Assessing adherence to objective disease monitoring and outcomes with adalimumab in a real-world IBD cohort.

BACKGROUND: Data suggests that tight objective monitoring may improve clinical outcomes in IBD. AIM: To assess the adherence to serial tight objective monitoring(clinical and biomarkers) and its effect on clinical outcomes. METHODS: We retrospectively reviewed the chart of 428 consecutive IBD patients started on adalimumab between January 1,2015-January 1,2019 [338 Crohn's disease(CD), 90 ulcerative colitis(UC)]. Clinical symptoms(assessed by Harvey-Bradshaw-Index,partial Mayo),C-Reactive Protein(CRP), and fecal calprotectin(FCAL) assessments were captured at treatment initiation and at 3,6,9, and12 months. Dose optimization and drug sustainability curves were plotted by Kaplan-Meier method. RESULTS: Clinical evaluation was available in nearly all patients at 3(CD-UC:95-94%), 6(90-83%), 9(86-85%) and 12(96-89%) months. CRP testing frequency decreased in CD patients over time. Compliance to serial FCAL testing was low. Clinical remission at one-year was higher in patients adherent to early assessment visit at 3 months(p = 0.001 for CD and UC). Adherence to early follow-up resulted in earlier dose optimization in CD and UC patients(pLogrank=0.026 for UC & p = 0.09 for CD). Overall drug sustainability did not differ. CONCLUSION: Clinical & CRP, but not FCAL, were frequently assessed in patients starting adalimumab. Adherence to early objective combined follow-up visits resulted in earlier dose optimization, improved one-year clinical outcomes but did not change drug sustainability.

Treatment-induced remission of medulloblastoma using a chemotherapeutic regimen devoid of vincristine in a child with Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth (cmt) disease is the most common form of inherited neuropathy. Core features include peripheral neuropathy and secondary axonal degeneration, with a noted distal predominance of limb-muscle wasting, weakness, and sensory loss. Given the significant prevalence of cmt, superimposed neoplastic disease can be encountered within this patient population. Malignancies that are treated with vincristine (a microtubule-targeting agent), even at low doses as part of standard treatment, pose a significant challenge for patients with cmt. Here, we present the case of a child with cmt who was successfully treated for medulloblastoma without vincristine, a standard drug used for treatment of that disease, to avoid the risk of severe debilitating neuropathy. This report is the first of a patient successfully treated for medulloblastoma without vincristine.

Photosensitizing antihypertensive drug use and risk of cutaneous squamous cell carcinoma.

BACKGROUND: Many antihypertensive drugs (ADs) are photosensitizing, heightening reactivity of the skin to sunlight. Photosensitizing ADs have been associated with lip cancer, but whether they impact the risk of cutaneous squamous cell carcinoma (cSCC) is unknown. OBJECTIVES: To examine the association between AD use and cSCC risk among a cohort of non-Hispanic white individuals with hypertension enrolled in a comprehensive integrated healthcare delivery system in northern California (n = 28 357). METHODS: Electronic pharmacy data were used to determine exposure to ADs, which were classified as photosensitizing, nonphotosensitizing or unknown, based on published literature. We identified patients who developed a cSCC during follow-up (n = 3010). We used Cox modelling to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Covariates included age, sex, smoking, comorbidities, history of cSCC and actinic keratosis, survey year, healthcare utilization, length of health plan membership and history of photosensitizing AD use. RESULTS: Compared with nonuse of ADs, risk of cSCC was increased with ever having used photosensitizing ADs (aHR = 1·17, 95% CI 1·07-1·28) and ever having used ADs of unknown photosensitizing potential (aHR = 1·11, 95% CI 1·02-1·20), whereas no association was seen with ever having used nonphotosensitizing ADs (aHR = 0·99; 95% CI 0·91-1·07). Additionally, there was a modest increased risk with an increased number of prescriptions for photosensitizing ADs (aHR = 1·12, 95% CI 1·02-1·24; aHR = 1·19, 95% CI 1·06-1·34; aHR = 1·41, 95% CI 1·20-1·67 for one to seven, eight to 15 and ≥ 16 fills, respectively). CONCLUSIONS: These findings provide moderate support for an increased cSCC risk among individuals treated with photosensitizing ADs.

Hydrochlorothiazide use is strongly associated with risk of lip cancer.

