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Two hundred and forty four patients were randomised to receive either diazepam or emulsified diazepam (diazemuls) intravenously prior to routine upper gastrointestinal endoscopy. The groups were comparable with regard to age, sex, medical condition, vein size, and amount of drug administered. A quantitative assessment of symptoms at the injection site during the ensuing week was made by analysing questionnaires on pain and tenderness, which the patients graded each day, on a scale 0-3. Twenty-one out of 82 patients who received diazepam (25.6%) and 22 out of 84 who received diazemuls (26.2%) had local symptoms. Although the mean symptom scores over 7 days for the two groups were not different (5.95 +/- 5.19 and 7.27 +/- 6.30 respectively), more patients who received diazepam reported induration (P = 0.033). In 112 patients, signs of thrombosis in the injected veins were looked for 3-7 weeks later without knowledge of the preparation given. Thrombosis was present in 13 (25%) patients who had received diazepam and two (3.6%) who had received diazemuls (P less than 0.002). Only eight (53%) patients with thrombosed veins had symptoms. Thrombosis after intravenous injection of diazepam or diazemuls may be symptomless, and is significantly less likely following diazemuls. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the use of endocervical curettage at the time of colposcopy for low-grade cytologic abnormalities. STUDY DESIGN: We conducted a retrospective chart review of women with low-grade Papanicolaou smears who had undergone satisfactory colposcopic examinations with identifiable lesions. We evaluated results during a 2-year period thereafter to determine whether endocervical curettage increased the diagnosis of high-grade dysplasia. RESULTS: The study group consisted of 374 patients. Of these patients, 16 had endocervical curettages suggestive of high-grade dysplasia. Of these 16 patients, 4 did not have concomitant high-grade dysplasia identified on ectocervical biopsy. Therefore, 93 to 94 endocervical curettages needed to be performed to detect 1 case of high-grade dysplasia that would not have been identified otherwise. CONCLUSION: Routine endocervical curettage at the time of satisfactory colposcopy for low-grade cytologic abnormalities with a visible lesion does not significantly improve the diagnosis of high-grade dysplasia. [ABSTRACT FROM AUTHOR]

The case being presented is a 35-year-old female with a 3-year history of progressive dyspnea and right-sided heart failure following spine surgery. Physical examination identified a continuous bruit in the lower abdomen radiating to her back which prompted further evaluation. Echocardiography showed normal left ventricle systolic function, enlarged right ventricle, functional tricuspid regurgitation, and moderate pulmonary hypertension. A computed tomography (CT) scan of the abdomen and pelvis demonstrated findings consistent with an arteriovenous fistula (AVF) between the right common iliac artery and the inferior vena cava. She underwent an uneventful endovascular repair without perioperative complication. The patient's symptoms resolved a few hours after the procedure and she continued to be symptom free at 3-month follow-up. This case illustrates an iatrogenic iliocaval fistula causing high-output cardiac failure which was successfully treated endovascularly with excellent clinical result., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Holodiastolic flow reversal in the descending aorta on echocardiogram suggests significant aortic regurgitation. The study aim was to determine whether the presence of holodiastolic flow reversal on cardiac magnetic resonance imaging (MRI) correlates with aortic valve regurgitant fraction. We retrospectively reviewed 166 cardiac MRIs (64 % male, age 14.1 ± 9.5 years) from January 2011 to May 2012 where velocity mapping was acquired at both the aortic valve and the descending aorta at the level of the diaphragm. Descending aorta velocity maps were checked for baseline offset using a static reference region. Holodiastolic flow reversal was defined as flow reversal throughout diastole both before and after baseline correction. Significant aortic regurgitation was defined as regurgitant fraction >10 %. Aortic valve regurgitant fraction was <10 % in 144 patients (Group A), 10-20 % inclusive in 7 patients (Group B), and >20 % in 15 patients (Group C). Though the aortic valve regurgitant fraction was significantly higher for patients with holodiastolic flow reversal versus those without (8.5 ± 14.2 vs. 3.8 ± 6.6 %, p = 0.02), holodiastolic flow reversal was present in 32 Group A patients (22 %). In comparison, 4 Group B patients (57 %) and 7 Group C patients (47 %) had holodiastolic flow reversal. The sensitivity (Groups B and C) was 0.5, and the specificity (Group A) was 0.78. Holodiastolic flow reversal in the descending aorta on cardiac MRI was neither sensitive nor specific for predicting significant aortic regurgitation in this study population. Holodiastolic flow reversal in the absence of significant aortic regurgitation may be a relatively common finding in patients with congenital heart disease.

In rough-skinned newts, Taricha granulosa, exposure to an acute stressor results in the rapid release of corticosterone (CORT), which suppresses the ability of vasotocin (VT) to enhance clasping behavior. CORT also suppresses VT-induced spontaneous activity and sensory responsiveness of clasp-controlling neurons in the rostromedial reticular formation (Rf). The cellular mechanisms underlying this interaction remain unclear. We hypothesized that CORT blocks VT-enhanced clasping by interfering with V1a receptor availability and/or VT-induced endocytosis. We administered a physiologically active fluorescent VT conjugated to Oregon Green (VT-OG) to the fourth ventricle 9 min after an intraperitoneal injection of CORT (0, 10, 40 μg/0.1mL amphibian Ringers). The brains were collected 30 min post-VT-OG, fixed, and imaged with confocal microscopy. CORT diminished the number of endocytosed vesicles, percent area containing VT-OG, sum intensity of VT-OG, and the amount of VT-V1a within each vesicle; indicating that CORT was interfering with V1a receptor availability and VT-V1a receptor-mediated endocytosis. CORT actions were brain location-specific and season-dependent in a manner that is consistent with the natural and context-dependent expression of clasping behavior. Furthermore, the sensitivity of the Rf to CORT was much higher in animals during the breeding season, arguing for ethologically appropriate seasonal variation in CORT's ability to prevent VT-induced endocytosis. Our data are consistent with the time course and interaction effects of CORT and VT on clasping behavior and neurophysiology. CORT interference with VT-induced endocytosis may be a common mechanism employed by hormones across taxa for mediating rapid context- and season-specific behavioral responses., (Copyright © 2014. Published by Elsevier Inc.)

Patients suffering from aneurysmal subarachnoid hemorrhage often present with electrocardiogram (ECG) abnormalities that mimic cardiac ischemia, but documented left ventricular regional wall-motion dysfunction has rarely been reported. This report is intended to raise the awareness of possible ECG changes secondary to subarachnoid hemorrhage (SAH). We cared for a 55-year-old female with an acute aneurysmal subarachnoid hemorrhage, whose evaluation was delayed and complicated by the presence of Takotsubo cardiomyopathy (TCM). Aneurysmal subarachnoid hemorrhage may induce Takotsubo cardiomyopathy that can present as an acute ST-elevation myocardial infarction. Physicians need to be aware of this possibility since it can lead to significant delays and treatment options for the patient.

