Spontaneous rupture of the liver upon revascularization during transplantation

Spontaneous rupture of the liver has been described in association with many benign and malignant conditions. We report, to our knowledge, the first case of spontaneous rupture of the liver upon revascularization, requiring total hepatectomy and portocaval shunt, followed by successful retransplantation. Routine pathological examination of the explanted liver failed to reveal the etiology of the rupture. However, electron microscopy demonstrated abnormal collagen in the hepatic arterial wall compatible with a collagen disorder such as Ehlers-Danlos type IV disease. We conclude that the donor liver had a previously undiagnosed collagen disorder. Review of the literature does not preclude the use of livers from donors with a history of connective tissue disorders. Based on our experience one should exercise caution when using livers from such donors. With a history of connective tissue disorder in an immediate family member, further tests should be performed in the donor to rule out a subclinical connective tissue disorder. In addition, a review of all patients reported thus far to have undergone total hepatectomy and portocaval shunt, followed by liver transplantation as a two-stage procedure is presented.     

Needle stick injuries among medical students

Questionnaires were distributed among 200 medical students regarding safety precautions observed while perfonning various invasive procedures during their clinical posting. Only 106 students responded with the completed questionnaire. The most common procedure performed by the students was drawing of blood, with an average frequency of 60.8 per month. Sixty-one per cent of the students reported being injured during the various procedures and only 3 5.5% of them used gloves. Resheathing the needle was responsible for causing injury to 69% of the students, which was significantly higher than injuries occurring while entry into the vein or withdrawing the needle (p<0.05).     

Enhanced oral paclitaxel absorption with vitamin E-TPGS: Effect on solubility and permeability in vitro, in situ and in vivo

Solubility and permeability being important determinants of oral drug absorption, this study was aimed to investigate the effect of d--tocopheryl polyethylene glycol 1000 succinate (TPGS) on the solubility and intestinal permeability of paclitaxel in vitro, in situ and in vivo, in order to estimate the absorption enhancement ability of TPGS. Aqueous solubility of paclitaxel is significantly enhanced by TPGS, where a linear increase was demonstrated above a TPGS concentration of 0.1 mg/ml. Paclitaxel demonstrated asymmetric transport across rat ileum with significantly greater (26-fold) basolateral-to-apical (B–A) permeability than that in apical-to-basolateral (A–B) direction. Presence of P-glycoprotein (P-gp) inhibitor, verapamil (200 μM), diminished asymmetric transport of paclitaxel suggesting the role of P-gp-mediated efflux. TPGS showed a concentration-dependent increase in A–B permeability and decreased B–A permeability. The maximum efflux inhibition activity was found at a minimum TPGS concentration of 0.1 mg/ml, however, further increase in TPGS concentration resulted in decreased A–B permeability with no change in B–A permeability. Thus, the maximum paclitaxel permeability attained with 0.1 mg/ml TPGS was attributed to the interplay between TPGS concentration dependent P-gp inhibition activity and miceller formation. In situ permeability studies in rats also demonstrated the role of efflux in limiting permeability of paclitaxel and inhibitory efficiency of TPGS. The plasma concentration of [¹⁴C]paclitaxel following oral administration (25 mg/kg) was significantly increased by coadministration of TPGS at a dose of 50 mg/kg in rats. Bioavailability is enhanced about 4.2- and 6.3-fold when [¹⁴C]paclitaxel was administrated with verapamil (25 mg/kg) and TPGS, respectively, as compared to [¹⁴C]paclitaxel administered alone. The effect of verapamil on oral bioavailability of [¹⁴C]paclitaxel was limited relative to the TPGS, consistent with the in vitro solubility and permeability enhancement ability of TPGS. In conclusion, the current data suggests that the coadministration of TPGS may improve the bioavailability of BCS class II–IV drugs with low solubility and/or less permeable as a result of significant P-gp-mediated efflux.     

