Anestesia Regional en el paciente anticoagulado: Definición de riesgos / Regional anesthesia in the patient one anticoagulado: Definition of risks

Se ha documentado en numerosos estudios clínicos la seguridad de administrar anestesia y analgesia neuroaxial en pacientes anticoagulados. El manejo de estos pacientes se basa en la relación entre el momento apropiado para colocar la aguja y retirar el catéter, con el tiempo en que se administró el fármaco anticoagulante. La familiaridad con la farmacología de los anticoagulantes, con los estudios clínicos realizados en pacientes que recibieron bloqueo neuroaxial estando bajo tratamiento con estos fármacos, y los reportes de casos de hematoma espinal, son los factores que deben guiar al clínico en la toma de decisiones. Han surgido nuevos retos en el manejo de pacientes anticoagulados que van a ser sometidos a bloqueo neuroaxial, a medida que se han establecido los protocolos para la prevención del tromboembolismo venoso perioperatorio. Igualmente, la introducción en el mercado de nuevos fármacos anticoagulantes y antiplaquetarios más eficaces ha ocasionado que el manejo de estos pacientes sea más complejo. En respuesta a estos tópicos que afectan la seguridad de estos pacientes, la Sociedad Americana de Anestesia Regional y Medicina del Dolor (ASRA) reunió la Segunda Conferencia de Consenso de Opinión sobre Anestesia Neuroaxial y Anticoagulación. Es importante hacer notar que aún cuando las declaraciones del Consenso se basan en una evaluación completa de la información disponible, en algunos aspectos la información es escasa. El desacuerdo con las recomendaciones contenidas en este documento puede ser aceptable si está basado en el buen juicio del anestesiólogo responsable. Las conclusiones del Consenso están diseñadas para fomentar la seguridad y la calidad del cuidado del paciente, pero no pueden garantizar un resultado específico. Ellas están sujetas a una revisión periódica, en la medida que la evolución de la información y de la práctica lo justifiquen. Finalmente, la información actual se enfoca en el bloqueo neuroaxial y los anticoagulantes; el riesgo que existe con la administración de técnicas regionales periféricas o de plexos en pacientes anticoagulados aun no se ha definido. Provisionalmente, las conclusiones de este Consenso de Opinión de Anestesia Neuroaxial y Anticoagulación pueden aplicarse de manera conservadora en las técnicas regionales periféricas y de plexos. Sin embargo, estas recomendaciones pueden ser más restrictivas de lo necesario...

Safety aspects of enterococci from the medical point of view.

Enterococci occur in a remarkable array of environments. They can be found in soil, food, and water, and make up a significant portion of the normal gut flora of humans (10(5)-10(7)/g of stool) and animals. As other bacteria of the gut flora, enterococci can also cause infectious diseases. Most clinical isolates are Enterocococus faecalis, which account for 80-90% of clinical strains. Enterocococus faecium accounts for 5-10% of such isolates. Typical enterococcal infections occur in hospitalised patients with underlying conditions representing a wide spectrum of severity of illness and immune modulation. Enterococci today rank second to third in frequency among bacteria isolated from hospitalised patients. They are isolated from urinary tract infections, intra-abdominal and pelvic infections, bacteremias, wound and tissue infections, and endocarditis--often as part of a polymicrobial flora. Surprisingly, little is known about the factors that contribute to the ability of enterococci to cause infections. Many strains of E. faecalis produce a cytolysin (haemolysin) exhibiting tissue-damaging capacity. Further extracellular products often observed in clinical isolates are a proteinase (gelatinase), hyaluronidase, and extracellular superoxide. Furthermore, many of the clinical isolates possess the aggregation substance on the surface and an extracellular surface protein, both contributing to the adherence to eucaryotic cells. Some strains of E. faecalis, and many E. faecium strains are resistant to multiple antimicrobials. The ultimate role of all these factors in enterococcal pathogenicity remains to be determined. It was previously thought that enterococcal infections were endogenously acquired from the patient's own gut flora. A rather new concept that has emerged is that enterococcal disease is a two-stage process. There is an initial colonisation of the gastrointestinal tract by enterococcal strains possessing virulence traits and/or antibiotic resistance. Subsequently, this population spreads, often facilitated by antibiotic elimination of competitors. For a selected number of patients, there is subsequent tissue invasion from the gastrointestinal tract reservoir. From this concept, it can be deduced that enterococcal strains without virulence traits and antibiotic resistances exogenously transferred into the human gut via food products or probiotics will not represent any risk for immunocompetent individuals. In very severely immunocompromised patients, however, a risk for enterococcal disease by such strains cannot completely be excluded.

