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Biomedical subjects

J J Brown

Publications and source records attributed to J J Brown.

At least 37 records · Page 2Linked to original sources
PubMed2000

Efficacy and safety of mangafodipir trisodium (MnDPDP) injection for hepatic MRI in adults: results of the U.S. Multicenter phase III clinical trials. Efficacy of early imaging.

The efficacy of contrast-enhanced magnetic resonance imaging (MRI) for detecting and characterizing, or excluding, hepatic masses was assessed in 404 patients, following the intravenous administration of mangafodipir trisodium (MnDPDP) injection, a hepatic MRI contrast agent. An initial contrast-enhanced computed tomography (CT) examination was followed by unenhanced MRI, injection of MnDPDP (5 micromol/kg IV), and enhanced MRI at 15 minutes post injection. Agreement of the radiologic diagnoses with the patients' final diagnoses was higher for enhanced MRI and for the combined unenhanced and enhanced MRI evaluations than for unenhanced MRI alone or enhanced CT using the clinical diagnosis as the gold standard. Mangafodipir-enhanced MRI uniquely provided additional diagnostic information in 48% of the patients, and patient management was consequently altered in 6% of the patients. MnDPDP-enhanced MRI was comparable or superior to unenhanced MRI and enhanced CT for the detection, classification, and diagnosis of focal liver lesions in patients with known or suspected focal liver disease.

Adult↗
PubMed2000

The clinical value of ferric ammonium citrate: a positive oral contrast agent for T1-weighted MR imaging of the upper abdomen.

This study was undertaken to determine whether ferric ammonium citrate (FAC), a positive magnetic resonance (MR) contrast agent, is of clinical value in demonstrating or excluding pathology of the upper gastrointestinal tract. A retrospective review was performed of pre- and post-FAC studies of MR examinations in 203 patients from phase II and III clinical trials in whom final diagnoses had been established based on the results of biopsy, surgery, or independent imaging procedures. Two independent reviewers made randomized and blinded assessments of the stomach, duodenum, and pancreas. FAC significantly increased the certainty of diagnosis for normal studies of the stomach and duodenum for both readers (P < 0.001) and for abnormal studies of the stomach for one reader (P = 0.004). FAC also significantly increased the certainty of diagnosis for normal pancreas for one reader (P < 0.001). FAC significantly (P < 0.001) increased accuracy and specificity for diagnoses involving the stomach and duodenum for both readers and for one reader for the pancreas. There was significant improvement in sensitivity for gastric diagnoses (P = 0.013) for one reader but not for the duodenum or pancreas. We conclude that FAC is helpful in demonstrating and excluding upper gastrointestinal pathology on MR.

Administration, Oral↗
PubMed2000

A long-term hepatitis B viremia model generated by transplanting nontumorigenic immortalized human hepatocytes in Rag-2-deficient mice.

Development of new therapies for human hepatitis B virus infection (HBV) would be greatly facilitated by the availability of a suitable small-animal model for HBV virus production in vivo. To develop a murine model for HBV production, we established an immortalized, cloned liver cell line by transferring the Simian Virus 40 Large T-Antigen into primary human hepatocytes. These cells were stably transfected with a full-length HBV genome to generate a clone that expresses HBV genes and replicates HBV. The HBV-producing cells were transplanted into the livers of mice with combined immunodeficiency (Rag-2 deficient) by intrasplenic injection. Survival of the engrafted human hepatocytes was shown in several ways: fluorescent in situ hybridization (FISH) with a human-chromosome-specific DNA probe (human alpha satellite), dot-blot hybridization of the genomic DNA extracted from liver biopsy specimens with a human-specific Alu repetitive DNA probe, Blur-8, as well as with an HBV DNA probe, and secretion of human proteins into plasma. Histological examination of mouse liver up to 8 months following human cell transplant shows completely normal architecture. Determination of plasma HBV DNA levels indicated that engrafted cells secreted 3x10(7) to 3x10(8) virions per mL into the blood, and HBsAg was detected in plasma. This new murine model of HBV viremia should be useful for in vivo HBV studies.

Animals↗
PubMed2000

A prospective assessment of breath-hold fast spin echo and inversion recovery fast spin echo techniques for detection and characterization of focal hepatic lesions.

