Forget the blood, not the stone! Microhaematuria in acute urolithiasis and the role of early CT scanning

BACKGROUND: Although urinalysis is simple and inexpensive to perform, the finding of microhaematuria on urinalysis may be unreliable for diagnosing urolithiasis. OBJECTIVE: To evaluate microhaematuria as a diagnostic marker for urolithiasis compared with low-dose unenhanced multidetector computed tomography (MDCT) as the "gold standard". SETTING: A level 1 emergency department in a tertiary referral university teaching hospital. DESIGN: Retrospective analysis. METHODS: A study was undertaken to assess whether the finding of microhaematuria was diagnostic for urolithiasis using a low-dose unenhanced MDCT-based diagnosis as the reference standard by reviewing the records of all patients who presented to the emergency department with colicky flank pain and underwent a CT scan between January 2003 and December 2005. RESULTS: Urolithiasis was present (as defined by low-dose unenhanced MDCT) in 507/638 patients (79%); 341/638 (53%) were true positive for urolithiasis, 76 (12%) were true negative, 55 (9%) were false positive and 166 (26%) were false negative. Microhaematuria as a test for urolithiasis in patients presenting to the emergency department therefore has a sensitivity, specificity, positive predictive value and negative predictive value of 67%, 58%, 86% and 31%, respectively. 58% of the urinalysis results were negative for haematuria in the subset of patients with significant alternative diagnoses. CONCLUSIONS: The sensitivity, specificity and negative predictive value of microhaematuria on urinalysis for urolithiasis using unenhanced MDCT as the reference standard were low. This suggests that, when urolithiasis is clinically suspected, unenhanced MDCT is indicated without urinalysis being a prerequisite.

Effects of Carnoy's solution on blood vessels of the axillary fossa of rats

Carnoy's solution is applied to reduce the recurrence of odontogenic keratocysts and unicystic ameloblastomas. The deleterious action of this fixative on nerves has been studied but no attention has been paid to its effects on nearby vessels. The aim of this study was to investigate the effects of Carnoy's solution on blood vessels. The rat axillary artery and vein were surgically exposed, soaked with Carnoy's solution and kept in place for 2, 5 or 10 min, depending on the treatment group. The 5-min group was followed for 1, 2 and 3 weeks postoperatively. The vessels in the 2-min and 5-min exposure groups showed histological changes to the vessels, represented by focal loss of the endothelium and hyalinization of the wall. These alterations increased in the 10-min group. The vessels in the 3-week observation period revealed signs of recovery. It is concluded that Carnoy's solution can damage blood vessels but the process is reversible for exposure times less than 5 min.

Blood pressure and vessel recanalization in the first hours after ischemic stroke

BACKGROUND AND PURPOSE: Transient elevation of arterial blood pressure (BP) is frequent in acute ischemic stroke and may help to increase perfusion of tissue jeopardized by ischemia. If this is true, recanalization may eliminate the need for this BP elevation. METHODS: We analyzed BP in 149 patients with acute ischemic stroke on admission to the hospital and 1 and 12 hours after intraarterial thrombolysis. BP values of patients with adequate recanalization were compared with BP values of patients with inadequate recanalization. Recanalization was determined on cerebral arteriography after thrombolysis using thrombolysis in myocardial infarction grades. RESULTS: Systolic, mean, and diastolic arterial BP decreased significantly from admission to 12 hours after thrombolysis in all patients (P<0.001). Before thrombolysis, patients with adequate and inadequate recanalization showed equal systolic (147.4 and 148.0 mm Hg), mean (102.1 and 104.1 mm Hg), and diastolic (79.5 and 82.1 mm Hg) BP values. Twelve hours after thrombolysis, patients with adequate recanalization had lower values than those with inadequate recanalization (systolic BP, 130 versus 139.9 mm Hg; mean BP, 86.8 versus 92.2 mm Hg; and diastolic, BP 65.2 versus 68.3 mm Hg). Two-way repeated ANOVA analysis showed a significant group x time interaction for systolic BP, indicating a larger systolic BP decrease when recanalization succeeded (P=0.019). CONCLUSIONS: The course of elevated systolic but not diastolic BP after acute ischemic stroke was found to be inversely associated with the degree of vessel recanalization. When recanalization failed, systolic BP remained elevated longer than when it succeeded.

