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Biomedical subjects

R Foster

Publications and source records attributed to R Foster.

At least 19 recordsLinked to original sources
PubMed2006

Primary systemic vasculitis: treatment of difficult cases.

The primary systemic necrotizing vasculitides are a severe group of diseases, which untreated have a high mortality. The majority respond to treatment with high dose steroids and cyclophosphamide, however a significant proportion of those treated suffer morbidity due to the side effects of these agents, and a number of patients are refractory to treatment. We review and discuss alternative and emerging treatment options for patients who fail or cannot tolerate conventional therapy. An interesting subgroup of patients with systemic vasculitis and antiphospholipid antibodies provides an additional diagnostic and therapeutic challenge. We review what is known about this subgroup, and suggest screening for antiphospholipid antibodies in all patients with systemic vasculitis.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2005

A case of disseminated histoplasmosis successfully treated with the investigational drug posaconazole.

A 79-year-old man with a 3-month history of weight loss and fever was diagnosed with disseminated histoplasmosis. When the infection became refractory to itraconazole therapy, posaconazole was prescribed. The patient became asymptomatic within 1 month of beginning treatment, and his general health improved. Posaconazole was discontinued after 6 months, and the patient has remained well since.

Aged↗
PubMed2005

A novel Shigella dysenteriae serovar isolated in Canada.

The etiological agent most commonly associated with bacillary dysentery is Shigella. As part of its mandate, the Bacteriology and Enteric Disease Program of Health Canada identifies and serotypes unusual isolates of Shigella received from provincial laboratories of public health. In this report, six unusual isolates from three provinces were analyzed biochemically and serologically using slide and tube agglutinations and molecularly using standard pulsed-filed gel electrophoresis (PFGE), PCR, and PCR-restriction fragment length polymorphism (RFLP) techniques. All six isolates were identical. PFGE analysis grouped these strains; biochemically, they were mannitol negative and consistent with the profile of Shigella. Serologically, these strains produced weak reactions in Shigella dysenteriae serovars 4 and 16 and Escherichia coli O159 and O173 antisera. Molecular serotyping by PCR-RFLP of the rfb gene produced an S. dysenteriae serovar 2/E. coli O112ac pattern. They were positive by PCR for ipaH and ial enteroinvasive genes but negative for all other genes tested. Antiserum was prepared from one of the isolates and tested against Shigella and E. coli reference strains as well as the other isolates. The antiserum reacted with the five remaining isolates and showed cross-reactivity with S. dysenteriae serovars 1, 4, and 16; Shigella flexneri type 3; and E. coli O118, O159, O168, O172, and O173 antigens. Absorbing the sera with E. coli O159 and S. dysenteriae serovar 4 antigen removed all cross-reactions and only slightly reduced the homologous titer. Based on biochemical, molecular, and complete serological analysis, we propose that these six isolates represent a new provisional serovar of S. dysenteriae, type strain BEDP 02-5104.

Adolescent↗
PubMed2005

Heat-shock proteins and their role in chondrocyte protection, an application for autologous transplantation.

Articular cartilage injury presents a unique therapeutic challenge. As cartilage possesses no blood or nerve supply of its own it has a particular susceptibility to early injury and a poor capacity for self-repair. Treatment options are limited and injury can eventually lead to osteoarthritis. Autologous chondrocyte transplantation is an exciting therapeutic development, but despite initial encouraging results, graft failure and formation of fibro- as opposed to hyaline cartilage remain problematic. Bleeding is an inevitable consequence of surgery, and blood-induced cartilage damage is well documented. It is hypothesised here that protecting chondrocytes against blood could significantly improve results. Heat-shock protein induction may confer chondroprotection. The expression of heat-shock proteins in human chondrocytes and rat femoral head cartilage following heat shock was analysed by Western blotting, and red-blood-cell-induced chondrocyte death was assessed by cell viability and apoptosis by flow cytometry. We demonstrate that heat-shock induced expression of heat-shock protein 70 (HSP70) (rat and human) and HSP32 (human). Blood and blood products reduced rat cartilage proteoglycan synthesis and human chondrocyte viability, and induced human chondrocyte apoptosis at concentrations considerably lower than those reported previously. The induction of HSP70 in rat cartilage was ineffective in reducing chondrocyte death in the absence or presence of red blood cells or red cell products. Heat shock to human chondrocytes reduced low levels of apoptosis (<20%) and cell death induced by low levels of blood products, but not higher levels. Induction of HSP32 with diacetylrhein appeared to be more effective and may hold greater promise. Blood has potent adverse effects on chondrocytes and the induction and chondroprotective effects of heat-shock proteins could be applied to increase the initial success of implanted chondrocytes improving the outcome of autologous chondrocyte transplantation.

