Enhanced Bone Regeneration Using Porcine Small Intestinal Submucosa

Small instestinal submucosa (SIS) is an easily produced material that has been used experimentally for tissue engineering. To evaluate the ability of SIS to facilitate bone growth within a long-bone defect, a segment of the radius was surgically removed in adult, female Sprague-Dawley rats. The defect was either left unfilled or implanted with SIS, demineralized cortical bone (DMCB), or ovalbumin. The defect was evaluated radiographically and histologically after 3, 6, 12, and 24 weeks. Tissue remodeling within the defect was evident by week 3 in SIS- and DMCB-treated rats. Filling was characterized initially by infiltration of mononuclear cells and extracellular material in SIS-implanted rats and multifocal remodeling bone particles and cartilage formation in DMCB implanted rats. Cartilage was observed as early as 3 weeks and bone as early as 6 weeks in SIS-implanted rats. Filling of the defect arose from multiple foci in DMCB-implanted rats, but was contiguous with and parallel to the ulnar shaft in SIS-implanted rats, suggesting that defect repair by SIS may be conductive rather than inductive. Rats in which the defect was left unfilled demonstrated slow but progressive filling of the defect, characterized by mononuclear cell infiltrates and fibrous extracellular material. In summary, SIS facilitated rapid filling of a longbone defect. These results suggest that SIS may be useful as a bone repair material.     

Studies on the effect of vanadate on endocytosis and shape changes in human red blood cells and ghosts

When amphipathic cationic drugs are added to intact human RBCs, the RBCs first undergo a stomatocytic shape change and then, if relatively large amounts of drug are added and if the metabolic state of the RBC is appropriate, endocytic vacuoles form. Vanadate has a structural similarity to the transition state of phosphate, which presumably accounts for its ability to inhibit phosphohydrolases, although other actions of vanadate have been described. Vanadate inhibited three forms of drug-induced endocytosis in intact RBCs despite the fact that the three drugs chosen (primaquine, chlorpromazine, and vinblastine) are known to have differing requirements for RBC ATP. Vanadate also inhibited the stomatocytic shape change produced by primaquine, chlorpromazine, and vinblastine, but not the stomatocytosis produced by low pH. Vanadate had no effect on RBC echinocytosis produced by lysophosphatidylcholine. In studying endocytosis in hypotonic, leaky, "white" ghosts, we discovered that vanadate inhibited only the endocytosis produced by Mg-ATP and not the endocytosis produced by manipulations that directly attack the cytoskeletal proteins. These findings suggest that ATP hydrolysis has a role in some forms of amphipathic cation-induced stomatocytosis and endocytosis in intact RBCs. In addition, studies in ghosts support the idea that Mg-ATP does indeed produce "energized" endocytosis dependent on utilization or hydrolysis of ATP.     

Molecular characterization of a high A2 beta thalassemia by direct sequencing of single strand enriched amplified genomic DNA

Two families, one of Anglo-Saxon-Dutch descent, and the other, West Indian black, have an atypical beta thalassemia characterized by an unusually high level of Hb A2 in the heterozygous state. Restriction endonuclease mapping showed a deletion of about 1.35 kilobase (kb) in the 5' region of the beta globin gene. Direct sequencing of a specific region of genomic DNA amplified by a new modification of the polymerase chain reaction defined the deletion to be 1,393 base pairs (bp) and to be the same in both families. The deletion extends from 485 bp 5' to the mRNA CAP site to the middle of the second intervening sequence. This deletion, together with three others previously described that remove the 5' end of the beta gene but leave the delta gene intact, are all associated with unusually high levels of Hb A2 in the heterozygous state.     

Modifiziertes McPeek-Punkte-System bei Polytraumapatienten

Background

Many commonly available trauma scores predict mortality, but to evaluate the success of a certain therapy or for difficult scientific and epidemiological purposes this may be insufficient in the face of improved survival rates. For outcome analysis of multiple trauma patients, the extent of medical resources needed could be an additional outcome measurement. McPeek et al. developed a potential scoring system for elective surgery patients, which was recently modified for multiple trauma patients.