Admission blood glucose is an independent predictive factor for hospital mortality in polytraumatised patients

PURPOSE: The goal of this study was to analyse a possible association of admission blood glucose with hospital mortality of polytraumatised patients and to develop an outcome prediction model for this patient group. METHODS: The outcome of adult polytraumatised patients admitted to the University Hospital of Berne, Switzerland, between 2002 and 2004 with an ISS > or = 17, and more than one severely injured organ system was retrospectively analysed. RESULTS: The inclusion criteria were met by 555 patients, of which 108 (19.5%) died. Hyperglycaemia proved to be an independent predictor for hospital mortality (P < 0.0001), following multiple regression analysis. After inclusion of admission blood glucose, the calculated mortality prediction model performed better than currently described models (P < 0.0001, AUC 0.924). CONCLUSION: In this retrospective, single-centre study in polytraumatised patients, admission blood glucose proved to be an independent predictor of hospital mortality following regression analysis controlling for age, gender, injury severity and other laboratory parameters. A reliable admission blood glucose-based mortality prediction model for polytraumatised patients could be established. This observation may be helpful in improving the precision of future outcome prediction models for polytraumatised patients. These observations warrant further prospective evaluation.

Culture-induced changes in blood-brain barrier transcriptome: implications for amino-acid transporters in vivo

Tight homeostatic control of brain amino acids (AA) depends on transport by solute carrier family proteins expressed by the blood-brain barrier (BBB) microvascular endothelial cells (BMEC). To characterize the mouse BMEC transcriptome and probe culture-induced changes, microarray analyses of platelet endothelial cell adhesion molecule-1-positive (PECAM1(+)) endothelial cells (ppMBMECs) were compared with primary MBMECs (pMBMEC) cultured in the presence or absence of glial cells and with b.End5 endothelioma cell line. Selected cell marker and AA transporter mRNA levels were further verified by reverse transcription real-time PCR. Regardless of glial coculture, expression of a large subset of genes was strongly altered by a brief culture step. This is consistent with the known dependence of BMECs on in vivo interactions to maintain physiologic functions, for example, tight barrier formation, and their consequent dedifferentiation in culture. Seven (4F2hc, Lat1, Taut, Snat3, Snat5, Xpct, and Cat1) of nine AA transporter mRNAs highly expressed in freshly isolated ppMBMECs were strongly downregulated for all cultures and two (Snat2 and Eaat3) were variably regulated. In contrast, five AA transporter mRNAs with low expression in ppMBMECs, including y(+)Lat2, xCT, and Snat1, were upregulated by culture. We hypothesized that the AA transporters highly expressed in ppMBMECs and downregulated in culture have a major in vivo function for BBB transendothelial transport.

Association of arterial blood pressure and vasopressor load with septic shock mortality: a post hoc analysis of a multicenter trial

INTRODUCTION: It is unclear to which level mean arterial blood pressure (MAP) should be increased during septic shock in order to improve outcome. In this study we investigated the association between MAP values of 70 mmHg or higher, vasopressor load, 28-day mortality and disease-related events in septic shock. METHODS: This is a post hoc analysis of data of the control group of a multicenter trial and includes 290 septic shock patients in whom a mean MAP > or = 70 mmHg could be maintained during shock. Demographic and clinical data, MAP, vasopressor requirements during the shock period, disease-related events and 28-day mortality were documented. Logistic regression models adjusted for the geographic region of the study center, age, presence of chronic arterial hypertension, simplified acute physiology score (SAPS) II and the mean vasopressor load during the shock period was calculated to investigate the association between MAP or MAP quartiles > or = 70 mmHg and mortality or the frequency and occurrence of disease-related events. RESULTS: There was no association between MAP or MAP quartiles and mortality or the occurrence of disease-related events. These associations were not influenced by age or pre-existent arterial hypertension (all P > 0.05). The mean vasopressor load was associated with mortality (relative risk (RR), 1.83; confidence interval (CI) 95%, 1.4-2.38; P < 0.001), the number of disease-related events (P < 0.001) and the occurrence of acute circulatory failure (RR, 1.64; CI 95%, 1.28-2.11; P < 0.001), metabolic acidosis (RR, 1.79; CI 95%, 1.38-2.32; P < 0.001), renal failure (RR, 1.49; CI 95%, 1.17-1.89; P = 0.001) and thrombocytopenia (RR, 1.33; CI 95%, 1.06-1.68; P = 0.01). CONCLUSIONS: MAP levels of 70 mmHg or higher do not appear to be associated with improved survival in septic shock. Elevating MAP >70 mmHg by augmenting vasopressor dosages may increase mortality. Future trials are needed to identify the lowest acceptable MAP level to ensure tissue perfusion and avoid unnecessary high catecholamine infusions.