The low solubility of many proteins hinders large scale expression and purification as well as biophysical measurements. Here, we devised a general strategy to solubilize a protein by conjugating it at a solvent-exposed position to a 6 kDa protein that was re-engineered to be highly soluble. We applied this method to the CARD domain of Apoptosis-associated speck-like protein containing a CARD (ASC), which represents one member of a class of proteins that are notoriously prone to aggregation. Attachment of the tag to a cysteine residue, introduced by site-directed mutagenesis at its self-association interface, improved the solubility of the ASC CARD over 50-fold under physiological conditions. Although it is not possible to use nuclear magnetic resonance (NMR) to obtain a high quality 2D correlation spectrum of the wild type domain under physiological conditions, we demonstrate that NMR relaxation parameters of the solubilized variant are sufficiently improved to facilitate virtually any demanding measurement. The method shown here represents a straightforward approach for dramatically increasing protein solubility, enabled by ease of labeling as well as flexibility in tag placement with minimal perturbation to the target., (© 2013 The Protein Society.)

Most studies describing phenotypic resistance to integrase strand transfer inhibitors have analyzed viruses carrying only patient-derived HIV-1 integrase genes (INT-recombinant viruses). However, to date, many of the patients on INSTI-based treatment regimes, such as raltegravir (RAL), elvitegravir (EVG), and dolutegravir (DTG) are infected with multidrug-resistant HIV-1 strains. Here we analyzed the effect of drug resistance mutations in Gag (p2/NCp7/p1/p6), protease (PR), reverse transcriptase (RT), and integrase (IN) coding regions on susceptibility to INSTIs and viral replicative fitness using a novel HIV-1 phenotyping assay. Initial characterization based on site-directed mutant INSTI-resistant viruses confirmed the effect of a series of INSTI mutations on reduced susceptibility to EVG and RAL and viral replicative fitness (0.6% to 99% relative to the HIV-1NL4-3 control). Two sets of recombinant viruses containing a 3,428-bp gag-p2/NCp7/p1/p6/pol-PR/RT/IN (p2-INT) or a 1,088 bp integrase (INT) patient-derived fragment were constructed from plasma samples obtained from 27 virologic failure patients participating in a 48-week dose-ranging study of elvitegravir, GS-US-183-0105. A strong correlation was observed when susceptibility to EVG and RAL was assayed using p2-INT- vs. INT-recombinant viruses (Pearson coefficient correlation 0.869 and 0.918, P<0.0001 for EVG and RAL, respectively), demonstrating that mutations in the protease and RT have limited effect on susceptibility to these INSTIs. On the other hand, the replicative fitness of viruses harboring drug resistance mutations in PR, RT, and IN was generally impaired compared to viruses carrying only INSTI-resistance mutations. Thus, in the absence of drug pressure, drug resistance mutations in the PR and RT contribute to decrease the replicative fitness of the virus already impaired by mutations in the integrase. The use of recombinant viruses containing most or all HIV-1 regions targeted by antiretroviral drugs might be essential to understand the collective effect of epistatic interactions in multidrug-resistant viruses.

CCR5 antagonists are a powerful new class of antiretroviral drugs that require a companion assay to evaluate the presence of CXCR4-tropic (non-R5) viruses prior to use in human immunodeficiency virus (HIV)-infected individuals. In this study, we have developed, characterized, verified, and prevalidated a novel phenotypic test to determine HIV-1 coreceptor tropism (VERITROP) based on a sensitive cell-to-cell fusion assay. A proprietary vector was constructed containing a near-full-length HIV-1 genome with the yeast uracil biosynthesis (URA3) gene replacing the HIV-1 env coding sequence. Patient-derived HIV-1 PCR products were introduced by homologous recombination using an innovative yeast-based cloning strategy. The env-expressing vectors were then used in a cell-to-cell fusion assay to determine the presence of R5 and/or non-R5 HIV-1 variants within the viral population. Results were compared with (i) the original version of Trofile (Monogram Biosciences, San Francisco, CA), (ii) population sequencing, and (iii) 454 pyrosequencing, with the genotypic data analyzed using several bioinformatics tools, i.e., the 11/24/25 rule, Geno2Pheno (2% to 5.75%, 3.5%, or 10% false-positive rate [FPR]), and webPSSM. VERITROP consistently detected minority non-R5 variants from clinical specimens, with an analytical sensitivity of 0.3%, with viral loads of ≥1,000 copies/ml, and from B and non-B subtypes. In a pilot study, a 73.7% (56/76) concordance was observed with the original Trofile assay, with 19 of the 20 discordant results corresponding to non-R5 variants detected using VERITROP and not by the original Trofile assay. The degree of concordance of VERITROP and Trofile with population and deep sequencing results depended on the algorithm used to determine HIV-1 coreceptor tropism. Overall, VERITROP showed better concordance with deep sequencing/Geno2Pheno at a 0.3% detection threshold (67%), whereas Trofile matched better with population sequencing (79%). However, 454 sequencing using Geno2Pheno at a 10% FPR and 0.3% threshold and VERITROP more accurately predicted the success of a maraviroc-based regimen. In conclusion, VERITROP may promote the development of new HIV coreceptor antagonists and aid in the treatment and management of HIV-infected individuals prior to and/or during treatment with this class of drugs.

The advantages and disadvantages of different methods of carrying objects on spine loading are still not fully understood. Previous studies have either examined the effects of carrying using physiological measures or examined isolated spine segments using biomechanical models. Additionally, most studies have been restricted to only a small number of carrying conditions. Very few studies have attempted to examine the various factors influencing spine loading together. To improve understanding of interacting factors on carrying, this study assessed the lumbar spine loads of 16 subjects as they assumed six styles of carrying at two weight levels and two activity levels (walking vs. standing). Concurrent with each trial, a subject-specific biomechanical model was used to assess spine forces over the full lumbar spine. Most carrying methods in the trials resulted in relatively low levels of spine loading. Anterior/posterior (A/P) shear loading was the only spine-loading dimension that reached biomechanically meaningful levels. Two carrying conditions, with bins carried in front of the body, significantly increased A/P shear compared with other carrying styles. This increase appeared to be due to the greater moment arms occurring in these conditions. Many of the other carrying styles produced A/P shears that were similar to those observed when carrying nothing at all. Of all the tasks, the backpack carry characteristically produced especially low spine loads. The findings of the study suggest that to achieve optimal carrying in terms of spine loading, loads should be positioned close to the body, even when carrying relatively light loads.

