Medetomidine continuous rate intravenous infusion in horses in which surgical anaesthesia is maintained with isoflurane and intravenous infusions of lidocaine and ketamine

OBJECTIVE: To evaluate medetomidine as a continuous rate infusion (CRI) in horses in which anaesthesia is maintained with isoflurane and CRIs of ketamine and lidocaine. STUDY DESIGN: Prospective, randomized, blinded clinical trial. ANIMALS: Forty horses undergoing elective surgery. METHODS: After sedation and induction, anaesthesia was maintained with isoflurane. Mechanical ventilation was employed. All horses received lidocaine (1.5 mg kg(-1) initially, then 2 mg kg(-1) hour(-1)) and ketamine (2 mg kg(-1) hour(-1)), both CRIs reducing to 1.5 mg kg(-1) hour(-1) after 50 minutes. Horses in group MILK received a medetomidine CRI of 3.6 mug kg(-1) hour(-1), reducing after 50 minutes to 2.75 mug kg(-1) hour(-1), and horses in group ILK an equal volume of saline. Mean arterial pressure (MAP) was maintained above 70 mmHg using dobutamine. End-tidal concentration of isoflurane (FE'ISO) was adjusted as necessary to maintain surgical anaesthesia. Group ILK received medetomidine (3 mug kg(-1) ) at the end of the procedure. Recovery was evaluated. Differences between groups were analysed using Mann-Whitney, Chi-Square and anova tests as relevant. Significance was taken as p < 0.05. RESULTS: FE'ISO required to maintain surgical anaesthesia in group MILK decreased with time, becoming significantly less than that in group ILK by 45 minutes. After 60 minutes, median (IQR) FE'ISO in MILK was 0.65 (0.4-1.0) %, and in ILK was 1 (0.62-1.2) %. Physiological parameters did not differ between groups, but group MILK required less dobutamine to support MAP. Total recovery times were similar and recovery quality good in both groups. CONCLUSION AND CLINICAL RELEVANCE: A CRI of medetomidine given to horses which were also receiving CRIs of lidocaine and ketamine reduced the concentration of isoflurane necessary to maintain satisfactory anaesthesia for surgery, and reduced the dobutamine required to maintain MAP. No further sedation was required to provide a calm recovery.

A shift from oral to intravenous iron supplementation therapy is observed over time in a large swiss cohort of patients with inflammatory bowel disease

BACKGROUND In 2007, leading international experts in the field of inflammatory bowel disease (IBD) recommended intravenous (IV) iron supplements over oral (PO) ones because of superior effectiveness and better tolerance. We aimed to determine the percentage of patients with IBD undergoing iron therapy and to assess the dynamics of iron prescription habits (IV versus PO). METHODS We analyzed anonymized data on patients with Crohn's disease and ulcerative colitis extracted from the Helsana database. Helsana is a Swiss health insurance company providing coverage for 18% of the Swiss population (1.2 million individuals). RESULTS In total, 629 patients with Crohn's disease (61% female) and 398 patients with ulcerative colitis (57% female) were identified; mean observation time was 31.8 months for Crohn's disease and 31.0 months for ulcerative colitis patients. Of all patients with IBD, 27.1% were prescribed iron (21.1% in males; 31.1% in females). Patients treated with steroids, immunomodulators, and/or anti-tumor necrosis factor drugs were more frequently treated with iron supplements when compared with those not treated with any medications (35.0% versus 20.9%, odds ratio, 1.94; P < 0.001). The frequency of IV iron prescriptions increased significantly from 2006 to 2009 for both genders (males: from 2.6% to 10.1%, odds ratio = 3.84, P < 0.001; females: from 5.3% to 12.1%, odds ratio = 2.26, P = 0.002), whereas the percentage of PO iron prescriptions did not change. CONCLUSIONS Twenty-seven percent of patients with IBD were treated with iron supplements. Iron supplements administered IV were prescribed more frequently over time. These prescription habits are consistent with the implementation of guidelines on the management of iron deficiency in IBD.

