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Biomedical subjects

James Jackson

Publications and source records attributed to James Jackson.

14 recordsLinked to original sources

An analog of thyrotropin-releasing hormone (TRH) is neuroprotective against glutamate-induced toxicity in fetal rat hippocampal neurons in vitro.

TRH has been found to be efficacious in treating certain neurodegenerative disorders such as epilepsy, Alzheimer's disease, neurotrauma and depression, however, its mechanism of action is poorly understood. Since glutamate (Glu) toxicity has been implicated in these disorders, we utilized primary enriched cultures of rat fetal (E 17) hippocampal neurons to test the hypothesis that an analog of TRH, 3-Methyl-Histidine TRH (3Me-H TRH), given concurrently with Glu would protect such neurons against cell damage and cell death. Cell viability was assessed via Trypan Blue exclusion cell counts, and neuronal damage was determined by assaying lactic acid dehydrogenase (LDH) released in the conditioned media. Fetal hippocampal neurons were cultured in neurobasal media for 7 days. On day 7, neurons (10(6)/well) were treated with: control media, 10 microM 3Me-H TRH, 500 microM Glu or 500 microM Glu with either 10, 1, 0.1, 0.01 or 0.001 microM 3Me-H TRH. Both media and neurons were harvested 16 h after treatment. Prolonged exposure to 10 microM 3Me-H TRH was not toxic to the cells, whereas neurons exposed to 500 microM Glu resulted in maximal cell death. Notably, 10, 1 and 0.1 microM 3Me-H TRH, when co-treated with 500 microM Glu, protected fetal neurons against cell death in a concentration-dependent manner. These results provide support for an important neuroprotective effect of TRH/analogs against glutamate toxicity in primary hippocampal neuronal culture and implicate a potentially beneficial role of TRH/analogs in neurodegenerative diseases.

Animals↗

Violet laser diodes in flow cytometry: an update.

INTRODUCTION: In previous studies we and others have demonstrated the usefulness of violet laser diodes (VLDs) as replacement laser sources for krypton-ion lasers on stream-in-air cytometers. Previously available VLDs had a maximum available power of less than 25 mW; this was sufficient for excitation of densely labeled cell surface antigens using fluorochromes such as Cascade Blue or Pacific Blue, but may have been insufficient for applications requiring higher levels of photon saturation, such as low-level expression of Cyan Fluorescent Protein (ECFP) in CFP-YFP FRET applications. In this follow-up study, we have tested more powerful VLDs emitting at 55 mW, and a beam-merged dual module VLD with 100 mW combined output, for their ability to excite a variety of violet-excited fluorochromes, including CFP. METHODS: A dual module VLD (two linear polarized VLDs with their beams merged by a polarized beam combiner) emitting at 404 nm was mounted on a BD FACSVantage DiVa stream-in-air cytometer. The individual polarized 55 mW beams or the 100 mW combined beams were used to analyze PBMCs labeled with the violet-excited probes Cascade Blue, Alexa Fluor 405, Cascade Yellow and Pacific Orange dyes. Violet-excited fluorescent microsphere mixtures with decreasing fluorescence levels were also used to detect the minimum sensitivity threshold and precision of these lasers. VLD excitation on a gel-coupled cuvette flow cytometer was used as a sensitivity baseline. RESULTS: The dual module 100 mW VLD gave both sensitivity and precision levels approaching that observed for lower-power sources on a cuvette cytometer. Single polarized VLD modules at 55 mW gave slightly decreased sensitivity for the microspheres standards and all the tested fluorochromes compared to the 100 mW source. CONCLUSIONS: While 55 mW laser sources performed adequately in the stream-in-air format, increasing the power to 100 mW did give a small but detectable increase in instrument sensitivity. This sensitivity level approached that of cuvette systems.

Animals↗

Fatal attraction: living with earthquakes, the growth of villages into megacities, and earthquake vulnerability in the modern world.

