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S Brown

Publications and source records attributed to S Brown.

At least 19 recordsLinked to original sources
PubMed2007

Acquired haemophilia masked by warfarin therapy.

Acquired haemophilia is a rare phenomenon and prompt diagnosis is essential for successful treatment. Early laboratory detection could minimize its potentially devastating consequences and reduce mortality but when a masking element such as anticoagulant therapy is present, delay in diagnosis is not uncommon. A prolonged activated partial thromboplastin time (APTT) may be falsely attributed to warfarin alone, particularly when it is associated with oral anticoagulant overdose. We describe two patients on treatment with warfarin who presented with a bleeding diathesis and disproportionately prolonged APTT, which led to the diagnosis of antibodies directed against factor VIII.

Aged↗
PubMed2006

Quality control limits for posaconazole disk susceptibility tests on Mueller-Hinton agar with glucose and methylene blue.

A multilaboratory collaborative study was performed in order to propose quality control limits for posaconazole disk diffusion susceptibility tests on Mueller-Hinton agar supplemented with 2% glucose and 0.5 microg of methylene blue per ml. Replicate tests were performed on three lots of prepared media using 5-microg posaconazole disks in each of eight laboratories to generate data to propose quality control zone diameter ranges for tests of Candida albicans ATCC 90028 (24 to 34 mm), C. parapsilosis ATCC 22019 (25 to 36 mm), C. tropicalis ATCC 750 (23 to 33 mm), and C. krusei ATCC 6258 (23 to 31 mm).

Agar↗
PubMed2006

Astrophysical reaction rate for the neutron-generator reaction 13C(alpha,n)16O in asymptotic giant branch stars.

The reaction 13C(alpha,n) is considered to be the main source of neutrons for the s process in asymptotic giant branch stars. At low energies, the cross section is dominated by the 1/2+ 6.356 MeV subthreshold resonance in (17)O whose contribution at stellar temperatures is uncertain by a factor of 10. In this work, we performed the most precise determination of the low-energy astrophysical S factor using the indirect asymptotic normalization (ANC) technique. The alpha-particle ANC for the subthreshold state has been measured using the sub-Coulomb alpha-transfer reaction ((6)Li,d). Using the determined ANC, we calculated S(0), which turns out to be an order of magnitude smaller than in the nuclear astrophysics compilation of reaction rates.

Journal Article↗
PubMed2006

Cardiovascular actions of adrenocorticotropin microinjections into the nucleus tractus solitarius of the rat.

The presence of adrenocorticotropin (ACTH) containing cells and melanocortin (MC) receptors has been reported in the nucleus tractus solitarius (NTS) of the rat. The importance of the NTS in the regulation of cardiovascular function is also well established. Based on these reports, it was hypothesized that ACTH acting within the NTS may modulate the central regulation of cardiovascular function. To test this hypothesis, cardiovascular effects of ACTH in the NTS were investigated in intact urethane-anesthetized and unanesthetized decerebrate, artificially ventilated, adult male Wistar rats. Microinjections of ACTH (0, 0.5, 1, 2, and 4 mM) into the medial subnucleus of NTS (mNTS) elicited decreases in mean arterial pressure (MAP; 0+/-0, 24.4+/-3.5, 35.7+/-4.3, 44.5+/-5.8 and 53.7+/-5.6 mm Hg, respectively) and heart rate (HR; 0+/-0, 25.7+/-5.3, 35.5+/-6.4, 47.5+/-12.1 and 55.0+/-5.6 beats/min, respectively). The onset and duration of the responses to microinjections of ACTH (0.5-4 mM) were 5-10 s and 45-120 s, respectively. Control microinjections of artificial cerebrospinal fluid (aCSF) did not elicit any response. The volume of all microinjections was 100 nl. The concentrations of ACTH that elicited depressor and bradycardic responses when microinjected into the mNTS (e.g. 1 or 2 mM, 100 nl), did not elicit a response when injected i.v. (n=5) or i.c.v. (n=2) indicating that there was no leakage of the drug from the injection site in the mNTS. Microinjections of MC3/4 receptor antagonists (acetyl-[Nle(4), Asp(5), d-2-Nal(7), Lys(10)]-cyclo-alpha-MSH amide, fragments 4-10 (SHU9119) and agouti-related protein (83-132) amide) into the mNTS blocked the responses to ACTH. Microinjections of ACTH (2 mM) into the mNTS decreased efferent greater splanchnic nerve activity. Bilateral vagotomy significantly attenuated ACTH-induced bradycardia. These results indicated that: 1) microinjections of ACTH into the mNTS elicited depressor and bradycardic responses, 2) these responses were mediated via MC3/4 receptors, 3) the depressor effects were mediated via a decrease in the activity of the sympathetic nervous system, and 4) the bradycardic responses were vagally mediated.

