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K Brown

Publications and source records attributed to K Brown.

At least 19 recordsLinked to original sources
PubMed2006

Prospective, blinded comparison of helical CT and CT arterial portography in the assessment of hepatic metastasis from colorectal carcinoma.

OBJECTIVE: This prospective blinded comparison of helical CT and helical CT arterial portography aimed to detect liver metastasis from colorectal carcinoma. METHODS AND MATERIALS: 50 patients with colorectal carcinoma were evaluated comparing helical CT with helical CT arterial portography. Each imaging study was evaluated on a 5-point ROC scale by radiologists blinded to the other imaging findings, and the results were compared, with the surgical and pathologic findings as the gold standard. RESULTS: Of the 127 lesions found at pathology identified as metastatic colorectal cancer, helical CT correctly identified 85 (69%) and CT portography 96 (76%). When subgroups with lesions <3 cm (48 patients) and patients with maximum tumor size <3 cm (18 patients) were considered, CT portography was always better than helical CT in terms of sensitivity, specificity, positive predictive value, and negative predictive value. ROC analysis adjusting for multiple lesions per patient revealed significantly greater area under the curve (AUC) for the subgroup of lesions <3 cm (CT-AUC of 77% and CT portography AUC of 81%; P = 0.002). CONCLUSIONS: For identification of large metastases, helical CT and CT portography have similar yield. However, for detection of small liver metastases, CT portography remains superior for lesion detectability.

Colorectal Neoplasms↗
PubMed2006

Renal disease burden following liver transplantation.

UNLABELLED: Significant chronic kidney disease (CKD) occurs following orthotopic liver transplant (OLT). Since CKD is associated with increased cardiovascular events, mortality, and hepatic allograft dysfunction, early recognition of CKD and implementation of changes may improve the long-term outcome. The purpose of this study was to determine the burden of renal disease following OLT. PATIENTS AND METHODS: We retrospectively reviewed our OLT recipients from 1997 until 2004. We calculated glomerular filtration rates (GFR) using the Modification of Diet in Renal Disease study (MDRD) method. The GFRs were further subdivided into pre-MELD and post-MELD eras. RESULTS: During the study period, we performed 407 OLTs. We censored data from living donor liver transplants (n = 14), combined liver-kidney transplants (n = 12), and from patients whom we did not have complete data for 6 months after transplant (n = 40). Mean MELD score at the time of transplant was 18 +/- 7 (mean +/- standard deviation). The mean GFR at 6 months following OLT was 63.7 +/- 30.2 mL/min per 1.73 m(2). Only 14% (n = 47) of our patients had normal renal function at 6 months, while 78% (n = 266) of our patients had mild to moderate risk for renal failure. Eight percent (n = 28) had stage 4 or 5 CKD. There were no differences between the pre-MELD and post-MELD GFRs. CONCLUSIONS: The burden of renal disease is significant in our patient population at 6 months posttransplantation. It may be important to introduce CKD management as early as 6 months after transplant to impact the outcomes of OLT recipients.

Adult↗
PubMed2006

Influence of hepatitis C on renal function after liver transplantation.

Liver transplantation (OLT) is often complicated by renal failure. Hepatitis C (HCV) is said to be a risk factor for renal failure after OLT, but few studies have analyzed this directly. We evaluated all patients who received a liver transplant from 1995 through 2003. There were 147 patients infected with HCV and 202 not infected. Patients with HCV were further divided into 114 patients with benign HCV and 33 patients with severe HCV defined by bridging fibrosis or cirrhosis. The groups were evaluated for the development of renal insufficiency defined as a creatinine above 1.8 mg/dL on three consecutive occasions or renal failure as defined by the need for dialysis or renal transplant. The incidence of renal failure in patients with HCV was 10.2% and in patients without HCV was 3.5% (P = .004). Patients with severe HCV had an incidence of 12.1% vs 9.7% for patients with mild HCV. The linear trend in renal failure from non-HCV to mild HCV to severe HCV was significant (P = .012). The incidence of renal insufficiency was 23.4% in patients with HCV and 14.9% in patients without HCV (P = .080). The incidence was 32.3% in patients with severe HCV and 20.6% in patients with mild HCV. The trend in renal insufficiency across the three groups was mildly significant (P = .042). On multivariate analysis, HCV was a risk factor for renal failure with a relative risk of 2.58 (P = .045). The study suggests that HCV and the severity of recurrent HCV are risk factors for renal dysfunction after liver transplantation.

