Encephalic hemodynamic phases in subarachnoid hemorrhage: how to improve the protective effect in patient prognoses

Subarachnoid hemorrhage is frequently associated with poor prognoses. Three different hemodynamic phases were identified during subarachnoid hemorrhage: oligemia, hyperemia, and vasospasm. Each phase is associated with brain metabolic changes. In this review, we correlated the hemodynamic phases with brain metabolism and potential treatment options in the hopes of improving patient prognoses.     

Stimulation of granulopoiesis by transforming growth factor beta: synergy with granulocyte/macrophage-colony-stimulating factor.

Transforming growth factor beta 1 (TGF-beta 1) is known to inhibit the growth of immature hematopoietic progenitor cells, whereas more mature, lineage-restricted progenitors are not inhibited. In contrast, in the presence of saturating concentrations of granulocyte/macrophage-colony-stimulating factor (GM-CSF), TGF-beta promoted a 3- to 5-fold increase in the number and size (greater than 0.5 mm) of bone marrow colonies in a dose-dependent manner with an ED50 of 10-20 pM; TGF-beta 1 alone had no effect. Morphological examination showed an increase in granulocyte colonies. In suspension cultures, TGF-beta 1 and GM-CSF stimulated an increase in total viable cells with markedly enhanced neutrophilic differentiation and a concomitant decrease in the number of monocytes/macrophages by day 6 in culture. Limiting dilution analysis demonstrated a 2- to 5-fold increase in the frequency of progenitor cells that responded to GM-CSF plus TGF-beta 1 vs. GM-CSF alone. Bone marrow progenitors obtained from mice 3 days after treatment with 5-fluorouracil responded to a combination of GM-CSF and TGF-beta 1, whereas either factor alone had no effect. A single-cell assay identified a progenitor cell that directly responded to TGF-beta and GM-CSF. TGF-beta increased the number of GM-CSF receptors on bone marrow cells. Thus, TGF-beta 1 can act as a bifunctional mediator of hematopoietic cell growth, and TGF-beta 1 and GM-CSF act together to stimulate granulopoiesis as measured by large granulocyte colony formation; the progenitor cell is tentatively designated granulocyte burst-forming unit.     

Cigarette smoking and non-fatal myocardial infarction in women: is the relation independent of coronary artery disease?

The relation of cigarette smoking to both coronary disease and non-fatal myocardial infarction was examined in a cross sectional study of 1053 women who underwent coronary arteriography. As compared with the 489 women who had never smoked cigarettes, ever-smokers (mean duration of smoking, 25 years) were 1.6 times as likely to have significant stenotic disease and were 1.9 times as likely to have suffered a myocardial infarction. These associations were strongest in women under 50 years of age, with odds ratios of 3.5 for coronary artery disease and 4.5 for myocardial infarction. Although the extent of stenotic disease and prior myocardial infarction were strongly associated, women who smoked cigarettes remained at increased risk of a myocardial infarction even after their increased coronary artery disease had been taken into account. For example, heavy smokers (greater than 30 pack-years) were 2.3 times as likely to have had a myocardial infarction as were non-smokers; controlling for the extent of stenotic disease (in addition to age and other risk factors) reduced the estimated relative risk to only 1.9. Stratified analyses showed that this increased risk for clinical disease among smokers was evident at all levels of occlusion, even among women with minimal stenotic disease. These results, collected at the time of arteriography, suggest that non-atherogenic mechanisms may be important in the aetiology of myocardial infarction among women who smoke cigarettes.     

