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Biomedical subjects

R Gordon

Publications and source records attributed to R Gordon.

At least 163 records · Page 9Linked to original sources
PubMed1987

The cytoskeletal mechanics of brain morphogenesis. Cell state splitters cause primary neural induction.

There is a functional device in embryonic ectodermal cells that we propose causes them to differentiate into either neuroepithelial or epidermal tissue during the process called primary neural induction. We call this apparatus the "cell state splitter." Its main components are the apical microfilament ring and the coplanar apical mat of microtubules, which exert forces in opposite radial directions. We analyze the mechanical interaction between these cytoskeletal components and show that they are in an unstable mechanical equilibrium. The role of the cell state splitter is thus to create a mechanical instability corresponding to the embryonic state of "competence" in an otherwise mechanically stable cell. When the equilibrium of the cell state splitter is disturbed so as to produce a slight contraction of the apical end, apical contraction continues and the distinctive columnar neuroepithelial cells are produced. A slight expansion from the equilibrium state, on the other hand, results in flattened epidermal cells. The calculated forces are consistent with the known constitutive and force-generating properties and morphology of microfilaments and microtubules, and with free tubulin concentrations. There are no free parameters in the analysis. The first cells to assume the neuroepithelial state lie over the notochord. Propagation of the neuroepithelial state (homoiogenetic induction) then proceeds via stretch-induced constriction of the apical microfilament rings, until a hemisphere is covered, at which point the high rate of change of the meridional stress component necessary for further propagation vanishes. The remaining cells are stretched somewhat by this process and become epidermis. A sharp boundary between the tissues is thus formed (explaining "compartmentalization" and the binary nature of differentiation in general). Normal induction apparently involves setup of the cell state splitters in all of the ectoderm cells, perhaps synchronously timed by global embryo tension. The initial transition of cells from the ectodermal to the neuroepithelial state begins at the notoplate, where cell attachments to the notochord may both cause basal actin deposition and significantly reduce the stress induced in the ectoderm by the global tension, biasing the notoplate cell state splitters toward the neuroepithelial state. Introduction of an organizer or other solid substrate (artificial inducer) elsewhere, to which ectodermal cells can adhere, may likewise have both of these effects. Differentiation to either epidermis or neuroepithelium is thus a mechanical event followed by the synthesis of specific proteins.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

A comparison of nalbuphine and meperidine in treatment of postoperative pain.

The analgesic efficacy and side effect profile of nalbuphine 20 mg IV and of nalbuphine 40 mg IV were compared to those of meperidine 75 mg IM in the immediate postoperative period. Pain intensity, pain relief, additional analgesic requirements and the overall acceptability of the treatment were recorded for 150 patients. No significant differences were found between the groups for any of the efficacy variables. Peak analgesic effects occurred at 15 minutes in both nalbuphine groups and at 30 minutes in the meperidine group. The mean time to additional analgesic medication was approximately 207 minutes in each group. The incidence of nausea and vomiting with meperidine was 22 per cent (95 per cent confidence interval 10 to 34 per cent) and with nalbuphine 20 mg the incidence was two per cent (95%CI -2 to 6 per cent). This difference was significant (p less than 0.01). The difference between nalbuphine 40 mg (10 per cent, 95%CI 1 to 19 per cent) and meperidine, was not considered statistically significant (p = 0.17). The analgesic efficacy of nalbuphine 20 mg was indistinguishable from that of nalbuphine 40 mg and from that of meperidine 75 mg. The significantly lower incidence of nausea and vomiting with nalbuphine is a major advantage for a recovery room analgesic.

Abdomen↗
PubMed1987

Androgen depletion and repletion as a means of potentiating the effect of cytotoxic chemotherapy in advanced prostate cancer.

Seventy-five patients with stage D-2 prostate cancer refractory to orchiectomy have been entered in a controlled trial to test whether androgen priming enhances the efficacy of chemotherapy. All patients are treated with aminoglutethimide and hydrocortisone as a means of achieving medical adrenalectomy and are given cyclic i.v. chemotherapy with cytoxan, adriamycin and 5-fluorouracil. Patients in the stimulation arm (N = 39) receive, in addition, fluoxymesterone (5 mg p.o. b.i.d.) for 3 days before and on the day of chemotherapy. A similar response rate was observed in the stimulation and control arm (83% vs 74% respectively) when the analysis was restricted to evaluable patients. When all patients were included, a significantly higher response rate was observed in the control arm (64% vs 49%, P less than 0.05) as a result of the larger fraction of unevaluable patients in the stimulation arm (41% vs 14%). Median duration of response is 9 months in the stimulation and 10 months in the control arm. Median overall survival in the stimulation and control group is 12 months and 16 months respectively. Significant toxicity consisting of exacerbation of bone pain and, in two patients, development of reversible spinal cord compression was observed following androgen priming. Our results suggest that combined medical adrenalectomy and chemotherapy are highly effective in the treatment of advanced prostate cancer. Thus far, no additional benefit has been observed with androgen priming.