Role of amylase, mucin, IgA and albumin on salivary protein buffering capacity: a pilot study

It has been suggested that proteins serve as major salivary buffers below pH5. It remains unclear, however, which salivary proteins are responsible for these buffering properties. The aim of this pilot study was to evaluate the correlation between salivary concentration of total protein, amylase, mucin, immunoglobulin A (IgA), albumin and total salivary protein buffering capacity at a pH range of 4-5. In addition, the buffering capacity and the number of carboxylic acid moieties of single proteins were assessed. Stimulated saliva samples were collected at 9:00, 13:00 and 17:00 from 4 healthy volunteers on 3 successive days. The buffering capacities were measured for total salivary protein or for specific proteins. Also, the concentration of total protein, amylase, mucin, IgA and albumin were analysed. Within the limits of the current study, it was found that salivary protein buffering capacity was highly positively correlated with total protein, amylase and IgA concentrations. A weak correlation was observed for both albumin and mucin individually. Furthermore, the results suggest that amylase contributed to 35 percent of the salivary protein buffering capacity in the pH range of 4-5.

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.

Intravenous mesenchymal stem cell therapy for traumatic brain injury.

OBJECT: Cell therapy has shown preclinical promise in the treatment of many diseases, and its application is being translated to the clinical arena. Intravenous mesenchymal stem cell (MSC) therapy has been shown to improve functional recovery after traumatic brain injury (TBI). Herein, the authors report on their attempts to reproduce such observations, including detailed characterizations of the MSC population, non-bromodeoxyuridine-based cell labeling, macroscopic and microscopic cell tracking, quantification of cells traversing the pulmonary microvasculature, and well-validated measurement of motor and cognitive function recovery. METHODS: Rat MSCs were isolated, expanded in vitro, immunophenotyped, and labeled. Four million MSCs were intravenously infused into Sprague-Dawley rats 24 hours after receiving a moderate, unilateral controlled cortical impact TBI. Infrared macroscopic cell tracking was used to identify cell distribution. Immunohistochemical analysis of brain and lung tissues 48 hours and 2 weeks postinfusion revealed transplanted cells in these locations, and these cells were quantified. Intraarterial blood sampling and flow cytometry were used to quantify the number of transplanted cells reaching the arterial circulation. Motor and cognitive behavioral testing was performed to evaluate functional recovery. RESULTS: At 48 hours post-MSC infusion, the majority of cells were localized to the lungs. Between 1.5 and 3.7% of the infused cells were estimated to traverse the lungs and reach the arterial circulation, 0.295% reached the carotid artery, and a very small percentage reached the cerebral parenchyma (0.0005%) and remained there. Almost no cells were identified in the brain tissue at 2 weeks postinfusion. No motor or cognitive functional improvements in recovery were identified. CONCLUSIONS: The intravenous infusion of MSCs appeared neither to result in significant acute or prolonged cerebral engraftment of cells nor to modify the recovery of motor or cognitive function. Less than 4% of the infused cells were likely to traverse the pulmonary microvasculature and reach the arterial circulation, a phenomenon termed the "pulmonary first-pass effect," which may limit the efficacy of this therapeutic approach. The data in this study contradict the findings of previous reports and highlight the potential shortcomings of acute, single-dose, intravenous MSC therapy for TBI.

Elevated albumin in retinas of monkeys with experimental glaucoma.

