Pulse-lavage washing is an effective method for defatting of morselized allograft bone in the operating theater

Background and purpose Incorporation of fresh-frozen allograft bone and safety aspects associated with this procedure can be improved by removing blood and lipids from the bone. We investigated in a quantitative manner how efficient pulse lavage might be for removal of adipose tissue from morselized allograft bone.

Methods Depending on the study, the washing was performed with an average of 0.8 L or 1.6 L of sterile saline at room temperature. Fat content of the morselized bone samples was determined using hexane elution. The efficiency of pulse lavage alone was compared with that after an additional wash in 12 L of warm water (55°C). Unprocessed controls were also included for comparison.

Results Pulse lavage with 0.8 L saline alone removed 80% of the fat from the bone, whereas 95% of the fat was removed when washing was performed with 1.6 L of saline. The cleansing efficacy was improved further when an additional wash with warm water was used.

Interpretation Our results indicate that pulse-lavage washing alone at room temperature is an effective method for defatting of morselized allograft bone, but an additional wash with warm water improves the cleansing efficiency. Pulse lavage is easily available and simple to use in the operating theater.     

Incidence of gliomas by anatomic location

The anatomic location of a glioma influences prognosis and treatment options. The aim of our study was to describe the distribution of gliomas in different anatomic areas of the brain. A representative population-based sample of 331 adults with glioma was used for preliminary analyses. The anatomic locations for 89 patients from a single center were analyzed in more detail from radiologic imaging and recorded on a three-dimensional 1 x 1 x 1-cm grid. The age-standardized incidence rate of gliomas was 4.7 per 100,000 person-years. The most frequent subtypes were glioblastoma (47%) and grade II-III astrocytoma (23%), followed by oligodendroglioma and mixed glioma. The gliomas were located in the frontal lobe in 40% of the cases, temporal in 29%, parietal in 14%, and occipital lobe in 3%, with 14% in the deeper structures. The difference in distribution between lobes remained after adjustment for their tissue volume: the tumor:volume ratio was 4.5 for frontal, 4.8 for temporal, and 2.3 for parietal relative to the occipital lobe. The area with the densest occurrence was the anterior subcortical brain. Statistically significant spatial clustering was found in the three-dimensional analysis. No differences in location were found among glioblastoma, diffuse astrocytoma, and oligodendroglioma. Our results demonstrate considerable heterogeneity in the anatomic distribution of gliomas within the brain.     

The quality of electronic patient records in Finnish primary healthcare needs to be improved

Objective

To analyse the technical quality of electronic patient records in relation to legislation and to evaluate their quality associated with the quality of consultations as rated by patients and GPs.

Design

Cross-sectional study of electronic patient records.

Setting

Four primary healthcare (PHC) centres in Finland using three different electronic patient record systems.

Subjects

Patient records of 175 PHC consultations by 50 GPs, rated as the best (n=86) and the worst (n=89) of a total of 2191 consultations.

Main outcome measures

Documentation of records compared with legislation, the general informative value of records, and its relation to the experienced quality of consultations and to the electronic system employed.

Results

Reason for encounter was mentioned in 79% of cases and patient history in 32%. An acute problem was described moderately well or well in 84%, examination findings in 62%, medical problem or diagnosis in 90%, and treatment in 95% of cases. Medication was documented adequately in 38% of the cases where medication was documented. Concerning general informative value, 18% were assessed as poor, 62% as moderate, and 20% as good. No correspondence was found between experienced quality of consultation and general informative value in the patient records. The quality of patient records was found to change according to the electronic system employed.

Conclusions

Finnish patient records are inadequate documents of consultations and below the standard of that country''s legislation. Developing better models of recording would guarantee a higher quality of work.     

