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Biomedical subjects

W J Adams

Publications and source records attributed to W J Adams.

At least 55 records · Page 3Linked to original sources
PubMed1993

The growth of carcinogen-induced colon cancer in rats is inhibited by cimetidine.

Colon cancer was induced in 40 Sprague Dawley rats using a 10-week course of 1,2 dimethylhydrazine (DMH). Twenty animals received cimetidine in their drinking water, commencing 5 weeks after concluding the course of DMH. After five weeks treatment of the animals were sacrificed and the colon and rectum excised. Tumours were assessed histologically for depth of invasion, inflammatory cell response and stained for Proliferating Cell Nuclear Antigen (PCNA), as a measure of tumour proliferative index. PCNA staining was measured using a computerized image analysis system. There were 25 tumours in the cimetidine treated group and 20 in controls. In the control group, 10% of the tumours were benign, 35% malignant polyps, 40% invading through submucosa and 15% invading through the bowel wall, as opposed to 40%, 44%, 8% and 8%, respectively in the cimetidine group (Chi squared test: P = 0.002). The mean proliferative index for control tumours was 27.9% and for the cimetidine tumours 23.1% t test: P = 0.002). It is concluded that cimetidine inhibits colon cancer cellular proliferation and slows early tumour invasion in this animal model.

1,2-Dimethylhydrazine↗
PubMed1992

Hartmann's procedure for carcinoma of the rectum and sigmoid colon.

A review of the Hartmann's operation for patients with rectal and sigmoid cancer over an 18 year period is presented. There were 1063 patients who had a resection for carcinoma of the rectum or sigmoid colon and 4.4% of these had a Hartmann's procedure. This operation was particularly useful in the management of patients who presented with a proximal obstruction or perforation at the tumour site. It was also effective in the elective treatment of elderly unfit patients who had locally advanced tumours or those with distant metastases. Re-anastomosis is recommended in those patients who are relatively fit and have had a potentially curative resection.

Age Factors↗
PubMed1992

Glyphosate degradation by immobilized bacteria: field studies with industrial wastewater effluent.

Immobilized bacteria have been shown in the laboratory to effectively remove glyphosate from wastewater effluent discharged from an activated sludge treatment system. Bacterial consortia in lab columns maintained a 99% glyphosate-degrading activity (GDA) at a hydraulic residence time of less than 20 min. In this study, a pilot plant (capacity, 45 liters/min) was used for a field demonstration. Initially, activated sludge was enriched for microbes with GDA during a 3-week biocarrier activation period. Wastewater effluent was then spiked with glyphosate and NH4Cl and recycled through the pilot plant column during start-up. Microbes with GDA were enhanced by maintaining the pH at less than 8 and adding yeast extract (less than 10 mg/liter). Once the consortia were stabilized, the column capacity for glyphosate removal was determined in a 60-day continuous-flow study. Waste containing 50 mg of glyphosate per liter was pumped at increasing flow rates until a steady state was reached. A microbial GDA of greater than 90% was achieved at a 10-min hydraulic residence time (144 hydraulic turnovers per day). Additional studies showed that microbes with GDA were recoverable within (i) 5 days of an acid shock and (ii) 3 days after a 21-day dormancy (low-flow, low-maintenance) mode. These results suggest that full-scale use of immobilized bacteria can be a cost-effective and dependable technique for the biotreatment of industrial wastewater.

Biodegradation, Environmental↗
PubMed1992

Glyphosate degradation by immobilized bacteria: laboratory studies showing feasibility for glyphosate removal from waste water.

