Análisis comparativo de los factores asociados a la mortalidad de las bacteriemas / Comparison of factors associated with mortality from bacteraemias in individuals aged 60-70 years old and in those aged more than 70 years

INTRODUCCIÓN: El objetivo de este estudio ha sido determinar los factores asociados, en relación con la evolución mortal, de las bacteriemias-fungemias ocurridas en un año, y comparar los resultados en la población con edades comprendidas entre 60 y 70 años y la población mayor de 70 años. PACIENTES Y MÉTODOS: Estudio descriptivo, prospectivo de todos los episodios de bacteriemias-fungemias producidos en el Hospital Universitario de la Princesa de Madrid, entre el 16 de mayo de 1996 y el 14 de mayo de1997. Se utilizaron las mismas definiciones en los dos grupos de estudio. El análisis univariado de los resultados se realizó con el test de la 2 y las variables con más de dos categorías mediante regresión logística, considerándose significación estadística un valor de p < 0,05. RESULTADOS: Un total de 250 episodios han sido analizados, 158 en personas mayores de 70 años frente a 92 episodios en el grupo de pacientes con edades comprendidas entre 60 y 70 años. Globalmente, no existe diferencia en cuanto a la mortalidad en ambos grupos (odds ratio [OR] = 1,22; intervalo, 0,662,24). El servicio que más episodios recibe en ambos grupos es el médico. Los microorganismos más frecuentes asociados a bacteriemia son los gramnegativos. La adquisición extrahospitalaria es la más habitual. El origen más frecuente es el vascular en el grupo de 60-70 años, y el genitourinario en el grupo de los mayores de 70 años. Hay un alto porcentaje de tratamientos quirúrgicos adecuados en ambos grupos. Las variables con significación clínica y estadística en cuanto a la evolución mortal en el grupo de 60-70 años son: adquisición intrahospitalaria (OR = 6,28 [1,9-20,7]); hipotensión (OR = 4,46 [1,14-17,4]); coagulación intravascular diseminada (OR = 4,93 [3,14-7,75]). Sin embargo, se asocia a menor evolución mortal la realización de un tratamiento quirúrgico adecuado (OR = 10,76 [2,017-57,05]).En el grupo de más de 70 años son factores asociados a mal pronóstico en cuanto a evolución a muerte: uso previo de antibióticos (OR = 2,71 [1,25-6,13]); hipotensión (OR = 3,35 [1,34-8,36]); trombopenia (OR = 2,7 [0,97-7,69]); coagulación intravascular diseminada (OR = 7,51 [0,65-83]). Sin embargo, también el tratamiento quirúrgico adecuado es un factor asociado a mejor pronóstico (OR = 6,03 [1,62-22,35]). CONCLUSIONES: No existen diferencias en cuanto a mortalidad en las personas con edades comprendidas entre 60 y 70 años y en los mayores de 70 años. Muchas de las variables se mantienen constantes en ambos grupos, lo que indica la potencia de dichas variables independientemente de la edad, siendo llamativa la asociación a mejor pronóstico del tratamiento quirúrgico adecuado, lo que debe favorecer dicho tipo de intervención terapéutica en caso necesario, independientemente de la edad (AU)

[Comparative study of prognostic and risk factors for mortality in polymicrobial bacteremia-fungemia in a university hospital: development over 10 years]. / Estudio comparativo de los factores de riesgo y pronósticos de mortalidad en las bacteriemias-fungemias polimicrobianas de un hospital universitario: evolución en 10 años.

OBJECTIVE: Eighty-two episodes of polymicrobial bacteremia in two time periods, 1986-87 and 1996-97, were compared to assess differences in risk factors and outcome to mortality. METHODS: A prospective, concurrent, anterograde study with univariate analysis of all episodes of polymicrobial bacteremia was performed in Hospital de la Princesa. Logistic regression analysis was applied to all significant variables (p < 0.05) in the univariate analysis in either of the two time periods. RESULTS: Variables showing statistically significant differences in incidence between the two time periods included the following: hospital acquired bacteremia; previous use of antibiotics; genitourinary, respiratory and cardiovascular manipulations; septic metastases; and absence of leukocytosis. These factors were more frequently present during 1986-87 than during 1996-97. The overall RR of outcome to mortality was five-fold greater during the first period than the second: RR 5.6 (CI 1.76-17.56) p < 0.001. The clinical characteristics at the onset of bacteremia associated with mortality in the first period were: underlying disease - < RR 2.20 (CI 1.18-4.08), steroid treatment - < RR 4.24 (CI 0.68-26.59), hypotension - < RR 2.05 (CI 1.0-4.17), and disseminated intravascular coagulation - < RR 2.31 (CI 1.69-3.35). Clinical characteristics at the onset of bacteremia associated with mortality in the second period were: hypotension - < RR 1.44 (CI 1.01-2.08), underlying disease - < RR 1.16 (CI 1.02-1.34), and disseminated intravascular coagulation - < RR 6.40 (CI 1.15-35.69). The variables independently associated with mortality in polymicrobial bacteremia were: period - < RR 2.05 (CI 1.50-2.10), underlying disease - < RR 7.05 (CI 2.68-7.50), hypotension - < RR 7.06 (CI 3.80-7.29), and (probably) vascular manipulations - < RR 3.41 (CI 0.85-4.53). CONCLUSION: Polymicrobial bacteremia-associated mortality was five-fold greater in 1986-87 than in 1996-97. The variables independently associated with mortality risk were underlying disease, hypotension, the period studied (which would include a number of variables not analyzed in this work) and, probably, vascular manipulations.

