Biomedical subjects

Steve Brown

Publications and source records attributed to Steve Brown.

13 recordsLinked to original sources

PubMed2006

Does coeliac disease affect colorectal practice?

INTRODUCTION: Screening studies of healthy volunteers have determined that coeliac disease affects 1% of the adult European population. Despite this, the majority of cases are unrecognised. Coeliac disease often presents in adults with non-specific gastrointestinal symptoms. This may suggest that unrecognised cases are being seen in colorectal clinics with vague gastrointestinal symptoms, iron deficiency anaemia or irritable bowel syndrome. In addition, cases of coeliac disease may also be presenting as an emergency admission with non-specific abdominal pain. OBJECTIVE: This review provides an update of the published data on case finding for coeliac disease, with the aim of improving the recognition of this disease in clinical practice.

Abdominal Pain↗

PubMed2005

Undetectable cerebrospinal fluid HIV RNA and beta-2 microglobulin do not indicate inactive AIDS dementia complex in highly active antiretroviral therapy-treated patients.

OBJECTIVE: To assess whether nonelevated cerebrospinal fluid (CSF) markers could delineate inactive AIDS dementia complex (ADC) in patients receiving highly active antiretroviral therapy (HAART), using neuropsychologic performance change as an indicator of ADC stability. METHODS: We used data from the abacavir (ABC) ADC trial (n = 78) and examined the patients' neuropsychologic performance change with the Reliable Change Index according to 3 cutoff groups: (1) CSF viral load (VL) <100 copies/mL, (2) CSF beta-2 microglobulin (beta2m) <2.2 mg/L, and (3) CSF VL and CSF beta2m below cutoffs. RESULTS: CSF marker cutoff groups did not define neuropsychologic change. Linear regression showed that only CSF VL was a weak predictor of neuropsychologic performance change. CONCLUSION: HAART-treated ADC patients with baseline CSF markers of viral and immunologic inactivity did not necessarily have inactive ADC when followed over 12 weeks. More sensitive CSF markers to judge the activity of ADC are urgently needed, whereas the interpretation of these markers should be considered with caution in HAART-treated ADC patients.

AIDS Dementia Complex↗

PubMed2005

Nicorandil and idiopathic anal ulceration.

PURPOSE: Several reports have implicated nicorandil as a reversible cause of anal ulceration. We have recently commenced a specialist clinic for patients presenting with severe anal ulceration to assess treatment in this difficult group. Recognition of this association may avoid unnecessary surgery. METHODS: Twenty-six patients treated with nicorandil had severe painful anal ulceration. Examination under anesthesia was required to biopsy the lesions to exclude neoplasia or inflammatory bowel disease. In total, three patients had proximal diverting stomas without subsequent ulcer resolution, two had perineal debridement with one requiring subsequent skin grafting, and one had an abdominoperineal excision for unremitting pain. RESULTS: The association of perianal ulceration with nicorandil became apparent only in the latter part of this series. Ten ulcers successfully re-epithelialized when nicorandil was stopped. Nine patients reported anal pain relief and partial healing on clinical examination at two months but failed to show subsequent complete resolution. One patient agreed to nicorandil cessation and reported symptomatic anal pain relief at two weeks but subsequently developed unstable angina requiring hospital admission. Nicorandil was recommenced with anal pain relapse. CONCLUSIONS: Failure to recognize nicorandil as an etiologic factor in the development of anal ulceration, when other potential underlying well-recognized inflammatory or neoplastic processes have been excluded, may lead to unnecessary surgical intervention in a group of high-risk patients. One of our patients had a potentially avoidable abdominoperineal resection. Pharmaceutical manipulation with alternative antiangina medication may induce healing. Pharmacologic manipulation should be coordinated with a physician to minimize precipitation of unstable angina.

Aged↗

PubMed2005

The role of high-magnification-chromoscopic colonoscopy in hereditary nonpolyposis colorectal cancer screening: a prospective "back-to-back" endoscopic study.