Creatinine↗
PubMed2006

Long-term stability of a patient-convenient 1 mg/ml suspension of tacrolimus for accurate maintenance of stable therapeutic levels.

Tacrolimus (Prograf, FK506, Fujisawa Healthcare) is a widely used immunosuppressive agent that is used both for the prevention and treatment of solid organ transplant rejection as well as for the prevention and treatment of graft-versus-host disease after allogeneic blood and marrow transplant. Oral preparations of tacrolimus are commercially available in 0.5, 1 and 5 mg gelatin capsules. Previously, only a 0.5 mg/ml oral suspension has been demonstrated to be stable for use in pediatric patients. On our bone marrow transplant service, we found that using this concentration of tacrolimus led to confusion, with patients and their caregivers confusing milligrams and milliliters, thus increasing errors with this formulation. We postulated that a 1 mg/ml oral formulation of tacrolimus would decrease the potential for medication errors. Our findings support new stability information of approximately 4 months for an extemporaneous oral suspension of tacrolimus at a concentration of 1 mg/ml.

Administration, Oral↗
PubMed2006

Short course continuous, hyperfractionated, accelerated radiation therapy (CHART) as preoperative treatment for rectal cancer.

Determine feasibility and toxicity of preoperative short course pelvic CHART (25 Gy in 15 fractions over 5 days) for treatment of clinically resectable primary rectal tumours. Between 1998 and 2004, 20 patients with clinically staged T3 resectable rectal carcinoma were treated in this prospective pilot study with preoperative short course CHART to their pelvis. The aim was for total mesorectal excision within 7 days. Radiation toxicity, surgical morbidity, locoregional control (LRC), overall (OS), cause specific (CSS) and disease free survival (DFS) outcomes were documented. Nineteen of the 20 patients completed planned radiotherapy. One discontinued radiotherapy due to toxicity. All patients underwent potentially curative radical surgery. One patient developed grade 3, and three patients grade 2 gastrointestinal toxicity. With a median follow-up of 31 months (range 0.9-88), there is no grade 3, 4 or 5 late toxicity. Two patients experienced grade 2, and three patients grade 1 late bowel toxicity. Two patients died from postoperative complications, and two developed grade 2 abdominal wound infections. At 3 years LRC is 95% (95% CI 83-100), OS 72% (95% CI 51-94), CSS 86% (95% CI 68-100) and DFS 80% (95% CI 60-100). Two patients died from metastatic disease, one patient from a second primary and one patient is alive after successful resection of hepatic metastases. This small study suggests preoperative short course CHART for clinically resectable rectal carcinoma is feasible with acceptable compliance and tolerable side effects.

Adenocarcinoma↗
PubMed2006

A single common urgent pathway for all colorectal referrals reduces time to diagnosis and treatment.

OBJECTIVE: Guidelines for the urgent referral of patients with suspected colorectal cancer were introduced in 2000. They aimed to facilitate the prompt diagnosis and treatment of patients with symptoms suggestive of malignant disease. Recent assessment of these guidelines has suggested that although they identify 9-14% of patients with colorectal cancer, they may be used inappropriately and may lead to delays in treatment for those patients with cancers whose symptoms do not fit the guidelines. We aimed to assess the effect of introducing a single pathway for all referrals irrespective of indicated urgency. METHOD: All referral letters to a single consultant colorectal surgeon over a 6-month period were coded 'urgent' irrespective of the indicated urgency on the original referral letter. Data was collected prospectively on 47 patients diagnosed with colorectal cancer identified over the trial period. Patient demographics, the mode of presentation, urgency of referral and waiting times were documented. RESULTS: Following the introduction of the common urgent referral pathway, no patient waited longer than 62 days from referral to treatment or 31 days from the decision to treat to first treatment, thus meeting government targets introduced in 2005. CONCLUSION: The introduction of the urgent referral guidelines has accelerated the referral pathway for patients with symptoms suggestive of colorectal cancer, although this is at the expense of the majority of patients who present via conventional pathways. The introduction of a common urgent pathway allows prompt diagnosis and treatment and is of particular benefit for the majority of patients not referred via the 2-week standard. Until a more accurate method of identifying the highest risk patients is implemented, we suggest that all patients are seen on an urgent basis.

