Intra-abdominal infection in patients with abdominal trauma

HYPOTHESIS: Identifying patients with risk factors associated with the development of intra-abdominal infections makes possible early interventions to minimize morbidity and mortality. We sought to determine the incidence of intra-abdominal infection (organ/space surgical site infection) in patients undergoing operation because of abdominal trauma, to identify the risk factors associated with the development of this complication, and to estimate the respective magnitudes of the risk factors. DESIGN: We performed a prospective cohort study in patients older than 12 years who were treated surgically for penetrating or blunt abdominal trauma, with or without other associated lesions. SETTING: Hospital Universitario San Vicente de Paul in Medellin, Colombia (HUSVP), a level I trauma center for referral and the general community. PATIENTS: From November 1, 2000, through August 31, 2002, 916 patients with abdominal trauma were admitted to the HUSVP trauma unit. Of these, we excluded 2 who underwent operation at different institutions; 97 (10.6%) who died within 48 hours after admission; and 55 (6.0%) in whom complete follow-up (until the 30th postoperative day) was not feasible. The final study sample consisted of 762 patients. MAIN OUTCOME MEASURE: We performed univariate analysis to explore in an isolated way the behavior of the dependent and independent variables. Bivariate analysis was carried out with each of the independent variables and the main outcome to establish the association between individual risk factors and intra-abdominal infection. Finally, a logistic regression model was developed using the SPSS 10.0 program and the forward method. RESULTS: Intra-abdominal infection developed in 81 patients (10.6%). Variables independently associated with this complication were an Abdominal Trauma Index greater than 24, abdominal contamination, and admission to the intensive care unit. CONCLUSIONS: The development of intra-abdominal infection in patients undergoing operation because of abdominal trauma is a complex phenomenon resulting from the multiple risk factors during the preoperative, intraoperative, and postoperative periods. Multivariate logistic regression analysis allowed us to identify an Abdominal Trauma Index greater than 24, contamination of the abdominal cavity, and admission to the intensive care unit as independent risk factors for the development of organ/space surgical site infection.     

Pharmacokinetic properties of single-dose loratadine and ambroxol alone and combined in tablet formulations in healthy men

BACKGROUND: Due to Mexico's complicated socioeconomic environment, causing a high occurrence of >1 person sharing a single room, respiratory conditions are spread easily. Respiratory conditions are the main reason for consultation with a physician. The most frequent symptoms are throat soreness and cough; therefore, a new formulation combining loratadine and ambroxol hydrochloride was designed to treat these 2 major symptoms. The combination is expected to provide relief when coprescribed with more specific therapies, such as antibiotics. OBJECTIVE: This study determined the pharmacokinetic profile of single-dose loratadine-ambroxol hydrochloride combination therapy versus each component given separately. The analyses included descarboethoxyloratadine (DCL), the primary active metabolite of loratadine. METHODS: This was a 4-week, single-center, randomized, open-label, 3-period crossover study in adult male volunteers aged 18 to 50 years and in good general health. Subjects were randomized to receive single doses of treatment A (2 loratadine 5-mg tablets + ambroxol 30-mg tablets), B (2 ambroxol 30-mg tablets), or C (1 loratadine 10-mg tablet) in 1 of 3 sequences (ABC, BCA, or CAB) per period. A 14-day washout period separated each treatment period. Plasma concentration-time data curves for each subject and treatment were analyzed by noncompart-mental methods to obtain values for area under the curve (AUC), maximum plasma concentration (C(max)), and time to reach C(max) (T(max)). RESULTS: Thirty subjects (mean [SD] age, 22.5 [2.6] years) were enrolled. All treatments were well tolerated. Formulations A and C produced similar loratadine and DCL AUC from time 0 to 24 hours (AUC(0-24)) values, but showed slightly high C(max). values for loratadine and slightly low C(max) values for DCL, indicating failure to demonstrate bioinequivalence. Formulations A and B produced similar ambroxol C(max), T(max), and AUC(0-24) values. CONCLUSIONS: In this population of healthy mate volunteers, results showed the bioavailability of loratadine and ambroxol from the new formulation and did not show impairment of absorption when the drugs were formulated in a combination tablet.     

Expression and characterization of recombinant canine IL-13 receptor alpha2 protein and its biological activity in vitro