The purpose of this study was to prospectively assess two breath-hold T(2)-weighted fast spin-echo sequences and two breath-hold inversion recovery fast spin-echo sequences to determine their relative ability to detect and characterize focal hepatic lesions. Fourteen patients with a total of nineteen proven focal hepatic lesions were imaged with two breath-hold T(2)-weighted (T2W) fast spin echo sequences (HASTE TE = 66 and HASTE TE = 120), two breath-hold inversion recovery fast spin echo sequences (IRFSE TE = 64 and IRFSE TE = 95), and a nonbreath-hold T(2)-weighted fast-spin echo sequence (FSE TE = 96-120). Contrast-to-noise ratios (CNRs) were measured for all proven lesions on all sequences. Both IRFSE sequences and the HASTE sequence with TE = 66 showed an improvement in lesion-liver and liver-spleen CNRs compared to the nonbreath-hold T2W sequence. The mean difference in CNR between benign and malignant lesions was largest for the HASTE TE = 120 sequence. These preliminary results suggest that a breath-hold IRFSE sequence (TE = 64 or 95) has an equal ability to detect focal hepatic lesions as a nonbreath-hold T2W FSE sequence (TE = 96-120). The HASTE TE = 120 showed the greatest ability to discriminate between benign and malignant lesions.

Adult↗
PubMed1999

A retrospective analysis of the accuracy of T2-weighted images and dynamic gadolinium-enhanced sequences in the detection and characterization of focal hepatic lesions.

The aim of this study was to determine the relative ability of T2-weighted and dynamic gadolinium-enhanced T1-weighted gradient-echo sequences to detect and characterize focal hepatic lesions. We retrospectively studied 37 patients with proven focal hepatic lesions using the following sequences: a T1-weighted spin-echo sequence (T1), a T2-weighted sequence (T2), and a series of breath-hold dynamic gadolinium-enhanced T1-weighted gradient-echo sequences (Gd). Two observers were asked to determine retrospectively the number and type of focal hepatic lesions present using images from three combinations of sequences (T1+T2, T1+Gd, T1+T2+Gd). Proof of the number and diagnosis of focal lesions in each patient was established using a consensus read. Both readers detected more focal lesions when both the T2-weighted sequences and the gadolinium-enhanced sequences were available than on either sequence alone, although this improvement reached statistical significance (P<0.05) only for one of the readers. There was no significant difference (P<0.05) in the ability to characterize lesions between any of the sets of sequences. The combination of dynamic gadolinium-enhanced images and T2-weighted images was shown to assess focal hepatic lesions better than either of these sequences alone.

Adolescent↗
PubMed1999

Pyogenic hepatic abscesses: MRI findings on T1- and T2-weighted and serial gadolinium-enhanced gradient-echo images.

The purpose of this study was to determine the magnetic resonance imaging (MRI) features of pyogenic hepatic abscesses on T1-weighted, T2-weighted, and serial gadolinium (Gd)-enhanced T1-weighted spoiled gradient-echo (SGE) images including images acquired in the immediate, intermediate, and late phases of enhancement. The MRI studies of 20 patients with pyogenic liver abscesses were retrospectively reviewed. All patients were examined on 1.5 (n = 19) and 1.0 (n = 1) T MR scanners. MR studies included T1-weighted, T2-weighted, and serial Gd-enhanced SGE images. The following determinations were made: signal intensity of the abscess cavity and perilesional liver tissue, and the presence of internal septations, layering material, or air in the abscess cavity. The pattern of enhancement of the abscess wall, internal septae and peri-abscess liver were evaluated on serial Gd-enhanced SGE images. A total of 53 abscesses were observed in the 20 patients. Fortyeight abscesses were hypointense on T1-weighted and hyperintense on T2-weighted images. Internal septations were present in four abscesses. Lower signal intensity material was observed in a dependent location on T2-weighted images in one abscess. Signal void foci of air located on the nondependent surface was observed in two abscesses. Two other abscesses contained signal void air that occupied the entire abscess cavity, observed on all imaging sequences. On serial gadolinium-enhanced images, all abscesses revealed early enhancement of the wall, which persisted with negligible change in degree of enhancement or thickness on delayed images. Abscess walls ranged in thickness from 2 to 5 mm. Internal septations ranged in thickness from 2 to 3 mm. Abscess walls and septations were relatively uniform in thickness with no evidence of focal nodularity. Periabscess liver tissue was mildly hypointense on T1-weighted and mildly hyperintense on T2-weighted images in 20 lesions, which were either circumferential (n = 12) or wedge-shaped (n = 8). All these regions enhanced more than the remainder of the liver on immediate post-gadolinium images and remained relatively hyperintense on late phase images. Periabscess liver parenchyma was isointense on both T1- and T2-weighted images in 18 lesions, and in these lesions wedge-shaped subsegmental (n = 6) or segmental (n = 12) enhancement was observed on immediate gadolinium-enhanced images, which faded to isointensity on intermediate phase images. No perilesional signal changes and enhancement difference was observed in 15 lesions. Characteristic features of abscesses include: intense mural enhancement on early gadolinium-enhanced images, which persists with negligible change in thickness and intensity on later post-gadolinium images, and the presence of periabscess increased enhancement on immediate post-gadolinium images. These MRI features may help to distinguish abscesses from other focal liver lesions during differential diagnosis.