The great earthquake belt which stretches from the Mediterranean through the Middle East into Central Asia results from the ongoing collision between the Eurasian plate and the African, Arabian and Indian plates to the south. Through much of this belt, the topography is created and controlled by fault movement in earthquakes. Many habitations are located at the foot of the fault-controlled mountain range-fronts that bound inhospitable deserts or elevated plateaus, in positions that are favourable for trade-routes, strategic control of access or for water supply. As a result, they are vulnerable to earthquakes, which often seem to have targeted population centres precisely. For many centuries, an uneasy accommodation was reached between human needs and the earthquake-controlled landscape, sometimes brilliantly exploited by local hydrological engineering, as in Iran. Occasional earthquakes would occur, killing a shocking proportion of the population, but the populations of the settlements themselves would be relatively small. Many once-small rural communities have now grown into towns, cities or megacities, while retaining their vulnerability through poor building standards. Earthquakes that occur in these places today now kill many more than they did in the past, as we have witnessed in the last few years. Extreme catastrophes have been rare only because the exposure of modern megacities to earthquake hazards has been relatively short (approx. 50 years); an increase in the number of such catastrophes now seems to be inevitable.

Disaster Planning↗

Use of inferior epigastric artery embolization to arrest bleeding at operative laparoscopy.

OBJECTIVE: To describe an innovative approach of embolization of the inferior epigastric artery after vascular trauma due to lateral trocar insertion at operative laparoscopy. DESIGN: Case report. SETTING: Operating theater and interventional radiology suite of a university hospital. PATIENT(S): A 26-year-old woman with polycystic ovaries refractory to clomiphene citrate undergoing laparoscopic ovarian drilling. INTERVENTION(S): Percutaneous selective left external iliac and left inferior epigastric angiography followed by embolization with platinum microcoils and polyvinyl alcohol. MAIN OUTCOME MEASURE(S): Satisfactory hemostasis following traumatic injury to the inferior epigastric artery. RESULT(S): Hemostasis was achieved using a novel interventive radiologic approach of embolization of the inferior epigastric artery after conventional surgical techniques had failed. CONCLUSION(S): Arterial embolization is a novel additional measure in the armamentarium of the laparoscopic surgeon faced with intractable bleeding from the inferior epigastric vessels.

Adult↗

A naturalistic comparison of amoxicillin/clavulanate extended release versus immediate release in the treatment of acute bacterial sinusitis in adults: A retrospective data analysis.

BACKGROUND: Choosing the most effective treatment for acute bacterial sinusitis (ABS) is helpful to avoid treatment failure. To date, studies comparing antibiotic options for ABS have compared amoxicillin/clavulanate (AMX/CA) immediate release (IR) versus other antibiotics, but have not included AMX/CA extended release (XR). OBJECTIVE: The purpose of this study was to determine whether the clinical advantages of AMX/CA XR found in a clinical trial setting translate to a naturalistic setting, relative to AMX/CA IR. METHODS: Data for this retrospective analysis were obtained from a managed care benchmark database that included >25 million patients from >30 health plans covering 7 US census divisions. Data from all patients aged > or =18 years with an index diagnosis of ABS between July 1, 2001, and December 31, 2003, were included. Episodes of ABS were classified as treatment successes (no additional prescriptions for antibiotics, ABS-related emergency department [ED] visits, or ABS-related inpatient hospitalizations within 30 days after the index prescription) or failures (> or =1 subsequent antibiotic prescription, an ABS-related ED visit, or an ABS-related inpatient hospitalization within 30 days after the index prescription). Treatment failures were subclassified as early or late. Mean costs were assessed for medical claims linked with a primary diagnosis of ABS and antibiotic pharmacy claims within the follow-up time period (through February 28, 2004). Descriptive statistics for demographic characteristics, utilization patterns, and success rates were calculated for each cohort. A multivariate general linear regression model was developed to assess differences in costs between the 2 cohorts. RESULTS: : Of the patients with an index antibiotic prescription filled within 3 days of ABS diagnosis (n = 241,511), a total of 3224 in the AMX/CA XR cohort (mean [SD] age, 41.8 [11.6] years; women, 57.7%) and 23,638 in the AMX/CA IR cohort (mean [SD] age, 41.9 [11.6] years; women, 62.7%) were included in the analysis. The rate of treatment success in patients treated with AMX/CA XR was 82.8% versus 81.0% in patients treated with AMX/CA IR (P < 0.015). Treatment success costs were significantly lower than treatment failure costs regardless of an early or late designation and ranged from 98 dollars to 110 dollars per episode (P < 0.001). After adjustment for background covariates, the mean cost of treating an episode of ABS was significantly lower for patients receiving AMX/CA XR versus those receiving AMX/CA IR (166.32 dollars vs 177.34 dollars [US 2004 dollars]; P < 0.001), representing a mean cost savings of 11.02 dollars per patient treated with AMX/CA XR over AMX/CA IR for ABS, regardless of treatment outcome. CONCLUSIONS: The results from this data analysis suggest that AMX/CA XR had significantly higher treatment success in ABS relative to AMX/CA IR in this naturalistic setting. AMX/CA XR was associated with significantly decreased total ABS-related costs in these adults.

