Pharmacokinetic variability of extended interval tobramycin in burn patients.

BACKGROUND: Aminoglycosides are mandatory in the treatment of severe infections in burns. However, their pharmacokinetics are difficult to predict in critically ill patients. Our objective was to describe the pharmacokinetic parameters of high doses of tobramycin administered at extended intervals in severely burned patients. METHODS: We prospectively enrolled 23 burned patients receiving tobramycin in combination therapy for Pseudomonas species infections in a burn ICU over 2 years in a therapeutic drug monitoring program. Trough and post peak tobramycin levels were measured to adjust drug dosage. Pharmacokinetic parameters were derived from two points first order kinetics. RESULTS: Tobramycin peak concentration was 7.4 (3.1-19.6)microg/ml and Cmax/MIC ratio 14.8 (2.8-39.2). Half-life was 6.9 (range 1.8-24.6)h with a distribution volume of 0.4 (0.2-1.0)l/kg. Clearance was 35 (14-121)ml/min and was weakly but significantly correlated with creatinine clearance. CONCLUSION: Tobramycin had a normal clearance, but an increased volume of distribution and a prolonged half-life in burned patients. However, the pharmacokinetic parameters of tobramycin are highly variable in burned patients. These data support extended interval administration and strongly suggest that aminoglycosides should only be used within a structured pharmacokinetic monitoring program.

Optical probing of sodium dynamics in neurons and astrocytes.

Changes in intracellular Na(+) concentration underlie essential neurobiological processes, but few reliable tools exist for their measurement. Here we characterize a new synthetic Na(+)-sensitive fluorescent dye, Asante Natrium Green (ANG), with unique properties. This indicator was excitable in the visible spectrum and by two-photon illumination, suffered little photobleaching and located to the cytosol were it remained for long durations without noticeable unwanted effects on basic cell properties. When used in brain tissue, ANG yielded a bright fluorescent signal during physiological Na(+) responses both in neurons and astrocytes. Synchronous electrophysiological and fluorometric recordings showed that ANG produced accurate Na(+) measurement in situ. This new Na(+) indicator opens innovative ways of probing neuronal circuits.

Abdominal infections in the intensive care unit: characteristics, treatment and determinants of outcome.

BACKGROUND: Abdominal infections are frequent causes of sepsis and septic shock in the intensive care unit (ICU) and are associated with adverse outcomes. We analyzed the characteristics, treatments and outcome of ICU patients with abdominal infections using data extracted from a one-day point prevalence study, the Extended Prevalence of Infection in the ICU (EPIC) II. METHODS: EPIC II included 13,796 adult patients from 1,265 ICUs in 75 countries. Infection was defined using the International Sepsis Forum criteria. Microbiological analyses were performed locally. Participating ICUs provided patient follow-up until hospital discharge or for 60 days. RESULTS: Of the 7,087 infected patients, 1,392 (19.6%) had an abdominal infection on the study day (60% male, mean age 62 ± 16 years, SAPS II score 39 ± 16, SOFA score 7.6 ± 4.6). Microbiological cultures were positive in 931 (67%) patients, most commonly Gram-negative bacteria (48.0%). Antibiotics were administered to 1366 (98.1%) patients. Patients who had been in the ICU for ≤ 2 days prior to the study day had more Escherichia coli, methicillin-sensitive Staphylococcus aureus and anaerobic isolates, and fewer enterococci than patients who had been in the ICU longer. ICU and hospital mortality rates were 29.4% and 36.3%, respectively. ICU mortality was higher in patients with abdominal infections than in those with other infections (29.4% vs. 24.4%, p < 0.001). In multivariable analysis, hematological malignancy, mechanical ventilation, cirrhosis, need for renal replacement therapy and SAPS II score were independently associated with increased mortality. CONCLUSIONS: The characteristics, microbiology and antibiotic treatment of abdominal infections in critically ill patients are diverse. Mortality in patients with isolated abdominal infections was higher than in those who had other infections.

Epidemiology of cleft palate in Europe: implications for genetic research.

OBJECTIVE: To describe the epidemiology of cleft palate (CP) in Europe. DESIGN AND SETTING: A descriptive epidemiological study on 3852 cases of CP, identified (1980 through 1996) from more than 6 million births from the EUROCAT network of 30 registers in 16 European countries. RESULTS: Significant differences in prevalence in Europe between registries and within countries were observed. A total of 2112 (54.8%) CP cases occurred as isolated, 694 (18.0%) were associated with other defects such as multiple congenital anomalies, and 1046 (27.2%) were in recognized conditions. The study confirmed the tendency toward female prevalence (sex ratio [SR] = 0.83), particularly among isolated cases (SR = 0.78) even if SR inversion is reported in some registries. A specific association with neural tube defects (NTDs) in some registers is reported. CONCLUSION: The differences identified in Europe (prevalence, sex, associated anomalies) can be only partially explained by methodological reasons because a common methodology was shared among all registries for case ascertainment and collection, and CP is an easy detectable condition with few induced abortions. The complex model of inheritance and the frequently conflicting results in different populations on the role of genes that constitute risk factors suggest the presence of real biological differences. The association of CP/NTD in an area with a high prevalence of NTDs can identify a group of conditions that can be considered etiologically homogeneous. The epidemiological evaluation can guide genetic research to specify the role of etiological factors in each different population

