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Biomedical subjects

Jeffrey Brown

Publications and source records attributed to Jeffrey Brown.

14 recordsLinked to original sources
PubMed2006

Multimodality imaging features in a case of bronchial carcinoid including FDG PET.

BACKGROUND: Pulmonary carcinoid tumors are rare, low-grade neuroendocrine malignancies which comprise 1-2% of all lung neoplasms. Approximately 80% of carcinoid tumors occur in the central airways and present clinically as obstructive pneumonia or hemoptysis. Experience with F18 FDG PET to image pulmonary carcinoid tumors is limited. CASE REPORT: A 67 year old woman presented with two episodes of hemoptysis within one month. A whole body FDG PET scan was performed in addition to a contrast enhanced chest CT, a whole body In111 octreotide scan, and quantitative lung perfusion scan during the diagnostic evaluation. An endobronchial lesion was discovered and the patient underwent a successful resection of the right middle and lower lobes. The histopathology of the lesion was consistent with a typical carcinoid tumor. CONCLUSIONS: We describe multimodality imaging findings along with the histopathology and a review of the literature, focusing on the role of FDG PET in the management of patients with bronchial carcinoid tumors.

Aged↗
PubMed2004

Genetic expression profiles during physiological and pathological cardiac hypertrophy and heart failure in rats.

Cardiac hypertrophy is a complex and nonhomogenous response to various stimuli. In this study, we used high-density oligonucleotide microarray to examine gene expression profiles during physiological hypertrophy, pathological hypertrophy, and heart failure in Dahl salt-sensitive rats. There were changes in 404/3,160 and 874/3,160 genes between physiological and pathological hypertrophy and the transition from hypertrophy to heart failure, respectively. There were increases in stress response genes (e.g., heat shock proteins) and inflammation-related genes (e.g., pancreatitis-associated protein and arachidonate 12-lipoxygenase) in pathological processes but not in physiological hypertrophy. Furthermore, atrial natriuretic factor and brain natriuretic protein showed distinctive changes that are very specific to different conditions. In addition, we used a resampling-based gene score-calculating method to define significantly altered gene clusters, based on Gene Ontology classification. It revealed significant alterations in genes involved in the apoptosis pathway during pathological hypertrophy, suggesting that the apoptosis pathway may play a role during the transition to heart failure. In addition, there were significant changes in glucose/insulin signaling, protein biosynthesis, and epidermal growth factor signaling during physiological hypertrophy but not during pathological hypertrophy.

Animals↗
PubMed2004

Wnt3a growth factor induces androgen receptor-mediated transcription and enhances cell growth in human prostate cancer cells.

The Wnt signaling pathway plays a critical role in embryogenesis and tumorigenesis. However, biological roles of Wnt growth factors have not been fully characterized in prostate development and the pathogenesis of prostate cancer. In this study, we used Wnt3a-conditioned medium (Wnt3a-CM) and purified Wnt3a proteins to investigate whether there is a direct effect of Wnt3a on androgen receptor (AR)-mediated transcription and to determine its role in the growth of prostate cancer cells. We demonstrated that Wnt3a-CM either induces AR activity in the absence of androgens or enhances AR activity in the presence of low concentrations of androgens, whereas purified Wnt3a showed a pronounced effect in the presence of low concentrations of ligands. We also showed that Wnt3a-CM and the purified Wnt3a enhance the level of cytosolic and nuclear beta-catenin, suggesting an involvement of beta-catenin in this regulation. Moreover, treatment of LNCaP cells with Wnt3a-CM and purified Wnt3a significantly enhances cell growth in the absence of androgens. Our findings demonstrate that Wnt3a plays an important role in androgen-mediated transcription and cell growth. These results suggest a novel mechanism for the progression of prostate cancer.

Androgens↗
PubMed2004

A retrospective data analysis of the impact of the New York triplicate prescription program on benzodiazepine use in medicaid patients with chronic psychiatric and neurologic disorders.