PURPOSE: To establish the identity of a prominent protein, approximately 70 kDa, that is markedly increased in the retina of monkeys with experimental glaucoma compared with the fellow control retina, the relationship to glaucoma severity, and its localization in the retina. METHODS: Retinal extracts were subjected to 2-D gel electrophoresis to identify differentially expressed proteins. Purified peptides from the abundant 70 kDa protein were analyzed and identified by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) separation, and collision-induced dissociation sequencing. Protein identity was performed on MASCOT (Matrix Science, Boston, MA) and confirmed by Western blot. The relationship between the increase in this protein and glaucoma severity was investigated by regression analyses. Protein localization in retina was evaluated by immunohistochemistry with confocal imaging. RESULTS: The abundant protein was identified as Macaca mulatta serum albumin precursor (67 kDa) from eight non-overlapping proteolytic fragments, and the identity was confirmed by Western blot. The average increase in retinal albumin content was 2.3 fold (P = 0.015). In glaucoma eyes, albumin was localized to some neurons of the inner nuclear layer, in the inner plexiform layer, and along the vitreal surface, but it was only found in blood vessels in control retinas. CONCLUSIONS: Albumin is the abundant protein found in the glaucomatous monkey retinas. The increased albumin is primarily localized to the inner retina where oxidative damage associated with experimental glaucoma is known to be prominent. Since albumin is a major antioxidant, the increase of albumin in the retinas of eyes with experimental glaucoma may serve to protect the retina against oxidative damage.

The effectiveness of a needleless intravenous system in prevention of percutaneous injury in two hospitals

This study assessed if hospital-wide implementation of a needleless intravenous connection system reduces the number of reported percutaneous injuries, overall and those specifically due to intravenous connection activities.^ Incidence rates were compared before and after hospital-wide implementation of a needleless intravenous system at two hospitals, a full service general hospital and a pediatric hospital. The years 1989-1991 were designated as pre-implementation and 1993 was designated as post-implementation. Data from 1992 were not included in the effectiveness evaluation to allow employees to become familiar with use of the new device. The two hospitals showed rate ratios of 1.37 (95% CI = 1.22-1.54, p $\le$.0001) and 1.63 (95% CI = 1.34-1.97, p $\le$.0001), or a 27.1% and a 38.6% reduction in overall injury rate, respectively. Rate ratios for intravenous connection injuries were 2.67 (95% CI = 1.89-3.78, p $\le$.0001) and 3.35 (95% CI = 1.87-6.02, p $\le$.0001), or a 62.5% and a 69.9% reduction in injury rate, respectively. Rate ratios for all non-intravenous connection injuries were calculated to control for factors other than device implementation that may have been operating to reduce the injury rate. These rate ratios were lower, 1.21 and 1.44, demonstrating the magnitude of injury reduction due to factors other than device implementation. It was concluded that the device was effective in reduction of numbers of reported percutaneous injuries.^ Use-effectiveness of the system was also assessed by a survey of randomly selected device users to determine satisfaction with the device, frequency of use and barriers to use. Four hundred seventy-eight surveys were returned for a response rate of 50.9%. Approximately 94% of respondents at both hospitals expressed satisfaction with the needleless system and recommended continued use. The survey also revealed that even though over 50% of respondents report using the device "always" or "most of the time" for intravenous medication administration, flushing lines, and connecting secondary intravenous lines, needles were still being used for these same activities. Compatibility, accessibility and other technical problems were reported as reasons for using needles for these activities. These problems must be addressed, by both manufacturers and users, before the needleless system will be effective in prevention of all intravenous connection injuries. ^

Ultra-early intravenous stroke thrombolysis: do all patients benefit similarly?

