Search PubMed⌕ Search

Biomedical subjects

W J Martin

Publications and source records attributed to W J Martin.

At least 163 records · Page 9Linked to original sources
PubMed1985

Pharmacokinetics and pharmacodynamics of cimetidine and metabolites in critically ill children.

Cimetidine and antacids are the mainstays of therapy for the prophylaxis of stress-induced ulceration in critically ill children. Previous cimetidine dosing recommendations have been empiric because of a lack of knowledge about cimetidine disposition kinetics in children. Thirty children, mean age 9 +/- 3.2 years, were admitted to the study with the following primary diagnoses: closed head injury (23 patients), sepsis (four), gunshot wound (two), and bleeding gastric ulceration (one). The mean dose of cimetidine was 26 mg/kg/day, administered intravenously over 15 minutes in four divided doses. Cimetidine disposition was best described by a biphasic elimination curve with t1/2 values for cimetidine, cimetidine sulfoxide, and hydroxymethyl cimetidine of 1.39, 2.6, and 4.7 hours, respectively. Cimetidine plasma concentrations were maintained at greater than or equal to 0.5 microgram/ml for a significantly longer time in patients who received greater than or equal to 20 mg/kg/day. Most patients had a plasma cimetidine concentration below 0.5 to 1.0 microgram/ml 4 hours after infusion. The mean apparent volume of distribution and total body clearance for cimetidine were 1.23 L/kg and 10.4 ml/min/kg, respectively. A significant correlation was found between age and either apparent volume of distribution (r = 0.76, P less than 0.001) or total body clearance (r = 0.75, P less than 0.001). No significant correlation between cimetidine concentrations in either plasma or gastric juice and gastric pH could be determined. However, seven of nine patients who received only cimetidine had a gastric pH of greater than or equal to 4 at 2 hours after infusion when the plasma cimetidine concentration was greater than or equal to 1.0 or the gastric juice concentration was greater than or equal to 2.0 microgram/ml. The mean gastric pH was 2.2 at 6 hours, when plasma and gastric juice concentrations of cimetidine were greater than or equal to 1.0 microgram/ml. On the basis of our data, a cimetidine dosage of 20 to 30 mg/kg/day administered in six divided doses should provide for average steady-state plasma cimetidine concentrations of 1.3 to 2.0 micrograms/ml.

Adolescent↗
PubMed1985

Clinical evaluation of the Lumac bioluminescence method for screening urine specimens.

A bioluminescence method for screening urine cultures to provide rapid reporting of negative specimens and to select appropriate urine cultures for direct application of automated identification methods was evaluated. A total of 2,000 specimens were processed in the Lumac Biocounter (3M, St. Paul, Minn.), and the results were compared with quantitative culture techniques by using a 0.001-ml inoculating loop. A total of 841 specimens were positive by the bioluminescence method; 291 specimens were culture positive (greater than or equal to 50,000 CFU of one or two organisms per ml). Positive cultures represented more than 20 different organisms. Approximately two-thirds of the false-positive results represented mixed flora or pure cultures of less than 5 X 10(4) organisms per ml. The predictive value of a negative result was 98.4%, reflecting a false-negative rate of only 0.7%. No advantages in cost or technician time were noted, but the Lumac method appears to be a useful technique in decreasing reporting time, especially for negative urine cultures.

Bacteriuria↗
PubMed1985

Reduction of neutrophil-mediated injury to pulmonary endothelial cells by dapsone.

The presence of activated neutrophils in the alveolar structures is thought to contribute to parenchymal cell injury in various acute and chronic lung disorders. This study indicates that dapsone (30 micrograms/ml), an agent with anti-inflammatory properties, can significantly reduce neutrophil-mediated injury to 51Cr-labeled bovine pulmonary artery endothelial (BPAE) cells with a reduction in the injury (expressed as a cytotoxic index) from 65 +/- 3 to 33 +/- 3 (p less than 0.001). Dapsone was unable to protect 51Cr-labeled BPAE cells injured by the chemical generation of superoxide, hydrogen peroxide, or neutrophil-derived, myeloperoxidase-dependent hypohalite ion. In contrast, dapsone significantly inhibited the respiratory burst of the neutrophil, with a reduction in the generation of superoxide, hydrogen peroxide, and conversion of nitroblue tetrazolium to formazan (p less than 0.01, all comparisons). Thus, dapsone appears to protect lung parenchymal cells such as endothelial cells from neutrophil-mediated injury by directly inhibiting the respiratory burst of the neutrophil, with a consequent diminution in the generation of toxic, oxygen-derived radicals.

