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Biomedical subjects

A Fraser

Publications and source records attributed to A Fraser.

At least 37 records · Page 2Linked to original sources
PubMed2004

Efficacy of anakinra in active ankylosing spondylitis: a clinical and magnetic resonance imaging study.

OBJECTIVE: To determine the efficacy of anakinra, an interleukin 1 receptor antagonist in active ankylosing spondylitis (AS), and to investigate the effect of anakinra treatment on spinal enthesitis/osteitis using magnetic resonance imaging (MRI). METHODS: A 3 month open label study of anakinra (100 mg subcutaneous injection daily) was carried out in nine patients with active AS who had back pain and an increased acute phase response, and who had failed to respond to at least one non-steroidal anti-inflammatory drug. Clinical assessment included the Bath AS Functional Index (BASFI), Bath AS Disease Activity Index (BASDAI), and AS Quality of Life (ASQoL) before and after treatment. Fat suppressed MRI of the spine and sacroiliac joints was performed with a 1.5 T scanner at baseline and at 3 months to determine the effect of treatment on spinal enthesitis/osteitis. RESULTS: Significant improvement was found in the BASFI (median baseline 5.88, 3 months 3.63, p = 0.021), BASDAI (median baseline 5.63, 3 months 3.48, p = 0.028), ASQoL (median baseline 12, 3 months 8, p = 0.011) and laboratory measures reflecting inflammation, with C reactive protein (median baseline 31 mg/l, 3 months 17 mg/l, p = 0.036) and erythrocyte sedimentation rate (median baseline 19 mm/1st h, 3 months 15 mm/1st h, p = 0.008) also showing significant improvement. Six patients (67%) achieved the Assessments in AS (ASAS) Working Group criteria of 20% improvement. Of the 38 regions of enthesitis/osteitis determined by MRI at baseline, 23 (61%) either improved or regressed completely. CONCLUSIONS: This open label pilot study suggests that anakinra is effective in controlling the clinical manifestations of AS. The clinical response was reflected by an improvement in MRI determined spinal enthesitis/osteitis.

Adult↗
PubMed2004

Therapeutic monitoring of cyclosporine in kidney transplantation: the Halifax experience.

Appropriate dosing of an immunosuppressive agent is critical to its efficacy and tolerability. Finding a simple and effective method of monitoring cyclosporine (CsA/CyA) has been formidable despite a long history of widespread usage. Earlier reports linked CsA dosing to trough levels (C0), whereas later more elaborate systems have evaluated efficacy linked to 12-hour area-under-the-curve (AUC(0-12)) as a measure of total drug exposure. Recent work done at our center and elsewhere has shown that the 2-hour postdose concentration (C2) to be simple and more effective than the C0 or the AUC. With C2 monitoring as a guide to CsA dosing, acute rejection (AR) and nephrotoxicity (NT) can be effectively reduced. Furthermore, absorption profile as per C2 levels further emphasizes the importance of achieving the targeted peak concentration in the first week of transplantation. The C2 concentration strategy is discussed in light of newer induction agents and other immunosuppression.

Administration, Oral↗
PubMed2004

Nicorandil associated anal ulceration.

OBJECTIVE: Nicorandil is a vasodilator used to control angina. It has been associated with oral and anal ulceration that resolves upon withdrawal of the drug. PATIENTS AND METHODS: We report a series of 13 patients with nonspecific anal ulceration all of whom were receiving nicorandil for control of symptoms of ischaemic heart disease. RESULTS: All the ulcers had similar clinical and histological appearances. All the ulcers healed on withdrawal of the drug. CONCLUSION: Nicorandil-associated anal ulceration should be considered in the differential diagnoses of nonhealing anal ulcers.

Aged↗
PubMed2003

Gastroschisis: determinants of neonatal outcome.

