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Biomedical subjects

R Allen

Publications and source records attributed to R Allen.

At least 109 records · Page 6Linked to original sources

Fast spin echo magnetic resonance imaging: clinical application in screening for acoustic neuroma.

The advent of magnetic resonance imaging has greatly improved our ability to diagnose acoustic tumors, but it is a relatively expensive imaging modality. In the present climate of medical cost restraints, methods that reduce costs but maintain quality are extremely desirable. We report a new magnetic resonance imaging technique that uses fast spin echo without gadolinium. It provides ultrahigh-resolution images of the internal auditory canal and cerebellopontine angle. The sensitivity of this technique for the detection of acoustic tumors is equivalent to conventional gadolinium-enhanced magnetic resonance imaging, but the global cost is comparable with that of brain stem audiometry. In our practice fast spin echo magnetic resonance imaging has replaced brain stem audiometry as a screening modality to evaluate most acoustic tumor suspects. Also, the intricate detail of the internal auditory canal anatomy provided by this technique is useful in planning surgical removal of acoustic tumors.

Adult↗

Levels of therapeutic antivenin and venom in a human snakebite victim.

An enzyme-linked immunosorbent assay was used to measure the levels of therapeutic antivenin (Antivenin [Crotalidae] Polyvalent, Wyeth-Ayerst) in serum and the levels of venom in the urine of a patient bitten by a western diamondback rattlesnake (Crotalus atrox). Serum and urine samples were taken on admission, during hospitalization, and during follow-up until 5 months after the bite. Photographs were taken of the bite site on admission to the hospital and during follow-up. Serum levels of therapeutic antivenin were highest between 1 and 3 days after the bite but were still detectable 46 days as well as 4 months after the bite. Crotalus atrox venom was detectable in the urine 4 days after the bite and was still measurable 6 days after the bite.

Animals↗

The inhibition of antigen-induced eosinophilia and bronchoconstriction by CDP840, a novel stereo-selective inhibitor of phosphodiesterase type 4.

1. The novel tri-aryl ethane CDP840, is a potent and selective inhibitor of cyclic AMP phosphodiesterase type 4 (PDE 4) extracted from tissues or recombinant PDE 4 isoforms expressed in yeast (IC50S: 4-45 nM). CDP840 is stereo-selective since its S enantiomer (CT 1731) is 10-50 times less active against all forms of PDE 4 tested while both enantiomers are inactive (IC50S: > 100 microM) against PDE types 1, 2, 3 and 5. 2. Oral administration of CDP840 caused a dose-dependent reduction of interleukin-5 (IL-5)-induced pleural eosinophilia in rats (ED50 = 0.03 mg kg-1). The eosinophils in pleural exudates from CDP840-treated animals contained higher levels of eosinophil peroxidase (EPO) than cells from control animals, suggesting a stabilizing effect on eosinophil degranulation. CDP840 was approximately equi-active with the steroid dexamethasone in this model and was 10-100 times more potent than the known PDE 4-selective inhibitors rolipram and RP73401. The activity of CDP840 was not influenced by adrenalectomy, beta-sympathomimetics or beta-sympatholytics. 3. Antigen-induced pulmonary eosinophilia in sensitized guinea-pigs was reduced dose-dependently by CDP840 (0.01-1 mg kg-1, i.p.) and intracellular EPO levels were significantly higher. CDP840 was more potent in these activities than CT1731 or rolipram and comparable in potency to RP73401. 4. Rolipram or CDP840 were less active than dexamethasone in preventing neutrophil accumulation, or exudate formation in carrageenan-induced pleurisy in rats and thus do not exhibit general anti-inflammatory activity. 5. In sensitized guinea-pigs, aerosols of the antigen ovalbumin caused a dose-dependent bronchoconstriction demonstrated by an increase in pulmonary inflation pressure. Administration of CDP840 (0.001-1.0 mg kg-1, i.p.), 1 h before antigen challenge, resulted in dose-dependent reduction in response to antigen. This activity was not due to bronchodilatation since higher doses of CDP840 (3 mg kg-1) did not significantly change the bronchoconstrictor response to histamine. Rolipram was approximately 10 times less active than CDP840 in preventing antigen-induced bronchoconstriction. 6. These results confirm the observations that selective PDE 4 inhibitors reduce antigen-induced bronchoconstriction and pulmonary eosinophilic inflammation. CDP840 is more potent than rolipram in inhibiting native or recombinant PDE 4. Unlike the recently described potent PDE 4 inhibitor RP73401, CDP840 is more active than rolipram in the rat IL-5 model following oral administration. The novel series of tri-aryl ethanes, of which CDP840 is the lead compound, could be the basis of an orally active prophylactic treatment for human asthma.