Bacterial phenotype variants in group B streptococcal toxic shock syndrome

We conducted genetic and functional analyses of isolates from a patient with group B streptococcal (GBS) necrotizing fasciitis and toxic shock syndrome. Tissue cultures simultaneously showed colonies with high hemolysis (HH) and low hemolysis (LH). Conversely, the HH and LH variants exhibited low capsule (LC) and high capsule (HC) expression, respectively. Molecular analysis demonstrated that the 2 GBS variants were of the same clonal origin. Genetic analysis found a 3-bp deletion in the covR gene of the HH/LC variant. Functionally, this isolate was associated with an increased growth rate in vitro and with higher interleukin-8 induction. However, in whole blood, opsonophagocytic and intracellular killing assays, the LH/HC phenotype demonstrated higher resistance to host phagocytic killing. In a murine model, LH/HC resulted in higher levels of bacteremia and increased host mortality rate. These findings demonstrate differences in GBS isolates of the same clonal origin but varying phenotypes.

Prolonged platelet activation in individuals with elevated blood pressure in response to a moderate exercise challenge

We examined the magnitude of 20-min moderate exercise-induced platelet activation in 50 volunteers with normal (n=31) or elevated blood pressure (EBP; n=19). Blood was drawn before, immediately after, and 25 min after exercise. Antibody-staining for platelet activation markers, P-selectin, and fibrinogen receptors was done with and without adenosine diphosphate (ADP) stimulation in whole blood for flow cytometric analyses. Exercise led to increases in percent aggregated platelets and percent platelets expressing P-selectin or PAC-1 binding (ps< or =.001). This increase in percent platelets expressing P-selectin continued even after a 25-min rest only in the EBP group (p< or =.01) accompanied by an increase in percent of aggregated platelets (p< or =.05). Although ADP stimulation led to increased platelet activation at rest, it was attenuated following exercise, even among EBP individuals. A moderate exercise challenge induced prolonged platelet activation in individuals with EBP but attenuation in activation to further stimulation by an agonist. Findings suggest that a recovery period after physical stress appears critical in individuals with high BP regarding platelet activation and aggregation, which can lead to an acute coronary syndrome in vulnerable individuals.

Angiotensin I-converting enzyme-gene-polymorphism: relationship to albumin excretion and blood pressure in pediatric patients with type-I-diabetes mellitus

The purpose of this study was the evaluation of a predictive genetic marker for nephropathy and hypertension in patients with type-I-diabetes mellitus (IDDM). The study was performed on 247 pediatric patients with IDDM. The mean age was 15.5 years (range 3.1-29.3), the mean duration of diabetes was 7.6 years (range 0.1-25.7). Age-related blood pressure and nocturnal albumin excretion rate were compared with the insertion/deletion-(I/D) polymorphism of the angiotensin-I converting enzyme gene. The genotype distribution did not differ significantly between IDDM patients (ID 48%, D 28%, I 24%) and the control group (ID 44%, D 37%, I 19%). Neither in the entire group, nor in patients with IDDM for more than 5 years, was a correlation found bet-ween allele distribution and albumin excretion rate. No correlation was found between genotype and blood pressure. When patients with a chronological age above 12 years were analysed separately, the genotype distribution between the groups with normal and elevated blood pressure showed no significant difference. The previously reported association of the I/D-polymorphism with nephropathy could not be confirmed in this study. The development of microalbuminuria, nephropathy and hypertension will be followed in our pediatric patients.

