Predictive value of urine interleukin-18 in the evolution and outcome of acute kidney injury in critically ill adult patients.

BACKGROUND: Interleukin-18 (IL-18) is a pro-inflammatory protein, which mediates ischaemic tubular injury, and has been suggested to be a sensitive and specific biomarker for acute kidney injury (AKI). The predictive value of IL-18 in the diagnosis, evolution, and outcome of AKI in critically ill patients is still unclear. METHODS: We measured urine IL-18 from critically ill patients at intensive care unit (ICU) admission and 24 h. We evaluated the association of IL-18 with developing new AKI, renal replacement therapy (RRT), and 90-day mortality. We calculated areas under receiver operating characteristics curves (AUCs), best cut-off values, and positive likelihood ratios (LR+) for IL-18 concerning these endpoints. Additionally, we compared the predictive value of IL-18 at ICU admission to that of urine neutrophil gelatinase-associated lipocalin (NGAL). RESULTS: In this study population of 1439 patients the highest urine IL-18 during the first 24 h in the ICU associated with the development of AKI with an AUC [95% confidence interval (CI)] of 0.586 (0.546-0.627) and with the development of Stage 3 AKI with an AUC (95% CI) of 0.667 (0.591-0.774). IL-18 predicted the initiation of RRT with an AUC (95% CI) of 0.655 (0.572-0.739), and 90-day mortality with an AUC (95% CI) of 0.536 (0.497-0.574). CONCLUSIONS: IL-18 had poor-to-moderate ability to predict AKI, RRT, or 90-day mortality in this large cohort of critically ill patients. Thus, it should be used with caution for diagnostic or predictive purposes in the critically ill.

Acute kidney injury in patients with severe sepsis in Finnish Intensive Care Units.

BACKGROUND: Severe sepsis is one of the leading causes of acute kidney injury (AKI). Patients with sepsis-associated AKI demonstrate high-hospital mortality. We evaluated the incidence of severe sepsis-associated AKI and its association with outcome in intensive care units (ICUs) in Finland. METHODS: This was a predetermined sub-study of the prospective, observational, multicentre FINNAKI study conducted in 17 ICUs during 1 September 2011 and 1 February 2012. All emergency ICU admissions and elective admissions exceeding 24 hours in the ICU were screened for presence of severe sepsis and AKI up to 5 days in ICU. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria and severe sepsis according to the American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) criteria. RESULTS: Of the 2901 included patients, severe sepsis was diagnosed in 918 (31.6%, 95% confidence interval [CI] 29.9-33.4%) patients. Of these 918 patients, 488 (53.2% [95% CI 49.9-56.5%]) had AKI. The 90-day mortality rate was 38.1% (95% CI 33.7-42.5%) for severe sepsis patients with AKI and 24.7% (95% CI 20.5-28.8%) for those without AKI. After adjusting for covariates, KDIGO stage 3 AKI was associated with an increased risk for 90-day mortality with an adjusted odds ratio (OR) of 1.94 (95% CI 1.28-2.94), but stages 1 and 2 were not. CONCLUSIONS: More than half of the patients with severe sepsis had AKI according to the KDIGO classification, and AKI stage 3 was independently associated with 90-day mortality.

Plasma neutrophil gelatinase-associated lipocalin and adverse outcome in critically ill patients with ventilatory support.