Colorectal Neoplasms↗
PubMed2006

Community-onset methicillin-resistant Staphylococcus aureus in an urban HIV clinic.

OBJECTIVES: To determine the proportion of skin/soft tissue infections (SSTIs) and to determine risks for MRSA infection caused by methicillin-resistant Staphylococcus aureus (MRSA) in HIV-infected out-patients. METHODS: We conducted a prospective study of SSTIs in HIV-infected out-patients. A questionnaire was used to record MRSA risk factors and treatment. In vitro testing for antibiotic susceptibility, inducible clindamycin resistance, panton-valentine leucocidin (PVL) toxin, and the staphylococcal chromosomal cassette mec (SCCmec) type was performed using standardized methods. Treatment outcomes included resolution of primary site of infection, nonresolution of infection and reinfection and were confirmed at clinic visit and/or telephone follow-up. RESULTS: Forty-one of 44 patients had an SSTI caused by MRSA. African-Americans comprised 21 of 41 MRSA patients. The median CD4 count of MRSA patients was 411 cells/microL. Four patients required hospitalization and three patients had secondary bacteraemia. Twenty-one of 41 MRSA patients had healthcare-associated (HCA) MRSA risk factors including a history of prior MRSA infection (n=9) and hospitalization within 6 months (n=11). Other prevalent MRSA risk factors included receipt of systemic antibiotics within 6 months (n=21) and previous incarceration (n=19). Twenty-two patients had a significant non-HIV-related comorbid illness. The majority of isolates were susceptible to trimethoprim-sulfamethoxazole, tetracycline, and clindamycin. Inducible clindamycin resistance was detected in 0 of 16 erythromycin-resistant, clindamycin-susceptible MRSA isolates. Twenty-one of 24 isolates tested positive for SCCmec type IV. Twenty-four of 24 isolates tested positive for the PVL gene. Antibiotic treatment was discordant (bacteria nonsusceptible to antibiotic used) in eight MRSA patients. The primary SSTI resolved in 37 of 40 MRSA patients. Recurrence of infection at a site other than the primary site was relatively common (11 patients). CONCLUSIONS: We found a high rate of MRSA causing SSTI in community-dwelling patients. The majority of isolates were positive for PVL and SCCmec IV, which is typical of community-associated MRSA isolates causing SSTIs in the general population. Inducible clindamycin resistance was not detected. Most patients had MRSA risk factors. The initial site of infection resolved in most cases but subsequent MRSA infection was relatively common.

Ambulatory Care Facilities↗
PubMed2005

DNA adducts: mass spectrometry methods and future prospects.

Detection of DNA adducts is widely used for the monitoring of exposure to genotoxic carcinogens. Knowledge of the nature and amounts of DNA adducts formed in vivo also gives valuable information regarding the mutational effects that may result from particular exposures. The power of mass spectrometry (MS) to achieve qualitative and quantitative analyses of human DNA adducts has increased greatly in recent years with the development of improved chromatographic interfaces and ionisation sources. Adducts have been detected on nucleic acid bases, 2'-deoxynucleosides or 2'-deoxynucleotides, with LC-MS/MS being the favoured technique for many of these analyses. Our current applications of this technique include the determination of N7-(2-carbamoyl-2-hydroxyethyl)-guanine, which was postulated to be found as a DNA repair product in urine following exposure to acrylamide, and of 8-oxo-7,8-dihydro-2'-deoxyguanosine and 8-oxo-7,8-dihydro-2'-deoxyadenosine, as markers of oxidative damage in human lymphocyte DNA. Higher sensitivity (with a detection limit of 1-10 adducts/10(12) nucleotides) may be achieved by the use of accelerator mass spectrometry (AMS), although this requires the presence of certain isotopes, such as [(14)C], in the material being analysed. In order to make this technique more amenable for studies of human exposure to environmental carcinogens, new postlabelling techniques, incorporating [(14)C] into specific DNA adducts after formation, are being developed. It is expected that combining the use of advanced MS techniques with existing (32)P-postlabelling and immunochemical methodologies will contribute greatly to the understanding of the burden of human exposure to environmental carcinogens.