Glycaemic control in type 1 diabetic patients using optimised insulin aspart or human insulin in a randomised multinational study

Insulin aspart (IAsp), is a rapid-acting analogue of human insulin (HI), for use in the meal related treatment of diabetes mellitus. The degree of glycaemic control achieved by IAsp in comparison with HI after algorithm-driven dose optimisation was tested over 3 months. The prospective, multicentre, randomised, open-label study with parallel groups was performed in 48 centres in 11 countries and included 423 basal-bolus treated patients with Type 1 diabetes. Main outcome measures were blood glucose control assessed by HbA1c, nine-point self-monitored blood glucose profiles, insulin dose, quality of life, hypoglycaemia and adverse events. An algorithm-driven increase occurred in the dose and number of daily injections of basal insulin, particularly in the IAsp group. After 12 weeks of treatment, HbA1c was significantly lower in IAsp compared to HI treated subjects by 0.17 (95% CI 0.30-0.04) (P<0.05). Comparison of the blood glucose profiles showed lower blood glucose levels with IAsp after breakfast (mean 8.4 vs 10.1 mmol/l; P<0.0001) and dinner (8.2 vs 9.3 mmol/l; P<0.01). There were no differences between treatments in the incidence of hypoglycaemic episodes or in the adverse event profiles. The WHO Diabetes Treatment Satisfaction Questionnaire score for perceived hyperglycaemia was lower with Iasp (P=0.005), and patients found the insulin aspart treatment more flexible (P=0.022). The current study underlines the need for optimising the basal insulin regimen in order to take full advantage of the pharmacodynamics of IAsp.     

Magnetic resonance imaging of wrist and finger joints in healthy subjects occasionally shows changes resembling erosions and synovitis as seen in rheumatoid arthritis

OBJECTIVE: To explore the presence of changes resembling rheumatoid arthritis erosions and synovitis in metacarpophalangeal (MCP) and wrist joints of healthy individuals on magnetic resonance imaging (MRI) and to compare the MRI findings with conventional radiographic, clinical, and biochemical findings. METHODS: Twenty-eight healthy individuals were studied. Contrast-enhanced MRI and conventional radiography of the dominant wrist and second through fifth MCP joints were performed, coupled with standard clinical assessments and biochemical analyses. MR images were evaluated according to the latest OMERACT (Outcome Measures in Rheumatology Clinical Trials) recommendations with respect to synovitis, erosions, and bone marrow edema. RESULTS: Conventional radiography revealed erosion-like changes in 1 of 224 MCP joint bones (0.4%) and in 1 of 420 wrist joint bones (0.2%). MRI depicted low-grade erosion-like changes in 5 of 224 MCP joint bones (2.2%) and in 7 of 420 wrist joint bones (1.7%), but postcontrast enhancement within the lesion was detected in only 8.3% of these. MRI depicted low-grade synovitis-like changes in 10 of 112 MCP joints (8.9%) and in 8 of 84 assessed wrist areas (9.5%), while only minimal early synovial enhancement was detected by dynamic MRI. Three subjects had elevated serum levels of C-reactive protein, and these subjects displayed 44.5% of the synovitis-like changes and 41.7% of the erosion-like changes. Bone marrow edema-like changes were not found in any joints. CONCLUSION: Changes resembling mild synovitis or small bone erosions are occasionally found in the MCP and wrist joints of healthy controls. Signs of synovitis on dynamic MRI, enhancement within bone erosion-like changes, and signs of bone marrow edema appear rarely or are absent in healthy controls. These signs may thus prove to be very specific in the distinction between arthritic and normal joints.     

Development of large numbers of mast cells at sites of idiopathic chronic dermatitis in genetically mast cell-deficient WBB6F1-W/Wv mice