BACKGROUND: The diuretic hydrochlorothiazide is amongst the most frequently prescribed drugs in the United States and Western Europe, but there is suggestive evidence that hydrochlorothiazide use increases the risk of lip cancer. OBJECTIVES: To study the association between use of hydrochlorothiazide and squamous cell carcinoma of the lip. METHODS: We conducted a case-control study using Danish nationwide registry data. From the Cancer Registry (2004-2012), we identified 633 case patients with squamous cell carcinoma (SCC) of the lip and matched them to 63 067 population controls using a risk-set sampling strategy. Hydrochlorothiazide use (1995-2012) was obtained from the Prescription Registry and defined according to cumulative use. Applying conditional logistic regression, we calculated odds ratios (ORs) for SCC lip cancer associated with hydrochlorothiazide use, adjusting for predefined potential confounders obtained from demographic, prescription and patient registries. RESULTS: Ever-use of hydrochlorothiazide was associated with an adjusted OR for SCC lip cancer of 2.1 (95% confidence interval (CI): 1.7-2.6), increasing to 3.9 (95%CI: 3.0-4.9) for high use (≥25 000 mg). There was a clear dose-response effect (P < 0.001), with the highest cumulative dose category of hydrochlorothiazide (≥100 000 mg) presenting an OR of 7.7 (95%CI: 5.7-10.5). No association with lip cancer was seen with use of other diuretics or nondiuretic antihypertensives. Assuming causality, we estimated that 11% of the SCC lip cancer cases could be attributed to hydrochlorothiazide use. CONCLUSIONS: Hydrochlorothiazide use is strongly associated with an increased risk of lip cancer.

Pilot study to evaluate a plasma device for the treatment of onychomycosis.

Onychomycosis is a fungal infection of the nail unit, and is the most common of the nail disorders. Current therapies for onychomycosis have less than ideal efficacy and have the potential for adverse effects. As previous studies have shown that nonthermal plasma inhibits the in vitro growth of Trichophyton rubrum, we conducted a pilot study on 19 participants with toenail onychomycosis. The primary endpoint was safety of the device, and secondary outcome measures were clinical efficacy and mycological cure. Patient satisfaction was measured using questionnaires at the completion of the study. All but one patient met the primary endpoint of safety and there were no long-term sequelae. The overall clinical cure was 53.8% and the mycological cure was 15.4%. The majority of patients were satisfied with the treatment. Our conclusions are that nonthermal plasma is a safe treatment and may have a beneficial effect on toenail onychomycosis.

γ134.5-deleted HSV-1-expressing human cytomegalovirus IRS1 gene kills human glioblastoma cells as efficiently as wild-type HSV-1 in normoxia or hypoxia.

Pathophysiological hypoxia, which fosters the glioma stem-like cell (GSC) phenotype, is present in high-grade gliomas and has been linked to tumor development, invasiveness and resistance to chemotherapy and radiation. Oncolytic virotherapy with engineered herpes simplex virus-1 (HSV-1) is a promising therapy for glioblastoma; however, the efficacy of γ(1)34.5-deleted HSVs, which have been used in clinical trials, was diminished in hypoxia. We investigated the ability of a chimeric human cytolomegalovirus (HCMV)/HSV-1 virus, which expresses the human CMV protein kinase R evasion gene IRS1 and is in preparation for clinical trials, to infect and kill adult and pediatric patient-derived glioblastoma xenografts in hypoxia and normoxia. Infectivity, cytotoxicity and viral recovery were significantly greater with the chimeric virus compared with the γ(1)34.5-deleted virus, regardless of oxygen tension. The chimeric virus infected and killed CD133+ GSCs similarly to wild-type HSV-1. Increased activation of mitogen-activated protein kinase p38 and its substrate heat-shock protein 27 (Hsp27) was seen after viral infection in normoxia compared with hypoxia. Hsp27 knockdown or p38 inhibition reduced virus recovery, indicating that the p38 pathway has a role in the reduced efficacy of the γ(1)34.5-deleted virus in hypoxia. Taken together, these findings demonstrate that chimeric HCMV/HSV-1 efficiently targets both CD133+ GSCs and glioma cells in hypoxia.

Guidelines for maintenance of adult patients with brain death and potential for multiple organ donations: the Task Force of the Brazilian Association of Intensive Medicine the Brazilian Association of Organs Transplantation, and the Transplantation Center of Santa Catarina.

