Biomedical subjects
P Goodwin
Publications and source records attributed to P Goodwin.
Motor responses to dopamine D1 and D2 agonists in the reserpine-treated mouse are affected differentially by the NMDA receptor antagonist MK 801.
The akinesia induced by reserpine in mice was effectively reversed by the dopamine D1 receptor agonists SKF 38393 (5-30 mg/kg IP) and CY 208-243 (1-5 mg/kg IP), and by the mixed D1/D2 agonist pergolide (5 mg/kg SC), but less well by the D2 agonists lisuride, PHNO, LY 171555 and RU 24213 (each at 5 mg/kg SC) and not at all by the NMDA receptor antagonist MK 801 (0.1-10 mg/kg IP). MK 801 potentiated D1-dependent locomotion, but always suppressed rearing and grooming. D2-dependent locomotion was inhibited by MK 801. The D2 agonist RU 24213 was antagonised by as little as 6.25 micrograms/kg MK 801, while PHNO and LY 171555 were antagonised by 0.1 mg/kg MK 801. Lisuride was not inhibited by up to 1.6 mg/kg MK 801. Importantly, all animals showed signs of incapacitation with MK 801 in certain elements of their behaviour, most notably ataxia and hind limb abduction. Thus whilst NMDA receptor blockade can facilitate the restoration of movement by dopamine D1 (though not D2) agonists in monoamine-depleted mice, the fluency of the motor response is adversely affected.
Storage phosphor imaging technique for detection and quantitation of DNA adducts measured by the 32P-postlabeling assay.
The 32P-postlabeling method has found wide application as a sensitive technique for detecting the presence of a broad range of bulky aromatic compounds covalently bound to DNA. In this method, the modified DNA is enzymatically degraded to 3'-mononucleotides and labeled with [32P]-phosphate at the 5'-position using [gamma-32P]ATP and T4 polynucleotide kinase. The 32P-labeled DNA digest is then chromatographed in two dimensions on polyethyleneimine - cellulose thin-layer plates. Screen-enhanced autoradiography is used to locate the presence of the radiolabeled adducts on the chromatogram, and the radioactive areas are generally excised and quantitated by liquid scintillation spectrometry. However, on a chromatogram with multiple adducts, it can be difficult to quantitative partially resolved adducts and evaluated background radioactivity levels. We have evaluated the use of storage phosphor imaging techniques to quantitate and map the radioactivity on chromatograms generated by the 32P-postlabeling method. The results showed that storage phosphor imaging was approximately 10 times more sensitive than screen-enhanced autoradiography at -80 degrees C for the detection of 32P, exhibits a greater linear range of response, has a resolution that compares favorably to film and has a lower background than does liquid scintillation spectrometry. Further, the generation of a digitized record of the distribution and intensity of radioactivity allows for computer-assisted assessment of adduct profiles and can facilitate quantitation of individual adducts and radioactive zones comprised of multiple overlapping adducts in complex chromatograms. Additionally, the permanent record created by the imaging technology permits facile retrospective analysis of samples, whereas with autoradiography and liquid scintillation spectrometry reanalysis of a replicate sample is required.
Quantitative structure-activity relationships of antitumor guanidinothiazolecarboxamides with survival enhancement for therapy in the 3LL Lewis lung carcinoma model.
Guanidinothiazolecarboxamides (GTCs) are a novel class of antitumor agents found to be systemically active against experimental pulmonary metastases of 3LL Lewis lung carcinoma. A series of substituted benzothiazole GTCs were found to produce enhancement of survival in this model by using 8 days of intraperitoneal dosing initiated 2 days after intravenous tumor challenge. Quantitative structure-activity relationships have been discovered in the GTC series with survival enhancement correlated to substituent parameters. Optimal correlations were found between the probit transform of the drug-induced increased lifespan (ILS) and field and pi parameters. Among the most effective analogues in this series was N-(5-fluorobenzothiazol-2-yl)-2-guanidinothiazole-4-carboxam ide.
Comparative efficacy and bioequivalence of a brand-name and a generic triamterene-hydrochlorothiazide combination product.
The clinical efficacy, safety, and bioavailability of a generic triamterene-hydrochlorothiazide product were compared with those of Dyazide. Thirty patients who had a diagnosis of nonlabile essential hypertension and who were receiving Dyazide (triamterene 50 mg and hydrochlorothiazide 25 mg) were continued on Dyazide maintenance for 16 days to determine the stability of blood pressure control and serum chemistry values. After this baseline period, the subjects were randomized to receive either Dyazide or a generic version for 21 days. They were then crossed over to receive the opposite product for another 21 days. Blood pressures were monitored throughout the study period, and blood samples were taken for measurement of serum electrolytes and of serum triamterene and its major metabolite, hydroxytriamterene sulfate. Hydrochlorothiazide was assayed in 24-hour urine samples. There were no statistically significant differences between regimens in recumbent and standing mean diastolic blood pressures or in mean concentrations of serum potassium, chloride, glucose, creatinine, and uric acid. Area under the concentration-time curve from 0 to 24 hours after drug administration, maximum concentration in serum, and time to achieve maximum concentration in serum did not differ significantly between regimens for triamterene and hydroxytriamterene sulfate. Similarly, there were no significant differences in excretion, maximum rate of excretion, and time to achieve maximum rate of excretion for urinary hydrochlorothiazide. Patients treated with a brand-name fixed-combination product containing triamterene 50 mg and hydrochlorothiazide 25 mg were given a generic formulation without loss of therapeutic efficacy or development of toxicity.
Hirschsprung's disease: a difficult diagnosis.
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Treatment of basal-cell carcinoma: comparison of radiotherapy and cryotherapy.
A prospective randomised trial to compare radiotherapy and cryotherapy in the treatment of basal-cell carcinomas was carried out in 93 patients. Two years after treatment, 4% of tumours treated with radiotherapy and 39% of those treated with cryotherapy had recurred. It is concluded that cryotherapy does not offer a satisfactory alternative to radiotherapy in the treatment of basal-cell carcinomas.
The effects of nicotine on laser Doppler measures of cochlear blood flow.
Anesthetized guinea pigs were given arterial bolus injections of saline or varying nicotine concentrations. Blood flow through the cochlea and skin were measured via laser Doppler and arterial blood pressure via an arterial cannula. Cochlear blood flow increased with low doses of nicotine but decreased with the highest dose, while blood pressure increased and skin flow decreased with all doses of nicotine. Control injections of saline vehicle had only minor and transient effects.
Fast track and flexible design cut costs.
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A case of ? epidermolysis bullosa.
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The cell cycle time in psoriasis. The uninvolved epidermis.
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Post-synthetic modifications of nuclear macromolecules.
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The effect of corticosteroids on cell turnover in the psoriatic patient. A review.
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DNA synthesis and mitosis in uninvolved epidermis of persistent palmoplantar pustulosis.
Mitotic and DNA synthesizing cell counts have been performed in uninvolved epidermis of twenty-one patients with persistent palmoplantar pustulosis (PPP). There was no difference in mitotic counts and DNA synthesis in PPP compared with normal epidermis, but both were significantly lower than those found in the clinically uninvolved epidermis of patients with psoriasis.
Onycholysis due to acrylic nail applications.
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D C shock: spontaneous reversion to sinus rhythm during anaesthesia with propanidid.
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Manners makyth man.
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