Donor genetic variants as risk factors for thrombosis after liver transplantation: A genome-wide association study

Thrombosis after liver transplantation substantially impairs graft- and patient survival. Inevitably, heritable disorders of coagulation originating in the donor liver are transmitted by transplantation. We hypothesized that genetic variants in donor thrombophilia genes are associated with increased risk of posttransplant thrombosis. We genotyped 775 donors for adult recipients and 310 donors for pediatric recipients transplanted between 1993 and 2018. We determined the association between known donor thrombophilia gene variants and recipient posttransplant thrombosis. In addition, we performed a genome-wide association study (GWAS) and meta-analyzed 1085 liver transplantations. In our donor cohort, known thrombosis risk loci were not associated with posttransplant thrombosis, suggesting that it is unnecessary to exclude liver donors based on thrombosis-susceptible polymorphisms. By performing a meta-GWAS from children and adults, we identified 280 variants in 55 loci at suggestive genetic significance threshold. Downstream prioritization strategies identified biologically plausible candidate genes, among which were AK4 (rs11208611-T, p = 4.22 × 10⁻⁰⁵) which encodes a protein that regulates cellular ATP levels and concurrent activation of AMPK and mTOR, and RGS5 (rs10917696-C, p = 2.62 × 10⁻⁰⁵) which is involved in vascular development. We provide evidence that common genetic variants in the donor, but not previously known thrombophilia-related variants, are associated with increased risk of thrombosis after liver transplantation.     

Allergy to pine nuts in a bird fancier

A patient is described with the bird-egg syndrome who experienced an anaphylactic reaction after eating some of her parrot's food (pine nuts: Pinus pinea ). Specific IgE against this nut and another pine nut ( P cembra ) was demonstrated by RAST. Cross-reactivity between these botanically related seeds was shown by RAST inhibition. Besides avian antigens, bird food antigens should be taken into consideration when symptoms of allergy occur on exposure to birds.     

Bacterial adhesion to medical polymers--use of radiation techniques for the prevention of materials-associated infections

The basic principles of the adhesion of bacteria to polymer surfaces are discussed, as the first important step in the pathogenesis of foreign-body infections. Strategies for the prevention of foreign-body infections by polymer modification with ionizing radiation are presented. These include the modification of polymer surfaces by radiation or glow discharge techniques to obtain antiadhesive or antimicrobial surfaces, as well as the fixation or incorporation of antibiotic drugs to or into the polymer.     

A multinational investigation of the impact of subcutaneous sumatriptan. I: Design, methods and clinical findings

This report describes the design, methods and clinical results of a prospective sequential multinational (5 countries) study conducted to evaluate the effects of subcutaneous sumatriptan on health-related quality of life, workplace productivity, clinical parameters and patient satisfaction. Adult patients with moderate to severe migraine initially received customary therapy for migraine episodes for 12 weeks, followed by 24 weeks' treatment with self-administered subcutaneous sumatriptan 6 mg. Demographic, baseline, health-related quality of life and patient satisfaction rating data were collected during visits to the clinic. Data relating to migraine symptoms, migraine therapy, work productivity and non-work activity time were collected on diary cards filled out by the patients. 749 patients were recruited to the study and 637 received at least 1 dose of sumatriptan. Overall, 75.5% of migraines were successfully treated within 2 hours with sumatriptan compared with 31.9% with customary therapy; 36% of patients reported complete relief at 2 hours with sumatriptan treatment compared with 1% of patients receiving customary therapy. 69% of patients successfully treated 70% of their migraines with sumatriptan within 2 hours, compared with 12% of patients with customary therapy. No serious adverse events were reported; 50% of patients reported an adverse event during the 12-week customary therapy phase and 89% of patients during the 24-week sumatriptan phase. These clinical results, which are consistent with those reported in randomised blinded studies of subcutaneous sumatriptan, suggest that relief of migraine symptoms occurs more often, and in less time, in patients receiving subcutaneous sumatriptan rather than customary therapy as their primary medication.     

Pancreatic growth after pancreatico-biliary diversion does not increase the capacity to secrete amylase

BACKGROUND/AIM: Cholecystokinin (CCK) stimulates secretion and evokes a hyperplastic response in the rat pancreas. The aims of this study were to measure the effect of chronic hyperCCKemia induced by pancreatico-biliary diversion (PBD) on pancreatic enzyme concentrations, on amylase secretion by dispersed acinar cells, and on the CCK-stimulated secretion of pancreatic juice in PBD-operated rats. MATERIAL AND METHODS: Forty-five Sprague-Dawley male rats had either PBD or sham operation 4 weeks before sacrifice or additional experiments. In the first study, 25 rats (13 PBD and 12 sham-operated rats) were either freely fed or fasted overnight before sacrifice. The pancreas was dissected out, weighed and analyzed. In the second study, the rats (6 PBD and 7 sham-operated rats) were fasted overnight before pancreatic acini were prepared. Secretion of amylase during stimulation of acini with CCK-8S and carbachol was measured. In the third study (5 sham-operated and 4 PBD rats), the rats were fasted overnight before basal and CCK-stimulated secretion was measured in vivo. RESULTS: PBD-operated rats showed a threefold increase in pancreatic wet weight with increased contents of DNA, protein and water. The concentration of pancreatic amylase was 7-12% of that found in control animals. The concentrations of trypsin and lipase were also lowered. Stimulation of dispersed pancreatic acini with CCK-8S or carbachol resulted in secretion of amylase to a similar extent in PBD and sham-operated rats. There was no difference in the secretion of pancreatic juice in response to CCK, but although the output of amylase from PBD-operated rats increased with CCK, it remained at a low level throughout the study period. CONCLUSION: PBD evoked hyperplastic changes in the rat pancreas and decreased the concentrations of amylase, trypsin and lipase. However, the capacity of acinar cells to secrete amylase remained intact. The stimulated pancreatic secretion was not changed in volume, but the output of amylase was low in PBD-operated rats. The findings are consistent with the idea that the enlargement of the pancreas following PBD does not improve the secretory capacity.     