Correolide and derivatives are novel immunosuppressants blocking the lymphocyte Kv1.3 potassium channels.

The voltage-gated potassium channel, Kv1.3, is specifically expressed on human lymphocytes, where it controls membrane potential and calcium influx. Blockade of Kv1.3 channels by margatoxin was previously shown to prevent T cell activation and attenuate immune responses in vivo. In the present study, a triterpene natural product, correolide, was found to block Kv1.3 channels in human and miniswine T cells by electrophysiological characterization. T cell activation events, such as anti-CD3-induced calcium elevation, IL-2 production, and proliferation were inhibited by correolide in a dose-dependent manner. More potent analogs were evaluated for pharmacokinetic profiles and subsequently tested in a delayed-type hypersensitivity (DTH) response to tuberculin in the miniswine. Two compounds were dosed orally, iv, or im, and both compounds suppressed DTH responses, demonstrating that small molecule blockers of Kv1.3 channels can act as immunosuppressive agents in vivo. These studies establish correolide and its derivatives as novel immunosuppressants.

Identification and biochemical characterization of a novel nortriterpene inhibitor of the human lymphocyte voltage-gated potassium channel, Kv1.3.

A novel nortriterpene, termed correolide, purified from the tree Spachea correae, inhibits Kv1.3, a Shaker-type delayed rectifier potassium channel present in human T lymphocytes. Correolide inhibits 86Rb+ efflux through Kv1.3 channels expressed in CHO cells (IC50 86 nM; Hill coefficient 1) and displays a defined structure-activity relationship. Potency in this assay increases with preincubation time and with time after channel opening. Correolide displays marked selectivity against numerous receptors and voltage- and ligand-gated ion channels. Although correolide is most potent as a Kv1.3 inhibitor, it blocks all other members of the Kv1 family with 4-14-fold lower potency. C20-29-[3H]dihydrocorreolide (diTC) was prepared and shown to bind in a specific, saturable, and reversible fashion (Kd = 11 nM) to a single class of sites in membranes prepared from CHO/Kv1.3 cells. The molecular pharmacology and stoichiometry of this binding reaction suggest that one diTC site is present per Kv1.3 channel tetramer. This site is allosterically coupled to peptide and potassium binding sites in the pore of the channel. DiTC binding to human brain synaptic membranes identifies channels composed of other Kv1 family members. Correolide depolarizes human T cells to the same extent as peptidyl inhibitors of Kv1.3, suggesting that it is a candidate for development as an immunosuppressant. Correolide is the first potent, small molecule inhibitor of Kv1 series channels to be identified from a natural product source and will be useful as a probe for studying potassium channel structure and the physiological role of such channels in target tissues of interest.

[Ganglion cyst of the cervical spine causing radiculopathy]. / Le kyste ganglionnaire de la colonne cervicale responsable d'une radiculopathie.

A case of ganglion cyst of the cervical spine causing radiculopathy is presented. This epidural mass is rare at the cervical level. Computed tomography suggests the diagnosis by the postero-lateral position of the mass close to facet joint. The trilobed configuration and the tissue characterisation of the cyst are well documented on MRI.

Evaluation of the anterior cruciate ligament of the knee: comparison between partial flexion true sagittal and extension sagittal oblique positions during MR imaging.

OBJECTIVE: To compare partial flexion true sagittal (FS) magnetic resonance (MR) images with extension sagittal oblique (ESO) MR images with regard to delineation of the anterior cruciate ligament (ACL) in the knee. DESIGN: To establish the appropriate degree of flexion of the knee joint, two human cadaveric knee joints were used as a supplementary technique. FS and ESO images then were performed in 17 knees with an intact ACL and six knees with a torn ACL. In 22 of the 23 knees in which the MR diagnosis of intact or torn ACL corresponded to that derived from arthroscopy, the paired MR images were rated by a three-point scale. RESULTS: FS images were rated superior to ESO images in 53%, 41% and 47% of cases with regard to femoral attachment sites, midportions and tibial attachment sites of intact ACLs, respectively. FS images allowed better assessment of disrupted ACLs and residual ligamentous structures. Overall the FS images were either equal to or better than the ESO in the majority of cases. CONCLUSION: FS images are useful when the ACL is not well visualized in initial ESO images.