Estudio comparativo de los factores de riesgo y pronósticos de mortalidad en las bacteriemias-fungemias polimicrobianas de un hospital universitario: evolución en 10 años / Prognostic factors and mortality outcome of polymicrobial bacteremia in a university hospital: evolution after a 10-year interval

OBJETIVO. Se han estudiado 82 episodios de bacteriemias-fungemias polimicrobianas (BFP) en dos diferentes períodos (1986-1987 y 1996-1997) para valorar las diferencias en los factores pronósticos con evolución a muerte. MÉTODO. Estudio prospectivo, concurrente y anterógrado con análisis univariado de todos los episodios de BFP en el Hospital de La Princesa. Posteriormente se realizó regresión logística de todas las variables que presentaron significación estadística en el análisis univariado en al menos alguno de los dos períodos. RESULTADOS. Las variables con diferencias en la incidencia entre los períodos de estudio estadísticamente significativas fueron adquisición intrahospitalaria, uso previo de antibióticos, manipulaciones genitourinarias, respiratorias y cardiovasculares, metástasis sépticas y ausencia de leucocitosis, que fueron más frecuentes durante 1986-1987 que durante 1996-1997. Globalmente el riesgo relativo (RR) de evolución a muerte fue 5 veces mayor durante el primer período que en el segundo (RR, 5,6 [IC, 1,76-17,56]) p < 0,001. Las variables que se asociaron a incremento de la mortalidad durante el primer período fueron: presencia de enfermedad de base (RR, 2,20 [IC, 1,18-4,08]), tratamiento esteroideo (RR, 4,24 [IC, 0,68-26,59]), hipotensión (RR, 2,05 [IC, 1,0-4,17]), y presencia de coagulación intravascular diseminada (CID) (RR, 2,31 [IC, 1,69-3,35]). Las variables asociadas a muerte en el segundo período fueron: hipotensión (RR, 1,44 [IC, 1,01-2,08]), la presencia de enfermedad de base (RR, 1,16 [IC, 1,02-1,34]), y la existencia de CID (RR, 6,40 [IC, 1,15-35,69]). Las variables que de forma independiente incrementan la mortalidad en las bacteriemias polimicrobianas son: período (RR, 2,05 [IC, 1,50-2,10]), presencia de enfermedad de base (RR, 7,05 [IC, 2,68-7,50]), y la existencia de hipotensión (RR, 7,06 [IC, 3,80-7,29]). CONCLUSIÓN. En el período entre 1986-1987 la mortalidad asociada a BFP fue 5 veces mayor que entre 1996-1997. Las variables que de forma independiente se asocian a este incremento de la mortalidad son la existencia de enfermedad de base, la presencia de hipotensión y el propio período (que incluiría toda una serie de variables que no se han analizado en este trabajo) (AU)

The Alzheimer's disease activities of daily living international scale (ADL-IS).