Pharmacological characterization and CNS effects of a novel highly selective alpha2C-adrenoceptor antagonist JP-1302

BACKGROUND AND PURPOSE: Pharmacological validation of novel functions for the alpha2A-, alpha2B-, and alpha2C-adrenoceptor (AR) subtypes has been hampered by the limited specificity and subtype-selectivity of available ligands. The current study describes a novel highly selective alpha2C-adrenoceptor antagonist, JP-1302 (acridin-9-yl-[4-(4-methylpiperazin-1-yl)-phenyl]amine). EXPERIMENTAL APPROACH: Standard in vitro binding and antagonism assays were employed to demonstrate the alpha2C-AR specificity of JP-1302. In addition, JP-1302 was tested in the forced swimming test (FST) and the prepulse-inhibition of startle reflex (PPI) model because mice with genetically altered alpha2C-adrenoceptors have previously been shown to exhibit different reactivity in these tests when compared to wild-type controls. KEY RESULTS: JP-1302 displayed antagonism potencies (KB values) of 1,500, 2,200 and 16 nM at the human alpha2A-, alpha2B-, and alpha2C-adrenoceptor subtypes, respectively. JP-1302 produced antidepressant and antipsychotic-like effects, i.e. it effectively reduced immobility in the FST and reversed the phencyclidine-induced PPI deficit. Unlike the alpha2-subtype non-selective antagonist atipamezole, JP-1302 was not able to antagonize alpha2-agonist-induced sedation (measured as inhibition of spontaneous locomotor activity), hypothermia, alpha2-agonist-induced mydriasis or inhibition of vas deferens contractions, effects that have been generally attributed to the alpha2A-adrenoceptor subtype. In contrast to JP-1302, atipamezole did not antagonize the PCP-induced prepulse-inhibition deficit. CONCLUSIONS AND IMPLICATIONS: The results provide further support for the hypothesis that specific antagonism of the alpha2C-adrenoceptor may have therapeutic potential as a novel mechanism for the treatment of neuropsychiatric disorders.     

The effects of d-cycloserine and MK-801 on the performance of rats in two spatial learning and memory tasks

The present study was undertaken to investigate the effects of modulation of the (NMDA) receptor on learning and memory. Thus, the performance of rats treated with d-cycloserine, a partial agonist at the glycine recognition site of the NMDA receptor complex, and MK-801, a noncompetitive NMDA receptor antagonist, either alone or concurrently were assessed in radial arm maze and water maze tasks. Administration of MK-801 (0.1 mg/kg, i.p.) impaired acquisition in the water maze (increased escape latency and distance) and working memory in the radial arm maze (increased re-entries) in rats. Moreover, in the radial arm maze, MK-801 disrupted locomotion (increased latencies and decreased arm entries per minute) and impaired the acquisition of reference memory (increased number of errors) performance of rats. d-Cycloserine (0.03, 0.3, 1.0, 3.0, 10 mg/kg, i.p.) had no effects on acquisition or memory performance of control or MK-801-treated rats in either of these tasks. However, d-cycloserine (0.03, 0.3, 3.0 mg/kg) reversed the MK-801-induced disruption in locomotion. Furthermore, 3.0 mg/kg d-cycloserine increased behavioral activity and also decreased the time needed to complete the task in control animals. To conclude, our results suggest that the consequences of NMDA receptor modulation on learning and memory processes and sensorimotor functions may be functionally different or have distinct anatomical locations.     

Variation in the use of renal replacement therapy in patients with septic shock: a substudy of the prospective multicenter observational FINNAKI study

Introduction

Indications for renal replacement therapy (RRT) have not been generally standardized and vary among intensive care units (ICUs). We aimed to assess the proportion, indications, and modality of RRT, as well as the association between the proportion of RRT use and 90-day mortality in patients with septic shock in Finnish adult ICUs.

Methods

We identified patients with septic shock from the prospective observational multicenter FINNAKI study conducted between 1 September 2011 and 1 February 2012. We divided the ICUs into high-RRT and low-RRT ICUs according to the median of the proportion of RRT-treated patients with septic shock. Differences in indications, and modality of RRT between ICU groups were assessed. Finally, we performed an adjusted logistic regression analysis to evaluate the possible association of the ICU group (high vs. low-RRT) with 90-day mortality.

