RESUMO
OBJECTIVE: This study was aimed to demonstrate the clinical benefits of rearranged during transfection (RET) genetic screening in patients with apparently sporadic medullary thyroid cancer (MTC) not only to identify the hereditary nature of the disease in the index case but also to discover family members harbouring the same germline mutations (i.e. gene carriers) who are unaware of their condition. CONTEXT: RET genetic screening allowed the identification of germline RET mutations in apparently sporadic MTC resulting in their re-classification as hereditary forms. PATIENTS AND MEASUREMENTS: RET genetic screening was performed in 729 apparently sporadic MTC patients by direct sequencing RET exons 5, 8, 10, 11 and 13-16. Clinical and biochemical evaluation of gene carriers was also performed. RESULTS: We discovered an unsuspected germline RET mutation in 47 of 729 (6·5%) apparently sporadic MTC who were re-classified as hereditary. We found 60 of 146 (41·1%) gene carriers, 35 of whom had biochemical or clinical evidence of MTC. Thirty gene carriers underwent total thyroidectomy and 27 of 30 (90%) were persistently cured after a mean follow-up of 6·0 years. As a further result of RET genetic screening, we observed a significantly higher prevalence of familial medullary thyroid cancer (FMTC) in our series with respect to the largest series of the International RET Consortium (P = 0·0002). CONCLUSIONS: RET genetic screening of patients with apparently sporadic MTC represents a major tool for the preclinical diagnosis and early treatment of unsuspected affected family members and allows the identification of a relevant percentage of hidden FMTC.
Assuntos
Testes Genéticos/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/diagnóstico , Carcinoma/genética , Carcinoma Medular/congênito , Carcinoma Neuroendócrino , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 2a/genética , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética , Reação em Cadeia da Polimerase , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Adulto JovemRESUMO
It has been clearly established that the inoculum size greatly affects the results of antibiotic susceptibility tests performed in both liquid and solid media in standard laboratory growth conditions (i.e. planktonic). Recently methods were developed to perform antibiotic susceptibility tests on bacteria growing in sessile conditions. The present study investigates the effect of the inoculum size on results obtained by these methods. Results show that the inoculum size does not affect tests performed in sessile conditions. A simple and reliable method is proposed to be applied to routine microbiological laboratory procedures.
Assuntos
Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana/métodos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus epidermidis/efeitos dos fármacos , Staphylococcus epidermidis/crescimento & desenvolvimento , Reprodutibilidade dos TestesRESUMO
The antibacterial activity of 6 antibiotics towards 10 gram-positive and 6 gram-negative glycocalyx-producing strains, has been evaluated by employing a method which partially simulates the in vivo colonization of prosthetic devices. The results showed that routine antibiotic sensitivity tests are not predictive about the response of the glycocalyx-embedded bacteria, and that prophylaxis may be useful with ofloxacin and clindamycin, before placing a prosthetic device. Once bacterial colonization had already occurred, however, none of the tested antibiotics was able to eradicate the sessile bacterial form. The minimum bactericidal concentration (MBC) values, indeed, were much higher than those determined on the planktonic form, and were much higher than serum and tissue levels that can be reached in vivo.
Assuntos
Antibacterianos/farmacologia , Bactérias/metabolismo , Infecções Bacterianas/metabolismo , Cateteres de Demora , Testes de Sensibilidade Microbiana , Próteses e Implantes , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Membrana Celular/metabolismo , Testes de Sensibilidade Microbiana/métodosRESUMO
The effect of the type of sugar used as substrate on the susceptibility of Streptococcus mutans to antibiotics was evaluated. Thirty strains, grown in excess of sucrose (s-MIC) and in excess of glucose (g-MIC), were tested for susceptibility to four cephalosporins. About 21% of the strains were sensitive in the presence of sucrose and resistant in the presence of glucose, whereas only 3% of the strains showed the opposite situation. The mean values of the s-MICs of the four cephalosporins were significantly lower than those of the g-MICs. These findings may also be explained by the synthesis, in excess of sucrose, of insoluble glucan by Streptococcus mutans which increases the interbacterial distance and promotes antibiotic diffusion. Given the susceptibility of Streptococcus mutans grown in excess of sucrose to cefotaxime and cefepime, these antibiotics may be used in the primary prevention of infective endocarditis, when subjects predisposed to endocarditis need invasive dental therapy.
