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Biomedical subjects

R Gordon

Publications and source records attributed to R Gordon.

At least 91 records · Page 5Linked to original sources
PubMed1995

Cyclooxygenase-2 inhibitors. Synthesis and pharmacological activities of 5-methanesulfonamido-1-indanone derivatives.

The recent discovery of an alternative form cyclooxygenase (cyclooxygenase-2, COX-2), which has been proposed to play a significant role in inflammatory conditions, may provide an opportunity to develop anti-inflammatory drugs with fewer side effects than existing non-steroidal anti-inflammatory drugs (NSAIDs). We have now identified 6-[(2,4-difluorophenyl)-thio]-5-methanesulfonamido-1-indanone++ + (20) (L-745,337) as a potent, selective, and orally active COX-2 inhibitor. The structure-activity relationships in this series have been extensively studied. Ortho- and para-substituted 6-phenyl substitutents are optimal for in vitro potency. Replacement of this phenyl ring by a variety of heterocycles gave compounds that were less active. The methanesulfonamido group seems to be the optimal group at the 5-position of the indanone system. Compound 20 has an efficacy profile that is superior or comparable to that of the nonselective COX inhibitor indomethacin in animal models of inflammation, pain, and fever and appears to be nonulcerogenic within the dosage ranges required for functional efficacy. Although 20 and its oxygen linkage analog 2 (flosulide) are equipotent in the in vitro assays, compound 20 is more potent in the rat paw edema assay, has a longer t1/2 in squirrel monkeys, and seems less ulcergenic than 2 in rats.

Animals↗
PubMed1995

Allelic losses on chromosome band 11q13 in aldosterone-producing adrenal tumors.

We examined loss of heterozygosity (LOH) in 14 aldosterone-producing adrenal tumors, with six linearly ordered restriction fragment length polymorphism (RFLP) markers that map within a 12-cM region containing the MEN1 locus on 11q13. Among 11 tumors that were informative for at least one marker, five showed LOH at one or more loci, and two distinct regions of deletion were identified. The proximal region overlapped with the location of the MEN1 locus previously predicted by linkage analyses in MEN1 families and the commonly deleted region in hyperparathyroid tumors. This suggests that one of the genes associated with development of aldosterone-producing adrenal tumors may coincide with the MEN1 locus, and that a second gene, distal to the MEN1 locus, may also play a role in the development of this type of tumor.

Adrenal Gland Neoplasms↗
PubMed1995

Arthroscopic treatment for posterior impingement in degenerative arthritis of the elbow.

Twenty-one patients underwent arthroscopic treatment for posterior impingement associated with degenerative elbow arthritis. Anterior debridement and removal of loose bodies was performed first. The posterior procedure consisted of three parts: removal of posterior loose bodies, removal of the posterior olecranon osteophyte, and removal of the osteophytes in the olecranon fossa to the point of fenestration. Patients were assessed for pain, strength, motion, stability, and function. They were classified as excellent, good, fair, or poor. Twenty-one of 25 patients were followed an average of 35 months. There was a statistically significant improvement in all criteria. There were 10 good and 11 fair ratings preoperatively; this improved to 14 excellent and 7 good results postoperatively (P = .0001). Arthroscopic treatment for posterior impingement in the degenerative elbow offers substantial improvement with minimal risk, provided proper intraoperative precautions are followed.

Adolescent↗
PubMed1995

CT in patients with scirrhous carcinoma of the GI tract: imaging findings and value for tumor detection and staging.

OBJECTIVE: The purposes of this study were to analyze the CT features of scirrhous carcinoma of the gastrointestinal (GI) tract and to assess the usefulness of CT in detecting and staging these lesions. MATERIAL AND METHODS: This is a retrospective evaluation of 31 proven cases of scirrhous carcinoma (linitis plastica) of the GI tract imaged in our institution from 1986 to 1994. Twenty-two patients had primary gastric carcinoma, and nine had carcinoma of the colon (rectosigmoid in eight and right colon in one). CT examinations were reviewed and correlated with pathologic and/or surgical findings in all patients and with barium examinations in 19 cases. A modified Dukes classification was used to stage these lesions without knowledge of the pathologic and surgical results. RESULTS: Four gastric lesions were missed during the initial CT examination. Seventeen patients had extensive circumferential lesions, and five had focal plaquelike lesions. The wall thickness ranged from 1 to 3 cm (mean, 1.8 cm). Homogeneous enhancement was seen in 17 patients, slightly heterogeneous enhancement was seen in one, a target configuration was present in two patients, and intramural calcification was present in one patient. All colonic lesions were circumferential, homogeneously enhancing with a wall thickness ranging from 1 to 3 cm (mean, 2 cm). CT scans showed limitations in evaluating local parameters. Compared with surgical and pathologic staging, CT correctly staged 26 patients, understaged four patients, and overstaged one patient. Among the 19 patients with pathologically proven stage D lesions (61%), CT correctly staged 17 patients (89%) and had a 100% positive predictive value. One case of hepatic metastases, 13 cases of malignant ascites, and 11 cases of omental and peritoneal metastases were found. CONCLUSION: CT is an important complimentary imaging technique to detect scirrhous carcinoma. The sensitivity of detection depends on the size of the lesion and the quality of the examination. CT has limitations in staging early lesions but shows a high sensitivity (89%) in detecting Dukes stage D lesions. Accurate CT staging in these individuals (61% in this series) allows a more adequate treatment strategy and avoids unnecessary exploratory laparotomies.