BACKGROUND: Benzodiazepines are treatment mainstays for several disorders, but there is often concern about dependency and addiction. In January 1989, New York implemented regulations requiring physicians to order benzodiazepines using state-monitored triplicate prescription forms. OBJECTIVE: The purpose of this study was to assess the effects of the triplicate prescription program (TPP) on changes in use of benzodiazepines and other psychoactive drugs in clinically vulnerable Medicaid populations. METHODS: Using an interrupted time series with comparison series design, psychoactive medication use was examined in the New York (intervention) and New Jersey (control) Medicaid programs before and after implementation of the New York benzodiazepine TPP among community-dwelling Medicaid beneficiaries aged >/=19 years continuously enrolled from January 1988 through December 1990 in New York or New Jersey with diagnoses of schizophrenia, schizophreniform disorder, schizoaffective disorder, schizoid personality disorder, or schizotypal personality disorder; bipolar disorder; epilepsy; and/or panic disorder, agoraphobia without history of panic disorder, social phobia, or specific phobia. RESULTS: A total of 125,837 New York and 139,405 New Jersey Medicaid beneficiaries were continuously enrolled and met the study inclusion criteria. Of these, there were 6054 Medicaid enrollees in New York and 6875 enrollees in New Jersey who were clinically vulnerable patients with >/=1 of the specified diagnoses. New York Medicaid patients with any of these diagnoses experienced a -48.1% relative change (95% CI, -50.0% to -46.2%) in benzodiazepine use at 6 months after TPP implementation, with no decline in use in New Jersey patients. The largest reduction in benzodiazepine use was seen among patients with seizure disorder (-59.9% at 6 months; 95% CI, -63.9% to -55.9%). Although use of substitute drugs increased slightly in New York after the TPP, it did not offset reductions in benzodiazepine use. The effects of TPP were sustained for 7 years of follow-up and had the greatest impact on nonproblematic benzodiazepine use. CONCLUSIONS: During the time period studied in this analysis, the New York TPP reduced benzodiazepine use among chronically ill patients for whom these agents represent effective treatment. Our findings suggest that many patients previously receiving benzodiazepines did not receive any pharmacologic intervention.

Adult↗
PubMed2004

Gadofosveset (EPIX/Schering).

EPIX Medical and Schering are developing gadofosveset, an albumin-binding gadolinium-based intravascular magnetic resonance imaging contrast agent, for the potential imaging of blood vessels and blood flow, particularly in patients with peripheral vascular disease (PVD). By February 2004, US approval of the agent was anticipated in October 2004, and in June 2004, Schering filed an MAA in the EU for PVD.

Animals↗
PubMed2003

The insulin-like growth factor 1 receptor induces physiological heart growth via the phosphoinositide 3-kinase(p110alpha) pathway.

Insulin-like growth factor 1 (IGF1) was considered a potential candidate for the treatment of heart failure. However, some animal studies and clinical trials have questioned whether elevating IGF1 chronically is beneficial. Secondary effects of increased serum IGF1 levels on other tissues may explain these unfavorable results. The aim of the current study was to examine the role of IGF1 in cardiac myocytes in the absence of secondary effects, and to elucidate downstream signaling pathways and transcriptional regulatory effects of the IGF1 receptor (IGF1R). Transgenic mice overexpressing IGF1R in the heart displayed cardiac hypertrophy, which was the result of an increase in myocyte size, and there was no evidence of histopathology. IGF1R transgenics also displayed enhanced systolic function at 3 months of age, and this was maintained at 12-16 months of age. The phosphoinositide 3-kinase (PI3K)-Akt-p70S6K1 pathway was significantly activated in hearts from IGF1R transgenics. Cardiac hypertrophy induced by overexpression of IGF1R was completely blocked by a dominant negative PI3K(p110alpha) mutant, suggesting IGF1R promotes compensated cardiac hypertrophy in a PI3K(p110alpha)-dependent manner. This study suggests that targeting the cardiac IGF1R-PI3K(p110alpha) pathway could be a potential therapeutic strategy for the treatment of heart failure.

Animals↗
PubMed2003

Cardiovascular effects of atomoxetine in children, adolescents, and adults.

