Biomedical subjects
Publications and source records attributed to M R Kibby.
Four spreadsheet templates have been devised to ease certain laboratory operations, namely preparing buffers by mixing solutions, calculating required rotor speeds to achieve particular g-values, preparing and utilising isokinetic gradients to determine sedimentation coefficients, and calculating purification tables. Their use in designing experiments is described briefly.
Four spreadsheet templates are presented to carry out routine statistical analyses with relatively small amounts of data: two-sample Student's t test, one-factor analysis of variance with replication, two-factor analysis of variance with replication, and Wilcoxon's non-parametric two-sample T-test (Mann and Whitney U-test). The use of sometimes complex IF and logic (AND, OR) functions in these templates is a means of maintaining a neat output presentation by avoiding error values, selection of appropriate forms of the t-test, and iteratively assigning mean ranks to data in the non-parametric test. The advantages of the spreadsheet approach accrue through using a multi-purpose package rather than dedicated statistics programs, having usually unobstructed access to the program for modification, relative ease of programming spreadsheets, and ease of correction and alteration of input data. Disadvantages are the limited size of templates and the small number of templates available. Spreadsheets represent a declarative form of programming rather than procedural, with consequent advantages in specifying the problem to be solved, which may have particular application in teaching statistics and programming at undergraduate level.
Electronic spreadsheets computerise the traditional layout of any tabulation or complex calculation done with pencil, paper and calculator. They therefore have great potential in aiding routine calculations which might be done by these means or with a small BASIC computer program. Their simple structure and strong affinity with traditional methods make them particularly suitable for those who have not yet mastered the art of programming. However, a necessarily brief review of their application to science and technology demonstrates that this potential is not being realised in comparison with their wide-spread usage in the business world. The application of both Multiplan and Visicalc running respectively on the Macintosh and the Apple IIe microcomputers in four types of calculation is demonstrated: tabulation, curve-fitting and statistics, simulation, and numerical approximation. Advantages are found in the concurrent display of data and results, the ease of correction or modification of data and the escape from traditional linear programming methods. The spreadsheet format imposes its own constraints. It is not so flexible as BASIC, it demands more memory and may have a slower execution time than a program written in a high-level language, and it is more difficult to produce graphical output.
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1. The metabolism of sulphadimethoxine (2,4-dimethoxy-6-sulphanilamidopyrimidine) was examined in nine species of primates and nine species of non-primates. 2. The main metabolite of the drug in the urine in man, rhesus monkey, baboon, squirrel monkey, capuchin, bushbaby, slow loris and tree shrew was sulphadimethoxine N(1)-glucuronide. In the green monkey, although the main metabolite was N(4)-acetylsulphadimethoxine, the N(1)-glucuronide was also a major metabolite. 3. In the dog, rat, mouse, guinea pig, Indian fruit bat and hen the N(1)-glucuronide was a minor metabolite in the urine, whereas in the cat, ferret and rabbit this glucuronide was not found in the urine. 4. All the species examined except the dog excreted some N(4)-acetylsulphadimethoxine, which was the major metabolite in the green monkey, rabbit and guinea pig. 5. In the tree shrew, a doubtful primate, N(1)-glucuronide formation was similar to that in the other primates. 6. It is suggested that the slow excretion of the drug by the rat may be due partly to strong binding of the drug to tissue proteins and that the strength of binding may vary with species. 7. In the rat the amount of N(1)-glucuronide found in the urine is not a true indication of the extent of this conjugation since much more of the conjugate was found in the bile (7% of the dose) than in the urine (1%). In the rabbit, no N(1)-glucuronide was found in the bile or urine, but a small amount of sulphadimethoxine N(4)-glucuronide was found in the bile of the rat (0.5% of dose) and rabbit (0.8%).
