Pancreatic trauma: acute and late manifestations

A retrospective analysis of 47 patients with pancreatic trauma is presented. A total of 43 patients presented with acute pancreatic injury, 32 after blunt abdominal trauma. Isolated blunt pancreatic injuries were a considerable diagnostic problem with a mean delay from trauma to operation of 9.4 days. At operation peripancreatic drainage in mild injuries and distal resection in cases of ductal injury were the commonest procedures. The overall mortality was 19 per cent, but only three of the eight deaths were attributable to the pancreatic injury. The overall complication rate was 63 per cent and the pancreatic complication rate was 33 per cent. Four patients presented with chronic pancreatitis resulting from previously untreated blunt abdominal trauma 0.5-21 years earlier. Clinically, they did not differ from the manifestations of chronic pancreatitis of other aetiological origins.     

Depression-executive dysfunction syndrome in stroke patients.

OBJECTIVE: It has been suggested that executive dysfunction could be the core defect in patients with geriatric or vascular depression, and that this depression-dysexecutive syndrome (DES) might be related to frontal-subcortical circuit dysfunction. The authors tested this hypothesis in 158 poststroke patients, of whom 21 had both depression and executive dysfunction. Methods: In this cross-sectional cohort study, a neurological, psychiatric, and neuropsychological examination was carried out 3 months after ischemic stroke, and brain infarcts, white-matter changes, and brain atrophy were recorded by MRI. RESULTS: The 21 patients with DES had significantly more brain infarcts affecting their frontal-subcortical circuit structures than the 137 patients without DES, or the 41 patients with depression but without executive dysfunction. Patients with DES also had more severe depressive symptoms and worse psychosocial functioning, and they coped less well in complex activities of daily living. CONCLUSIONS: DES is a valid concept and may define a subgroup of poststroke patients with frontal-subcortical pathology and with distinct prognosis and treatment options.     

A peptide inhibitor of vascular adhesion protein-1 (VAP-1) blocks leukocyte-endothelium interactions under shear stress

Vascular adhesion protein-1 (VAP-1) is an endothelial adhesion molecule mediating leukocyte interactions with blood vessels during leukocyte extravasation. Molecularly VAP-1 is a cell-surface-expressed ecto-enzyme belonging to the group of semicarbazide-sensitive amine oxidases (SSAO; EC 2.4.6.3), which deaminate primary amines. Here we asked whether peptides displaying a suitable free amine group could be a substrate or inhibitor of SSAO and thus regulate VAP-1-mediated leukocyte adhesion. On the basis of a molecular model of VAP-1, we designed synthetic peptides that fit to the substrate channel of VAP-1. One of these lysine-containing peptides effectively inhibits VAP-1-dependent lymphocyte rolling and firm adhesion to primary endothelial cells under physiologically relevant shear conditions. The same peptide inhibits the SSAO activity of endothelial and recombinant VAP-1 in a selective and long-lasting manner. We also show that all enzymatically active VAP-1 is displayed on the cell surface. Our results suggest that, in addition to soluble amines, specific cell-surface-bound molecules containing free NH(2) groups in a suitable position may modulate the enzymatic activity of SSAO. Moreover, the inhibitory peptide diminishes leukocyte interactions with endothelial cells under conditions of shear, and thus it may be useful to treat inflammatory conditions.     

Expression of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 (KDR/Flk-1) in ischemic skeletal muscle and its regeneration

Vascular endothelial growth factor (VEGF) is a hypoxia-inducible endothelial cell mitogen and survival factor. Its receptor VEGFR-2 (KDR/Flk-1) mediates these effects. We studied the expression of VEGF and VEGFR-2 in ischemic human and rabbit skeletal muscle by immunohistochemistry and in situ hybridization. Human samples were obtained from eight lower limb amputations because of acute or chronic critical ischemia. In chronically ischemic human skeletal muscle VEGF and VEGFR-2 expression was restricted to atrophic and regenerating skeletal myocytes, whereas in acutely ischemic limbs VEGF and VEGFR-2 were expressed diffusely in the affected muscle. Hypoxia-inducible factor-1alpha was associated with VEGF and VEGFR-2 expression both in acute and chronic ischemia but not in regeneration. Hindlimb ischemia was induced in 20 New Zealand White rabbits by excising the femoral artery. Magnetic resonance imaging and histological sections revealed extensive ischemic damage in the thigh and leg muscles of ischemic rabbit hindlimbs with VEGF expression similar to acute human lower limb ischemia. After 1 and 3 weeks of ischemia VEGF expression was restricted to regenerating myotubes and by 6 weeks regeneration and expression of VEGF was diminished. VEGFR-2 expression was co-localized with VEGF expression in regenerating myotubes. Macrophages and an increased number of capillaries were associated with areas of ischemic muscle expressing VEGF and VEGFR-2. In conclusion, two patterns of VEGF and VEGFR-2 expression in human and rabbit ischemic skeletal muscle are demonstrated. In acute skeletal muscle ischemia VEGF and VEGFR-2 are expressed diffusely in the affected muscle. In chronic skeletal muscle ischemia and in skeletal muscle recovering from ischemia VEGF and VEGFR-2 expression are restricted to atrophic and regenerating muscle cells suggesting the operation of an autocrine pathway that may promote survival and regeneration of myocytes.     