Animals↗
PubMed1985

The pharmacokinetics of cimetidine and metabolites in a neonate.

Limited pharmacokinetic data have been reported concerning the use of cimetidine in the neonate for the management of gastrointestinal hemorrhage. After receiving cimetidine at a dose of 10 mg/kg/d in a full-term infant, the steady-state peak and four-hour concentrations were 3.5 and 1.8 micrograms/ml, respectively. A mean half-life of 3.6 h for cimetidine and 2.2 h for cimetidine sulfoxide were determined. The cimetidine half-life was prolonged, and the total body clearance decreased as compared with values reported in critically ill children and adults.

Biotransformation↗
PubMed1985

Amiodarone pulmonary toxicity. Assessment by bronchoalveolar lavage.

Bronchoalveolar lavage was used to demonstrate morphologic changes in alveolar macrophages characteristic of amiodarone effect in lung tissue obtained by biopsy. This procedure may be useful in the assessment of abnormal chest x-ray findings in patients suspected to have amiodarone toxicity.

Amiodarone↗
PubMed1985

Nitrofurantoin-stimulated oxidant production in pulmonary endothelial cells.

Nitrofurantoin, a urinary antiseptic, is associated with significant pulmonary toxicity. Our study indicates that nitrofurantoin may produce lung injury by directly stimulating lung parenchymal cells to generate toxic oxygen species such as superoxide and hydrogen peroxide, which can overwhelm cellular antioxidant defenses and result in permanent injury to the cells. Nitrofurantoin (10(-3) mol/L) stimulates bovine pulmonary artery endothelial cells to release 3.7 +/- 0.4 mumol/L superoxide per 10(5) cells and 4.4 +/- 0.5 mumol/L hydrogen peroxide per 10(5) cells (p less than 0.001 compared with endothelial cells without nitrofurantoin). Endothelial cells treated with nitroblue tetrazolium, a yellow dye reduced by superoxide to insoluble blue formazan, can be monitored both spectrophotometrically and morphologically. Nitrofurantoin (10(-5), 10(-4), and 10(-3) mol/L) stimulated pulmonary endothelial cells to reduce nitroblue tetrazolium monitored spectrophotometrically as 0.022 +/- 0.001, 0.032 +/- 0.002, and 0.071 +/- 0.004 delta A515 per 10(5) cells per hour, respectively (p less than 0.001, comparison of cells with 10(-4) and 10(-3) mol/L nitrofurantoin vs. control cells. From the same dose-response curve, endothelial cells incubated with nitrofurantoin morphologically demonstrated formazan granules in the cytoplasm in 17% +/- 6%, 71% +/- 9%, and 92% +/- 5% of cells. Nitrofurantoin (10(-5), 10(-4), and 10(-3) mol/L) directly injures 51Cr-labeled pulmonary endothelial cells, with injury expressed as a cytotoxic index of 1 +/- 1, 20 +/- 4, and 51 +/- 3, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Amiodarone-induced lung toxicity. In vitro evidence for the direct toxicity of the drug.

Amiodarone, a new antiarrhythmic agent, is associated with serious lung toxicity. This study indicates that in vitro amiodarone can directly induce bovine pulmonary artery endothelial cells to form cytoplasmic lamellar inclusions characteristic of the lung biopsy findings described in vivo. These morphologic changes occur as soon as 4 hours after incubation with the drug and with as little as 1 microgram/ml (within the therapeutic range). Amiodarone-induced endothelial cell injury, monitored by 51Cr release, occurs with as little as 10-20 micrograms/ml. The data suggest that amiodarone toxicity to the lung may be primarily related to its direct toxic effect on lung cells, and that the characteristic morphologic changes of cytoplasmic inclusions may represent an early sign of the drug's effect.