3',5'-Cyclic-AMP Phosphodiesterases↗

The relationship between anxiety and problem-solving skills in children with and without learning disabilities.

This study compared the effects of low, medium, and high pretest anxiety levels on the social and nonsocial problem-solving performance of 45 boys with learning disabilities (LD) and 45 boys with no learning disabilities (NLD). Participants ranged from 9 to 11 years of age. Boys with LD reported significantly higher pretest trait and state anxiety on the State-Trait Anxiety Inventory for Children than did NLD boys, and their perceived state anxiety escalated over the course of the problem-solving session. There were no pervasive effects of LD status on problem solving by itself, boys with LD being as effective in problem solving as NLD boys. However, means for task solution suggest a tendency for an interaction between group and anxiety level, which should be examined using a larger, well-defined sample and an unstructured task.

Achievement↗

Pleomorphic xanthoastrocytoma presenting with massive intracranial hemorrhage.

A 46-year-old woman presented with massive left temporal lobe intraparenchymal and diffuse subarachnoid hemorrhage on CT. Lack of enhancement excluded intermediate and high-grade primary tumor or metastasis as likely causes. At surgery, a fibrovascular left temporal lobe mass adherent to the dura proved to be a pleomorphic xanthoastrocytoma. The unusual hemorrhagic presentation of this typically benign entity is thought to be related to the meningeal involvement, which itself is characteristic of this neoplasm.

Astrocytoma↗

Assessing clinical skills of medical students.

The clinical skills of sophomore medical students at the University of Arkansas are being assessed through the use of the Objective Structured Clinical Examination (OSCE). This exam was developed in order to better standardize the evaluation of practical clinical skills. The exam uses standardized patients, who are lay people trained to accurately and consistently portray a patient encounter. Faculty members at UAMS authored clinical cases for 20 patient encounters that test history taking, physical examination and communication skills. Each student interacts with the patient while being assessed in a standardized way, and then is given educational feedback by a faculty member. Students who do not pass the exam, undergo a remediation program prior to entering the junior year.

Arkansas↗

Chronic feeding study of pyrilamine in Fischer 344 rats.

The antihistamine, pyrilamine maleate, was fed for up to 2 years to groups of 57 Fischer 344 (F344) rats of each sex at dietary levels of 0, 300, 1500, or 3000 ppm (free base). Eight or nine of these rats per sex and dose group were killed at 65 weeks to analyze hematology and clinical chemistry in all groups and histopathology of control and high-dose animals. Histopathology also was performed on all dead or moribund rats and on all that survived for 2 years. Average daily exposures were 11 to 150 mg/kg pyrilamine compared to human dosages up to 3 mg/kg. Pyrilamine treatment did not reduce survival. Final body weights were reduced relative to controls (mid-dose males, 93%, females, 82%: high-dose males, 82%, females, 70%). The incidences of inflammation of the nasolacrimal duct (chronic in females; suppurative in males), liver cytoplasmic vacuolization (males), and the combination of animals with either liver basophilic or clear cell foci (males) tended to significantly increase with dose. Adrenal pheochromocytomas, mammary gland fibroadenomas, and neoplasms of the clitoral gland, thyroid c-cell, and pituitary gland all tended to decrease with increasing dose in females. In males only preputial gland neoplasms exhibited a similar negative trend. While two ovarian granulosatheca cell benign tumors occurred in high-dose females, these were thought to be a random occurrence. There was no evidence for the carcinogenicity of pyrilamine in F344 rats in the current study.

