Relationship between sensorial and physical characteristics of topical creams: A comparative study on effects of excipients.

Rising consumer demands for safer, more natural, and sustainable topical products have led to increased interest in finding alternative excipients, while retaining functionality and cosmetic appeal. Particle-stabilized Pickering creams have emerged as possible alternatives to replace traditional surfactant-stabilized creams and are thus one of the focuses in this study. The aim of this paper was to study relationships between sensorial characteristics and physical properties to understand how different excipients affect these aspects, comparing one starch particle-stabilized and three surfactant-stabilized formulations. A human panel was used to evaluate sensorial perception, while physical properties were deduced by rheology and tactile friction, together with in vivo and ex vivo skin hydration measurements. The results show that sensorial attributes related to the application phase can be predicted with rheology, while afterfeel attributes can be predicted with tactile friction studies. Differences in rheological and sensory properties among surfactant-based creams could mainly be attributed to the type of emollients used, presence of thickeners and surfactant composition. Differences between surfactant-based creams and a Pickering cream were more evident in relation to the afterfeel perception. Presence of starch particles in the residual film on skin results in high tactile friction and low perception of residual coating, stickiness, greasiness, and slipperiness in sensorial afterfeel.

Hypothesis Tests for Neyman's Bias in Case-Control Studies.

Survival bias is a long-recognized problem in case-control studies, and many varieties of bias can come under this umbrella term. We focus on one of them, termed Neyman's bias or "prevalence-incidence bias." It occurs in case-control studies when exposure affects both disease and disease-induced mortality, and we give a formula for the observed, biased odds ratio under such conditions. We compare our result with previous investigations into this phenomenon and consider models under which this bias may or may not be important. Finally, we propose three hypothesis tests to identify when Neyman's bias may be present in case-control studies. We apply these tests to three data sets, one of stroke mortality, another of brain tumors, and the last of atrial fibrillation, and find some evidence of Neyman's bias in the former two cases, but not the last case.

Chronic urticaria in the real-life clinical practice setting in Sweden, Norway and Denmark: baseline results from the non-interventional multicentre AWARE study.

BACKGROUND: Chronic urticaria (CU) is characterized by the recurrence of itchy hives and/or angioedema for more than 6 weeks. AWARE (A World-wide Antihistamine-Refractory Chronic Urticaria Patient Evaluation) is a multinational study designed to document the real-life treatment situation, burden of disease and clinical resource usage of H1-antihistamine-refractory CU patients. OBJECTIVE: To examine baseline data from Scandinavian AWARE patients. METHODS: AWARE is a prospective, non-interventional, multinational, umbrella design study, which includes adults (≥18 years) with a confirmed CU diagnosis (>2 months) that is refractory to H1-antihistamines. Baseline patient characteristics, disease activity (urticaria control test [UCT]), pharmacological treatment, comorbidities and healthcare usage were documented by the treating physician. Quality of life (QoL; dermatology life quality index [DLQI]; chronic urticaria quality of life questionnaire [CU-Q2 oL; Danish patients only]) and work productivity and activity impairment (WPAI) scores were also assessed. RESULTS: Overall, 158 CU patients from seven centres in Denmark (n = 80), Norway (n = 50) and Sweden (n = 28) were included in this baseline analysis. Mean age and BMI were 40.3 years and 26.5 kg/m2 , respectively. The majority of patients were female (69.6%), had uncontrolled CU (75.6%; UCT score <12) and had a 'spontaneous' component to their CU (61.4% CSU; 20.3% both CSU and chronic inducible urticaria). Common comorbidities included asthma (19.6%), allergic rhinitis (16.5%) and food allergies (8.2%). Overall, 60.1% of patients reported using treatments for CU including non-sedative H1-antihistamines (40.5%), corticosteroids (19%), montelukast (14.6%) and omalizumab (8.2%). Pharmacological treatment rates increased to 96.2% during the baseline visit. On average, patient QoL was moderately affected (mean DLQI score 7.7) and healthcare resource usage was high. CONCLUSION: Adult Scandinavian H1-antihistamine-refractory CU patients reported high rates of healthcare usage and QoL impairment. Rates of pharmacological treatment use were low before study enrolment but increased to almost 100% during the baseline visit.