Quantitative assessment of the contribution of sodium‐dependent taurocholate co‐transporting polypeptide (NTCP) to the hepatic uptake of rosuvastatin,pitavastatin and fluvastatin

Hepatic uptake transport is often the rate‐determining step in the systemic clearance of drugs. The ability to predict uptake clearance and to determine the contribution of individual transporters to overall hepatic uptake is therefore critical in assessing the potential pharmacokinetic and pharmacodynamic variability associated with drug–drug interactions and pharmacogenetics. The present study revisited the interaction of statin drugs, including pitavastatin, fluvastatin and rosuvastatin, with the sodium‐dependent taurocholate co‐transporting polypeptide (NTCP) using gene transfected cell models. In addition, the uptake clearance and the contribution of NTCP to the overall hepatic uptake were assessed using in vitro hepatocyte models. Then NTCP protein expression was measured by a targeted proteomics transporter quantification method to confirm the presence and stability of NTCP expression in suspended and cultured hepatocyte models. It was concluded that NTCP‐mediated uptake contributed significantly to active hepatic uptake in hepatocyte models for all three statins. However, the contribution of NTCP‐mediated uptake to the overall active hepatic uptake was compound‐dependent and varied from about 24% to 45%. Understanding the contribution of individual transporter proteins to the overall hepatic uptake and its functional variability when other active hepatic uptake pathways are interrupted could improve the current prediction practice used to assess the pharmacokinetic variability due to drug–drug interactions, pharmacogenetics and physiopathological conditions in humans. Copyright © 2013 John Wiley & Sons, Ltd.     

Hospital recovery following Thermachoice ablation is not dependent on setting (outpatient or daycase) or rescue analgesia: unexpected result

BACKGROUND: Thermal balloon endometrial ablation (TBEA) is increasingly being performed in the outpatient setting under local anaesthesia (LA) rather than in a daycase setting under general anaesthesia (GA). Our aim was to compare the post operative rescue analgesia requirements and duration of hospital stay in women undergoing outpatient (LA) and daycase (GA) TBEA. METHODS: Prospective observational study of consecutively recruited women who underwent outpatient (LA) TBEA (n=51) and daycase (GA) TBEA (n=50) over the same time period. Analgesia that was provided additional to the standard administered analgesic regimen was considered rescue analgesia. The main outcome measures were requirement for rescue analgesia and duration of hospital stay in both cohorts. RESULT(S): LA compared to GA cohorts had shorter hospital stays (11h [95% CI 9-13] vs. 17h [95% CI 14-20]) and lower analgesia requirements. However, multivariate regression, correcting for all known confounders, showed that duration of stay was independent of setting for ablation or amount of rescue analgesia. CONCLUSION(S): Duration of hospital stay is not entirely dependent on whether outpatient or daycase endometrial ablation is considered. This unexpected preliminary finding deserves to be validated in future confirmatory trials that compare outpatient and daycase treatments. We also discuss the confounding factors that should be considered when designing such trials.     

On the Morphological Deviation in Additive Manufacturing of Porous Ti6Al4V Scaffold: A Design Consideration

Additively manufactured Ti scaffolds have been used for bone replacement and orthopaedic applications. In these applications, both morphological and mechanical properties are important for their in vivo performance. Additively manufactured Ti6Al4V triply periodic minimal surface (TPMS) scaffolds with diamond and gyroid structures are known to have high stiffness and high osseointegration properties, respectively. However, morphological deviations between the as-designed and as-built types of these scaffolds have not been studied before. In this study, the morphological and mechanical properties of diamond and gyroid scaffolds at macro and microscales were examined. The results demonstrated that the mean printed strut thickness was greater than the designed target value. For diamond scaffolds, the deviation increased from 7.5 μm (2.5% excess) for vertical struts to 105.4 μm (35.1% excess) for horizontal struts. For the gyroid design, the corresponding deviations were larger, ranging from 12.6 μm (4.2% excess) to 198.6 μm (66.2% excess). The mean printed pore size was less than the designed target value. For diamonds, the deviation of the mean pore size from the designed value increased from 33.1 μm (−3.0% excess) for vertical struts to 92.8 μm (−8.4% excess) for horizontal struts. The corresponding deviation for gyroids was larger, ranging from 23.8 μm (−3.0% excess) to 168.7 μm (−21.1% excess). Compressive Young’s modulus of the bulk sample, gyroid and diamond scaffolds was calculated to be 35.8 GPa, 6.81 GPa and 7.59 GPa, respectively, via the global compression method. The corresponding yield strength of the samples was measured to be 1012, 108 and 134 MPa. Average microhardness and Young’s modulus from α and β phases of Ti6Al4V from scaffold struts were calculated to be 4.1 GPa and 131 GPa, respectively. The extracted morphology and mechanical properties in this study could help understand the deviation between the as-design and as-built matrices, which could help develop a design compensation strategy before the fabrication of the scaffolds.     