Animals↗
PubMed2005

Rituximab in combination with fludarabine chemotherapy in low-grade or follicular lymphoma.

PURPOSE: To evaluate the safety and efficacy of fludarabine plus rituximab in treatment-naive or relapsed patients with low-grade and/or follicular non-Hodgkin's lymphoma. PATIENTS AND METHODS: This was an open-label, single-arm, single-center phase II study enrolling 40 patients. During the first week of the study, patients received two infusions of rituximab 375 mg/m2 administered 4 days apart. Seventy-two hours after the second infusion of rituximab, patients received the first of six cycles of fludarabine chemotherapy (25 mg/m2/d for 5 days on a 28-day cycle). Single infusions of rituximab were administered 72 hours before the second, fourth, and sixth cycles of fludarabine, and two infusions of rituximab were given 4 weeks after the last cycle of fludarabine. Treatment duration was 26 weeks. RESULTS: An overall response rate of 90% (80% complete response rate) was achieved in the intent-to-treat population. Similar response rates were seen in treatment-naive and previously treated patients. The median duration of response has not been reached at 40+ months. The median follow-up time in this study is 44 months (range, 15 to 66 months). In patients positive for the 14;18 translocation in blood and/or marrow at enrollment, molecular remission was achieved in 88% of cases, with patients remaining negative for up to 4 years to date. Hematologic toxicity was manageable, and except for a 15% incidence of herpes simplex/zoster infections, infectious complications were rare. Nonhematologic toxicities were minimal. CONCLUSION: Rituximab plus fludarabine was well tolerated and associated with an excellent complete response rate, including molecular remissions, in patients with low-grade or follicular lymphoma.

Adult↗
PubMed2005

Assessment of potential atmospheric transport and deposition patterns due to Russian Pacific Fleet operations.

A probabilistic analysis of atmospheric transport and deposition patterns from two nuclear risk sites-Kamchatka and Vladivostok-situated in the Russian Far East to countries and geographical regions of interest (Japan, China, North and South Koreas, territories of the Russian Far East, State of Alaska, and Aleutian Chain Islands, US) was performed. The main questions addressed were the following: Which geographical territories are at the highest risk from hypothetical releases at these sites? What are the probabilities for radionuclide atmospheric transport and deposition on different neighboring countries in case of accidents at the sites? For analysis, several research tools developed within the Arctic Risk Project were applied: (1) isentropic trajectory model to calculate a multiyear dataset of 5-day forward trajectories that originated over the site locations at various altitudes; (2) DERMA long-range transport model to simulate 5-day atmospheric transport, dispersion, and deposition of 137Cs for 1-day release (at the rate of 10(10) Bq/s); and (3) a set of statistical methods (including exploratory, cluster, and probability fields analyses) for evaluation of trajectory and dispersion modeling results. The possible impact (on annual, seasonal, and monthly basis) of selected risk sites on neighboring geographical regions is evaluated using a set of various indicators. For trajectory modeling, the indicators examined are: (1) atmospheric transport pathways, (2) airflow probability fields, (3) fast transport probability fields, (4) maximum possible impact zone, (5) maximum reaching distance, and (6) typical transport time fields. For dispersion modeling, the indicators examined are: (1) time integrated air concentration, (2) dry deposition, and (3) wet deposition. It was found for both sites that within the boundary layer the westerly flows are dominant throughout the year (more than 60% of the time), increasing with altitude of free troposphere up to 85% of the time. For the Kamchatka site, the US regions are at the highest risk with the average times of atmospheric transport ranging from 3 to 5.1 days and depositions of 10(-1) Bq/m2 and lower. For the Vladivostok site, the northern China and Japan regions are at the highest risk with the average times of atmospheric transport of 0.5 and 1.6 days, respectively, and depositions ranging from 10(0) to 10(+2) Bq/m2. The areas of maximum potentially impacted zones are 30 x 10(4) km2 and 25 x 10(4) km2 for the Kamchatka and Vladivostok sites, respectively.

Air Movements↗
PubMed2005

Transjugular intrahepatic portosystemic shunts for refractory ascites after liver transplantation.

