Vascular plasticity in cerebrovascular disorders

Cerebral ischemia remains a major cause of morbidity and mortality with little advancement in subacute treatment options. This review aims to cover and discuss novel insight obtained during the last decade into plastic changes in the vasoconstrictor receptor profiles of cerebral arteries and microvessels that takes place after different types of stroke. Receptors like the endothelin type B, angiotensin type 1, and 5-hydroxytryptamine type 1B/1D receptors are upregulated in the smooth muscle layer of cerebral arteries after different types of ischemic stroke as well as after subarachnoid hemorrhage, yielding rather dramatic changes in the contractility of the vessels. Some of the signal transduction processes mediating this receptor upregulation have been elucidated. In particular the extracellular regulated kinase 1/2 pathway, which is activated early in the process, has proven to be a promising therapeutic target for prevention of vasoconstrictor receptor upregulation after stroke. Together, those findings provide new perspectives on the pathophysiology of ischemic stroke and point toward a novel way of reducing vasoconstriction, neuronal cell death, and thus neurologic deficits after stroke.     

Differential induction of apoptosis in lymphoid tissues during sepsis: variation in onset, frequency, and the nature of the mediators

Apoptosis (Ao), is a process by which cells undergo a form of nonnecrotic cellular suicide. Although for most cells this is a constitutive process, it can be induced in immature and differentiating immune cell populations by stress mediators associated with inflammation. This inducible form of A(o) is referred to as programmed cell death. However, it is not clear whether hematopoietic cell populations such as the thymus and bone marrow are induced to undergo A(o) during polymicrobial sepsis. To assess this, thymocytes, bone marrow cells, or splenocytes (as a source of comparative nonhematopoietic cells) were harvested from C3H/HeN mice at 1, 4, or 24 hours after cecal ligation and puncture (CLP; to induce polymicrobial sepsis) or sham-CLP (Sham). The results showed that mixed bone marrow cells ex vivo, although not to the same extent as thymus, showed a marked increase in the percentage of cells in A(o), increased endonuclease activity, and a significant decrease in cell yield at 24 hours but not at 4 hours after CLP. Similar changes were not evident in splenocytes. Phenotypic, as well as morphologic assessment, indicated that most of the increase in apoptotic cells in the thymus was associated with the immature T cells (CD4+CD8+) and CD8-CD4- cells. In contrast, the increase in bone marrow cell A(o) was associated with only the B220+ cells, with no significant contribution from myeloid cells. Treatment of CLP mice in vivo with either RU-38486 or PEG-(rsTNF- R1)2 was unable to reverse the increased A(o) in the bone marrow of these animals. Taken together, these findings indicate that A(o) as a process induced by polymicrobial sepsis is not limited to the thymus, but can also be detected in the bone marrow. However, unlike thymic A(o), bone marrow is not affected directly/indirectly by glucocorticoids or tumor necrosis factor released during sepsis.     

Genetic characterisation of an influenza A virus of unusual subtype (H1N7) isolated from pigs in England

Summary.  An H1N7 influenza A virus, isolated from pigs in England in 1992, was examined genetically to determine the characteristics and probable origin of the eight gene segments. Six of the RNA segments encoding PB2, PB1, PA, HA, NP and NS were related most closely to those of human viruses, whilst two of the RNA segments (NA and M) were related most closely to those of equine viruses. The HA gene was most similar to that of A/USSR/90/77 (H1N1) but amino acid differences suggested independent genetic drift. In contrast, there were relatively few changes in the NA and M genes compared to those of A/equine/Prague/1/56 (H7N7). Accepted November 12, 1996 Received November 12, 1996     

How interdisciplinary teams can create multi-disciplinary education: the interplay between team processes and educational quality

CONTEXT: Many undergraduate medical education programmes offer integrated multi-disciplinary courses, which are generally developed by a team of teachers from different disciplines. Research has shown that multi-disciplinary teams may encounter problems, which can be detrimental to productive co-operation, which in turn may diminish educational quality. Because we expected that charting these problems might yield suggestions for addressing them, we examined the relationships between team diversity, team processes and course quality. METHODS: We administered a questionnaire to participants from 21 interdisciplinary teams from 1 Dutch and 1 German medical school, both of which were reforming their curriculum. An adapted questionnaire on team learning behaviours, which had been validated in business contexts, was used to collect data on team processes, team learning behaviours and diversity within teams. We examined the relationship between the team factors and educational quality measures of the courses designed by the teams. RESULTS: A total of 84 teachers (60%) completed the questionnaire. Bivariate correlation analysis showed that several aspects of diversity, conflict, working climate and learning behaviour were correlated with course quality. CONCLUSIONS: The negative effects of the diversity measures, notably, value diversity, on other team processes and course quality and the positive association between psychological safety and team learning suggest that educational quality might be improved by enhancing the functioning of multi-disciplinary teams responsible for course development. The relationship between team processes and educational quality should be studied among larger study populations. Student ratings should also be considered in measuring educational quality.     

Increased gall bladder volume in primary sclerosing cholangitis.

BACKGROUND: The diagnosis of primary sclerosing cholangitis (PSC) requires invasive procedures such as liver biopsy and endoscopic retrograde cholangiography (ERC). Sonographic measurement of fasting gall bladder volume, which has been reported to be enlarged in PSC, could serve as a non-invasive screening test. METHODS: Fasting gall bladder volume was studied in patients with PSC (n = 24), primary biliary cirrhosis (PBC, n = 13), liver cirrhosis due to other causes (n = 18), ulcerative colitis (n = 15), and healthy controls (n = 23). Meal induced gall bladder emptying was studied in patients with PSC, patients with PBC, and healthy controls. RESULTS: In patients with PSC gall bladder volume was greatly enlarged (72.9 (SEM 3.7) ml) compared with healthy controls (25.4 (1.7) ml, and patients with PBC (30.9 (2.7) ml), liver cirrhosis (31.3 (4.0) ml) or ulcerative colitis (25.8 (2.0) ml) (p < 0.0005 v all). In four patients with PSC the gall bladder wall was irregularly thickened (> 4 mm) as previously described in PSC. Postprandial residual fractions (% of fasting volume) were comparable between patients with PSC (17.5 (3.7)%) and those with PBC (23.6 (7.1%) and healthy controls (12.7 (2.3)%) Although gall bladder emptying seems normal, increased biliary pressure in patients with PSC cannot be excluded. CONCLUSION: Apart from wall thickening, patients with PSC often present with enlargement of the gall bladder. Sonographic determination of fasting gall bladder volume may be a useful, non-invasive, and easy to perform tool in the evaluation of patients suspected of having PSC.