Aminoglutethimide↗
PubMed1987

Inflammatory aneurysm of aorta: development documented by computed tomography.

Aortic aneurysmal disease appears to be the central focus of the inflammatory process resulting in inflammatory aneurysm formation. Some authors believe that inflammatory aortic aneurysm disease is a distinct clinicopathologic entity; however, others have included it with retroperitoneal fibrosis. The histologic features of inflammatory aneurysm suggest an immunologic basis for the lesion, with the atherosclerotic aorta as a possible source of the allergen.

Aorta, Abdominal↗
PubMed1987

REV 5901: an orally effective peptidoleukotriene antagonist, detailed biochemical/pharmacological profile.

REV 5901 [alpha-pentyl-3-(2-quinolinylmethoxy)-benzene-methanol] has been shown to be a competitive antagonist of peptidoleukotrienes. In vitro it has a Ki value of 0.7 microM vs. [3H]leukotriene D4 ([3H]-LTD4) binding to membranes from guinea pig lung. Against LTC4-, LTD4- and LTE4-induced contractions of guinea pig parenchymal strips, it has Kb values of ca 3 microM and was relatively ineffective against contractions induced by other spasmogens. The peptiodoleukotriene-antagonist activity is also demonstrable against the hemodynamic and vasoconstriction effects of LTD4 in isolated guinea pig hearts. Oral antagonist activity has been shown with an LTD4-induced bronchoconstriction model and with an LTD4-induced wheal response model in guinea pigs. Unlike other reported antagonists, REV 5901 is ineffective against the multiple forms of cyclic nucleotide phosphodiesterases. Thus, in addition to its previously reported activity as a 5-lipoxygenase inhibitor, REV 5901 is a p.o. active antagonist of peptidoleukotrienes and represents a good tool for understanding the role of peptidoleukotrienes in disease.

1-Methyl-3-isobutylxanthine↗
PubMed1987

Results with cyclosporine in renal transplantation in patients who have lost two previous allografts.

We investigated the fate of the cadaver renal transplant done with cyclosporine and prednisone immunosuppression into a recipient who had suffered the loss of at least two prior allografts. Nineteen cadaver renal allografts were transplanted into 18 recipients. All 18 recipients had previously rejected at least two prior allografts. One of these rejected an allograft done at our institution with cyclosporine and prednisone and was included a second time in this series when a fourth allograft was received. Nine of 19 allografts were successfully transplanted. Average follow-up time was 39 months. Eight allografts were rejected. One graft was lost to technical complications. In one instance, the recipient died with a functioning graft. Duration of function of previous allografts was not found to be a critical determinant of third or fourth graft survival. Human leukocyte antigen matching was not a statistically significant determinant. Panel reactive antibody was higher in those who rejected the third or fourth allograft, but not with statistical significance. Recipients with the blood type A were less likely to enjoy successful third or fourth cadaver renal transplantation. We concluded that the "two time loser" renal allograft recipient should not be systematically denied subsequent transplantation.

Cadaver↗
PubMed1987

Pediatric liver transplantation.

Liver transplantation, which once was an experimental procedure of no practical interest, has become the preferred treatment for infants and children dying of almost all non-neoplastic end-stage liver diseases. Liver replacement is being provided by many well-trained teams on all of the continents, as is evident from the program today--the first international symposium on pediatric liver transplantation. I have been honored in giving the first paper in the process of introducing the remarkable work of a gifted younger generation of physicians and surgeons.

Cyclosporins↗
PubMed1987

Orthotopic liver transplantation for alpha-1-antitrypsin deficiency: an experience in 29 children and ten adults.