Staphylococcus aureus colonization related to severity of hand eczema.

Knowledge on Staphylococcus aureus colonization rates and epidemiology in hand eczema is limited. The aim of this study was to clarify some of these issues. Samples were collected by the "glove juice" method from the hands of 59 patients with chronic hand eczema and 24 healthy individuals. Swab samples were taken from anterior nares and throat from 43 of the 59 patients and all healthy individuals. S. aureus were spa typed and analysed by DNA-microarray-based genotyping. The extent of the eczema was evaluated by the hand eczema extent score (HEES). The colonization rate was higher on the hands of hand eczema patients (69 %) compared to healthy individuals (21 %, p < 0.001). This was also seen for bacterial density (p = 0.002). Patients with severe hand eczema (HEES ≥ 13) had a significantly higher S. aureus density on their hands compared to those with milder eczema (HEES = 1 to 12, p = 0.004). There was no difference between patients and healthy individuals regarding colonization rates in anterior nares or throat. spa typing and DNA-microarray-based genotyping indicated certain types more prone to colonize eczematous skin. Simultaneous colonization, in one individual, with S. aureus of different types, was identified in 60-85 % of the study subjects. The colonization rate and density indicate a need for effective treatment of eczema and may have an impact on infection control in healthcare.

Effect of CTA Tube Current on Spot Sign Detection and Accuracy for Prediction of Intracerebral Hemorrhage Expansion.

BACKGROUND AND PURPOSE: Reduction of CT tube current is an effective strategy to minimize radiation load. However, tube current is also a major determinant of image quality. We investigated the impact of CTA tube current on spot sign detection and diagnostic performance for intracerebral hemorrhage expansion. MATERIALS AND METHODS: We retrospectively analyzed a prospectively collected cohort of consecutive patients with primary intracerebral hemorrhage from January 2001 to April 2015 who underwent CTA. The study population was divided into 2 groups according to the median CTA tube current level: low current (<350 mA) and high current (≥350 mA). CTA first-pass readings for spot sign presence were independently analyzed by 2 readers. Baseline and follow-up hematoma volumes were assessed by semiautomated computer-assisted volumetric analysis. Sensitivity, specificity, positive and negative predictive values, and accuracy of spot sign in predicting hematoma expansion were calculated. RESULTS: This study included 709 patients (288 and 421 in the low- and high-current groups, respectively). A higher proportion of low-current scans identified at least 1 spot sign (20.8% versus 14.7%, P = .034), but hematoma expansion frequency was similar in the 2 groups (18.4% versus 16.2%, P = .434). Sensitivity and positive and negative predictive values were not significantly different between the 2 groups. Conversely, high-current scans showed superior specificity (91% versus 84%, P = .015) and overall accuracy (84% versus 77%, P = .038). CONCLUSIONS: CTA obtained at high levels of tube current showed better diagnostic accuracy for prediction of hematoma expansion by using spot sign. These findings may have implications for future studies using the CTA spot sign to predict hematoma expansion for clinical trials.

Ultrasound-targeted hepatic delivery of factor IX in hemophiliac mice.

Ultrasound-targeted microbubble destruction (UTMD) was used to direct the delivery of plasmid and transposase-based vectors encoding human factor IX (hFIX) to the livers of hemophilia B (FIX-/-) mice. The DNA vectors were incorporated into cationic lipid microbubbles, injected intravenously, and transfected into hepatocytes by acoustic cavitation of the bubbles as they transited the liver. Ultrasound parameters were identified that produced transfection of hepatocytes in vivo without substantial damage or bleeding in the livers of the FIX-deficient mice. These mice were treated with a conventional expression plasmid, or one containing a piggyBac transposon construct, and hFIX levels in the plasma and liver were evaluated at multiple time points after UTMD. We detected hFIX in the plasma by western blotting from mice treated with either plasmid during the 12 days after UTMD, and in the hepatocytes of treated livers by immunofluorescence. Reductions in clotting time and improvements in the percentage of FIX activity were observed for both plasmids, conventional (4.15±1.98%), and transposon based (2.70±.75%), 4 to 5 days after UTMD compared with untreated FIX (-/-) control mice (0.92±0.78%) (P=0.001 and P=0.012, respectively). Reduced clotting times persisted for both plasmids 12 days after treatment (reflecting percentage FIX activity of 3.12±1.56%, P=0.02 and 3.08±0.10%, P=0.001, respectively). Clotting times from an additional set of mice treated with pmGENIE3-hFIX were evaluated for long-term effects and demonstrated a persistent reduction in average clotting time 160 days after a single treatment. These data suggest that UTMD could be a minimally invasive, nonviral approach to enhance hepatic FIX expression in patients with hemophilia.

