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Biomedical subjects

C R Martin

Publications and source records attributed to C R Martin.

At least 37 records · Page 2Linked to original sources

Ventilation-perfusion relationships in preterm infants after surfactant treatment.

Arterial-alveolar partial pressure differences for oxygen, carbon dioxide, and nitrogen were measured before and after surfactant replacement therapy on 15 occasions in 14 ventilator-dependent preterm infants with hyaline membrane disease (HMD). Eight treatments resulted in a significant improvement in arterial partial pressure of oxygen (PaO2) 2 hr after treatment; 7 did not. Neither group showed any significant change in arterial-alveolar partial pressure differences for oxygen, nitrogen, and carbon dioxide. This observation suggests that if surfactant replacement therapy produces an improvement in PaO2 it does so by recruitment of atelectatic alveoli with a balanced ventilation/perfusion ratio rather than by redistribution of ventilation within already ventilated alveoli.

Biological Products↗

Developmental genetic studies of the moss, Physcomitrella patens.

The development of the haploid gametophyte stage of Physcomitrella patens presents excellent opportunities for the detailed study of plant morphogenesis at the cellular level. The filamentous protonema undergoes a number of developmental transitions that can be observed directly in living material using time-lapse video microscopy and that can be manipulated both by treatment with phytohormones and by environmental stimuli. Mutants affecting these processes can be isolated and can be analysed using conventional as well as parasexual methods. Molecular biological techniques are now being established since these will be essential if the mechanisms that bring about morphogenetic processes are to be understood at the molecular level. A technique for genetic transformation has been devised and is being exploited to attempt to tag developmentally-relevant genes using maize transposons. Changes in gene activity associated with developmental transitions and in response to treatment with phytohormones and environmental stimuli are being studied using cDNA library subtraction techniques. Heterologous genes involved in the control of transcription and of the cell cycle are being used to probe the P. patens genome to identify possible homologues involved in developmental regulation.

Cytokinins↗

Cerebrospinal fluid content of manganese, platinum, and strontium in patients with cerebral tumors, leukemia, and other noncerebral neoplasms.

Electrothermal atomic absorption spectrophotometry was employed to measure the concentrations of manganese, platinum, and strontium in the cerebrospinal fluid (CSF) of 47 patients with brain neoplasms (34 benign and 13 malignant), 17 leukemic patients, 10 patients with lymphoma or non-cerebral solid tumors, and 27 control patients. According to the data obtained, manganese appears to be significantly (p less than 0.015) depleted from the CSF of leukemic patients, whereas platinum is diminished in CSF of patients with brain tumors, leukemia, lymphoma, or noncerebral solid tumors; the ratios for the mean CSF concentration of platinum in these tumor patients/control patients ranged between 0.52 and 0.7. There was no significant difference in CSF concentrations of strontium among the groups examined.

Adolescent↗

Functional reconstitution of the bovine brain GABAA receptor from solubilized components.

The GABAA/benzodiazepine receptor has been solubilized from membrane preparations of bovine cerebral cortex and has been reconstituted, in a functionally active form, into phospholipid vesicles. In preliminary experiments, the receptor was labeled with the photoactive benzodiazepine [3H]flunitrazepam prior to solubilization. A peptide of apparent molecular weight 53,500 was specifically labeled by this method, and this was used as a marker for the receptor during the reconstitution procedures. The labeled protein was solubilized with approximately 40% efficiency by 1% beta-octyl glucoside. Reconstitution was achieved by mixing the solubilized proteins with a 4:1 mixture of soybean asolectin and bovine brain phospholipids, followed by chromatography on Sephadex G-50-80 to remove detergent. The incorporation of the GABAA receptor into membrane vesicles has been verified by sucrose gradient centrifugation in which the [3H]-flunitrazepam-labeled peptide comigrated with [14C]phosphatidylcholine used as a lipid marker. Vesicles prepared without labeled markers retained the ability to bind both [3H]flunitrazepam and the GABA analogue [3H]muscimol. Furthermore, the binding parameters were very similar to those measured using native membrane preparations. A novel fluorescence technique has been used to measure chloride transport mediated by the GABAA receptor in reconstituted vesicles. Chloride influx was rapidly stimulated in the presence of micromolar concentrations of muscimol and was blocked by preincubation of the membranes with muscimol (desensitization). Flux was also blocked by pretreatment with the competitive GABAA receptor blocker bicuculline or with the noncompetitive GABAA receptor antagonist picrotoxin.

Animals↗

Acetylator phenotypes of Saudi Arabians by a simplified caffeine metabolites test.