OBJECTIVE: Plasma neutrophil gelatinase-associated lipocalin (pNGAL) has been introduced as an early and sensitive biomarker of acute kidney injury (AKI), with an increased risk for renal replacement therapy (RRT) and adverse outcome in selected critically ill patient groups. Acute respiratory failure is the most common organ dysfunction in critically ill patients with an increased risk for AKI. Accordingly, we hypothesized that pNGAL would independently predict adverse outcome in a heterogeneous group of critically ill adult patients with acute respiratory failure. DESIGN AND SETTING: Prospective, multi-centre study in 25 Finnish intensive care units. PATIENTS AND METHODS: pNGAL was measured from critically ill patients with acute respiratory failure. We evaluated the predictive value of pNGAL for RRT, and hospital and 90-day mortality first separately, second in addition to the Simplified Acute Physiology Score (SAPS II), and third to RIFLE (Risk, Injury, Failure, Loss, End-Stage Renal Disease) AKI classification. Additionally, we assessed the factors associated with pNGAL by linear regression analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 369 patients. Median (interquartile range) baseline pNGAL was 169 (92-370) ng/ml. The areas under receiver operating characteristic curves of baseline pNGAL were as follows: 0.733 [95% confidence interval (CI) 0.656-0.810] for RRT, 0.627 (95% CI 0.561-0.693) for hospital, and 0.582 (95% CI 0.520-0.645) for 90-day mortality. Present infection, baseline creatinine, operative status, and pancreatitis were independently associated with baseline pNGAL. CONCLUSIONS: Baseline pNGAL gives no additional value into prediction of hospital and 90-day mortality compared with RIFLE or SAPS II, and has only moderate predictive power regarding RRT in critically ill adult patients with acute respiratory failure.

Effector memory T-cells dominate immune responses in tuberculosis treatment: antigen or bacteria persistence?

OBJECTIVE: To compare ex vivo immunological responses upon stimulation of lymphocytes with Mycobacterium tuberculosis-specific antigens in three groups: 1) subjects diagnosed with tuberculosis (TB) in the early 1940s and 1950s but who did not receive anti-tuberculosis chemotherapy (n = 5), 2) subjects treated with anti-tuberculosis agents prior to the rifampicin (RMP) era (n = 26) and 3) subjects who received RMP as a part of modern combination therapy (n = 7). DESIGN: A total of 38 healthy subjects, mean age 70 +/- 13 years, with a history of previously treated TB were recruited. Peripheral blood mononuclear cells were collected and analysed as a batch by ELISpot. Representative samples with high reactivities were further immunophenotypically characterised. RESULTS: No differences between the studied groups were detected with regard to the frequencies of reactive lymphocytes. The dominant immunophenotypic profile of the representative responders, irrespective of the treatment schemes, was CD4+CD45RO+CD45RA-CD27-CD28-CCR7-, compatible with the fast reacting effector memory T-cell lineage (T(EM)). CONCLUSION: Specific T(EM) cells persist even in subjects treated for TB decades ago with modern anti-tuberculosis chemotherapy. Additional studies are needed to address the question of what drives the survival of T(EM) after adequate treatment: persistence of antigens or bacteria.

Influence of the injection site (L2/3 or L3/4) and the posture of the vertebral column on selective spinal anesthesia for ambulatory knee arthroscopy.

BACKGROUND: We tested the hypothesis that selective spinal anesthesia for ambulatory knee arthroscopy can be accomplished with a small dose of bupivacaine at the L3/4 interspace with or without a head-down tilt of 5 degrees when the patients were in the lateral decubitus position. METHODS: In this double-blind study, 123 patients were randomly allocated to receive spinal anesthesia with 4 mg of hyperbaric bupivacaine inserted at either the L2/3 interspace, while the vertebral column was kept horizontal (L2/3 group), or the L3/4 level, with the vertebral column horizontal (L3/4H) or tilted 5 degrees head-down (L3/4T). At 7 min, an additional head down tilt was used in all groups if the sensory block was inadequate. RESULTS: In the L3/4T group the sensory block (Th8) reached a significantly higher level 30 min after spinal injection, compared with both the L2/3 (Th10) and L3/4H (Th11) groups. In the L3/4H group, 39% of the patients needed an additional tilt for 3 min at 7 min, compared with 10% (P=0.004) in the L3/4T group. Sacral block developed later and recovered faster (P<0.05) in the L3/4T group compared to the L3/4H group. Home-readiness was achieved equally fast in all groups. CONCLUSION: When producing selective spinal anesthesia, the posture of the vertebral column is a major determinant of both sensory and motor segments to be blocked. A 4-mg dose of hyperbaric bupivacaine at the L3/4 interspace with a 5 degrees head-down tilt of the vertebral column for 6 min is recommended for knee arthroscopy.

Ondansetron does not prevent pruritus induced by low-dose intrathecal fentanyl.