INTRODUCTION: The organ shortage for transplantation, the principal factor that increases waiting lists, has become a serious public health problem. In this scenario, the intensivist occupies a prominent position as one of the professionals that first has a chance to identify brain death and to be responsible for the maintenance of the potential deceased donor. OBJECTIVE: This report attempts to establish guidelines for care and maintenance of adult deceased donor organs guiding and standardizing care provided to patients with brain death. METHOD: These guidelines were composed by intensivists, transplant coordinators, professionals from various transplant teams, and used transplant center. The formulated questions were forwarded to all members and recommendations were constructed after an extensive literature review selecting articles with the highest degree of evidence. RESULTS: Guidelines were developed in the form of questions reflecting frequent experiences in clinical intensive care practices. The main questions were: Is there an optimal interval for keeping organs of deceased donors viable? What actions are considered essential for maintaining deceased donors in this period? What are the limits of body temperature? How should the patient be warmed? Which laboratory tests should be performed? What is the collection interval? What are the limits in the laboratory and the capture scenario? What are the limits of blood pressure? When and how should one use catecholamines? CONCLUSIONS: This pioneer project involved a multidisciplinary team working in organ transplantation seeking to provide treatment guidance to increase the number of viable organs from deceased adult donors.

Comparison of low and high dose cosyntropin stimulation tests in the diagnosis of adrenal insufficiency in septic shock patients.

Stress situations such as septic shock are accompanied by activation of the HPA axis. Some patients do not activate this axis in stress situations. This blunted response is currently designated as critical illness-related corticosteroid insufficiency (CIRCI). Currently the 250 µg cosyntropin stimulation test is the preferred diagnostic test for CIRCI. Few papers explored the role of the 1 µg cosyntropin test in septic shock patients. In this study, we compared both tests in septic shock patients taking a special interest in the population with intermediary baseline cortisol. Prospective noninterventional study included 74 septic shock patients. After measurement of baseline cortisol all patients received 1 µg of cosyntropin i. v. and 4 h later 249 µg of cosyntropin. We compared the cortisol increase after each test and its relation to mortality and vasopressor therapy. There was a moderate correlation in response to low and high dose cosyntropin, r(s)=0.55. This correlation in patients with baseline cortisol between 10-34 µg/dl is, r(s)=0.67. The increase induced by both tests was equally accurate to identify mortality and time of vasopressor withdrawal. Low and high dose cosyntropin tests presented a moderate correlation in patients with baseline cortisol between 10-34 µg/dl. Both tests are equally accurate to identify mortality and time of vasopressor therapy. These results suggest that both tests could be used to diagnose CIRCI.

Systolic blood pressure and mortality in prevalent haemodialysis patients in the HEMO study.

Previous studies of blood pressure and mortality in haemodialysis have yielded mixed results, perhaps due to confounding by comorbid conditions. We hypothesized that after improved accounting for confounding factors, higher systolic blood pressure (SBP) would be associated with higher all-cause mortality. We conducted a secondary analysis of data from the haemodialysis study, a randomized trial in prevalent haemodialysis patients. We used three proportional hazard models to determine the relative hazard at different levels of SBP: (1) Model-BL used baseline SBP; (2) Model-TV used SBP as a time-varying variable; and (3) Model-TV-Lag added a 3-month lag to Model-TV to de-emphasize changes in SBP associated with acute illness. In all the models, pre-dialysis SBP <120 mm Hg was associated with a higher risk of mortality compared with the referent group (140-159 mm Hg); higher pre-dialysis SBP was not associated with higher risk of mortality. In conclusion, we observed a robust association between lower pre-dialysis SBP and higher risk for all-cause and cardiovascular mortality in a well-characterized cohort of prevalent haemodialysis patients. Randomized clinical trials are needed to define optimal blood pressure targets in the haemodialysis population.

Nonconverging hysteresis cycles in random spin networks.

Behavior of hysteretic trajectories for cyclical input is investigated as a function of the internal structure of a system modeled by the classical random network of binary spins. Different regimes of hysteretic behavior are discovered for different network connectivity and topology. Surprisingly, hysteretic trajectories which do not converge at all are observed. They are shown to be associated with the presence of specific topological elements in the network structure, particularly with the fully interconnected spin groups of size equal to or greater than 4.

A pathogenic role for JNK signaling in experimental anti-GBM glomerulonephritis.