PURPOSE: To study the efficacy of transjugular intrahepatic portosystemic shunts (TIPS) in the management of refractory ascites after liver transplantation. PATIENTS AND METHODS: Between January 1995 and December 2003, 309 primary adult liver transplants were performed. Refractory ascites was defined as active interventions (salt restriction, diuretic use, repeated paracentesis) needed beyond 30 days after transplantation. These patients were managed with TIPS placement. RESULTS: Eight TIPS were placed in 8 patients at a mean of 11.5 months after transplantation (range, 2-36 months). There were 5 males and 3 females, age 54 +/- 8.2 years. Hepatitis C was the primary diagnosis in 7 patients and primary biliary cirrhosis in 1. Indications for TIPS included refractory ascites (8), associated variceal bleeding (2), and various degrees of hepatic vein outflow stenosis (3). Seven patients had resolution of ascites and associated findings of portal hypertension, and 1 patient with persistent ascites had severe hepatic vein outflow stenosis and associated hepatitis C in the allograft. Two patients required retransplantation for recurrent hepatitis C. There were 3 deaths: liver failure (1), organ failure after retransplantation (1), and lung cancer 5 months after TIPS (1). Currently, 5 patients are alive without clinical evidence of ascites 9, 13, 15, 24, and 70 months after TIPS. CONCLUSIONS: The TIPS device can be used safely and effectively to control refractory ascites after liver transplantation. In the setting of organ dysfunction, these patients should be considered sooner for retransplantation.

Adult↗
PubMed2005

Inequalities in glycaemic control in patients with Type 2 diabetes in primary care.

AIMS: To quantify relationships between patient and practice factors and glycaemic control in patients with Type 2 diabetes. METHODS: A cross-sectional study involving 1534 patients with Type 2 diabetes from 42 general practices in Nottingham, UK was undertaken. Patient characteristics were assessed by a clinical interview and case note review and practice characteristics by a questionnaire. The outcome measure was serum HbA(1c) concentration measured at entry to the study. Random effects linear regression was used to model patient and practice factors associated with glycaemic control. RESULTS: In multivariable regression analysis, HbA(1c) increased with increasing body mass index (BMI) [change in HbA(1c) for one unit increase in BMI: 0.03%, 95% confidence interval (CI) 0.01, 0.04], and was higher in those using oral medication (mean difference 0.75%, 95% CI 0.59, 0.92) or insulin compared with diet (mean difference 1.36%, 95% CI 1.10, 1.62). There was a dose-response relationship between HbA(1c) and increasing time since diagnosis. HbA(1c) was negatively associated with age (change per year -0.01%, 95% CI -0.02, -0.004). Patients registered at the most deprived practices had higher HbA(1c) values than those in the least deprived practices (mean difference 0.42%, 95% CI 0.14, 0.71), as did those in practices where annual reviews were carried out by the nurse alone (mean difference 0.24%, 95% CI 0.04, 0.44). CONCLUSIONS: Several patient and practice factors are related to glycaemic control. Poorer glycaemic control was associated with practice level deprivation and nurses undertaking annual reviews alone. Further research is required to explore outcomes of annual reviews undertaken by nurses alone. Greater resources may be needed by primary care teams working in deprived areas to address inequalities in diabetic control.

Administration, Oral↗
PubMed2004

1,3-Dihydro-2,1,3-benzothiadiazol-2,2-diones and 3,4-dihydro-1H-2,1,3-benzothidiazin-2,2-diones as ligands for the NOP receptor.

A series of 1,3-dihydro-2,1,3-benzothiadiazol-2,2-diones (I) and 3,4-dihydro-1H-2,1,3-benzothidiazin-2,2-diones (II) were prepared. While the five-member ring series (I) did not show good affinity for opioid receptors, the six-member ring series (II) exhibited extremely high affinity and selectivity for the NOP receptor and showed full agonist activity, as determined by stimulation of GTPgamma[35S] binding.

Animals↗
PubMed2004

Redundant data and exact helical cone-beam reconstruction.