BACKGROUND AND PURPOSE We previously reported increased benefit and reduced mortality after ultra-early stroke thrombolysis in a single center. We now explored in a large multicenter cohort whether extra benefit of treatment within 90 minutes from symptom onset is uniform across predefined stroke severity subgroups, as compared with later thrombolysis. METHODS Prospectively collected data of consecutive ischemic stroke patients who received i.v. thrombolysis in 10 European stroke centers were merged. Logistic regression tested association between treatment delays, as well as excellent 3-month outcome (modified Rankin scale, 0-1), and mortality. The association was tested separately in tertiles of baseline National Institutes of Health Stroke Scale. RESULTS In the whole cohort (n=6856), shorter onset-to-treatment time as a continuous variable was significantly associated with excellent outcome (P<0.001). Every fifth patient had onset-to-treatment time≤90 minutes, and these patients had lower frequency of intracranial hemorrhage. After adjusting for age, sex, admission glucose level, and year of treatment, onset-to-treatment time≤90 minutes was associated with excellent outcome in patients with National Institutes of Health Stroke Scale 7 to 12 (odds ratio, 1.37; 95% confidence interval, 1.11-1.70; P=0.004), but not in patients with baseline National Institutes of Health Stroke Scale>12 (odds ratio, 1.00; 95% confidence interval, 0.76-1.32; P=0.99) and baseline National Institutes of Health Stroke Scale 0 to 6 (odds ratio, 1.04; 95% confidence interval, 0.78-1.39; P=0.80). In the latter, however, an independent association (odds ratio, 1.51; 95% confidence interval, 1.14-2.01; P<0.01) was found when considering modified Rankin scale 0 as outcome (to overcome the possible ceiling effect from spontaneous better prognosis of patients with mild symptoms). Ultra-early treatment was not associated with mortality. CONCLUSIONS I.v. thrombolysis within 90 minutes is, compared with later thrombolysis, strongly and independently associated with excellent outcome in patients with moderate and mild stroke severity.

Safety and efficacy of thrombolysis with intravenous alteplase in older stroke patients.

Stroke is a common cause of death and persisting disability worldwide, and thrombolysis with intravenous alteplase is the only approved treatment for acute ischaemic stroke. Older age is the most important non-modifiable risk factor for stroke, and demographic changes are also resulting in an increasingly ageing population. However, clinical trial evidence for the use of intravenous alteplase is limited for the older age group where stroke incidence is highest. In this article, the current evidence regarding the safety and efficacy of intravenous thrombolytic therapy in stroke patients aged ≥80 years is critically analysed and the gap in current knowledge highlighted. In summary, intravenous thrombolysis in stroke patients aged ≥80 years seems to be associated with less favourable clinical outcomes and higher mortality than in younger patients, which is consistent with the natural course in untreated patients. The risk of symptomatic intracranial haemorrhage does not appear to be significantly higher in the elderly group, suggesting that intracranial bleeding complications are unlikely to outweigh the potential benefit in this age group. Overall, withholding thrombolytic treatment in ischaemic stroke on the basis of advanced age alone is no longer justifiable.

Relationship between cobalamin-dependent metabolites and both serum albumin and alpha1 -proteinase inhibitor concentrations in hypocobalaminemic dogs of 7 different breeds.

BACKGROUND Increased serum concentrations of homocysteine (HCY) and methylmalonic acid (MMA), the 2 main cobalamin-dependent metabolites, as well as decreased serum albumin and canine alpha1 -proteinase inhibitor (cα1 -PI) concentrations have previously been described in hypocobalaminemic dogs with gastrointestinal disease. However, no studies have been conducted to evaluate potential relationships between these serum biomarkers. OBJECTIVE The aim of this study was to evaluate the relationship between HCY and MMA, 2 cobalamin-dependent metabolites, and both serum albumin and cα1 -PI concentrations in hypocobalaminemic dogs. METHODS Serum samples from 285 dogs including 7 different breeds (Beagle, Boxer, Cocker Spaniel, German Shepherd, Labrador Retriever, Chinese Shar-Pei, and Yorkshire Terrier) with hypocobalaminemia were used. Serum HCY, MMA, albumin, and cα1 -PI concentrations were determined. RESULTS There was a significant correlation between serum HCY and albumin concentrations, as well as serum HCY and cα1 -PI concentrations (ρ = 0.62 and ρ = 0.37, respectively; P < .0001). No correlations were observed between serum MMA and albumin concentrations, or cα1 -PI concentrations (ρ = 0.01 and ρ = 0.08, respectively; P > .05). In addition, significant breed-specific correlations were observed between serum MMA and albumin concentrations in German Shepherds, and serum HCY and MMA concentrations in Chinese Shar-Peis with hypocobalaminemia. CONCLUSIONS This study shows a correlation between serum albumin and cα1 -PI and HCY concentrations, but not with serum MMA concentration in dogs with hypocobalaminemia. In addition, significant breed-specific correlations were observed between serum MMA and albumin concentrations in German Shepherds, as well as serum HCY and MMA concentrations in Chinese Shar-Peis, emphasizing the unique metabolic interactions in those dog breeds affected by hypocobalaminemia.

