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Biomedical subjects

J Palmer

Publications and source records attributed to J Palmer.

At least 91 records · Page 5Linked to original sources

Acute and chronic effects of ginseng total saponin and amphetamine on fixed-interval performance in rats.

The effect of ginseng total saponin (GTS) on amphetamine (AMPH)-induced disruption of fixed-interval (FI) responding in rats was examined. GTS (50 mg/kg) significantly improved the temporal responding impaired by 2 mg/kg of AMPH. A higher dose of 100 mg/kg GTS disrupted performance when given alone; this disruption was reversed by a low dose of AMPH (0.5 mg/kg) and tolerance developed to the effects of GTS with its repeated administration. Neurochemical analysis revealed that GTS (50 mg/kg) attenuated the increase in striatal dopamine caused by AMPH leading to the conclusion that brain dopamine may partially mediate the behavioral effects of GTS.

Amphetamines↗

Improved classifications of myocardial bull's-eye scintigrams with computer-based decision support system.

UNLABELLED: In a recent study, artificial neural networks were trained to detect coronary artery disease using scintigraphic data as input. The performance of the networks was better than that of human experts using coronary angiography as a gold standard. In clinical practice, this type of neural networks will not take over the decision-making process from the physician but will assist by proposing an interpretation of the scintigram. The purpose of this study was to assess the influence of such decision support on the interpretations of the physicians. METHODS: A population of 135 patients who had undergone both myocardial 99mTc-sestamibi rest/stress scintigraphy and coronary angiography within a 3-mo period was studied. An image set consisting of the bull's-eye rest, stress, difference and quote images was constructed for each patient. Three experienced physicians independently classified all image sets regarding the presence and/or absence of coronary artery disease in two vascular territories using a four-grade scale. The physicians classified the image sets twice with and twice without the advice of artificial neural networks. RESULTS: The joint evaluation of the three physicians showed significantly improved performance with decision support, measured as increases in the areas under the receiver operating characteristic curves from 0.65 to 0.70 (P = 0.018) and from 0.79 to 0.82 (P = 0.006) for two vascular territories. Furthermore, the joint evaluation showed significantly less intraobserver and interobserver variability with decision support. CONCLUSION: Physicians classifying myocardial bull's-eye images benefit from the advice of artificial neural networks. These results show the high potential for neural networks as clinical decision support systems.

Adult↗

Cisplatin, ifosfamide, and prolonged oral etoposide in the treatment of patients with extensive small cell lung carcinoma.

BACKGROUND: The combination of cisplatin, ifosfamide, and prolonged oral etoposide (PIE) was studied in patients with extensive small cell lung carcinoma (SCLC) in a Phase I trial followed by a Phase II trial to determine the maximum tolerated dose (MTD), characterize toxicity, and estimate response and median survival rates. METHODS: Thirty-three patients were treated between October 1991 and December 1994. Doses for the initial cohort were cisplatin 20 mg/m2/day, ifosfamide 1500 mg/m2/day with mesna (all given intravenously on Days 1-3), and oral etoposide 50 mg/m2 on Days 4-17. This cycle was repeated every 4 weeks for up to 6 cycles. The MTD was reached for the first 9 patients. For these 9 patients and the next 24 patients, who were entered in the Phase II trial, response and survival were estimated. RESULTS: Dose-limiting toxicity was manifested as Grade 4 neutropenia in 3 of 3 patients (associated with fever in 2 of 3), and Grade 4 thrombocytopenia was encountered in 2 of 3 patients at the second dose level. Of 6 patients treated at the first dose level, 4 achieved targeted myelosuppression (absolute granulocyte count nadir <1000), but only 1 experienced Grade 4 neutropenia, defining this level as the MTD. Grade 4 neutropenia and/or thrombocytopenia was observed in 36 (24%) of a total of 152 courses administered at or below the MTD. Nonhematologic toxicity above Grade 2 was uncommon, excluding nausea and vomiting. Overall objective response rate was 93% of 30 evaluable patients: 5 (17%) complete responses and 23 partial responses (76%). Median failure free and overall survival durations were 36 and 54 weeks, respectively. CONCLUSIONS: The combination of cisplatin, ifosfamide, and oral etoposide produced encouraging failure free and overall median survival rates in patients with extensive SCLC. These results warrant further evaluation of this regimen in the initial therapy of patients with limited stage disease.

Administration, Oral↗

Charged chelate-capillary electrophoresis of endogenous corticosteroids.

Separation of endogenous 17- or 18-hydroxylated corticosteroids (of the 21-hydroxylated 4-pregnen series) as charged chelates in capillary electrophoresis with borate as the ligand is demonstrated. Aldosterone, 18-hydroxycorticosterone, 18-hydroxy-11-deoxycorticosterone, cortisone, cortisol, and 11-deoxycortisol are separated and resolved by 400 mM borate buffer at pH 9.0. Separation characteristics of the corticosteroid charged chelates were examined by varying the separation buffer borate concentration, pH, ionic strength, and addition of organic modifiers. The borate ion [B(OH)4]- is identified as the critical buffer component. Corticosteroids chelate borate with proximal hydroxyls composed of either the 17- or 18-hydroxyl in combination with the 21-position hydroxyl. Corticosteroid/borate chelation as indicated by CE results is corroborated with 11B-nuclear magnetic resonance (11B-NMR) spectra. Chelation is a readily reversible process, with the strength of the resultant chelate, as opposed to the charge-to-mass ratio, predominantly determining analyte mobility in charged chelate - capillary electrophoresis (CC-CE).