BACKGROUND: In hereditary nonpolyposis colorectal cancer flat and diminutive adenomas occur, particularly in the right colon. Such lesions may assume a high risk of malignant transformation. Interval cancers are known to occur in this group. Chromoscopic colonoscopy enhances detection in patients assuming a moderate to high lifetime risk of colorectal cancer. AIM: To prospectively assess the efficacy of high-magnification-chromoscopic colonoscopy for the detection of neoplastic lesions in patients undergoing hereditary nonpolyposis colorectal cancer screening. METHODS: Twenty-five asymptomatic patients fulfilling modified Amsterdam criteria underwent "back-to-back" colonoscopy. Conventional colonoscopy with targeted chromoscopy was performed initially followed by pan-colonic chromoscopic colonoscopy. Diagnostic extubation times and volumes of normal saline and indigo carmine (IC) were controlled. RESULTS: Using conventional colonoscopy and targeted chromoscopy 24 lesions were detected in 13 patients (20 exophytic/4 flat). Pan-colonic chromoscopy identified a further 52 lesions in 16 patients (17 exophytic/35 flat). Pan-chromoscopy identified significantly more adenomas than conventional colonoscopy (p= 0.001) and a significantly high number of flat adenomas (p= 0.004). CONCLUSIONS: Pan-colonic chromoscopic colonoscopy improves detection of significant neoplastic lesions in hereditary nonpolyposis colorectal cancer screening. Pan-chromoscopy may help better stratify colorectal cancer "risk" in this cohort and aid planning of surveillance colonoscopic follow-up.

Adult↗

PubMed2005

Hyaluronic acid production in Bacillus subtilis.

The hasA gene from Streptococcus equisimilis, which encodes the enzyme hyaluronan synthase, has been expressed in Bacillus subtilis, resulting in the production of hyaluronic acid (HA) in the 1-MDa range. Artificial operons were assembled and tested, all of which contain the hasA gene along with one or more genes encoding enzymes involved in the synthesis of the UDP-precursor sugars that are required for HA synthesis. It was determined that the production of UDP-glucuronic acid is limiting in B. subtilis and that overexpressing the hasA gene along with the endogenous tuaD gene is sufficient for high-level production of HA. In addition, the B. subtilis-derived material was shown to be secreted and of high quality, comparable to commercially available sources of HA.

Bacillus subtilis↗

PubMed2005

A web-services architecture designed for intermittent connectivity to support medical response to disasters.

To support mobile computing systems for first responders at mass casualty sites, as part of the WIISARD (Wireless Internet Information System for Medical Response in Disasters) project, we have developed a data architecture to gracefully handle an environment with frequent network failure and, multiple writers that also supports rapid dissemination of updates that could be critical to the safety of responders. This is accomplished by allowing for a subset of the overall information available in a disaster scene to be cached locally on a responder's device and locally modified with or without network access. When the network is available, the local subset of the model is automatically synchronized with a server that contains the full model, and conflicts are resolved. When changes from a device are committed, the changes are instantly sent to any connected devices where the local subset would be modified by the changes.

Computer Systems↗

PubMed2005

Role-tailored software systems for medical response to disasters: enhancing the capabilities of "mid-tier" responders.

WIISARD (Wireless Internet Information System for Medical Response in Disasters) is developing wireless technology to coordinate and enhance the care of mass casualties at disaster sites. Mid-tier personnel (area supervisors) play a critical role in disaster response, supervising care processes in the triage, Treatment and Transport areas of the attack site. The design of a software tool to support mid-tier activities focuses on providing supervisors aggregate information on patient conditions and needs, real-time data on ambulance availability and location, and hospital status and on coordinating care delivery among triage, treatment and transport areas.

Computer Systems↗

PubMed2004

The European dimension for the mouse genome mutagenesis program.

The European Mouse Mutagenesis Consortium is the European initiative contributing to the international effort on functional annotation of the mouse genome. Its objectives are to establish and integrate mutagenesis platforms, gene expression resources, phenotyping units, storage and distribution centers and bioinformatics resources. The combined efforts will accelerate our understanding of gene function and of human health and disease.

Animals↗

PubMed2003

Phase I study of replication-competent adenovirus-mediated double-suicide gene therapy in combination with conventional-dose three-dimensional conformal radiation therapy for the treatment of newly diagnosed, intermediate- to high-risk prostate cancer.