Aim

The current study investigated if the McPeek score could be prospectively used in multiple trauma patients and whether it could become an additional helpful tool in outcome assessment. Applicability was assessed by practical examples.

Material and methods

In this prospective single-centre study at the University Hospital of Innsbruck, Austria, between December 2008 and November 2010 multiple trauma patients (≥?18 years) with an injury severity score (ISS) ≥?17 were enrolled. Besides demographic data, prehospital vital parameters and diagnoses, all diagnoses from the trauma, mortality, length of stay in the intensive care unit and the hospital were recorded. The commonly used trauma scores ISS, revised trauma score (RTS), a severity characterization of trauma (ASCOT) and trauma and injury severity score (TRISS) were applied and an observed McPeek score was allocated following end of hospitalization. The McPeek scoring system was used according to the latest modifications. A correlation between trauma scores and the McPeek score was performed. The McPeek score was then predicted by a common trauma score using ordinal regression with the polytomous universal model (PLUM method). By subtracting the predicted from the observed McPeek scores the residual McPeek value was calculated and used for practical examples of outcome analysis with the McPeek scoring system.

Results

Out of 406 identified multiple trauma patients during the study phase, 183 had to be excluded due to missing data (mainly prehospital or following transfer). A total of 223 patients (mean ISS 31.2, mean age 47.2 years) were enrolled and assigned to the population-based observed McPeek score (median 4.0). Correlation coefficients were Glasgow coma scale (GCS) 0.59, ISS 0.62, RTS 0.65, TRISS 0.74 and ASCOT 0.77 (p?<?0.0001). The TRISS predicted the McPeek score best in ordinal regression (pseudo-R²?=?0.944, p?<?0.0001). The residual McPeek score (observed minus predicted) was used to illustrate the influence of the blood glucose level on admission and the influence of head injury on outcome of multiple injury patients in detail.

Conclusion

The modified McPeek score is applicable to multiple trauma patients to assess outcome for scientific or epidemiological purposes. Its main advantage is that it quantifies outcome independently of regional or national circumstances.     

Modulation of affective face processing deficits in Schizophrenia by congruent emotional sounds

Schizophrenia is a psychiatric disorder resulting in prominent impairments in social functioning. Thus, clinical research has focused on underlying deficits of emotion processing and their linkage to specific symptoms and neurobiological dysfunctions. Although there is substantial research investigating impairments in unimodal affect recognition, studies in schizophrenia exploring crossmodal emotion processing are rare. Therefore, event-related potentials were measured in 15 patients with schizophrenia and 15 healthy controls while rating the expression of happy, fearful and neutral faces and concurrently being distracted by emotional or neutral sounds. Compared with controls, patients with schizophrenia revealed significantly decreased P1 and increased P2 amplitudes in response to all faces, independent of emotion or concurrent sound. Analyzing these effects with regard to audiovisual (in)congruence revealed that P1 amplitudes in patients were only reduced in response to emotionally incongruent stimulus pairs, whereas similar amplitudes between groups could be observed for congruent conditions. Correlation analyses revealed a significant negative correlation between general symptom severity (Brief Psychiatric Rating Scale-V4) and P1 amplitudes in response to congruent audiovisual stimulus pairs. These results indicate that early visual processing deficits in schizophrenia are apparent during emotion processing but, depending on symptom severity, these deficits can be restored by presenting concurrent emotionally congruent sounds.     