Acute Disease↗

Diabetes disease management in Medicaid managed care: a program evaluation.

The objective of this study was to evaluate the outcomes of a diabetes disease management initiative among TennCare's Medicaid Population. A quasi-experimental group design was conducted using a control group and a diabetes disease management intervention group. Primary outcomes measures were rates for three key recommended tests (ie, microalbuminuria, lipids, and hemoglobin A1c). Secondary performance measures --patient satisfaction and program evaluation issues -- also were assessed. The study was performed among TennCare beneficiaries with diabetes mellitus. It utilized a quasi-experimental nonequivalent control group design, with 993 intervention participants in Knoxville and 1167 control group members in Chattanooga. Variables analyzed included testing rates for hemoglobin A1c, lipids, microalbuminuria, and demographics. A logistic regression model using baseline covariates was constructed to analyze the differences between the intervention and the control groups. Intracluster correlations were accounted for by generalized estimating equations. Statistical process control detected process changes in testing rates over time. There were meaningful changes in the rate of ordering recommended tests. The odds of an individual in the intervention group having at least one microalbuminuria test were 196% more (confidence interval [CI] = 1.50, 5.82; p = 0.002); the odds of having at least one lipid profile were 43% more (CI = 1.01, 2.02; p = 0.042); and the odds of having two or more hemoglobin A1c tests were 39% more (CI = 0.87, 2.23; p = 0.165) than the odds of an individual in the control group. The analysis also showed a high rate of satisfaction among patients in the intervention group. The program was successful in meeting its stated goals of providing effective disease management for TennCare patients with diabetes.

Adult↗

Impact of brachytherapy on regional, racial, marital status, and age-related patterns of definitive treatment for clinically localized prostate carcinoma.

BACKGROUND: The impact of the increased use of permanent prostate brachytherapy compared with other treatment modalities (such as radical prostatectomy and external-beam radiation therapy [EBRT]) for the treatment of clinically localized prostate carcinoma, and the previously reported regional, racial, and age-related variations in prostate carcinoma treatment, have not been well characterized to date. Therefore, the authors evaluated the impact of permanent prostate brachytherapy on the relative rates of the use of specific prostate carcinoma treatment modalities over time. METHODS: Surveillance, Epidemiology, and End Results (SEER) cancer registry data from 1995 to 2000 were analyzed in a longitudinal, observational study utilizing bivariate and multivariate techniques. RESULTS: Differential changes in the use of specific definitive treatment modalities were noted by region, age group, racial/ethnic group, and marital status. Increasing use of permanent prostate brachytherapy, with and without concomitant EBRT, was proportional to the decreasing use of radical prostatectomy alone and EBRT alone over time. CONCLUSIONS: The current study revealed that permanent prostate brachytherapy appears to be replacing other treatment modalities in increasing numbers of clinically localized prostate carcinoma cases. Persistent regional, racial/ethnic, marital status, and age-related differences in the use of permanent prostate brachytherapy merit further investigation.

