Fixed-diameter polyethylene cuffs applied to the rat sciatic nerve induce a painful neuropathy: ultrastructural morphometric analysis of axonal alterations.
Polyethylene cuffs of varying inner diameters were applied to the rat sciatic or sural nerve with the aim of inducing a standardized nerve injury, as assessed by morphometric analyses of fiber-size spectrum alterations, associated with behavioral manifestations of neuropathic pain. The temporal sequence of axonal degeneration and regeneration was examined in parallel with behavioral analyses of pain initiation and recovery over a 6-week postoperative (PO) period. Cuffs of 0.028-0.030" inner diameter loosely enclosed sciatic nerves of young rats and elicited relatively uniform axonal degeneration and 'pain'. Large myelinated axons underwent an early and sustained numerical depletion. Both the thinly myelinated and unmyelinated axon populations were initially diminished, but later rose to levels significantly greater than control values, likely the result of: (1) demyelination, (2) early stages of remyelination, (3) regenerative sprouting, and/or (4) collateral sprouting of undamaged unmyelinated axons. Pathological alterations of the injured nerve included edematous swelling, hypertrophy of the perineurial sheath, infiltration of fibroblasts and collagen into the intraneurial compartment, increasing interaxonal space and decreasing order and density of axonal packing. Animals displayed maximal pain-related behaviors, including gait and postural asymmetries and hypersensitivity to mechanical compression and cold, during the 2nd week PO and had largely recovered by approximately 4 weeks PO. Consistent behavioral manifestations of pain were achieved over a wide range of fiber spectrum alteration; however, with the largest cuffs or 'bracelets' used in this study, a substantial axonal fiber spectrum change was produced without inducing pain-related behavior, suggesting that decrement in the number of myelinated axons was not always sufficient to elicit pain. Similar morphometric and pathological results were achieved with sural neuropathy after 0.010" ID cuffs and 14 days PO survival. Considering the lack of correlation between axonal alterations and pain, modification in the local intraneurial microenvironment at the site of injury may be a key component of peripheral pain mechanisms; these include changes in the biochemical milieu, increased intraneurial pressure, and altered nociceptor sensitivity or impulse propagation in the relatively intact unmyelinated axon population.


Immobilization of beta-galactosidase onto magnetic beads.
A study of the cross-linking of beta-galactosidase on magnetic beads is reported here. The magnetic beads were prepared from artemisia seed gum, chitosan, and magnetic fluid in the presence of a cross-linking regent (i.e., glutaraldehyde). The reactive aldehyde groups of the magnetic beads allowed the reaction of the amino groups of the enzymes. The animated magnetic beads were used for the covalent immobilization of beta-galactosidase. The effect of various preparation conditions on the activity of the immobilized beta-galactosidase, such as immobilizing time, amount of enzyme, and the concentration of glutaraldehyde, were investigated. The influence of pH and temperature on the activity and the stability of the enzyme, both free and immobilized, have been studied. And o-nitrophenyl-beta-D: -galactopyranoside (ONPG) was chosen as a substrate. The beta-galactosidase immobilized on the magnetic beads resulted in an increase in enzyme stability. Optimum operational temperature for immobilized enzyme was 10 degrees Celsius higher than that of free enzyme and was significantly broader.


Are there salvage routes within the general secretory pathway in yeast?
It is generally accepted that both extracellular protein secretion and plasma membrane expansion in yeast occur basically as in higher eukaryotic cells. In addition to the constitutive (default) secretory pathway, some specialized mammalian cells possess a regulated route which at present has not been detected in yeast. However, there is a body of experimental results suggesting that under certain circumstances export of integral plasma membrane and exocellular proteins may take place through alternative (salvage) pathways. The existence of these latter routes would enable the yeast cell to adapt more efficiently to distinct or adverse conditions requiring the secretion of discrete amounts of specific sets of proteins.