BACKGROUND: Activities of daily living (ADL) deficits are integral components of dementia disorders, and ADL measures are among the most robust markers of the course of Alzheimer's disease (AD). Despite this acknowledged importance, no clearly useful ADL instrument for cross-cultural application in pharmacologic trials in the early stages of AD had been available. METHOD: An international effort was launched to develop an ADL scale for pharmacologic trials in early AD. Steps taken from 1990 to the present included: (1) international scientific working group meetings and reviews, (2) reviews of existing measures, (3) collating of existent, nonredundant items, (4) querying experts for new items, (5) interviews with informants and subjects in the USA, France, and Germany, toward the identification of potential new items, (6) identification of an item pool based upon these procedures, (7) creation of a trial instrument, (8) piloting of this instrument, and (9) refinement of the scale based upon statistical analysis of the pilot data. Final item selection was based upon: (1) relevance for > or = 80% of subjects in severity-stratified USA and German samples; (2) absence of gender and national biases; (3) significant (p <.05) discrimination between (a) normal versus mildly impaired and (b) mildly impaired versus moderately to moderately severely impaired subjects; and (4) Global Deterioration Scale (GDS) scores accounting for > or = 12% of variance in the item after controlling for age and gender. RESULTS: An ADL scale consisting of 40 items that correlate with the global and cognitive progress of AD is developed for international usage in pharmacologic trials in incipient, mild, moderate, and moderately severe AD. The scale contains 40 items falling within 13 ADL categories. The 40-item scale is shown to have .81 correlation with GDS staging, .81 with mental status assessment (Mini-Mental State Examination), and .81 with a psychometric test (the SKT) (p values < .001). CONCLUSION: This scale can be used to measure therapeutic response in AD.

Abdomen agudo por rotura diferida de diafragma / Acute abdomen due delayed diaphragmatic rupture

La rotura traumática del diafragma es una lesión poco frecuente que puede pasar desapercibida a menos que exista un elevado índice de sospecha. En el intervalo entre la rotura y la herniación del contenido abdominal hacia la cavidad torácica, los síntomas y signos son inespecíficos y las pruebas diagnósticas como la radiografía de tórax pueden ser normales. Presentamos un caso de manifestación tardía de una rotura diafragmática izquierda secundaria a un traumatismo torácico en accidente de tráfico. El paciente pedeció la estrangulación del segmento herniado del estómago en el tórax. Se revisa el mecanismo de la lesión y las técnicas diagnósticas de imagen (AU)

Informant-rated activities-of-daily-living (ADL) assessments: results of a study of 141 items in the U.S.A., Germany, Russia, and Greece from the International ADL Scale Development Project.

The analyses of an international pilot study presented in this article focused on the development of a cross-nationally valid activities-of-daily-living (ADL) scale sensitive to therapeutic effects in patients with mild memory impairment and mild to moderately severe dementia. The present report, which is part of an ongoing international research project, describes field testing results for 141 informant-rated items. The comparability of samples investigated in research centers in the U.S.A., Germany, Russia, and Greece concerning cognitive decline was evaluated globally as well as psychometrically using the Global Deterioration Scale, the Short Cognitive Performance Test, and the Mini-Mental State Examination. In the participating countries, a composite ADL score discriminated well between different stages of cognitive impairment because of dementia. However, international differences between the applied measures were observed. A practical ADL scale showing therapeutic sensitivity and international utility, will be constructed from the 141 informant-rated items under investigation in this pilot work.

Pharmacokinetic studies on clavulanate potentiated ticarcillin in normal subjects and patients with renal insufficiency.

Pharmacokinetics of the novel combination of ticarcillin with the beta-lactamase inhibitor clavulanic acid (BRL 28500, Timentin, Betabactyl) was investigated in order to calculate the dose reduction factor (DRF) and elaborate dosage recommendations for patients with varying degrees of renal impairment. Serum and urine levels of ticarcillin and clavulanic acid have been determined following the i.v. application of 3.2 g and 5.2 g BRL 28500 consisting of 3.0 g and 5.0 g ticarcillin, respectively, and 0.2 g of clavulanic acid each. 10 healthy volunteers and 9 patients received the 5.2 g formulation, and 6 normal subjects and 9 patients the 3.2 g formulation. The pharmacokinetics of both components of BRL 28500 behave fairly similarly and provides the combination with a logic basis. The dose reduction factor, being 1 by definition in normal renal function, rises in final renal failure to 2-3 for clavulanic acid and to 4-5 for ticarcillin. A dosis reduction to 1/2-1/4 will roughly produce the same AUC in a patient with terminal renal insufficiency as the normal dosage in a healthy subject. The distribution volume of ticarcillin and clavulanic acid was found to be enlarged probably due to overhydration in this group of patients. The recovery of both BRL 28500 components decreased with impaired renal function. The recovery 6 h after administration of 0.2 g clavulanic acid in the 5.2 g (3.2 g) BRL 28500 formulation fell from 58 +/- 12% (52 +/- 6) in healthy subjects to 25 +/- 14% (25 +/- 13) in patients with renal insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Timentin in the treatment of nosocomial bronchopulmonary infections in intensive care units.