The authors examined acetylator phenotypes of 296 Saudi subjects of Arabic origin by measuring the molar concentration ratio of two caffeine metabolites, 5-acetylamino-6-formylamino-3-methyluracil (AFMU) and 1-methylxanthine (1MX), using a simplified version of a previously reported high-performance liquid chromatographic method. Spot urine samples were collected from the subjects who regularly drink coffee, tea, or other caffeinated beverages. The subjects were originally from different regions of Saudi Arabia but currently live primarily in the capital city of Riyadh. The day-to-day reproducibility of the molar concentration ratio of AFMU/1MX was established in 14 randomly selected subjects. These metabolites were stable in urine at 4 degrees and -20 degrees, but AFMU was unstable at room temperature (23 degrees). The frequency distribution data indicate that 72.3% of the subjects are of slow acetylator phenotype.

Acetylation↗

Pharmacokinetics of platinum in cancer patients treated with carboplatin in combination with high-dose methotrexate.

The pharmacokinetics of platinum was investigated in 10 cancer patients treated with a 1-hr infusion of 300 mg/m2 of carboplatin which was given 2-4 days after the administration of 100 mg/kg (20-mg/kg bolus and 80-mg/kg intravenous infusion) of methotrexate. Platinum was analyzed in the samples by flameless atomic absorption spectrophotometry. The concentration vs time data for total platinum in plasma followed a two-compartment model and the mean (and SE) values for beta, TBC, Vc, and RC were 0.0827 (0.22) hr-1, 2.355 (0.252) liters/hr . m2, 10.74 (0.62) liters/m2, and 2.405 (0.228) liters/hr . m2, respectively. There was no significant change in the creatinine clearance or TBC with repeated treatment. The ultrafilterable platinum which was measured in the plasma of two patients constituted 82 and 11.3% of the total platinum at 1 and 24 hr, respectively, and the data conformed to the one-compartment model. The mean (SE) values for t 1/2, TBC, and Vd for free platinum were 1.844 (0.208) hr, 4.583 (1.059) liters/hr . m2, and 11.88 (1.45) liters/m2, respectively. The above data are in good agreement with those reported earlier for platinum following the administration of carboplatin as a single agent. These results suggest that high-dose methotrexate therapy, when administered 2-4 days before carboplatin, does not affect the pharmacokinetics of platinum in the plasma.

Adolescent↗

A simplified and rapid test for acetylator phenotyping by use of the peak height ratio of two urinary caffeine metabolites.

We describe a simplified liquid-chromatographic test in which acetylator phenotype is determined by measuring the peak height ratio of two urinary caffeine metabolites, 5-acetylamino-6-formylamino-3-methyluracil and 1-methylxanthine. We applied this test to determine the acetylator phenotypes of 52 subjects who regularly drink coffee, tea, or caffeinated beverages. Also, we determined the acetylator phenotypes of these subjects according to a well-established sulfasalazine test, which yielded identical results. We established the reproducibility of the described test by determining the acetylator phenotypes of 10 additional subjects on two different days separated by a period of two to five weeks. Of the 52 subjects examined by both tests, 40 (76.9%) were classified as slow acetylators, which agrees well with the percentage reported elsewhere for 297 similar subjects from the Saudi population.

Acetylation↗

Capillary gas chromatography and thermionic N-P-specific detection of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in stability and pharmacokinetic studies.

An expedient, rapid, and sensitive capillary gas chromatographic method for the analysis of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in plasma is described. Separation of the underivatized nitrosourea compounds was performed on a 0.33-mm-i.d., 25-m fused-silica, SE-30 capillary column, and detection was carried out using a thermionic N-P-specific detector. The compounds were extracted from plasma with benzene with a yield of greater than 87%. The assay was linear in the ranges of 0.001 to 0.5 and 0.5 to 25 micrograms/ml for CCNU or 0.003 to 0.50 and 0.5 to 25 micrograms/ml for BCNU, with correlation coefficients from 0.9914 to 0.9999 and coefficients of variation (CV) of less than 3.3%. Other antineoplastic agents did not interfere in the assay. The method was employed to study the pharmacokinetics of BCNU in rabbits. The plasma concentration-time curves were fit to a two-compartment model with a mean (SE) alpha, beta, and total-body clearance of 2.898 (0.913) hr-1, 0.1228 (0.0179) hr-1, and 7.211 (2.862) liters/hr.kg, respectively. Further, the stability of BCNU and CCNU in solution was examined at different temperatures. Both compounds were stable in benzene or acetone (4 to 37 degrees C) but labile in plasma even if refrigerated. The apparent rate constants for degradation of BCNU and CCNU were 0.09921 and 0.02853 hr-1 at 4 degrees C and 5.998 and 2.553 hr-1 at 37 degrees C, respectively.

Animals↗

Concentrations of chromium, cesium, and tin in cerebrospinal fluid of patients with brain neoplasms, leukemia or other noncerebral malignancies, and neurological diseases.