Single-agent capecitabine in patients with metastatic colorectal cancer refractory to 5-fluorouracil/leucovorin chemotherapy.
The effectiveness of capecitabine, an oral fluoropyrimidine carbamate, is well documented in previously untreated metastatic colorectal cancer patients (overall response rate: 25%). However, its efficacy in patients with metastatic colorectal cancer refractory to 5-fluorouracil/leucovorin (5-FU/LV) has not been determined. This study was performed to evaluate the efficacy and to identify the side-effects of capecitabine in patients with metastatic colorectal cancer showing progression despite 5-FU/LV-based combination chemotherapy. Fifty-one metastatic colorectal cancer patients who showed progressive disease in 5-FU/LV-containing regimens (median: two regimes) were treated with capecitabine 1,250 mg/m(2) twice daily (days 1-14 repeated every 3 weeks). Only one partial response was observed (response rate: 2%). Twenty-seven patients (53%) showed stable disease after two cycles. The median time to disease progression of either a partial response or stable disease was 3.4 months. Hand-foot syndrome was the main toxicity of capecitabine and occurred in 35% of cases (grade 3 or 4 in 6%). The median number of cycles administered was two and the relative dose intensity of capecitabine was 80%. The response rate to capecitabine was low in metastatic colorectal cancers that were refractory to 5-FU/LV-containing chemotherapy. However, disease stabilization was seen in a significant number of patients.


Preparedness planning and care of patients under investigation for or with Ebola virus disease: A survey of physicians in North America.
The West African Ebola virus disease (EVD) epidemic of 2014-2015 required North American hospitals to undertake comprehensive planning and training for the potential need to care for patients with EVD. Here we describe physician contributions to EVD preparedness planning and the care of persons under investigation for or patients with EVD.


Preventing injury and injury-related disability in children and adolescents.
Injury is the leading cause of death and a prevalent source of disability and excess health expenditures in children and adolescents. There are predictable patterns to injury that provide clues to prevention. Epidemiologically-based theoretical frameworks are available to guide development of injury prevention strategies, to add structure to our observations, and focus to our prevention activities. While all-cause injury mortality rates have decreased in children and adolescents over the last 20 years, large ethnic disparities persist, indicating the need for intensified efforts in high-risk communities. Strong leadership from pediatric surgeons and pediatricians operating hospital-based community injury prevention programs has produced successful reductions in child and adolescent injury rates in resource-limited and minority neighborhoods. Among the program features considered essential are: (1) an ongoing injury surveillance system; (2) well-focused, multifaceted prevention activities, including both passive and active prevention approaches; (3) education; (4) enlistment of other health professionals, local government officials, community leaders, and the public; and (5) evaluation and refinement of prevention activities.


Novel extracellular matrix structures in the neural stem cell niche capture the neurogenic factor fibroblast growth factor 2 from the extracellular milieu.
The novel extracellular matrix structures called fractones are found in the lateral ventricle walls, the principal adult brain stem cell niche. By electron microscopy, fractones were shown to contact neural stem and progenitor cells (NSPC), suggesting a role in neurogenesis. Here, we investigated spatial relationships between proliferating NSPC and fractones and identified basic components and the first function of fractones. Using bromodeoxyuridine (BrdU) for birth-dating cells in the adult mouse lateral ventricle wall, we found most mitotic cells next to fractones, although some cells emerged next to capillaries. Like capillary basement membranes, fractones were immunoreactive for laminin beta1 and gamma1, collagen IV, nidogen, and perlecan, but not laminin-alpha1, in the adult rat, mouse, and human. Intriguingly, N-sulfate heparan sulfate proteoglycan (HSPG) immunoreactivity was restricted to fractone subpopulations and infrequent subependymal capillaries. Double immunolabel for BrdU and N-sulfate HSPG revealed preferential mitosis next to N-sulfate HSPG immunoreactive fractones. To determine whether N sulfate HSPG immunoreactivity within fractones reflects a potential for binding neurogenic growth factors, we identified biotinylated fibroblast growth factor 2 (FGF-2) binding sites in situ on frozen sections, and in vivo after intracerebroventricular injection of biotinylated FGF-2 in the adult rat or mouse. Both binding assays revealed biotinylated FGF-2 on fractone subpopulations and on infrequent subependymal capillaries. The binding of biotinylated FGF-2 was specific and dependent upon HSPG, as demonstrated in vitro and in vivo by inhibition with heparatinase and by the concomitant disappearance of N-sulfate HSPG immunoreactivity. These results strongly suggest that fractones promote growth factor activity in the neural stem cell niche.