18-Hydroxycorticosterone↗

Scintigraphic diagnosis of coronary artery disease: myocardial bull's-eye images contain the important information.

The bull's-eye image, also called polar map image, has been developed as an important display for the visual and quantitative analysis of myocardial perfusion scintigrams. Quantitative analysis can be performed for example by comparing areas in the bull's-eye image with normal limits or by processing it using artificial neural networks. The usefulness of such methods is highly dependent on the information content of the bull's-eye image. The purpose of this study was to investigate whether there is more diagnostically important information in a set consisting of the myocardial bull's-eye image plus tomographic slice image than in the bull's-eye image alone. A population of 135 patients who had undergone both myocardial scintigraphy and coronary angiography, with no more than 3 months elapsing between the two examinations, was studied retrospectively. Four experienced observers independently classified visually all scintigrams regarding the presence/absence of coronary artery disease in two vascular territories using a four-grade scale. The observers classified the scintigrams once viewing bull's-eye images only, and once viewing tomographic slices and bull's-eye images. Coronary angiography was used as gold standard. The classifications were evaluated using the areas under the receiver operating characteristics (ROC) curves. The classifications based on bull's-eye images only were slightly more accurate than those based on tomographic slices and bull's-eye images in one of the two vascular territories (ROC areas of 0.66 vs. 0.64). The opposite relationship was found in the other vascular territory (0.78 vs. 0.81). None of the differences was statistically significant. In conclusion, the diagnostically important information for the diagnosis of coronary artery disease by myocardial perfusion scintigraphy is present in the bull's-eye image.

Adult↗

Attitudes to LIS education and academic-practitioner liaison: results of a survey of members of the Library Association Health Libraries Group.

A questionnaire survey was conducted by the Library Association Health Libraries Group in October-December 1996. Information practitioners in the health care sector were asked what they considered were the education and research needs of the profession, their opinion of Library and Information Sciences education, and their views on practitioner input to education and research. They were also asked whether they would be prepared to give talks to students and to offer student placements. The results show that there is still a considerable gulf between academics and practitioners, and that although practitioners are enthusiastic about getting more involved in liaison, they are constrained by lack of time and resources. Practical solutions need to be found to encourage greater understanding and closer working relationships, to achieve the benefits of academic-practitioner liaison.

Adult↗

Evaluation of a live attenuated recombinant virus RAV 9395 as a herpes simplex virus type 2 vaccine in guinea pigs.

Recombinant virus RAV 9395 was constructed by deleting both copies of the gamma(1)34.5 gene, and the UL55 and UL56 open reading frames from herpes simplex virus type 2 (HSV-2) strain G. The potential use of RAV 9395 as an HSV-2 vaccine was investigated by evaluating the ability of RAV 9395 to protect guinea pigs from severe disease by HSV-2(G) challenge. RAV 9395 administered intramuscularly reduced both lesion development and severity in a dose-dependent manner in guinea pigs challenged with HSV-2(G). The frequency of reactivation of RAV 9395 from explanted dorsal root ganglia was low compared with that of HSV-2(G). Immunization with RAV 9395 at doses of 1 x 10(5) pfu and above generally precluded the establishment of latency by the challenge virus. The results presented in this report lend support for the development of genetically engineered live HSV vaccines.

Animals↗

Cysteine protease inhibitors alter Golgi complex ultrastructure and function in Trypanosoma cruzi.

Cruzain, the major cysteine protease of the protozoan parasite Trypanosoma cruzi, is a target of rational drug design for chemotherapy of Chagas' disease. The precise biological role of cruzain in the parasite life cycle and the mechanism involved in the trypanocidal effect of cysteine protease inhibitors are still unclear. Here we report biological and ultrastructural alterations caused by cysteine protease inhibitors in T. cruzi epimastigotes. Cruzain, a glycoprotein that transits the Golgi-endosomal pathway, localized to pre-lysosomes/lysosomes in the posterior end of untreated epimastigotes by fluorescent microscopy utilizing either a biotinylated cysteine protease inhibitor to tag the active site, or a specific anti-cruzain antibody. Radiolabeled or biotinylated cysteine protease inhibitors bound exclusively to cruzain in intact epimastigotes confirming that cruzain is accessible to, and is targeted by the inhibitors. Treatment of T. cruzi epimastigotes with specific cysteine protease inhibitors arrested growth, altered the intracellular localization of cruzain, and induced major alterations in the Golgi complex. Following treatment, cruzain accumulated in peripheral dilations of Golgi cisternae. There was a concomitant 70% reduction in gold-labeled cruzain transported to lysosomes. Cisternae abnormalities in the Golgi compartment were followed by distention of ER and nuclear membranes. Brefeldin A increased the number and size of cisternae in epimastigotes. Pre-treatment of epimastigotes with cysteine protease inhibitors followed by exposure to brefeldin A induced a more rapid appearance of the cysteine protease inhibitor-induced Golgi alterations. Our results suggest that cysteine protease inhibitors prevent the normal autocatalytic processing and trafficking of cruzain within the Golgi apparatus. Accumulation of cruzain may decrease mobility of Golgi membranes and result in peripheral distention of cisternae. These major alterations of the Golgi complex parallel the death of T. cruzi epimastigotes.