Amiodarone↗
PubMed1985

Stability of morphine sulfate and meperidine hydrochloride in a parenteral nutrient formulation.

The compatibility, stability, and availability of morphine sulfate and meperidine hydrochloride prepared in total parenteral nutrient (TPN) solution, 5% dextrose injection, and sterile water for injection in polyvinyl chloride (PVC) bags were evaluated. A 300-mg dose of each narcotic was mixed in 0.25-L bags of 5% dextrose injection and sterile water for injection, and in 3-L bags of TPN and sterile water for injection. Each solution was examined visually for precipitation, color change, turbidity, and the evolution of gas immediately after the addition of the drug to the bag and every 12 hours for a 36-hour period. Narcotic concentrations in each solution were determined by high-pressure liquid chromatography before and for 36 hours after the addition of the drugs to the bags. No loss of either drug because of adsorption to the PVC bags was found. Morphine sulfate and meperidine hydrochloride were chemically compatible and stable in TPN and 5% dextrose injection for 36 hours. Solutions of morphine sulfate or meperidine hydrochloride in PVC bags containing TPN or 5% dextrose injection are visually and chemically compatible, as well as stable and available for 36 hours when stored at 21.5 degrees C with no protection from environmental light.

Chemistry, Pharmaceutical↗
PubMed1984

Intravenous tubing with burettes can be safely changed at 48-hour intervals.

No studies of safety in changing intravenous systems containing in-line burettes at 48 hours in an intensive care setting have been performed. Patients entering a surgical intensive care unit were alternatively assigned to have any line with an in-line burette changed at either 24-hour (64 patients) or 48-hour (59 patients) intervals. Daily quantitative cultures with a 2-mL aliquot of burette fluid were obtained. Contaminated burette fluid was detected in nine of 452 (2.0%; 95% confidence interval, 0.7% to 3.3%) samples from 24-hour interval burettes and in nine of 224 (4.0%; 95% confidence interval, 1.4% to 6.6%) samples from 48-hour interval burettes. Bacterial contamination of burette fluid with ten or more colonies per milliliter occurred in only five (1.1%) cultures from patients in the 24-hour interval group compared with only two cultures (0.9%) in the 48-hour group. None of the contaminated burette fluids was associated with primary bacteremia. Change of in-line burettes in intensive care at 48-hour intervals is safe and should result in substantial cost savings.

Bacteria↗
PubMed1984

Clinical evaluation of the improved streptex method for grouping streptococci.

The improved Streptex method for serogrouping streptococci incorporates a new extraction enzyme and a simplified procedure requiring no centrifugation. A total of 114 clinical isolates of beta-hemolytic streptococci were serogrouped from primary plates, isolation plates, and Todd-Hewitt broth cultures using this system. Results were compared to those of the heat extraction Lancefield precipitin method. An additional 33 stock culture isolates of related streptococcal species and 5 strains of Listeria were serogrouped to assess the specificity of the test. Agreement between the two methods was 82.5% with primary plates and 96.5% with both isolation plates and broth cultures. Four isolates from three different serogroups were nongroupable by the Lancefield method, but did agglutinate in specific Streptex antisera; therefore, the enzyme extraction procedure appeared more sensitive than the heat extraction method. Streptex accurately grouped five isolates of gamma-hemolytic group B streptococci, but failed to detect antigen in 33% of the group D streptococcal extracts tested. In addition, cross-reactions were observed with strains of alpha-hemolytic streptococci. Streptex produced fewer ambiguous results and required fewer repeat tests. When used with isolation plates or broth cultures, Streptex is both sensitive and specific for the grouping of beta-hemolytic streptococci of groups A, B, C, F, and G.

Evaluation Studies as Topic↗
PubMed1984

Comparison of media for isolation of Ureaplasma urealyticum and genital Mycoplasma species.