Results

Of the 726 patients with septic shock, 131 (18.0%, 95% CI 15.2 to 20.9%) were treated with RRT. The proportion of RRT-treated patients varied from 3% up to 36% (median 19%) among ICUs. High-RRT ICUs included nine ICUs (354 patients) and low-RRT ICUs eight ICUs (372 patients). In the high-RRT ICUs patients with septic shock were older (P = 0.04), had more cardiovascular (P <0.001) and renal failures (P = 0.003) on the first day in the ICU, were more often mechanically ventilated, and received higher maximum doses of norepinephrine (0.25 μg/kg/min vs. 0.18 μg/kg/min, P <0.001) than in the low-RRT ICUs. No significant differences in indications for or modality of RRT existed between the ICU groups. The crude 90-day mortality rate for patients with septic shock was 36.2% (95% CI 31.1 to 41.3%) in the high-RRT ICUs compared to 33.9% (95% CI 29.0 to 38.8%) in the low-RRT ICUs, P = 0.5. In an adjusted logistic regression analysis the ICU group (high-RRT or low-RRT ICUs) was not associated with 90-day mortality.

Conclusions

Patients with septic shock in ICUs with a high proportion of RRT had more severe organ dysfunctions and received more organ-supportive treatments. Importantly, the ICU group (high-RRT or low-RRT group) was not associated with 90-day mortality.     

Proteomic profiling of dog urine after European adder (Vipera berus berus) envenomation by two-dimensional difference gel electrophoresis

Between April and September every year, many dogs in Finland are bitten by Vipera berus berus, also known as the European adder, the only venomous snake in the area. Exposure to snake bite venom causes local and systemic symptoms and in severe cases can lead to death. Urine samples were collected from four dogs bitten by V.berus berus and treated in the intensive care unit of the Veterinary Teaching Hospital at the University of Helsinki. The inclusion criteria were a strong suspicion of an adder bite no more than two days before admission and clinical signs of an adder bite. Exclusion criteria were defined as ongoing treatment with glucocorticoids or a known history of liver or kidney diseases. Six privately owned, healthy dogs were obtained as controls. Samples were subjected to 2D-DIGE analysis. Image analysis was performed with DeCyder 7.0 2D software, and protein spots demonstrating a minimum 1.5-fold difference in average spot volume ratios between envenomed and control dogs with a Student's t-test p-value of less than 0.05 were picked and identified using LC-MS/MS. In 2D-DIGE analysis, seven proteins were significantly (p < 0.05) over-expressed in the urine of dogs bitten by V.berus berus compared to the control group. From these, five proteins were identified: beta-2-microglobulin (b2MG), alpha-1-antitrypsin (AAT), albumin, fetuin-B and superoxide dismutase (SOD1). Results indicate that envenomation by V.berus berus alter the urinary protein profile in dogs.     

Juvenile nasopharyngeal angiofibroma: no evidence for inheritance or association with familial adenomatous polyposis

Juvenile nasopharyngeal angiofibromas (JNAs) are rare tumors with prominent vascularity and locally destructive growth. The pathogenesis of JNA is largely unknown. A causal association between JNA and familial adenomatous polyposis has been suggested. Twenty-one patients diagnosed with juvenile angiofibroma filled out a detailed patient questionnaire. No patients reported any relatives with nasopharyngeal angiofibroma or familial adenomatous polyposis. No significant regional clustering suggestive for founder effect could be identified. We believe that if there were a strong genetic predisposition or association with familial adenomatous polyposis, it should have been seen in this patient sample.     

Expression of pertussis toxin subunit S4 as an intracytoplasmic protein in Bacillus subtilis

The expression and secretion of pertussis toxin subunits S1 to S5 in Bacillus subtilis by the aid of a bacillar signal sequence has been reported. While secretion of subunit S1 was high, that of others was low. Ways have now been explored to improve the yield, using S4 as an example. The addition of a protease inhibitor was found to increase the amount of S4 in the culture supernatant, but the final amount was still much below that of S1. However, intracellular expression of S4 gave a high yield (500 mg I⁻¹) and the aggregated protein could easily be isolated in a few simple steps.