Adrenocorticotropic Hormone↗
PubMed2006

The diagnosis and management of factor VIII and IX inhibitors: a guideline from the United Kingdom Haemophilia Centre Doctors Organisation.

The revised UKHCDO factor (F) VIII/IX Inhibitor Guidelines (2000) are presented. A schema is proposed for inhibitor surveillance, which varies according to the severity of the haemophilia and the treatment type and regimen used. The methodological and pharmacokinetic approach to inhibitor surveillance in congenital haemophilia has been updated. Factor VIII/IX genotyping of patients is recommended to identify those at increased risk. All patients who develop an inhibitor should be considered for immune tolerance induction (ITI). The decision to attempt ITI for FIX inhibitors must be carefully weighed against the relatively high risk of reactions and the nephrotic syndrome and the relatively low response rate observed in this group. The start of ITI should be deferred until the inhibitor has declined below 10 Bethesda Units/ml, where possible. ITI should continue, even in resistant patients, where it is well tolerated and so long as there is a convincing downward trend in the inhibitor titre. The choice of treatment for bleeding in inhibitor patients is dictated by the severity of the bleed, the current inhibitor titre, the previous anamnestic response to FVIII/IX, the previous clinical response and the side-effect profile of the agents available. We have reviewed novel dose-regimens and modes of administration of FEIBA (factor VIII inhibitor bypassing activity) and recombinant activated FVII (rVIIa) and the extent to which these agents may be used for prophylaxis and surgery. Bleeding in acquired haemophilia is usually treated with FEIBA or rVIIa. Immunosuppressive therapy should be initiated at the time of diagnosis with Prednisolone 1 mg/kg/d +/- cyclophosphamide. In the absence of a response to these agents within 6 weeks, second-line therapy with Rituximab, Ciclosporin A, or other multiple-modality regimens may be considered.

Evidence-Based Medicine↗
PubMed2006

Long-term safety and efficacy of poly-L-lactic acid in the treatment of HIV-related facial lipoatrophy.

OBJECTIVE: We evaluated the long-term safety and efficacy of injectable poly-L-lactic acid (PLLA) for the correction of facial lipoatrophy. METHODS: This was a randomized, open-label, comparative, single-centre study of injected PLLA in patients with HIV-related facial lipoatrophy. Thirty subjects were randomized to immediate or delayed PLLA treatments, administered as three sets of bilateral injections, 2 weeks apart, into the deep dermis above the buccal fat pad. Week 24 results have been published previously (Moyle et al, HIV Medicine 2004, Vol. 5, pp. 82-87). Long-term efficacy was assessed at a recall visit using visual analogue scales (VASs) to record patient satisfaction, and by the Hospital Anxiety and Depression Scale (HADS). Patients also reported any adverse events (AEs) during the treatment period and at the recall visit. RESULTS: Twenty-seven patients returned for the recall visit, a minimum of 18 months post final study treatment. Fourteen of these patients were excluded from the recall visit because of additional treatment with PLLA. Improvements in VAS scores for facial appearance were sustained from baseline to the recall visit in both randomization groups (P<0.05 and P<0.001). Trends in improvement in HADS scores were also noted, with patients in the delayed group experiencing significant improvements in depressive symptoms (P<0.05). One case of injection-site induration and nine cases of injection-site nodules were noted at the recall visit, none of which was described as serious or severe. CONCLUSIONS: Physical and psychological benefits of PLLA are sustained over at least 18 months. Delayed AEs include mild nodularity at the treatment site.

Adult↗
PubMed2005

Phase I trial of UCN-01 in combination with topotecan in patients with advanced solid cancers: a Princess Margaret Hospital Phase II Consortium study.