Validation of sun exposure and protection index (SEPI) for estimation of sun habits.

BACKGROUND: In both Sweden and Australia high incidence rates of skin cancer have become a major health problem. In prevention and risk communication, it is important to have reliable ways for identifying people with risky sun habits. In this study the validity and reliability of the questionnaire Sun Exposure Protection Index (SEPI), developed to assess individual's sun habits and their propensity to increase sun protection during routine, often brief, clinical encounters, has been evaluated. The aim of our study was to evaluate validity and reliability of the proposed SEPI scoring instrument, in two countries with markedly different ultraviolet radiation environments (Sweden and Australia). METHOD: Two subpopulations in Sweden and Australia respectively were asked to fill out the SEPI together with the previously evaluated Readiness to Alter Sun Protective Behaviour questionnaire (RASP-B) and the associated Sun-protective Behaviours Questionnaire. To test reliability, the SEPI was again filled out by the subjects one month later. RESULTS: Comparison between SEPI and the questions in the Sun-protective Behaviours Questionnaire, analyzed with Spearman's Rho, showed good correlations regarding sun habits. Comparison between SEPI and RASP-B regarding propensity to increase sun protection showed concurrently lower SEPI mean scores for action stage, but no difference between precontemplation and contemplation stages. The SEPI test-retest analysis indicated stability over time. Internal consistency of the SEPI, assessed with Cronbach's alpha estimation showed values marginally lower than the desired >0.70 coefficient value generally recommended, and was somewhat negatively affected by the question on sunscreen use, likely related to the classic "sunscreen paradox". There were some differences in the performance of the SEPI between the Swedish and Australian samples, possibly due to the influence of "available" sunlight and differing attitudes to behaviour and protection "at home" and on vacation. CONCLUSIONS: SEPI appears to be a stable instrument with an overall acceptable validity and reliability, applicable for use in populations exposed to different UVR environments, in order to evaluate individual sun exposure and protection.

Validation of phototesting for estimation of individual skin ultraviolet sensitivity based on a lengthwise attenuating ultraviolet B field.

Conventional skin UV-sensitivity phototesting is based on semi-quantitative assessment of minimal erythema dose (MED). This study demonstrates a method for quantitative MED determination, using a lengthwise attenuating UVB-field combined with tissue viability imaging (TiVi). The study aim was to investigate the agreement between MED acquired by traditional phototest and by the new method. Forty-seven voluntary subjects underwent phototesting with a traditional phototest and with the new technique. Test reading, carried out after 24 h, showed moderate agreement between the methods when assessed with TiVi (Kappa value=0.46) and visually (Kappa value=0.48). For the new method, no systematic differences were seen between outcomes assessed with TiVi or visually (95% CI for the mean difference=-1.6-2.0). In conclusion, the results give promising support for the concept of achieving a more precise MED estimation by combining continuous attenuating UV fields with new available bioengineering technology.

Haemostatic factors, lipoproteins and long-term mortality in a multi-ethnic population of Gujarati, African-Caribbean and European origin.