Real-time diffraction computed tomography data reduction.
Diffraction imaging is an X-ray imaging method which uses the crystallinity information (cell parameter, orientation) as a signal to create an image pixel by pixel: a pencil beam is raster-scanned onto a sample and the (powder) diffraction signal is recorded by a large area detector. With the flux provided by third-generation synchrotrons and the speed of hybrid pixel detectors, the acquisition speed of these experiments is now limited by the transfer rate to the local storage as the data reduction can hardly be performed in real time. This contribution presents the benchmarking of a typical data analysis pipeline for a diffraction imaging experiment like the ones performed at ESRF ID15a and proposes some disruptive techniques to decode CIF binary format images using the computational power of graphics cards to be able to perform data reduction in real time.


Addition of epinephrine to intrathecal bupivacaine and sufentanil for ambulatory labor analgesia.
The intrathecal combination of sufentanil and bupivacaine provides rapid, effective analgesia for labor with a limited duration. Many anesthesiologists have concerns that the use of intrathecal local anesthetics precludes maternal ambulation. This prospective, randomized, double-blind study was designed to determine whether the addition of epinephrine to the combination of sufentanil and bupivacaine would prolong intrathecal analgesia for labor. Patients' ability to ambulate was also assessed. Thirty-nine patients received either an intrathecal control dose of 10 micrograms sufentanil plus 2.5 mg bupivacaine plus 0.2 ml normal saline (control group); or 10 micrograms sufentanil plus 2.5 mg bupivacaine plus 0.2 ml (0.2 mg) of epinephrine (EPI group). Seven patients (3 control, 4 EPI) delivered vaginally and two (1 control, 1 EPI) required cesarean delivery before requesting epidural analgesia. The duration (mean +/- SD) of intrathecal labor analgesia was prolonged significantly by the addition of epinephrine: control (n = 15): 145 +/- 23 min; EPI (n = 15): 188 +/- 25 min (P < 0.0001). Maternal ambulation was demonstrated in 100% (19 of 19) of the control group and in 80% (16 of 20) of the EPI group (P = NS). The addition of 0.2 mg epinephrine to the intrathecal combination of sufentanil and bupivacaine significantly prolonged labor analgesia without causing adverse effects to the mother or fetus. The intrathecal combination of sufentanil and bupivacaine, with or without epinephrine, provided rapid, profound labor analgesia and allowed most patients to ambulate.


[Cochrane EPOC group: closing the gap between quality assurance and organization of care research and front line professionals].
Keeping physicians informed on an ongoing basis is a new challenge for continuing medical education and quality assurance. In Italy over the last 5 years interest in evidence based literature is growing. This is demonstrated by the launch of an Italian edition of Clinical Evidence and by the growing number of guidelines and systematic reviews produced by Italian authors and institutions. However, there is some uncertainty concerning the familiarity of Italian policy makers and public health physicians with the evidence-based resources, including also how to access them. This article attempts to close this gap, by describing the activities of the Cochrane Collaboration and, within it, of the Cochrane Effective Practice and Organisation of Care Group (EPOC), both aim to prepare and maintaining SR of health care interventions. Specifically, the EPOC group develops systematic reviews of professional, financial, organisational and regulatory interventions that are designed to improve professional practice and the delivery of effective health services. EPOC has 31 reviews and 24 protocols published in Issue 4, 2004 of the Cochrane Library and has developed standard methods to assist people, such as quality criteria for study design specific to health services research. The EPOC specialized register contains details of over 2200 studies that fall within the group's scope. Systematic reviews provide a valuable and efficient source of information for policy makers and health care professionals aimed at implementing effective and efficient strategies to encourage medical behavioural change and deliver of high quality services.