Adult↗

Racial treatment trends in localized/regional prostate carcinoma: 1992-1999.

BACKGROUND: African-American men have a greater incidence of and mortality from prostate carcinoma compared with white men, and they are less likely to receive definitive therapy (radical prostatectomy or external beam radiation therapy). During the 1990s, the use of brachytherapy increased; however, its influence on racial and ethnic prostate carcinoma treatment trends remains unclear. The objective of this study was to describe treatment trends over the period 1992-1999 for localized/regional prostate carcinoma among white, Hispanic, and African-American men. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) registry data from 1992 through 1999, logistic regression models were used to determine whether the odds of receiving a specific treatment modality differed by racial and ethnic group and whether the differences changed over time when the models were adjusted for age, marital status, tumor grade, and SEER site (geography). RESULTS: The authors identified 142,340 men, including white men (81.6%), Hispanic men (6.4%), and African-American men (12.0%). Racial and ethnic differences in the rates of use of androgen-deprivation therapy/expectant management were noted; however, these differences appeared to lessen over time (P < 0.001). The rate of utilization of radical prostatectomy increased for Hispanic men, remained flat for African-American men, and decreased for white men. The utilization of brachytherapy and combination therapy increased for all three groups; however, the greatest increase in utilization was among white men. CONCLUSIONS: Further research will be required to determine the patient-level and provider-level variables that influence racial and ethnic treatment differences in localized/regional prostate cancer.

Black or African American↗

Delirium: acute cognitive dysfunction in the critically ill.

PURPOSE OF REVIEW: The management of sepsis and the multiple organ dysfunction syndrome has traditionally been centered on dysfunction of organs other than the brain (e.g., heart, lungs, or kidneys), although the brain is one of the most prevalent organs involved. Recent studies indicate that nonpulmonary acute organ dysfunction may contribute significantly to mortality and other important clinical outcomes. Acute confusional states (delirium) occur in 10 to 60% of the older hospitalized population and in 60 to 80% of patients in the intensive care unit, yet go unrecognized by the managing physicians and nurses in 32 to 66% of cases. Delirium is an important independent prognostic determinant of hospital outcomes, including duration of mechanical ventilation, nursing home placement, functional decline, and death. Recently, new monitoring instruments have been validated for monitoring of delirium in noncommunicative patients receiving mechanical ventilation. Hence, critical care physicians and nurses should routinely assess their patients for delirium and develop strategies for its prevention and treatment. RECENT FINDINGS: This state-of-the-art review discusses in depth the delirium monitoring instruments, the pathophysiology and risk factors of delirium, its prognostic implications, and strategies (including ongoing clinical trials) to prevent and treat delirium. SUMMARY: Delirium is extremely common and has significant prognostic implications in critically ill patients. Routine monitoring and a multimodal approach to prevent or reduce the prevalence of delirium are of paramount importance.

Aged↗

Psychosocial factors in medical and psychological treatment avoidance: the role of the doctor-patient relationship.

A community sample of 1106 adults was examined to assess the impact of the doctor-patient relationship on participants' avoidance of treatment for a recognized medical or psychological problem. Of five aspects of participants' previous experience with their physicians, all but waiting time predicted participants' self-reported treatment avoidance. In two logistic regression models participants who felt their physicians listened more to their concerns were less likely to avoid treatment for both medical and psychological problems during the previous 12 months. These findings suggest that patients' perceptions of how they are treated by physicians may help explain why many people delay or avoid healthcare treatment, even when faced with a significant health problem.

Adolescent↗

Cell membrane fatty acid composition differs between normal and malignant cell lines.