Radioembolisation is a way of providing targeted radiotherapy to colorectal liver metastases. Results are encouraging but there is still no standard method of assessing the response to treatment. This paper aims to review the current experience assessing response following radioembolisation. A literature review was undertaken detailing radioembolisation in the treatment of colorectal liver metastases comparing staging methods, criteria, and response. A search was performed of electronic databases from 1980 to November 2011. Information acquired included year published, patient numbers, resection status, chemotherapy regimen, criteria used to stage disease and assess response to radioembolisation, tumour markers, and overall/progression free survival. Nineteen studies were analysed including randomised controlled trials, clinical trials, meta-analyses, and case series. There is no validated modality as the method of choice when assessing response to radioembolisation. CT at 3 months following radioembolisation is the most frequently modality used to assess response to treatment. PET-CT is increasingly being used as it measures functional and radiological aspects. RECIST is the most frequently used criteria. Conclusion. A validated modality to assess response to radioembolisation is needed. We suggest PET-CT and CEA pre- and postradioembolisation at 3 months using RECIST 1.1 criteria released in 2009, which includes criteria for PET-CT, cystic changes, and necrosis.

Central administration of corticotropin-releasing hormone (CRH) is known to enhance locomotion across a wide range of vertebrates, including the roughskin newt, Taricha granulosa. The present study aimed to identify the CRH effects on locomotor-controlling medullary neurons that underlie the peptide's behavioral stimulating actions. Single neurons were recorded from the rostral medullary reticular formation before and after intraventricular infusion of CRH in freely behaving newts and newts paralyzed with a myoneural blocking agent. In behaving newts, most medullary neurons showed increased firing 3-23 min after CRH infusion. Decreases in firing were less common. Of particular importance was the finding that in behaving newts, medullary neurons showed a cyclic firing pattern that was strongly associated with an increase in the incidence of walking bouts, an effect blocked by pretreatment with the CRH antagonist, alpha-helical CRH and not seen following vehicle administration. In contrast, the majority of medullary neurons sampled in immobilized newts lacked temporal cyclicity in their firing patterns following intraventricular infusion of CRH. That is, there was no evidence for a fictive locomotor activity pattern. Our results indicate that the actual expression of locomotion is a critical factor in regulating the behavior-activating effects of CRH and underscore the importance of using an awake, unrestrained animal for analysis of a hormone's neurobehavioral actions., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Twenty-six antiretroviral drugs (ARVs), targeting five different steps in the life cycle of the human immunodeficiency virus type 1 (HIV-1), have been approved for the treatment of HIV-1 infection. Accordingly, HIV-1 phenotypic assays based on common cloning technology currently employ three, or possibly four, different recombinant viruses. Here, we describe a system to assess HIV-1 resistance to all drugs targeting the three viral enzymes as well as viral assembly using a single patient-derived, chimeric virus. Patient-derived p2-INT (gag-p2/NCp7/p1/p6/pol-PR/RT/IN) products were PCR amplified as a single fragment (3,428 bp) or two overlapping fragments (1,657 bp and 2,002 bp) and then recombined into a vector containing a near-full-length HIV-1 genome with the Saccharomyces cerevisiae uracil biosynthesis gene (URA3) replacing the 3,428 bp p2-INT segment (Dudley et al., Biotechniques 46:458-467, 2009). P2-INT-recombinant viruses were employed in drug susceptibility assays to test the activity of protease (PI), nucleoside/nucleotide reverse transcriptase (NRTI), nonnucleoside reverse transcriptase (NNRTI), and integrase strand-transfer (INSTI) inhibitors. Using a single standardized test (ViralARTS HIV), this new technology permits the rapid and automated quantification of phenotypic resistance for all known and candidate antiretroviral drugs targeting all viral enzymes (PR, RT, including polymerase and RNase H activities, and IN), some of the current and potential assembly inhibitors, and any drug targeting Pol or Gag precursor cleavage sites (relevant for PI and maturation inhibitors) This novel assay may be instrumental (i) in the development and clinical assessment of novel ARV drugs and (ii) to monitor patients failing prior complex treatment regimens.

Background: The long-term outcomes of patients with acute myocardial infarction (AMI) according to the universal classification (UC) are unknown. We investigated whether the outcome of these patients is better predicted by the UC than the ST-segment classification (STC)., Methods: We conducted a retrospective study of 348 consecutive patients with AMI with mean follow-up of 30.6 months. The primary outcome was major adverse cardiovascular events (MACE) [composite of all causes of death and AMI]., Results: The study included ST-segment elevation (STEMI) = 168 (48%), non-ST-segment elevation (NSTEMI) = 180 (52%), Type 1 = 278 (80%), Type 2 = 55 (15.8%), Type 3 = 5 (1.4%), Type 4a = 2 (0.6%), Type 4b = 5 (1.4%), and Type 5 = 3 (0.9%). During follow-up, 102 (29.3%) patients had MACE, 80 (23%) patients died, and 31 (8.9%) had an AMI. The adjusted risk of MACE was similar for NSTEMI and STEMI (HR 1.26, 95% CI 0.77-2.03, P = .35) but was significantly lower for patients with Type 2 AMI as compared to Type 1 (HR 0.44, 95% CI 0.21-0.90, P= .02). The UC, peak troponin levels, discharge glomerular filtration rate <60 ml/min per 1.73 m(2), and thrombolysis in myocardial infarction risk score were independent predictors of MACE (all, P<.05)., Conclusions: The UC is an independent predictor of long-term outcomes in AMI patients compared to the STC. Type 2 AMI has less than half the risk of MACE as Type 1 AMI. Future studies should report outcomes of AMI patients according to the UC types., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Rheumatic heart disease (RHD) results in morbidity and mortality that is disproportionate among individuals in developing countries compared to those living in economically developed countries. The global burden of disease is uncertain because most previous studies to determine the prevalence of RHD in children relied on clinical screening criteria that lacked the sensitivity to detect most cases. The present study was performed to determine the prevalence of RHD in children and young adults in León, Nicaragua, an area previously thought to have a high prevalence of RHD. This was an observational study of 3,150 children aged 5 to 15 years and 489 adults aged 20 to 35 years randomly selected from urban and rural areas of León. Cardiopulmonary examinations and Doppler echocardiographic studies were performed on all subjects. Doppler echocardiographic diagnosis of RHD was based on predefined consensus criteria that were developed by a working group of the World Health Organization and the National Institutes of Health. The overall prevalence of RHD in children was 48 in 1,000 (95% confidence interval 35 in 1,000 to 60 in 1,000). The prevalence in urban children was 34 in 1,000, and in rural children it was 80 in 1,000. Using more stringent Doppler echocardiographic criteria designed to diagnose definite RHD in adults, the prevalence was 22 in 1,000 (95% confidence interval 8 in 1,000 to 37 in 1,000). In conclusion, the prevalence of RHD among children and adults in this economically disadvantaged population far exceeds previously predicted rates. The findings underscore the potential health and economic burden of acute rheumatic fever and RHD and support the need for more effective measures of prevention, which may include safe, effective, and affordable vaccines to prevent the streptococcal infections that trigger the disease.