Animals↗
PubMed2005

A case of clozapine-induced tonic-clonic seizures managed with valproate: implications for clinical care.

We describe a case of clozapine-induced seizures in a patient with treatment-resistant schizophrenia. She had previously been treated unsuccessfully with a number of atypical antipsychotic medications, before she was eventually started on clozapine. She experienced two separate episodes of observed fits whilst on an initial daily dose of 125 mg and, subsequently, on a daily dose of 237.5 mg. Following discontinuation of clozapine, she was rechallenged and again was observed to have seizures. Appropriate investigations ruled out any organic cause of the fits and clozapine was successfully restarted, together with sodium valproate. By the time of treatment stabilization, the patient had not experienced any further fits. These findings suggest that clozapine-induced seizures can be successfully treated, that gradual dose titration can reduce the likelihood of further episodes of seizures and that concomitant use of a suitable mood stabilizer/anti-epileptic medication can improve the outcome of treatment-resistant schizophrenia. Furthermore, the concomitant use of fluoxetine and clozapine is discouraged, with citalopram suggested as a suitable antidepressant in those depressed patients receiving clozapine.

Adult↗
PubMed2003

Antiretroviral therapy-induced psychosis: case report and brief review of the literature.

OBJECTIVE: We present a case of psychosis in an individual with known HIV infection whose symptoms developed approximately 1 month following the commencement of combination antiretroviral therapy consisting of abacavir (ABC), nevirapine and combivir. She presented with severe persecutory delusions, accompanied by mutism, posturing and catatonia. Following cessation of therapy and the introduction of a low-dose antipsychotic, her mental state resolved to a stable premorbid level, and no further disturbances of behaviour were noted. Furthermore, when re-challenged with the above combination minus ABC, there were no further episodes of psychosis. It is proposed that the aetiology of the psychosis was related to her antiretroviral therapy. METHODS: Cessation of antiretroviral medication and initiation of antipsychotic medication with appropriate monitoring and assessment. RESULTS: Subjective and objective improvements in psychotic symptoms and presentation. CONCLUSION: The current case suggests that sudden onset psychotic disturbances in HIV-infected individuals in the absence of other known organic or other causal factors could be related to treatment with antiretroviral therapy, and that cessation of this can markedly improve psychiatric morbidity. Furthermore, treatment with antipsychotic medication can lead to alleviation of psychotic symptoms and enable the re-introduction of antiretroviral medication.

Adult↗
PubMed2002

Review article: faecal markers in the assessment of activity in inflammatory bowel disease.

The fundamental pathological process behind ulcerative colitis and Crohn's disease is intestinal inflammation. As the precise cause of this is not yet completely understood, current treatment strategies are aimed at reducing or eliminating the inflammation. Endoscopic examination and histological analysis of biopsy specimens remain the 'gold standard' methods for detecting and quantifying bowel inflammation; however, these techniques are costly, invasive, and repeated examinations are unpopular with patients. Disease activity questionnaires and laboratory 'inflammatory markers', although widely used, show an unreliable correlation with endoscopy and histology. New markers need to be developed to detect and quantify bowel inflammation. These would be of use diagnostically and also an aid to pharmacological treatment.

Biomarkers↗
PubMed2001

Photic entrainment of the circadian clock: from Drosophila to mammals.

Entrainment is as fundamental to an organism's circadian timing as are the molecular mechanisms involved in the functioning of the intracellular clock oscillator. In nature, one of the principle, although not the only, circadian entraining stimulus (Zeitgeber) is provided by the daily light--dark cycles. In animals, the visual processing apparatus alone is inadequate to accomplish the task of transducing circadian photic signals to the clockwork machinery. In fact, it is ever more appreciated by circadian biologists that organisms as divergent as plants and mammals have evolved a wonderfully complex array of partly redundant specializations which can guarantee the precise alignment of biological and environmental time. Research in circadian biology is cruising at such a rate that attempts to review the state of the art can only hope, at best, to provide a snapshot of the speeding cruiser from its wake. This paper will hopefully provide a reasonably sharp portrayal of what is at hand.

Animals↗
PubMed2001

Molecular discrimination of garfish Hyporhamphus (Beloniformes) larvae in southern Australian waters.

A multiplex polymerase chain reaction (PCR) assay developed for discrimination between garfish larvae (family Hemiramphidae, order Beloniformes) found in southern Australian waters was based on species-specific amplification of part of the mitochondrial control region. The species were easily discerned by the number and distinct sizes of PCR products (Hyporhamphus melanochir, 443 bp; H. regularis, 462 and 264 bp). Although based on a single gene, the method will correctly identify the species of individuals in at least 96% of tests for H. melanochir and 94% of tests for H. regularis.