Our previous study showed that recombinant canine IL-13 (rcaIL-13) stimulated production of allergen-specific IgE in vitro by peripheral blood mononuclear cells (PBMC) from flea allergen-sensitized dogs. This has also been demonstrated using human IL-13 (huIL-13) and PBMC isolated from human allergy patients. The stimulatory activity of rcaIL-13 was specifically inhibited by a fusion protein of the extracellular domain of canine IL-13Ralpha2 and the Fc fragment of canine IgG heavy chain (rcaIL-13Ralpha2-Fc). In this communication, we report the construction and expression of a non-fused recombinant extracellular domain of canine IL-13Ralpha2 (rcaIL-13Ralpha2) in an E. coli expression system. The E. coli expressed rcaIL-13Ralpha2 was isolated in inclusion bodies, then solubilized in buffer containing denaturants and reducing agents. After refolding and purification, the biological activity of rcaIL-13Ralpha2 was found in the monomer fraction resulting from gel filtration and ion exchange chromatographies. Biological activity of purified rcaIL-13Ralpha2 was demonstrated by the specific inhibition of rcaIL-13 activity in a TF-1 cell proliferation assay. Additionally, rcaIL-13Ralpha2 was found to be active in neutralizing rcaIL-13 induced upregulation of IgE mRNA levels in PBMCs of "high IgE" dogs, which have been bred to exhibit a predisposition for high IgE production and are used as a model for allergic asthma. The data confirm our previous report that the regulatory effects of IL-13 on IgE production in canine PBMCs are similar to those reported in humans. Thus, allergic dogs, such as the "high IgE" producing dogs, may be excellent models for research on IgE-mediated diseases in humans.     

Docetaxel and high-dose epirubicin as neoadjuvant chemotherapy in locally advanced breast cancer

Purpose Epirubicin and docetaxel are two of the most active drugs against breast carcinoma. As the achievement of a pathological complete response (pCR) is important for survival of patients with locally advanced disease, we used both drugs as neoadjuvant chemotherapy.Patients and methods Women with locally advanced or inflammatory breast cancer received epirubicin 120 mg/m² followed by docetaxel 75 mg/m², both on day 1, every 21 days for four cycles. Lenograstim was administered for 10 days in all cycles.Results Of 51 patients included, 50 received a total of 188 cycles, with a median of 4 per patient. The median age was 47 years, tumour stage was IIIA in 14 patients and IIIB in 36. Oestrogen receptors were positive in 65% of tumours. There were 10 clinical complete responses (20%) and 29 partial responses (58%). Surgery consisted of mastectomy in 40 patients and tumorectomy in 6. After surgery, 9 pCR were recorded (18%). One patient progressed and died soon after the end of chemotherapy. After a median follow-up of 22 months, the median disease-free survival was 33.7 months. Grade 3/4 neutropenia was observed in 32% of patients, anaemia in 6%, and thrombocytopenia in 4%. Five patients had febrile neutropenia. There were no toxic deaths or grade 4 nonhaematological toxicities.Conclusions Docetaxel plus high-dose epirubicin showed promising activity in patients with locally advanced and inflammatory breast cancer, at the cost of moderate toxicity.     

The endogenous cannabinoid anandamide inhibits alpha7 nicotinic acetylcholine receptor-mediated responses in Xenopus oocytes

The effect of the endogenous cannabinoid ligand anandamide on the function of the cloned alpha7 subunit of the nicotinic acetylcholine (ACh) receptor expressed in Xenopus oocytes was investigated by using the two-electrode voltage-clamp technique. Anandamide reversibly inhibited nicotine (10 microM) induced-currents in a concentration-dependent manner (10 nM to 30 microM), with an IC50 value of 229.7 +/- 20.4 nM. The effect of anandamide was neither dependent on the membrane potential nor meditated by endogenous Ca2+ dependent Cl- channels since it was unaffected by intracellularly injected BAPTA and perfusion with Ca2+-free bathing solution containing 2 mM Ba2+. Anandamide decreased the maximal nicotine-induced responses without significantly affecting its potency, indicating that it acts as a noncompetitive antagonist on nicotinic acetylcholine (nACh) alpha7 receptors. This effect was not mediated by CB1 or CB2 receptors, as neither the selective CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (SR 141716A) nor CB2 receptor antagonist N-((1S)-endo-1,3,3-trimethyl-bicyclo-heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR 144528) reduced the inhibition by anandamide. In addition, inhibition of nicotinic responses by anandamide was not sensitive to either pertussis toxin treatment or to the membrane permeable cAMP analog 8-Br-cAMP (0.2 mM). Inhibitors of enzymes involved in anandamide metabolism including phenylmethylsulfonyl fluoride, superoxide dismutase, and indomethacin, or the anandamide transport inhibitor AM404 did not prevent anandamide inhibition of nicotinic responses, suggesting that anandamide itself acted on nicotinic receptors. In conclusion, these results demonstrate that the endogenous cannabinoid anandamide inhibits the function of nACh alpha7 receptors expressed in Xenopus oocytes in a cannabinoid receptor-independent and noncompetitive manner.     

Inflammatory C2-3 subluxation: a Grisel's syndrome variant

The concurrence of non-traumatic atlanto-axial subluxation with inflammation of the adjacent neck tissues is known as Grisel's syndrome. We report a 5 year old boy with recurring episodes of head tilt and painful and restricted neck movements that developed after repeated bouts of sinusitis. Radiographs showed a subluxation of the C2-3 joint. Medical treatment, with cervical collar, physiotherapy, and non-steroid anti-inflammatory agents, led to complete cure of the disease. We suggest that Grisel's syndrome can occur in a location different from the classic atlanto-axial joint. To the best of our knowledge, this is the first report of a symptomatic case of Grisel's syndrome occurring at the C2-3 segment.