This retrospective study elicits information regarding the dependence of neonatal outcome in gastroschisis upon: (1) the mode of delivery, (2) place of birth, (3) time for birth to surgery, (4) method of closure, (5) time from operation to commencement of first enteral feeds. The neonatal intensive care database from five major tertiary centres was used to identify 181 neonates with gastroschisis from 1990 to 2000. There were 8 deaths. There were no significant differences in outcome for infants delivered vaginally (102) versus Caesarean section (79), those born near the tertiary centre (133) as compared to infants born away (48), ones operated within 7 hours (125) compared with those operated after 7 hours (56), with delayed closure (30) versus primary closure (151). Neonates fed within 10 days of operation (85) had significantly lower incidence of sepsis, duration of TPN and hospital stay when compared to those fed after 10 days (96). Early commencement of feeds decreases the incidence of sepsis, duration of total parenteral nutrition (TPN) and hospital stay. Place of delivery, mode of delivery, time to surgery and type of closure do not influence neonatal outcome.

Delivery, Obstetric↗
PubMed2003

Basiliximab widens the therapeutic window for AUC-monitored neoral therapy early after kidney transplantation.

Early adequate cyclosporine exposure has been shown to predict low acute rejection. Recently basiliximab induction has been added to immunosuppressive regimens to further reduce rejection. The aim of this study was to determine the importance of achieving the early cyclosporine therapeutic threshold with basiliximab induction. A retrospective analysis of first cadaver and nonidentical living donor transplant recipients treated with or without basiliximab induction was performed. All patients (n = 170) received neoral, mycophenolate mofetil, and prednisone. The cyclosporine absorption profile was measured on day 3. Adequate cyclosporine exposure was defined as area under the curve (AUC) 0-4: >4400 microg x h/L at day 3. The primary outcome was acute rejection (AR) within the first 6 month. In the no basiliximab (control) group, AR occurred in 22% (17/78) of recipients and was strongly associated with low cyclosporine exposure on day 3. AR occurred in 39% (9/23) with cyclosporine AUC0-4 < 4400 microg x h/L compared with 15% (8/55) with AUC0-4 > 4400 microg x h/L (P =.016). In the basiliximab group, AR occurred in only 9% (8/92) of recipients and did not correlate with cyclosporine exposure. AR occurred in 8% (2/24) with cyclosporine AUC0-4 < 4400 microg x h/L compared with 9% (6/68) with AUC0-4 > 4400 microg x h/L (P =.94). Achieving cyclosporine therapeutic targets by day 3 may not be required when anti-IL2 induction is used.

Antibodies, Monoclonal↗
PubMed2003

Tacrolimus monitoring by simplified sparse sampling under the concentration time curve.

The purpose of this study was to determine which tacrolimus pharmacokinetic parameters best predicted efficacy in kidney transplantation. Blood tacrolimus levels at 0, 1, 2, 3, and 4 hours postdose were measured in 28 kidney transplants. All received tacrolimus-based triple-drug therapy with mychophenolate mofetil and prednisone. Associations between blood concentrations at each sampling time point and the area under the curve (AUC) 0-4 were measured by Pearson's correlation coefficients. Tacrolimus dosing was based on C0 not AUC. AUC and blood concentrations at each sampling time were retrospectively compared with C0 as predictor of acute rejection and nephrotoxicity. Although tacrolimus C0 correlated with AUC0-4 (r =.86), correlations were higher with C2 and C3 (r =.96 and r =.94, respectively). C0 levels were not significantly different in six patients with acute rejection and 23 patients without. There was a trend toward lower tacrolimus C3 in patients with AR than without AR (P =.06). C2 and C3 correlate better with AUC0-4 than C0. Early tacrolimus C3 levels may be a better than C0 as a predictor of efficacy.

Adult↗
PubMed2003

Partial characterisation of carbohydrate-rich Echinococcus granulosus coproantigens.