Adrenal Medulla↗

Chronic study of triprolidine for oncogenicity in mice.

Triprolidine hydrochloride was fed to groups of 60 B6C3F1 mice per sex at dietary levels of 0, 500, 2000, or 4000 ppm (as the free base) for up to 2 years. Up to 12 mice of each sex and dose group were terminated after 65 weeks for hematology and clinical chemistry. The control and high-dose groups were examined histologically. A complete histopathological examination was performed on the remaining 48 mice from each dose group when removed from study due to moribund condition, early death, or terminal euthanization at 105 weeks. Triprolidine did not significantly alter the survival of either sex. High-dose male and mid- and high-dose female body weights were significantly less than controls at the end of the study. Significant trends toward lower frequency with increasing dose were noted in females for fatty change in the liver and lymphomas (combination of lymphocytic, mixed, and histiocytic lymphomas). Similar negative trends in males were for lymphocytic cellular infiltration in multiple organs and lung alveolar/bronchiolar adenomas or the combination of alveolar/bronchiolar adenomas or carcinomas. Significant trends toward increased frequency with increasing dose were found in female mice for lymphocytic infiltration in multiple organs and cytoplasmic alterations of the acinar cells of the parotid gland. Similar positive trends were found in males for cytoplasmic alterations of the parotid gland and various hepatocellular changes (e.g., hypertrophy and altered foci). While there was a positive dose response trend for hepatocellular adenomas in males the combination of these and hepatocellular carcinomas eliminated the significant trend, and it was concluded that there was no evidence of a carcinogenic response to triprolidine in B6C3F1 mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Triprolidine: 104-week feeding study in rats.

The antihistamine triprolidine hydrochloride, was fed at dietary concentrations of 0, 250, 1000, or 2000 ppm (as the free base) to groups of 60 Fischer 344 (F344) rats of each sex for up to 2 years to evaluate its potential carcinogenicity. Up to 12 per sex from each group were killed at 65 weeks, and hematology, clinical chemistry, and histopathology were evaluated. A complete histopathological evaluation was performed on all other animals; survivors were killed at 2 years. Survival was significantly extended in triprolidine-treated males and females, particularly at the high dose. At the close of the study high-dose males and females had gained significantly less body weight than controls. Among rats killed at 65 weeks females in the mid- and high-dose groups weighed significantly less than controls, but weights of control and dosed males were not significantly different. The incidences of numerous lesions tended to decrease with increasing triprolidine dose. In females, clitoral gland adenomas, thyroid c-cell hyperplasia and neoplasia, mammary gland hyperplasia and fibroadenomas, and uterine stromal polyps, and in males, anterior pituitary gland adenomas, preputial gland neoplasia, thyroid c-cell pancreatic islet neoplasia, mononuclear cell leukemia, and the combination of lymphocytic, histiocytic, and undifferentiated cell malignant lymphomas and mononuclear leukemia, all exhibited negative dose trends. Cytoplasmic alterations of the parotid gland and numerous liver lesions tended to be more frequent in treated than in control animals. Liver lesions that exhibited positive dose trends include chronic inflammation and centrilobular fatty change in both sexes, mixed cell foci, and the combination of mixed cell foci and eosinophilic foci in females, and in males, basophilic foci and eosinophilic foci. Triprolidine was not carcinogenic in F344 rats.

Animals↗

Expression and immune recognition of stress proteins in sarcoidosis and other chronic interstitial lung diseases.

Stress proteins (SP) are major immunogens in a number of microbial infections and have been implicated in some autoimmune diseases. The aetiology of sarcoidosis, a non-caseating granulomatous disease, remains unknown, but mycobacteria as well as autoimmunity have been considered. In the present study, patients diagnosed with sarcoidosis and other interstitial lung diseases (ILD), as well as healthy volunteers were studied to determine: (i) the level of expression of SP in alveolar macrophages and blood monocytes; (ii) the serum levels of antibodies specific for mycobacterial SP65 and SP70; and (iii) the reactivity of peripheral blood and alveolar lymphocytes to mycobacterial SP65. Our results suggest that SP are expressed constitutively at high levels in alveolar macrophages, retrieved by bronchoalveolar lavage, from all individuals regardless of health status. In contrast, freshly isolated blood monocytes express low levels of SP, which are, however, readily upregulated following exposure to IFN-gamma and TNF-alpha. Lymphocyte reactivity and presence of antibodies against mycobacterial SP may reflect the current state of in vivo inflammation rather than the cause of inflammation.