OBJECTIVES: To examine the relations between haemostatic factors and lipoproteins with mortality in British Europeans, African-Caribbeans (AfC) and Gujarati Indians. METHODS: A prospective cohort study of 331 subjects (40-79 years), followed-up over 26 years for mortality. Apolipoprotein-A1 (Apo-A1), apolipoprotein-B (Apo-B), factor VII coagulant activity (FVIIc), fibrinogen and von Willebrand Factor (vWF) were measured at baseline in 118 Europeans, 100 AfC and 113 Gujaratis. Aortic pulse wave velocity (aPWV) was measured in 174 participants. RESULTS: 147 (44.4%) subjects died during a median of 24 years follow-up with 69 cardiovascular deaths. Women at baseline had higher, and AfC males the lowest FVIIc and Apo-A1 levels. Baseline age-sex and ethnicity adjusted FVIIc levels were higher in those who died (131.0 vs. 117.4%; P = 0.048). In similarly adjusted partial correlations, Apo-A1 was inversely related to arterial stiffness (ρ = -0.23, P = 0.04). Over the 26 years follow-up, participants below the median (i.e. with lower concentration) of FVIIc, Fibrinogen, Apo-B and vWF had better survival rates than those with higher concentrations; those with higher concentrations of Apo-A1 had better survival. In Cox multivariable regression analyses including sex, ethnicity and aPWV, independently increased risk of all-cause mortality came only from SBP (per 5 mmHg); P = 0.011), age (per year); P < 0.0001 and FVIIc at 7% (per 10-unit; HR 1.07 (1.02, 1.12); P = 0.008. Separately, Apo-A1 (HR 0.12 (0.02, 0.75; P = 0.029) was independently associated with a very significant 88% reduction in all-cause mortality. CONCLUSIONS: Despite a relatively small sample size, long-term follow-up suggests an independent effect of the prothrombotic state (via FVIIc) and apo-A1 (a constituent of HDL) on mortality.

Brain-derived neurotrophic factor enhances cholinergic contraction of longitudinal muscle of rabbit intestine via activation of phospholipase C.

Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family of proteins best known for its role in neuronal survival, differentiation, migration, and synaptic plasticity in central and peripheral neurons. BDNF is also widely expressed in nonneuronal tissues including the gastrointestinal tract. The role of BDNF in intestinal smooth muscle contractility is not well defined. The aim of this study was to identify the role of BDNF in carbachol (CCh)- and substance P (SP)-induced contraction of intestinal longitudinal smooth muscle. BDNF, selective tropomyosin-related kinase B (TrkB) receptor agonists, and pharmacological inhibitors of signaling pathways were examined for their effects on contraction of rabbit intestinal longitudinal muscle strips induced by CCh and SP. BDNF activation of intracellular signaling pathways was examined by Western blot in homogenates of muscle strips and isolated muscle cells. One-hour preincubation with BDNF enhanced intestinal muscle contraction induced by CCh but not by SP. The selective synthetic TrkB agonists LM 22A4 and 7,8-dihydroxyflavone produced similar effects to BDNF. The Trk antagonist K-252a, a TrkB antibody but not p75NTR antibody, blocked the effect of BDNF. The enhancement of CCh-induced contraction by BDNF was blocked by the phospholipase C (PLC) antagonist U73122, but not by ERK1/2 or Akt antagonists. Direct measurement in muscle strips and isolated muscle cells showed that BDNF caused phosphorylation of TrkB receptors and PLC-γ, but not ERK1/2 or Akt. We conclude that exogenous BDNF augments the CCh-induced contraction of longitudinal muscle from rabbit intestine by activating TrkB receptors and subsequent PLC activation.

Influence of age, gender, educational level and self-estimation of skin type on sun exposure habits and readiness to increase sun protection.

BACKGROUND: Sun exposure habits and the propensity to undertake sun protection differ between individuals. Not least in primary prevention of skin cancer, aiming at reducing ultraviolet (UV) exposure, knowledge about these factors may be of importance. The aim of the present study was to investigate, in a primary health care (PHC) population, the relationship between sun exposure habits/sun protection behaviour/readiness to increase sun protection and gender, age, educational level and skin UV-sensitivity. METHODS: The baseline data from a previously performed RCT on skin cancer prevention was used. 415 patients, aged > 18 years, visiting a PHC centre in southern Sweden, filled-out a questionnaire mapping sun exposure, readiness to increase sun protection according to the Transtheoretical Model of Behaviour Change (TTM), and the above mentioned factors. RESULTS: Female gender was associated with more frequent suntanning (p < 0.001) and sunbed use (p < 0.05), but also with more extensive sunscreen use (p < 0.001). High age was in general associated with low level of sun exposure and high level of protection. Subjects with low educational level reported less frequent sunscreen use than those with higher educational level, and also chose lower SPF (p < 0.001). For almost all parameters, high skin UV-sensitivity was associated with markedly lower sun exposure (p < 0.001) and more pronounced readiness to increase sun protection. Females and subjects with high educational level reported higher readiness to increase sunscreen use than males and subjects with lower educational level (p < 0.001). CONCLUSIONS: Gender, age, educational level and skin type appear to be important factors affecting sun exposure habits and sun protection behaviour, which supports the idea of appropriate mapping of these factors in patients in order to individualise sun protection advice according to the individual patient situation and capabilities.