Adenocarcinoma, Scirrhous↗
PubMed1995

Pharmacology of a selective cyclooxygenase-2 inhibitor, L-745,337: a novel nonsteroidal anti-inflammatory agent with an ulcerogenic sparing effect in rat and nonhuman primate stomach.

Recent studies have shown that there are two isoforms of cyclooxygenases. The constitutive form, cyclooxygenase 1 (COX-1), is believed to be involved in the maintenance of physiological functions. A second isoform, cyclooxygenase 2 (COX-2), has been shown to be induced in inflammation. In the present study, the pharmacology of a selective inhibitor of COX-2, L-745,337 (5-methanesulfonamido-6-(2,4-difluorothiophenyl)-1-indano ne), is described. L-745,337 has IC50 values of 23 +/- 8 nM and > 10 microM for the inhibition of prostaglandin E2 production in whole-cell assays for COX-2 and COX-1, respectively. This compound inhibited carrageenan-induced rat paw edema and rat paw hyperalgesia with ID50 values of 2.00 and 0.37 mg/kg, respectively. In an endotoxin-induced pyresis assay in the rat, L-745,337 significantly reversed the pyretic responses (ID50 = 3.75 mg/kg). L-745,337 did not cause visible gastric lesions in rats at up to 30 mg/kg (4 hr after dosing). In a fecal 51chromium (51Cr) excretion assay to detect gastrointestinal integrity in rats and primates, L-745,337 had no effect at doses up to 100 mg/kg (rat) or after chronic dosing at 20 mg/kg per day for 5 days (primates). In contrast, oral administration of indomethacin, diclofenac or flurbiprofen resulted in substantial increase in fecal 51Cr excretion and/or frank gastric ulceration (rats). L-745,337 significantly inhibited the prostaglandin E2 levels in the inflammatory exudates from the rat pleural cavity after injection with carrageenan but did not inhibit prostaglandin E2 levels in the stomach.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Patients achieve accurate home blood pressure measurement following instruction.

This study evaluates the effects of an instruction program conducted by registered nurses on subjects' ability to achieve three blood pressure measurements that were within 2 mmHg of simultaneous readings taken by an instructor listening through a dual headed stethoscope. The sample comprised 30 subjects aged between 22 and 76 years who were referred to a Hypertension Unit over a two month period for home blood pressure instruction. After approximately 45 minutes of individual instruction and practice in the use of an aneroid home blood pressure machine, subjects' ability to measure their blood pressure was assessed by the accuracy of their readings, their responses to a multiple choice knowledge questionnaire, their self-reported confidence in their ability to measure their blood pressure at home and an instructor's evaluation of their technique. Twenty seven percent of subjects achieved three measurements that were the same as those of their instructor, 57% and 17% obtained readings that were within 2 mmHg and 4 mmHg of an instructor respectively. Ninety percent of subjects obtained perfect scores in the knowledge questionnaire, 93% obtained perfect scores in the technique competency checklist and 100% of subjects either strongly agreed or agreed with the statement 'I feel confident enough to measure my blood pressure at home'. The study demonstrates that patients can be taught to accurately measure their blood pressure at home and, herefore, to provide reliable data to assist in the diagnosis and treatment of hypertension and hypotension.

Adult↗
PubMed1995

The healing event in Graeco-Roman folk-medicine.

The inexplicit character of Graeco-Roman folk-medicine, together with the distorted and haphazard nature of our evidence, has led to easy denigration of its aims and methods. Analysis of the structure of the healing event, especially its spoken component, the charm, provides some insight into tacit beliefs about illness, and into the skills through which folk-practitioners won reputations for competence. Just as in school medicine, the basic aim is acquisition of the authority to intervene: correct diagnosis, drawing upon folk-categories, is followed by the reassertion of order through setting the present contingency into the context of a natural law or regularity, drawing upon the stock of shared knowledge.

Greece, Ancient↗
PubMed1994

Furrowing surface contraction wave coincident with primary neural induction in amphibian embryos.

