Finding new solutions to old problems.
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Biomedical subjects
Publications and source records attributed to M A Gaston.
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Based on the principle of bioisosterism, a successful strategy in the planning of new drugs, we describe in this work the synthesis and the analgesic activity of the new functionalized arylcarbaldehyde 4-(1-phenyl-3-methylpyrazolo[3,4-b]pyridine) hydrazone derivatives 5a-m. These derivatives (5a-m) were synthesized in ca. 45% overall yield, using 4-(1-phenyl-3-methylpyrazolo[3,4-b]pyridinyl) hydrazine 6, as key intermediate. by applying classical synthetic methods to construct the aryl-hydrazone unit at C-4 of the heterocyclic system. Compound 6 was prepared from the corresponding 4-chloro-(N-phenyl-3-methylpyrazolo[3,4-b]pyridine) derivative 7 in very high yield. The antinociceptive activity of these new compounds 5a was evaluated by a test of abdominal contortions induced by 0.6% acetic acid solution i.p. in albino mice. The compounds 5f, 5g, 5j and 5k were strongly active showing a good analgesic profile.
The health practices and needs of two samples of older individuals with mental retardation were examined and contrasted over a period of 5 years. Their health status varied markedly, but most had poor health maintenance practices, and almost all had difficulty communicating with health care providers. Those who lived in community residential facilities or relatives' homes usually had adequate health care provided for them, whereas individuals who lived more independently had difficulty accessing health care. There is a pressing need for health care advocacy programs to help prevent chronic disability.
The purpose of this study was to determine the types and frequency of ethical problems encountered by dental hygienists, and to determine the type of instruction they have received in ethical theory and problem solving. A 40-item questionnaire mailed to 2,251 American Dental Hygienists' Association members resulted in a stratified random sample of 1,523 (68% response rate). The three ethical dilemmas most frequently encountered in dental hygiene practice are (1) observation of behavior in conflict with standard infection control procedures (66%); (2) failure to refer patients to a specialist such as a periodontist (60%); and (3) nondiagnosis of dental disease (58%). While almost 86% of the respondents received formal instruction in ethical theory, only 51% received formal instruction in methods for solving ethical problems. More hygienists (74%) felt their ethical principles were influenced by role models rather than by formal instruction (63%). This study indicates that serious ethical dilemmas are encountered by the majority of dental hygienists and that some modification of current entry-level education, as well as of continuing professional education, should be considered to prepare dental hygienists to recognize and resolve ethical problems.
Hospital isolates of Enterobacter cloacae were analysed by polyacrylamide gel electrophoresis for enzyme polymorphism and the results were compared with established serotyping, phage typing and biotyping techniques. Initially, the diversity of electromorphs of 13 enzymes was determined on a representative set of 62 distinct strains. Two broad clusters of strains were found in the species, and analysis by serotype suggested a limited diversity within the most frequent O serotypes. A subset of three enzymes, lactate dehydrogenase, 6-phosphogluconate dehydrogenase, glutamate dehydrogenase and an unidentified marker, were selected and used to type groups of hospital isolates. There was good general agreement between the two systems, although the enzyme method failed to distinguish between some strains with the same serotype. This method provided useful epidemiological information and, in the absence of established typing systems, it is a practical approach to subdividing the species.
Twenty cultures comprising 13 clinical isolates of Enterobacter cloacae from two hospitals, the type and another reference stain of E. cloacae and the type strains of four other Enterobacter sp. and of Escherichia coli, were characterized by one-dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of whole-cell proteins. The protein patterns were highly reproducible and were used as the basis of a numerical analysis which divided the clinical isolates into nine clearly defined protein types. Comparison with established typing methods indicated that the discrimination of SDS-PAGE was similar to that achieved with conventional typing methods and all strain groups recognized by combined sero/phage typing were also found by SDS-PAGE. In addition, protein typing sub-divided a group of four serotype O3 isolates that were difficult to distinguish by phage typing. We conclude that high-resolution SDS-PAGE of proteins provides an effective method of typing isolates of E. cloacae.
O antigens of the 24 O-serotype strains of Serratia marcescens were investigated in dot enzyme immunoassay with whole-cell antigens and by immunoblotting with lipopolysaccharide (LPS) antigens. Three pairs of strains, O2/O3, O6/O7, and O12/O14, had indistinguishable LPS antigens, despite having distinct specificities in agglutination tests with whole-cell antigens. Strong cross-reactions were also found in LPS antigens from strains O9/O15, O17/O19, O10/O22, and O16/O20. No high-molecular-weight LPS corresponding to O-side-chain material was detected in strain O11 or O13. A panel of absorbed antisera was prepared to facilitate the detection of a reduced set of LPS antigens in a dot enzyme immunoassay. We conclude that there are discrepancies between the existing serotypes as defined by agglutination tests and the antigenic composition of LPS antigens extracted from the serotype strains and that surface antigens other than LPS make a major contribution to the definition of serotype in the species.
In a previous study, we found that some O serotypes of Serratia marcescens, as defined by agglutination tests, were not based on lipopolysaccharide (LPS) O antigens. We developed a dot enzyme immunoassay with a high degree of LPS specificity and tested 104 distinct clinical strains. Only 7 of the 24 existing O antigens were found in more than one strain: O12/O14 (30.8% of strains examined), O21 (12.5%), O8 (8.7%), O6/O7 (5.8%), O4 (3.8%), O18 (2.9%), and O9 (2.9%). Two new antigens, S1254 (13.5%) and S3255 (3.8%), were also found. Agglutination tests with O antisera identified the LPS antigen in only 36 strains. Prodigiosin production was restricted to serotypes O8, O6, and S3255 and strains with a rough or semirough LPS phenotype. Dot immunoassay appears to offer greater accuracy than agglutination tests for serotype identification in S. marcescens.
The applicability of Enterobacter cloacae and Klebsiella typing reagents for classifying clinical strains of Enterobacter aerogenes was evaluated. Of 75 strains, none were agglutinated by E. cloacae O antisera or were sensitive to E. cloacae bacteriophages. In contrast, 70 strains reacted with Klebsiella capsular antisera. Two-thirds of the strains were lysed by Klebsiella typing phages. A set of five E. aerogenes bacteriocin producers classified 92% of strains into 15 sensitivity types. In conclusion, E. aerogenes may be typed with Klebsiella reagents, and the simple bacteriocin test provides further discrimination between strains. The limited number of capsular antigens in the species and their apparent similarity to Klebsiella capsular antigens warrant further investigation.
To simplify the selection of tests for bacteriological typing methods, such as bacteriophage, bacteriocin, and biotyping, a computerised method was assessed. This uses a numerical index of discrimination (D) to facilitate the selection of an efficient typing set. The computer programs take the most discriminatory test as the initial test in the partial typing set, and then select the next test by combining each of the remaining candidates with the partial set and choosing the test which maximises D. This cycle is repeated until the remaining candidates do not increase the discriminatory power of the typing set. Options are provided for the investigator to pre-select certain tests for inclusion or exclusion from the typing set. It is concluded that the numerical index D is a simple means of test selection, but it must be emphasised that it is important to combine its use with data on the incidence of reaction in each test, on reproducibility, and on the similarity among tests.
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