Predicted altitudinal shifts and reduced spatial distribution of Leishmania infantum vector species under climate change scenarios in Colombia.
Visceral leishmaniasis (VL) is caused by the trypanosomatid parasite Leishmania infantum (=Leishmania chagasi), and is epidemiologically relevant due to its wide geographic distribution, the number of annual cases reported and the increase in its co-infection with HIV. Two vector species have been incriminated in the Americas: Lutzomyia longipalpis and Lutzomyia evansi. In Colombia, L. longipalpis is distributed along the Magdalena River Valley while L. evansi is only found in the northern part of the Country. Regarding the epidemiology of the disease, in Colombia the incidence of VL has decreased over the last few years without any intervention being implemented. Additionally, changes in transmission cycles have been reported with urban transmission occurring in the Caribbean Coast. In Europe and North America climate change seems to be driving a latitudinal shift of leishmaniasis transmission. Here, we explored the spatial distribution of the two known vector species of L. infantum in Colombia and projected its future distribution into climate change scenarios to establish the expansion potential of the disease. An updated database including L. longipalpis and L. evansi collection records from Colombia was compiled. Ecological niche models were performed for each species using the Maxent software and 13 Worldclim bioclimatic coverages. Projections were made for the pessimistic CSIRO A2 scenario, which predicts the higher increase in temperature due to non-emission reduction, and the optimistic Hadley B2 Scenario predicting the minimum increase in temperature. The database contained 23 records for L. evansi and 39 records for L. longipalpis, distributed along the Magdalena River Valley and the Caribbean Coast, where the potential distribution areas of both species were also predicted by Maxent. Climate change projections showed a general overall reduction in the spatial distribution of the two vector species, promoting a shift in altitudinal distribution for L. longipalpis and confining L. evansi to certain regions in the Caribbean Coast. Altitudinal shifts have been reported for cutaneous leishmaniasis vectors in Colombia and Peru. Here, we predict the same outcome for VL vectors in Colombia. Changes in spatial distribution patterns could be affecting local abundances due to climatic pressures on vector populations thus reducing the incidence of human cases.


Downregulation of miR-424 in placenta is associated with severe preeclampsia.
Previous studies have suggested that altered miRNA expression in the placenta is associated with preeclampsia. The aim of this study was to investigate the expression of miR-424 in placental samples of severe preeclampsia (sPE) and uncomplicated pregnancy patients. miRNA was isolated from placentas obtained from 30 sPE patients and 30 healthy women. Quantitative real-time polymerase chain reaction was used to analyze the expression of miR-424. The prediction of target genes of miR-424 was performed using miRGen database. The function of these target genes was analyzed further by DAVID and Gorilla software. The expression of miR-424 was significantly lower in patients with sPE than in healthy controls. Changed expression of miR-424 in the case of pregnancy-related hypertensive disorders might affect the Wnt signaling pathway. These factors have a strong correlation with the development of PE. Expression of miR-424 in placenta was lower in patients with sPE, suggesting its role in the pathology of sPE.


Photochemical intramolecular aromatic substitutions of the imidazol-2-yl radical are superior to those mediated by Bu3SnH.
Six-membered photochemical cyclisations of 2-iodo-N-(2-arylethyl)imidazoles proceeded regioselectively in higher yields than the equivalent tin hydride-mediated reactions. The decrease in yield of cyclisation products, 5,6-dihydroimidazo[2,1-a]isoquinolines containing strongly deactivating substituents on the aryl ring confirmed the electrophilic nature of the sigma-imidazol-2-yl radicals. The seven-membered cyclisation was only successful under photochemical conditions, as radical reduction occurred with tin hydride. Nitration of 5,6-dihydroimidazo[2,1-a]isoquinoline with nitric/sulfuric acid occurred at the 2- and 8-positions.


