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Biomedical subjects

R W Walker

Publications and source records attributed to R W Walker.

At least 91 records · Page 5Linked to original sources
PubMed1983

Brain metastases in children.

We reviewed the records of 31 children under the age of 21 years with parenchymal brain metastases diagnosed by CT scan (13 patients) or necropsy (18). Brain metastases were found in 18 of 139 (13%) children with solid tumors in whom complete postmortem examinations were done. Osteogenic sarcoma and rhabdomyosarcoma were the most frequent primary tumors causing brain metastases in patients younger than 15 years, and testicular germ cell tumor, from age 15 to 21 years. Evidence of intratumoral hemorrhage was found in 50% of autopsy cases. Pulmonary metastases were present in 28 of 31 (90%). The median interval from recognition of pulmonary metastases to the development of brain metastases was 10 months. No patient had evidence of brain metastases at diagnosis of the systemic cancer. In only one patient was the brain the only site of relapse. Following detection of brain metastases, the median survival was seven months in six patients who underwent surgery and whole-brain radiation therapy and four months in 15 given radiotherapy (3000 rads) alone. Patients with relatively radioresistant brain metastases may benefit from surgical excision or higher doses of radiation, or both.

Adolescent↗
PubMed1983

Platelet storage pool disease in women.

Menstrual abnormalities in adolescents are usually diagnosed as dysfunctional uterine bleeding. It is generally regarded as characteristic of the young hypophyseal-pituitary system, which with time will stop naturally. The possibility of platelet storage pool diseases as a cause of irregular bleeding is often overlooked. We have treated five patients with proven or suspected platelet storage pool disease who had a history of adolescent hypermenorrhea and other bleeding. Patients with this type of history should have a comprehensive hematologic evaluation because platelet storage pool disease is not demonstrated by conventional coagulation studies. Our patients were treated with medroxyprogesterone acetate, oral contraceptives, and an avoidance of aspirin.

Adenosine Diphosphate↗
PubMed1983

Biochemical and biomedical applications of capillary column GLC using SIM.

This report focuses on recent applications of capillary column GLC to the analysis of drugs and metabolites, other xenobiotics, natural products, and environmental contaminants in samples of biological origin. The increasing use of selected ion monitoring, combined with stable isotope methods as a means of GLC detection and quantification, is emphasized. Specific topics covered include the use of capillary column GLC for 1) determining the pharmacokinetics of timolol (BLOCADREN) in human volunteers by simultaneous oral and intravenous administration of this beta-blocker and its 13C3-labeled analog; 2) measuring residue levels of the forced molting agent, xylonidine, in yolk and albumen of chicken eggs; 3) monitoring animal plasma and tissues for the depletion of 5-hydroxy-1,3-dioxane and 4-hydroxymethyl-1,3-dioxolane (isomeric components of glycerol formal, an animal drug formulation component); 4) detecting 13C, 15N-methyltryptamine (a biosynthesis product from 13C, 15N-tryptamine) in human urine; and 5) measuring estradiol levels in biological samples.

Animals↗
PubMed1982

Identification of protein bands in polyacrylamide gel by protein printing.

Previously described methods for identification of proteins separated in cylindrical polyacrylamide gels have been found to be costly in time and antiserum and difficult to apply to small amounts of protein as are found in cerebrospinal fluid. We describe a method which involves printing of the proteins on the cut surface of the gel onto nitrocellulose paper. The protein bands of the imprint can then be identified using labelled antibodies. We have found this to be economical and quick, and it has permitted sensitive and reliable identification of proteins in unconcentrated cerebrospinal fluid and aqueous humour.

Blood Proteins↗
PubMed1982

Nitrocellulose immunofixation following agarose electrophoresis in the study of immunoglobulin G subgroups in unconcentrated cerebrospinal fluid.