Stress-induced release or central administration of corticotropin-releasing factor (CRF) enhances locomotion in a wide range of vertebrates, including the roughskin newt, Taricha granulosa. Although CRF's stimulatory actions on locomotor behavior are well established, the target neurons through which CRF exerts this effect remain unknown. To identify these target neurons, we utilized a fluorescent conjugate of CRF (CRF-TAMRA 1) to track this peptide's internalization into reticulospinal and other neurons in the medullary reticular formation (MRF), a region critically involved in regulating locomotion. Epifluorescent and confocal microscopy revealed that CRF-TAMRA 1 was internalized by diverse MRF neurons, including reticulospinal neurons retrogradely labeled with Cascade Blue dextran. In addition, we immunohistochemically identified a distinct subset of serotonin-containing neurons, located throughout the medullary raphé, that also internalized the fluorescent CRF-TAMRA 1 conjugate. Chronic single-unit recordings obtained from microwire electrodes in behaving newts revealed that intracerebroventricular (icv) administration of CRF-TAMRA 1 increased medullary neuronal firing and that appearance of this firing was associated with, and strongly predictive of, episodes of CRF-induced locomotion. Furthermore, icv administered CRF-TAMRA 1 produced behavioral and neurophysiological effects identical to equimolar doses of unlabeled CRF. Collectively, these findings provide the first evidence that CRF directly targets reticulospinal and serotonergic neurons in the MRF and indicate that CRF may enhance locomotion via direct effects on the hindbrain, including the reticulospinal system., (Copyright 2009 Elsevier Inc. All rights reserved.)

Background: The prognostic value of peak cardiac troponin (cTn) in different types of acute myocardial infarction (AMI) under the universal clinical classification is unknown., Hypothesis: We tested the hypothesis that the prognostic value of cTn varies with its peak level and type of AMI., Methods: We studied 345 consecutive patients with AMI with mean follow-up of 30.6 months according to quartiles of peak cTn level (QPTL) and the type of AMI. The study outcomes were the major adverse cardiovascular events (MACE; composite of all causes of mortality and recurrent AMI) and the individual components of MACE., Results: The study included patients with AMI Type 1 (n = 276), type 2 (n = 54), ST-segment elevation myocardial infarction (STEMI; n = 159), and non-ST-segment elevation myocardial infarction (NSTEMI; n = 186). Overall, peak cTn level was an independent predictor of MACE (hazard ratio [HR]: 1.001, 95% confidence interval [CI]: 1.000-1.003, P = 0.01) and death (HR: 1.002, 95% CI: 1.001-1.004, P = 0.003), but not of recurrent AMI. The highest risk of MACE and death was in the highest QPTL (61.6%, P = .016 and 66.3%, P = 0.021, respectively) while the highest risk of recurrent AMI was in the lowest QPTL (83.7%, P = 0.04). Quartiles of peak cTn level were significantly associated with increased risk of MACE and death in patients with Type 1 (all P = 0.01) and STEMI (P = 0.01 and P = 0.02, respectively), but no association existed in type 2 or NSTEMI patients., Conclusions: Overall, peak cTn predicts the risk of MACE and death but not the risk of AMI. While in Type 1 and STEMI patients, QPTL are associated with risk of MACE and death, no association exists in type 2 or NSTEMI patients.

Corticotropin-releasing factor (CRF) is a peptide well known for its role in coordinating various neuroendocrine, autonomic, and behavioral components of the vertebrate stress response, including rapid enhancement of locomotor activity. Although CRF's locomotor enhancing properties are well documented, the neuronal mechanisms and specific target neurons that underlie the peptide's effect on locomotor behavior remain poorly understood. In the present study, we describe the synthesis and functional characteristics of a CRF rhodamine analogue TAMRA-X conjugate mixture (CRF-TAMRA 1), to be used for tracking this peptide's internalization into target neurons in the brainstem of an amphibian, the roughskin newt (Taricha granulosa). CRF-TAMRA 1 conjugate administration into the lateral cerebral ventricle resulted in a rapid, endosomal-like internalization of fluorescence into brainstem medullary neurons. In addition, central CRF-TAMRA 1 administration produced neurobehavioral effects comparable to the native peptide, effects that were blocked by pre-treatment with the CRF receptor antagonist, alpha-helical CRF. Taken together, our results show the efficacy of CRF-TAMRA 1 as a novel tool for tracking CRF internalization into targets neurons in vivo and ultimately, aiding in elucidating the neuronal mechanisms and circuitry underlying CRF's influence on behavioral and physiological responses to stress.

Purpose of Review: HIV-1 entry into target cells is a complex multistage process involving the envelope glycoprotein, primary cellular receptor CD4, and at least two main cellular coreceptors, CCR5 and CXCR4. The identification of the HIV-1 coreceptors led to the rapid development of several drug candidates that selectively block this interaction, that is, CCR5 or CXCR4 antagonists. Here, we review different methodologies used to determine the ability of the virus to use one or both coreceptors and their potential role in managing HIV-infected individuals treated with these novel drugs., Recent Findings: Most commercially available HIV-1 tropism assays are cell-based (phenotypic) tests, which use different methodologies to generate env-recombinant viruses and distinct detection systems. On the other hand, a large effort is being devoted to develop more robust bioinformatic (genotypic) tools that may expedite HIV-1 tropism assays without compromising their accuracy. The main goal, however, continues to be to improve the sensitivity to detect minor CXCR4-tropic variants within the in-vivo HIV-1 quasispecies., Summary: An accurate determination, and perhaps quantification, of HIV-1 coreceptor usage is necessary for the successful management of HIV-infected individuals in the new era of entry inhibitors. Further studies, aimed to the development of novel methodologies, are essential for the success of this new class of drugs.