Unusual metastases from esophageal carcinoma: computed tomography demonstration

The computed tomography findings of large subcutaneous metastatic implants in the pelvic and inguinal regions from an epidermoid carcinoma of the esophagus are presented. To the best of the authors' knowledge, this appearance has not previously been reported.     

Radiographic measures of hyperinflation in clinical emphysema. Discrimination of patients from controls and relationship to physiologic and mechanical lung function

In a retrospective study we investigated the accuracy of radiographic measurements of hyperinflation in distinguishing a sample of patients with a clinical diagnosis of pulmonary emphysema (n = 44) from a sample of age- and sex-matched control subjects (n = 39). The relationship of the hyperinflation parameters to pulmonary function test results (PFTs) and arterial blood gas measurements (ABGs) in the emphysema patients was also examined. The radiographic measurements were diaphragmatic angle of depression, lung height, lung width, heart size, diaphragm level, radiographic total lung capacity (TLC), and size of the retrosternal air space. By discriminant function analysis, the best contributors to the function were lung height and diaphragmatic angle of depression, followed by radiographic TLC and heart size. The derived classification rule had a diagnostic accuracy of 88 percent. The radiographic measures, largely independent of one another, showed moderate correlations with percentage PFTs, ABGs, portable percentage spirometric studies, height, and weight. High correlations were found between several of the radiographic measurements and the PFTs that represent actual static lung volumes. The correlation between radiographically measured TLC and PFT TLC measured by the helium dilution technique was .90.     

The Constipation Severity Instrument: A Validated Measure

Purpose This study was designed to develop and test the validity and reliability of the Constipation Severity Instrument. Methods Scale development was conducted in two stages: 1) 74 items were generated through a literature review and focus groups of constipated patients and medical providers; and 2) a preliminary instrument was administered to 191 constipated patients and 103 healthy volunteers. Test-retest reliability of the constipated group was assessed (N = 90). Content, convergent, divergent, and discriminant validity were evaluated by using other validated measures by performing one-way analysis of variance and Pearson correlations. Results Exploratory and confirmatory factor analysis revealed three subscales: obstructive defecation, colonic inertia, and pain. Internal consistency (α = 0.88–0.91) and test-retest reliability (intraclass correlation coefficients = 0.84–0.91) were high for all subscales. Constipated patients were grouped by Rome II criteria: functional constipation (22 percent), pelvic floor dyssynergia (15 percent), constipation predominant irritable bowel syndrome (23 percent), and no specific criteria (40 percent). Those with constipation predominant irritable bowel syndrome or pelvic floor dyssynergia scored higher on the Obstructive Defecation and Colonic Inertia subscales than those with functional constipation or no specific criteria (P = 0.001–0.058). Subjects with functional constipation had much lower scores on the pain subscale than constipation predominant irritable bowel syndrome, functional constipation, or no specific criteria (P < 0.009).The Constipation Severity Instrument subscale and total score correlated very highly with the subscales and total score of the Patient Assessment of Constipation Symptom measure. The Constipation Severity Instrument subscales discriminated well between constipated patients and healthy volunteers (P < 0.001) and demonstrated excellent divergent validity. Higher Constipation Severity Instrument scores inversely correlated with general quality of life. Conclusions The Constipation Severity Instrument is a reliable and valid instrument for assessing constipated patients. Administration of the Constipation Severity Instrument to other constipated patients will further validate its use. Supported by the University of California San Francisco Hellman Family Award for Early Career Faculty. Read at the meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, June 2 to 6, 2007. Reprints are not available.