BACKGROUND: Addition of an opioid to low-dose spinal anesthesia with bupivacaine improves the quality and success of anesthesia. However, the intrathecal fentanyl-induced pruritus is as high as 75%. We hypothesized that after administration of 4 or 8 mg of prophylactic IV ondansetron, the incidence of pruritus induced by low-dose intrathecal fentanyl would be significantly lower than after placebo. METHODS: In this double-blind study, 90 outpatients undergoing knee arthroscopy received 3 mg of bupivacaine + 10 micro g fentanyl intrathecally. Before spinal puncture, the patients received randomly either saline (P) or ondansetron 4 mg (O4) or 8 mg (O8) IV. They were asked about pruritus frequently, and they estimated its severity on a scale of 0-10. RESULTS: There was no difference in the incidence of pruritus between the three groups: pruritus occurred in 17 (57%), in 21 (75%) and in 19 patients (70%) in P, O4 and O8 groups, respectively. The pruritus was mostly mild. Four patients in the placebo group, three in the O4 and four patients in the O8 groups considered it severe. One patient in each group requested treatment for pruritus; after IV naloxone their pruritus was relieved. Neither time to pruritus nor duration of pruritus differed between the groups. One patient in each group developed a long-lasting (>10 h) pruritus. CONCLUSIONS: After prophylactic administration of 4 or 8 mg of ondansetron IV, the incidence, duration and severity of pruritus were similar to placebo. Ondansetron does not prevent pruritus induced by low-dose intrathecal fentanyl.

Intrathecal hyperbaric bupivacaine 3 mg + fentanyl 10 microg for outpatient knee arthroscopy with tourniquet.

BACKGROUND: Combination of local anesthetic and opioid enables the use of less spinal anesthetic and increases the success of anesthesia. Intrathecal opioid does not prolong motor recovery and thus should not delay discharge home. We hypothesized that 3 mg of hyperbaric bupivacaine with 10 microg of fentanyl permits fast-tracking or shorter stay in post anesthesia care unit (PACU), and earlier discharge home, compared with 4 mg of hyperbaric bupivacaine. METHODS: In this double-blind study, 100 outpatients undergoing knee arthroscopy received randomly either 4 mg of bupivacaine (B4) or 3 mg of bupivacaine + 10 microg fentanyl (B3F) intrathecally. The volume of 0.8 ml was injected at the L2/3 interspace over a 2-min period. A lateral decubitus position was maintained for 10 min. The sensory block was recorded by using thermal stimuli, and motor block was assessed according to a modified Bromage scale. Fast-tracking criteria were complete recovery of motor block, sensory block Th12 or lower and stable vital signs. RESULTS: One block (1%) failed. Motor recovery was faster in the B3F group: 60% of the patients recovered in 80 min or less compared with 28% in group B4 (P = 0.002). The PACU-time was shorter: 36 (10-103) vs. 55 (10-140) min, respectively (P = 0.005). Seventeen (B3F) vs. nine patients (B4) could bypass PACU (NS). Time to discharge home was similar in both groups. In the B3F group, 75% of the patients developed pruritus. CONCLUSION: Both solutions produced reliable spinal anesthesia for outpatient knee arthroscopy. The PACU-time was shorter in the bupivacaine-fentanyl group, but both groups reached home-readiness equally.

Selective spinal anesthesia: a comparison of hyperbaric bupivacaine 4 mg versus 6 mg for outpatient knee arthroscopy.

IMPLICATIONS: A low-dose (4 mg), low-volume (0.8 mL), low-flow (2 min) technique with hyperbaric bupivacaine toward the dependent side oriented injection and maintenance of the lateral decubitus position for 10 min produced selective spinal anesthesia with rapid recession of motor block and early discharge home.

Summer spores of birch rust fungus in Papanicolaou smears from healthy mass screening participants.

