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Biomedical subjects

A Franklin

Publications and source records attributed to A Franklin.

At least 19 recordsLinked to original sources
PubMed2002

Antimicrobial susceptibility of udder pathogens isolated from dairy herds in the west littoral region of Uruguay.

A total of 522 strains belonging to streptococci, enterococci and staphylococci isolated from sub-clinical and clinical cases of bovine mastitis from the west littoral region of Uruguay were analysed for their susceptibility to several antimicrobial agents. The susceptibility patterns were studied by agar disk diffusion methods (ADDM) and broth micro-dilution to determine the minimum inhibitory concentration (MIC). The concentration that inhibits 90% (MIC90) of the analysed strains reported in micrograms per millilitre, for Staphylococcus aureus were > 8, 8, < or = 0.5, < or = 4, < or = 1, < or = 0.5, > 64, < or = 0.25, 0.5, < or = 1 and < or = 1 to penicillin, ampicillin, oxacillin, cephalotin, gentamicin, erythromycin, oxitetracycline, enrofloxacin, trimethoprim/sulfamethoxazole, neomycin, and clindamycin, respectively. Coagulase-negative staphylococci (CNS) had different values for penicillin (4) and ampicillin (2), while the other antimicrobial agents had the same MIC90 values as reported for S. aureus. The MIC90 values for streptococci were 0.12, 0.25, < or = 4, 16, < or = 0.25, 0.5, 0.25 for penicillin, ampicillin, cephalotin, gentamicin, erythromycin, oxytetracycline and trimethoprim-sulfamethoxazole, whereas MIC90 for enterococci were 4, 4, 4, < or = 0.5, 2, > 8 for penicillin, ampicillin, gentamicin, erythromycin, oxytetracycline and trimethoprim-sulfamethoxazole, respectively. Of 336 strains of S. aureus, 160 (47.6%) were resistant to penicillin. For 41 CNS strains, 10 (27%) presented penicillin-resistance. All the streptococcal strains were susceptible to penicillin, while 3 (7%) of the 43 enteroccocal strains were resistant. Non significant statistical differences were found between the results obtained by ADDM and broth micro-dilution for classifying bacterial isolates as susceptible or resistant according to the National Committee of Clinical Laboratory Standards.

Animals↗
PubMed2001

A dominant interference collagen X mutation disrupts hypertrophic chondrocyte pericellular matrix and glycosaminoglycan and proteoglycan distribution in transgenic mice.

Collagen X transgenic (Tg) mice displayed skeleto-hematopoietic defects in tissues derived by endochondral skeletogenesis.(1) Here we demonstrate that co-expression of the transgene product containing truncated chicken collagen X with full-length mouse collagen X in a cell-free translation system yielded chicken-mouse hybrid trimers and truncated chicken homotrimers; this indicated that the mutant could assemble with endogenous collagen X and thus had potential for dominant interference. Moreover, species-specific collagen X antibodies co-localized the transgene product with endogenous collagen X to hypertrophic cartilage in growth plates and ossification centers; proliferative chondrocytes also stained diffusely. Electron microscopy revealed a disrupted hexagonal lattice network in the hypertrophic chondrocyte pericellular matrix in Tg growth plates, as well as altered mineral deposition. Ruthenium hexamine trichloride-positive aggregates, likely glycosaminoglycans (GAGs)/proteoglycans (PGs), were also dispersed throughout the chondro-osseous junction. These defects likely resulted from transgene co-localization and dominant interference with endogenous collagen X. Moreover, altered GAG/PG distribution in growth plates of both collagen X Tg and null mice was confirmed by a paucity of staining for hyaluronan and heparan sulfate PG. A provocative hypothesis links the disruption of the collagen X pericellular network and GAG/PG decompartmentalization to the potential locus for hematopoietic failure in the collagen X mice.

Animals↗
PubMed2001

Traumatic asymmetrical bilateral hip dislocation in an adult.