Does single use of an autologous transfusion system in TKA reduce the need for allogenic blood?: a prospective randomized trial

BACKGROUND Mechanical autotransfusion systems for washed shed blood (WSB) were introduced to reduce the need for postoperative allogenic blood transfusions (ABTs). Although some authors have postulated decreased requirements for ABT by using autologous retransfusion devices, other trials, mostly evaluating retransfusion devices for unwashed shed blood (USB), verified a small or no benefit in reducing the need for postoperative ABT. Because of these contradictory findings it is still unclear whether autologous retransfusion systems for WSB can reduce transfusion requirements. QUESTIONS/PURPOSES We therefore asked whether one such autologous transfusion system for WSB can reduce the requirements for postoperative ABT. METHODS In a prospective, randomized, controlled study, we enrolled 151 patients undergoing TKA. In Group A (n=76 patients), the autotransfusion system was used for a total of 6 hours (intraoperatively and postoperatively) and the WSB was retransfused after processing. In Control Group B (n=75 patients), a regular drain without suction was used. We used signs of anemia and/or a hemoglobin value less than 8 g/dL as indications for transfusion. If necessary, we administered one or two units of allogenic blood. RESULTS Twenty-three patients (33%) in Group A, who received an average of 283 mL (range, 160-406 mL) of salvaged blood, needed a mean of 2.1 units of allogenic blood, compared with 23 patients (33%) in Control Group B who needed a mean of 2.1 units of allogenic blood. CONCLUSIONS We found the use of an autotransfusion system did not reduce the rate of postoperative ABTs. LEVEL OF EVIDENCE Level II, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Intraoperative Continuous Norepinephrine Infusion Combined with Restrictive Deferred Hydration Significantly Reduces the Need for Blood Transfusion in Patients Undergoing Open Radical Cystectomy: Results of a Prospective Randomised Trial

BACKGROUND Open radical cystectomy (ORC) is associated with substantial blood loss and a high incidence of perioperative blood transfusions. Strategies to reduce blood loss and blood transfusion are warranted. OBJECTIVE To determine whether continuous norepinephrine administration combined with intraoperative restrictive hydration with Ringer's maleate solution can reduce blood loss and the need for blood transfusion. DESIGN, SETTING, AND PARTICIPANTS This was a double-blind, randomised, parallel-group, single-centre trial including 166 consecutive patients undergoing ORC with urinary diversion (UD). Exclusion criteria were severe hepatic or renal dysfunction, congestive heart failure, and contraindications to epidural analgesia. INTERVENTION Patients were randomly allocated to continuous norepinephrine administration starting with 2 μg/kg per hour combined with 1 ml/kg per hour until the bladder was removed, then to 3 ml/kg per hour of Ringer's maleate solution (norepinephrine/low-volume group) or 6 ml/kg per hour of Ringer's maleate solution throughout surgery (control group). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Intraoperative blood loss and the percentage of patients requiring blood transfusions perioperatively were assessed. Data were analysed using nonparametric statistical models. RESULTS AND LIMITATIONS Total median blood loss was 800 ml (range: 300-1700) in the norepinephrine/low-volume group versus 1200 ml (range: 400-2800) in the control group (p<0.0001). In the norepinephrine/low-volume group, 27 of 83 patients (33%) required an average of 1.8 U (±0.8) of packed red blood cells (PRBCs). In the control group, 50 of 83 patients (60%) required an average of 2.9 U (±2.1) of PRBCs during hospitalisation (relative risk: 0.54; 95% confidence interval [CI], 0.38-0.77; p=0.0006). The absolute reduction in transfusion rate throughout hospitalisation was 28% (95% CI, 12-45). In this study, surgery was performed by three high-volume surgeons using a standardised technique, so whether these significant results are reproducible in other centres needs to be shown. CONCLUSIONS Continuous norepinephrine administration combined with restrictive hydration significantly reduces intraoperative blood loss, the rate of blood transfusions, and the number of PRBC units required per patient undergoing ORC with UD.