Low specificity of the bacterial index for the diagnosis of bacterial pneumonia by bronchoalveolar lavage.

The bacterial index (BI) as defined by the sum of log10 colony-forming units (cfu) of microorganisms per milliliter of bronchoalveolar lavage (BAL) fluid, i.e., a multiplication of the single cfu/ml, has been used to distinguish between polymicrobial pneumonia (BI> or =5) and colonization (BI<5). Since many false-positive results are to be expected using this parameter, the diagnostic value of the BI was studied prospectively by obtaining bacteriologic cultures of BAL fluid in 165 consecutive unselected patients. In 27 cases the diagnosis of bacterial pneumonia was established on clinical criteria. In 133 patients pneumonia could be excluded, and in five patients the diagnosis remained unclear. Using a cut-off of > or = 10(5) cfu/ml BAL fluid, sensitivity and specificity for the diagnosis of pneumonia were 33% (9/27) and 99% (132/133), respectively. Sensitivity was mainly influenced by prior treatment with antibiotics, being 70% (7/10) in untreated and 12% (2/17) in treated patients. Applying the BI methodology at a cut-off of > or =5, however, resulted in an unacceptably high rate of 16 additional false-positive results, thus lowering the specificity to 87% (116/133; P<0.0001) while increasing the sensitivity to only 41% (11/27; P = 0.77). In conclusion, given the high rate of false-positive results, the methodology of the BI is of doubtful value for the diagnosis of bacterial pneumonia by BAL in an unselected patient group. By applying the absolute number of cfu/ml BAL fluid, however, positive bacteriologic cultures of BAL fluid are highly specific for the diagnosis of pneumonia. Their sensitivity is limited by previous antibiotic therapy.

[Sensitivity of bacteria to therapeutic drugs (Zurich 1996)]. / Die Empfindlichkeit von Bakterien gegen Chemotherapeutika (Zürich, 1996).

This paper describes the frequency of susceptibility of Gram-negative and Gram-positive bacteria against antibacterial agents. The data are based on all susceptibility tests performed in 1996 at the Department of Medical Microbiology of the University of Zurich and at the private medical laboratory "medica" in Zurich. The evaluation of the results from 1975 to 1996 shows that susceptibilities against the antimicrobial agents tested have not changed markedly in this period with few exceptions. The tables may be a help for the physician in his decision for a "calculated chemotherapy" of bacterial infections.

Evidence of the subperiosteal origin of osteoid osteomas in tubular bones: analysis by CT and MR imaging.

OBJECTIVE: A large series of patients with pathologically proven osteoid osteoma of tubular bones was reviewed to determine the frequency of a subperiosteal site of origin. MATERIALS AND METHODS: Thirty-eight cases that were included met two criteria: the tumor was located in a tubular bone, and the lesion had been evaluated by CT scanning or MR imaging, or both. The location of the osteoid osteoma was categorized as intracortical, sub-periosteal, endosteal, or medullary. RESULTS: Among the 38 cases, 19 were imaged with CT scanning, 14 with MR imaging, and five with both techniques. The most common affected sites were the femur (n = 13), tibia (n = 15), and humerus (n = 4). Among these 38 cases, 18 were intracortical, two were intramedullary, and 18 were subperiosteal. CONCLUSION: Osteoid osteomas occurring in a subperiosteal or surface location are not rare. Indeed, many osteoid osteomas arising in a tubular bone possibly originate in a subperiosteal site and later appear as an intracortical lesion. This site of origin appears to relate principally to continual remodeling of bone with subperiosteal deposition and endosteal erosion.

Survey and molecular genetics of SHV beta-lactamases in Enterobacteriaceae in Switzerland: two novel enzymes, SHV-11 and SHV-12.