Measuring sun exposure habits and sun protection behaviour using a comprehensive scoring instrument--an illustration of a possible model based on Likert scale scorings and on estimation of readiness to increase sun protection.

BACKGROUND: Few attempts to present a comprehensive scoring instrument for sun exposure and protection have been made. The present paper aims to describe a possible set of questions suitable for such an instrument, comprising the most important aspects of sun exposure and protection. METHODS: The material from a previously performed intervention study, using a questionnaire based on Likert scales and on the Transtheoretical Model of Behaviour Change (TTM), was utilised. 213 primary healthcare patients filled in the questionnaire and were randomised into two groups receiving sun protection advice, in Group 1 in letter-form, and in Group 2 orally during a doctor's consultation. In the original study, increased sun protection/readiness to increase sun protection was demonstrated for several items in Group 2, at six months. To compose a comprehensive scoring instrument, five questions concerning sun exposure/protection (intentional tanning, sunscreen use, choice of SPF, number of occasions with sunburn, and time spent in the sun at midday), were selected to give a 20 point behavioural score. Similarly, four TTM-based questions (giving up sunbathing, using clothes for sun protection, using sunscreens, and staying in the shade) gave a 16 point "propensity-to-change"-score. RESULTS: At follow-up, increased sun protection reflected in the behavioural score occurred only in Group 2 (p < 0.001). For the propensity-to-change-score, increased readiness to increase sun protection occurred in both groups, but the change was significantly higher in Group 2 (p < 0.05). Categorisation of the 20 point behavioural score, into three risk levels, revealed a significantly higher shift of subjects moving to a lower risk level in Group 2 compared to Group 1 (p<0.05). CONCLUSIONS: In conclusion, twinning of a summarised Likert scale behavioural score with a TTM-based propensity-to-change-score seems promising for the creation of a questionnaire-based, comprehensive scoring instrument for sun exposure and protection.

Statin use and outcome after intracerebral hemorrhage: case-control study and meta-analysis.

OBJECTIVES: Intracerebral hemorrhage (ICH) is a highly lethal disease of the elderly. Use of statins is increasingly widespread among the elderly, and therefore common in patients who develop ICH. Accumulating data suggests that statins have neuroprotective effects, but their association with ICH outcome has been inconsistent. We therefore performed a meta-analysis of all available evidence, including unpublished data from our own institution, to determine whether statin exposure is protective for patients who develop ICH. METHODS: In our prospectively ascertained cohort, we compared 90-day functional outcome in 238 pre-ICH statin cases and 461 statin-free ICH cases. We then meta-analyzed results from our cohort along with previously published studies using a random effects model, for a total of 698 ICH statin cases and 1,823 non-statin-exposed subjects. RESULTS: Data from our center demonstrated an association between statin use before ICH and increased probability of favorable outcome (odds ratio [OR] = 2.08, 95% confidence interval [CI] 1.37-3.17) and reduced mortality (OR = 0.47, 95% CI 0.32-0.70) at 90 days. No compound-specific statin effect was identified. Meta-analysis of all published evidence confirmed the effect of statin use on good outcome (OR = 1.91, 95% CI 1.38-2.65) and mortality (OR = 0.55, 95% CI 0.42-0.72) after ICH. CONCLUSION: Antecedent use of statins prior to ICH is associated with favorable outcome and reduced mortality after ICH. This phenomenon appears to be a class effect of statins. Further studies are required to clarify the biological mechanisms underlying these observations.

Scoring of hand eczema: good agreement between patients and dermatological staff.