Utilization and yield of drug screening in the emergency department

Emergency qualitative tests for drugs are commonly ordered during evaluation of cases of suspected drug overdose. We prospectively compared the utilization and yield of drug screens based on urine and of identical tests of gastric contents under actual clinical conditions in a busy metropolitan emergency department. During the 4.5-month study period, physicians ordered drug screening in 405 of 582 (70%) study cases. Screens of both types of body fluid were ordered in only 95 cases (16%), suggesting study physicians regarded these tests to be functionally equivalent. Drug screens of gastric fluid were favored in cases involving acute ingestion and in medically complicated cases requiring gastric lavage. Urine drug screens were favored in clinically stable cases with primarily thought or behavior disorders. In the 95 cases for which both drug screens were ordered, gastric screens in 18 cases detected 20 drugs not detected by urine drug screening. Urine screening, on the other hand, identified 74 drugs not found on gastric screening in 48 cases. Gastric drug screening also performed poorly in comparison to quantitative serum drug levels. Seventeen false-positive urine or gastric screens were noted as well. Despite significant technical limitations, physicians frequently order drug screens in our emergency department. Qualitative drug screening of gastric fluid may prove useful in cases involving acute ingestion, but samples of urine and serum must also be submitted for analysis if optimal test performance is to be achieved.     

Risk factors associated with having psoriatic arthritis in patients with cutaneous psoriasis

The aim of this study was to determine if the following characteristics were associated with the presence of psoriatic arthritis in a sample of psoriasis patients: race, family history of psoriasis and psoriatic arthritis, age of onset of psoriasis, smoking, alcohol consumption and the maximum body surface area (BSA) affected by psoriasis. This was a case–control study involving 400 psoriasis patients who attended the Psoriasis and Photo‐medicine clinic in the National Skin Center of Singapore over a 1‐year period. Cases were psoriasis patients with psoriatic arthritis while controls were psoriasis patients without psoriatic arthritis. The diagnosis of psoriatic arthritis was made by rheumatologists and participants completed a self‐administered standardized questionnaire. The maximum BSA involved was determined from the case notes. Psoriatic arthritis was not significantly associated with sex, race, age of onset of psoriasis, a family history of psoriasis, smoking and alcohol consumption but was significantly associated with a family history of psoriatic arthritis (P < 0.001) and the maximum body surface involved (P = 0.05). Using multivariate analysis to control for variables, the presence of psoriatic arthritis was significantly associated with a family history of psoriatic arthritis (odds ratio [OR] = 20.5; 95% confidence interval [CI] = 2.49–169.10) and the maximum BSA involved (OR = 2.52; 95% CI = 1.33–4.75). Indian psoriatic patients were more likely to have psoriatic arthritis compared to the other races. A family history of psoriatic arthritis and a greater maximum body surface involved may be associated with having psoriatic arthritis in this study population of psoriasis patients.     

Erythrocyte membrane proteins reactive with IgG (warm-reacting) anti- red blood cell autoantibodies: II. Antibodies coprecipitating band 3 and glycophorin A

In our initial immunochemical study of the red blood cell (RBC) membrane proteins targeted in 20 cases of warm-antibody autoimmune hemolytic anemia (AHA), RBC eluates of 6 patients mediated immunoprecipitation (IP) of both band 3 and glycophorin A (GPA). This dual IP pattern had previously been observed with murine monoclonal antibodies (MoAbs) against the high frequency blood group antigen, Wrb (Wright), suggesting that the Wrb epitope may depend on a band 3-GPA interaction. Earlier, anti-Wrb had been identified serologically as a prominent non-Rh specificity of AHA autoantibodies. In the present study, 6 autoantibody eluates immunoprecipitating band 3 and GPA from common Wr(b+) RBCs were retested, in parallel with murine anti-Wrb MoAbs, against very rare Wr(a+b-)En(a+)RBCs. One patient's autoantibodies were unreactive with the Wr(b-) RBCs by either IP or indirect antiglobulin test (IAT) and were judged to have "pure" anti- Wrb specificity. Two other patients' autoantibodies displayed both IP and serologic evidence for anti-Wrb as a major component in combination with one or more additional specificities. However, among 3 other patients whose autoantibodies coprecipitated band 3 and GPA, there was no reduction in IP or IAT reactivity with Wr(b-) RBCs in 2 and only slight reduction in the third. We conclude (1) that human anti-Wrb autoantibodies, like their murine monoclonal counterparts, coprecipitate band 3 and GPA from human RBCs; but (2) that not all antibodies with this IP behavior have anti-Wrb serologic specificity, as defined by this donor's Wr(b-) RBCs. The possibility of an additional (non-Wrb) RBC epitope dependent on a band 3-GPA interaction is raised.