BACKGROUND: 7-Hydroxystaurosporine (UCN-01) inhibits serine-threonine kinases including the Ca2+ and phospholipid-dependent protein kinase C (PKC), CDKs 2, 4, 6, Chk-1 and PDK1. UCN-01 mediates distinct effects in vitro/in vivo: cell cycle arrest in G1, abrogation of G2 arrest by inhibiting chk1, induction of apoptosis and potentiation of cytotoxicity of S-phase-active chemotherapeutics including the topoisomerase 1 inhibitor topotecan (T). This phase I study was designed to determine the maximal tolerated dose (MTD), recommended phase 2 dose (RPTD), toxicity profile, pharmacokinetics and antitumor activity of T and UCN-01 in patients with refractory solid tumors. DESIGN: Both agents were administered every 21 days intravenously through central venous access in escalating doses to eligible patients. On day 1, following antiemetic prophylaxis with dexamethasone and a serotonin type 3(A) receptor (5HT3) inhibitor, UCN-01 was infused over 3 h, followed by T infused over 30 min. On days 2-5, patients received T only. UCN-01 doses were reduced by 50% in cycles 2 and beyond because of its prolonged half-life. RESULTS: Thirty-three patients were entered in three cohorts: Dose Level (DL) 1 (UCN-01 70 mg/m2, T 0.75 mg/m2), three patients; DL 2 (UCN-01 70 mg/m2, T 1.0 mg/m2), 24 patients; DL 3 (UCN-01 90 mg/m2, T 1.0 mg/m2), six patients. All but three patients were PS 0 or 1, median age was 54 years (range, 29-72), 91% were female. Primary tumor types: ovary/peritoneal (23 patients), colon (three patients), salivary gland (two patients), others (five patients). All patients were eligible for adverse event (AE) analysis and 22 patients were eligible for survival and tumor response analysis. Two of six patients had dose limiting toxicity (DLT) at DL 3 (grade 3 N/V; grade 4 neutropenia with infection). One DLT was seen in one patient at DL 2, consisting of grade 4 leukopenia. This cohort was expanded and no further DLTs were observed. Most common drug-related AEs were mild (grade 1-2). Non-hematological grade 3-4 AEs consisted of transient hyperglycemia (4), infection (3), coagulation, fatigue, hypotension, nausea (2), hypomagnesemia, vomiting, headache (1). Hematologic toxicities occurred in 100% of patients. Grade 3-4 hematologic abnormalities included neutropenia (16, including three with infection), leukopenia (11), lymphopenia (7), thrombocytopenia (5). Best response for 22 evaluable patients was PD (8), SD for at least six cycles (12), PR (1: carcinoma of ovary, dose level 2) and one not assessable. Pharmacokinetic analysis confirmed the prolonged half-life of UCN-01 of approximately 15 days. CONCLUSIONS: DLT was observed at DL 3 and RPTD was determined to be DL 2. To date, this combination has been relatively well tolerated with some preliminary evidence of efficacy. A phase II study of this combination in patients with ovarian cancer is underway.

Adult↗
PubMed2005

L3 and adult Ostertagia (Teladorsagia) circumcincta exhibit cyanide sensitive oxygen uptake.

Oxygen consumption by L3 and adult Ostertagia (Teladorsagia) circumcincta was examined in vitro to determine whether oxygen can be utilised in metabolism. The oxygen concentration in the abomasal fluid of sheep infected with O. circumcincta was also measured. Rates of consumption (in nmol O2/h/1000 worms) were 13+/-1 in sheathed L3, 34+/-6 in ex-sheathed L3, and 1944+/-495 in adult worms. Constant rates of consumption were maintained until media oxygen concentration dropped to between 10 and 20 microM. Consumption was inhibited 95% by cyanide in L3 and 74% in adults. Oxygen concentration in abomasal fluid varied between 10 and 30 microM in both infected and uninfected animals. During infection, oxygen concentration decreased slightly with increased abomasal pH, though the correlation between the two was poor (r=-0.30). In conclusion, O. circumcincta can consume oxygen and oxygen concentration at the infection site is sufficient to support at least some aerobic metabolism.

Abomasum↗
PubMed2005

Reduction of incarcerated inguinal hernia in infants using caudal epidural anaesthesia.

Incarcerated inguinal hernias in infants are commonly encountered. Reduction with intravenous sedation using morphine and related drugs carries risks of apnoea and/or respiratory arrest, especially in small, ex-premature babies who have an increased incidence of incarceration and thus opiate use is best avoided. Caudal epidural anaesthesia is widely used as pre- and post-operative analgesia in elective inguinal herniotomy in infants. In this study we sought to determine if caudal epidural anaesthesia would allow reduction of an incarcerated inguinal hernia in the acute setting, thereby obviating the need for intravenous sedation. A retrospective review of 12 male infants, with irreducible, incarcerated inguinal hernias was done. Each hernia was successfully reduced with the help of caudal epidural anaesthesia. This group of babies was treated at The Royal Belfast Hospital for Sick Children. Twelve male infants were identified with an incarcerated inguinal hernia in whom attempted reduction, without sedation had failed. Using Bupivacaine (1 ml/kg 0.25%), placed into the caudal space, these hernias were successfully reduced non-operatively. Ages at presentation ranged from 2 to 17 weeks with a median gestational age of 36 weeks (range 29-39 weeks). Caudal epidural anaesthesia is a safe, feasible and effective method of achieving reduction of irreducible, incarcerated inguinal hernias. It is especially useful in low-birth weight, premature infants where intravenous opiate sedation is best avoided.