The normal skin and other tissues of adult mast cell-deficient WBB6F1- W/Wv or WCB6F1-Sl/Sld mice contain less than 1.0% the number of mast cells present in the corresponding tissues of the congenic normal (+/+) mice. As a result, genetically mast cell-deficient WBB6F1-W/Wv or WCB6F1-Sl/Sld mice are widely used for studies of mast cell differentiation and function. We found that mast cells developed at sites of idiopathic chronic dermatitis in WBB6F1-W/Wv mice and that the number of mast cells present in the skin of WBB6F1-W/Wv mice was proportional to the severity of the dermatitis (in ear skin, there were 33 +/- 4 mast cells/mm2 of dermis at sites of severe dermatitis v 9 +/- 3 at sites of mild dermatitis, 0.8 +/- 0.3 in skin without dermatitis, and 100 +/- 7 in the normal skin of congenic WBB6F1-+/+ mice; in back skin, the corresponding values were 2.0 +/- 0.6, 1.1 +/- 0.9, 0.025 +/- 0.025, and 26.2 +/- 3.2). The development of mast cells was a local, not systemic, consequence of the dermatitis. Thus, WBB6F1-W/Wv mice with severe dermatitis lacked mast cells in skin not showing signs of dermatitis and also in the peritoneal cavity, stomach, cecum, and tongue. Idiopathic chronic dermatitis was not associated with the local development of mast cells in WCB6F1-Sl/Sld mice, a mutant whose mast cell deficiency is due to a mechanism distinct from that of WBB6F1-W/Wv mice. These findings may have implications for understanding the nature of the mast cell deficiency in WBB6F1-W/Wv and WCB6F1-Sl/Sld mice and for the use of these mutants to analyze mast cell differentiation and function.     

A novel approach to improve undergraduate surgical teaching

Background:

Undergraduate surgery is at an important crossroads. Many departments report significant difficulties delivering effective teaching. Our student feedback indicated a dated surgical curriculum lacking structure, quality and uniformity. We report on a new ”blended” approach employing a combination of professional DVDs, case based discussions, online material and traditional bedside teaching designed to provide structure, standardization, and equality of learning .

Methods:

Year 4 students who had undertaken the new course and year 5 students who had participated in the traditional teaching programme were compared. Students completed a 20 item questionnaire about their experiences of the surgical teaching programme.

Results:

One hundred and seventy-one year 4 (70%) and148 year 5 students (66%) responded. Domains relating to “Overall Satisfaction with the course”, “Approval of innovative teaching methods and interactivity” and “Satisfaction with the clarity of course information” showed improvements when comparing the new and old programmes. However bedside teaching was not rated as highly in the new programme (p<0.05).

Conclusion:

This blended approach has resulted in improved student understanding and engagement. The apparent compromise of bedside teaching may be a reflection of higher expectations. We believe that a similar blended approach has the potential to re-invigorate surgical teaching elsewhere.     

Co-circulation of classic and novel astrovirus strains in patients with acute gastroenteritis in Germany

Objectives

In order to analyze the molecular epidemiology of human astroviruses (HAstV) in Germany, a retrospective long-term study was performed to characterize circulating human astrovirus in patients with acute gastroenteritis in Germany.

Induction of ppp(A2''p)nA-dependent RNase in murine JLS-V9R cells during growth inhibition.

We recently reported that interferon induces the synthesis of ppp(A2'p)nA(n = 2 to greater than or equal to 4) (2-5A)-dependent RNase in the murine cell line JLS-V9R. These cells normally contain very low levels of the nuclease; after interferon treatment, however, they develop levels approaching those found in murine L or Ehrlich ascites tumor cells. Here, we report a similar increase in the nuclease levels in JLS-V9R cells during the transition from the subconfluent actively growing state to the confluent stationary phase. Levels of 2-5A synthetase increased in parallel with the nuclease. The induced levels of both the nuclease and synthetase returned to low basal amounts after trypsinization, dilution, and culturing of the cells at subconfluent densities. The addition of anti-murine interferon (alpha + beta) antibodies to the medium did not affect the induction of the nuclease nor could any interferon be detected in the culture supernatants as determined by the lack of antiviral activity. The increase in the enzymes was not, therefore, due to the spontaneous production of interferon. The induction of the nuclease during confluency preceded an inhibition of [3H]-thymidine incorporation by the cells into DNA. The regulation of the 2-5A-dependent RNase in JLS-V9R cells may, therefore, be related to the control of cell growth.