Bilateral hip dislocation occurring as a result of trauma is a rare condition. Simultaneous anterior and posterior traumatic dislocation of both hips is even more unusual. A case is reported of asymmetrical bilateral traumatic hip dislocation without an associated fracture of the pelvis or femur occurring in a young adult with no previous history of hip abnormality or ligamentous laxity. An unusual mechanism for this injury is also described.

Accidents, Traffic↗
PubMed2001

NeuroD homologue expression during cortical development in the human brain.

Neurogenesis and neuronal differentiation are determined by the NeuroD homologues, transcription factors belonging to a family of basic helix-loop-helix proteins. The authors used in situ hybridization with full-length riboprobes for NeuroD1, NeuroD2, and NeuroD3 to describe the expression of the NeuroD homologues in a gestational sequence of human fetal brains. Acridine orange histofluorescence was used to differentiate neuronal from non-neuronal cell precursors. At the earliest gestational age examined (gestational week 16), signals for all three homologues could be identified but that for NeuroD3 was most intense. Peak expression of NeuroD1 and NeuroD2 followed at gestational weeks 19 and 20, respectively. Although similar to the expression of these homologues in the mouse cerebrum, notable differences were observed. Specifically, signals for all three homologues were detected in the marginal zone and the ventricular zone, including the ganglionic eminence. The temporal order of expression in the human is similar to that in the mouse, in spite of these anatomic differences. These data are consistent with NeuroD3 serving as a determination factor, which commits the post-mitotic progenitor cell to a neuronal fate, whereas NeuroD1 and NeuroD2 appear more likely to play a role in neuronal differentiation.

Basic Helix-Loop-Helix Proteins↗
PubMed2001

Antimicrobial resistance: harmonisation of national antimicrobial resistance monitoring and surveillance programmes in animals and in animal-derived food.

A guideline on the harmonisation of national antimicrobial resistance monitoring and surveillance programmes in animals and animal-derived foods has been developed by the Ad hoc Group of experts on antimicrobial resistance of the Office International des Epizooties. The objective of the guideline is to allow the generation of comparable data from various national surveillance and monitoring systems in order to compare the situations in different regions or countries and to consolidate results at the national, regional and international level. Definitions of surveillance and monitoring are provided. National systems should be able to detect the emergence of resistance, and to determine the prevalence of resistant bacteria. The resulting data should be used in the assessment of risks to public health and should contribute to the establishment of a risk management policy. Specific factors identified for harmonisation include the animal species, food commodities, sampling plans, bacterial species, antimicrobials to be tested, laboratory methods, data reporting, database structure and the structure of reports.

Animals↗
PubMed2001

Antimicrobial resistance: standardisation and harmonisation of laboratory methodologies for the detection and quantification of antimicrobial resistance.

The Ad hoc Group of experts on antimicrobial resistance of the Office International des Epizooties has developed a guideline on the standardisation and harmonisation of laboratory methodologies used for the detection and quantification of antimicrobial resistance. The existing methods (disk diffusion [including concentration gradient strips], agar dilution and broth dilution) are reviewed, including a comparison of their advantages and disadvantages. The definitions of resistance characteristics of bacteria (susceptible, intermediate and resistant) are addressed and the criteria for the establishment of breakpoints are discussed. Due consideration has to be given to these aspects in the interpretation and comparison of resistance monitoring or surveillance data. The use of validated laboratory methods and the establishment of quality assurance (internal and external) for microbiological laboratory work and the reporting of quantitative test results is recommended. Equivalence of different methods and laboratory test results is also recommended to be established by external proficiency testing, which should be achieved by the means of a reference laboratory system. This approach allows the comparison of test results obtained using different methods generated by laboratories in different countries.

Animals↗
PubMed2001

Antimicrobial resistance: monitoring the quantities of antimicrobials used in animal husbandry.