A total of 484 frozen patient specimens originally positive for Ureaplasma urealyticum or Mycoplasma spp. or both were recultured, and the results were compared on the following media: Shepard's A7 agar, modified phenol red-urea, SP-4-urea, modified phenol red-arginine, and SP-4-arginine broths. Of 351 specimens positive for U. urealyticum, 30 (8.5%) were detected only in one or more of the broth media, whereas 117 (33%) were positive only on A7 agar. Separate use of the SP-4-urea broth or modified phenol red-urea broth isolated all but 1 and 2, respectively, of the negative A7 agar cultures. Of the 76 specimens positive for large colony Mycoplasma spp., 58 (76.3%) were not grown on the primary plating (A7) agar. Of 73 broth isolates, 73 (100%) grew in SP-4-arginine broth, and 64 (87.7%) grew in modified phenol red-arginine broth. Modified SP-4 broth appears to be a useful supplement to the A7 plating medium commonly used in the diagnostic laboratory for the isolation of U. urealyticum and Mycoplasma spp.

Culture Media↗
PubMed1984

Paraquat-induced injury of type II alveolar cells. An in vitro model of oxidant injury.

Paraquat, a widely used herbicide, causes severe, often fatal lung damage. In vivo studies suggest the alveolar epithelial cells (types I and II) are specific targets of paraquat toxicity. This study used 51Cr-labeled type II cells to demonstrate that paraquat (10-5 M) resulted in type II cell injury in vitro, independent of interacting immune effector agents. With 51Cr release expressed as the cytotoxic index (Cl), type II cell injury was found to accelerate with increasing paraquat concentrations (10(-5) M, 10(-4) M, and 10(-3) M, resulting in a Cl of 12.5 +/- 2.2, 22.8 +/- 1.8, and 35.1 +/- 1.9, respectively). Paraquat-induced cytotoxicity (10(-4) M, with a Cl of 22.8 +/- 1.8) was effectively reduced by catalase 1,100 U/ml (Cl 8.0 +/- 3.2, p less than 0.001), superoxide dismutase, 300 U/ml (Cl 17.4 +/- 1.7, p less than 0.05), alpha tocopherol, 10 micrograms/ml (Cl 17.8 +/- 1.6, p less than 0.05). Paraquat toxicity (10(-3) M) was potentiated in the presence of 95% O2 with an increase in Cl from 31.1 +/- 1.7 to 36.4 +/- 2.3 (p less than 0.05). Paraquat-induced type II cell injury was noted as early as 4 h incubation by electron microscopic evidence of swelling of mitochondrial cristae and dispersion of nuclear chromatin. Thus, this in vitro model indicates that paraquat-induced type II cell injury can be quantified, confirmed by morphologic ultrastructural changes, significantly reduced by antioxidants, and potentiated by hyperoxia.

Animals↗
PubMed1984

Neutrophils kill pulmonary endothelial cells by a hydrogen-peroxide-dependent pathway. An in vitro model of neutrophil-mediated lung injury.

Neutrophil-mediated injury to lung parenchymal cells has been proposed as an important step in the pathogenesis of many acute and chronic lung disorders. As an in vitro model of neutrophil-mediated injury, this study used activated human neutrophils as effector cells in an 18-h cytotoxicity assay with 51Cr-labeled bovine pulmonary artery endothelial cells serving as target cells. Neutrophils effectively injured pulmonary endothelial cells, expressed as cytotoxic index (CI), of 63.8 +/- 5.4, and this injury could be significantly reduced by several agents, including 1% dimethyl sulfoxide (CI, 51.3 +/- 3.7), 50 micrograms/ml ascorbic acid (CI, 40.8 +/- 4.7), and especially 1,100 U/ml catalase (CI, 14.3 +/- 4.1). As cell-free models of neutrophil-mediated endothelial cell injury, H2O2 (30 microM), O2- (generated by 0.5 mU xanthine oxidase), and the myeloperoxidase-dependent (0.32 U) hypohalite ion were each capable of injuring the target cells with CI of 6.21 +/- 2.8, 53.6 +/- 5.3, and 21.2 +/- 1.5, respectively. Catalase was effective in reducing the injurious effect of each of these oxidant-generating systems (p less than 0.01, all comparisons), confirming the important role for H2O2 in the mediation of this injury. The data indicate that neutrophils are capable of killing pulmonary endothelial cells by a pathway largely dependent on the generation of H2O2, and suggest the possibility that removal of H2O2 from the alveolar structures in subjects with these disorder might be an effective future therapeutic approach.

Animals↗