Single Strand Conformation Polymorphism analysis (SSCP) and automated sequencing of SSCP variants. PATIENTS: Thirty-three parathyroid glands and the corresponding blood samples were obtained from 33 patients (26 females and seven males) who underwent parathyroidectomy for primary hyperparathyroidism. RESULTS: Loss of heterozygosity was detected in 13 of 33 (39%) cases at 11q13, 6 of 33 (18%) cases at 1p, and in three of 33 (9%) cases at 1q (in conjunction with 1p loss). Only one of the 18 tumours in which LOH was detected, showed LOH at both chromosome 1 and chromosome 11. Additionally, those tumours found to exhibit LOH at 11q13 were screened for MEN1 mutations using single strand conformation polymorphism analysis (SSCP) and automated sequencing. Nine novel somatic mutations were found on the remaining allele in 13 (69%) tumours. CONCLUSIONS: This study consolidates the role of multiple loci in the pathogenesis of sporadic parathyroid tumours. The results indicate that there are at least two genetic loci involved in sporadic parathyroid tumourigenesis on chromosome 1, one of which has been linked to the distinct familial parathyroid condition, hyperparathyroidism-jaw tumour (HPT-JT) syndrome. The high frequency of loss of heterozygosity at 1p suggests the presence of a tumour suppressor at this locus.

Adenoma↗
PubMed2000

Anaesthetic simulators: training for the broader health-care profession.

BACKGROUND: The use of high-fidelity patient simulators for training health-care professionals has increased rapidly in recent years. Approximately 150 simulation training centres operate internationally. Australasia has acquired four centres since 1997. A large component of simulator-based training is experiential. METHODS: Participants manage clinical scenarios on lifelike computer-controlled mannikins within realistic clinical environments. Afterwards they actively reflect upon the experience, an exercise that is facilitated by observation of a video replay of the event. RESULTS: This approach to training promotes a consideration of broader issues which can influence clinical practice and patient outcomes. This has particular relevance to emergencies. Here, events that are by nature infrequent and unscheduled can be addressed in a controlled fashion, in an environment that is supportive and separated from actual patients. CONCLUSIONS: A broad range of skills can be addressed with this resource. Of key importance are situational management and team effectiveness skills. Deficiencies with respect to these 'non-clinical' skills are being increasingly identified for their contribution to preventable adverse events within the health-care environment. Multidisciplinary operation-room team training has the potential to address these issues as they relate to the perioperative environment.

Anesthesiology↗
PubMed2000

Outcome of pregnancies complicated by pre-gestational diabetes mellitus.

Pregestational diabetes mellitus (DM) is associated with adverse fetal and maternal outcomes. Studies suggest that optimal control of diabetes before and during pregnancy minimises these risks. There are few recent reviews of outcomes of pregnancies complicated by DM in Australia. Ninety-three pregnancies in women with DM at our hospital since 1989 were identified. We collected data for maternal age, type of diabetes, duration of therapy, complications of diabetes, maternal complications of pregnancy and fetal outcomes including malformations. The rate of pregnancy planning with optimal glycaemic control at conception was low in our population, particularly in patients with Type 1 diabetes. Women who smoked had worse glycaemic control, and a higher rate of miscarriage. There was a high rate of Caesarean section, particularly in those women with Type 1 diabetes (77.4%). The rate of Caesarean section was lower in planned pregnancies. There were no perinatal deaths. The number of neonates with major congenital anomalies was high (13%) in the Type 1 population. It is important to increase the rates of prepregnancy planning and to optimise glycaemic control before pregnancy. In many cases there has been a long interval between diagnosis and pregnancy, so all women with diabetes should receive counselling at frequent intervals about pregnancy and the importance of planning. Women who planned their pregnancies had improved outcomes, with decreased rate of Caesarean section, better glycaemic control and better neonatal Apgar scores. Women with diabetes should not smoke during pregnancy because of the increased risk of miscarriage and poorer glycaemic control.

Adult↗