Anesthesia, Caudal↗
PubMed2005

Tree allometry and improved estimation of carbon stocks and balance in tropical forests.

Tropical forests hold large stores of carbon, yet uncertainty remains regarding their quantitative contribution to the global carbon cycle. One approach to quantifying carbon biomass stores consists in inferring changes from long-term forest inventory plots. Regression models are used to convert inventory data into an estimate of aboveground biomass (AGB). We provide a critical reassessment of the quality and the robustness of these models across tropical forest types, using a large dataset of 2,410 trees >or= 5 cm diameter, directly harvested in 27 study sites across the tropics. Proportional relationships between aboveground biomass and the product of wood density, trunk cross-sectional area, and total height are constructed. We also develop a regression model involving wood density and stem diameter only. Our models were tested for secondary and old-growth forests, for dry, moist and wet forests, for lowland and montane forests, and for mangrove forests. The most important predictors of AGB of a tree were, in decreasing order of importance, its trunk diameter, wood specific gravity, total height, and forest type (dry, moist, or wet). Overestimates prevailed, giving a bias of 0.5-6.5% when errors were averaged across all stands. Our regression models can be used reliably to predict aboveground tree biomass across a broad range of tropical forests. Because they are based on an unprecedented dataset, these models should improve the quality of tropical biomass estimates, and bring consensus about the contribution of the tropical forest biome and tropical deforestation to the global carbon cycle.

Biomass↗
PubMed2005

High magnification chromoscopic colonoscopy or high frequency 20 MHz mini probe endoscopic ultrasound staging for early colorectal neoplasia: a comparative prospective analysis.

BACKGROUND: Successful endoscopic management of early colorectal cancer using endoscopic mucosal resection requires the mandatory prediction of invasive depth and lymph node metastasis. Previous data using the Nagata crypt types Vn(B)/(C) as clinical indicators of T2/N+ disease have shown low specificity (50%) with a tendency to over stage lesions. New mini probe ultrasound "through the scope" imaging permits staging of lesions proximal to the rectum using direct endoscopic visualisation. AIM: To compare the staging accuracy of the Nagata crypt type V with mini probe high frequency 20 MHz endoscopic ultrasound. METHODS: Sixty two patients with a Paris type II flat cancer were imaged using magnification colonoscopy followed by 20/12.5 MHz ultrasound in a "back to back" design. Crystal violet staining (0.05%) at 100x magnification permitted Nagata crypt criteria to be defined. Submucosal deep invasion (sm3+) was defined at ultrasound by the presence or absence of a disrupted third sonographic layer. Predicted T0/1:N0 lesions were resected using endoscopic mucosal resection with the remaining referred for surgery. Ultrasound and magnification staging were then compared with the resected histopathological specimens. RESULTS: One patient was excluded from the study due to poor bowel preparation. Fifty two lesions from 52 patients therefore met inclusion criteria (12 sm1/13 sm2/27 sm3+). Ultrasound (20 MHz) was significantly more accurate for invasive depth staging compared with Nagata stage (p<0.0001) (overall accuracy 93% and 59%, respectively). The sensitivity for lymph node metastasis detection using ultrasound and magnification was 80% and 31%, respectively (p<0.001). The negative predictive value of ultrasound for invasive depth was better than that observed using magnification (88%/47%, respectively). The prevalence of nodal disease overall was 19% (10/52), with 80% (8/10) node positive lesions occurring in the sm3+ lesion group. CONCLUSIONS: High frequency 20 MHz ultrasound is superior to magnification alone when differentiating T1/2 disease with a high positive predictive value for sm3 differentiation. Sm3+ invasion was associated with nodal metastasis.

Adult↗
PubMed2005

Determination of perchlorate in selected surface waters in the Great Lakes Basin by HPLC/MS/MS.

Surface water samples were collected from 55 sites in the Great Lakes Basin and analyzed for the presence of perchlorate using HPLC/MS/MS with an isotopically enriched internal standard. Sites included areas impacted by heavy industry, urbanization, agriculture and atmospheric deposition. Perchlorate was detected at several of the sites at concentrations close to the method detection limit (0.2 microg/l). Despite these low concentrations, its presence was confirmed by sample concentration and determination of the isotopic ratio of perchlorate. The presence of perchlorate at two of the sites was related to a fireworks display which had occurred prior to sampling. The other detections of perchlorate were in rivers/creeks draining watersheds which had high density livestock and crop farming activity. We suspect the two are related. To our knowledge, these are the first reported concentrations of perchlorate in Canadian surface waters.

