Publications

SCOPUS: re.j

Severe sepsis is a common disease process affecting some 2-11% of hospital admissions in the US. Severe sepsis and septic shock are associated with considerable morbidity and mortality, and account for a large part of intensive care unit costs. Until recently, the management of septic shock relied on the treatment of underlying infection with antimicrobial agents and surgical removal of any infectious source, and individual support of failing organs. However, in the last few years we have seen huge strides being made in our understanding of the pathophysiology of the sepsis response, and in our ability to manipulate that response. In the last couple of years these advances have come to fruition with the development of a drug, drotrecogin alfa, which specifically reduces mortality from this all too often fatal disease. While intensive early resuscitation remains the cornerstone of management, new approaches are beginning to form part of sepsis management protocols and will lead to improved outcomes for patients with this disease process.

<h3>Objective.</h3> —To determine the prevalence of intensive care unit (ICU)—acquired infections and the risk factors for these infections, identify the predominant infecting organisms, and evaluate the relationship between ICU-acquired infection and mortality. <h3>Design.</h3> —A 1-day point-prevalence study. <h3>Setting.</h3> —Intensive care units in 17 countries in Western Europe, excluding coronary care units and pediatric and special care infant units. <h3>Patients.</h3> —All patients (&gt;10 years of age) occupying an ICU bed over a 24-hour period. A total of 1417 ICUs provided 10 038 patient case reports. <h3>Main Outcome Measures.</h3> —Rates of ICU-acquired infection, prescription of antimicrobials, resistance patterns of microbiological isolates, and potential risk factors for ICU-acquired infection and death. <h3>Results.</h3> —A total of 4501 patients (44.8%) were infected, and 2064 (20.6%) had ICU-acquired infection. Pneumonia (46.9%), lower respiratory tract infection (17.8%), urinary tract infection (17.6%), and bloodstream infection (12%) were the most frequent types of ICU infection reported. Most frequently reported microorganisms were Enterobacteriaceae (34.4%),<i>Staphylococcus aureus</i>(30.1%; [60% resistant to methicillin]),<i>Pseudomonas aeruginosa</i>(28.7%), coagulase-negative staphylococci (19.1%), and fungi (17.1%). Seven risk factors for ICU-acquired infection were identified: increasing length of ICU stay (&gt;48 hours), mechanical ventilation, diagnosis of trauma, central venous, pulmonary artery, and urinary catheterization, and stress ulcer prophylaxis. ICU-acquired pneumonia (odds ratio [OR], 1.91; 95% confidence interval [CI], 1.6 to 2.29), clinical sepsis (OR, 3.50; 95% CI, 1.71 to 7.18), and bloodstream infection (OR, 1.73; 95% CI, 1.25 to 2.41) increased the risk of ICU death. <h3>Conclusions.</h3> —ICU-acquired infection is common and often associated with microbiological isolates of resistant organisms. The potential effects on outcome emphasize the importance of specific measures for infection control in critically ill patients. (<i>JAMA</i>. 1995;274:639-644)

PsCyp15a is a gene that encodes a vacuolar cysteine protease expressed in wilt-induced shoots of Pisum sativum (pea) and in root nodules. To further the understanding of nodular PsCyp15a expression, a region 5' to the coding sequence of the gene was cloned. Varying lengths of 5' untranslated sequence were fused with the uidA coding region and introduced from Agrobacterium rhizogenes into "hairy roots" of Vicia hirsuta. In this transgenic root nodulation assay, a promoter sequence of 900 bp was sufficient to give an expression pattern indistinguishable from that obtained in pea nodules by in situ hybridization. An orthologue of PsCyp15a was cloned from nodule mRNA of Medicago sativa and a corresponding gene identified in M. truncatula was also shown to express strongly in nodules. With molecular mapping techniques, it was demonstrated that these genes map to a syntenic genome location in pea and Medicago spp., but the map positions of the Cyp15a genes cannot be correlated with existing nodulation mutants.

Serotonin can induce pulmonary hypertension, hypoxia and bronchoconstriction, and ketanserin has been shown to reverse these effects on various experimental models of acute respiratory failure. In the present study, the hemodynamic and gasometric effects of ketanserin were studied during acute respiratory failure induced by an air infusion at a rate of 10 ml/min in dogs. During a 60-min air infusion, 10 dogs received 4 mg of ketanserin i.v. and 10 dogs served as control. Ketanserin-treated dogs had similar pulmonary hypertension even though more significant decreases in arterial pressure and systemic vascular resistance characterized the systemic effects of ketanserin. Similarly, a marked increase in hematocrit observed in control dogs (from 36.9 to 43.8%, p less than 0.01) was totally prevented by ketanserin (from 40.3 to 40.4%, NS). Hypoxia was similar, although the increase in pulmonary shunt was attenuated (259 instead of 468%). Therefore, the influence of serotonin is very limited in acute respiratory failure secondary to air embolization. Serotonin might have a more important influence on the systemic than on the pulmonary vasculature in these conditions.

Hyperlactataemia, a marker of poor prognosis in intensive care patients, is most frequently found in cases of acute circulatory failure ; however, it may be due to factors other than cellular hypoxia. The level of blood lactate is determined by the balance between its production and its elimination, which can be influenced by various factors. For example, the influence of medication on blood lactate levels should not be underestimated, whether in anaesthesiology, with the use of propofol, or with certain anti-retrovirals in HIV seropositive patients. And in oncology, blood lactate can derive from anaerobic metabolism, characteristic of tumour cells. The differential diagnosis of hyperlactataemia can, therefore, sometimes be more complex than initially thought.