Haemorrhagic complications of pancreaticoduodenectomy

BACKGROUND: Haemorrhagic complication occurs in 5-16% of patients following pancreaticoduodenectomy (PD). We report an analysis of patients with post-PD bleed, to identify predictors of bleed, predictors of survival following bleed and the management of post-PD bleed. METHODS: Two hundred and eighteen patients with periampullary cancers underwent PD from 1989 to 2002. Forty-four (20.2%) patients had a bleeding complication. Of these, 25 patients had an intra-abdominal (IA) bleed and 21 had gastrointestinal (GI) bleed (two had both IA and GI bleed). Clinical, biochemical and tumour characteristics were analysed to identify factors influencing bleeding complications. RESULTS: The median time to presentation was 4.5 days (0-21 days). Serum bilirubin (P = 0.000, OR: 1.090) and pancreaticojejunostomy (PJ) leak (P = 0.009, OR: 3.174) were significant independent factors predicting bleeding complications. Forty-three per cent of patients each had early bleed (<48 h after PD) or delayed bleed (7 days after PD). Comparison of early and late bleeds showed that IA bleed (P = 0.02) presented as early bleeds. Male sex (P = 0.00) longer duration of jaundice (P = 0.02), PJ leak (P = 0.001), HJ leak (P = 0.001), duct to mucosa type of PJ anastomosis (P = 0.03) and IA abscess (P = 0.00) were associated with a significantly higher incidence of late bleeds. Overall mortality after PD was 9.6% with 34% and 3% in bleeders and non-bleeders, respectively. Septicaemia (P = 0.01, OR: 5.49), and acute renal failure (P = 0.01) were associated with increased mortality. CONCLUSIONS: Bleeding complications following PD were seen in one-fifth of patients and were associated with high mortality. Serum bilirubin levels and PJ leak were significant factors associated with bleeding complications. Septicaemia and acute renal failure were significant factors associated with mortality in the bleeders.     

Are Small GTPases Signal Hubs in Sugar-Mediated Induction of Fructan Biosynthesis?

External sugar initiates biosynthesis of the reserve carbohydrate fructan, but the molecular processes mediating this response remain obscure. Previously it was shown that a phosphatase and a general kinase inhibitor hamper fructan accumulation. We use various phosphorylation inhibitors both in barley and in Arabidopsis and show that the expression of fructan biosynthetic genes is dependent on PP2A and different kinases such as Tyr-kinases and PI3-kinases. To further characterize the phosphorylation events involved, comprehensive analysis of kinase activities in the cell was performed using a PepChip, an array of >1000 kinase consensus substrate peptide substrates spotted on a chip. Comparison of kinase activities in sugar-stimulated and mock(sorbitol)-treated Arabidopsis demonstrates the altered phosphorylation of many consensus substrates and documents the differences in plant kinase activity upon sucrose feeding. The different phosphorylation profiles obtained are consistent with sugar-mediated alterations in Tyr phosphorylation, cell cycling, and phosphoinositide signaling, and indicate cytoskeletal rearrangements. The results lead us to infer a central role for small GTPases in sugar signaling.     

Abnormal neurotransmitter release underlying behavioral and cognitive disorders: toward concepts of dynamic and function-specific dysregulation.

Abnormalities in the regulation of neurotransmitter release and/or abnormal levels of extracellular neurotransmitter concentrations have remained core components of hypotheses on the neuronal foundations of behavioral and cognitive disorders and the symptoms of neuropsychiatric and neurodegenerative disorders. Furthermore, therapeutic drugs for the treatment of these disorders have been developed and categorized largely on the basis of their effects on neurotransmitter release and resulting receptor stimulation. This perspective stresses the theoretical and practical implications of hypotheses that address the dynamic nature of neurotransmitter dysregulation, including the multiple feedback mechanisms regulating synaptic processes, phasic and tonic components of neurotransmission, compartmentalized release, differentiation between dysregulation of basal vs activated release, and abnormal release from neuronal systems recruited by behavioral and cognitive activity. Several examples illustrate that the nature of the neurotransmitter dysregulation in animal models, including the direction of drug effects on neurotransmitter release, depends fundamentally on the state of activity of the neurotransmitter system of interest and on the behavioral and cognitive functions recruiting these systems. Evidence from evolving techniques for the measurement of neurotransmitter release at high spatial and temporal resolution is likely to advance hypotheses describing the pivotal role of neurotransmitter dysfunction in the development of essential symptoms of major neuropsychiatric disorders, and also to refine neuropharmacological mechanisms to serve as targets for new treatment approaches. The significance and usefulness of hypotheses concerning the abnormal regulation of the release of extracellular concentrations of primary messengers depend on the effective integration of emerging concepts describing the dynamic, compartmentalized, and activity-dependent characteristics of dysregulated neurotransmitter systems.     

Multilevel surgery in spastic diplegia: evaluation by physical examination and gait analysis in 25 children

Gait improvement surgery was performed on 25 ambulatory children with the diplegic type of cerebral palsy. Multiple soft tissue and bony procedures were performed (mean 8.2 procedures) according to criteria defined on the basis of physical examination and gait analysis. Relevant physical examination findings and kinematic and kinetic data in the sagittal plane were evaluated before surgery and at least 3 years after surgery. Physical examination showed a reduction in the ankle plantar-flexor power and in the range of hip flexion and ankle plantarflexion after surgery. Analysis of gait data showed significant improvements in the sagittal plane kinematics and the power generation at the hip and the ankle. At the knee joint there was maintenance of power of the flexor and extensor group of muscles on physical examination, with significant improvements in the kinematics after surgery. The authors conclude that well-selected surgery improves function of the spastic muscle. The importance of assessing clinical, kinematic, and kinetic data together for proper evaluation of gait is stressed.     

Frosted branch angiitis associated with rapidly progressive glomerulonephritis

Simultaneous occurrence of frosted branch angiitis and immune-mediated rapidly progressive glomerulonephritis is reported. The two diseases possibly share a common immune mechanism. Patients of frosted branch angiitis should undergo complete systemic evaluation including renal function tests even if the patient is systemically asymptomatic.     

Oral controlled release formulation of diclofenac sodium by microencapsulation with ethyl cellulose

The aim of this study was to formulate and evaluate microencapsulated controlled release preparations of diclofenac sodium (DFS) using different proportions of ethyl cellulose (EC) as the retardant material to extend the release. The formulated microcapsules were then compressed into tablets to obtain controlled release oral formulations. Phase separation-coacervation technique was employed to prepare microcapsules of DFS using different proportions of EC in cyclohexane. Physical characteristics of microcapsules and their tablets, in vitro release pattern of the designed microcapsules and their tablets prepared from them were studied using USP dissolution apparatus (USP 2000) type 2 (paddle method) in triple distilled water. The prepared microcapsules were white, free flowing and spherical in shape, with the particle size varying from 49.94-52.72 microm. The duration of DFS release from microcapsules was found to be directly proportional to the proportion of EC and, thus, coat thickness. All tablets were of good quality with respect to appearance, drug content uniformity, hardness, weight variation, friability and thickness uniformity. In vitro release study of the tabletted microcapsules in triple distilled water showed a zero order release kinetics and extended release beyond 24 h. A good correlation was obtained between drug release (t(60)) and proportion of EC in the microcapsules. In the case of tabletted microcapsules, very good correlation could be established between t(60), proportion of EC, weight of the tablets and between release rate constant (K) and proportion of EC. All the formulations were highly stable and possessed reproducible release kinetics across the batches.