This paper is about helical cone-beam reconstruction and the use of redundant data in the framework of two reconstruction methods. The first method is the approximate wedge reconstruction formula introduced by Tuy at the 3D meeting in 1999. The second method is a (exact) hybrid implementation of the exact filtered backprojection formula of Katsevich (2004 Adv. Appl. Math. at press) that combines filtering in the native cone-beam geometry with backprojection in the wedge geometry. The similarity of the two methods is explored and their image quality performance is compared for geometries with up to 112 detector rows. Furthermore, the concept of aperture weighting is introduced to allow the handling of variable amounts of redundant data. A reduction of motion artefacts using redundant data is demonstrated for geometries with 16, 32 and 112 detector rows using a pitch factor of 1.25. For scans with up to 100 rows, utilizing 50% of the redundant data provided excellent results without any introduction of cone-beam artefacts. For larger cone angles, an alternative approach that utilizes all available redundant data, even at reduced pitch factors, is suggested.

Algorithms↗
PubMed2004

Characterization of a peptide adduct formed by N-acetoxy-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a reactive intermediate of the food carcinogen PhIP.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a member of a class of compounds known as the heterocyclic amines (HCAs) that are formed in meat during cooking. It is a multi-organ carcinogen in rodents forms adducts and with DNA and protein. Although protein adducts are not thought to be involved in cancer development, they may be useful as internal dosimeters of PhIP exposure and bioactivation. Towards the goals of characterizing the adducts formed in humans and the development of an assay for quantitation of adduct levels, we have characterized a peptide adduct formed by the putative genotoxic metabolite, N-acetoxy-PhIP. A model peptide with the internal sequence Leu-Gln-Lys-Cys-Pro-Tyr, which is homologous to a potential target sequence for HCAs in human serum albumin, was reacted with N-acetoxy-PhIP and an adduct was identified and further characterized by LC-ESI-MS/MS. N-acetoxy-PhIP is covalently bound to the peptide via cysteine and the exocyclic amino group of PhIP. Future work is needed to establish if this adduct is formed and is stable in vivo in humans following exposure to PhIP.

Carcinogens↗
PubMed2004

Single nucleotide polymorphisms in the leptin receptor gene: studies in anorexia nervosa.

Anorexia nervosa is an eating disorder of unknown aetiology. There is significant evidence for a genetic component in the pathogenesis of this disorder. A region on chromosome 1 has been identified as a susceptibility locus. The leptin receptor has been mapped to a similar region, further upstream of this susceptibility locus. Leptin and its receptor are known to be important factors in the control and regulation of body weight. Single nucleotide polymorphisms (SNPs) in the leptin receptor are associated with measures of body weight. In the present study, SNPs in the coding region of the leptin receptor were analysed and their possible association with anorexia nervosa was investigated. Two cohorts of young women, 176 Caucasian anorexia nervosa patients and 152 normal Caucasian females, were genotyped for three SNPs in the leptin receptor. There was no significant difference in allele or genotype frequency, for any SNP, between the normal controls and the cohort of anorexia subjects. There were no significant associations with any genotype and body mass index in either the control or anorexic cohorts. When the anorexic cohort was subdivided into restricting and bingeing/purging behaviours, we found no significant association with any genotype. Analysis of haplotypes showed no significant evidence of association with anorexia. In summary, leptin receptor SNPs do not appear to be important factors in the regulation of body weight in young, pre-menopausal women or have any significant association with anorexia nervosa.

Adult↗
PubMed2004

High risk of recurrent venous thromboembolism in men.

BACKGROUND: We have analyzed the influence of gender on risk of recurrence after a first episode of venous thromboembolism (VTE). METHODS: The Cambridge Venous Thromboembolism Study (CVTE) is a single-center study of a cohort of unselected patients with a first episode of objectively proven VTE. RESULTS: Recurrence rates were significantly higher in men compared with women [log rank chi2=11.82; hazard ratio (HR) 2.66; 95% confidence interval (CI) 1.49, 4,77; P=0.0006]. The cumulative recurrence rate at 2 years was 19.2% in men and 7.7% in women. There was no evidence of a difference in recurrence between men with or without thrombophilia (log rank chi2=0.03; HR 1.08; 95% CI 0.49, 2.37; P=0.855). The high recurrence rate in men compared with women was still observed when only patients with idiopathic VTE were analyzed (log rank chi2=4.38; HR 2.31; 95% CI 1.027, 5.20; P=0.0363). The recurrence risk was highest in men with a first idiopathic event at 25.7% compared with 11.7% for women in the same category. CONCLUSION: The risk of recurrent VTE is higher in men than in women.

Adolescent↗