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R C Lawrence

Publications and source records attributed to R C Lawrence.

At least 37 records · Page 2Linked to original sources

Estimates of the prevalence of selected arthritic and musculoskeletal diseases in the United States.

The National Arthritis Data Workgroup focused its studies primarily on joint disease with the addition of osteoporosis which is a frequently occurring musculoskeletal condition and public health problem. We used national data sets as well as published studies to estimate prevalence in the United States. We report on prevalence rather than incidence because of the difficulty in defining the point of onset and because primary national data sources currently available are concerned with disease prevalence.

Adolescent↗

Routine quality evaluation of benzodiazepine drugs to USP-NF specifications.

A GLC procedure was developed for the evaluation of diazepam, chlordiazepoxide, and flurazepam formulations to USP-NF specifications for drug content, content uniformity, impurities, and identity by retention times and peak areas. The polyimide column, instrument zone temperatures, gas flows, internal standard solution, extraction solvent, and auxiliary equipment were the same for each drug. No derivatization of the samples was required. The GLC assay values (mean of 10 individual dosage units) for diazepam and flurazepam products were in good agreement with the results obtained by the pharmacopeial composite assays. With chlordiazepoxide capsules, when the levels of the two pharmacopeial impurities determined by GLC were added to the GLC assay results (mean of 10), athe aggregate values were consistent wit the drug content results found by the nonspecific USP method. The procedure can be made sensitive to impurity levels of approximately 0.01% for 2-amino-5-chlorobenzophenone and to approximately 0.2% for 7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one 4-oxide. With the equipment used, the estimated potential outputs in lots per working day for a complete quality profile (drug content, content uniformity, purity, and identity) were seven for chlordiazepoxide if no impurity test was required, five if such a test was required, eight for diazepam, and seven for flurazepam.

Anti-Anxiety Agents↗

Impurities in drugs V: Meprobamate.

One lot of meprobamate raw material and 28 lots of tablets were examined for impurities by TLC. All lots contained di-(2-methyl-2-propyl-3-carbamoyloxypropyl) carbonate (V) at levels that ranged between 0.1 and 1.0% of the total drug content. Nine lots also contained low levels of a second impurity (approximately 0.1%), and one of these lots contained a third impurity (approximately 0.1%), neither of which was identified. Estimates of the unidentified impurities were based on the assumption of a TLC response with furfural-hydrochloric acid spray equivalent to that of meprobamate. Compound V was identified by mass spectrometry and PMR and IR spectroscopy and by comparison of the TLC Rf value to that of a synthesized sample of V.

Chromatography, Thin Layer↗

Simple GLC analysis of anticonvulsant drugs in commercial dosage forms.

A simple, specific GLC procedure is described for the analysis of one sedative and six anticonvulsant drugs in pharmaceutical dosage forms. Sample aliquots of ethotoin, glutethimide, mephenytoin, methsuximide, and phensuximide were shaken with or extracted into ethyl acetate, diluted with the internal standard (diphenyl phthalate) solution, injected into a gas chromatograph, and eluted from a methylsilicon column. Primidone and phenytoin samples (extracted as the free acid) required derivatization with N,O-bis(trimethylsilyl)acetamide prior to chromatography. The same temperature programming conditions and flow rate settings were used for all seven drugs. The GLC results agreed well with those obtained using the pharmacopeial methods.

Anticonvulsants↗

Selective GLC determination of epinephrine, isoproterenol, and phenylephrine in pharmaceutical dosage forms.

A simple, specific GLC analytical procedure for the quantitation of epinephrine, isoproterenol, and phenylephrine in commercial tablets, powders, inhalation solutions, ophthalmic and nasal drops, and injectable preparations is presented. Samples are taken to dryness where required, the dried residue is reacted with an appropriate trimethylsilylating reagent, and the derivatives are eluted from a methyl silicone column using temperature programming. Quantitation of the flame-ionization detector signal is achieved relative to the dibenzyl succinate internal standard by an electric integrator. The results obtained by applying the method to the analysis of each of the three drugs in several simulated decomposed mixtures were in good agreement with theoretical values, even at impurity levels of up to 80% by weight. When applied to commercial formulations, the procedure was feasible for tablets, powders, and solutions at drug concentrations of 0.2% or greater. The commonly incorporated buffering and antioxidant excipients did not interfere.

Chemical Phenomena↗

Specific quantitative gas-liquid chromatographic analysis of methyldopa and some foreign related amino acids in raw material and commercial tablets.

A relatively simple gas-liquid chromatographic (GLC) procedure has been designed for the rapid detection and accurate quantitation of some theoretically possible foreign related amino acid contaminants in alpha-methyldopa raw material and commercial tablets. After trimethylsilylation of the drug or drug mixture with N,O-bis(trimethylsilyl)acetamide in acetonitrile at ambient temperature for 90 min, the derivatives are eluted from a methylsilicone column isothermally at 170 degrees. Quantitation of the components is effected by simple computation relative to dibenzyl succinate as the internal standard. The results obtained by applying the GLC procedure to the analysis of a number of multicomponent synthetic mixtures are in good agreement with the theoretical values. The percentage of label claim values obtained by the GLC method for commercial tablets are compared to those measured colorimetrically by the official U.S.P. procedure. No foreign related amino acid impurities were detected in any of the three commercial dosage forms examined.