Sixty isolates of Enterobacteriaceae resistant to beta-lactam antibiotics were collected over a period of 2 years in Switzerland and screened by hybridization for the carriage of SHV genes. Thirty-four positive strains were found, and their SHV genes were amplified and sequenced. SHV extended-spectrum beta-lactamases (ESBLs) were found: 13 strains contained SHV-2a, 12 harbored SHV-2, and SHV-5 was found twice. Four strains were shown to contain SHV-1. In addition, we report two new SHV variants, termed SHV-11 (non-ESBL) and SHV-12 (ESBL). In spite of the carriage of SHV ESBLs, many strains showed only low resistance to one or more third-generation cephalosporins. In addition, 26 did not transfer the blaSHV gene in mating experiments.

Impact of sar and agr on methicillin resistance in Staphylococcus aureus.

The global regulators agr and sar control expression of cell wall and extracellular proteins. Inactivation of either sar and/or agr in a typical heterogeneously methicillin-resistant Staphylococcus aureus resulted in a small but reproducible decrease in the number of cells in the subpopulation expressing high methicillin resistance. The amount of low affinity penicillin-binding protein PBP2', the prerequisite for methicillin resistance, was apparently not affected, however, a reduction in PBP1 and PBP3 production was observed, suggesting that these resident PBPs of the cells might be involved somehow together with PBP2' in high level methicillin resistance.

Prospective evaluation of a semiquantitative dip slide method compared with quantitative bacterial cultures of BAL fluid.

BACKGROUND: Quantitative bacteriologic workup of BAL fluid (BALF) has evolved as a sensitive and specific technique for the diagnosis of bacterial pneumonia. Conventional quantitative cultures are expensive, time-consuming, and often unavailable on a 24-h basis. Therefore, we evaluated a dip slide method for the semiquantitative measurement of bacterial cultures in BALF specimens and compared the results with those from conventional quantitative cultures. METHODS: Fifty BALF specimens from 45 patients with suspected pulmonary infection were examined prospectively with both methods. We compared the microbiologic results of conventional quantitative cultures with those of the dip slide method that is commercially available for blood cultures. Cost-effectiveness analysis of both methods was performed. RESULTS: In 37 BALF specimens, 64 bacterial strains were detected with both techniques. The dip slide method and conventional cultures showed a high correlation with respect to the colony counts of the individual organisms per milliliter BALF (r=0.935; p= 0.0001) and the sum of colony counts in individual patients (r=0.947; p=0.0001). Although five strains were not detected by the dip slide technique, the diagnostic accuracy was not influenced. In 13 BALF samples, there was no growth of bacteria with both techniques. While the diagnostic yield of both methods was similar, the dip slide technique was 44 to 66% less expensive than conventional cultures. CONCLUSIONS: The examination of BALF with a clip slide method is highly comparable to conventional quantitative culture techniques, less expensive, and can be used independently of a specialized microbiology laboratory on a 24-h basis.

Detection of genes coding for extended-spectrum SHV beta-lactamases in clinical isolates by a molecular genetic method, and comparison with the E test.

A highly sensitive and specific method, termed PCR/NheI, for the detection of genes coding for SHV extended-spectrum beta-lactamases (ESBL) in clinical isolates is presented. It is based on polymerase chain reaction (PCR) amplification of the blaSHV genes, followed by restriction with NheI. Due to the glycine (positive 238) (SHV-non-ESBL)-->serine (position 238) (SHV-ESBL) mutation, only PCR fragments from the genes coding for SHV-ESBLs were cleaved. A commercially available test for ESBLs, the E test ESBL, identified 52% of our 29 clinical isolates carrying blaSHV-ESBL genes as ESBL producers.

Sequence and characterization of a novel chromosomal aminoglycoside phosphotransferase gene, aph (3')-IIb, in Pseudomonas aeruginosa.

A novel, probably chromosomally encoded, aminoglycoside phosphotransferase gene was cloned on a 2,996-bp PstI fragment from Pseudomonas aeruginosa and designated aph (3')-IIb. It coded for a protein of 268 amino acids that showed 51.7% amino acid identity with APH (3')-II [APH(3') is aminoglycoside-3' phosphotransferase] from Tn5. Two other open reading frames on the cloned fragment showed homology to a signal-transducing system in P. aeruginosa.

Antimicrobial susceptibilities and serotypes of invasive Streptococcus pneumoniae strains in Switzerland.