We tested whether the sex pheromones that stimulate courtship clasping in male roughskin newts do so, at least in part, by amplifying the somatosensory signals that directly trigger the motor pattern associated with clasping and, if so, whether that amplification is dependent on endogenous vasotocin (VT). Female olfactory stimuli increased the number of action potentials recorded in the medulla of males in response to tactile stimulation of the cloaca, which triggers the clasp motor reflex, as well as to tactile stimulation of the snout and hindlimb. That enhancement was blocked by exposing the medulla to a V1a receptor antagonist before pheromone exposure. However, the antagonist did not affect medullary responses to tactile stimuli in the absence of pheromone exposure, suggesting that pheromones amplify somatosensory signals by inducing endogenous VT release. The ability of VT to couple sensory systems together in response to social stimulation could allow this peptide to induce variable behavioural outcomes, depending on the immediate context of the social interaction and thus on the nature of the associated stimuli that are amplified. If widespread in vertebrates, this mechanism could account for some of the behavioural variability associated with this and related peptides both within and across species.

Background: Since its introduction, transjugular intrahepatic portosystemic shunt (TIPS) has been extensively used for treatment of portal hypertension. We report a decade of experience with particular emphasis on characterizing post-TIPS hepatic encephalopathy (HE)., Aim: To determine the frequency of clinically evident or minimal HE post-TIPS, identify predisposing factors and determine the impact of minimal HE on quality of life., Design: Prospective data collection and retrospective case notes analysis., Methods: Of 197 patients referred for TIPS insertion, 136 patients who survived the procedure by more than 4 weeks were available for assessment. Data collected at TIPS insertion was supplemented by case note analysis. Psychometric testing was performed and health profile questionnaires administered on patients still attending., Results: Most patients had alcoholic liver disease (62.4%) and bleeding varices unresponsive to endoscopic therapy (86%). Clinically evident post-TIPS HE developed in 34.5% of patients, was of similar frequency in the groups treated with polytetrafluoroethylene covered and uncovered stents, and the only significant predictor was pre-TIPS HE. Post-TIPS HE necessitating liver transplant or contributing to death occurred in only 14 (10.3%) patients. Minimal encephalopathy (abnormal psychometry) was present in 49% of patients at 26 (3-123) months after TIPS but this frequency was similar in a cohort of cirrhotics being assessed for liver transplant. However, patients with abnormal psychometry had significantly lower quality of life scores than those with normal psychometry., Conclusion: Although, HE is relatively common after TIPS insertion, with careful selection of patients it is usually short-lived and easily managed. Minimal HE is no more prevalent than expected in a cirrhotic population without TIPS.

Objective: Supra-renal fixation in endovascular aneurysm repair (SR-EVR) is used to improve the proximal seal of aortic stent grafts and appears to have minimal effect on serum creatinine. Serum cystatin C (CC) is a more sensitive marker of renal injury and, unlike creatinine, is unaffected by non-renal influence. The aim of this study was to assess the true renal effect of SR-EVR using this superior renal index., Methods: Consecutive patients undergoing SR-EVR were prospectively recruited and compared to control groups undergoing open aneurysm repair (OR) and colorectal resection (CR). Serum CC and creatinine clearance (CrC) were determined pre-operatively and at 3, 6 and 12 months post-surgery. Renal function was compared using analyses of covariance (ANCOVA)., Results: Sixty-five patients (M:F; 52:13, median age 74 years) were enrolled (24 SR-EVR, 28 OR, 13 CR). Pre-operative renal function and risk factors were comparable (CC 1.04mg/l, SR-EVR; 0.96mg/l, OR; 0.97mg/l, CR). Adjusting for baseline renal function, there was no significant difference in CC or CrC between study and both control groups at 3, 6 or 12-months post-operatively., Conclusion: Using cystatin C as a more sensitive renal index, there was no detectable evidence of kidney dysfunction at up to one-year following EVR with uncovered bare-metal supra-renal fixation.

Anthropomorphism, the use of human characteristics as a foundation for interpreting behavior and mental capacities of animals, is a bias undermining our understanding of other species, especially species as evolutionarily distant from humans as fishes. Anthropomorphism is not justified by allusions to evolutionary continuity among vertebrates, because no living vertebrate was ever a descendant of humans, so none could have inherited human traits. Nonetheless, it has recently been claimed that fishes are capable of conscious experiences of pain and emotional feelings and that mental welfare is an important issue for fishes. This paper shows that the evidence supporting claims for experiences of pain or conscious emotions by fishes is conceptually and methodologically flawed. In addition, the paper shows that the natural history and behavior of diverse fish species is inconsistent with a presumption of human-like awareness. This behavioral evidence is in accord with neurobiological observations showing that fishes are very different from us and are unlikely to have a capacity for awareness of pain or emotional feelings that meaningfully resemble our own. The factors that are detrimental to fish welfare have been well delineated by valid, objective indicators of physiological and behavioral well-being. This knowledge should guide welfare decisions. An empirical and non-anthropomorphic examination of diverse fishes and their adaptations should be the foundation for welfare decisions that would be truly beneficial to fishes and humans alike.

For animals in the wild, survival depends on being able to detect and respond rapidly to danger by switching from risky (e.g. conspicuous courtship) to survival-oriented behaviors. Very little is known about the hormonal or neuroendocrine mechanisms that control the rapid switch in behavioral state that occurs when an animal detects threats or other stressors. Prior studies with rough-skinned newts (Taricha granulosa), an amphibian model, found that stress-induced suppression of male sexual behaviors (amplectic clasping) involves corticosterone (CORT) and that this steroid hormone uses a novel membrane receptor and modulates the responsiveness of medullary neurons in clasp-controlling neural circuits. We provide evidence that this rapid suppression of male sex behaviors, when induced by either acute stress or CORT administration, involves activation of endocannabinoids signaling in the hindbrain. In a series of behavioral studies, administration of a cannabinoid antagonist, AM281, blocked the suppressive effects of exposure to acute stress or an injection of CORT on the performance of clasping behaviors in sexually active males. Similarly, in electrophysiological studies, prior treatment with AM281 blocked CORT-induced suppression of spontaneous neuronal activity and sensory responsiveness of hindbrain neurons in clasp-controlling neural circuits. These data suggest that, in response to acute stress, elevated CORT concentration increases endocannabinoid signaling in the hindbrain and alters sexual behaviors by modulating the excitability of medullary circuits.