This guideline, developed by the Office International des Epizooties for the monitoring of the quantities of antimicrobials used in animal husbandry, provides the methodology required to assess the amounts of antimicrobials used, to supply data to be used for risk analysis and to improve guidance on the appropriate use of antimicrobials. Information may be gathered from a number of sources, such as the competent authorities, industry and users. The usefulness of different types of information is discussed and recommendations are given on how to collect detailed information, each year, on the antimicrobial quantities used per class and active substance. Information should also be collected on the route of administration (oral and parenteral) and the animal species.

Animal Husbandry↗
PubMed2001

Antimicrobial resistance: responsible and prudent use of antimicrobial agents in veterinary medicine.

A guideline on the responsible and prudent use of antimicrobials in animal husbandry has been developed by the Ad hoc Group of experts on antimicrobial resistance, created by the Office International des Epizooties. The objectives of responsible use are to maintain antibiotic efficacy, to avoid the dissemination of resistant bacteria or resistance determinants and to avoid the exposure of humans to resistance through food. The guideline attributes a central role to the competent authorities responsible for granting marketing authorizations for antimicrobial substances. Requirements before and after granting of marketing authorizations are defined. Important aspects include the control of the pharmaceutical product quality and the therapeutic efficacy, the assessment of the selection pressure, the protection of the environment, specific and non-specific antimicrobial resistance surveillance. The guideline is also addressed to the veterinary pharmaceutical industry, veterinary practitioners, dispensing pharmacists and farmers. The respective roles and responsibilities of these groups are defined.

Animal Husbandry↗
PubMed2001

Antimicrobial resistance: risk analysis methodology for the potential impact on public health of antimicrobial resistant bacteria of animal origin.

The Ad hoc Group of experts on antimicrobial resistance, appointed by the Office International des Epizooties, has developed an objective, transparent and defensible risk analysis process, providing a valid basis for risk management decisions in respect to antimicrobial resistance. The components of risk analysis and of different possible approaches in risk assessment (qualitative, semiquantitative and quantitative) are defined. The Ad hoc Group recommended the following: an independent risk assessment based on scientific data; an iterative risk analysis process; a qualitative risk assessment systematically undertaken before considering a quantitative approach; the establishment of a risk assessment policy; and the availability of technical assistance for developing countries.

Animals↗
PubMed2001

Susceptibility to pleuromutilins in Brachyspira (Serpulina) hyodysenteriae.

The pleuromutilins are the only antimicrobial agents with sufficient minimum inhibitory concentration (MIC) values left to treat swine dysentery in Sweden. Other antimicrobials are either not approved for use against swine dysentery or only partly active against Brachyspira hyodysenteriae. To date, in Sweden two pleuromutilins, tiamulin and valnemulin, are authorized for use in pigs. This study includes a comparison between MICs of tiamulin and valnemulin for Swedish field isolates of B. hyodysenteriae, as determined by broth dilution. For different isolates the MIC of tiamulin was between 0 and 8 times higher than that of valnemulin. No resistance to pleuromutilins was recorded (tiamulin MIC range 0.031-2 microg/ml, valnemulin MIC range < or =0.016-1 microg/ml). In vitro development of tiamulin resistance was also studied. Two B. hyodysenteriae and two B. pilosicoli strains became resistant to tiamulin following reiterated passages on agar containing tiamulin in increasing concentrations. The resistance emerged slowly and three of the strains that went through more than 60 passages increased their tiamulin MICs from 0.031-0.25 to more than 128 microg/ml. The tiamulin MIC for one B. hyodysenteriae strain that went through 29 passages increased from 0.0125 to 4 microg/ml. One B. pilosicoli strain developed cross-resistance to valnemulin; the MIC increased from 0.25 to more than 64 microg/ml. The valnemulin MIC for one B. hyodysenteriae strain increased from 0.031 microg/ml to 32 microg/ml. Valnemulin MIC was not determined for the B. hyodysenteriae strain that only went through 29 passages. The valnemulin MIC of the other B. pilosicoli strain increased from 0.031 to 4 microg/ml.