OBJECTIVE: To evaluate the origin and identification of mysterious particles in Papanicolaou smears from healthy, asymptomatic women participating in a local mass screening program. STUDY DESIGN: The material consisted of 16,000 cerricovaginal smears studied at the cytology laboratory of Pathology Laboratory of South-Western Finland Ltd. Unidentified particles were found in four apparently independent smears. All the slides were rescreened, but no further positive cases were found. RESULTS: Several swab samples were collected from the investigation room, but all were negative. Attempts at identification included numerous consultations. A telepathology consultation with the Cellular Division, Armed Forces Institute of Pathology, Washington, D.C., U.S.A., was conducted. Another teleconsultation with the reference laboratoryfor intestinal parasites in Iceland was conducted. Finally, the Aerobiology Unit, University of Turku, was consulted. The aerobiologist suggested that the particles were most probably summer spores of birch rust fungus (Melampsoridium betulinum). To confirm this we obtained a reference specimen of the fungus from the herbarium at the University of Turku. The morphology of the spore particles was identical to that in the cervicovaginal smears, proving that the smears were contaminated with birch rust fungus spores. CONCLUSION: Birch rust is ubiqutitous in Finland. Outside the hospital window there is a wide lawn behind which, at a distance of 70 m, there is a forest of birch trees. It is most likely that the rust spores flew in through the open window, to settle down on the surface of material that was used in sample taking. Airborne dust may cause misleading and surprising artefacts. Protection of specimens and instruments against dust should minimize the problem.

Altered phospholipid-apoB-100 interactions and generation of extra membrane material in proteolysis-induced fusion of LDL particles.

Lipid droplets and membrane material are produced in the extracellular matrix of the arterial intima during atherogenesis. Both in vitro and in vivo experimentation suggests that fusion of modified LDL particles leads to formation of such lipid droplets. Here we applied proton NMR spectroscopy to probe surface phospholipids phosphatidylcholine (PC) and sphingomyelin (SM) of LDL particles during proteolytic degradation of apolipoprotein B-100 (apoB-100). Initiation of apoB-100 degradation was accompanied by the abruptly increased intensity of the choline -N(CH(3))(3) resonance of PC molecules, indicating disruption of their interactions with apoB-100. However, subsequent particle fusion was accompanied by a steady decrease in the intensity of the choline resonances of both PC and SM. Electron microscopy of the proteolyzed LDL revealed irregularly shaped multilamellar membranes attached to aggregates of fused particles. This suggests formation of membrane material with low hydration, in which some of the atomic motions are hindered. Characterization of the behavior of the surface lipids of LDL particles during apoB-100 degradation and other types of LDL modification will aid in understanding molecular mechanisms leading to fusion and generation of multilamellar membrane material in the arterial intima during atherogenesis.

Remodeling of HDL by phospholipid transfer protein: demonstration of particle fusion by 1H NMR spectroscopy.

There is evidence that phospholipid transfer protein (PLTP) can increase reverse cholesterol transport by inducing favorable subclass distribution in the high density lipoprotein (HDL) fraction. This includes generation of initial cholesterol acceptor particles, pre beta-HDL, and of enlarged particles that are rapidly cleared from the circulation. However, partly because of methodological difficulties, the mechanisms behind the PLTP-mediated interconversion of HDL particles are not fully understood. In this communication, we describe the use of a novel methodology, based on 1H NMR spectroscopy, to study the PLTP-induced size changes in the HDL particles. In accordance with native gradient gel electrophoresis, the 1H NMR data revealed a gradual production of enlarged HDL particles in the HDL3+ PLTP mixtures. In addition, according to a physical model for lipoprotein particles, relating the frequency shifts observable with NMR to the size of the lipoprotein particles, the NMR data demonstrated that PLTP-mediated HDL remodeling involves fusion of the HDL particles.

Detection of low density lipoprotein particle fusion by proton nuclear magnetic resonance spectroscopy.