The neural circuits of the piriform cortex mediate field potential oscillations and complex functions related to integrating odor cues with behavior, affective states, and multisensory processing. Previous anatomical studies have established major neural pathways linking the piriform cortex to other cortical and subcortical regions and major glutamatergic and GABAergic neuronal subtypes within the piriform circuits. However, the quantitative properties of diverse piriform interneurons are unknown. Using quantitative neural anatomical analysis and electrophysiological recording applied to a GAD65-EGFP transgenic mouse expressing GFP (green fluorescent protein) under the control of the GAD65 promoter, here we report a novel inhibitory network that is composed of neurons positive for GAD65-EGFP in the posterior piriform cortex (PPC). These interneurons had stereotyped dendritic and axonal properties that were distinct from basket cells or interneurons expressing various calcium-binding proteins (parvalbumin, calbindin, and calretinin) within the PPC. The GAD65-GFP neurons are GABAergic and outnumbered any other interneurons (expressing parvalbumin, calbindin, and calretinin) we studied. The firing pattern of these interneurons was highly homogenous and is similar to the regular-spiking nonpyramidal (RSNP) interneurons reported in primary sensory and other neocortical regions. Robust dye coupling among these interneurons and expression of connexin 36 suggested that they form electrically coupled networks. The predominant targets of descending axons of these interneurons were the dendrites of Layer III principal cells. Additionally, synapses were found on dendrites and somata of deep Layer II principal neurons and Layer III basket cells. A similar interneuronal subtype was also found in GAD65-EGFP-negative mouse. The extensive dendritic bifurcation at superficial lamina IA among horizontal afferent fibers and unique axonal targeting pattern suggests that these interneurons may play a role in direct feedforward inhibitory and disinhibitory olfactory processing. We conclude that the GAD65-GFP neurons may play distinct roles in regulating information flow and olfactory-related oscillation within the PPC in vivo.

Objective: The aim of this study was to assess the mid term effect of proximal bare metal fixation design on renal function in patients undergoing endovascular repair (EVR) of abdominal aortic aneurysm (AAA)., Methods: Consecutive EVR patients for AAA from December 1995-2001 were included and grouped to either infrarenal (Group 1) or uncovered suprarenal (Group 2) fixation. Peri-operative renal function and at 6, 12 and 24 months was determined by serum creatinine (sCr mmol l(-1)) and Cockroft-Gault creatinine clearance (CrC ml min(-1)). Changes in renal function were compared using non-parametric analysis., Results: Of the 179 EVR procedures during this six-year period, paired renal data was available for 135 patients at a minimal follow-up of 6 months (Gp1, n = 63; Gp2, n = 72). Median pre-EVR sCr and CrC were 113, 57 in Group 1 and 108, 58 in Group 2, p = NS. There was no significant deterioration in renal function within or between either group at 2 years post-EVR: median sCr, CrC values were 118, 56 (Group 1) and 111, 56 (Group 2), all p = NS., Conclusion: This study suggests mid-term renal function remains unaffected following EVR of AAA, irrespective of proximal fixation type. Designs to improve stent durability and EVR applicability do not appear to compromise renal function.

Arginine8 vasotocin (AVT), a neurohypophyseal peptide in nonmammalian vertebrates, plays a key role in the regulation of social behaviors related to reproduction. In male roughskin newts (Taricha granulosa), AVT is an important facilitator of several reproductive behaviors, including courtship clasping of females. Although AVT is known to act in certain brain regions and AVT receptors have been localized to some extent, specific target neurons for this peptide have not been identified in any species. Internalization of a receptor-specific conjugate of AVT and the fluorescent dye Oregon green was used to identify AVT target cells in the medulla of male roughskin newts. Medullary neurons are of interest because they appear to mediate facilitation of clasping by AVT. Direct application of AVT-Oregon green to the fourth ventricular surface of the medulla in vivo resulted in conjugate internalization by a widespread population of medullary neurons, particularly in the medial reticular formation and nuclei of cranial nerves V, VII, VIII, IX, and X. Some fourth-ventricle ependymal cells were also labeled. Reticulospinal neurons, which play an important role in clasping, were identified by retrograde labeling with tetramethylrhodamine dextran amine. AVT-Oregon green was internalized by 72% of these neurons. These results show that AVT can directly affect a very large and diverse medullary neuronal population, which may underlie the peptide's role in multiple neuroendocrinological processes, including autonomic and behavioral regulation. Selectivity of the AVT action may arise through interactions between AVT and steroids such as corticosterone., (2005 Wiley-Liss, Inc.)

This study extends earlier reports regarding the in vitro and in vivo efficacies of the nitroimidazopyran PA-824 against Mycobacterium tuberculosis. PA-824 was tested in vitro against a broad panel of multidrug-resistant clinical isolates and was found to be highly active against all isolates (MIC<1 microg/ml). The activity of PA-824 against M. tuberculosis was also assessed grown under conditions of oxygen depletion. PA-824 showed significant activity at 2, 10, and 50 microg/ml, similar to that of metronidazole, in a dose-dependent manner. In a short-course mouse infection model, the efficacy of PA-824 at 50, 100, and 300 mg/kg of body weight formulated in methylcellulose or cyclodextrin/lecithin after nine oral treatments was compared with those of isoniazid, rifampin, and moxifloxacin. PA-824 at 100 mg/kg in cyclodextrin/lecithin was as active as moxifloxacin at 100 mg/kg and isoniazid at 25 mg/kg and was slightly more active than rifampin at 20 mg/kg. Long-term treatment with PA-824 at 100 mg/kg in cyclodextrin/lecithin reduced the bacterial load below 500 CFU in the lungs and spleen. No significant differences in activity between PA-824 and the other single drug treatments tested (isoniazid at 25 mg/kg, rifampin at 10 mg/kg, gatifloxacin at 100 mg/kg, and moxifloxacin at 100 mg/kg) could be observed. In summary, its good activity in in vivo models, as well as its activity against multidrug-resistant M. tuberculosis and against M. tuberculosis isolates in a potentially latent state, makes PA-824 an attractive drug candidate for the therapy of tuberculosis. These data indicate that there is significant potential for effective oral delivery of PA-824 for the treatment of tuberculosis.

As an extension of previous work with bis(POM) nucleotide prodrugs, we report the synthesis and biological evaluation in tumor cell culture of the bis(pivaloyloxymethyl) phosphotriester prodrug of slightly cytotoxic 2'-deoxy-4'-thioadenosine and its alpha-anomer. We have experienced need for an alternative phosphate masking group, particularly with purine nucleosides. Accordingly, we report synthesis and biological evaluation of the bis(tBuSA TE) phosphotriester prodrugs of 8-azaguanosine and 6-methylpurine riboside, nucleoside analogs with moderate to significant cytotoxicity. All four prodrugs were examined in tumor cell culture in parallel with the parent nucleosides. Synthetic routes and biological data are presented.

