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Intracerebral hemorrhage is the most devastating stroke subtype with high rates of mortality and morbidity. Furthermore, no clinically approved treatment exists that effectively increases survival or improves quality of life for survivors. Effective modeling is necessary to elucidate the pathophysiological mechanisms of intracerebral hemorrhage and evaluate potential therapeutic approaches. Rodent models are most utilized because of their cost-effectiveness, and because rodent brain development and structures are well documented. Herein, we describe two intracerebral hemorrhage mouse models: the autologous blood double-injection and collagenase infusion models.

Adropin is expressed in the CNS and plays a crucial role in the development of stroke. However, little is currently known about the effects of adropin on the blood-brain barrier (BBB) function after intracerebral hemorrhage (ICH). In this study, the role of adropin in collagenase-induced ICH was investigated in mice. At 1-h post-ICH, mice were administered with recombinant human adropin by intranasal. Brain water +content, BBB permeability, and neurological function were measured at different time intervals. Proteins were quantified using western blot analysis, and the localizations of adropin and Notch1 were visualized via immunofluorescence staining. It is shown that adropin reduced brain water content and improved neurological functions. Adropin preserved the functionality of BBB by increasing N-cadherin expression and reducing extravasation of albumin. Moreover, in vivo knockdown of Notch1 and Hes1 both abolished the protective effects of adropin. Taken together, our data demonstrate that adropin constitutes a potential treatment value for ICH by preserving BBB and improving functional outcomes through the Notch1 signaling pathway., (© 2017 International Society for Neurochemistry.)

Background: This article describes the process of including people with intellectual disabilities (ID) and carers of people with ID as researchers and participants in randomised controlled trial (RCT) research. People with ID are rarely involved in research about their health, either as researchers or participants. Carers are often included as research informants, but family carers are rarely involved as researchers., Method: Four teams of researchers each comprising a researcher with ID, a supporting professional and a carer researcher, were recruited to complete a health intervention RCT. Accessible measures were selected and/or devised. Baseline interviews were completed by researchers with ID and/or carers of people with ID by asking participants with ID and/or carers of the participant about the health of the person with ID. Follow-up health interviews were administered after the intervention had been in place for a year., Results: The researchers completed 331 interviews with carers and 196 with participants with ID. Over 50% of participants with ID completed baseline assessments. Positive feedback on the process and outcomes was given by the researchers involved., Conclusion: The inclusion of people with ID both as researchers and as participants was achieved through an appropriate design, strong research partnerships, adequate and flexible resources, promotion of teamwork and a strong task focus., (© 2011 Blackwell Publishing Ltd.)

Objective: To investigate the relationship of mortality to early resuscitation using two levels of oxygen delivery (DO2) in critically ill surgical patients > or =50 yrs of age who were stratified into groups: age < or =75 yrs (age 50 to 75 yrs group); and age >75 yrs (age >75 yrs group)., Design: A prospective, randomized trial, continued from a previous project., Setting: Surgical intensive care unit, university affiliated., Patients: Consecutive patients, >50 yrs of age, unable to generate a DO2 of > or =600 mL/min/m2 with fluid resuscitation alone, with a diagnosis of systemic inflammatory response syndrome, sepsis, severe sepsis, septic shock, and/or acute respiratory distress syndrome., Interventions: During the first 24 hrs of resuscitation, patients were randomized to receive fluids, blood transfusions, and vasoactive agents in order to achieve DO2 treatment goals of > or =600 mL/ min/m2 in the protocol group and 450 to 550 mL/min/m2 in the control group., Measurements and Main Results: One hundred five patients completed the study. In patients aged 50 to 75 yrs, the mortality rate was 21% (9/43) in the protocol group and 52% (12/23) in the control group (p=.01, 95% confidence interval of -58% to -4%). In patients >75 yrs of age, the mortality rate was 57% (12/21) in the protocol group and 61% (11/18) in the control group. Oxygen extraction ratios (O2ER) and oxygen consumption values were significantly (p=.02) lower in the age >75 yrs group compared with the age 50 to 75 yrs group., Conclusions: Patients 50 to 75 yrs of age receiving a DO2 of > or =600 mL/min/m2 demonstrated a statistically significant (p=.01) improved survival rate over patients in the control group. Patients >75 yrs of age demonstrated no benefit from attempts to increase DO2 to >600 mL/min/m2, and they may have been overtreated as reflected by the lower O2ER values in this age group. Treating to an O2ER that reflects a balance between oxygen consumption and DO2 may be an alternative goal that allows individual titration.