S-nitroso albumin enhances bone formation in a rabbit calvaria model.

Nitric oxide (NO) is a mediator involved in bone regeneration. We therefore examined the effect of the novel NO donor, S-nitroso human serum albumin (S-NO-HSA) on bone formation in a rabbit calvaria augmentation model. Circular grooves (8 mm diameter, two per animal) were created by a trephine drill in the cortical bone of 40 rabbits and titanium caps were placed on the rabbit calvaria bone filled with a collagen sponge soaked with either 100 μL S-NO-HSA (5%, 20%) or human albumin (5%, 20%). After 4 weeks the titanium hemispheres were subjected to histological and histomorphometric analysis. Bone formation and the volume of the residual collagen sponge were evaluated. S-NO-HSA treatment groups had a significantly higher volume of newly formed bone underneath the titanium hemispheres compared to the albumin control groups (5%: 15.5 ± 4.0% versus 10.6 ± 2.9%; P < 0.05; 20%: 14.0 ± 4.6% versus 6.0 ± 3.8%; P < 0.01). The volume of residual collagen sponge was also significantly lower in the S-NO-HSA groups compared to the control groups (5%: 0.4 ± 0.5% versus 2.6 ± 2.4%; P < 0.05 and 20%: 1.5 ± 2.7% versus 13.0 ± 18.7%; P < 0.01). This study demonstrates for the first time that S-NO-HSA promotes bone formation by slow NO release. Additionally, S-NO-HSA increases collagen sponge degradation.

Protein-glycan interactions as targets of intravenous/subcutaneous immunoglobulin (IVIg/SCIg) preparations

Post Presentation

Effect of IgG for intravenous use on Fc receptor-mediated phagocytosis by human monocytes

Polyspecific IgG given intravenously at high doses (IVIG) is used for immunomodulatory therapy in autoimmune diseases such as idiopathic thrombocytopenic purpura and myasthenia gravis. It is assumed that the clinical effect is brought about in part by a modulation of mononuclear phagocyte function, in particular by an inhibition of Fc receptor (FcR) mediated phagocytosis. In the present study, the effect of IVIG on FcR-mediated phagocytosis by monocytes was analysed in vitro. Since monocytes exposed to minute amounts of surface-bound IgG displayed impaired phagocytosis of IgG-coated erythrocytes (EA), the effect of IVIG was studied with mononuclear cells suspended in teflon bags in medium containing 10% autologous serum and IVIG (2-10 mg/ml). Monocytes pre-exposed to IVIG and then washed, displayed impaired ingestion of EA when compared with control cells cultured in 10% autologous serum only. The decrease in phagocytosis was observed with sheep erythrocytes treated with either rabbit IgG or bovine IgG1 and with anti-D-treated human erythrocytes. This suggests that phagocytosis via both FcR type I (FcRI) and type II (FcRII) was decreased. The impairment of phagocytosis was dependent on the presence of intact IgG and was mediated by IVIG from nulliparous donors and from multigravidae to the same extent, suggesting that alloantibodies contained in IVIG have a minor role in modulating FcR-mediated phagocytosis by monocytes. A flow cytometric analysis using anti-FcRI, FcRII and FcRII monoclonal antibodies showed that IVIG treatment upregulated FcRI expression but did not significantly alter the expression of FcRII and FcRIII.