To evaluate immobilized bacteria technology for the removal of low levels of glyphosate (N-phosphonomethylglycine) from aqueous industrial effluents, microorganisms with glyphosate-degrading activity obtained from a fill and draw enrichment reactor inoculated with activated sludge were first exposed to glyphosate production wastes containing 500-2000 mg glyphosate/L. The microorganisms were then immobilized by adsorption onto a diatomaceous earth biocarrier contained in upflow Plexiglas columns. The columns were aerated, maintained at pH 7.0-8.0, incubated at 25 degrees C, supplemented with NH4NO3 (50 mg/L), and exposed to glyphosate process wastes pumped upflow through the biocarrier. Glyphosate degradation to aminomethylphosphonic acid was initially > 96% for 21 days of operation at flows yielding hydraulic residence times (HRTs) as short as 42 min. Higher flow rate studies showed > 98% removal of 50 mg glyphosate/L from the waste stream could be achieved at a HRT of 23 min. Glyphosate removal of > 99% at a 37-min HRT was achieved under similar conditions with a column inoculated with a pure culture of Pseudomonas sp. strain LBr, a bacterium known to have high glyphosate-degrading activity. After acid shocking (pH 2.8 for 18 h) of a column of immobilized bacteria, glyphosate-degrading activity was regained within 4 days without reinoculation. Although microbial growth and glyphosate degradation were not maintained under low organic nutrient conditions in the laboratory, the low levels of degradable carbon (45-94 mg/L) in the industrial effluent were sufficient to support prolonged glyphosate-degrading activity. The results demonstrated that immobilized bacteria technology is effective in removing low levels of glyphosate in high-volume liquid waste streams.

Bacteria↗
PubMed1991

Volume rendering and connectivity algorithms for MR angiography.

Several display algorithms for three-dimensional angiographic data are evaluated. The mathematical analysis assumes additive Gaussian noise to predict the background distribution function for maximum intensity projection, sum projection, and connectivity display methods. In the maximum intensity projection method the mean noise level increases with the number of voxels in the ray, while in the sum projection the noise distribution width increases with the projection thickness, but the mean level remains constant. Comparisons of maximum intensity projection, sum projection, and connectivity algorithms applied to an MR angiogram of the circle of Willis are made. Measurements of the noise distribution are in agreement with the analysis. Algorithms combining connectivity with maximum intensity and sum projection are also evaluated. In these methods, a projection image is created using only the voxels marked by connectivity, typically with a 6% threshold of the data. Fine vessels are resolved and background noise is reduced in agreement with the analysis.

Algorithms↗
PubMed1991

The Allen Brown shunt: a useful option for vascular access.

This study analyzes the performance of 273 Allen Brown arteriovenous shunts inserted in the thigh and anastomosed to the superficial femoral artery and either the superficial femoral vein or the long saphenous vein. The median duration of shunt function was 9 weeks (range: 0 to 175 weeks). A significantly longer median function time of 22 weeks was found in patients who had had more than five previous access procedures (p less than 0.02). No other independent variable affecting shunt function time was identified. There were 84 complications (56 due to infection) and 2 deaths in the series. The infection rate was not improved by the use of perioperative antibiotics, with most infections occurring more than 6 weeks after insertion. Since the complication rate for Allen Brown shunts was no greater than that reported for subclavian catheters, and their function no less reliable than that reported for Quinton-Scribner shunts, the Allen Brown shunt is a useful option for short- and medium-term vascular access. It may also be useful for longer-term access in the patient in whom failure of multiple previous access procedures has occurred.

Adolescent↗
PubMed1991

Wound infiltration with 0.25% bupivacaine not effective for postoperative analgesia after cholecystectomy.

The instillation of local anaesthetic agents into surgical wounds has been reported to be an effective method of reducing pain and narcotic requirements, using both local injection and topical application techniques. We performed a double-blind trial to test the value of the long-acting local anaesthetic, bupivacaine, in this role. Eighty patients undergoing elective cholecystectomy were entered into the study. They were divided into 2 groups of 40 patients to compare a local injection technique with a topical application technique. For each route of application, 20 patients received a test solution containing 0.25% plain bupivacaine, and 20 received 0.9% NaCl as a control. Postoperative analgesia in the form of intramuscular pethidine (1-1.5 mg/kg) was made available to all patients on request. The degree of postoperative pain was assessed using three criteria: the time from operation to the first request for analgesia, the total dose of postoperative pethidine required during the first 3 postoperative days and the patient's rating of pain on a 10 cm linear analogue scale at 24 h and 72 h. There was no statistically significant difference between the degree of postoperative pain experienced by patients receiving bupivacaine and those receiving NaCl, when assessed by any criterion. There was also no significant difference found between patients receiving bupivacaine by local infiltration and those receiving the drug topically. It is concluded that the local application of bupivacaine to the wound is not an effective analgesic technique following laparotomy for cholecystectomy.