Objective: To evaluate the agreement of continuous cardiac output and mixed venous oxygen saturation measurements, obtained with a modified pulmonary artery catheter, with those values obtained by standard intermittent bolus thermodilution and cooximetry., Design: Prospective, clinical investigation., Setting: A surgical intensive care unit in a tertiary referral center., Patients: Twenty-one adult critically ill surgical patients, requiring pulmonary artery catheter monitoring., Interventions: None., Measurements and Main Results: A modified pulmonary artery catheter capable of continuous monitoring of cardiac output and mixed venous oxygen saturation was used with either an 8.5-Fr or a 9-Fr introducer. At random intervals, the continuous cardiac output measurement was compared with the cardiac output obtained using standard intermittent bolus thermodilution. The system was calibrated every 24 hrs for mixed venous oxygen saturation monitoring. Each saturation obtained by the laboratory cooximeter was compared with that value recorded using the catheter. Data points for 202 pairs of cardiac output (21 patients, 31 catheters) and 65 pairs of mixed venous oxygen saturation (20 patients, 28 catheters) were obtained. The bias and precision of the cardiac output data were 0.49 and 1.01 L/min, respectively. The agreement between the continuous and bolus values decreased as the cardiac output increased. Heart rate did not affect the agreement between the continuous and bolus techniques. The bias and precision of the mixed venous oxygen saturation data were -0.57% and 3.76%, respectively. The hematocrit did not affect the bias or precision of the venous saturation data over the hematocrit range observed (23.2% to 44.6%). Fewer catheter malfunctions were observed when the catheter was used with a 9-Fr introducer than with an 8.5-Fr introducer., Conclusions: The test catheter adequately measures continuous cardiac output and mixed venous oxygen saturation in the clinical setting. Because intermittent bolus thermodilution is not a true "gold standard" for cardiac output determination, new techniques compared with bolus thermodilution may fail to achieve accuracy expectations. A 9-Fr introducer is recommended, as fiberoptic damage may have occurred when the 8.5-Fr introducer was used.

A case of colonoscopic polypectomy complicated by perforation, pneumoperitoneum, bilateral pneumothoraces, pneumopericardium, pneumomediastinum, and subcutaneous emphysema is presented. The anatomic basis for the various clinical presentations of extraluminal air following colonoscopy as well as the option of conservative therapy of select cases of perforation is discussed.

Objective: The existence of oxygen supply dependency, defined as oxygen consumption (VO2) limited by oxygen delivery (DO2), is still questioned. This study examined the relationship between VO2 and DO2 in two groups of critically ill surgical patients 50 years and older in the first 24 hours of resuscitation after pulmonary artery catheter insertion. Group 1 patients had systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock, and adult respiratory distress syndrome (ARDS). Group 2 patients had hemorrhagic shock., Methodology: Study methodology included (1) augmenting DO2 with fluids, blood, and vasopressors, (2) measuring VO2 by indirect calorimetry to avoid the problem of mathematical coupling with DO2 calculation, and (3) analyzing data during steady states of temperature, sedation, paralyzing agents, and vasopressors., Results: Six to 18 measurements collected on all study patients during a period within the first 24 hours were analyzed using a linear regression analysis. Statistical significance was set at p < or = 0.05. Seven of nine patients in group 1 demonstrated positive, statistically significant relationships between VO2 and DO2. Of six patients in group 2, one patient demonstrated a positive, significant relationship of VO2 and DO2, three demonstrated inverse relationships, and two patients did not show a DO2/VO2 relationship. Supply dependency did not exist in all patients but was present in seven out of nine patients with systemic inflammatory response syndrome, sepsis, severe sepsis, septic shock, and adult respiratory distress syndrome in the first 24 hours of treatment.