Contrast Media↗
PubMed1999

A multisite phase III study of the safety and efficacy of a new manganese chloride-based gastrointestinal contrast agent for MRI of the abdomen and pelvis.

The purpose of this study was to evaluate the safety and efficacy of a manganese chloride-based oral magnetic resonance (MR) contrast agent during a Phase III multisite clinical trial. Two hundred seventeen patients were enrolled who were already scheduled for MRI of the abdomen and/or pelvis. In this group of patients, it was postulated that the use of an oral agent would better allow discrimination of pathology from bowel. Patients with known gastrointestinal pathology including peptic ulcer disease, inflammatory bowel disease, obstruction, or perforation were excluded to minimize confounding variables that could affect the safety assessment. Of these 217 patients, 18 received up to 900 mL of placebo, and 199 patients were given up to 900 mL of a manganese chloride-based oral contrast agent, LumenHance (Bracco Diagnostics, Inc.). Safety was determined by comparing pre- and post-dose physical examinations, vital signs, and laboratory examinations and by documenting adverse events. Efficacy was assessed by unblinded site investigators and two blinded reviewers who compared pre- and post-dose T1- and T2-weighted MRI scans of the abdomen and/or pelvis. In 111 (57%) of the 195 cases evaluated for efficacy by site investigators (unblinded readers), MRI after LumenHance provided additional diagnostic information. Increased information was found by two blinded readers in 52% and 51% of patients, respectively. In 44/195 cases (23%) unblinded readers felt the additional information would have changed patient diagnosis and in 50 patients (26%), it would have changed management and/or therapy. Potential changes in patient diagnosis or management/therapy were seen by the two blinded readers in 8-20% of patients. No clinically significant post-dose laboratory changes were seen. Forty-eight patients (24%) receiving LumenHance and four patients (22%) receiving placebo experienced one or more adverse events. Gastrointestinal tract side effects were most common, seen in 29 (15%) of LumenHance patients and in 3 (17%) of the placebo patients. LumenHance is a safe and efficacious oral gastrointestinal contrast agent for MRI of the abdomen and pelvis.

Abdomen↗
PubMed1999

A methodological strategy for a one-number census in the UK.

"As a result of lessons learnt from the 1991 [U.K.] census, a research programme was set up to seek improvements in census methodology. Underenumeration has been placed top of the agenda in this programme, and every effort is being made to achieve as high a coverage as possible in the 2001 census. In recognition, however, that 100% coverage will never be achieved, the one-number census (ONC) project was established to measure the degree of underenumeration in the 2001 census and, if possible, to adjust fully the outputs from the census for that undercount. A key component of this adjustment process is a census coverage survey (CCS). This paper presents an overview of the ONC project, focusing on the design and analysis methodology for the CCS. It also presents results that allow the reader to evaluate the robustness of this methodology."

Censuses↗
PubMed1998

Cyclic AMP-dependent protein kinase (PKA) gene expression is developmentally regulated in fetal lung.

We characterized the ontogeny of cAMP-dependent protein kinase (PKA) enzymatic activity and PKA subunit mRNA expression in developing lung. The lungs of fetal Sprague-Dawley rat pups were removed after 16, 18, or 20 days of gestation and at term. PKA activity was greatest in the 18- and 20-day gestation lungs. Tissue cAMP levels were lowest in the 16-day lungs and increased with lung maturity. We were able to detect only low levels of mRNA for the C beta subunit of PKA by northern blot analysis of total lung RNA and we were able to detect mRNA for the RI beta and RII beta subunits only by RT-PCR. Therefore, we limited our analysis of PKA subunit mRNA levels to those for C alpha, RI alpha and RII alpha. The mRNA levels for C alpha, were highest in the 16-day lung, decreased at 18 and 20 days, were lower in the newborn and lowest in the adult lung. RI alpha mRNA levels were also highest at 16 days and lowest in the adult lung. However, RII alpha mRNA levels were similar in the 18-day, 20-day and newborn lungs. Dexamethasone treatment of fetal lung explants resulted in a small decrease in RI alpha mRNA levels but was not associated with a change in PKA activity. We conclude that PKA activity and PKA subunit mRNA expression are developmentally regulated in fetal lung. Such regulation results in optimal PKA activity at the time of type II alveolar cell differentiation, presumably in preparation for air breathing. The absence of an effect of glucocorticoid on PKA activity suggests that glucocorticoids are not responsible for the increase in PKA activity which accompanies this critical time in lung maturation.