Recent evidence suggests that fusion of low density lipoprotein (LDL) particles is a key process in the initial accumulation of lipid in the arterial intima. In order to gain a better understanding of this early event in the development of atherosclerosis, it would thus be necessary to characterize the process of LDL fusion in detail. Such studies, however, pose severe methodological difficulties, such as differentiation of particle fusion from aggregation. In this paper we describe the use of novel methodology, based on 1H NMR spectroscopy, to study lipoprotein particle fusion. To test the methodology, we chose proteolytic fusion of LDL particles, an in vitro model that has been well characterized in our laboratory. The spectroscopic data suggested that proteolysis of LDL with alpha-chymotrypsin induced slow initiation of fusion, which was followed by particle fusion at an increased rate. Moreover, 1H NMR spectroscopic data on different kinds of LDL interactions, for example, when LDL formed aggregates with antibodies against human apolipoprotein B-100, were obtained and compared with the electron microscopic characteristics of these preparations. An important finding was that limited aggregation of LDL particles did not disturb the 1H NMR spectroscopic parameters used for the detection of particle fusion and preserved the physico-chemical information on the particles. The 1H NMR methodology developed is sensitive to and specific for low density lipoprotein (LDL) fusion and may also allow for studies of the fate of LDL particles in other in vitro preparations that mimic the arterial interactions in vivo.

Accumulation of strontium and fluoride in approximal dental plaque and changes in plaque microflora after rinsing with chlorhexidine-fluoride-strontium solution.

OBJECTIVES: To find out if strontium is incorporated into plaque and enamel in vivo during a 2-week rinsing period with a chlorhexidine-fluoride-strontium solution and to determine the effects of the rinsing on the numbers of mutans streptococci and lactobacilli in plaque. SUBJECTS AND METHODS: A total of 18 adult participants rinsed their mouths twice a day for 2 weeks, first with a placebo solution and subsequently, separated by a 1-week interval without rinsing, with a chlorhexidine gluconate (0.05%)-sodium fluoride (0.04%)-strontium (100 ppm as SrCl2) rinsing solution (CXFSr) for another 2 weeks. RESULTS: After the CXFSr rinsing period the strontium and fluoride contents (microgram g-1 plaque dry weight; mean +/- sr) of approximal plaque were 32.5 +/- 4.7 and 72.8 +/- 9.0, compared with the respective contents of 8.4 +/- 1.2 and 42.0 +/- 4.8 after placebo rinsing (P = 0.0001 for both comparisons). The strontium content remained elevated for 6 weeks. The median proportion of mutans streptococci of approximal plaque of the total viable count of bacteria was 1% after placebo rinsing but decreased to 0.2% after CXFSr rinsing. The proportion of mutans streptococci remained low at 3 weeks (P = 0.018 vs placebo) but had reached the placebo level at 6 weeks. Rinsing with CXFSr solution did not reduce lactobacilli in plaque. The strontium or fluoride contents of the enamel surfaces subjected to tooth brushing did not significantly change. CONCLUSIONS: Strontium and fluoride accumulated in dental plaque during a 2-week CXFSr rinsing period and the proportion of mutans streptococci in approximal plaque was reduced at least for 3 weeks after completion of the rinsing.

Effects of dietary fluoride and magnesium supplements on cyclic adenosine monophosphate (cAMP), calcium and magnesium levels in aorta of genetically hypercholesterolaemic RICO rats.

Previous observations have suggested that low intakes of fluoride prevent pathological calcifications of internal organs, including the aortic wall, in experimental animals, fed a basically low magnesium diet. Our group found recently that fluoride has some potentially preventive effect against atherosclerotic serum lipid profiles in genetically hypercholesterolaemic rats. To study whether the apparently positive potential of fluoride against atherosclerosis is also reflected in aortic tissue, through its well known activation of adenylate cyclase, the aortic cAMP content of the rats used in our recent study was determined. Out of a total of 56 male RICO rats, mean weight 160 g, the control group C was fed an adequate diet, with 44% sucrose, a magnesium content of 883 p.p.m. and with 0.5% cholesterol. Group D had the same diet as group C except that the magnesium content was reduced to 200 p.p.m. Group E had the same diet as group D but with the fluoride content elevated from 1.9 to 12 p.p.m. Group G had the same diet as group E but with the magnesium content elevated from 200 to 300 p.p.m. After a feeding period of 6 weeks, the aortas of the animals were removed, cleaned and kept at -70 degrees C until analysed. The mean cAMP content of the aortas, measured by radioimmunoassay, in groups C, D E and G was 439, 546, 681, and 1394 mumol mg-1 protein, respectively. In group G only, the cAMP content was significantly higher than that of the other groups (p < 0.001). The mean calcium and magnesium contents of the aortas of different groups did not significantly differ from each other. Thus in RICO rats, fed a high-sugar low-magnesium diet with cholesterol, supplementation of the diet with a small amount of fluoride elevates the cAMP content of the aorta, provided that the intake of Mg is not very low.