Unidades térmicas e produtividade em genótipos de milheto semeados em duas épocas

O objetivo deste trabalho foi avaliar o acúmulo de unidades térmicas (UT) e de biomassa em genótipos de milheto semeados nas águas e na seca, sem irrigação e adubação, em delineamento experimental de blocos ao acaso. Nas águas, o ciclo do BRS 1501 foi de 76 dias, com 1.239 UT, e ENA 1 teve ciclo de 82 dias, com 1.325 UT, sem diferenças de produtividade de biomassa e grãos. O genótipo Souna III acumulou 1.352 UT, com a maior produção de biomassa, mas não de grãos. Na floração, nessa época, BRS 1501 acumulou menos UT (517 UT) e menos biomassa, enquanto ENA 1 acumulou 545 UT e mais biomassa. Na seca, BRS 1501 teve ciclo de 80 dias, tendo requerido 1.123 UT, enquanto ENA 1 teve ciclo de 76 dias, com 1.074 UT; não houve diferença significativa na produção de biomassa e grãos. Na floração, nessa época, ENA 1 acumulou 447 UT e o BRS 1501, 461 UT. Não houve diferença no acúmulo de biomassa. O genótipo ENA 1 pode ser usado para a produção de biomassa, no sistema de plantio direto, e BRS 1501, para a produção de biomassa e de grãos, principalmente na seca.

Early EEG correlates of neuronal injury after brain anoxia.

OBJECTIVES: EEG and serum neuron-specific enolase (NSE) are used for outcome prognostication in patients with postanoxic coma; however, it is unclear if EEG abnormalities reflect transient neuronal dysfunction or neuronal death. To assess this question, EEG abnormalities were correlated with NSE. Moreover, NSE cutoff values and hypothermic EEG features related with poor outcome were explored.¦METHODS: In a prospective cohort of 61 adults treated with therapeutic hypothermia (TH) after cardiac arrest (CA), multichannel EEG recorded during TH was assessed for background reactivity and continuity, presence of epileptiform transients, and correlated with serum NSE collected at 24-48 hours after CA. Demographic, clinical, and functional outcome data (at 3 months) were collected and integrated in the analyses.¦RESULTS: In-hospital mortality was 41%, and 82% of survivors had good neurologic outcome at 3 months. Serum NSE and EEG findings were strongly correlated (Spearman rho = 0.45; p < 0.001). Median NSE peak values were higher in patients with unreactive EEG background (p < 0.001) and discontinuous patterns (p = 0.001). While all subjects with nonreactive EEG died, 5 survivors (3 with good outcome) had NSE levels >33 μg/L.¦CONCLUSION: The correlation between EEG during TH and serum NSE levels supports the hypothesis that early EEG alterations reflect permanent neuronal damage. Furthermore, this study confirms that absent EEG background reactivity and presence of epileptiform transients are robust predictors of poor outcome after CA, and that survival with good neurologic recovery is possible despite serum NSE levels> 33 μg/L. This underscores the importance of multimodal assessments in this setting.

Evaluation of a polymerase chain reaction-restriction fragment length polymorphism assay for dermatophyte and nondermatophyte identification in onychomycosis.

BACKGROUND: Dermatophytes are the main cause of onychomycoses, but various nondermatophyte filamentous fungi are often isolated from abnormal nails. The correct identification of the aetiological agent of nail infections is necessary in order to recommend appropriate treatment. OBJECTIVE: To evaluate a rapid polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay based on 28S rDNA for fungal identification in nails on a large number of samples in comparison with cultures. METHODS: Infectious fungi were analysed using PCR-RFLP in 410 nail samples in which fungal elements were observed in situ by direct mycological examination (positive samples). The results were compared with those previously obtained by culture of fungi on Sabouraud agar from the same nail samples. RESULTS: PCR-RFLP identification of fungi in nails allowed validation of the results obtained in culture when Trichophyton spp. grew from infected samples. In addition, nondermatophyte filamentous fungi could be identified with certainty as the infectious agents in onychomycosis, and discriminated from dermatophytes as well as from transient contaminants. The specificity of the culture results relative to PCR-RFLP appeared to be 81%, 71%, 52% and 63% when Fusarium spp., Scopulariopsis brevicaulis, Aspergillus spp. and Candida spp., respectively, grew on Sabouraud agar. It was also possible to identify the infectious agent when direct nail mycological examination showed fungal elements, but negative results were obtained from fungal culture. CONCLUSIONS: Improved sensitivity for the detection of fungi in nails was obtained using the PCR-RFLP assay. Rapid and reliable molecular identification of the infectious fungus can be used routinely and presents several important advantages compared with culture in expediting the choice of appropriate antifungal therapy.