Administration, Cutaneous↗
PubMed1991

A study of the shape of dose-response curves for acute lethality at low response: a "megadaphnia study".

Dose-response curves were developed for the immobilization response in Daphnia magna to four toxicants. The purpose of this work was to study the effect of the form of the model and the number of concentration levels used on the estimates of typical low-dose effective concentrations (1%, 5%, 10%). The generalized four-parameter logistic model was used as the reference. When using 12 concentration levels, one of the logistic family two- or three-parameter models was shown reliably to represent each of these various sets of dose-response data, and to provide adequate estimates of EC01 and EC05, as well as EC10 and EC50. For two of the toxicants, an asymmetric model was required. When reducing the number of concentrations to five, the EC10 and EC50 were well estimated by the probit model, with acceptable results at the EC05 level.

Animals↗
PubMed1990

Influence of H2 receptor antagonists on the disposition of flurbiprofen enantiomers.

The effect of oral cimetidine or ranitidine on the pharmacokinetics of the R and S enantiomers of the nonsteroidal anti-inflammatory drug flurbiprofen and its major metabolite, 4'-hydroxyflurbiprofen, was evaluated. Nine healthy volunteers participated in a randomized crossover design study with the following treatments: (A) flurbiprofen 200 mg; (B) flurbiprofen 200 mg plus ranitidine 150 mg bid for 7 days before and for 2 days after receiving flurbiprofen and (C) flurbiprofen 200 mg plus cimetidine 300 mg qid for 7 days before and for 2 days after receiving flurbiprofen. Blood and urine samples were collected at various intervals during a 48-hour period. These samples were assayed stereospecifically for flurbiprofen and its metabolite. Small but statistically significant differences in the terminal elimination rate constant (K), maximum peak serum drug concentration (Cmax), time to reach peak concentration (tmax), oral clearance (Cl/F) and area under the curve (AUC) were noted for flurbiprofen enantiomers. No significant treatment*isomer interactions were observed, indicating that neither cimetidine nor ranitidine interacted stereospecifically with flurbiprofen. Cimetidine, but not ranitidine, resulted in small (less than or equal to 15%) but statistically significant changes in flurbiprofen pharmacokinetic parameters. The interaction between H2-antagonists and flurbiprofen is unlikely to be clinically important.

Adult↗
PubMed1990

HPLC and flow cytometric analyses of uptake of adriamycin and menogaril by monolayers and multicell spheroids.

We have used both HPLC and flow cytometry to measure and compare the uptake of two anthracyclines, menogaril (MEN) and Adriamycin (ADR), in V79 Chinese hamster lung fibroblasts grown as monolayers and as 650 microns multicell spheroids. In order to compare intracellular drug accumulation in spheroid cells measured by the two methods, we converted mean channel fluorescence of the flow cytometer to drug uptake expressed as ng/10(6) cells by using a standard curve. The standard curve related the flow cytometric mean channel fluorescence, of monolayer cells exposed to either drug, to the intracellular drug accumulation determined by HPLC. This standard curve was then used to convert the mean channel fluorescence of cells from drug-exposed spheroids to ng/10(6) cells. Our results show that equal intracellular drug accumulation (determined by HPLC) in spheroids and monolayers does not result in equal cellular fluorescence emission (determined by flow cytometry) by these 2 cell populations. For example, monolayer cells with an intracellular MEN accumulation of 650 ng/10(6) cells, emit 40 units of fluorescence as measured by flow cytometry. However, spheroid cells with the same intracellular accumulation emit about 80 units of fluorescence. This results in the intracellular MEN uptake in spheroids measured by flow cytometry being as much as 2- to 3-fold higher than that measured by HPLC. Intracellular ADR accumulation measured by flow cytometry was also higher than that obtained by HPLC. In spite of the quantitative difference between the two methods, qualitatively both methods gave similar results. Thus, both techniques showed that at equal drug concentration in medium drug uptake in monolayers was much greater than in spheroids.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Biodegradation of p-nitrophenol in an aqueous waste stream by immobilized bacteria.