Journal Article↗
PubMed2001

Analysis of candidate antagonists of IAP-mediated caspase inhibition using yeast reconstituted with the mammalian Apaf-1-activated apoptosis mechanism.

We have reconstituted the Apaf-1-activated apoptosis mechanism in Sacchromyces cerevisiae such that the presence of a constitutively active form of Apaf-1 together with both Caspase-9 and Caspase-3 results in yeast death. This system is a good model of the Apaf-1-activated pathway in mammalian cells: MIHA (XIAP/hILP), and to a lesser degree MIHB (c-IAP1/HIAP2) and MIHC (c-IAP-2/HIAP1) can inhibit caspases in this system, and protection by IAPs (inhibitor of apoptosis) can be abrogated by coexpression of the Drosophila pro-apoptotic proteins HID and GRIM or the mammalian protein DIABLO/Smac. Using this system we demonstrate that unlike DIABLO/Smac, other proteins which interact with mammalian IAPs (TAB-1, Zap-1, Traf-1 and Traf-2) do not act to antagonise IAP- mediated caspase inhibition.

Animals↗
PubMed2001

Faecal calprotectin and faecal occult blood tests in the diagnosis of colorectal carcinoma and adenoma.

BACKGROUND AND AIMS: Testing for faecal occult blood has become an accepted technique of non-invasive screening for colorectal neoplasia but lack of sensitivity remains a problem. The aim of this study was to compare the sensitivity and specificity of faecal calprotectin and faecal occult blood in patients with colorectal cancer and colonic polyps. METHODS: Faecal calprotectin and occult blood were assessed in 62 patients with colorectal carcinoma and 233 patients referred for colonoscopy. The range of normality for faecal calprotectin (0.5-10.5 mg/l) was determined from 96 healthy subjects. RESULTS: Median faecal calprotectin concentration in the 62 patients with colorectal carcinoma (101 mg/l, 95% confidence interval (CI) 57-133) differed significantly from normal (2.3 mg/l, 95% CI 1.6-5.0) with 90% of patients having elevated levels (normal <10 mg/l) whereas only 36/62 (58%) had positive faecal occult bloods. There was no significant difference in faecal calprotectin levels when considering location or Dukes' staging of tumour. Percentage positivity of faecal occult bloods was significantly higher for Dukes' stage C and D cancers compared with Dukes' A and B. In the colonoscopy group, 29 patients with adenomatous polyps were detected in whom the median faecal calprotectin was 12 mg/l (95% CI 2.9-32). Sensitivity for detection of adenomatous polyps was 55% using the calprotectin method and 10% using faecal occult blood testing. The overall sensitivity and specificity of calprotectin for colorectal cancer and adenomatous polyps as a combined group was 79% and 72%, respectively, compared with a sensitivity and specificity of faecal occult blood of 43% and 92%. CONCLUSIONS: Faecal calprotectin is a simple and sensitive non-invasive marker of colorectal cancer and adenomatous polyps. It is more sensitive than faecal occult blood tests for detection of colorectal neoplasia at the cost of a somewhat lower specificity.

Adenoma↗
PubMed2001

Safety and efficacy of preoperative administration of meloxicam, compared with that of ketoprofen and butorphanol in dogs undergoing abdominal surgery.

OBJECTIVE: To compare the safety and efficacy of preoperative administration of meloxicam with that of ketoprofen and butorphanol in dogs undergoing abdominal surgery. ANIMALS: 36 dogs undergoing laparotomy, splenectomy, or cystotomy. PROCEDURE: Dogs were randomly assigned to 1 of 3 groups. In the first part of the study, dogs were given a single dose of meloxicam, ketoprofen, or a placebo, and buccal mucosal bleeding times were measured. In the second part of the study, dogs were given meloxicam, ketoprofen, or butorphanol prior to surgery. Dogs in the butorphanol group received a second dose immediately after surgery. Pain scores (1 to 10) were assigned hourly for 20 hours after surgery and used to determine an overall efficacy score for each dog. Dogs with a pain score > or =3 were given oxymorphone for pain. Dogs were euthanatized 8 days after surgery, and gross and histologic examinations of the liver, kidneys, and gastrointestinal tract were conducted. RESULTS: Overall efficacy was rated as good or excellent in 9 of the 12 dogs that received meloxicam, compared with 9 of the 12 dogs that received ketoprofen and only 1 of the 12 dogs that received butorphanol. No clinically important hematologic, biochemical, or pathologic abnormalities were detected. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that preoperative administration of meloxicam is a safe and effective method of controlling postoperative pain for 20 hours in dogs undergoing abdominal surgery; the analgesic effects of meloxicam were comparable to those of ketoprofen and superior to those of butorphanol.

Analgesics, Non-Narcotic↗
PubMed2001

Elevated and altered expression of the multifunctional DNA base excision repair and redox enzyme Ape1/ref-1 in prostate cancer.