A method is presented which enables the study of cerebrospinal fluid proteins in minimal volumes of unconcentrated fluid. The method involves agarose electrophoresis followed by transfer of the proteins to a nitrocellulose membrane and then demonstration of their distribution using a double-antibody immunoperoxidase technique. The method is used here for the study of immunoglobulin G and its subgroups, and clearly shows that the oligoclonal pattern observed in multiple sclerosis is not restricted to any one subgroup.

Collodion↗
PubMed1981

Oxidation reactions by prostaglandin cyclooxygenase-hydroperoxidase.

oxidations of organic sulfides, amines, and even enzymes catalyzed by purified and microsomal forms of prostaglandin cyclooxygenase-hydroperoxidase have been studied using O2 incorporation into arachidonic acid to monitor oxygenase and [14C]15-hydroperoxyprostaglandin E2 reduction to prostaglandin E2 to measure hydroperoxidase. The oxygenase was protected by phenol against the irreversible deactivation induced by low levels of hydroperoxides. Furthermore, the EPR signal noted during reactions with the microsomal enzyme probably reflected the adventitious oxidation of endogenous materials. As described previously for phenol and other reducing cosubstrates, methyl phenyl sulfide (MPS) increased hydroperoxidase activity at all concentrations studied, while stimulating oxygenase at low levels and inhibiting it at 5-10 mM. In stoichiometric equivalence with 15-hydroperoxyprostaglandin E2 reduction, MPS was enzymatically oxidized to its analogous sulfoxide, methylphenyl sulfoxide, acquiring an oxygen atom exclusively from the hydroperoxide and demonstrating some chiral character. In contrast, other oxidizable compounds such as N,N-dimethylphenylenediamine and aminopyrine reacted via radical intermediates. Phenylbutazone, which is oxidized using dissolved molecular oxygen, did not compete with MPS oxidation. Hence, MPS was oxidized while bound to the enzyme, whereas the amine oxidation occurred in solution via an enzyme-formed oxidant. The Soret peak noted with cyclooxygenase-hydroperoxidase was examined as a possible measure of this binding, but was also noted in denatured and deactivated enzyme, suggesting that its relevance should be reconsidered. Despite the similarities in their drug-metabolizing profiles, cyclooxygenase-hydroperoxidase is clearly distinct from cytochrome P-450. The mechanism of this hydroperoxidase is considered in the context of other more extensively studied peroxidases.

Amino Acids↗
PubMed1980

Capillary column GLC-mass spectrometric assay with selected-ion monitoring for timolol and [13C3]timolol in human plasma.

A method for the measurement of the beta-blocker timolol and its 13C3-labeled analog in human plasma is described. A known amount of an internal standard, [2H9]timolol, is added to each plasma sample. The method employs a reversed-phase C18 cartridge for isolation of the drug-containing fraction, capillary column GLC of the trimethylsilyl derivatives, and detection via selected-ion monitoring. The ions monitored for quantification (m/e 86 from timolol and m/e 89 and 95 from the 13C3- and 2H9-labeled analogs, respectively) arise from the side chains of the three compounds [e.g., CH2N+HC(CH3)3 for m/e 86]. Plasma levels of timolol and [13C3]timolol in human subjects given 5 or 10 mg of each compound were followed simultaneously for 12 hr postdosing. A detection level of 0.5 ng/ml of plasma was found. No evidence was found for a metabolic kinetic isotope effect since the ratios of the two species of drug in the plasma samples were the same as the ratios in the administered dose.

Gas Chromatography-Mass Spectrometry↗
PubMed1979

Electron-capture GLC assay of dichlorphenamide.

GLC with electron-caputre detection was applied to the assay of the carbonic anhydrase inhibitor dichlorphenamide and demonstrated a sensitivity of 10 ng in 0.5 ml of rabbit serum or whole aqueous humor (congruent to 0.25 ml) from one rabbit eye. After extraction of the drug and internal standard (monochlorphenamide) from the biological fluid, these compounds were converted to their tetramethyl derivatives by a nucleophilic alkylation method. Dichlorphenamide contents of aqueous humor and serum of rabbits treated with this drug are reported.