Coproantigen ELISA based tests for diagnosis of canine echinococcosis provide high specificity and sensitivity. However, the antigenic molecules present in faeces from infected dogs have not yet been characterised. While initial attempts to determine the molecular weights of Echinococcus granulosus coproantigens by SDS-PAGE and Western blotting with coproantigen reactive capture antibodies were equivocal, they suggested presence of a significant carbohydrate component. Periodate treatment of coproantigen positive faecal supernatants resulted in a significant reduction (53%) in ELISA activity, suggesting that carbohydrates are involved in the antigenic structure of E. granulosus coproantigens. Protease treatment of antigenic molecules resulted in an 11% reduction in absorbance in ELISA, indicating that protein components were also present which affected by enzyme activity. Lectin-binding ELISA assays indicated strong affinity of E. granulosus coproantigens to concanavalin agglutinin and Lens culinaris agglutinin, and moderate binding to wheat-germ agglutinin and peanut agglutinin. No binding was detectable to Ulex europaensis agglutinin-I, Bandeiraea simplicifolia or Dolichos biflorus agglutinin. These data indicate that E. granulosus coproantigens from infected dog faeces possibly contained alpha-D-mannose and/or alpha-D-glucose, beta-galactose and N-acetyl-beta-glucosamine residues. To verify the role of carbohydrate moieties in coproantigens, faecal samples were treated with exoglycosidase and tested in the coproantigen ELISA. Treatment with beta-galactosidase or N-acetyl-beta-glucosamine reduced ELISA activity by 44 and 30%, respectively. Incubation with a panel of other specific exoglycosidases including alpha-galactosidase as well as alpha-L-fucosidase, alpha-mannosidase, beta-mannosidase, alpha-glucosidase, beta-glucosidase, beta- fructosidase, or neuraminidase, did not alter coproantigen detection in ELISA. The results indicate that coproantigens present in faeces from E. granulosus naturally infected dogs were highly glycosylated and contain beta- galactose and N-acetyl-beta-glucosamine. The putative relationship of antigenic molecules with the tapeworm glycocalyx is discussed.

Acetylglucosamine↗
PubMed2002

Chemotherapy of porcine cysticercosis with albendazole sulphoxide.

Cysticercosis is a zoonotic disease of humans produced by the larval stage of swine parasite, Taenia solium. Chemotherapy of infected pigs is a possible strategy for avoiding disease transmission and improving health programs in endemic areas of cysticercosis. In this preliminary study, seven naturally infected pigs from 6 to 12 months of age were allotted to treated (n = 4) and control groups (n = 3). The treated animals received a subcutaneous injection in their forelegs and thighs of 15 mg/kg per body weight of albendazole sulphoxide (ABZSO; Pisa, Mexico) once per day for 8 days. At the same time, the control group received a subcutaneous injection of saline solution (9% NaCl). After 12 weeks, all the animals were slaughtered and at least 200 metacestodes were isolated from the muscles and brain of each animal. Using histology and the metacestode viability criteria described in this study, treated animals had no viable cysts in their muscle (0/200), while 7 of 17 (41.1%) viable cysts were observed in those isolated from their brains. In the control group, 183/200 (91.5%) muscle metacestodes were viable and from brain, 22/29 (75.8%) metacestodes were viable. The 15 mg/kg per body weight dosage of ABZSO was 100% effective against muscular cysticercosis as shown by the lack of viable cysts and the micro-calcifications in meat from the treated pigs.

Albendazole↗
PubMed2002

Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2).

Streptomyces coelicolor is a representative of the group of soil-dwelling, filamentous bacteria responsible for producing most natural antibiotics used in human and veterinary medicine. Here we report the 8,667,507 base pair linear chromosome of this organism, containing the largest number of genes so far discovered in a bacterium. The 7,825 predicted genes include more than 20 clusters coding for known or predicted secondary metabolites. The genome contains an unprecedented proportion of regulatory genes, predominantly those likely to be involved in responses to external stimuli and stresses, and many duplicated gene sets that may represent 'tissue-specific' isoforms operating in different phases of colonial development, a unique situation for a bacterium. An ancient synteny was revealed between the central 'core' of the chromosome and the whole chromosome of pathogens Mycobacterium tuberculosis and Corynebacterium diphtheriae. The genome sequence will greatly increase our understanding of microbial life in the soil as well as aiding the generation of new drug candidates by genetic engineering.

Bacterial Proteins↗
PubMed2002

Structure-dependent vibrational lifetimes of hydrogen in silicon.