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1. A comparative study was made in man, rhesus monkey, rat and rabbit of the urinary excretion of 2-, 4- and 5-methoxy- and 2,4-, 2,5- and 4,5-dimethoxy-6-sulphanilamidopyrimidines given orally. 2. In the rabbit, 70-80% of the dose of each drug was excreted in 2 days, mainly as N(4)-acetyl derivatives, except 2,5-dimethoxy-6-sulphanilamidopyrimidine, which was mainly excreted unchanged. 3. In the rat, 50-70% of the dose of each drug was excreted in 2 days, except the 2-methoxy and 2,4-dimethoxy compounds, whose excretion was about 30%. The N(4)-acetyl derivatives accounted for 20-70% of the drugs excreted, except the 2,5-dimethoxy derivative, which was excreted unchanged. 4. In the rhesus monkey, some 40-60% of the dose of the 2-methoxy, 2,4-dimethoxy and 2,5-dimethoxy compounds was excreted in 2 days, but the 4-methoxy, 5-methoxy and 4,5-dimethoxy compounds were excreted at less than half this rate. The 4-methoxy, 5-methoxy and 4,5-dimethoxy compounds were highly acetylated (80-90%) whereas the 2-methoxy compound was poorly acetylated (17%) and the 2,5-dimethoxy compound hardly at all. The major metabolite of the 2,4-dimethoxy compound in the monkey was the N(1)-glucuronide. 5. In man, 30% of the dose of the 4-methoxy and 2,4-dimethoxy compounds was excreted in 24 hr., whereas the 4,5-dimethoxy compound (Fanasil) was very slowly excreted (12% in 2 days). The 4-methoxy compound was well acetylated (65%), but the 2,4- and 4,5-dimethoxy compounds were not (20-30%). The main metabolite of the 2,4-dimethoxy compound in man was the N(1)-glucuronide. 6. N(1)-Glucuronide formation occurred extensively only with the 2,4-dimethoxy compound and only in man and the rhesus monkey. It did not occur in the rabbit and only to a minor extent in the rat. 7. The 2,5-dimethoxy compound was not significantly acetylated in vivo in the rabbit, rat or monkey, but acetylation occurred in vitro in rabbit or monkey liver homogenates. 8. These findings are discussed.
1. The fate of sulphadimethoxine (2,4-dimethoxy-6-sulphanilamidopyrimidine) was studied in man, rhesus monkey, dog, rat, guinea pig and rabbit. 2. About 20-46% of the dose (0.1g./kg.) of the drug is excreted in the urine in 24hr. in these species, except the rat, in which only 13% is excreted. 3. In man and the monkey sulphadimethoxine N(1)-glucuronide is the major metabolite in the urine. In the rabbit and guinea pig N(4)-acetylsulphadimethoxine is the main metabolite. In the dog the drug is excreted mainly unchanged. In the rat equal amounts of the unchanged drug and its N(4)-acetyl derivative are the main products. 4. Small amounts of sulphadimethoxine N(4)-glucuronide are found in the urine of all the species. Sulphadimethoxine N(1)-glucuronide occurs in small amounts in the urine of rat, dog and guinea pig; none is found in rabbit urine. 5. Sulphadimethoxine N(4)-sulphate was synthesized and found to occur in small amounts in rat urine. 6. Monkey liver homogenates fortified with UDP-glucuronic acid are able to synthesize sulphadimethoxine N(1)-glucuronide with the drug as substrate. Rat liver has also this ability to a slight extent, but rabbit liver is unable to do so. 7. Sulphadimethoxine N(4)-glucuronide is formed spontaneously when the drug is added to human urine. 8. The biliary excretion of the drug and its metabolites was examined in rats. The drug is excreted in rat bile mainly as the N(1)-glucuronide. The N(1)- and N(4)-glucuronides administered as such are extensively excreted in the bile by rats.
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1. The major metabolite of 2,4-dimethoxy-6-sulphanilamidopyrimidine (sulphadimethoxine) in urine in man is a non-reducing glucuronide, which has been isolated and characterized as its S-benzylthiouronium salt. 2. The same compound was made synthetically by standard methods from sodium sulphadimethoxine and methyl 2,3,4-tri-O-acetyl-1-bromoglucuronate. 3. On hydrolysis with acid, the glucuronide yielded sulphanilic acid, glucuronic acid and barbituric acid, and with beta-glucuronidase it slowly yielded sulphadimethoxine and glucuronic acid. 4. Evidence based on infrared spectra and other data showed that the urinary and synthetic glucuronide was 1-deoxy-1-[N(1)'-(2'',4''-dimethoxypyrimidin-6'' -yl)sulphanilamido-beta-d-glucosid]uronic acid or sulphadimethoxine N(1)-glucuronide. 5. N(1)-Methyl- and N(ring)-methyl derivatives of sulphadimethoxine and 4-methoxy-6-sulphanilamidopyrimidine were prepared and their infrared and ultraviolet spectra determined for comparison.