Animals↗
PubMed1998

Back pain in a large Canadian police force.

STUDY DESIGN: A survey of a random sample of 1002 members of the Royal Canadian Mounted Police to determine their experience with low back pain. OBJECTIVES: To determine the prevalence of low back pain among Royal Canadian Mounted Police members and to assess the validity of the perception that the patrol car seat and the duty belt are causing a higher rate of low back pain among members of the Royal Canadian Mounted Police than in the general population. SUMMARY OF BACKGROUND DATA: Low back pain is a common problem throughout the industrialized world, with reported 1-year prevalence rates between 25% and 62%. Prevalence of low back pain among people who drive motor vehicles for a significant part of the day appears higher than in the general population. Among police officers, 1-year prevalence rates of between 44% and 62% have been reported. METHODS: A computerized database of 14,897 serving regular members was used to identify a sample of officers on active duty. A low back pain questionnaire was mailed to each selected member, eliciting information regarding their experience with low back pain, their exposure to known and putative risk factors, and their opinions about the contribution of these potential risk factors. The respondents to the questionnaire remained anonymous. RESULTS: The response rate was 80%. The prevalence of "chronic or recurring low back pain since joining the force" was 54.9%, which is comparable with the lifetime prevalence reported for the general population. Of those who reported having back problems, only 8.5% had such problems before joining the force. Seventy-six percent who had low back pain reported having a problem within the last year, giving an overall 1-year prevalence of 41.8%, which is comparable with that for the general population. The a priori assumption that driving or wearing a duty belt contributed to the problem was shared by most police officers surveyed. However, only about half of the members who replied drove for more than half the working day or wore the duty belt. These members had the same prevalence of low back pain as those who did not drive or wear the duty belt. CONCLUSIONS: The prevalence of low back pain in this police force is comparable with that in the general population, and driving a patrol car or wearing the duty belt does not appear to influence the prevalence rate in this population.

Adult↗
PubMed1998

Osmotic effects as a factor modifying insecticide toxicity on Aedes and Artemia.

Euryhaline species are more tolerant of various insecticides under isosmotic conditions. Two euryhaline species, Aedes taeniorhynchus (Wiedemann) and Artemia sp., were exposed to four insecticides (aldicarb, dimethoate, imidacloprid, tebufenozide), under isosmotic and hyperosmotic conditions. Mortality under these two osmotic conditions was observed and compared to evaluate salinity as a contributing factor to insecticide toxicity. Artemia was more tolerant of all chemicals tested than A. taeniorhynchus under isosmotic conditions based on the percentage mortality observed. Mortality of Artemia under isosmotic conditions was dependent on the length of exposure; A. taeniorhynchus did not exhibit time dependence. Less mortality was observed in populations of both test species under isosmotic conditions compared with hyperosmotic conditions. However, the variation in mortality due to exposure to test chemicals was of greater magnitude in A. taeniorhynchus than Artemia. This result indicates that higher salinity is a greater stress on A. taeniorhynchus than Artemia when exposed to the test insecticides at the concentration ranges tested in this study.

Aedes↗
PubMed1998

Management of the neck in nasopharyngeal carcinoma (NPC).

Management of cervical nodal metastasis from nasopharyngeal carcinoma (NPC) begins with a thorough assessment of the patient to determine extent of the disease process at the primary site, regionally and systematically. Detailed knowledge of the anatomy of the head and neck will facilitate an accurate diagnosis and subsequent staging of each individual patient. The use of the appropriate diagnostic tools such as imaging, fine-needle aspiration studies, and serology direct the clinician to the appropriate management scheme. This article attempts to cull information from various clinicians who treat the majority of NPC patients, and to raise the issue of the need for more innovative approaches.