The lifetimes of the Si-H vibrational stretch modes of the H(*)(2) ( 2062 cm(-1)) and HV.VH((110)) ( 2072.5 cm(-1)) defects in crystalline Si are measured directly by transient bleaching spectroscopy from 10 K to room temperature. The interstitial-type defect H(*)(2) has a lifetime of 4.2 ps at 10 K, whereas the lifetime of the vacancy-type complex HV.VH((110)) is 2 orders of magnitude longer, 295 ps. The temperature dependence of the lifetime of H(*)(2) is governed by TA phonons, while HV.VH((110)) is governed by LA phonons. This behavior is attributed to the distinctly different local structure of these defects and the accompanying local vibrational modes.

Journal Article↗
PubMed2002

The genome sequence of Schizosaccharomyces pombe.

We have sequenced and annotated the genome of fission yeast (Schizosaccharomyces pombe), which contains the smallest number of protein-coding genes yet recorded for a eukaryote: 4,824. The centromeres are between 35 and 110 kilobases (kb) and contain related repeats including a highly conserved 1.8-kb element. Regions upstream of genes are longer than in budding yeast (Saccharomyces cerevisiae), possibly reflecting more-extended control regions. Some 43% of the genes contain introns, of which there are 4,730. Fifty genes have significant similarity with human disease genes; half of these are cancer related. We identify highly conserved genes important for eukaryotic cell organization including those required for the cytoskeleton, compartmentation, cell-cycle control, proteolysis, protein phosphorylation and RNA splicing. These genes may have originated with the appearance of eukaryotic life. Few similarly conserved genes that are important for multicellular organization were identified, suggesting that the transition from prokaryotes to eukaryotes required more new genes than did the transition from unicellular to multicellular organization.

Base Sequence↗
PubMed2002

Malignant bronchosubcutaneous fistula presenting as subcutaneous emphysema.

A bronchosubcutaneous fistula is a communication between the subcutaneous tissues, the pleural cavity, and the bronchial system. It is a rare manifestation of primary pulmonary disease. The authors present a very unusual case of bronchosubcutaneous fistula that presented as subcutaneous emphysema after palliative radiation therapy for primary carcinoma of the lung.

Bronchial Fistula↗
PubMed2002

Taenia solium metacestode viability in infected pork after preparation with salt pickling or cooking methods common in Yucatán, Mexico.

The cestode parasite Taenia solium is an important cause of foodborne infection throughout tropical and subtropical regions. Ingestion of pork meat infected with T. solium larvae can lead to taeniasis infection in humans. With tourism and the consumption of native food increasing, it is important to investigate potential risks of transmission associated with food preparation methods. In this study, traditional Mexican salt pickling and two methods of pork preparation (as roast pork [cochinita pibil] and in pork and beans [frijol con puerco]) were evaluated in order to determine their effects on T. solium cyst viability in infected tissue. In the control groups, all metacestodes isolated were 100% viable, and only small changes in pH (from 6.0 to 5.9) and temperature (29 to 30 degrees C) were recorded. No viable cysts were detected after 12 and 24 h of salt pickling. The pH of the meat during salting dropped from 6.0 to 5.3. Osmotic changes and dehydration from the salting, rather than a change in pH, could be considered the main cause of cyst death. Temperatures of >65 degrees C damaged T. solium metacestodes in roast pork and in pork and beans. The results of this study indicate that if traditional pork dishes are prepared properly, T. solium cysts are destroyed. The criteria used in this study to evaluate the viability of tissue cysts are discussed.

Animals↗
PubMed2001

Suppression of IL-2-induced T cell proliferation and phosphorylation of STAT3 and STAT5 by tumor-derived TGF beta is reversed by IL-15.

