Publications by authors named "Houghton P"

Following endoscopic gastric juice aspiration, intragastric bile acids were measured in 105 patients undergoing routine or review gastroscopy. Subsequently, duodenogastric reflux was assessed using 99mTc butyliminodiacetic acid (BIDA) scintigraphy and intragastric bile acid levels compared with the grades of reflux assessed scintigraphically. There was a significant correlation between both free and total intragastric bile acid levels and the degree of radiological bile reflux, especially when reflux was severe.

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The influence of GTP on the formation and stability of [3H] vincristine (VCR)-tubulin complexes in cytosols from two human rhabdomyosarcoma xenografts which have different sensitivities to VCR has been evaluated. After removal of endogenous GTP the initial rate of [3H]VCR binding and the maximal level of bound drug were 2- to 3-fold higher in the presence of 0.1 mM GTP than in its absence.

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The locomotor activity of freely-moving rats was increased substantially by injections of L-sodium glutamate or of picrotoxin, a GABA antagonist, into the region of the tegmental pedunculopontine nucleus. The onset of hyper-motility was more rapid with L-glutamate than with picrotoxin and the duration shorter. Locomotor activity from injecting amphetamine unilaterally into the nucleus accumbens was reduced by injections of GABA into the ipsilateral pedunculopontine nucleus.

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Thirty five patients with early gastric cancer have been treated at the Bristol Royal Infirmary since 1965. The number of cases diagnosed has doubled in the last 10 years. Epigastric pain (74%), loss of weight (63%), and gastrointestinal bleeding (43%) were the most common presenting symptoms, with a median length of history of 12 months (range five days to 72 months).

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The selective action of vincristine (VCR) has been correlated with longer retention of the drug in neoplastic tissue compared with normal tissues of the mouse (J. A. Houghton, L.

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The antitumor activity of 4'-deoxyepivincristine (vinepidine, VNP) was examined against a human rhabdomyosarcoma line, HxRh12, grown as a xenograft in immune-deprived mice. The efficacy of VNP was lower than that of vincristine (VCR) but far superior to that of vinblastine (VLB) in this model. After i.

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In order to simulate more closely conditions in which resistance to vincristine (VCR) is selected in human solid tumors, a human rhabdomyosarcoma grown as a xenograft in immune-deprived mice has been selected for resistance in situ. Karyotype analysis showed the resistant line, HxRh18/VCR-3, to have a diploid modal number, with no apparent translocations, whereas the predominant population in the parental, sensitive HxRh18 xenograft demonstrated a modal number near-tetraploid with many marker chromosomes. From the rapid rate at which resistance was selected and from karyotypic evidence, data strongly suggest that HxRh18/VCR-3 was a subpopulation within the parent tumor.

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Immune-deprived female CBA/CaJ mice bearing xenografts of six different human rhabdomyosarcoma lines were treated with 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea (MeCCNU). Tumor responses were compared with levels of O6-methylguanine-DNA methyltransferase activity because of evidence indicating that repair of DNA interstrand cross-link precursors, mediated by the transferase, may be an important determinant of MeCCNU cytotoxicity. Levels of methyltransferase in tumor extracts were measured by determining the loss of O6-methylguanine from 3H-labeled methylated DNA.

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A list of 136 plants used for medicinal purposes by the Mapuche Amerindians of Chile has been compiled. This is the first such list in English and is important due to the disappearance of Mapuche culture with increasing urbanisation. Some introduced plants have been incorporated into the traditional medicine of the Mapuche since the advent of European settlers but there is also a wealth of information about the uses of many indigenous species.

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The mortality and morbidity of 151 elderly patients (greater than 64 years of age) undergoing biliary surgery for benign disease were prospectively studied. The overall mortality was 3.3 per cent.