Animals↗
PubMed1979

Indomethacin in rheumatoid arthritis: clinical effects, pharmacokinetics, and platelet studies in responders and nonresponders.

Twenty patients with definite or classical rheumatoid arthritis entered and completed a sequential study of placebo for 1 week, oral indomethacin 25 mg 3 times a day for 3 weeks, and oral indomethacin 25 mg 3 times a day plus 100 mg indomethacin suppository at night for 3 weeks. Twelve of the patients had previously been classified as responders and eight as nonresponders to indomethacin by an independent assessor. At the end of each period patients were assessed by a blind observer for duration of morning stiffness, pain score, digital joint size, grip strength, articular index, analgesic tablet usage, and the patient's own overall global assessment and comparative global assessment. In 8 of the 9 tests used responders improved on indomethacin in comparison with placebo, while nonresponders did not improve. There were no significant differences between responders and nonresponders in the plasma half-life, plasma clearance of indomethacin, protein binding of indomethacin, or urinary excretion of free or conjugated indomethacin. There were no significant differences between responders and nonresponders in the urinary excretion of 7HDPA or in the platelet aggregation or platelet malonyldialdehyde production tests. In responders there was a significant positive correlation between the plasma indomethacin concentration (r=0.44, P<0.05) and the percentage inhibition of malonyldialdehyde production by the platelets. However, in nonresponders this correlation, while significant (P<0.05), was negative (r=-0.498). Both for responders and nonresponders there was a significant correlation between plasma indomethacin concentration and the percentage reduction in 7HDPA. There was no correlation between the clinical response and the plasma concentration of indomethacin. There appears to be a biochemical difference between responders and nonresponders, which, while not necessarily causally linked with the clinical response to indomethacin, is worthy of further study.

Adult↗
PubMed1978

An improved polystyrene polymeric XAD-2 resin column extraction of 5beta-cholestan-3beta-ol from polluted water.

Appropriate methods and criteria for judging the degree of sewage contamination of water and its suitability for drinking or recreational uses are essential to safeguard the public health. 5beta-cholestan-3beta-ol seems to satisfy many, if not all, of the criteria required of a good indicator of fecal pollution. It was shown that this fecal sterol was strongly adsorbed to the polystyrene polymeric XAD-2 adsorbents at low pH, resulting in a 100% retention. The adsorbed sterols could be easily removed from the columns with acetone adjusted to pH 8.5-9 with concentrated NH4OH. It has also been demonstrated that large volumes of both fresh and sea water samples can be extracted by the "closed" column method in a relatively short time. The sensitivity of the column exceeded that of the conventional liquid-liquid partitioning procedure. With some modifications, the column extraction process can be incorporated in a fully- or semi-automated analytical procedure.

Cholestanols↗
PubMed1977

Neutral lipid biosynthesis in Mycobacterium smegmatis.

The biosynthesis of neutral lipids in Mycobacterium smegmatis was studied using cell free extracts. Maximum neutral lipid production was obtained when the reaction mixture (400 microliter) consisted of 0.25 M potassium phosphate buffer (pH 7.5), 0.125 mM oleoyl-CoA, 3.75 mM sn-glycerol-3-P, 10 mM MgCl2 and 1.85 mg bovine serum albumin. No magnesium dependency for the acylation of sn-glycerol-3-P was observed. A slight stabilizing effect seemed to occur due to this ion. The enzyme phosphatidate phosphohydrolase, on the other hand, was shown to be magnesium dependent. The activity of this enzyme also appeared to be stimulated by high concentration (0.75 to 1.25 mM) of ATP which enhanced lipid formation at all concentrations tested (0.25 to 3.75 mM). A heat-stable protective factor having a molecular weight less than 16 000 which caused a stimulatory effect on sn-glycerol 3-phosphate acyltransferase activity was found in the cell-free extracts. Preliminary experiments suggest that the factor might be polysaccharide in nature.

Acyl Coenzyme A↗