Thirty-nine patients (29 children and ten adults) underwent OLT for liver disease associated with A1AD from March 1980 to March 1986. Thirty of thirty-six patients (83%) with available data were homozygous phenotype PiZZ. The other six were Pi heterozygotes, being either PiMZ or PiSZ. The mean A1A activity in homozygous and heterozygous patients was 38.8 mg/dL and 114.3 mg/dL respectively. Eight patients died during the first 3 months after OLT (20%). The 5-year actuarial survival is 83% and 60% in pediatric and adult recipients respectively. Today 30 (76%) of the recipients are alive, with follow-ups of 8 to 64 months (average 27 months). The quality of life in the surviving patients is excellent.

Adolescent↗
PubMed1987

Analgesic activity following combined oral administration of flupirtine maleate and peripherally acting analgesics in mice and rats.

Concomitant administration of flupirtine maleate at a single low dose (15 mg/kg, mice; 35 mg/kg, rats) with a wide range of doses of each of the peripherally acting analgesics enhanced the antinociceptive activity of paracetamol, acetylsalicyclic acid and ibuprofen in the acetic acid writhing test, acetylsalicylic acid in the hot plate test and paracetamol, acetylsalicyclic acid and ibuprofen in the Randall-Selitto test. The concomitant administration of a single low dose of the peripherally acting analgesics (at about 1/2 ED50) with a wide range of doses of flupirtine maleate resulted in enhancement of flupirtine maleate analgesic activity by paracetamol (in the hot plate and Randall-Selitto tests), acetylsalicyclic acid (in the acetic acid writhing test), ibuprofen (in the Randall-Selitto test) and indomethacin (in the acetic acid and Randall-Selitto tests). Thus flupirtine maleate enhanced the analgesic activity of paracetamol, acetylsalicyclic acid and ibuprofen in mice and rats. Each of the peripherally acting analgesics enhanced the analgesic activity of flupirtine maleate in one or more of the analgesic tests used.

Acetaminophen↗
PubMed1987

Abuse potential and physical dependence liability studies with flupirtine maleate in laboratory animals.

Flupirtine maleate is a centrally acting analgesic with a novel chemical structure and pharmacological profile. Because of its central mechanism(s) of action, flupirtine maleate was studied for physical dependence liability and abuse potential using the following four laboratory animal models: (1) mouse jumping test--jumping behaviour after narcotic antagonist challenge; (2) Hosoya test in rats--body weight reduction after drug withdrawal or narcotic antagonist challenge; (3) tolerance in mice--reduced analgesic activity after repeated dosing; and (4) self-administration in addicted Rhesus monkeys. Unlike the narcotic analgesic agents morphine and codeine, flupirtine maleate did not display evidence of physical dependence liability or abuse potential as measured by jumping behaviour in mice or body weight reduction in rats following repeated oral administration. Doses equal to or in excess of its analgesic dose were given for up to five weeks in these studies. No tolerance developed to the analgesic activity of flupirtine maleate in mice or rats dosed for up to 19 consecutive days. Finally, in morphine-dependent Rhesus monkeys, there was no difference in the rate of self-administration of flupirtine maleate when compared to the saline vehicle. Therefore, these results clearly show that flupirtine maleate, in animals, is without abuse potential and physical dependence liability.

Aminopyridines↗
PubMed1987

Effect of flupirtine maleate on the nociceptive pathway, EEG, evoked potentials and polysynaptic reflexes in laboratory animals.

Flupirtine maleate (3, 6 and 10 mg/kg, i.v.) elevated the pain threshold following electrical stimulation of rabbit tooth pulp with a peak effect at 10 minutes, suggesting central analgesic activity. Codeine (1, 3 and 6 mg/kg, i.v.), but not zomepirac (3, 6 and 10 mg/kg, i.v.), was also effective. In the cat, electrical stimulation of the tooth pulp or the contralateral sciatic nerve (central and peripheral nociceptive pathways, respectively) results in evoked potentials (activation) in the midbrain (MRF), thalamus (VPL) and sensory cortex. Flupirtine maleate (1 mg/kg, i.v.) did not alter the evoked responses. But at 3 and 6 mg/kg, i.v. it effectively blocked activation in the MRF, VPL and sensory cortex, primarily following tooth pulp stimulation rather than after sciatic nerve stimulation, suggesting that flupirtine was a selective antagonist of the central nociceptive pathway. Furthermore, in the cat, flupirtine at 3 mg/kg, i.v. blocked cortical and hippocampal arousal (activation) following MRF stimulation. At 6 and 10 mg/kg it partially antagonized the linguomandibular reflex (central polysynaptic reflex) but had little or no effect on the flexor reflex (peripheral polysynaptic reflex). The results of these investigations demonstrate the central nervous system activity of flupirtine maleate.

Aminopyridines↗