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Six chromone alkaloids were isolated from the root bark of SCHUMANNIOPHYTON MAGNIFICUM Harms. Three of these were identified as the known alkaloids schumanniophytine, schumannificine and N-methylschumannificine. The other three alkaloids are novel and were named isoschumanniophytine, anhydroschumannificine and N-methylanhydroschumannificine.

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Melphalan has been evaluated against a series of seven childhood rhabdomyosarcomas, each derived from a different patient and maintained in vivo as xenografts in immune-deprived mice. Six lines were derived from untreated tumors and one from a patient refractory to conventional therapy. At the maximum tolerated dose (LD10) a single administration of melphalan caused complete regressions of advanced tumor in six of seven lines, including xenografts derived from the refractory patient.

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The majority of currently available colostomy bridges lie on the skin surface. Until their removal around the seventh postoperative day, they frequently prevent the formation of a complete seal between the appliance and the skin, resulting in faecal leakage. This is distressing to the new stoma patient.

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A technique is described by which colony formation in agarose may be rapidly and reproducibly determined with the use of a modified Coulter particle counter (CPC). The cloning efficiency of RD human rhabdomyosarcoma cells after exposure to vincristine sulfate or cisplatin has been compared with the CPC method or by conventional visual counting. These techniques give very similar results.

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Buddleja species play a minor role in the ethnopharmacology of several areas of the world where they are indigenous. Phytochemical investigation of the genus has been somewhat neglected but a picture is emerging of the type of constituents which are present in reasonable quantities, namely iridoid and flavonoid glycosides. Many of the uses of Buddleja in folk medicine such as a topical antiseptic and a diuretic can be partially explained at least by the known biological activity of compounds identical or similar to those found in the genus.

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A laboratory model of childhood rhabdomyosarcoma (RMS) has been used to evaluate cytotoxic agents used in current clinical protocols, and DNA-reacting agents that have had either limited or no evaluation in this histiotype. Seven lines of RMS each derived from a different patient were grown as xenografts in immune-deprived mice, six of these being from specimens derived from previously untreated patients. Of the 'conventional' agents, vincristine was the most effective.

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The determinants of intrinsic sensitivity to Vinca alkaloids in vivo were examined in 3 pediatric rhabdomyosarcoma xenografts maintained s.c. in immune-deprived mice.

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The evolution of an intensive care facility in a District General Hospital is recorded. Optimum use of the Unit was achieved by accepting both critically ill and high dependency care patients. This has been of benefit to both the staff and patients and may be reflected in the falling mortality of the critically ill surgical patient.

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A method for extracting from biological tissues vincristine, vinblastine, and their metabolites and analysis by high-performance liquid chromatography has been developed. After excision tissues are rapidly frozen in liquid nitrogen (less than 10 s) and powders are made under liquid N2. Extraction of blood, plasma, or tissue powders was achieved using ethanol (95%) acidified to pH 4.

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Hypoxanthine (Hx) and allopurinol (HPP) have been shown experimentally to reduce the conversion of 5-fluorouracil (FUra) to FUMP by orotate phosphoribosyltransferase (OPRTase). This study was designed to elucidate the major pathway by which FU ra was metabolized to ribonucleotides by human colorectal tumors. Consequently, the effect of Hx and HPP on the metabolism of [6-3H]-FUra was examined in 5 human colorectal adenocarcinomas maintained as xenografts in immune-deprived mice.

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This study was designed to examine the possibilities for increasing the therapeutic index in the treatment of human colon adenocarcinomas maintained as xenografts in immune-deprived mice using combinations of methotrexate (MTX) that preceded 5-fluorouracil (FUra). MTX, at a dose level of 100 mg/kg, increased the 5-phosphoribosyl-1-pyrophosphate (PRPP) concentration in three colon xenograft lines to a maximum between 14 and 24 hr after treatment. In murine bone marrow, concentrations of PRPP decreased progressively after MTX treatment, but in ileum there was a dramatic increase such that by 4 hr PRPP was 968% of control.

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