Erythropoietin neuroprotection is enhanced by direct cortical application following subdural blood evacuation in a rat model of acute subdural hematoma

Recombinant human erythropoietin (EPO) has been successfully tested as neuroprotectant in brain injury models. The first large clinical trial with stroke patients, however, revealed negative results. Reasons are manifold and may include side-effects such as thrombotic complications or interactions with other medication, EPO concentration, penetration of the blood-brain-barrier and/or route of application. The latter is restricted to systemic application. Here we hypothesize that EPO is neuroprotective in a rat model of acute subdural hemorrhage (ASDH) and that direct cortical application is a feasible route of application in this injury type. The subdural hematoma was surgically evacuated and EPO was applied directly onto the surface of the brain. We injected NaCl, 200, 2000 or 20,000IU EPO per rat i.v. at 15min post-ASDH (400μl autologous venous blood) or NaCl, 0.02, 0.2 or 2IU per rat onto the cortical surface after removal of the subdurally infused blood t at 70min post-ASDH. Arterial blood pressure (MAP), blood chemistry, intracranial pressure (ICP), cerebral blood flow (CBF) and brain tissue oxygen (ptiO2) were assessed during the first hour and lesion volume at 2days after ASDH. EPO 20,000IU/rat (i.v.) elevated ICP significantly. EPO at 200 and 2000IU reduced lesion volume from 38.2±0.6mm(3) (NaCl-treated group) to 28.5±0.9 and 22.2±1.3mm(3) (all p<0.05 vs. NaCl). Cortical application of 0.02IU EPO after ASDH evacuation reduced injury from 36.0±5.2 to 11.2±2.1mm(3) (p=0.007), whereas 0.2IU had no effect (38.0±9.0mm(3)). The highest dose of both application routes (i.v. 20,000IU; cortical 2IU) enlarged the ASDH-induced damage significantly to 46.5±1.7 and 67.9±10.4mm(3) (all p<0.05 vs. NaCl). In order to test whether Tween-20, a solvent of EPO formulation 'NeoRecomon®' was responsible for adverse effects two groups were treated with NaCl or Tween-20 after the evacuation of ASDH, but no difference in lesion volume was detected. In conclusion, EPO is neuroprotective in a model of ASDH in rats and was most efficacious at a very low dose in combination with subdural blood removal. High systemic and topically applied concentrations caused adverse effects on lesion size which were partially due to increased ICP. Thus, patients with traumatic ASDH could be treated with cortically applied EPO but with caution concerning concentration.

Botulinum toxin A and B raise blood flow and increase survival of critically ischemic skin flaps

BACKGROUND Botulinum toxin (BTX) A and B are commonly used for aesthetic indications and in neuromuscular disorders. New concepts seek to prove efficacy of BTX for critical tissue perfusion. Our aim was to evaluate BTX A and B in a mouse model of critical flap ischemia for preoperative and intraoperative application. METHODS BTX A and B were applied on the vascular pedicle of an axial pattern flap in mice preoperatively or intraoperatively. Blood flow, tissue oxygenation, tissue metabolism, flap necrosis rate, apoptosis assay, and RhoA and eNOS expression were endpoints. RESULTS Blood-flow measurements 1 d after the flap operation revealed a significant reduction to 53% in the control group, while flow was maintained or increased in all BTX groups (103%-129%). Over 5 d all BTX groups showed significant increase in blood flow to 166-187% (P < 0.01). Microdialysis revealed an increase of glucose and reduced lactate/pyruvate ratio and glycerol levels in the flap tissue of all BTX groups. This resulted in significantly improved tissue survival in all BTX groups compared with the control group (62% ± 10%; all P < 0.01): BTX A preconditioning (84% ± 5%), BTX A application intraoperatively (88% ± 4%), BTX B preconditioning (91% ± 4%), and intraoperative BTX B treatment (92% ± 5%). This was confirmed by TUNEL assay. Immunofluorescence demonstrated RhoA and eNOS expression in BTX groups. All BTX applications were similarly effective, despite pharmacologic dissimilarities and different timing. CONCLUSIONS In conclusion, we were able to show on a vascular, tissue, cell, and molecular level that BTX injection to the feeding arteries supports flap survival through ameliorated blood flow and oxygen delivery.