Twenty-eight fatty acids (C8:0 to C24:l n-9) were measured by gas chromatography in four normal cell lines (C3H / 10T1 / 2, CCD-18Co, CCD-25SK and CCD-37Lu) and seven cancer cell lines (C-41, Caov-3, LS-180, PC-3, SK-MEL-28, SK-MES-1 and U-87 MG). Results show differences in the content and proportions of fatty acids when comparing cancer cell lines with their normal counterparts. Cancer cell lines showed lower C20: 4 n-6, C24:1 n-9, polyunsaturated fatty acids (PUFA's) and ratios of C20:4 n-6 to C20:5 n-3 and C16:0 to C18:1 n-9 and stearic to oleic (SA/OA) than their normal counterparts. All cancer cell lines had SA/OA ratios lower than 7.0 while normal cell lines had ratios greater than 0.7 (p<0.05). In addition, the ratios of total saturated fatty acids (SFA) to PUFA'S and the concentration of C18:1 n-9, C18:2 n-6, C20:5 n-3 were higher in cancer cell lines as compared to normal cell lines. A positive correlation was detected between C16:0 and longer SFA'S (r = +0.511, p<0.05) in normal cell lines whereas a negative correlation (r=0.608, p<0.05) was obtained for malignant cell lines. Moreover, cancerous cell lines exhibited a particular desaturation defect and an abnormal incorporation of C18:2 n-6 and C20-4 n-6 fatty acids.

Animals↗

Pharmacological analysis of calcium responses mediated by the human A3 adenosine receptor in monocyte-derived dendritic cells and recombinant cells.

Extensive characterization of adenosine receptors expressed by human monocyte-derived dendritic cells (MDDCs) was performed with quantitative polymerase chain reaction, radioligand binding, and calcium signaling. Transcript for the A3 adenosine receptor was elevated more than 100-fold in immature MDDCs compared with monocyte precursors. A3 receptor transcript was substantially diminished, and A2A receptor transcript increased, by lipopolysaccharide maturation of MDDCs. Saturation binding of N(6)-(3-[(125)I]iodo-4-aminobenzyl)-adenosine-5'-N-methyluronamide ([(125)I]AB-MECA) to membranes from immature MDDCs yielded B(max) of 298 fmol/mg of protein and K(D) of 0.7 nM. Competition against [(125)I]AB-MECA binding confirmed the site to be the A3 receptor. Adenosine elicited pertussis toxin-sensitive calcium responses with EC(50) values ranging as low as 2 nM. The order of potency for related agonists was N(6)-(3-iodobenzyl)-adenosine-5'-N-methylcarboxamide (IB-MECA) >/= I-AB-MECA > 2Cl-IB-MECA >/= adenosine > 2-[p-(2-carboxyethyl)phenylethylamino]-5'-N-ethylcarboxyamidoadenosine (CGS21680). The order of efficacy was adenosine >/= CGS21680 > IB-MECA >/= I-AB-MECA > 2Cl-IB-MECA. Calcium responses to 2Cl-IB-MECA and CGS21680, and the lower range of adenosine concentrations, were completely blocked by 10 nM N-(2-methoxyphenyl)-N-[2-(3-pyridyl)quinazolin-4-yl]urea (VUF5574) but not by 7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (SCH58261) or 8-cyclopentyl-1,3-dipropylxanthine. Pretreatment with 100 nM 2Cl-IB-MECA eliminated responses to CGS21680 but not to monocyte inhibitory protein-1alpha. For comparison, dose-response functions were obtained from double-recombinant human embryonic kidney 293 cells expressing the human A3 receptor and a chimeric Galphaq-i3 protein, which was required to establish A3-mediated calcium signaling. The pharmacological profile of calcium signaling elicited by adenosine-related agonists in the double-recombinant cells was essentially identical to that obtained from immature MDDCs. Our results provide an extensive analysis of A3-mediated calcium signaling and unequivocally identify immature MDDCs as native expressers of the human A3 receptor.

Adenosine↗