We predicted, and have now observed, a surface contraction wave in axolotl (Ambystoma mexicanum) embryos that appears to coincide temporally and spatially with primary neural induction and homoiogenetic induction, and with involution of the chordomesoderm. The wave starts from a focus anterior to the dorsal lip of the blastopore and spreads as an ellipse, until part of it encounters the rim of the blastopore and vanishes there. The remaining arc then continues over the dorsal hemisphere until it reforms an ellipse that decreases in size. About 9 to 12 hours after it begins, the wave vanishes at a focus diametrically opposite its point of origin. The wave involves both local contraction and furrowing in the monolayer ectoderm. To a good approximation, the hemispherical portion of the ectoderm traversed by the wave becomes neuroepithelium, while the ectoderm not traversed by the wave becomes epidermis. The wave might provide a mechanism to determine the time and location at which neuroepithelial differentiation occurs.

Ambystoma mexicanum↗
PubMed1994

Distribution of catecholamine(s) in the nervous system of a mermithid nematode, Romanomermis culicivorax.

The nervous system of the mermithid nematode Romanomermis culicivorax was investigated at different developmental stages for the distribution of catecholamine(s). The catecholaminergic nervous system increased in complexity during development. In the adult nematode, catecholamine(s) occurred in the nerve ring and associated ganglia, cephalic nerves, ventral and dorsal nerve cords and mid-body region ganglia. The distribution of catecholaminergic ganglia in the tail region was different for each sex. The tail region of males contained 16-20 catecholaminergic ganglia, whereas the tail of females contained only 2 ganglia. The catecholamine widely distributed throughout the nervous system of R. culicivorax is not dopamine, since immunoreactivity to dopamine was observed only in the amphids. The results suggest that the catecholamine(s) is widely distributed within the nervous system of R. culicivorax and might function as a neurohormone or neurotransmitter in controlling physiological and developmental processes.

Aedes↗
PubMed1994

Distribution of FMRF-amide-like peptide in the nervous system of a mermithid nematode, Romanomermis culicivorax.

The nervous system of the mermithid nematode Romanomermis culicivorax was investigated at different developmental stages for the distribution of the neuropeptide FMRF-amide. An FMRF-amide-like peptide was detected by an indirect immunofluorescence technique. The peptidergic nervous system increased in complexity during development. In adults, FMRF-amide-like peptide was present in the nerve ring, cephalic papillary ganglia, cephalic nerves, amphids, ganglia posterior to the nerve ring, longitudinal nerve cords and several mid-body region ganglia. The distribution of peptidergic ganglia in the tail region was different for each sex. Four clusters of ganglia were present in the tail of females, whereas such ganglia were absent in the tail of males. The results suggest that FMRF-amide-like peptide is widely distributed within the nervous system of R. culicivorax and might function as a neurohormone or neurotransmitter in controlling physiological and developmental processes.

Aedes↗
PubMed1994

L-745,337: a selective inhibitor of cyclooxygenase-2 elicits antinociception but not gastric ulceration in rats.

L-745,337 [5-methanesulphonamido-6-(2,4-difluorothiophenyl)-1-indan one] a selective cyclooxygenase-2 inhibitor reversed hyperalgesia induced by carrageenan in rats without causing gastric ulceration at doses 100 times those causing antinociception. In contrast, piroxicam and indomethacin produced ulcerations at antinociceptive doses. These findings demonstrate that L-745,337 possesses antinociceptive activity but has a reduced liability for gastric ulceration.

Analgesics↗
PubMed1994

Evolution escapes rugged fitness landscapes by gene or genome doubling: the blessing of higher dimensionality.

Evolution on rugged landscapes ceases when a local maximum is attained. This poses the problem of how evolution could approach or attain a global maximum, especially for large genomes for which quasispecies are ineffective. I show how increasing the dimensionality of the landscape, which occurs every time there is a gene or higher order duplication (up to polyploidy), may solve this problem. Epistasis or complementarity between the duplicated genes provides an all uphill pathway towards the global maximum. The evolution of hemoglobin and other dimeric and tetrameric proteins provides a testable case, since fitness is readily defined.

Animals↗
PubMed1994

Surface contraction and expansion waves correlated with differentiation in axolotl embryos--I. Prolegomenon and differentiation during invagination through the blastopore, as shown by the fate map.

We have discovered a series of expansion and contraction, solitary waves that correlate with discrete steps of differentiation in the urodele amphibian axolotl embryo (Ambystoma mexicanum). Here we examine in detail the proposition that the blastopore is a set of differentiation waves. We superimposed the image of the axolotl fate map onto our digitized video images of normal gastrulation and matched the fate map to pigmentation irregularities on the embryo. We were then able to track the invagination of the fate map by tracking the variegated pigmentation on several embryos as gastrulation proceeded. We show a particular expansion and contraction wave sequence for every tissue in the blastula stage fate map and can now explain precisely why the fate map has the shape it does and its relationship to the embryo at subsequent stages. Each tissue can be assigned a differentiation code and placed on a hierarchical, binary differentiation tree.

Ambystoma mexicanum↗