Microbiological analyses of activated sludge reactors after repeated exposure to 100 mg of p-nitrophenol (PNP) per liter resulted in the isolation of three Pseudomonas species able to utilize PNP as a sole source of carbon and energy. Cell suspensions of the three Pseudomonas sp., designated PNP1, PNP2, and PNP3, mineralized 70, 60, and 45% of a 70-mg/liter dose of PNP in 24, 48, and 96 h, respectively. Mass-balance analyses of PNP residues for all three cultures showed that undegraded PNP was less than 1% (less than 50 micrograms); volatile metabolites, less than 1%; cell residues, 8.4 to 14.9%; and water-soluble metabolites, 1.2 to 6.7%. A mixed culture of all three PNP-degrading Pseudomonas sp. was immobilized by adsorption onto diatomaceous earth biocarrier in a 1.75-liter Plexiglas column. The column was aerated and exposed to a synthetic waste stream containing 629 to 2,513 mg of PNP per liter at flow rates of 2 to 15 ml/min. Chemical loading studies showed that the threshold concentration for acute toxicity of PNP to the immobilized bacteria was 2,100 to 2,500 mg/liter. Further studies at PNP concentrations of 1,200 to 1,800 mg/liter showed that greater than 99 and 91 to 99% removal of PNP was achieved by immobilized bacteria at flow rates of 10 and 12 ml/min, respectively. These values represent hydraulic retention times of 48 to 58 min and PNP removal rates of 0.99 to 1.1 mg/h per g of biocarrier at 25 degrees C under optimal conditions. This study shows the successful use of immobilized bacteria technology to remove high concentrations of PNP from aqueous waste streams.

Adsorption↗
PubMed1989

Pharmacokinetics and systemic bioavailability of menogaril, an anthracycline antitumor agent, in the mouse, dog, and monkey.

Menogaril is an antitumor agent of the anthracycline type which is less cardiotoxic than doxorubicin in a chronic rabbit model and is active in experimental tumor systems when given by p.o. or parenteral routes. It is currently undergoing i.v. and p.o. Phase II clinical evaluation. We report here the results of pharmacokinetic and systemic bioavailability studies of menogaril in three species (mouse, dog, and monkey). Upon i.v. administration, menogaril plasma concentration-time curves declined in a biexponential (dog) or triexponential (mouse and monkey) manner, with the terminal disposition half-life (t1/2) being considerably shorter in the dog (2.86 +/- 0.47 h) than in the mouse and monkey (21.6 and 19.0 +/- 3.7 h, respectively). The systemic clearance (CL, in liters/h/kg) was highest in mouse (6.2), followed by dog (2.9) and then monkey (1.4). The drug was extensively distributed in all three species, with steady state volumes of distribution being 88.5, 9.8, and 27.9 liters/kg in the mouse, dog, and monkey, respectively. One, two, and three metabolites were detected in the plasma of mice, monkeys, and dogs, respectively, using reverse phase high performance liquid chromatography. The major fluorescent metabolite in all species coeluted with authentic N-demethyl-menogaril; the other two metabolites were present at low concentrations relative to unchanged menogaril and its putative N-demethylated metabolite. One of these metabolites, which was found in both the dog and monkey, eluted with authentic (7R)-nogarol. Mean maximum plasma concentrations of the putative N-demethylmenogaril metabolite were approximately one-tenth those of menogaril in all three species following i.v. drug administration. Upon p.o. treatment, first-pass metabolism or incomplete absorption reduced the systemic bioavailability to 12% in the dog and 33% in the mouse and monkey. N-Demethylmenogaril was the major fluorescent metabolite observed in the plasma of p.o. treated animals. Interspecies comparison of menogaril pharmacokinetic parameters in mice, dogs, monkeys, and humans using allometric techniques indicated that the parameters for mice, monkeys, and humans were highly correlated; in each of these species presystemic metabolism of p.o. administered menogaril reduced its systemic bioavailability to an equivalent extent (30-35%). To determine if metabolically formed N-demethylmenogaril might contribute to the overall antitumor activity of menogaril, we determined the effect of synthetic N-demethylmenogaril on the life span of mice bearing P388 leukemia. Results indicated that the metabolite is marginally active compared to menogaril itself.