Animals↗

Teamwork in the operating department.

The Gynaecology theatre team of the Leicester Royal Infirmary NHS Trust were runners-up in the 1997 3M/NATN joint award. This article is a report of their work on the concept of teamwork and its benefits to the organisation and delivery of patient care in the operating department.

Hospital Restructuring↗

Relationship among cystectomy, microvessel density and prognosis in stage T1 transitional cell carcinoma of the bladder.

PURPOSE: The selection of therapy for stage T1 bladder cancer is controversial, and reliable biomarkers that identify patients likely to require cystectomy for local disease control have not been established. We evaluated our experience with T1 bladder cancer to determine whether early cystectomy improves prognosis, and whether microvessel density has prognostic value for T1 lesions and could be used for patient selection. MATERIALS AND METHODS: We retrospectively reviewed the records of 88 patients with T1 transitional cell carcinoma of the bladder. Patient outcome was correlated with therapeutic intervention. Paraffin embedded tissue from 54 patients was available for factor VIII immunohistochemical staining for microvessel density quantification. RESULTS: Median followup was 48 months (range 12 to 239). Of the patients 34% had no tumor recurrence. The rates of recurrence only and progression to higher stage disease were 41 and 25%, respectively. The survival of patients in whom disease progressed was diminished (p = 0.0002). Grade did not predict recurrence or progression nor did cystectomy provide a survival advantage. Microvessel density did not correlate with recurrence or progression. CONCLUSIONS: Patients with T1 bladder cancer have a high risk of recurrence and progression. Tumor progression has a significant negative impact on survival. Neither grade nor early tumor recurrence predicted disease progression. Because early cystectomy did not improve patient outcome, we suggest reserving cystectomy for patients with progression or disease refractory to local therapy. Microvessel density is not a prognostic marker for T1 bladder cancer and has no value in selecting patients with T1 disease for cystectomy.

Capillaries↗

Comparison of morphologic assessment of hypertrophic cardiomyopathy by magnetic resonance versus echocardiographic imaging.

To compare the value of echocardiography and magnetic resonance imaging (MRI) in the assessment of the amount and extent of hypertrophy in hypertrophic cardiomyopathy (HC) and, second, to correlate the degree of hypertrophy, as assessed by MRI, with clinical and electrocardiographic parameters, 30 consecutive patients (16 men and 14 women, aged 20 to 74 years) with HC were studied. Measurements of left ventricular wall thickness were performed at 11 predetermined segments (5 basal, 5 midventricular, and 1 apical) by 2-dimensional echocardiography and MRI. Two parameters derived from MRI studies were considered as indicators of the degree and extent of hypertrophy: (1) mean of the measured wall thickness at the 11 segments, and (2) the number of segments with thickness > 15 mm. Results showed that, from a total of 330 myocardial segments, thickness could be measured by echocardiography in 221 (67%), whereas MRI allowed measurement of 320 segments (97%). When compared with clinical and electrocardiographic data, no correlation was found regarding mean wall thickness and number of hypertrophied segments by MRI except for the presence of an abnormal electrocardiographic repolarization pattern. It is concluded that MRI allows a better assessment of the degree and extension of left ventricular hypertrophy than echocardiography in HC. Despite the precise information on hypertrophy provided by MRI, the amount and degree of hypertrophy bears no correlation with most of the clinical data in these patients.

Adult↗

Infant color vision: moving tritan stimuli do not elicit directionally appropriate eye movements in 2- and 4-month-olds.

The purpose of the present study was to investigate the capacity of infants to code the direction of motion of moving tritan-modulated gratings. Infant and adult subjects were tested with 0.2 c/d sinusoidal gratings moving at a speed of 20 deg/sec. Three conditions were tested: luminance-modulated gratings, tritan-modulated gratings, and luminance- vs tritan-modulated gratings superimposed and moving in opposite directions in a chromatic motion nulling paradigm. Two-month-old infants were tested in all three conditions, while 4-month-olds were tested in only the first two conditions. For infant subjects, an adult observer reported the direction of the slow phase of the infant's eye movements; adult subjects judged the perceived direction of motion of the stimuli. Luminance-modulated gratings produced directionally appropriate eye movements (DEM) in all age groups. Tritan gratings presented alone did not produce DEM in either 2- or 4-month-olds, but did so in adults. Mean equivalent luminance contrasts were near zero in 2-month-olds, and small but reliably above zero in adults. In sum, the present study provides no evidence that infants can code the direction of motion of moving tritan gratings.

Adult↗