BACKGROUND: Assessment of hand eczema in a clinical study has been achieved using a scoring system which documents extent of eczema on different areas of the hand. OBJECTIVES: To investigate whether the same scoring system could be used by patients to communicate current status of hand eczema. METHODS: In a study of 62 patients (36 women and 26 men, age range 19-75 years), the patient's own assessment was compared with the assessment by a dermatologist and a dermatological nurse. Standardized information was given to the patient and the form was filled in independently by the patient, the nurse and the dermatologist, during the patient's visit to the clinic. Individual area scores were summed to a total score. RESULTS: The overall agreement was good, with an interclass correlation (ICC) of 0·61 between patient and dermatologist for the total score. The ICC between nurse and dermatologist was 0·78. Differences between observers were more pronounced for the more severe cases - those with higher numerical scores as assessed by the dermatologist. There was a tendency for women and for patients over the median age of 44 years to set a lower point score than the dermatologist. The concordance of observations from individual anatomical areas was higher for fingertips and nails and lower for the palm and dorsum of the hand. CONCLUSIONS: Patients are able to report the extent of hand eczema with good accuracy. Self-assessment protocols for hand eczema may well have a place in the monitoring of hand eczema extent over time.

Characterization of HCV-specific CD4+Th17 immunity in recurrent hepatitis C-induced liver allograft fibrosis.

Hepatitis C virus (HCV) recurrence with accelerated fibrosis following orthotopic liver transplantation (OLT) is a universal phenomenon. To evaluate mechanisms contributing to HCV induced allograft fibrosis/cirrhosis, we investigated HCV-specific CD4+Th17 cells and their induction in OLT recipients with recurrence utilizing 51 HCV+ OLT recipients, 15 healthy controls and 9 HCV- OLT recipients. Frequency of HCV specific CD4+ Tcells secreting IFN-γ, IL-17 and IL-10 was analyzed by ELISpot. Serum cytokines and chemokines were analyzed by LUMINEX. Recipients with recurrent HCV induced allograft inflammation and fibrosis/cirrhosis demonstrated a significant increase in frequency of HCV specific CD4+Th17 cells. Increased pro-inflammatory mediators (IL-17, IL-1ß, IL-6, IL-8 and MCP-1), decreased IFN-γ, and increased IL-4, IL-5 and IL-10 levels were identified. OLT recipients with allograft inflammation and fibrosis/cirrhosis demonstrated increased frequency of Foxp3+ regulatory T cells (Tregs) that inhibited HCV specific CD4+Th1 but not Th17 cells. This suggests that recurrent HCV infection in OLT recipients induces an inflammatory milieu characterized by increased IL-6, IL-1ß and decreased IFN-γ which facilitates induction of HCV specific CD4+Th17 cells. These cells are resistant to suppression by Tregs and may mediate an inflammatory cascade leading to cirrhosis in OLT recipients following HCV recurrence.

Increased cutaneous oxygen availability by topical application of hydrogen peroxide cream enhances the photodynamic reaction to topical 5-aminolevulinic acid-methyl ester.

Topical 5-aminolevulinic acid (ALA) and methyl aminolevulinate (MAL) photodynamic therapy (PDT) of skin lesions is an accepted treatment for skin tumours but success rates need improvement. The effectiveness of PDT is influenced by availability of oxygen. The aim of this study was to demonstrate, in normal skin, whether a decrease in skin oxygen tension reduces the photodynamic reaction (PDR); and whether the addition of topical hydrogen peroxide can reverse the effect. Topical MAL and red light were administered to the inner forearms of 40 healthy volunteers. Skin oxygen availability was lowered during the illumination phase of the PDT, by applying blanching pressure with a plastic slide. Topical hydrogen peroxide was applied under the pressure slide, immediately prior to illumination, to reverse the effect. Erythema was assessed by naked eye and laser Doppler perfusion imaging (LDPI), at baseline and at 1, 5, 24 and 48 h following illumination. Decreasing oxygen availability by pressure altered the PDR with a larger number of subjects (17.5%) not demonstrating any visible erythema at any time point after plastic slide pressure compared to a PDR Control site (7.5%). The addition of topical hydrogen peroxide during pressure application, restored the number of subjects showing no visible erythema compared to that of PDR Control. LDPI data showed that there was a decrease in mean perfusion after plastic slide pressure when comparing the change from baseline to 24 h (P < 0.05) with the PDR Control. The addition of hydrogen peroxide not only restored but also increased the mean perfusion compared to that of PDR Control when comparing the change from baseline to 5 h and the change from baseline to 24 h (P < 0.001). Increasing oxygen availability increased the PDR in normal skin. The possibility that addition of topical hydrogen peroxide to PDT protocols for non-melanoma skin cancer may increase reactivity and, thus, be relevant for outcomes warrants further study.