Biopsy, Needle↗
PubMed1998

Clobetasol propionate emollient 0.05% in the treatment of atopic dermatitis.

A 4-week, double-blind, randomized clinical trial, comparing the efficacy and safety of clobetasol propionate emollient cream 0.05% and its vehicle, was conducted at four private dermatology clinics in 81 non-hospitalized patients (> or = 12 years old) with moderate-to-severe atopic dermatitis covering 2% or more of their body surface. All patients had at least one lesion 2 cm or more in diameter. Three signs/symptoms of target lesions (erythema, pruritus, and induration/papulation) were scored by investigators on a scale of 0-3 (in 0.5-point increments; 0 = absent, 1 = mild, 2 = moderate, and 3 = severe); the total of the three scores had to be > or = 6 for patients to qualify for study entry. Patients were excluded if they were immunocompromised, pregnant, or nursing; had skin atrophy, telangiectasia or striae in skin areas to be treated; or had received topical treatments for atopic dermatitis within 1 week prestudy, intramuscular triamcinolone within 6 weeks prestudy, or long-term systemic corticosteroid usage within 6 months prestudy. Patients were randomized in a 1:1 ratio to receive either clobetasol propionate emollient 0.05% twice daily (n = 41), or the emollient vehicle twice daily (n = 40), for 4 weeks. A fingertip unit, equaling approximately 0.5 g in males and 0.43 g in females (enough to cover approximately 2% of the body), was used to measure and apply a thin film of study drug to the affected areas. The efficacy was evaluated by investigators and patients on days 4, 8, 15, and 29 after initiation of therapy, and 2 weeks after the end of treatment (day 43). Investigators performed a physician's gross assessment based on the percentage improvement of the target lesion. They also rated changes from baseline in mean severity scores for six individual signs/symptoms (erythema, pruritus, induration/papulation, lichenification, erosion/oozing/crusting, and scaling/dryness) and for total signs/symptoms according to the severity scoring system described above. Patients rated their response to treatment as excellent, good, fair, poor, or worse. Laboratory assessments were made on days 15, 29, and (if necessary) day 43.

Administration, Topical↗
PubMed1998

papG alleles of Escherichia coli strains causing first-episode or recurrent acute cystitis in adult women.

The distribution of the three alleles of the P adhesin gene papG (classes I-III) was assessed among 74 Escherichia coli urine isolates from women with first-episode or recurrent cystitis, and papG genotype was compared with clinical origin, O serogroup, agglutination of Gal(alpha1-4)Gal-coated latex beads and human or sheep erythrocytes, and hemolysin production. The class-III-only papG genotype (27% of strains) predominated over the I + III (3%) and II-only (7%) genotypes, irrespective of clinical category. In contrast to the class II papG allele, the class III allele was significantly concentrated in serogroups O6 and O18. Agglutination phenotypes corresponded significantly but incompletely with papG genotype, whereas hemolysin production and papG positivity were tightly correlated. These findings suggest that in acute cystitis in adult women, the class III papG allele predominates, confers distinctive agglutination phenotypes, and is restricted to specific E. coli lineages.

Adhesins, Escherichia coli↗
PubMed1998

Clonal distribution of the three alleles of the Gal(alpha1-4)Gal-specific adhesin gene papG among Escherichia coli strains from patients with bacteremia.

The three alleles of papG, the Gal(alpha1-4)Gal-specific adhesin gene of Escherichia coli P fimbriae, were detected in 101 (54%) of 187 E. coli bacteremia isolates from Boston, Long Beach, California, and Nairobi, Kenya, by a polymerase chain reaction-based assay, and their distribution was compared with clonal structure and other bacterial and host characteristics. Allele II predominated overall (57% of papG+ strains, vs. 32% for III and 2% for I). Allele distribution differed significantly between centers. Alleles segregated according to enzyme electrophoretic lineage and O serogroup in patterns suggesting both vertical and horizontal transmission and emergence within E. coli in the temporal sequence II-->III-->I. Strains containing allele III preferentially agglutinated sheep erythrocytes, whereas strains containing allele II preferentially agglutinated human erythrocytes. Allele III was associated with hly, sfa, multiple copies of the pap operon, and cluster III of the phylogenetic tree. These findings indicate that among bacteremia isolates of E. coli, the three papG alleles exhibit distinctive associations with evolutionary lineages, hemagglutination phenotypes, and non-pap virulence properties.

Adhesins, Escherichia coli↗