Improved short-term survival with polyethylene glycol modified hemoglobin liposomes in critical normovolemic anemia

OBJECTIVE: To investigate the efficacy of a polyethylene glycol (PEG) modified formulation of liposome-encapsulated hemoglobin (LEH) as an oxygen-carrying blood substitute in the treatment of critical normovolemic anemia. DESIGN AND SETTING: Prospective, controlled, randomized experimental study in a university research facility. SUBJECTS: 14 anesthetized and mechanically ventilated beagle dogs. INTERVENTIONS: Animals were splenectomized and hemodiluted by exchange of whole blood for iso-oncotic hetastarch (HES). Target parameter of the hemodilution protocol was the individual critical hemoglobin concentration (Hb(crit)) corresponding with the onset of O(2) supply dependency of total body O(2) consumption. At Hb(crit) animals were randomized to receive a bolus infusion (20[Symbol: see text]ml/kg) of either LEH (n[Symbol: see text]=[Symbol: see text]7) or normal saline (NS; n[Symbol: see text]=[Symbol: see text]7). Subsequently animals were observed without further intervention. MEASUREMENTS AND RESULTS: The primary endpoint was survival time after the completion of treatment; secondary endpoints were parameters of central hemodynamics, O(2) transport and tissue oxygenation. Animals in the LEH group survived significantly longer after completion of treatment (149[Symbol: see text]+/-[Symbol: see text]109 vs. 43[Symbol: see text]+/-[Symbol: see text]56[Symbol: see text]min). Immediately after treatment LEH-treated animals presented with a more stable cardiovascular condition. After 30[Symbol: see text]min tissue O(2) tension on the surface of a skeletal muscle was significantly higher in the LEH group (23[Symbol: see text]+/-[Symbol: see text]8 vs. 9[Symbol: see text]+/-[Symbol: see text]2[Symbol: see text]mmHg). Nevertheless, treatment with LEH did not decrease mortality within the observation period. CONCLUSIONS: In this present experimental study the infusion of a PEG-modified LEH provided adequate tissue oxygenation, hemodynamic stability, and a prolongation of survival time after critical anemia. However, these effects were sustained for only a short period of time.     

Sustainability of remission of pediatric primary nocturnal enuresis--comparison of remission using Try for Dry vs. non-Try for Dry treatment plans

This study examined the sustainability of remission of primary nocturnal enuresis (PNE) using an algorithm-based multimodal treatment plan, Try for Dry. Remission of PNE using the Try for Dry treatment method was retained longer and more often than using a non-Try for Dry plan.     

Reduced colonization and infection with miconazole-rifampicin modified central venous catheters: a randomized controlled clinical trial

OBJECTIVE: Central venous catheters (CVC) are a major cause of nosocomial bloodstream infections. Catheters modified with miconazole and rifampicin that constantly and slowly release antimicrobial substances are assumed to be beneficial in reducing rates of colonization and catheter-related infections. DESIGN AND SETTING: Prospective controlled non-blinded randomized clinical trial in two German university hospitals. PATIENTS: 223 adult inpatients with CVC between October 2000 and February 2002. Baseline characteristics, APACHE II score and therapeutic interventions were comparable. INTERVENTION: Randomization to receive either a miconazole and rifampicin modified catheter (n=118) or a standard triple-lumen CVC (n=105). MEASUREMENTS, DEFINITIONS: Microbiological evaluation was done after CVC removal. A catheter was considered colonized if growth of > or =15 cfu was found by semi-quantitative roll-plate technique from a proximal or distal catheter segment. A catheter-related infection (CRI) was defined as a colonized catheter with local signs of inflammation. A catheter-related bloodstream infection (CR-BSI) was defined as a colonized catheter with isolation of the same organism from the patient's blood with accompanying clinical signs of infection. RESULTS: A colonization of CVC was observed in six patients (5.1%) with a modified catheter and 38 patients (36.2%) with a standard catheter (P < 0.001). Five patients in the modified group (4.2%) and 18 in the standard group (17.1%) developed CRI (P=0.002). One assumed CR-BSI was detected in the standard group, with none in the modified group. No adverse effects related to the modified catheters and no antimicrobial resistance were observed. CONCLUSION: CVC supersaturated with miconazole and rifampicin were associated with a significantly lower risk for catheter colonization and catheter-related infections compared to standard catheters.     

Time-dependent interventions

The contribution by Pepe and colleagues provides additional evidence that initial defibrillation is not necessarily the optimal intervention for victims of cardiac arrest and especially when cardiac arrest has been untreated for more than 3 min. Precordial compression therefore remains the mainstay of basic life support cardiopulmonary resuscitation after sudden death. It is increasingly apparent that neither epinephrine whether in conventional or high doses nor vasopressin improve ultimate survival. To the contrary, there is evidence favoring β₁-adrenergic blockade.     