Administration, Oral↗
PubMed1989

Quantitative determination of itazigrel in rodent diet by reversed-phase HPLC and evaluation of its stability at 20 degrees C.

A simple, accurate and precise procedure for the quantitation of itazigrel (a potent lipophilic inhibitor of collagen and arachidonic acid-induced aggregation being studied for its effects on peripheral vascular disease) from granulated rodent diet is presented. The drug was extracted from rodent diet using methanol + water (80:20) following dissolution of the diet in water. Samples of the supernatant were injected into the HPLC and the eluent was monitored with a fluorescent detector (lambda ex = 320 and lambda em = 430) to achieve analytical specificity. Interday coefficients of variation of the calibration curve slope were +/- 6% on standards between 0 and 1000 micrograms/g. Potency and homogeneity of the drug spiked diet prepared over a 1 year interval at 70, 200 and 600 micrograms/g was 99.3 +/- 2.5%, 100 +/- 1.8%, and 101 +/- 1.9% of label, respectively. Samples prepared for chromatography were stable for 24 h at 20 degrees C, and drug in diet was stable for 102 days when protected from light and stored at 20 degrees C.

Animal Feed↗
PubMed1989

Acute toxicity and urinary excretion of diphenyldiselenide.

The acute toxicity of diphenyldiselenide (DPDS) in the male Swiss mouse was found to be enhanced by pretreatment with phenobarbital of SKF-525A. DPDS decreased hepatic glutathione content by 50% at 1 h after administration. Following administration of 14C-DPDS, labelled metabolites were found in urine but not in bile or feces. Analysis of the urinary metabolites of 14C-DPDS showed that selenium-containing metabolites elute from a DEAE-Sephadex column in two fractions: the first has not been chemically characterized, while the second peak contained the glucuronide conjugates of C6H4(OH)SeH and C6H5SeH. Virtually all of the administered selenium is excreted within 5 days, while only about 36% of the 14C is excreted in the same time period. This discrepancy indicates metabolic scission of the carbon-selenium bond.

Animals↗
PubMed1989

Pharmacokinetics of intravenously administered cefmetazole and cefoxitin and effects of probenecid on cefmetazole elimination.