Severe developmental timing defects in the prothoracicotropic hormone (PTTH)-deficient silkworm, Bombyx mori.
The insect neuropeptide prothoracicotropic hormone (PTTH) triggers the biosynthesis and release of the molting hormone ecdysone in the prothoracic gland (PG), thereby controlling the timing of molting and metamorphosis. Despite the well-documented physiological role of PTTH and its signaling pathway in the PG, it is not clear whether PTTH is an essential hormone for ecdysone biosynthesis and development. To address this question, we established and characterized a PTTH knockout line in the silkworm, Bombyx mori. We found that PTTH knockouts showed a severe developmental delay in both the larval and pupal stages. Larval phenotypes of PTTH knockouts can be classified into three major classes: (i) developmental arrest during the second larval instar, (ii) precocious metamorphosis after the fourth larval instar (one instar earlier in comparison to the control strain), and (iii) metamorphosis to normal-sized pupae after completing the five larval instar stages. In PTTH knockout larvae, peak levels of ecdysone titers in the hemolymph were dramatically reduced and the timing of peaks was delayed, suggesting that protracted larval development is a result of the reduced and delayed synthesis of ecdysone in the PG. Despite these defects, low basal levels of ecdysone were maintained in PTTH knockout larvae, suggesting that the primary role of PTTH is to upregulate ecdysone biosynthesis in the PG during molting stages, and low basal levels of ecdysone can be maintained in the absence of PTTH. We also found that mRNA levels of genes involved in ecdysone biosynthesis and ecdysteroid signaling pathways were significantly reduced in PTTH knockouts. Our results provide genetic evidence that PTTH is not essential for development, but is required to coordinate growth and developmental timing.


Idiopathic chronic calcifying pancreatitis with diabetes mellitus. Analysis of pancreatic stone protein gene.
We present a case of a 27-year-old female suffering from chronic calcifying pancreatitis with diabetes mellitus. Radiographic examinations and exocrine pancreatic function tests revealed considerable dilatation of pancreatic ducts with large intraductal calculi and exocrine pancreatic insufficiency, respectively. Recent literature indicates that a decrease in the activity of pancreatic stone protein (PSP), which inhibits CaCO3 crystal formation in pancreatic juice, is closely related to the development of chronic calcifying pancreatitis. The patient had no apparent cause or family history of pancreatitis. We therefore investigated the possibility that alterations in the PSP gene might explain the chronic pancreatitis seen in this patient. Six exons of the PSP gene amplified by polymerase chain reaction were directly sequenced, but there was no apparent base mutation observed. Furthermore, Southern blot analysis revealed neither rearrangement nor deletion of the PSP gene in the genomic DNA of this case. However, this genetic approach will be useful for future study of the etiology of hereditary pancreatitis.


Do tastants have a smell?
The stimuli used in taste research are usually considered to be odourless. This was tested in two experiments with aqueous solutions of two representative compounds for each of the five taste qualities including umami. In the first experiment elderly and young subjects rated the intensity and pleasantness of three concentrations of the stimuli, while wearing or not wearing a noseclip. Saliva production was also measured. Blocking olfaction only influenced salivation for umami. It reduced taste intensity ratings, but as in an earlier experiment with the same compounds in food products, this effect was stronger in the young, who also liked the stimuli better wearing the noseclip. In the second experiment, another group of young people tried to detect the odours of the tastants dissolved in demineralized, double-distilled or Evian water. A considerable number of subjects could regularly detect seven of the ten tastants by olfaction and the extent to which they did correlated significantly with the reduction in taste intensity ratings for the different tastants found in the first experiment. We suggest that most tastants can be smelled and that this smell contributes to taste intensity ratings.


[Localized amyloidosis of the cavum].
Amyloidosis is characterized by extracellular deposits of proteins. A 66 year-old patient presented with a pseudo-tumoral amyloidosis of the cavum. Clinical and biological examinations confirmed the localized aspect of the disease and immunohistochemical exploration identified a type AL amyloidosis. The disease may be diffuse involving many organs and leading to various clinical manifestations. It can also be localized and take on a pseudo-tumoral aspect. Localised amyloidosis is a rare lesion of the upper aero-digestive tract, predominating in the larynx. Nasopharyngeal involvement is exceptional.


Dyke-Davidoff-Masson syndrome in postcerebral malaria.
Dyke-Davidoff-Masson syndrome is a disorder involving hemiatrophy or hypoplasia of 1 cerebral hemisphere secondary to an insult in the developing brain. Often this will manifest with seizures, hemiparesis, mental retardation, and facial changes. Associated with this pathology are the radiologically evident changes, such as thickening of the calvarium, hyperpneumatization of the sinuses, and dilation of the ipsilateral lateral ventricle among others. The following is a case presentation of an 18-year-old female emigrating from Ghana who presented to the emergency department with complaints of seizures diagnosed as being caused by cerebral malaria at 13 years of age. We hypothesize that the cerebral malaria and related vascular occlusion are the causes of her acquired cerebral changes. Included are computed tomography images.