Assuntos
Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Glucose/farmacologia , Streptococcus mutans/efeitos dos fármacos , Sacarose/farmacologia , Criança , Pré-Escolar , Humanos , Resistência beta-LactâmicaRESUMO
The percentage of anaerobic micro-organisms in the subgingival microflora represents a simple microbiological index which not only refers to the state but also the risks of periodontal health. The present study aimed to compare two different methods of calculating this index. The study was performed in 45 subjects with moderate gingivitis provoked by the previous application of dental fixtures anchored to both arches. A sample of subgingival microflora was collected from each patient at the level of the vestibular gingival sulcus of the first upper right molar. This was then vortexed, diluted and inoculated in three series of plates. It was chosen to use Walker's culture medium. The total bacterial count was evaluated by incubating the first series of plates in anaerobiosis; the anaerobic bacterial was calculated by subtracting from the total the of facultative aerobic-anaerobic micro-organisms, which in turn was obtained using two methods: the first (method AE) consisted of incubating another series of plates in aerobiosis; the second (method M) involved incubating the last series of plates in anaerobiosis, and adding metronidazole to the culture medium in a solution of 2.5 mg/l. The plates were then kept at 37 degrees C for seven days. The mean percentage of anaerobic microorganisms, given by the percentage ratio between anaerobic and total, relating to the 45 cases studied, was as follows: using method AE: 57.8 +/- 26.3%, and using method M: 40.2 +/- 27.2%. Both figures come close to that proposed and calculated using a much more sophisticated method by Slots, namely 41.5 +/- 19.2% in the event of gingivitis.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Bactérias Anaeróbias/isolamento & purificação , Gengiva/microbiologia , Adolescente , Adulto , Bactérias Anaeróbias/efeitos dos fármacos , Contagem de Colônia Microbiana/instrumentação , Contagem de Colônia Microbiana/métodos , Estudos de Avaliação como Assunto , Gengivite/microbiologia , Humanos , Metronidazol/farmacologiaAssuntos
Bacillus cereus/enzimologia , Dicloxacilina/farmacologia , Penicilinase/biossíntese , Ampicilina , Bacillus cereus/efeitos dos fármacos , Sítios de Ligação , Ligação Competitiva , Ácidos Carboxílicos/farmacologia , Indução Enzimática/efeitos dos fármacos , Cinética , Matemática , Rotação Ocular , Oxazóis/farmacologia , Ligação Proteica , Relação Estrutura-Atividade , Temperatura , Fatores de Tempo , Inibidores de beta-LactamasesAssuntos
Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Cefalosporinas/farmacologia , Animais , Bacillaceae/efeitos dos fármacos , Bacteroides/efeitos dos fármacos , Cefoperazona , Cefalosporinas/uso terapêutico , Enterobacteriaceae/efeitos dos fármacos , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Propionibacterium/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , beta-Lactamases/metabolismoAssuntos
Antibacterianos/farmacologia , Leucomicinas/farmacologia , Animais , Antibacterianos/uso terapêutico , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Leucomicinas/uso terapêutico , Camundongos , Testes de Sensibilidade Microbiana , Miocamicina , Peritonite/tratamento farmacológicoRESUMO
On the premise that a microorganism is sensitive or resistant to a chemoantibiotic according to it's concentrations in biological fluids and tissues, the A. examines those methods available in chemoantibiotic titration such as chemical, enzymatic, radio-immunologic, turbidimetric, potentiometric and agar-diffusion methods. By further evaluating the limits and capacities of these different methods, the A. describes in larger detail the agar-diffusion method which is considered more sensitive, practical and efficient. A brief report is made on the possibility of measuring antibiotic association.
Assuntos
Anti-Infecciosos/análise , Ágar , Difusão , Concentração de Íons de Hidrogênio , Métodos , Nefelometria e Turbidimetria , Potenciometria , Radioimunoensaio , Distribuição TecidualRESUMO
The microbiological properties of cephapirin, a new semisynthetis cephalosporin, have been studied. This antibiotic, if compared with ampicillin, shows a greater activity against gram positive bacteria, a lack of sensitivity to staphlococcal beta-lactamase, and a lower sensitivity to those produced by gram-negative bacteria. Useful therapeutic of cephapirin levels can be detected in human serum 6 h after administration of 500 and 1,000 mg parenterally.
Assuntos
Bactérias/efeitos dos fármacos , Cefalosporinas/farmacologia , Cefapirina/farmacologia , Ampicilina/sangue , Ampicilina/farmacologia , Animais , Bactérias/enzimologia , Proteínas Sanguíneas/metabolismo , Cefapirina/sangue , Avaliação Pré-Clínica de Medicamentos , Escherichia coli/efeitos dos fármacos , Humanos , Hidrolases/farmacologia , Klebsiella pneumoniae/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Ligação Proteica , Staphylococcus/efeitos dos fármacosRESUMO
The validity of nonsimultaneous association of penicillinase-sensitive beta-lactam antibiotics with halogenated isoxazolylpenicillins was tested in various Enterobacteriaceae strains. With several bacterial strains, expecially if producers of beta-lactamase type IV, exposure of either the bacterial suspensions of the brothsupernatant to the isoxazolylpenicillins appears both in vivo and in vitro to reduce the extent of subsequent hydrolysis of penicillinase-sensitive beta-lactam antibiotics.
Assuntos
Antibacterianos/farmacologia , Enterobacteriaceae/efeitos dos fármacos , Isoxazóis/farmacologia , Oxazóis/farmacologia , Penicilinase/farmacologia , Penicilinas/farmacologia , Animais , Enterobacteriaceae/enzimologia , Halogênios/farmacologia , Camundongos , Testes de Sensibilidade Microbiana , Penicilinase/biossíntese , beta-Lactamas/farmacologiaRESUMO
We found that nalidixic acid is a good inhibitor of conjugal transfer of R-plasmids and that related compounds show the same properties. We investigated recently synthetized quinolinic molecules. The inhibition was not due to bacterial activity of the compounds against donors, recipients or R transconjugants; in fact, the drug concentrations were twice or four times lower than the M.I.C. values. The new molecules showed a marked inhibitory effect in various R-mating experiments.