Purpose: To report the results of a multicenter experience with the Viatorr expanded polytetrafluoroethylene-covered stent-graft for transjugular intrahepatic portosystemic shunt (TIPS) creation in which patency and clinical outcome were evaluated., Materials and Methods: One hundred consecutive patients with portal hypertension, with a mean age of 52 years (range, 22-86 years), underwent implantation of the Viatorr TIPS stent-graft at one of three hospital centers. The indications for TIPS creation were variceal bleeding (n = 81) and refractory ascites (n = 19). Twenty patients had Child-Pugh class A disease, 46 had class B disease, and 34 had class C disease. Eighty-seven patients underwent de novo TIPS placements, with 13 treated for recurrent TIPS stenosis. Sixty-two patients were available for follow-up portal venography and portosystemic pressure gradient (PSG) measurement commencing 6 months after Viatorr stent-graft placement., Results: The technical success rate was 100%. TIPS creation resulted in an immediate decrease in mean PSG (+/-SD) from 21 mm Hg +/- 6 to 7 mm Hg +/- 3. Acute repeat intervention (within 30 days) was required for portal vein thrombosis (n = 1), continued bleeding (n = 3), and encephalopathy (n = 1). The all-cause 30-day mortality rate was 12%. Two patients developed acute severe refractory encephalopathy, which led to death in one case. New or worsening encephalopathy was identified in 14% of patients. The incidence of recurrent bleeding was 8%. The cumulative survival rate at 1 year was 65%. Sixty-two patients available for venographic follow-up had a mean PSG of 9 mm Hg +/- 5 at a mean interval of 343 days (range, 56-967 days). There were four stent-graft occlusions (6%) and seven hemodynamically significant stenoses (11%), four within the stent-graft and three in the non-stent-implanted hepatic vein. The primary patency rate at 1 year by Kaplan-Meier analysis was 84%., Conclusions: This retrospective multicenter experience with the Viatorr stent-graft confirms the preliminary findings of other investigators of good technical results and improved patency compared with bare stents. Early mortality and symptomatic recurrence rates are low by historical standards. The theoretical increase in TIPS-related encephalopathy was not demonstrated. Longer-term follow-up will be required to determine whether the additional cost of the Viatorr stent-graft will be offset by reduced surveillance and repeat intervention.

Aortic stent grafting may be an alternative to surgery for patients with an abdominal aortic aneurysm and coexistent horseshoe kidney but is not without difficulties. This study examines the renal consequences of aortic stent grafting in such patients. This is a retrospective review of patients with horseshoe kidney in whom aortic stent grafting was performed between December 1995 and August 2000. Follow-up occurred within the EUROSTAR protocol and included measurement of serum creatinine. Of 130 patients in whom aortic stent grafting was performed, 4 had coexistent horseshoe kidney. In all patients the aneurysm was successfully excluded with the occlusion of between one and four anomalous renal arteries. At follow-up, no clinically significant renal impairment was detected. Endovascular aneurysm repair is an attractive option for patients with a horseshoe kidney and normal preoperative creatinine levels.

The effects of neuropeptides on the brain are a major focus of neuroendocrine research, and little progress has been made in the identification of the target neurons for many neuropeptides. Arginine8-vasotocin (AVT) is a neurohypophyseal peptide present in nonmammalian vertebrates that controls many neural and behavioral functions. Here we describe synthesis and functional characterization of an AVT-Oregon green conjugate 1 (AVT-OG 1) that can be used in vivo to identify AVT target neurons. Application of AVT-OG 1 to the brainstem of an amphibian produces rapid, endosome-like internalization together with typical AVT-like neurophysiological effects. Thus, preparation of AVT-OG 1, which preserves the peptide's neurophysiological effects, is useful as a fluorescent marker for AVT target neurons. Consequently, AVT-OG 1 conjugate will have considerable utility for analyzing the neural actions of AVT in the intact brain.

Purpose: Despite initial enthusiasm for endovascular aortic repair, few descriptions of longer-term follow-up of any endovascular device have been published. This paper represents the experience of a single centre with the Vanguard device over a 5-year period., Methods: Fifty-five patients with a median age of 71 years (range 45-87 years) and aneurysm diameter of 59 mm (45-84 mm) received a bifurcated Vanguard stent-graft between December 1995 and July 1999. Follow-up was according to the Eurostar criteria (clinical assessment, plain film radiography and computed tomography) at 1, 3, 6, 12, 18 and 24 months and then annually thereafter., Results: All primary stent deployments were successful. Median duration of surgery was 120 min (70-360 min). Median post-operative stay was 3 days (1-19 days) with a peri-operative mortality of 5.5%. In the follow-up period (median 40 months, range 6-64 months) there was one aneurysm associated death, and 14 deaths due to other causes. There have been three device migrations, 12 occluded graft limbs, four type II endoleaks and nine type III endoleaks. At 48 months, this has resulted in a survival rate of 67%, an endoleak free survival of 81% and intervention free survival of 59% (Kaplan-Meier)., Conclusion: Medium term results with the Vanguard device appear to be at least equivalent to open repair with regard to morbidity and mortality. Nevertheless, several delayed complications appear to be related to endograft limb distortion. Important lessons have been learnt in relation to the deployment of bifurcated endografts to reduce the incidence of secondary limb related problems.

Eighty-two patients with a chief complaint of plantar heel pain were evaluated for sensory abnormalities within the cutaneous distribution of both the medial calcaneal nerve and the medial plantar nerve, using quantitative neurosensory testing with a pressure-specified sensory device. The results showed that 22.68% of the patients displayed isolated abnormal sensory function within the distribution of the medial calcaneal nerve, whereas 49.48% of the patients displayed abnormal function within the distribution of both the medial calcaneal and the medial plantar nerves. Thus, 72.17% of the patients displayed abnormal sensory function within the distribution of the medial calcaneal nerve. Statistical analysis of the results, using the Pearson chi-square statistic and odds ratio, indicated that a significant percentage of patients with plantar heel pain, even early in the clinical course of plantar heel pain, display abnormal sensibility within the branches of the posterior tibial nerve, and specifically, within the distribution of the medial calcaneal nerve (P <.0008) and the medial plantar nerve (P <.0001).

Courtship clasping, a reproductive behavior in male roughskin newts (Taricha granulosa), is rapidly blocked by an action of corticosterone (CORT) at a specific neuronal membrane receptor. The CORT-induced impairment of clasping in behaving newts appears to be mediated partly by an elimination of clasping-related activity in medullary reticulospinal neurons. Previous studies of rapid CORT actions in Taricha have focused on the brain, so existence of CORT action in the spinal cord or peripheral nervous system has not been assessed. The present study used newts with a high cervical spinal transection to examine potential spinal or peripheral CORT effects on clasping by the hindlimbs in response to pressure on the cloaca. Spinal transection causes clasps elicited by cloacal stimulation to be very sustained beyond the termination of the eliciting stimulus. In spinally transected newts, CORT caused a dose-dependent depression in the duration as well as quality of the clasp that appeared within 10 min of injection. CORT selectively impaired the usual sustained maintenance of a clasp after termination of cloacal stimulation, but not clasp elicitation during stimulation. These effects were not produced by dexamethasone, a synthetic glucocorticoid that binds poorly to the CORT membrane receptor. The CORT effect on clasp maintenance but not clasp elicitation implies selective action on an intraspinal generator for clasping but not on sensory or efferent neuromuscular aspects of the response. These results indicate the presence in the newt spinal cord of the CORT membrane receptor that exerts functional effects distinctly different from those on the brainstem.