Identification of Bacteroides forsythus in subgingival dental plaque with the aid of a rapid PCR method.

Bacteroides forysthus has been shown to be prevalent among patients with periodontitis. Conventional microbiological methods used to identify this bacterium, however, are laborious and time-consuming and are therefore not well-suited for screening purposes. We have developed a polymerase chain-reaction (PCR) method which is rapid, specific, and simple to perform and does not require other sample pre-treatment except a brief centrifugation. This method was applied to the detection of B. forsythus in subgingival plaque of 58 periodontitis patients. When compared with the results of conventional culturing, the PCR method always confirmed the culture-positive results, while none of the PCR negative samples was shown to be culture-positive. The PCR method appeared to give more than double the number of samples positive for B. forsythus than culturing (89.7% vs. 37.9%). The analysis requires less than 4 hrs to perform, and is specific only to B. forsythus and sensitive enough to detect fewer than 5 bacteria.

[The Oulu University Hospital has developed day case surgery for children]. / Yksilövastuinen hoitotyö lasten päiväkirurgiassa.

After several changes the children's day surgery was moved to new premises--to the day case surgery unit. Due to these changes there was an excellent opportunity to question the former care practices and to "turn over a new leaf" in the new premises. Care is implemented according to primary nursing. The primary nurse cares for the patient/ the family from hospitalization to discharge. Individuality, family-centerdness, safety and comprehensiveness are emphasized. The personnel and the patients are satisfied with the changes in care practices.

Assessment of cholesteryl ester transfer protein function in lipoprotein mixtures by 1H NMR spectroscopy.

Studies of cholesteryl ester transfer protein (CETP) function in lipoprotein mixtures pose many difficulties by conventional biochemical methods. For instance, studies on the effects of CETP on the composition of apolipoprotein B containing lipoproteins (very low and low density lipoproteins) in lipoprotein mixtures are tedious due to repeated ultracentrifugational isolations and have thus rarely been performed. Here we present a new 1H NMR spectroscopy technique to assess the CETP function in lipoprotein mixtures. This technique does not require repeated physical isolations of the lipoprotein particles but uses mathematical separation of the fractions on the basis of biochemical prior knowledge based lineshape fitting analysis of specific lipid resonances in the 1H NMR spectra. The lipoproteins are separated according to their size related chemical shift which allows for distinct quantification between very low and low density lipoproteins, the two major apolipoprotein B containing fractions. The methodological basis of the technique is discussed here together with a demonstration that this kind of approach allows dynamic follow up of the lipid transfer reactions in complex lipoprotein and CETP mixtures. The results revealed a consistent behaviour which corroborated the recent findings suggesting that the neutral lipid mass transfer among lipoproteins is not an equimolar heteroexchange.

Simultaneous detection of Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis by a rapid PCR method.

The identification of periodontal pathogens by conventional methods is time-consuming and difficult. Therefore, a multiplex PCR method for simultaneous detection of Actinobacillus actinomycetemcomitans (A.a.) and Porphyromonas gingivalis (P.g.) was developed for rapid and easy determination of these risk-indicator bacteria in human periodontal disease. The PCR primers were designed to hybridize to various regions of 16S rRNA genes, and a hot-start technique was used to obtain maximum sensitivity and specificity. This method can detect both of these bacteria in subgingival plaque samples at concentrations as low as 5 to 50 cells per sample. The sensitivity, however, was even 10 times better when the bacteria were analyzed in a water suspension. Since the only step between sample collection and the actual analysis is a brief centrifugation of the patient sample, the detection can be readily carried out in four hours. The performance of the method was studied with 36 patient samples. The results showed that the PCR method detected A.a. (44% vs. 25%, respectively) and P.g. (56% vs. 42%, respectively) more often than the conventional culture in plaque samples. Thus, our multiplex PCR method is rapid and more effective than conventional protocols in detecting these periodontal pathogens.