Bright-light exposure combined with physical exercise elevates mood

BACKGROUND: Physical exercise alleviates depressive symptoms, as does exposure to bright light, especially in those with seasonal variation. Our objective was to compare the effect of exercise alone or combined with morning bright light on mood and the health-related quality of life in healthy subjects. METHODS: Study subjects were working-age adults, randomized in two groups (n=80): exercise in bright light (group A), or exercise in normal indoor illumination (group B). Intervention lasted for 8 weeks and questionnaire data on mood and the health-related quality of life were collected at study entry, and at weeks 4 and 8. RESULTS: Physical exercise both in normal indoor illumination and in bright light was effective at alleviating depressive symptoms. The exercise was significantly more effective at alleviating so-called atypical depressive symptoms when combined with bright-light exposure. LIMITATIONS: There was no active placebo condition, but a comparative, randomized trial was executed. CONCLUSIONS: Physical exercise in bright light had a positive effect on mood and health-related quality of life in a sample of healthy, working-age people. Further research is needed to explore the mechanisms of the apparent additive effect of exercise and light.     

Function-blocking antibodies to human vascular adhesion protein-1: a potential anti-inflammatory therapy

Human vascular adhesion protein-1 (VAP-1) is a homodimeric 170-kDa sialoglycoprotein that is expressed on the surface of endothelial cells and functions as a semicarbazide-sensitive amine oxidase and as an adhesion molecule. Blockade of VAP-1 has been shown to reduce leukocyte adhesion and transmigration in in vivo and in vitro models, suggesting that VAP-1 is a potential target for anti-inflammatory therapy. In this study we have constructed mouse-human chimeric antibodies by genetic engineering in order to circumvent the potential problems involved in using murine antibodies in man. Our chimeric anti-VAP-1 antibodies, which were designed to lack Fc-dependent effector functions, bound specifically to cell surface-expressed recombinant human VAP-1 and recognized VAP-1 in different cell types in tonsil. Furthermore, the chimeric antibodies prevented leukocyte adhesion and transmigration in vitro and in vivo. Hence, these chimeric antibodies have the potential to be used as a new anti-inflammatory therapy.     

CNS-induced natriuresis is not mediated by the atrial natriuretic factor

Studies were performed on anaesthetized Wistar-Kyoto rats to investigate whether the natriuretic response to stimulation of the cerebroventricular system with a hypertonic sodium solution is in part caused by increased plasma concentrations of atrial natriuretic factor (ANF). Through a cannula inserted into a lateral cerebral ventricle a solution with a normal (CSF, 152 mmol l-1) or high (NaCSF, 1,000 mmol l-1) sodium ion content was infused. In the stimulated animals which received NaCSF, the sodium excretion increased more than 13-fold, from 0.07 +/- 0.02 (mean +/- SEM) to 0.97 +/- 0.22 mumol min-1 g-1 kidney wt (P less than 0.01). Potassium excretion rose more than eight-fold, from 0.37 +/- 0.05 to 3.01 +/- 0.13 mumol min-1 g-1 kidney wt (P less than 0.001), and the urine flow rate more than seven-fold, from 1.35 +/- 0.11 to 9.74 +/- 1.23 microliters min-1 g-1 kidney wt (P less than 0.001). The mean arterial blood pressure increased from 100 +/- 3 to 129 +/- 7 mmHg (P less than 0.001). In the control animals which received CSF throughout the experiment there was no significant change in the above variables. The concentrations of ANF in plasma taken at the end of the experiments were determined by a radioimmunoassay. The mean plasma concentration of ANF in animals receiving CSF throughout the experiment was 175 +/- 36 pg ml-1. This was not significantly different from the corresponding value in animals which were given NaCSF (118 +/- 34 pg ml-1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Apparent genotype–phenotype correlation in childhood,adolescent, and adult Chediak‐Higashi syndrome

Chediak‐Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by severe immunologic defects, reduced pigmentation, bleeding tendency, and progressive neurological dysfunction. Most patients present in early childhood and die unless treated by bone marrow transplantation. About 10–15% of patients exhibit a much milder clinical phenotype and survive to adulthood, but develop progressive and often fatal neurological dysfunction. Very rare patients exhibit an intermediate adolescent CHS phenotype, presenting with severe infections in early childhood, but a milder course by adolescence, with no accelerated phase. Here, we describe the organization and genomic DNA sequence of the CHS1 gene and mutation analysis of 21 unrelated patients with the childhood, adolescent, and adult forms of CHS. In patients with severe childhood CHS, we found only functionally null mutant CHS1 alleles, whereas in patients with the adolescent and adult forms of CHS we also found missense mutant alleles that likely encode CHS1 polypeptides with partial function. Together, these results suggest an allelic genotype–phenotype relationship among the various clinical forms of CHS. © 2002 Wiley‐Liss, Inc.     

Solid-phase enzyme immunoassay for the detection of HMG nonhistone proteins in their native structure

The use of purified specific antibodies against HMG1 and HMG17 (high mobility group nonhistone chromosomal proteins), together with a very sensitive solid phase enzyme immunoassay, allows the detection of nanograms of these proteins free in solution or in chromatin native structure, and the measurement of their accessibility. The sensitivity of the assay is comparable to that of the radioimmunoassay, with the advantage of avoiding the handling of radioactive materials.