The primary study objective was to determine the safety of intraprostatic administration of a replication-competent, oncolytic adenovirus containing a cytosine deaminase (CD)/herpes simplex virus thymidine kinase (HSV-1 TK) fusion gene concomitant with increasing durations of 5-fluorocytosine and valganciclovir prodrug therapy and conventional-dose three-dimensional conformal radiation therapy (3D-CRT) in patients with newly diagnosed, intermediate- to high-risk prostate cancer. Secondary objectives were to determine the persistence of therapeutic transgene expression in the prostate and to examine early posttreatment response. Fifteen patients in five cohorts received a single intraprostatic injection of 10(12) viral particles of the replication-competent Ad5-CD/TKrep adenovirus on day 1. Two days later, patients were administered 5-fluorocytosine and valganciclovir prodrug therapy for 1 (cohorts 1-3), 2 (cohort 4), or 3 (cohort 5) weeks along with 70-74 Gy 3D-CRT. Sextant needle biopsy of the prostate was obtained at 2 (cohort 1), 3 (cohort 2), and 4 (cohort 3) weeks for determination of the persistence of transgene expression. There were no dose-limiting toxicities and no significant treatment-related adverse events. Ninety-four percent of the adverse events observed were mild to moderate and self-limiting. Acute urinary and gastrointestinal toxicities were similar to those expected for conventional-dose 3D-CRT. Therapeutic transgene expression was found to persist in the prostate for up to 3 weeks after the adenovirus injection. As expected for patients receiving definitive radiation therapy, all patients experienced significant declines in prostate-specific antigen (PSA). The mean PSA half-life in patients administered more than 1 week of prodrug therapy was significantly shorter than that of patients receiving prodrugs for only 1 week (0.6 versus 2.0 months; P < 0.02) and markedly shorter than that reported previously for patients treated with conventional-dose 3D-CRT alone (2.4 months). With a median follow-up of only 9 months, 5 of 10 (50%) patients not treated with androgen-deprivation therapy achieved a serum PSA < or = 0.5 ng/ml. The results demonstrate that replication-competent adenovirus-mediated double-suicide gene therapy can be combined safely with conventional-dose 3D-CRT in patients with intermediate- to high-risk prostate cancer. The shorter than expected PSA half-life in patients receiving more than 1 week of prodrug therapy may suggest a possible interaction between the oncolytic adenovirus and/or double-suicide gene therapies and radiation therapy.

Adenoviruses, Human↗

PubMed2003

Autonomous detection of aerosolized Bacillus anthracis and Yersinia pestis.

We have developed and tested a fully autonomous pathogen detection system (APDS) capable of continuously monitoring the environment for airborne biological threat agents. The system is designed to provide early warning to civilians in the event of a terrorist attack. The final APDS will be completely automated, offering aerosol sampling, in-line sample preparation fluidics, multiplexed detection and identification immunoassays, and orthogonal, multiplexed PCR (nucleic acid) amplification and detection. The system performance (current capabilities include aerosol collection, multiplexed immunoassays, sample archiving, data reporting, and alarming) was evaluated in a field test conducted in a Biosafety Level 3 facility, where the system was challenged with, and detected, a series of aerosolized releases containing two live, virulent biological threat agents (Bacillus anthracis and Yersinia pestis). Results presented here represent the first autonomous, simultaneous measurement of these agents.

Aerosols↗

PubMed2003

Antimicrobial resistance among isolates of respiratory tract infection pathogens from the southern United States: data from the PROTEKT US surveillance program 2000/2001.

BACKGROUND: PROTEKT US (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin in the United States) was established in 2000 to monitor antimicrobial resistance among respiratory tract pathogens across the United States. METHODS: During 2000 to 2001, 75 southern US centers collected 3,867 Streptococcus pneumoniae, 1,455 Streptococccus pyogenes and 1,042 Haemophilus influenzae. RESULTS: Overall, 46.1% of S. pneumoniae isolates were nonsusceptible to penicillin, 35.8% were resistant to erythromycin, and 0.5% were resistant to fluoroquinolones. Against S. pneumoniae the most active agents were telithromycin (99.7% susceptible), linezolid (99.8%) and the fluoroquinolones (levofloxacin 99.4%, gatifloxacin 99.5%). The prevalence of erythromycin-resistant S. pyogenes isolates was 4.5%. Telithromycin, at concentration of < or = 1 mg/L, inhibited 99.9% of S. pyogenes. The prevalence of beta-lactamase positive H. influenzae was 26.2%. Telithromycin was active (MIC90 4 mg/L) against H. influenzae, irrespective of beta-lactamase production. CONCLUSION: The prevalence of penicillin and macrolide resistance among respiratory tract pathogens from the southern United States is high. Fluoroquinolone resistance is low. Telithromycin is highly active against respiratory tract pathogens with reduced susceptibility to beta-lactams, macrolides, and fluoroquinolones.

Anti-Bacterial Agents↗

PubMed2002

Efficacy and toxicity of replication-competent adenovirus-mediated double suicide gene therapy in combination with radiation therapy in an orthotopic mouse prostate cancer model.