Sixteen healthy male volunteers participated in a randomized, balanced, three-way crossover study comparing the pharmacokinetics of cefmetazole, cefoxitin, and cefmetazole with probenecid pretreatment. Single 2-g doses of cefmetazole sodium and cefoxitin sodium were given intravenously as a 5-min infusion. Concentrations of cefmetazole and cefoxitin were determined by using a specific semiautomated high-performance liquid chromatographic method. Concentration-time profiles of cefmetazole and cefoxitin declined in a biexponential manner from peak levels. Compared with cefoxitin, cefmetazole had a significantly (P less than 0.05) higher mean (+/- standard error of the mean) peak concentration in serum (290 +/- 11 versus 244 +/- 10 micrograms/ml), a longer terminal disposition half-life (1.50 +/- 0.14 versus 0.81 +/- 0.04 h), lower systemic clearance (111.7 +/- 4.7 versus 279 +/- 12 ml/min) and renal clearance (78.7 +/- 4.3 versus 221 +/- 14 ml/min) of intact drug, and a slightly smaller steady-state volume of distribution (10.3 +/- 0.21 versus 12.8 +/- 0.48 liters). Mean recoveries of cefmetazole and cefoxitin in urine were approximately 71 and 77%, respectively. Pretreatment of volunteers with probenecid (1 g orally) significantly (P less than 0.05) increased concentrations of cefmetazole in serum 1 h after drug administration without significantly increasing maximum concentrations in serum. Mean areas under the concentration-time curve (466 +/- 27 versus 295 +/- 13 micrograms.h/ml) and terminal disposition half-lives (2.27 +/- 0.13 versus 1.50 +/- 0.14 h) of cefmetazole increased. Systemic clearance (72.1 +/- 4.0 versus 111.7 +/- 4.7 ml/min) and renal clearance (47.4 +/- 4.0 versus 78.7 +/- 4.3 ml/min) of intact antibiotic decreased. Mean recoveries (65.9 +/- 3.7 versus 71.0 +/- 3.2%) of intact cefmetazole in urine were not significantly (P > 0.05) different. Elimination of cefmetazole in urine was also significantly prolonged by probenecid, with substantial concentrations of cefmetazole (>/= 20 micrograms/ml) found in the 12- to 24-h urine collection for 14 to 16 volunteers. The results show that cefmetazole remains at clinically relevant concentrations (1 to 2 micrograms/ml) approximately twice as long as cefoxitin, that serum cefmetazole can be maintained longer at clinically significant concentrations with preadministration of probenecid, and that cefmetazole is partially eliminated by renal tubule secretion.

Adult↗
PubMed1989

Pharmacokinetics of single-dose cefmetazole following intramuscular administration of cefmetazole sodium to healthy male volunteers.

The tolerance and pharmacokinetics of cefmetazole were studied in healthy male volunteers who received a placebo (sterile saline) or a single dose of cefmetazole sodium intramuscularly. Drug-treated volunteers received one of four doses, 0.375, 0.750, 1, or 2 g. The drug was well tolerated, with no adverse medical events or laboratory changes observed during the study that could affect the pharmacokinetic interpretation of the data. Cefmetazole concentrations were determined by using a specific high-performance liquid chromatographic method. Serum cefmetazole concentrations were well described by a one-compartment open model with first-order absorption and elimination. Cefmetazole was rapidly absorbed in most volunteers, with a mean time to maximum concentration in serum of 1.24 +/- 0.12 h (+/- standard error of the mean), and the mean maximum concentration in serum increased from 17.0 +/- 1.6 to 74.2 +/- 9.5 micrograms/ml over the 0.375- to 2-g dose range. Maximum concentrations in serum, areas under serum concentration-time curve, and urinary excretion of intact drug increased in proportion to cefmetazole sodium dose. Times at which maximum concentrations in serum occurred, apparent volumes of distribution, steady-state volumes of distribution, absorption and elimination half-lives, and systemic clearances did not change significantly (P greater than 0.05) with drug dose. Although absorption and elimination half-lives were not significantly different in 10 of 40 volunteers (P greater than 0.05), in a majority of subjects elimination half-lives were approximately 10 times longer than absorption half-lives. The mean recovery of intact drug in urine ranged from 68.8 to 86.0% over the dose range studied, with a mean recovery over all doses of 77.1 +/- 2.4%. Rental clearances were significantly lower (P < 0.05) for the two lowest doses (93.0 and 84.3 versus 115.0 and 118.0 ml/min); these differences are not considered clinically important. The results of this study indicate that cefmetazole pharmacokinetics are linear after administration of single intramuscular doses ranging from 0.375 to 2 g, that clinically relevant concentrations of cefmetazole in serum (1 to 2 micrograms/ml) persist in a majority of volunteers for more than 8 h after administration of 0.750-g or higher doses, and that clinically relevant concentrations of cefmetazole continue to be excreted in urine 8 to 12 h after administration of 0.375- to 2-g doses.

Adolescent↗