MR contribution in surgery of epilepsy

The contribution of MR imaging in patients with drug-resistant epilepsy considered for surgical therapy is discussed. In this review we focus on: (a) focal abnormalities (mesial temporal sclerosis, focal migration disorders, hamartomatous lesions and low-grade tumours, phakomatosis and vascular malformations) associated with therapy-resistant partial epilepsy, requiring resective surgery; (b) abnormalities leading to generalized seizures that require more drastic surgical procedures, such as callosotomy and functional hemispherectomy; and (c) localisation of implanted depth-electrodes. Received: 6 April 1998; Revision received: 2 June 1998; Accepted: 3 June 1998     

55Cobalt (Co) as a PET-tracer in stroke, compared with blood flow, oxygen metabolism, blood volume and gadolinium-MRI

Axonal degeneration plays an important role in the accumulation of disability in patients with multiple sclerosis (MS). Pathological studies have demonstrated axonal damage, particularly in areas of acute inflammation and demyelination, and in chronic lesions. Axonal loss and its progression, which is associated with neurological disability, has also been demonstrated by magnetic resonance imaging (MRI) studies. The mechanisms of axonal loss are uncertain, but may involve axonal degeneration secondary to demyelination, or damage to the axonal cytoskeleton. Inflammatory mediators, including cytokines and proteolytic enzymes may contribute to axonal damage, as may nitric oxide. Axonal destruction may also be due to immune attack directed at axonal components. The realisation that axonal degeneration is a fundamental component of MS that may occur early in the disease course should alter the approach to management and open avenues to a more targeted immunotherapy aimed at reducing the progression of disability.     

The in vitro effects of instrumentation on multilevel cervical strut-graft mechanics

STUDY DESIGN: Biomechanical study using a programmable testing apparatus that replicated physiologic flexion-extension cervical spine motion, and loading mechanics. OBJECTIVES: To determine the influence of anterior, posterior, or combined plating on multilevel cervical strut-graft mechanics in vitro. SUMMARY OF BACKGROUND DATA: The addition of instrumentation does not prevent construct failure in multilevel (more than two levels) cervical corpectomy. METHODS: Six fresh human cadaveric cervical spines (C2-T1) were tested in six sequential conditions that included harvested (H), C4-6 corpectomy, strut grafted, strut grafted with an anterior cervical plate (SGAP), strut grafted with posterior plates (SGPP), and strut grafted with combined anterior and posterior plates (SGAPP). A customized force-sensing strut graft (FSSG) was used to measure axial compression-tension, flexion-extension and lateral bending moments, and axial torsion. Parameters of stiffness, segmental vertebral motion, and strut-graft loads were compared, to determine differences among the spine conditions. RESULTS: Flexion of the strut-grafted spine loaded the FSSG, and extension motion unloaded the FSSG. With the anterior plate, flexion of the SGAP spine significantly unloaded the FSSG; extension loaded the FSSG more than flexion of the unplated spine (P = 0.03). The opposite occurred with the posterior plates (SGPP), where flexion of the spine significantly loaded the FSSG (more than the strut grafted spine) and extension unloaded the FSSG (P < 0.03). The combined construct (SGAPP) counteracted the tension band effect of the individual plates and demonstrated significantly less overall FSSG load change than either plate alone (P = 0.03). CONCLUSIONS: Multilevel cervical instrumentation effectively increases stiffness after corpectomy. However, anterior or posterior plating alone excessively loads the graft with small degrees of motion, which may promote pistoning and failure of multilevel constructs.     

Recording of swallowing events using electromyography as a non-invasive measurement of salivation

The present study examined whether the measurement of swallowing activity by electromyography (EMG) provides a sensitive and valid method for the assessment of the amount of saliva secreted. Thirteen subjects tasted lemon juice and water, and smelled lasagna and hay, while the amount of saliva, measured with the aid of cotton dental rolls, was compared with the number of peaks in the EMG activity of the musculus digastricus. Swallowing indeed differentiated between the stimuli and the correlation between the number of swallows and the amount of saliva was significant. The present data suggest that monitoring the swallowing movement using EMG might be a sensitive, valid and reliable method for the measurement of salivary flow. The use is recommended for the measurement of salivation when a simple and non-invasive method is needed.