PURPOSE: The purpose of this study was to evaluate the efficacy and toxicity of replication-competent adenovirus-mediated double suicide gene therapy in an adjuvant setting with external beam radiation therapy (EBRT) in an experimental prostate cancer model in preparation for a Phase I clinical study in humans. METHODS: For efficacy studies, i.m. DU145 and intraprostatic LNCaP C4-2 tumors were established in immune-deficient mice. Tumors were injected with the lytic, replication-competent Ad5-CD/TKrep adenovirus containing a cytosine deaminase (CD)/herpes simplex virus thymidine kinase (HSV-1 TK) fusion gene. Two days later, mice were administered 1 week of 5-fluorocytosine + ganciclovir (GCV) prodrug therapy and fractionated doses of EBRT (trimodal therapy). Tumor control rate of trimodal therapy was compared to that of EBRT alone. For toxicology studies, immune-competent male mice received a single intraprostatic injection (10(10) vp) of the replication-competent Ad5-CD/TKrep adenovirus. Two days later, mice were administered 4 weeks of 5-fluorocytosine + GCV prodrug therapy and 56 Gy EBRT to the pelvic region. The toxicity of trimodal therapy was assessed by histopathologic analysis of major organs and clinical chemistries. RESULTS: In both the i.m. DU145 and intraprostatic LNCaP C4-2 tumor models, trimodal therapy significantly improved primary tumor control beyond that of EBRT alone. In the DU145 model, trimodal therapy resulted in a tumor growth delay (70 days) that was more than twice that (32 days) of EBRT alone. Whereas EBRT failed to eradicate DU145 tumors, trimodal therapy resulted in 25% tumor cure. In the LNCaP C4-2 tumor model, EBRT slowed the growth of intraprostatic tumors, but resulted in no tumor cures, and 57% of the mice developed retroperitoneal lymph node metastases at 3 months. By contrast, trimodal therapy resulted in 44% tumor cure and reduced significantly the percentage (13%) of lymph node metastases relative to EBRT alone. Overall, trimodal therapy was associated with little toxicity. A comparison of the major histopathologic findings among the treatment groups indicated that most of the locoregional (prostate, seminal vesicles, urinary bladder) pathology was attributable to the combined effects of the Ad5-CD/TKrep vector and EBRT and that the prodrugs contributed little to this effect. Importantly, trimodal therapy did not exacerbate inflammation of the rectum and intestines beyond that of EBRT alone. CONCLUSION: Together, the results support the thesis that replication-competent adenovirus-mediated double suicide gene therapy may be a safe and effective adjuvant to EBRT and provide a sound scientific rationale for human trials.

Adenoviridae↗

PubMed2002

Phase I study of replication-competent adenovirus-mediated double suicide gene therapy for the treatment of locally recurrent prostate cancer.

Adenovirus-mediated suicide gene therapy may hold promise in the treatment of human cancer. We have developed a novel approach that utilizes a lytic, replication-competent adenovirus (Ad5-CD/TKrep) to deliver a cytosine deaminase/herpes simplex virus-1 thymidine kinase fusion gene to tumors. The cytosine deaminase and herpes simplex virus-1 thymidine kinase suicide genes render malignant cells sensitive to specific pharmacological agents and, importantly, sensitize them to radiation. The Phase I study described here represents the first gene therapy trial in which a replication-competent virus was used to deliver a therapeutic gene to humans. The indication is local recurrence of prostate cancer after definitive radiation therapy. An escalating dose (10(10), 10(11), and 10(12) viral particles) of the Ad5-CD/TKrep virus was injected intraprostatically under transrectal ultrasound guidance into 16 patients in four cohorts. Two days later, patients were given 5-fluorocytosine and ganciclovir prodrug therapy for 1 (cohorts 1-3) or 2 (cohort 4) weeks. There were no dose-limiting toxicities, and the maximum tolerated dose of the Ad5-CD/TKrep vector was not defined. Ninety-four percent of the adverse events observed were mild or moderate (grade 1/2) in nature. Seven of 16 (44%) patients demonstrated a >or=25% decrease in serum prostate-specific antigen, and 3 of 16 (19%) patients demonstrated a >or=50% decrease in serum prostate-specific antigen. Transgene expression and tumor destruction at the injection site were confirmed by sextant needle biopsy of the prostate at 2 weeks. Two patients were negative for adenocarcinoma at 1 year follow-up. Although Ad5-CD/TKrep viral DNA could be detected in blood as far out as day 76, no infectious adenovirus was detected in patient serum or urine. Together, the results demonstrate that intraprostatic administration of the replication-competent Ad5-CD/TKrep virus followed by 2 weeks of 5-fluorocytosine and ganciclovir prodrug therapy can be safely applied to humans and is showing signs of biological activity.

Adenoviruses, Human↗