Thoracoscopic segmentectomy: one vessel may hide a second one.

We report the case of an asymptomatic neonate prenatally diagnosed with a left basal pulmonary sequestration. The preoperative chest computed tomography with contrast showed 2 aberrant arteries arising from the distal thoracic aorta and supplying the intralobar left inferior lung malformation. Strategy and treatment by thoracoscopic segmentectomy are presented.

2010 Calendar Year Annual Report of the Watershed Improvement Review Board

The Board, codified in Chapter 466A, is an independent, self-governing body directed to award grants for water quality improvement and flood prevention in the state. The Board is authorized to request applications from soil and water conservation districts, local watershed improvement committees, public water supply utilities, counties, county conservation boards and cities and award grants to these entities. These grants are issued from the Watershed Improvement Fund. Annual appropriations plus interest earned on the Watershed Improvement Fund allowed the Board to issue three Request For Applications in 2010. On February 19, the Board awarded grants to five applicants for a total of $1,647,600. On July 23, the Board awarded grants to five applicants for a total of $796,500. Finally, on November 5, the Board awarded grants to eight applicants for a total of $1,203,500.

Extensive (8 to 12 cm2) noncircumferential endoscopic mucosal resection for early esophageal cancer.

Background: Endoscopic mucosal resection (EMR) is an appealing method for treating intramucosal esophageal cancer but must comply with the following stringent requirements: proper preoperative staging, complete resection of the lesion, obtaining a resected specimen for histologic analysis of safety margins, and squamous reepithelialization without stricture formation. Methods: A rigid esophagoscope was created to resect up to 12 cm(2) of esophageal mucosa in a single specimen and at a constant depth through the submucosa. Under visual control, the esophageal mucosa is sucked into a transparent window and resected with a thin diathermy wire loop in 10 seconds. After extensive preclinical studies in a sheep model, this article reports our early experience in humans. Results: Twenty-one hemi-circumferential EMRs were performed for 11 dysplastic Barrett's esophagi and 10 early squamous cell carcinomas with no perforation, one hemorrhage controlled by embolization of the left gastric artery, and one incomplete resection. Deep safety margins were clear in 19 of 21 resected specimens (2 patients, unfit for operations, had submucosal invasion of squamous cell carcinoma and adenocarcinoma, respectively). Lateral margins were not clear by definition in 7 circumferential Barrett's esophagi, but were clear in 4 incomplete Barrett's esophagi and 10 early squamous cell carcinomas. Conclusions: Large EMRs of 12 cm(2) can safely be performed at the submucosal level in the esophagus. Although feasible in one session, circumferential EMR in humans is not yet advisable because of the risk of stricture formation during the healing phase. The rate of complications of this series of 21 EMRs in humans is acceptable. (Ann Thorac Surg 2010; 89: S2151-5) (C) 2010 by The Society of Thoracic Surgeons

Prospective assessment of trocar-specific morbidity in laparoscopy.

BACKGROUND: The purpose of the present study was to challenge the hypothetical advantage of single port laparoscopy (SPL) over conventional laparoscopy by measuring prospectively the morbidity specifically related to conventional trocar sites (TS). METHODS: From November 2010 to December 2011, 300 patients undergoing various laparoscopic procedures were enrolled. Patient, surgery, and trocar characteristics were recorded. We evaluated at three time points (in-hospital and at 1 and 6 months postoperatively) specifically for each TS, pain (Visual Analog Scale), morbidity (infection, hematoma, hernia), and cosmesis (Patient Scar Assessment Score; PSAS). Patients designated their "worst TS," and a composite endpoint "bad TS" was defined to include any adverse outcome at a TS. RESULTS: We analyzed 1,074 TS. Follow-up was >90 %. Pain scores of >3/10 at 1 and 6 months postoperatively, were reported by 3 and 1 % of patients at the 5 mm TS and by 9 and 1 % at the larger TS, respectively (5 mm TS vs larger TS; p = 0.001). Pain was significantly lower for TS located in the lower abdomen than for the upper abdomen or the umbilicus (p = 0.001). The overall complication rate was <1 % and significantly lower for the 5 mm TS (hematoma p = 0.046; infection p = 0.0001). No hernia was found. The overall PSAS score was low and significantly lower for the 5 mm TS (p = 0.0001). Significant predictors of "bad TS" were larger TS (p = 0.001), umbilical position (p = 0.0001), emergency surgery (p = 0.0001), accidental trocar exit (p = 0.022), fascia closure (p = 0.006), and specimen extraction site (p = 0.0001). CONCLUSIONS: Specific trocar morbidity is low and almost negligible for 5 mm trocars. The umbilicus appears to be an unfavorable TS.