Activation of the c-Jun NH2-terminal kinase (JNK) signaling pathway is involved in the immune response; however, little is known of its role in immune-induced renal injury. In this study, we examine JNK signaling in the rat anti-glomerular basement membrane (GBM) disease model using CC-401, a specific JNK inhibitor. Animals were given CC-401, vehicle alone or no treatment starting before anti-GBM serum injection and continued treatment until killing. In acute disease, CC-401 blocked JNK signaling and reduced proteinuria in the first 24 h. The transient neutrophil influx seen at 3 h of disease was not affected, however. Continued CC-401 treatment suppressed glomerular and tubulointerstitial damage usually seen at 14 days. The protective effect may be due to modulation of macrophage activation, as CC-401 had no effect upon glomerular macrophage infiltration at day 14 despite the suppression of glomerular lesions and a marked reduction in renal tumor necrosis factor-alpha and inducible nitric oxide synthase messenger RNA levels. Treatment with CC-401 had no apparent effect on T cell or humoral immune responses. These studies suggest that JNK signaling promotes renal injury in acute and progressive rat anti-GBM disease. JNK inhibitors may be a novel therapeutic approach for the treatment of human glomerulonephritis.

Adaptive Support Ventilation as the sole mode of ventilatory support in chronically ventilated patients.

OBJECTIVE: To describe the outcome of patients admitted to a new private facility for chronically ventilated patients in the Ashdod area of Israel. METHODS: On arrival, all patients were placed on Adaptive Support Ventilation (ASV) at 90% of target minute ventilation for lean body weight, reducing progressively in weekly decrements of 10% down to 60% of target minute ventilation if adequate spontaneous ventilation was maintained by the patient. RESULTS: Almost half (12/27) of these patients admitted in the first 12 months following establishment of the facility were successfully weaned from mechanical ventilation within 2 weeks to 2 months of admission. CONCLUSIONS: The cost effectiveness of this form of closed loop mechanical ventilation in achieving weaning automatically, without the need for respiratory therapists or continuous attendance by intensive care specialists to conduct weaning trials is demonstrated by these results.

The kinetics and saturation of reversible adsorption on patterned (heterogeneous) surfaces.

We analytically examine the time-dependent adsorption of analyte (solute) on a finite-sized adsorption region as a model for sensors utilizing patterned or heterogeneous surfaces. We account for both reversible adsorption (assuming first-order reaction) and saturation of the adsorption patch that may arise either from packing constraints (finite area) or because of a finite number of binding sites (ligands). Our main conclusions include the following: (1) Saturation effects, due to either finite patch size or finite number of binding sites, become significant at extremely short times. (2) Increasing the strength of binding between the analyte and the adsorption sites increases the adsorbed amount at short times, but, at long times, the mass adsorbed on a weakly binding patch is higher than that on a strongly binding one. (3) The sensitivity of detection, as defined by the adsorption of the minimal analyte mass required for signaling, over a fixed period of time, does not scale as 1/detection time. As a result, increasing the time over which adsorption occurs increases sensitivity, but not linearly. Sensitivity of detection also increases with increasing patch area and initial binding strength.

Cooperativity in the adsorption of magnetic colloidal particles.

In this paper we investigate the adsorption of magnetic particles onto magnetically patterned substrates. We find that the adsorption process is cooperative, where the probability of adsorption decreases with increasing substrate occupancy (namely, density of adsorbed particles). The effect of cooperativity can be accounted for by a simple modification of the adsorption probability as manifested by the binomial distribution. The negative cooperativity found in the magnetic particle adsorption is not due to direct repulsion between particles, but to screening of the surface's magnetic field by previously adsorbed particles. Thus, the adsorption of magnetic colloids on magnetic substrates is a self-limiting process.

Combined use of sirolimus and voriconazole in renal transplantation: a report of two cases.

Voriconazole is currently contraindicated for use with sirolimus. We report our experience with voriconazole/sirolimus in two renal transplant recipients. To our knowledge, this is the first experience with voriconazole/sirolimus. An interaction requiring a 75% to 87.5% sirolimus dose reduction was noted, but goal trough levels and clinical tolerability were achieved.

There is no difference in the disease severity of gastro-oesophageal reflux disease between patients infected and not infected with Helicobacter pylori.