A clinical trial with Timentin (ticarcillin plus clavulanic acid) was undertaken in patients with hospital-acquired lower respiratory tract infections. Two formulations, 3.2 and 5.2 g consisting of 200 mg clavulanic acid and 3 or 5 g ticarcillin, respectively were usually given three times daily. Eighty-one patients were evaluable for clinical efficacy and 89 for tolerance. The clinical cure rate was 96% of the assessable cases even though all patients had severe concurrent or underlying diseases. The pronounced synergism between ticarcillin and clavulanic acid resulted in a bacteriological elimination rate of 94%. Adverse effects were very rare and of a mild nature, and restricted to those usually seen with the well-tolerated penicillins. No toxicological abnormalities could be detected in extensive laboratory screening. Timentin is a highly effective broad-spectrum antibiotic with good tolerance. Its potentiated action in comparison to other penicillins against beta-lactamase-producing strains, could reduce the usage of aminoglycosides in the future.

Clinical evaluation of Timentin in complicated urinary tract infections.

Timentin proved to be highly effective in the treatment of 70 urological patients suffering from complicated urinary tract infections. There were few adverse effects, and development of resistance was not observed. Surgical treatment was possible in each case, without any septic complications. The results show that Timentin is a very useful drug for the urologist who often treats complicated urinary tract infections, especially because of its low re- and super-infection rate and the absence of development of resistance.

Single dose therapy with temocillin in acute gonorrhoea.

Temocillin has pronounced in vitro activity against both penicillin-sensitive and penicillinase-producing gonococci. A single intramuscular injection of temocillin 0.5 g or 1.0 g resulted in the disappearance of the infecting gonococci in 91% of 75 patients and 94% of 192 patients in 2 separate trials. The systemic and local tolerance of the drug was unusually favourable and no serious side effects were observed.

Different classes of nucleotide binding sites in the (Na+ + K+)-ATPase studied by affinity labeling and nucleotide-dependent SH-group modifications.

The ATP analog 6-[(3-carboxy-4-nitrophenyl)thiol]-9-beta-D-ribofuranosylpurine 5'-triphosphate (Nbs6ITP) is slowly hydrolyzed at pH 7.4 by the (Na+ + K+)-ATPase, whereas it binds covalently at pH 8.5 and inhibits the enzyme irreversibly. Time courses of irreversible inhibition could only be fitted to a model in which the enzyme can exist in two slowly interchangeable states, one of which is enzymatically active and binds Nbs6ITP first reversibly and then covalently. Arguments that the covalent binding occurs at a low affinity nucleotide binding site are: (a) similarity of the Ki Nbs6ITP for the reversible and the irreversible inhibition and of K0.5 for ATP protection; (b) stoichiometry of covalent Nbs6ITP binding per alpha subunit of 0.8; and (c) change of complex substrate dependence of the enzyme to a Michaelis-Menten type after Nbs6ITP modification. This change in kinetics and the finding that the Nbs6ITP inactivation at a low affinity nucleotide binding site is increased by micromolar ADP concentrations indicates that the (Na+ + K+)-ATPase contains two different nucleotide binding sites. Since studies of nucleotide effects on enzyme inactivation by 5,5'-dithiobis(2-nitrobenzoic acid) did not confirm the hypothesis of an SH-group in a nucleotide binding site, Nbs6ITP may bind to another functional group, e.g. to an OH-group of tyrosine.

Kinetic studies on bacterial plasma membrane ATPase (F1). Nucleotide-induced long term inactivation of ATP hydrolyzing activity is linked to the formation of multiple "tight" enzyme nucleotide complexes.

ADP and the ATP analogs Nb-S6ITP (6-[(3-carboxy-4-nitrophenyl)thio]-9-beta-D-ribofuranosylpurine 5'-triphosphate) and AMP-P(NH)P (adenyl-5'-yl imidodiphosphate) interact with soluble plasma membrane ATPase (F1) from Micrococcus species in two ways: (i) at short incubation times, these inhibitors exhibit the kinetics of competitive inhibition, (ii) at long incubation times, these inhibitors induce an inactivation of the ATPase which can be reversed only in the case of AMP-P(NH)P. Kinetic treatment of the long term inactivation by ADP or Nb-S6ITP reveals a pseudo-first order process via the formation of an enzyme-inhibitor complex for which a Km analogous constant is obtained that is identical with the corresponding Ki value of the competitive inhibition. The long term inactivation by ADP and Nb-S6ITP involves the successive "tight" binding of 6 +/- 1 nucleotides/F1 molecule. One additional ADP molecule/F1 complex which is also "tightly" bound has no effect on the ATPase activity. The long term inactivation by ADP and Nb-S6ITP is inhibited at higher inhibitor concentrations according to a kinetics analogous to a substrate excess inhibition. Evidence is presented indicating that the mechanism of ATP hydrolysis by F1 and the long term inactivation by ADP or Nb-S6ITP are related processes. The mechanism of long term inactivation by AMP-P(NH)P appears to be different from that of ADP or Nb-S6ITP.