BACKGROUND: Atomoxetine is a highly specific presynaptic inhibitor of the noradrenaline (norepinephrine) transporter that was recently approved in the US for the treatment of patients with attention-deficit/hyperactivity disorder (ADHD). Adverse effects on the cardiovascular system, including abnormalities in heart rate, blood pressure, or cardiac rhythm have been associated with several noradrenergic medications. OBJECTIVE: To further elucidate the magnitude and impact of blood pressure and pulse elevations in patients taking atomoxetine. STUDY DESIGN: Short-term cardiovascular safety in children, adolescents, and adults with ADHD was assessed in five randomised, double-blind trials (duration up to 10 weeks) with atomoxetine (n = 612) or placebo (n = 474). Long-term cardiovascular safety in children and adolescents (n = 169) was assessed in patients who entered an open-label extension or a blinded continuation following short-term treatment. METHODS: Adverse events, blood pressure, sitting pulse, and electrocardiograms (ECGs) were collected throughout the trials. QT intervals were corrected for heart rate by a data-specific correction factor (QTcD; derived from baseline ECGs) as well as standard methods. RESULTS: Atomoxetine treatment was associated with small but statistically significant increases in mean systolic blood pressure in adults and diastolic blood pressure in children and adolescents. Mean pulse rate increased for all atomoxetine treatment groups. The increases in blood pressure and pulse tended to occur early in therapy, stabilised, and returned toward baseline upon drug discontinuation. There was no significant difference between atomoxetine and placebo treatment groups in change in QTcD interval for all study populations. Palpitations in the adult patient population were the only significant cardiovascular adverse event (p = 0.037) occurring more frequently in the atomoxetine treatment group (3.7%) than in the placebo group (0.8%). Discontinuations due to cardiovascular-related events were very uncommon in the adult group, and did not occur in the child/adolescent group. CONCLUSION: While atomoxetine has noradrenergic activity, increases in pulse and blood pressure were small and of little, if any, clinical significance. Atomoxetine was not associated with QT interval prolongation. Cardiovascular effects of atomoxetine were minimal, and atomoxetine was well tolerated in short- and long-term studies.

Adolescent↗
PubMed2002

John M. Eisenberg Patient Safety Awards. System innovation: Concord Hospital.

BACKGROUND: The Cardiac Surgery Program at Concord Hospital (Concord, NH) restructured clinical teamwork for improved safety and effectiveness on the basis of theory and practice from human factors science, aviation safety, and high-reliability organization theory. A team-based, collaborative rounds process--the Concord Collaborative Care Model--that involved use of a structured communications protocol was conducted daily at each patient's bedside. METHODS: The entire care team agreed to meet at the same time each day (8:45 AM to 9:30 AM) to share information and develop a plan of care for each patient, with patient and family members as active participants. The cardiac surgery team developed a structured communications protocol adapted from human factors science. To provide a forum for discussion of team goals and progress and to address system-level concerns, a biweekly system rounds process was established. RESULTS: Following implementation of collaborative rounds, mortality of Concord Hospital's cardiac surgery patients declined significantly from expected rates. Satisfaction rates of open heart patients scores were consistently in the 97th-99th percentile nationally. A quality of work life survey indicated that in every category, providers expressed greater satisfaction with the collaborative care process than with the traditional rounds process. Practice patterns in the Cardiac Surgery Program at Concord Hospital have changed to a much more collaborative and participatory process, with improved outcomes, happier patients, and more satisfied practitioners. A culture of continuous program improvement has been implemented that continues to evolve and produce benefits.

Awards and Prizes↗
PubMed2002

Multimodality diagnosis of liver tumors: feature analysis with CT, liver-specific and contrast-enhanced MR, and a computer model.

RATIONALE AND OBJECTIVES: The purpose of this study was to measure and to clarify the diagnostic contributions of image-based features in differentiating benign from malignant and hepatocyte-containing from non-hepatocyte-containing liver lesions. MATERIALS AND METHODS: Six experienced abdominal radiologists each read images from 146 cases (including a contrast material-enhanced computed tomographic [CT] scan and contrast-enhanced and unenhanced magnetic resonance [MR] images) following a checklist-questionnaire requiring them to rate quantitatively each of as many as 131 image features and then reported on each of the two differentiations. The diagnostic value of each feature was assessed, and linear discriminant analysis was used to develop statistical prediction rules (SPRs) for merging feature data into computerized "second opinions." For the two differentiations, accuracy (area under the receiver operating characteristic curve [Az]) was then determined for the radiologists' readings by themselves and for each of three SPRs. RESULTS: Thirty-seven candidate features had diagnostic value for each of the two differentiations (a slightly different feature set for each). Radiologists' performance at both differentiations was excellent (Az = 0.929 [benign vs malignant] and 0.926 [hepatocyte-containing vs non-hepatocyte-containing]). Performance of the SPR that operated on the features from all modalities together was better than that of radiologists (Az = 0.936 [benign vs malignant] and 0.951 [hepatocyte-containing vs non-hepatocyte-containing]), but this difference was of marginal statistical significance (P = .11). Contrast-enhanced MR imaging and contrast-enhanced CT each made significant adjunctive contributions to accuracy compared with unenhanced MR imaging alone. CONCLUSION: Many CT- and MR imaging-based features have diagnostic value in differentiating benign from malignant and hepatocyte-containing from non-hepatocyte-containing liver lesions. Radiologists could also benefit from the fully informed SPR's "second opinions."