Amino Acids↗

Glucose repression of enterotoxins A, B and C and other extracellular proteins in staphlyococci in batch and continuous culture.

The production of enterotoxins, lipase and total extracellular protein by four strains of Staphylococcus aureus grown in batch culture at a controlled pH of 6.5 in a completely defined medium was markedly reduced by glucose or glycerol constantly maintained at 0.I M. A concomitant increase in the production of deoxyribonuclease, up to 13-fold, showed however that not all extracellular proteins are under the same control mechanism. The presence of glucose and glycerol in the medium also resulted in a rapid increase in the specific growth rate. However, growth of S. aureus s6 in Mgilimited continuous culture showed that glucose repression of enterotoxin B when the growth rate was held constant was more than twice that in batch culture. Therefore glucose repression can occur independently of an increase in growth rate. The specific rate of production of enterotoxin B, lipase, deoxyribonuclease, beta-haemolysin and total extracellular protein by S. aureus s6 increased as the growth rate increased from 0.07 to 0.24 h-1. Non-replicating cells grown in the absence of glucose produced considerable amounts of enterotoxin, and production was not repressed by the presence of glucose in the resuspension medium. In contrast, no enterotoxin B or C was obtained from nonreplicating cells grown in the presence of glucose. Chloramphenicol completely inhibited enterotoxin production by non-replicating cells, indicating that synthesis of new protein was required.

Bacterial Proteins↗

Production of staphylococcal enterotoxins A, B, and C under conditions of controlled pH and aeration.

The production of enterotoxins A, B, and C by nine strains of Staphylococcus aureus has been studied under controlled conditions in a fermenter. The strain to strain differences between staphylococci producing a specific enterotoxin were very marked. Increasing aeration in shake flasks improved both growth and production of all extracellular proteins measured other than that of enterotoxin C, the yield of which was decreased in one strain at high aeration. Silicone antifoam decreased the production of extracellular proteins, although enterotoxin A production from three strains was much less affected than that of enterotoxins B and C. In a detailed study of three strains, production of enterotoxins A and C was considerably greater in a defined amino acid medium than in a casein hydrolysate medium and was optimal for all three enterotoxins between pH 6.5 and 7.3. Changes in the pH or medium used in the fermenter that led to increased enterotoxin production could generally be correlated with a change in growth pattern, showing an extended transition period from exponential to stationary phase. Three out of five enterotoxin-A producing strains produced significantly more enterotoxin at a controlled pH of 6.5 in the fermenter than in shake-flask cultures. The yields with strain 100 were about five times greater than hitherto reported. Since many foods are buffered at pH 6 to 6.5, some strains may, therefore, produce sufficient enterotoxin A to cause food poisoning, although little or none may be produced when grown under normal testing procedures.

Bacterial Proteins↗

Production of extracellular enzymes and enterotoxins A, B, and C by Staphylococcus aureus.

Eighty-seven strains of Staphylococcus aureus were examined for their ability to produce enterotoxins A, B, and C, deoxyribonuclease, lysozyme, proteinase, lipase, and alpha-, beta-, and delta-hemolysins. Enterotoxigenic strains showed a significant tendency to be high lipase producers, but none of the other enzymes formed were correlated with the ability of the staphylococci to produce enterotoxins A, B, or C. The conversion of ent(-) to ent(+) strains by lysogenization did not affect significantly the ability of the strains to produce any of the above extracellular enzymes. The formation of enzymes such as deoxyribonuclease and lysozyme by staphylococci is not therefore an indication, necessarily, of their potential enterotoxigenicity.

Bacterial Proteins↗

Typing of coagulase-positive staphylococci by proteolytic activity on buffered caseinate-agar, with special reference to bacteriophage nontypable strains.

The specificities of the proteinases produced by 136 strains of coagulase-positive staphylococci on a buffered caseinate-agar medium at 37 C were investigated. Five well-defined groups of staphylococci could be differentiated by the patterns of precipitation zones obtained as a result of proteolysis. Within these five groups, slight variations in zone types were observed. The type of zone produced by any one strain was, however, highly reproducible, suggesting that the proteinases produced by staphylococci are strain-specific. Strains could be further differentiated by the patterns of precipitation obtained at 30 C. The differences in zone types on caseinateagar can be used as an adjunct to standard typing procedures, being particularly valuable in epidemiological investigations and in the differentiation of phage "non-typable" strains. In this survey, 63 of the strains investigated could not be typed by the international set of typing phages but could be readily differentiated in terms of their proteolytic activities at 37 and 30 C. No correlation was found between proteolytic activity, phage type, origin of the strains, or the production of enterotoxins A, B, or C.

Journal Article↗