Comparison of rectilinear biphasic waveform with biphasic truncated exponential waveform in a pediatric defibrillation model

OBJECTIVE: To compare the rectilinear biphasic waveform with a biphasic truncated exponential waveform for pediatric defibrillation. DESIGN: Prospective, randomized study. SETTING: Experimental laboratory of a university-affiliated research institute. SUBJECTS: Male domestic piglets (4-24 kg). INTERVENTIONS: Eleven piglets (4-8 kg), which represented a patient <1 yr old, and ten piglets (16-24 kg), which represented a pediatric patient between the ages of 2 and 8 yrs, were anesthetized, intubated, and mechanically ventilated. Ventricular fibrillation was induced and maintained for 30 secs, and a predetermined shock was then delivered to defibrillate. Following defibrillation, the animal was permitted to stabilize hemodynamically for 4 mins. Fifty shocks were applied to each animal using a randomization schedule based on a predetermined permutation of 50. The 50 shocks were 25 shocks for each rectilinear biphasic and biphasic truncated exponential waveforms, comprising five shocks at five energy settings. Each group of five shocks was fixed at a predetermined energy value, depending on the body weight of the animal. Dose-response curves were constructed using logistic regression. Aortic pressure, electrocardiogram, left ventricular pressure, and left ventricular pressure value of 40 mm Hg were continually measured. MEASUREMENTS AND MAIN RESULTS: Dose-response curves determined defibrillation thresholds at 50% (D50) and 90% (D90) probability of success. The rectilinear biphasic waveform defibrillated with <90% of the D50 and D90 energies required for a biphasic truncated exponential waveform. The rectilinear biphasic waveform also successfully defibrillated with significantly less energy per body weight and per heart weight compared with a biphasic truncated exponential waveform. CONCLUSIONS: The rectilinear biphasic waveform has superior defibrillation performance compared with a biphasic truncated exponential waveform in a piglet defibrillation model for young children.     

Cognitive behavioural therapy group work with voice hearers. Part 1

This study presents a small, randomised control trial of cognitive behavioural interventions within a group setting for the treatment of auditory hallucinations. In a sample of 20 voice hearers, 10 were randomly allocated to an eight-session cognitive behavioural therapy group, and 10 underwent psychiatric 'treatment as usual'. Baseline assessments were undertaken. Measures of control, power, frequency and symptoms of distress and anxiety, were recorded on assessment and on completion of the group. The groups achieved a significant reduction in frequency of auditory hallucinations and in the beliefs about the power of the voice. Satisfaction measures also suggested that the group participants valued the group and benefited from the structured sessions. Universality, the recognition that other people experience very similar problems, was one of the most beneficial factors of the intervention. This study suggests that group cognitive behavioural therapy was helpful in the treatment of auditory hallucinations.     

Spinal HMGB1 induces TLR4-mediated long-lasting hypersensitivity and glial activation and regulates pain-like behavior in experimental arthritis

Extracellular high mobility group box-1 protein (HMGB1) plays important roles in the pathogenesis of nerve injury- and cancer-induced pain. However, the involvement of spinal HMGB1 in arthritis-induced pain has not been examined previously and is the focus of this study. Immunohistochemistry showed that HMGB1 is expressed in neurons and glial cells in the spinal cord. Subsequent to induction of collagen antibody-induced arthritis (CAIA), Hmgb1 mRNA and extranuclear protein levels were significantly increased in the lumbar spinal cord. Intrathecal (i.t.) injection of a neutralizing anti-HMGB1 monoclonal antibody or recombinant HMGB1 box A peptide (Abox), which each prevent extracellular HMGB1 activities, reversed CAIA-induced mechanical hypersensitivity. This occurred during ongoing joint inflammation as well as during the postinflammatory phase, indicating that spinal HMGB1 has an important function in nociception persisting beyond episodes of joint inflammation. Importantly, only HMGB1 in its partially oxidized isoform (disulfide HMGB1), which activates toll-like receptor 4 (TLR4), but not in its fully reduced or fully oxidized isoforms, evoked mechanical hypersensitivity upon i.t. injection. Interestingly, although both male and female mice developed mechanical hypersensitivity in response to i.t. HMGB1, female mice recovered faster. Furthermore, the pro-nociceptive effect of i.t. injection of HMGB1 persisted in Tlr2- and Rage-, but was absent in Tlr4-deficient mice. The same pattern was observed for HMGB1-induced spinal microglia and astrocyte activation and cytokine induction. These results demonstrate that spinal HMGB1 contributes to nociceptive signal transmission via activation of TLR4 and point to disulfide HMGB1 inhibition as a potential therapeutic strategy in treatment of chronic inflammatory pain.     

An unsuspected metabolic role for atrial natriuretic peptides: the control of lipolysis, lipid mobilization, and systemic nonesterified fatty acids levels in humans

In normal and obese humans, lipid mobilization and systemic nonesterified fatty acid levels are thought to be acutely controlled by catecholamines (ie, epinephrine and norepinephrine) and insulin. Natriuretic peptides (NPs) are known to play a key role in the regulation of salt and water balance and blood pressure homeostasis. They are involved in the pathophysiology of hypertension and heart failure. NPs have recently been found to exert potent lipolytic effects (ie, activating the breakdown of stored triacylglycerols) in isolated human fat cells and to promote lipid mobilization in vivo. Atrial natriuretic peptide increases the intracellular 3', 5'-cyclic guanosine monophosphate (cGMP) concentration which activates cGMP-dependent protein kinase leading to perilipin and hormone-sensitive lipase phosphorylation and lipolysis. NPs promote lipid mobilization when administered intravenously. NPs are also responsible for the residual lipid-mobilizing action observed under oral beta-blockade in subjects performing physical exercise. NPs are therefore novel factors which may open promising research pathways to explain the control of lipid mobilization in physiological and pathological conditions. The metabolic impact of altered production and circulation of NPs remains to be established. The potential influence of NPs on the development of lipid disorders, obesity-related cardiovascular events, and cardiac cachexia will be discussed in this review.