IL-2 responses are susceptible to suppression by TGFbeta, a cytokine widely implicated in suppression of inflammatory responses and secreted by many different tumor cell types. There have been conflicting reports regarding inhibition of IL-2-induced STAT3 and STAT5 phosphorylation by TGFbeta and subsequent suppression of immune responses. Using TGFbeta-producing multiple myeloma tumor cells we demonstrate that tumor-derived TGFbeta can block IL-2-induced proliferation and STAT3 and STAT5 phosphorylation in T cells. High affinity IL-2R expression was required for the suppression of IL-2 responses as a novel CD25(-) T cell line proliferated and phosphorylated STAT3 when cultured with tumor cells or rTGFbeta1. Activating T cells with IL-15, which does not use the high affinity IL-2R, completely restored the ability of T cells to phosphorylate STAT3 and STAT5 when cultured with tumor cells. IL-15-treated T cells proliferated normally when cocultured with tumor cells or rTGFbeta1, whereas IL-2 responses were consistently inhibited. Preincubation with IL-15 also restored the ability of T cells to respond to IL-2 by phosphorylating STAT3 and STAT5, and proliferating normally in the presence of tumor cells. IL-2 pretreatment did not restore T cell function. IL-15 also restored T cell responses by T cells from multiple myeloma patients, and against freshly isolated bone marrow tumor samples. Thus, activation of T cells by IL-15 renders T cells resistant to suppression by TGFbeta1-producing tumor cells and rTGFbeta1. This finding may be exploited in the design of new immunotherapy approaches that will rely on T cells avoiding tumor-induced suppression.

Cells, Cultured↗
PubMed2001

Paternal and maternal components of the predisposition to preeclampsia.

BACKGROUND: There is an inherited maternal predisposition to preeclampsia. Whether there is a paternal component, however, is not known. METHODS: We used records of the Utah Population Database to identify 298 men and 237 women born in Utah between 1947 and 1957 whose mothers had had preeclampsia during their pregnancy. For each man and woman in the study group, we identified two matched, unrelated control subjects who were not the products of pregnancies complicated by preeclampsia. We then identified 947 children of the 298 male study subjects and 830 children of the 237 female study subjects who had been born between 1970 and 1992. These children were matched to offspring of the control subjects (1950 offspring of the male control group and 1658 offspring of the female control group). Factors associated with preeclampsia were identified, and odds ratios were calculated with the use of stepwise logistic-regression analysis. RESULTS: In the group whose mothers had had preeclampsia (the male study group), 2.7 percent of the offspring (26 of 947) were born of pregnancies complicated by preeclampsia, as compared with 1.3 percent of the offspring (26 of 1973) in the male control group. In the female study group, 4.7 percent of the pregnancies (39 of 830) were complicated by preeclampsia, as compared with 1.9 percent (32 of 1658) in the female control group. After adjustment for the offspring's year of birth, maternal parity, and the offspring's gestational age at delivery, the odds ratio for an adult whose mother had had preeclampsia having a child who was the product of a pregnancy complicated by preeclampsia was 2.1 (95 percent confidence interval, 1.0 to 4.3; P=0.04) in the male study group and 3.3 (95 percent confidence interval, 1.5 to 7.5; P=0.004) in the female study group. CONCLUSIONS: Both men and women who were the product of a pregnancy complicated by preeclampsia were significantly more likely than control men and women to have a child who was the product of a pregnancy complicated by preeclampsia.

Adult↗
PubMed2001

Massive gene decay in the leprosy bacillus.

Leprosy, a chronic human neurological disease, results from infection with the obligate intracellular pathogen Mycobacterium leprae, a close relative of the tubercle bacillus. Mycobacterium leprae has the longest doubling time of all known bacteria and has thwarted every effort at culture in the laboratory. Comparing the 3.27-megabase (Mb) genome sequence of an armadillo-derived Indian isolate of the leprosy bacillus with that of Mycobacterium tuberculosis (4.41 Mb) provides clear explanations for these properties and reveals an extreme case of reductive evolution. Less than half of the genome contains functional genes but pseudogenes, with intact counterparts in M. tuberculosis, abound. Genome downsizing and the current mosaic arrangement appear to have resulted from extensive recombination events between dispersed repetitive sequences. Gene deletion and decay have eliminated many important metabolic activities including siderophore production, part of the oxidative and most of the microaerophilic and anaerobic respiratory chains, and numerous catabolic systems and their regulatory circuits.

Animals↗