Animals↗
PubMed2000

Mutation analysis of 3 genes in patients with Leber congenital amaurosis.

OBJECTIVE: To assess the frequency of mutations in the CRX, GUCY2D, and RPE65 genes in patients with Leber congenital amaurosis (LCA). PATIENTS: One hundred seventy-six probands with a clinical diagnosis of LCA were from 9 countries, with the largest subgroup being 39 probands from India. METHODS: Samples were screened with single-strand conformation polymorphism analysis followed by DNA sequencing of 3 genes (CRX, GUCY2D, and RPE65) known to be associated with LCA. RESULTS: Of the 176 probands, 28 (15.9%) harbored possible disease-causing mutations. The relative contribution of each gene to the total number of mutations was as follows: CRX, 2.8%; GUCY2D, 6.3%; and RPE65, 6.8%. No patients who harbored mutations in these genes had associated systemic abnormalities. Molecular diagnosis allowed definitive genetic counseling in a family affected with Best disease and LCA. CONCLUSIONS: Molecular diagnosis may be of benefit to patients affected with LCA. The relative paucity of mutations found in this study suggests that more LCA-associated genes remain to be discovered. CLINICAL RELEVANCE: Molecular diagnosis can confirm and clarify the diagnosis of LCA. As genotype data accumulate, clinical phenotypes associated with specific mutations will be established. This will facilitate the counseling of patients on their visual prognosis and the likelihood of associated systemic anomalies.

Adolescent↗
PubMed2000

Epidemiology and ecology of enterococci, with special reference to antibiotic resistant strains, in animals, humans and the environment. Example of an ongoing project within the European research programme.

The objectives of the present study are to generate knowledge of the ecology and epidemiology of enterococci in the food chain by studying the following: (1) the population structure (in measures of abundance, number of vancomycin resistant strains, antibiotic resistance patterns, diversity, and stability) among enterococcal populations in different geographical regions and in different links of the food chain (2) possible transmission of strains through the food chain and between hospital environments and the food chain (3) the association between vancomycin resistance and individual strains of enterococci and (4) the diversity of the drug resistance genes in enterococci. So far, 1578 samples have been collected from different countries within the EU (Sweden, Denmark, UK and Spain), and from different habitats (pig farms, carcasses in slaughter houses, soil, manure, water, sewage, and humans). Total and vancomycin resistant enterococcal populations in each sample have been enumerated and more than 12000 isolates have been characterised by phenotyping. Representative isolates are further species identified and characterised by genotyping and MIC determination and from antibiotic resistant isolates the resistance genes are characterised.

Animals↗
PubMed2000

Genetic studies in neural tube defects. NTD Collaborative Group.

Neural tube defects (NTD) are one of the most common birth defects and are caused by both environmental and genetic factors. The approach to identifying the genes predisposing to NTD, through linkage analysis and candidate gene analysis, is reviewed along with characteristics of a large, nationally ascertained cohort of families. Results from specific assessments of p53, PAX3 and MTHFR failed to suggest that these genes play a major role in NTD development in these families. Advances in genetic laboratory and statistical techniques have made this a prime opportunity for investigation into the causes of complex disorders, such as NTD. However, traditional approaches may prove to be challenging due to the difficulty of ascertaining samplable multiplex families.

Animals↗
PubMed1999

Genetic basis of macrolide and lincosamide resistance in Brachyspira (Serpulina) hyodysenteriae.

Macrolide antibiotic resistance is widespread among Brachyspira hyodysenteriae (formerly Serpulina hyodysenteriae) isolates. The genetic basis of macrolide and lincosamide resistance in B. hyodysenteriae was elucidated. Resistance to tylosin, erythromycin and clindamycin in B. hyodysenteriae was associated with an A-->T transversion mutation in the nucleotide position homologous with position 2058 of the Escherichia coli 23S rRNA gene. The nucleotide sequences of the peptidyl transferase region of the 23S rDNA from seven macrolide and lincosamide resistant and seven susceptible strains of Brachyspira spp. were determined. None of the susceptible strains were mutated whereas all the resistant strains had a mutation in position 2058. Susceptible strains became resistant in vitro after subculturing on agar containing 4 micrograms ml-1 of tylosin. Sequencing of these strains revealed an A-->G transition mutation in position 2058.