Vasotocin (AVT) and vasopressin (AVP) are potent modulators of social behaviors in diverse species of vertebrates. This review addresses questions about how and where AVT and AVP act to modulate social behaviors, focusing on research with an amphibian model (Taricha granulosa). In general, the behaviorally important AVT and AVP neurons occur in the forebrain and project to sites throughout the brain. Social behaviors are modulated by AVT and AVP acting at multiple sites in the brain and at multiple levels in the behavioral sequence. This review proposes that AVT and AVP can act on sensory pathways to modulate the responsiveness of neurons to behaviorally relevant sensory stimuli and also can act on motor pathways in the brainstem and spinal cord to modulate the neuronal output to behavior-specific pattern generators. This neurobehavioral model, in which AVT and AVP are thought to modulate social behaviors by affecting sensorimotor processing, warrants further research.

A common reason for the lack of cytotoxicity of certain nucleosides is thought to be their inability to be initially activated to the monophosphate level by a nucleoside kinase or other activating enzyme. In a search for other nucleosides that might be worthwhile anticancer agents, we have begun to examine the utilization of monophosphate prodrugs in order to explore whether any enhanced cytotoxicity might be found for the prodrugs of candidate nucleosides that have little or no cytotoxicity. To that end, 5'-bis(pivaloyloxymethyl) phosphate prodrugs of two weakly cytotoxic compounds, 8-aza-2'-deoxyadenosine (5) and 8-bromo-2'-deoxyadenosine (9), have been prepared. These prodrugs (8 and 12) were examined for their cytotoxicity in CEM cells and were found to possess significantly enhanced cytotoxicity when compared with the corresponding parent nucleosides. Further cell culture experiments were conducted to gain insight into the mechanisms of cytotoxicity of these two prodrugs, and those data are reported.

Analogs of trehalose are reported that were designed to interfere with mycolylation pathways in the mycobacterial cell wall. Several derivatives of 6,6'-dideoxytrehalose, including N,N'-dialkylamino and 6,6'-bis(sulfonamido) analogs, were prepared and evaluated for antimycobacterial activity against Mycobacterium tuberculosis H(37)Ra and a panel of clinical isolates of Mycobacterium avium. 6,6'-Diaminotrehalose and its diazido precursor were both inactive, but significant activity apparently related to aliphatic chain length was found among the sulfonamides, N-alkylamines, and one of the amidines.

Diastasis of the distal tibiofibular syndesmosis is commonly seen with ankle fractures, but is a rare finding in the absence of fracture. The anatomy, biomechanics, mechanism of injury, evaluation, and radiographic assessment of the tibiofibular syndesmosis are reviewed. The authors present a review and two cases of traumatic ankle diastasis without ankle fracture.

Background: The aim of portal vein embolisation is to induce hyperplasia of normal tissue when resection of a cancerous portion of the liver is contraindicated only by the volume of liver that would remain following operation., Methods: Eight patients with inoperable liver tumours (3 women and 5 men, median age 69.5 years, 3 colorectal hepatic metastasts, 2 choloangiocarcinomas and 3 hepatocellular cancers) were selected for portal vein embolisation. Selected portal branches were occluded with microparticles and coils. Liver volumes were determined by magnetic resonance imaging (MRI) before embolisation and again before operation., Results: Embolisation was successfully performed in all 8 patients, 7 by the percutaneous-transhepatic route, while one patient required open cannulation of a mesenteric vein. Management was altered in 6 patients who proceded to 'curative' resection; projected remaining liver volumes increased (Wilcoxon's matched pairs test p=0.02) from a median of 361 cc to a median of 550 cc; two patients had disease progression such that operation was no longer indicated. In one patient a misplaced coil unintentionally occluded a portal branch to normal liver., Conclusions: Portal vein embolisation produced appreciable hyperplasia of the normal liver and extended the option of 'curative' operation to 6 out of the 8 cases attempted. Complications can occur. The long-term results following operation are unknown.

The transjugular intrahepatic portosystemic shunt (TIPSS) has become an effective method of treatment for the complications of portal hypertension, however shunt dysfunction is common. Covered stent-grafts have been tested in animal models, and customized or "home-made" devices have been deployed in several institutions. We report the use of a new commercially available TIPSS stent-graft in six patients undergoing primary shunting as well as two cases of revision or secondary TIPSS. The device has proved relatively easy to handle and appears to have the technical features likely to improve primary patency. Further follow-up is required to properly assess shunt patency and re-intervention rates.

Limbic and basal forebrain-hypothalamic regions from male sheep differing in sexual performance were quantified for fos-like immunoreactivity. Rams classified as high-sexually performing (HP), low-sexually performing (LP), and male-oriented (MO) received noncontact sensory stimulation from either ewes in estrus (HP, n=5; LP, n=4; MO, n=4) or other males (HP, n=5; LP, n=4; MO, n=5) for a 4-h period on each of 3 consecutive days. Following exposure to stimulus animals on the third day, rams were euthanized and their brains were perfused with a 1% paraformaldehyde/1.5% glutaraldehyde solution and sections were analyzed for fos-like immunoreactivity. Brain regions analyzed were the medial amygdala (meAMY), medial preoptic area (mPOA), bed nucleus of the stria terminalis (BNST), and ventromedial hypothalamic nucleus (VMH). Fos-like immunoreactivity differed between groups in the mPOA and BNST but not in the meAMY or VMH. LP rams exposed to estrous ewes had more (P<.05) neurons staining positive for fos and fos-related antigens (FRA) in the mPOA and BNST than LP rams exposed to other rams or MO rams exposed to either estrous ewes or other rams. Numbers of neurons staining positive for FRA in the mPOA and BNST of LP rams exposed to estrous ewes, however, were not different (P>.05) from HP rams exposed to either estrous ewes or other rams. The similar fos-like immunoreactivity in areas important for the display of sexual behavior in HP and LP rams may reflect similar sensory input in these two groups of rams; however, LP rams, in contrast to HP rams, do not appear to respond similarly to the same sensory stimulus.