No abstract

The aim of the present study was to obtain clinical experience with the use of high-dose ciprofloxacin as monotherapy for the treatment of febrile neutropenia episodes (granulocyte count, <500/mm 3 ) compared to a standard regimen and to clarify whether ciprofloxacin administration may be switched to the oral route. In a prospective randomized study ciprofloxacin was given at 400 mg three times a day (t.i. 113 patients), respectively, in a per-protocol analysis (P values for one-sided equivalence, 0.0485 and 0.0516, respectively; ␦ ‫؍‬ 10%), with no significant differences among patients with bacteremia and other microbiologically or clinically documented infections and fever of unknown origin. For 82 (66.1%) patients, it was possible to switch from parenteral ciprofloxacin to the oral ciprofloxacin, and the response was successful for 61 (74.4%) patients. The efficacies of the regimens against streptococcal bacteremias were 16.6% (one of six patients) for the ciprofloxacin group and 33.3% (one of three patients) for the combination group (it was not statistically significant), with one breakthrough streptococcal bacteremia observed among the ciprofloxacin-treated patients. Adverse events were mostly self-limited and were observed in 27 (20.6%) ciprofloxacin-treated patients and 26 (19.7%) patients who were receiving the combination. This study demonstrates that high-dose ciprofloxacin given intravenously for at least 3 days and then by the oral route is therapeutically equivalent to the routine regimen of intraveneous ceftazidime plus amikacin even in febrile patients with severe neutropenia (polymorphonuclear leukocyte count, <100 mm 3 ). However, it is very important that before an empirical therapy is chosen each hospital determine bacteriologic predominance and perform resistance surveillance.

According to the widely accepted myeloma staging system, the bulk of paraprotein is the main determinant of disease stage. However, myelomatous plasma cells differ considerably in their ability to synthesize and secrete monoclonal paraprotein. We determined plasma cell secreting potential (PCSP) as the amount of M-component, divided by the percentage of marrow plasmacytic infiltration, in 240 patients with myeloma, and correlated our results with chain isotype, plasma cell morphology, severity of bone disease, well-recognized prognostic factors, such as serum LDH, CRP, albumin and beta2-microglobulin, treatment response and overall survival. PCSP was higher in IgG than in other myeloma types, and was an almost constant parameter for each individual patient, in 134/166 cases. A > 10% decrease of PCSP in 26 patients was associated with disease aggressiveness and treatment failure. Patients with MGUS had significantly higher PCSP than those with myeloma of the same chain type. Higher PCSP was associated with stage I, absence of Bence-Jones proteinuria and indolent forms of disease with lower proliferating cell nuclear antigen (PCNA) positivity, serum LDH, alpha2-globulins, CRP and beta2-microglobulin and higher albumin levels. Conversely, patients with immature/plasmablastic morphology and those with severe bone disease had lower PCSP. Good responders to treatment had significantly higher PCSP than moderate and poor responders and PCSP was strongly correlated with overall survival in IgG and IgA myeloma. In conclusion, PCSP reflects the maturation status of myelomatous cells and therefore can be used as a prognostic factor, since patients with high secreting potential represent a lower malignancy group, in comparison to those with a low secreting potential.

Acenocoumarol is mainly catabolized by CYP2C9 isoform of cytochrome P450 (CYP) liver complex and exerts its anticoagulant effect through the inhibition of Vitamin K Epoxide Reductase (VKOR). The most important genetic polymorphisms which lead to an impaired enzymatic activity and therefore predispose to acenocoumarol sensitivity, are considered to be CYP2C9*2 (Arg144Cys), CYP2C9*3 (Ile359Leu) and VKORC1-1639G>A, respectively. In this study we compared the results of the PGXThrombo StripAssay kit (ViennaLab Diagnostics,Vienna, Austria) with direct DNA sequencing and in house Restriction Fragment Length Polymorphisms (RFLP) for the detection of the aforementioned Single Nucleotide Polymorphisms (SNPs). The reverse hybridization StripAssay was found to be equally effective with RFLP and direct DNA sequencing for the detection of CYP2C9*2 and CYP2C9*3 polymorphisms, respectively. The comparison of the RFLP reference method with the reverse hybridization StripAssay for the detection of VKORC1-1639 G>A polymorphism showed that the reverse hybridization StripAsssay might misclassify some A/A homozygotes as heterozygotes. Optimization of the hybridization procedures may eliminate the extra low signal band observed in some samples at the reverse hybridization StripAssay and improve its diagnostic value.

Purpose: To describe the epidemiology of the acute respiratory distress syndrome (ARDS) in a Brazilian ICU. Methods: This prospective observational, non-interventional study, included all consecutive patients with ARDS criteria [1] admitted in the ICU of a Brazilian tertiary hospital, between January 1997 and September 2001. Were collected in a prospective fashion the following variables: age, gender, APACHE II score at ICU admission and at ARDS diagnosis, cause of ARDS, presence of AIDS, cancer and immunosuppression, occurrence of barotrauma, performance of traqueostomy, mortality, duration of mechanical ventilation (MV), length of stay (LOS) in ICU and in hospital. The lung injury score (LIS) [2] was used to quantify the degree of pulmonary injury in the first week of ARDS. Results: There was 2182 patients (P) admitted in ICU during the study period, of whom 141 (6.46%) had ARDS criteria. Seventy-six (54%) were men, the mean age was 46 ± 18 years, APACHE II 18 ± 7 and 19 ± 7 at admission and at ARDS diagnosis, respectively. Septic shock accounted for 42% (60 P) of the ARDS causes, sepsis 22% (31 P), diffuse pulmonary infection 16% (23 P), aspiration pneumonia 11% (15 P), non-septic shock 5% (7 P) and others 4% (5 P). Ten percent (14 P) had AIDS, 30% (43 P) cancer and 25% (36 P) immunosuppression. All patients were mechanically ventilated with Tidal Volume between 4 and 8 ml/kg. Only 3.5% (5 P) had barotrauma and 10% (14 P) performed traqueostomy. Mortality rate was 79% in the ICU. The patients required 12 ± 10 days on MV, ranging from 1 to 55 days. The LOS in ICU and hospital was 14 ± 13 (1-69) days and 28 ± 32 (1-325) days, respectively. There was a time delay of 3.7 ± 4.5 days between admission in ICU and the onset of ARDS. The Murray score (mean ± SD) was 3.2 ± 0.4, 3 ± 0.5, 3 ± 0.5, 2.9 ± 0.6, 2.8 ± 0.7, 2.7 ± 0.7 and 2.6 ± 0.8 in the first 7 days, respectively. Conclusions: ARDS in our hospital has a similar incidence of reports in the USA and Europe. There was a higher mortality, which could be explained by a high incidence of infection causes of ARDS, mainly septic shock, and elevated combined occurrence of AIDS, cancer and immunosuppression, along the degree of LIS. The incidence of barotrauma was low, as a consequence of the current mechanical ventilation strategies.