In 1993 and 1994, 10 microbiological laboratories in Switzerland collected 351 strains of Streptococcus pneumoniae from invasive infections. Susceptibilities to the main representatives of the chemical classes were as follows: penicillin, 93%; chloramphenicol, 92%; erythromycin, 94%; sulfamethoxazole-trimethoprim, 86%; tetracycline, 92%; vancomycin, 100%. Forty-three strains showed resistance to one agent, and 35 strains showed resistance to two or more antimicrobial agents simultaneously; i.e., 22% of the strains were resistant to at least one antimicrobial agent. Four strains (1%) were fully resistant to penicillin, whereas 21 strains (6%) showed reduced susceptibility. Of these 25 strains not fully susceptible to penicillin, 10 were resistant to one, 3 were resistant to two, and 8 were resistant to three additional antimicrobial agents. Of the quinolones, sparfloxacin was the most active substance, with an MIC at which 90% of the strains are inhibited of 0.5 mg/liter. The most common serotypes were types 6 (13.6% of isolates), 7 (10.5%), 19 (10.5%), 14 (9.1%), and 1 (8.5%) as well as 3 and 23 (8.0% each). Reduced susceptibility to penicillin was found mainly among serotypes 6, 14, 19, and 23. The currently available 23-valent pneumococcal vaccine covers 320 (91%) of the pneumococci isolated. Regional differences within Switzerland with regard to serotypes and antimicrobial resistance were not observed.

A comparative structural study on the steroids [1,2,5]oxadiazolo[3', 4':3,4]-5 alpha-pregn-16-en-20-one oxime (HS998), [1,2,5]oxadiazolo[3, 4':3,4]-5 beta-pregn-16-en-20-one (HS973) by NMR, molecular modeling, and X-ray investigations.

The molecular structure of the steroids [1,2,5]oxadiazolo[3', 4':3,4]-5 alpha-pregn-16-en-20-one oxime, [1,2,5]oxadiazolo[3',4':3, 4':3,4]-5 alpha-pregn-16-en-20-one and [1,2,5]oxadiazole]3',4':3,4]-5 beta-pregn-16-en-20-one has been determined. The proton-proton distances in the solid state from previous crystallographic studies are compared with the corresponding distances from novel and previous solution NMR as well as from novel in vacuo modeling studies.

New system based on site-directed mutagenesis for highly accurate comparison of resistance levels conferred by SHV beta-lactamases.

We developed a system based on site-directed mutagenesis that allows a precise comparison of SHV enzymes under isogenic conditions. In addition, the influences of two different, naturally occurring promoters were examined for each SHV derivative. The system comprised two separately cloned DNA fragments, each the size of 3.6 kb. Both fragments encoded an SHV gene originating from clinical isolates but with different promoters. The structural genes were made identical by site-directed mutagenesis. Other mutations were then introduced into both fragments by means of site-directed mutagenesis, resulting in the SHV derivatives SHV-1, SHV-2, SHV-2a, SHV-3, and SHV-5. The amino acid exchange of glutamic acid at position 235 for lysine in SHV-5 resulted in the highest resistance levels. SHV-3, differing from SHV-2 by the exchange of arginine at position 201 for leucine and previously described as indistinguishable from SHV-2, was shown to cause slightly higher resistance to ceftazidime and lower resistance to ceftriaxone, cefotaxime, and cefepime than SHV-2. The point mutation in SHV-2a, with the leucine-to-glutamine replacement at the unusual position 31, previously considered almost insignificant, proved to increase resistance to ceftazidime but reduced the MICs of all other cephalosporins tested when compared with those for SHV-2. For all clones harboring SHV derivatives, resistance was increased by a stronger promoter, in some cases masking the effect of the point mutation itself and demonstrating the importance of regulatory mechanisms of resistance.

Synthesis, Characterization and In vitro Antitumour Activity of Novel Organotin Derivatives of 1,2- and 1,7-Dicarba-Closo-dodecaboranes.

Several organotin derivatives of 1,2- and 1,7-dicarba-closo-dodecaboranes were synthesized and characterized by (119)Sn Mössbauer, (1)H, (13)C and (119)Sn NMR spectroscopy. Their antitumour activities in vitro against cancerous cell lines of human origin are reported.