BACKGROUND: The role of Helicobacter pylori in gastro-oesophageal reflux disease (GERD) is controversial. AIM: To compare the severity of GERD in infected vs. non-infected patients, as part of an ongoing randomized controlled trial that examines the impact of H. pylori eradication on GERD-related outcomes. METHODS: Consecutive GERD patients underwent urea breath testing and completed validated GERD symptom severity, and quality of life questionnaires as well as, 24-h pH-metry. These parameters, as well as demographics and endoscopic findings were assessed in double-blinded fashion and compared between H. pylori-infected and non-infected subjects. RESULTS: Helicobacter pylori-infected GERD patients (n=50) were significantly older and less educated than non-infected patients (n=51). They also used proton pump inhibitors less often but had no difference in symptoms (as measured with both the Spechler's Activity Index and the Gastrointestinal Symptom Rating Scale), quality of life, endoscopic findings or 24-h pH-metry findings. CONCLUSION: This prospective, double-blind study demonstrates, using excellent GERD quantifying measures including validated symptom severity scores, endoscopy, and 24-h pH-metry, that there exist no clinically significant differences in clinical or laboratory-related GERD manifestations between H. pylori-infected and non-infected GERD patients.

Methotrexate related adverse effects in patients with rheumatoid arthritis are associated with the A1298C polymorphism of the MTHFR gene.

BACKGROUND: There is an association between C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene and methotrexate related toxicity. OBJECTIVE: To examine the relations between the recently described A1298C polymorphism of the MTHFR gene, plasma homocysteine, methotrexate toxicity, and disease activity in patients with rheumatoid arthritis. DESIGN: A cross sectional study on 93 methotrexate treated patients with rheumatoid arthritis, comprising a clinical interview and physical examination to determine disease activity and methotrexate related adverse reactions. Genotype analysis of the MTHFR gene was carried out and fasting plasma homocysteine and serum folate concentrations were measured. The data were analysed using univariate analysis. Allele and genotype distributions were compared with those of a healthy control group. RESULTS: The frequency of the 1298CC genotype (24.7%) in the rheumatoid study group was greater than expected in the general population (12.8%, p<0.001). This genotype was associated with a significantly low rate of methotrexate related side effects. The odds ratio for side effects in patients with wild type 1298AA genotype v 1298CC genotype was 5.24 (95% confidence interval, 1.38 to 20). No correlation of disease activity variables or plasma homocysteine with MTHFR A1298C and C677T polymorphisms was observed. CONCLUSIONS: 1298CC polymorphism was more common in methotrexate treated rheumatoid patients than expected in the population, and was associated with a reduction in methotrexate related adverse effects. The A1298C polymorphism of the MTHFR gene may indicate a need to adjust the dose of methotrexate given to patients with rheumatoid arthritis.

Cell death in cultured human Saos2 osteoblasts exposed to low-density lipoprotein.

Osteoporosis (OP) and atherosclerotic-cardiovascular diseases (and possibly dementia) constitute emerging age-related co-morbidity states that might share risk factors. Blood-born lipids, like LDL involved in atherosclerosis and apolipoprotein-E4 (ApoE4) involved in dementia, may also be implicated in development of OP. We examined osteoblast cell lines as a culture model for OP by exposure to lipoproteins. ApoE expression in Saos2 and U2OS osteoblasts was confirmed by PCR. ApoE4 did decrease cell counts relatively to ApoE3, especially in Saos2 cells in which it was less selective for cells with higher alkaline phosphatase (ALP, an osteoblast marker) activity than ApoE3. This associates with ApoE4, being a risk factor for both dementia and OP. Saos2, but not U2OS, showed a decrease in cell counts after 48 h exposure to native LDL (NLDL). Both cell lines had decreased cell counts already after 24 h when exposed to oxidized-LDL (OxLDL) for which Saos2 also showed a higher sensitivity than U2OS. Exposure of Saos2 to both, OxLDL at low concentration (5 microg/ml) and NLDL revealed a shrunken size cell fraction of 17-23% on the fluorescence-activated cell sorter (FACS) analysis. Such shrunken cell fraction was not seen when Saos2 cells were exposed to 50 microg/ml of OxLDL or to OxLDL combined with 10 nM dexamethasone (DEX, a stimulator of osteoprogenitor differentiation). DEX treatment has lysed the cells earlier than 24 h post exposure and has selected more resistant cells that did not show apoptotic shrinkage in the FACS analysis done after 24 h. We interpret this as a failure to detect the apoptotic cell fraction due to their lysis prior to the FACS analysis. Western blots performed at different time points (10 min, 30 min, 4 h, 24 h, and 48 h) under OxLDL + DEX revealed a fall in the positive regulator of pp60Src-kinase phosphotyrosine (pY)418 relative to the DEX controls during the first 4 h. This is consistent with DEX osteogenic induction, known to be negatively regulated by c-Src, although the pY418/pY529 ratios (negative/positive kinase regulation) fell only at the 10 min time point. Contrarily the pY418/pY529 ratio increased, relative to untreated controls, under 5 microg/ml and 50 microg/ml of NLDL at the 4 h time point and under 50 microg/ml NLDL only at the 10 min time point, being consistent with the ability of a higher dose of LDL to antagonize osteoblast differentiation. This could be even more acceptable if the NLDL would have become minimally oxidized during its long purification procedure. Under NLDL, the Bcl-2/Bax ratio was pro-apoptotic at 10 min, 30 min, and 4 h only under 50 microg/ml, whereas under OxLDL + DEX it was pro-apoptotic only after 4 h suggesting that additional pathways contribute to cell death. These results indicate that lipid effects on human osteoblast lines in culture may be used as a model to identify molecular targets shared between OP and atherosclerosis for intervention in this co-morbidity.