Adult↗
PubMedDate not supplied

Renal oncocytoma on 1-11C acetate positron emission tomography: Case report and literature review.

Renal oncocytomas are uncommon tumors of the renal collecting duct. Although generally benign, these tumors pose a diagnostic and therapeutic dilemma in that they can not be differentiated noninvasively from renal cell carcinomas. We report a 67-year-old man who underwent a clinical 1-11C acetate positron emission tomography (PET) scan for evaluation of possible metastatic prostate carcinoma. The study demonstrated a nodule at the inferior pole of the right kidney with more uptake than the remainder of the kidney. Correlation was made with MRI, which demonstrated that the nodule was solid, and enhanced after contrast agent administration. Upon resection, this nodule was determined to be an oncocytoma. To our knowledge, this marks the first report of the 1-11C acetate PET scan appearance of a renal oncocytoma Possible mechanisms for increased uptake include dysfunctional, but up-regulated oxidative phosphorylation or uptake through lipid biosynthesis pathways.

Adenoma, Oxyphilic↗
PubMedDate not supplied

Toxicity assessment of sediment cores from Santa Monica Bay, California.

During the summer of 1997, sediment core samples were taken at 25 stations in Santa Monica Bay. Toxicity testing was performed on 4-cm sections of the entire length of each core using purple sea urchin fertilization and amphipod survival tests. The sea urchin test identified sections as being toxic at six stations, all located near current or former Hyperion Treatment Plant (HTP) wastewater outfall locations. The amphipod test identified sections from 17 stations as having toxic sediments. The stations having toxic sediments were scattered throughout the bay and toxicity was identified at numerous core depths. Spatial and temporal patterns indicated that toxicity was most strongly associated with the historical disposal of municipal wastewater sludge. Many of the sections toxic to the amphipods did not have chemical levels expected to cause toxicity and were in locations where a source of toxicity was not apparent.

Amphipoda↗
PubMedDate not supplied

Forgotten fathers: an exploratory study of mothers' report of drug and alcohol problems among fathers of urban newborns.

OBJECTIVES: To investigate the relationship between fathers' substance use and maternal and paternal background characteristics, infant outcome measures, and fathers' frequency of caregiving at 6 months postpartum in a cohort of cocaine-exposed and unexposed infants. METHODS: Secondary analysis was completed on data collected through interviews and medical records obtained from 252 mothers participating in an ongoing longitudinal study of cocaine-exposed and unexposed mothers and infants. RESULTS: By maternal report, 22% of the mothers reported that the father of the baby had a history of a drug and/or alcohol problem. Mothers who were classified as heavier cocaine users were 1.6 times more likely than lighter cocaine users and 2.6 times more likely than nonusers to report that the father of the baby had a history of a drug and/or alcohol problem. There was a significant relationship between the father's reported history of a drug and/or alcohol problem and the mother's history of mental and physical abuse during pregnancy; P=.03, P=.001, respectively). Fathers with a history of a drug and/or alcohol problem were more likely to have been in jail (P=.001) and to be unemployed at the time of delivery (P=.04) than fathers without a history of a drug and/or alcohol problem. On bivariate analysis, newborns of fathers with a history by mother's report of a drug or alcohol problem had significantly lower mean birthweights (3003 vs. 3213 g, P=.005) and lengths (47.5 vs. 48.6 cm, P=.01) than newborns of fathers with no such history. However after control for mothers' prenatal use of cocaine, marijuana, cigarettes, and alcohol and for infant gender and gestational age, the differences were not statistically significant (P=.15 for both measurements). Head circumference did not differ significantly between groups in either bivariate or multivariate analyses. Fathers with a reported history of drug and/or alcohol problems were more likely to care for the baby at least once a week than fathers without such a history of a drug and/or alcohol problem at 6 months postpartum. CONCLUSIONS: Childhood cognitive and behavioral outcomes currently attributed to maternal substance abuse may also reflect the genetic, teratogenic, and social influence of fathers. Within an urban, at-risk population, it is important to inquire about the father's participation in the day-to-day life of the infant and to address the father's as well as the mother's possible need for substance abuse treatment and support in parenting.

Alcohol Drinking↗