Chronic tachycardia-induced dilated cardiomyopathy causes increased plasma catecholamines and alterations in beta-adrenergic responsiveness in vivo. However, whether isolated myocyte contractile response to beta-stimulation is directly affected by the development of cardiomyopathy and how these changes are related to alterations in the beta-adrenergic receptor system remain unclear. Accordingly, isolated myocyte function and beta-adrenergic responsiveness were examined in two groups of 12 pigs each: sham controls, and with supraventricular tachycardia induced cardiomyopathy (SVT; pace: 240 beats/min, 3 weeks). Isolated LV myocyte percent and velocity of shortening were examined at baseline, with isoproterenol (2-100 nM), and forskolin (0.1-4 microM). Baseline percent and velocity of shortening were significantly reduced with SVT compared to controls (1.6 +/- 0.1 vs 5.4 +/- 0.2%, 56 +/- 3 vs 25 +/- 1 micron/s, respectively, P < 0.05). The maximal increase in the percent and velocity of shortening with isoproterenol was significantly blunted in the SVT myocytes compared with controls (3.2 +/- 0.4 vs 9.7 +/- 1.0%, 48.0 +/- 5.3 vs 122.6 +/- 15.5 micron/s, respectively, P < 0.05). Similarly, maximal increase in the percent and velocity of shortening with forskolin were reduced with SVT compared to controls (3.3 +/- 0.4 vs 10.5 +/- 0.6%, 50.7 +/- 6.4 vs 120.1 +/- 9.7 micron/s, respectively, P < 0.05). In order to determine the cellular basis for these changes in beta-adrenergic response, myocyte structure, sarcolemmal beta-receptor density and affinity, and adenylate cyclase activity were examined. There was a 25% reduction in beta-receptor number with SVT (P < 0.05) but no change in affinity. Basal adenylate cyclase activity was lower with SVT compared to control (46 +/- 3 vs 77 +/- 10 pmol cyclic AMP/mg/min, P < 0.05), and exhibited a blunted response with both isoproterenol (1 mM; 106 +/- 19 vs 203 +/- 26 pmol cyclic AMP/mg/min, P < 0.05) and forskolin (100 microns: 209 +/- 35 vs 378 +/- 58 pmol cyclic AMP/mg/min, P < 0.05). Finally, myofibrillar content within SVT myocytes was significantly reduced from controls (43 +/- 7 vs 63 +/- 4%, P < 0.05). In summary, the cellular basis for the depressed myocyte contractile response to beta-stimulation with tachycardia induced SVT are probably due to several factors which include: decreased expression of beta-receptors, alterations in beta-receptor transduction, reduced adenylate cyclase activity, and decreased myocyte contractile protein content.

Chronic supraventricular (or ventricular) tachycardia causes a dilated cardiomyopathy. Effective treatment requires ablation of the tachycardia using antiarrhythmic agents, cryoablation, electroablation, or surgical interruption/excision. However, the underlying pathophysiologic mechanisms responsible for the development of supraventricular tachycardia-induced cardiomyopathy have not been fully identified. We hypothesized that chronic supraventricular tachycardia is associated with significant changes in the beta-adrenergic system that may have implications for the pathophysiology and treatment of supraventricular tachycardia-induced cardiomyopathy. Accordingly, we examined the relationship between left ventricular function, plasma norepinephrine level, beta-receptor number and affinity, and response to a beta-agonist (isoproterenol) infusion in eight control pigs and eight pigs subjected to supraventricular pacing-induced tachycardia (240 beats/min for 3 weeks). Left ventricular function was measured using simultaneous echocardiography and catheterization. Left ventricular end-diastolic dimension and pressure increased in pigs with supraventricular tachycardia (5.1 +/- 0.4 cm and 27 +/- 2 mm Hg) versus control pigs (3.8 +/- 0.3 cm and 8 +/- 2 mm Hg), p < 0.05. Left ventricular fractional shortening decreased in supraventricular tachycardia (10 +/- 1%) versus control pigs (34 +/- 1%), p < 0.05. In addition, in the pigs with supraventricular tachycardia the fractional shortening versus left ventricular end-systolic stress relationship fell below the control relationship. Plasma norepinephrine level (measured by high-performance liquid chromatography) increased in pigs with supraventricular tachycardia (3592 +/- 1606 pg/ml plasma) versus control pigs (323 +/- 74 pg/ml plasma), p < 0.05. beta-Receptor number and affinity (measured by [3H]dihydroalprenolol binding) did not change in supraventricular tachycardia (98.6 +/- 11.5 fmol/mg protein and 7.2 +/- 1.1 nmol) versus control pigs (99.1 +/- 9.4 fmol/mg protein and 6.8 +/- 0.5 nmol). The response to isoproterenol infusion (10 micrograms/kg) in supraventricular tachycardia was blunted: the absolute increase in left ventricular peak (+)dP/dt was reduced in supraventricular tachycardia (833 +/- 233 mm Hg/sec) versus control pigs (2180 +/- 139 mm Hg/sec), p < 0.05. Chronic supraventricular tachycardia caused a decreased contractile state, increased plasma norepinephrine level, and caused no change in beta-receptor number or affinity; however, the response to beta-agonist infusion was blunted. These results suggest that chronic supraventricular tachycardia is associated with uncoupling of the beta-receptor from subsequent intracellular components of the beta-adrenergic system. Therefore medical management of chronic supraventricular tachycardia-induced cardiomyopathy before and immediately after definitive ablation may require use of pharmacologic agents whose actions do not depend on an intact beta-adrenergic pathway.

Fifty randomly selected references from a single monthly issue of The American Journal of Surgery; Surgery, Gynecology and Obstetrics; and Surgery were evaluated for citation and quotation errors. Thirteen major and 41 minor citation errors were found in the three journals. Thirty-seven major quotation errors were identified. The data support the hypothesis that authors do not check their references or may not even read them. This hypothesis may be expanded to maintain that reviewers do not check references.