The role of liver transplantation for hepatic adenomatosis in the pediatric population: case report and review of the literature.

Hepatic adenomas are benign lesions often found in young women during childbearing age. These tumors are often solitary but can also be multiple in which case this is referred to as hepatic adenomatosis (HA). HA is defined as having greater than or equal to ten adenomas within an otherwise normal liver. We present a case of a teenager with HA who underwent an orthotopic liver transplant for complications of her HA. To date there are only four reports of teenagers, without an underlying glycogen storage disease, who have undergone a liver transplant for HA. Liver transplantation within the pediatric population is an acceptable treatment for HA that are deemed unresectable.

The effect of recipient-specific surgical issues on outcome of liver transplantation in biliary atresia.

Biliary atresia (BA), the most common reason for orthotopic liver transplantation (OLT) in children, is often accompanied by unique and challenging anatomical variations. This study examines the effect of surgical-specific issues related to the presence of complex vascular anatomic variants on the outcome of OLT for BA. The study group comprised 944 patients who were enrolled in the Studies of Pediatric Liver Transplantation (SPLIT) registry and underwent OLT for BA over an 11-year period. 63 (6.7%) patients met the study definition of complex vascular anomalies (CVA). Patient survival, but not graft survival, was significantly lower in the CVA group, (83 vs. 93 % at 1-year post-OLT). The CVA group had a significantly higher incidence of all reoperations, total biliary tract complications, biliary leaks and bowel perforation. The most frequent cause of death was infection, and death from bacterial infection was more common in the CVA group. Pretransplant portal vein thrombosis and a preduodenal portal vein were significant predictors of patient survival but not graft survival. This study demonstrates that surgical and technical factors have an effect on the outcome of BA patients undergoing OLT. However, OLT in these complex patients is technically achievable with an acceptable patient and graft survival.

2-APB protects against liver ischemia-reperfusion injury by reducing cellular and mitochondrial calcium uptake.

Ischemia-reperfusion (I/R) injury is a commonly encountered clinical problem in liver surgery and transplantation. The pathogenesis of I/R injury is multifactorial, but mitochondrial Ca(2+) overload plays a central role. We have previously defined a novel pathway for mitochondrial Ca(2+) handling and now further characterize this pathway and investigate a novel Ca(2+)-channel inhibitor, 2-aminoethoxydiphenyl borate (2-APB), for preventing hepatic I/R injury. The effect of 2-APB on cellular and mitochondrial Ca(2+) uptake was evaluated in vitro by using (45)Ca(2+). Subsequently, 2-APB (2 mg/kg) or vehicle was injected into the portal vein of anesthetized rats either before or following 1 h of inflow occlusion to 70% of the liver. After 3 h of reperfusion, liver injury was assessed enzymatically and histologically. Hep G2 cells transfected with green fluorescent protein-tagged cytochrome c were used to evaluate mitochondrial permeability. 2-APB dose-dependently blocked Ca(2+) uptake in isolated liver mitochondria and reduced cellular Ca(2+) accumulation in Hep G2 cells. In vivo I/R increased liver enzymes 10-fold, and 2-APB prevented this when administered pre- or postischemia. 2-APB significantly reduced cellular damage determined by hematoxylin and eosin and terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling staining of liver tissue. In vitro I/R caused a dissociation between cytochrome c and mitochondria in Hep G2 cells that was prevented by administration of 2-APB. These data further establish the role of cellular Ca(2+) uptake and subsequent mitochondrial Ca(2+) overload in I/R injury and identify 2-APB as a novel pharmacological inhibitor of liver I/R injury even when administered following a prolonged ischemic insult.