We measured the concentrations of chromium, cesium, and tin in the cerebrospinal fluid (CSF) of 29 patients with brain tumors [21 benign (BBT) and eight malignant (MBT)], 28 leukemic patients, 14 patients with lymphoma or noncerebral solid tumors (NLCT), and 32 control patients (15 with neurological disorders and 17 with noneurological conditions) by use of flameless atomic absorption spectrophotometry. We detected chromium in 94% of the patients, tin in 79%, and cesium in 50%. The mean (and SEM) concentrations (micrograms/L) of these metals in the control group were 4.7 (1.1) for chromium, 3.8 (1.6) for cesium, and 6.4 (1) for tin. We observed significant differences (P less than 0.05) in the concentration of chromium in CSF between the MBT group and all other tumor groups; the ratios for the mean CSF concentration of chromium in patients with BBT, leukemia, or NLCT to that in patients with MBT were 2.6, 2.1, or 4.4, respectively. We saw no significant differences in the concentrations of cesium or tin among the various groups investigated.

Adolescent↗

Improved assay for etoposide in plasma by radial-compression liquid chromatography with electrochemical detection.

We describe a rapid, sensitive, and expedient radial-compression liquid-chromatographic method for routine quantification of etoposide (VP-16-213) in plasma of cancer patients undergoing chemotherapy with this agent. Teniposide was used as the internal standard. The mobile phase was a mixture of 10 mmol/L phosphate solution and methanol (50.7/49.3, by vol), adjusted to pH 3 with phosphoric acid. The flow rate was 2 mL/min. We used a 5-micron particle size C18 cartridge with a radial-compression separation system. The effluent was monitored with an electrochemical detector. Plasma samples are extracted with chloroform and the chloroform is evaporated. The residue, reconstituted in mobile phase, is injected onto the cartridge. Assay results were linearly related to concentration (r greater than 0.9944) over the range examined, 0.010-28.0 mg/L. The intra-run CV was less than 4.4%, and we encountered no interference from anticancer drugs or other compounds. We present data for plasma sampled at different intervals from two cancer patients being infused with etoposide.

Adolescent↗

Vitamin D, parathyroid, and thymus gland influences on seasonal variations in renal electrolyte excretion.

Effects of the thymus gland and vitamin D and other calcium-regulating hormones on electrolyte balance were investigated. In studies conducted over 3 successive years male hooded rats excreted more chloride (Cl) and less inorganic phosphate (P) in April-August (summer) than in November-March (winter) when subjected to sham operation (SHAM) or to the surgical procedures described herein and exposed to natural sunlight in temperature- and humidity-controlled rooms. Parathyroidectomy, combined with sham thymectomy (PX), thymectomy (PX-TMX), thyroidectomy-sham thymectomy (TPX), or thyroidectomy-thymectomy (TPX-TMX), significantly increased Cl excretion during both seasons. The same surgical procedures also reduced P excretion in the winter. However, PX and PX-TMX lowered the P values only slightly in summer, and the effects were reversed by thyroid ablation. Thymectomy (TMX), alone or in combination with PX or TPX, increased Cl excretion during the summer, but it did not affect the outputs of winter animals with intact thyroid or parathyroid glands. Vitamin D3 (400 IU) injected three times weekly for 3 weeks increased the Cl excretion of all surgical groups during the winter. In the summer, it increased the Cl excretion of SHAM only, and it diminished the Cl excretion of thyroidectomized rats. Significant increases in P excretion were found only in PX-winter and TMX-summer groups. A vitamin D-deficient diet during the summer resulted in a more than four-fold increase in P excretion in TMX and SHAM rats, and it significantly reduced Cl excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Determination of propranolol in plasma by radial compression liquid chromatography with fluorometric detection.

This radial compression liquid-chromatographic assay for propranolol in plasma is rapid, reproducible, and suitable for use in routine monitoring. A 10-micron particle, 8 mm X 10 cm CN cartridge is used in conjunction with a radial compression separation system. The mobile phase is monobasic sodium phosphate (pH 3) solution/methanol/acetonitrile (760/84/156 by vol), the flow rate 6 mL/min. Propranolol was detected by use of a spectrofluorometer equipped with a 20-microL flow-through cell, at excitation and emission wavelengths of 250 and 336 nm. The retention times for propranolol and metoprolol (the internal standard) are 3.13 and 1.42 min, respectively. A one-step extraction with chloroform yields "clean" chromatograms, with greater than 90% of the drug being analytically accounted for. Under these conditions, results are precise and accurate. Currently we are using this method to monitor propranolol in hypertensive neonates. Data on changes in the concentrations of propranolol in plasma with time are presented for one such patient.

Chromatography, Liquid↗