Assuntos
4-Quinolonas , Antibacterianos/farmacologia , Anti-Infecciosos , Conjugação Genética/efeitos dos fármacos , Ácido Nalidíxico/farmacologia , Quinolinas/farmacologia , Quinolonas , Ciprofloxacina , Escherichia coli/efeitos dos fármacos , Ácido Nalidíxico/análogos & derivados , NorfloxacinoRESUMO
We found it of interest to try to determine a microbiological parameter for the effects that sub-inhibitory doses of a chemotherapeutic agent may have on bacteria. To this end, the antibacterial activity of nalidixic acid was analyzed and our attention was directed to evidence of the production of beta-lactamase by 60 strains. The tests carried out showed that sub-inhibitory concentrations of nalidixic acid, from 2 to 64 times lower than the MIC (minimum inhibitory concentrations), were able to inhibit production of penicillinases in the 14 strains of Staphylococcus spp. tested, while only in 7 of the 21 strains of Gram-negative bacteria. Strains from our collection of beta-lactamase producing bacteria were analyzed, and our results confirmed that nalidixic acid inhibits plasmidic and chromosomic beta-lactamases.
Assuntos
Bactérias Gram-Negativas/enzimologia , Bactérias Gram-Positivas/enzimologia , Ácido Nalidíxico/farmacologia , beta-Lactamases/biossíntese , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacosRESUMO
Nalidixic acid and two recently synthetized 4-quinolones eliminated F'lac and R-plasmids from E. coli at concentrations of one half or one quarter of the minimum inhibitory concentration (MIC). Two of the three plasmids tested were cured by all derivatives, although with different frequencies. Pefloxacin was the most effective compound compared with the other quinolones and nalidixic acid the least active.
Assuntos
Escherichia coli/efeitos dos fármacos , Ácido Nalidíxico/farmacologia , Ofloxacino/farmacologia , Pefloxacina/farmacologia , Plasmídeos/efeitos dos fármacos , Testes de Sensibilidade MicrobianaRESUMO
Four fluoroquinolones (norfloxacin, ciprofloxacin, ofloxacin, and pefloxacin) were compared with nalidixic acid for their inhibitory effect on conjugal plasmid transfer. The inhibition was observed in mating experiments using various combinations of drugs at subinhibitory concentrations and 3 different plasmids in the E. coli k12 genetic background. Fluoroquinolones inhibited plasmid transfer to a greater extent than nalidixic acid. Ofloxacin and pefloxacin were consistently the most active agents, causing 90 to 100% inhibition of plasmid transfer in all mating systems studied.
Assuntos
Anti-Infecciosos/farmacologia , Conjugação Genética/efeitos dos fármacos , Ácido Nalidíxico/farmacologia , Fatores R/efeitos dos fármacos , Fenômenos Químicos , Química , Ciprofloxacina/farmacologia , Escherichia coli/efeitos dos fármacos , Norfloxacino/farmacologia , Ofloxacino/farmacologia , Pefloxacina/farmacologiaRESUMO
The antimicrobial activities of nalidixic acid-cephalexin (ratio 1:1) and cinoxacin-cefadroxil (ratio 1:2) combinations have been evaluated against 396 clinical isolates; many of them were nalidixic acid- or cinoxacin-resistant organisms (MIC greater than or equal to 100 micrograms/ml). We have also tested the nalidixic acid-amoxicillin combination (ratio 1:1) against 225 amoxicillin-resistant bacterial strains (MIC greater than or equal to 800 micrograms/ml). Synergy was found for 62-70% of the Enterobacteriaceae and nonfermenter bacilli tested and for 85-92% of the gram-positive bacterial strains. The 225 clinical isolates resistant to amoxicillin (MIC greater than or equal to 800 micrograms/ml) were synergistically inhibited by the nalidixic acid-amoxicillin combination.
Assuntos
Cefadroxila/farmacologia , Cefalexina/farmacologia , Cinoxacino/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Ácido Nalidíxico/farmacologia , Piridazinas/farmacologia , Amoxicilina/farmacologia , Sinergismo Farmacológico , Enterobacteriaceae/efeitos dos fármacos , Humanos , Testes de Sensibilidade MicrobianaRESUMO
The reliability of bioluminescence assays which employ the luciferin-luciferase ATP-dependent reaction to evaluate bacterial counts was studied, both in vitro and on urine specimens. Bioluminescence and cultural results for the most common urinary tract pathogens were analyzed. Furthermore, the influence of the culture medium, of the assaying method, and of the phase of growth on bioluminescence readings was studied. Results show that Proteus, Providencia, and Morganella strains are not correctly detected, neither in vitro nor in urine samples, by the standard assaying method. The analysis of assaying parameters demonstrated that some modifications to the extraction procedure of bacterial ATP could improve the reliability of this technique.