Acute haemodynamic effects of a hypertonic saline/dextran solution in stable patients with severe sepsis.

OBJECTIVE: To study the haemodynamic effects of a hypertonic saline/dextran solution compared with a normal saline solution in patients with severe sepsis. DESIGN: Prospective double blind and control-randomised study. SETTING: Adult intensive care unit in a university hospital. PATIENTS: Twenty-nine patients with sepsis with a pulmonary artery occlusion pressure (PAOP) lower than 12 mmHg. INTERVENTIONS: Patients were randomised to receive 250 ml of blinded solutions of either normal saline (SS group, n=16) or hypertonic saline (NaCl 7.5%)/dextran 70 8% (HSS group, n=13) solutions. MEASUREMENTS AND RESULTS: Haemodynamic, blood gas, and sodium data were collected at the following time points: baseline, 30 min, 60 min, 120 min, and 180 min. PAOP was higher in the HSS group at 30 min (10.7+/-3.2 mmHg vs 6.8+/-3.2 mmHg) and 60 min (10.3+/-3 mmHg vs 7.4+/-2.9 mmHg); P<0.05. The cardiac index increased in the HSS group and it was greater than the SS group at 30 min (6.5+/-4.7 l min(-1) m(-2) vs 3.8+/-3.4 l min(-1) m(-2)), 60 min (4.9+/-4.5 l min(-1) m(-2) vs 3.7+/-3.3 l min(-1) m(-2)), and 120 min (5.0+/-4.3 l min(-1) m(-2) vs 4.1+/-3.4 l min(-1) m(-2)); P<0.05. The stroke volume index followed a comparable course and it was higher at 30 min [53.6(39.2-62.8) ml m(-2) vs 35.6(31.2-49.2) ml m(-2)] and 60 min [46.8(39.7-56.6) ml m(-2) vs 33.9(32.2-47.7) ml m(-2)]; P<0.05. Systemic vascular resistance decreased in the HSS group and became significantly lower at 30 min (824+/-277 dyne s(-1) cm(-5) m(-2) vs 1139+/-245 dyne s(-1) cm(-5) m(-2)), 60 min (921+/-256 dyne s(-1) cm(-5) m(-2) vs 1246+/-308 dyne s(-1) cm(-5) m(-2)), and 120 min (925+/-226 dyne s(-1) cm(-5) m(-2) vs 1269+/-494 dyne s(-1) cm(-5) m(-2)). Sodium levels increased in the HSS group (P=0.056) and were higher than in the SS group at 30 min (145+/-3 mEq l(-1)vs 137+/-7 mEq l(-1)), 60 min (143+/-4 mEq l(-1) vs 136+/-7 mEq l(-1)), 120 (142+/-5 mEq l(-1)vs 136+/-7 mEq l(-1)), and 180 min (142+/-5 mEq l(-1) vs 136+/-8 mEq l(-1)). CONCLUSION: Hypertonic saline/dextran solution may improve cardiovascular performance in severe sepsis without significant side effects. The haemodynamic effect appears related mainly to a volume effect.