F1-ATPase from Micrococcus sp. ATCC 398. Purification by ion-exchange chromatography and further characterization. (Auto)proteolysis and dissociative effects.

The preparation of highly purified F1-ATPase from Micrococcus sp. ATCC 398 by application of DEAE-Sepharose CL-6B chromatography as final step is described. This enzyme consists of five subunits of different molecular weight: alpha (65000), beta (55000),gamma (35000), delta (20000), and epsilon (17000). Disc electrophoresis on 5% polyacrylamide gels removes the epsilon-polypeptide yielding an active ATPase complex with four different subunits: alpha, beta, gamma, delta. Additionally, by variation of the ionic strength delta can (partly) removed allowing the isolation by disc electrophoresis of an active ATPase complex which consists only of three different subunits alpha, beta, and gamma. If the DEAE-Sepharose chromatography is carried out in the absence of diisopropyl phosphofluoridate (auto)proteolysis yields both an active ATPase with the subunits alpha+ (mol. wt 61000), beta, gamma, and delta and an inactive protein complex with the subunits alpha+, beta, gamma, delta, and two additional polypeptides a (mol. wt 38000) and b (mol. wt 23000). The latter two polypeptides are supposedly fragments of alpha+-chains which have become partially cleaved by (auto)proteolysis.

The polymerization reaction of muscle actin.

Recent advances in the studies of the aggregation of G-actin monomers, containing one molecule of ATP, to long filaments of F-actin, with a concomitant hydrolysis of the nucleotide to ADP, are reviewed. With the aid of omega-ATP, the association and dissociation rate constant of the nucleotide could be determined. The binding of the nucleotide is enhanced by the binding of one Ca++ ion, probably at a different site. The delta G value of the Mg++ or Ca++ induced polymerization has been determined to --39 to--59 kJ/mole, the critical protein concentration for the ATP-G-actin to ADP-F-actin conversion is very strongly influenced by the concentration of bivalent cations. The rate constants of the protein monomers, and the rate and equilibrium constants for the propagation step show the process to be extremely cooperative. Actin shows the interesting phenomenon of translocational head-to-tail polymerization, which may be regulated by ATP. The contact sites between the monomers in F-actin have been labeled by chemical modification. Two tryosine residues, 53 and 69, are probably close to one of the two sites. The ATP binding sites has been labeled by an ATP analog, and there is evidence that it is close to the contact site.

Membrane-bound F1 ATPase from Micrococcus Sp. ATCC 398E. Purificationa and characterization ny affinity chromatography.

A chemically reactive ATP analogue, 6-[(3-carboxy-4-nitrophenyl)thio]-9-beta-D-ribofuranosylpurine 5'-triphosphate (Nbs6ITP) has been synthesized. It has the ability to form stable thioether bonds between the 6-position of the purine ring and aliphatic mercapto groups. The nucleotide moiety of the reagent has been covalently bound to agarose, via iminobispropylamine and N-acetyl-homocysteine as space with the purpose of producing an affinity chromatography material. The affinity matrix binds solubilized F1 ATPase from a crude extract of Micrococcus sp. membranes. Afterwards the enzyme can be selectively eluted from the column at a defined ATP concentration. This method is superior to the conventional purification with respect to speed and convenince of the preparation. The affinity chromatography leads in a one-step process to the same purity to enzyme, substituting several steps of the conventional method. In addition, the affinity matrix was used for binding studies. Although the presence of Mg2+ ions is a prerequisite for the hydrolysis of nucleoside 5'-triphosphates, evidence is presented indicating that the binding of the nucleoside triphosphates to highly purified F1 ATPase from Micrococcus sp. appears not to be influenced by Mg2+ ion concentrations so far examined.

Me2+-(13 S) ATPase from Micrococcus sp. ATCC 398E. The effect of trypsin on the purified enzyme.

By trypsin treatment of highly purified ATPase (EC 3.6.1.3) from Micrococcus sp. ATCC 398E, two enzyme modifications have been obtained. (i) ATPase Ta, which has about the same activity as untreated ATPase. (ii) A protein complex Ti, which lacks ATPase activity, but nevertheless binds ATP as shown by affinity chromatography. Trypsin primarily shortens the alpha-chains of the "native" enzyme to alpha-chains and removes the gamma-subunit, thus yielding ATPase Ta. The formation of the protein complex Ti appears to be due to additional cleavage of one alpha-chain into at least two more fractions.