The DNA base excision repair pathway is responsible for the repair of cellular alkylation and oxidative DNA damage. A crucial step in the BER pathway involves the cleavage of baseless sites in DNA by an apurinic/apyrimidinic or baseless (AP) endonuclease (Ape1/ref-1), which is a multifunctional enzyme that acts not only as an AP endonuclease but also as a redox-modifying factor for a variety of transcription factors including Fos, Jun, paired box containing genes (PAX), nuclear factor-kappaB, hypoxia-inducible factor alpha (HIF-1alpha), HIF-like factor (HLF), p53, and others. The expression of Ape1/ref-1 in prostate has not been characterized previously. Ape1/ref-1 nuclear immunohistochemistry levels, scored for intensity as 1+, 2+, or 3+, were 91, 3, and 6% in benign hypertrophy (BPH), 0, 42, and 58% in prostatic intraepithelial neoplasia (PIN) and 3, 30, and 67% in prostate cancer, respectively, clearly showing an increase in Ape1/ref-1 nuclear staining in the PIN and cancer compared with BPH. Furthermore, the level of cytoplasmic staining of Ape1/ref-1 in cancer and PIN were elevated (42 and 36%, respectively) compared with BPH (5%). There was no correlation with prostate-specific antigen values or doubling times to Ape1/ref-1 levels. In conclusion, we have demonstrated that Ape1/ref-1 is dramatically elevated in prostate cancer, the level of staining of Ape1/ref-1 increases from low in BPH to intense in PIN and cancer, and there is an increase in the amount of Ape1/ref-1 in the cytoplasm of PIN and cancer compared with BPH. Given these results, we conclude that Ape1/ref-1 may be a diagnostic marker for early prostate cancer and play a role, through its repair, redox, or both functions, in the physiology of the early development of prostate cancer.

Biomarkers, Tumor↗
PubMed2001

Control of specific gene expression by gibberellin and brassinosteroid.

We identified a recessive, brassinolide-insensitive mutant caused by a deletion allele (bri1-201) of the brassinosteroid (BR) receptor BRI1. The bri1-201 mutant displayed altered expression levels of genes differentially regulated by gibberellin (GA). RNA-blot analysis revealed that BR and GA antagonistically regulate the accumulation of mRNAs of the GA-responsive GASA1 gene, as well as the GA-repressible GA5 gene. Expression studies with cycloheximide indicated that the antagonistic effects of GA and BR on GA5 require de novo protein synthesis. Reporter transgene analyses and RNA-blot analysis showed that BR and GA modulate GA5 expression, at least in part, at the transcriptional level, and that the signals are independent and subtractive.

Arabidopsis↗
PubMed2000

Predicting species diversity in tropical forests.

A fundamental question in ecology is how many species occur within a given area. Despite the complexity and diversity of different ecosystems, there exists a surprisingly simple, approximate answer: the number of species is proportional to the size of the area raised to some exponent. The exponent often turns out to be roughly 1/4. This power law can be derived from assumptions about the relative abundances of species or from notions of self-similarity. Here we analyze the largest existing data set of location-mapped species: over one million, individually identified trees from five tropical forests on three continents. Although the power law is a reasonable, zeroth-order approximation of our data, we find consistent deviations from it on all spatial scales. Furthermore, tropical forests are not self-similar at areas </=50 hectares. We develop an extended model of the species-area relationship, which enables us to predict large-scale species diversity from small-scale data samples more accurately than any other available method.

Journal Article↗
PubMed2000

Influence of acebutolol and metoprolol on cardiac output and regional blood flow in rats.

Beta-adrenoceptor blocking drugs are widely used as effective antihypertensive and antianginal agents. We have determined the effect of beta-blockade in the rat to ascertain whether there are differences between metoprolol (MET) and acebutolol (AC) with respect to regional blood flow (RBF). Both AC and MET were administered as a single or multiple intravenous (iv) doses in Sprague-Dawley rats. Microspheres labelled with (85)Sr and (141)Ce were used to measure cardiac output (CO) and RBF before and after drug administration. CO and RBF were measured 1 and 10 min after the i.v. administration of AC (30 mg/kg) and MET (10 mg/kg). After acute administration of MET, CO decreased by 65% and 31% after 1 and 10 min measurements, respectively. These values were 54% and 28% for AC as compared with baseline values. After chronic administration of either AC or MET, however, there were no significant reductions in CO as compared with saline. Both MET and AC significantly reduced RBF in most organs either after 1 or 10 min measurements when compared with the baseline values. It is concluded that both AC and MET reduced CO and RBF after acute administration. The CO and RBF however, returned to normal after chronic administration.

Acebutolol↗