Antibodies, Monoclonal↗

The influence of the dialysate flow rate on hollow fiber hemodialyzer performance.

The clearance characteristics of two sizes of hemodialyzers (0.9 m2 and 1.5 m2) from the same range of products have been studied over the dialysate flow range of 500-3,000 ml/min to establish the device's overall mass transfer resistance characteristics. The results obtained demonstrate a difference in the overall mass transfer resistance which is most marked at the commonly used dialysate flow rate of 500 ml/min. This difference suggests that the increase in size results in the introduction of flow imperfections which reduces the benefit that might be gained by the use of a larger surface area. Results established indicate a reduction in the overall mass transfer resistance with an increasing dialysate flow rate. This reduction is attributed to the presence of turbulence in the dialysate pathway at higher flow rates. The presence of such turbulence was confirmed by visual inspection of the dialyzer after the completion of the study when it was noted that the original well-ordered configuration present in a new dialyzer had been substantially disturbed. Correlation of the dialysate flow rate with overall mass transfer resistance by the use of a Wilson plots indicates a nonlinear relationship. This nonlinearity is attributed to a nonfully developed turbulent flow profile in the dialysate pathway.

Hydrostatic Pressure↗

Stimulus and cell-specific expression of C-X-C and C-C chemokines by pulmonary stromal cell populations.

Chronic inflammatory responses in the lung rely on the continual recruitment of leukocytes to the site of inflammation. Recent data have demonstrated a possible role for stromal cell-derived chemokines in leukocyte recruitment. In the present study we examined the production of interleukin (IL)-8 and ENA-78, members of the C-X-C family of chemokines, and macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta, members of the C-C chemokine family, from pulmonary smooth muscle and endothelial cells. The production of IL-8 and ENA-78 was induced by early response cytokines, IL-1 and tumor necrosis factor (TNF), but not by immune-associated cytokines, IL-4, IL-10, or interferon (IFN)-gamma. In contrast, the production of MIP-1 alpha and MIP-1 beta by pulmonary vascular smooth muscle cells increased when stimulated by immune-associated cytokines as well as with IL-1 beta and TNF. The level of MIP-1 alpha production induced in smooth muscle cells by the immune-associated cytokines, IL-4, IFN-gamma, and IL-10 ranged from 0 to 340 pg/ml. The production of MIP-1 beta in response to the immune-associated cytokines IL-4, IFN-gamma, and IL-10 in smooth muscle cells ranged from 260 to 940 pg/ml. Human pulmonary artery endothelial cells did not generate MIP-1 alpha or MIP-1 beta in response to graded doses of any of the cytokines. These data demonstrate differential induction of C-X-C and C-C chemokines from nonimmune stromal cell populations.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemokine CCL4↗

Synthesis and evaluation of 7 alpha-iodo-5 alpha-dihydrotestosterone as a potential radioligand for androgen receptor.

7 alpha-Iodo-17 beta-hydroxy-5 alpha-androstan-3-one (7 alpha-iodo-5 alpha-dihydrotestosterone, 7 alpha-IDHT) has been synthesized as a potential radioligand for the detection and measurement of androgen receptor and for imaging of androgen-receptor-containing tissues when labeled with the gamma-emitting radionuclides 125I and 123I, respectively. In vitro binding studies show that 7 alpha-IDHT binds with high affinity to the rat and human androgen receptor (RBA = 74) compared to R1881 (RBA = 100). Further, this compound showed high specificity for the androgen receptor. 7 alpha-IDHT showed only a marginal affinity for the progestin receptor and even less affinity for the estrogen receptor. No binding was detected to the glucocorticoid receptor. These characteristics make 7 alpha-IDHT a potentially ideal agent for imaging and evaluation of androgen-receptor-containing tissues.

Animals↗