Anti-Bacterial Agents↗
PubMed1999

Possible interaction of genotypes at cystathionine beta-synthase and methylenetetrahydrofolate reductase (MTHFR) in neural tube defects. NTD Collaborative Group.

Neural tube defects are a common, complex disorder with genetic and environmental components to risk. We investigated the previously reported interaction between homozygosity for the thermolabile variant at the methylenetetrahydrofolate reductase and heterozygosity for the 844ins68 allele at the cystathionine beta-synthase loci in cases with lumbosacral myelomeningocele and their parents. Using control allele frequencies from our sample pooled with those published in the literature, we confirm a marginally significant interaction at these two loci. This finding suggests that additional, larger studies are warranted to investigate this possible interaction in more detail.

Alleles↗
PubMed1999

Repeated administration of trimethoprim/sulfadiazine in the horse--pharmacokinetics, plasma protein binding and influence on the intestinal microflora.

Six healthy adult horses were given repeated administrations of trimethoprim/ sulfadiazine (TMP/SDZ) intravenously (i.v.) (2.5 mg/kg TMP and 12.5 mg/kg SDZ) and orally (p.o.) as a paste (5 mg/kg TMP and 25 mg/kg SDZ). Both formulations were given twice daily for 5 days, with a 3-week interval between i.v. and oral administration. The influence of the drug combination on the intestinal microflora was examined and the plasma concentrations, pharmacokinetic parameters and plasma protein binding were determined. There were no major changes in the bacterial intestinal flora and no clinical evidence of gastrointestinal disturbances following the i.v. and oral TMP/SDZ administration. An initial reduction in the number of coliform bacteria during the treatment was notable, though with no evident difference between i.v. and oral treatment. The minimum concentration during a dose interval at steady state (Cminss), the elimination half-life (t1/2beta) and the mean residence time (MRT) were significantly greater after oral administration compared to i.v. for both TMP and SDZ. The plasma protein binding was measured to be 20% for SDZ and 35% for TMP. Oral administration of TMP/SDZ in a dose of 30 mg/kg given twice daily in the form of paste appeared as a satisfactory method for obtaining plasma levels above MIC (minimum inhibitory concentration in vitro) values during the interdosing interval.

Administration, Oral↗
PubMed1999

Pharmacokinetics of sulphadiazine-trimethoprim in lactating dairy cows.

Five Finnish Ayrshire cows in mid or end-lactation were treated with 40 mg sulphadiazine/kg and 8 mg trimethoprim/kg using intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) routes. Elimination of sulphadiazine was not affected by the route of administration (median t1/2 4.4-5.0 h) while elimination of trimethoprim was strongly limited by slow absorption from the injection site after s.c. and i.m. administration (median for apparent t1/2 21-25 h) compared to that after i.v. administration (median t1/2 1.2 h; p < 0.05). The median bioavailability of trimethoprim was also decreased, being 37% and 55% after s.c. and i.m. administration, respectively. When i.v. administration was used, trimethoprim concentration exceeded 0.1 mg/l in milk between 0.15-8 h while sulphadiazine concentrations above 2 mg/l were maintained from 0.5-2 h to 8 h. After s.c. and i.m. administration sulphadiazine in milk behaved similar to that after i.v. administration, while trimethoprim time-concentration curves were flat and trimethoprim concentrations were around 0.1 mg/l for an extended period of time (8-12 h). Median Cmax values in milk were only 0.07 mg/l and 0.10 mg/l for s.c. and i.m. administrations, respectively. After s.c. administration, 4 out of 5 cows showed signs of pain. After i.m. administration, 2 of the cows showed clear signs of pain and one had some local tenderness at the site of injection.

Animals↗