Canada↗
PubMed2005

Pulmonary hypertension due to recurrent juvenile laryngeal papillomatosis.

Although pulmonary hypertension secondary to upper airway obstruction caused by adenotonsillar hyperplasia has been well described, the association between laryngeal papillomatosis and pulmonary hypertension has not previously been documented. We report three patients with pulmonary hypertension due to upper airway obstruction caused by laryngeal papillomatosis. Pulmonary hypertension can contribute to significant preoperative and postoperative morbidity and cause intraoperative complications. Preoperative diagnosis and treatment of pulmonary hypertension is therefore essential in these patients.

Airway Obstruction↗
PubMed2005

Traveling wave solutions of a reaction diffusion model for competing pioneer and climax species.

Presented is a reaction-diffusion model for the interaction of pioneer and climax species. For certain parameters the system exhibits bistability and traveling wave solutions. Specifically, we show that when the climax species diffuses at a slow rate there are traveling wave solutions which correspond to extinction waves of either the pioneer or climax species. A leading order analysis is used in the one-dimensional spatial case to estimate the wave speed sign that determines which species becomes extinct. Results of these analyses are then compared to numerical simulations of wave front propagation for the model on one and two-dimensional spatial domains. A simple mechanism for harvesting is also introduced.

Animals↗
PubMed2005

Endoscopic ultrasound miniprobe staging of colorectal cancer: can management be modified?

BACKGROUND AND STUDY AIMS: Miniprobe ultrasound technology allows in-vivo luminal staging of colorectal cancer with a probe that passes directly through the colonoscope's instrument port. Conventional rigid radial echoscopes are limited by the need for a second examination, an inability to image stenotic lesions, and the inaccessibility of proximal tumours. Since minimally invasive resection techniques are now possible, a sensitive preoperative staging tool is needed to optimize patient selection. The aim of this study was to examine the accuracy of miniprobe ultrasound imaging in the preoperative staging of colorectal cancer and to examine the value of the technique for management decisions. PATIENTS AND METHODS: In a prospective study, a total of 131 consecutive patients with adenocarcinoma or broad-based polyps of the colorectum underwent 12.5-MHz miniprobe ultrasonography examinations conducted by a single endoscopist. Staging criteria for depth of tumour infiltration and nodal status were determined. Nodal disease was defined as the presence of a hypoechoic, round, defined boundary lesion larger than 10 mm in diameter. T0-T1N0 lesions were resected using endoscopic mucosal resection, and patients with lesions staged as T2N1 were referred for surgical resection. Tumour staging using endoscopic ultrasonography was then compared with the histopathological specimens. RESULTS: The accuracy of T staging using endoscopic ultrasonography was 96 % in comparison with the histopathological specimen. Five lesions (4 %) were incorrectly overstaged as T3 - pathology stage T2. Understaging occurred in three lesions (endoscopic ultrasound stage T3 - pathology stage T4). The overall accuracy of nodal staging using endoscopic ultrasonography was 87 % (sensitivity 0.95, specificity 0.71, positive predictive value 0.87, negative predictive value 0.88). CONCLUSIONS: Miniprobe ultrasonography has a high overall accuracy for both T staging and N staging of colorectal cancer and may have an important role in selecting patients suitable for minimally invasive resection techniques.

Adult↗
PubMed2005

Assessment of the genetic causes of recessive childhood non-syndromic deafness in the UK - implications for genetic testing.

Approximately one in 2000 children is born with a genetic hearing impairment, mostly inherited as a non-syndromic, autosomal recessive trait, for which more than 30 different genes have been identified. Previous studies have shown that one of these genes, connexin 26 (GJB2), accounts for 30-60% of such deafness, but the relative contribution of the many other genes is not known, especially in the outbred UK population. This lack of knowledge hampers the development of diagnostic genetic services for deafness. In an effort to determine the molecular aetiology of deafness in the population, 142 sib pairs with early-onset, non-syndromic hearing impairment were recruited. Those in whom deafness could not be attributed to GJB2 mutations were investigated further for other mapped genes. The genetic basis of 55 cases (38.7%) was established, 33.1% being due to mutations in the GJB2 gene and 3.5% due to mutations in SLC26A4. None of the remaining 26 loci investigated made a significant contribution to deafness in a Caucasian population. We suggest that screening the GJB2 and SLC26A4 genes should form the basis of any genetic testing programme for childhood deafness and highlight a number of important issues for consideration and future work.

Cadherin Related Proteins↗