[Hemangiopericytoma of the greater omentum. Videolaparoscopic treatment: case report and review of the literature].
Although hemangiopericytoma (HPT) may arise in any anatomic site, it rarely develops in the greater omentum. To our knowledge, only twelve cases have been reported to date in the English language literature. In this report, we describe the case of a patient with sudden severe lower abdominal pain caused by primary HPT in the greater omentum treated with laparoscopic approach and a review of the reported cases is made.


A meta-analysis of positive and negative age stereotype priming effects on behavior among older adults.
Evidence has shown that age stereotypes influence several behavioral outcomes in later life via stereotype valence-outcome assimilation; however, a direct comparison of positive versus negative age stereotyping effects has not yet been made. PsycINFO and Pubmed were used to generate a list of articles (n = 137), of which seven were applicable. From these articles, means, standard errors (SEs), and other relevant data were extracted for 52 dependent measures: 27 involved negative age primes and 25 involved positive age primes. Independent samples analysis of variance tests were used to explore the influence of prime valence and awareness on behavior compared with a neutral referent. A significant main effect for prime valence was found such that negative age priming elicited a greater effect on behavior than did positive age priming (F(1,48) = 4.32, p = .04). In fact, the effects from negative age priming were almost three times larger than those of positive priming when compared with a neutral baseline. This effect was not influenced by prime awareness, discipline of study, study design, or research group. Findings show that negative age stereotyping has a much stronger influence on important behavioral outcomes among older adults than does positive age stereotyping.


Haemangiopericytoma presenting with acute intracerebral haemorrhage.
Clinical presentation of brain tumour by acute haemorrhage is well known and occurs in around 5% of the cases. Haemangiopericytoma (HPC) is a richly vascularized tumour, but its clinical manifestation is most frequently related to tumour mass effect or seizures. We present the eighth case reported of a patient with acute intracerebral bleeding caused by HPC. Though HPC represents only about 2% of intracranial meningeal neoplasms it must be included in the differential diagnosis of intracranial haemorrhage.


Dichelyne (Cucullanellus) bodiani n. sp. and Cucullanus hansoni Olsen, 1952 (Nematoda: Cucullanidae) from fishes off New Caledonia.
Two species of cucullanid nematodes collected from the intestine of marine fishes off New Caledonia were studied with the use of light and scanning electron microscopy (SEM): Dichelyne (Cucullanellus) bodiani n. sp. from Bodianus perditio (Quoy & Gaimard) (Perciformes: Labridae), characterised mainly by the small size of the body (males and gravid females 2.26-3.13 mm and 2.46-3.32 mm long, respectively), the presence of very long spicules (1.53-1.66 mm in length), the remarkably large seminal vesicle and the arrangement of caudal papillae, is the second known species of Dichelyne Jägerskiöld, 1902 parasitising fishes of the Labridae and the second nominal species of this genus recorded from fishes in New Caledonian waters. Cucullanus hansoni Olsen, 1952, originally described from Hawaii, is now, after 67 years, again reported from its type-host, Sufflamen fraenatum (Latreille) (Tetraodontiformes: Balistidae), from off New Caledonia. The SEM examination of C. hansoni, used in this species for the first time, revealed some new morphological details, such as the presence of a median precloacal cuticular elevation or the shape of deirids and distal tips of spicules, as well as the exact location of caudal papillae and phasmids in the male. This is the seventh species of Cucullanus Müller, 1777 recorded from fishes off New Caledonia.


Direct thrombin inhibitor use during percutaneous coronary intervention.
Direct thrombin inhibitors (DTI) are emerging as alternative anticoagulants to unfractionated heparin and indirect thrombin inhibitors in patients undergoing percutaneous coronary intervention (PCI). We review the pharmacological properties of these newer antithrombotic agents and evaluate the clinical data demonstrating their use in patients undergoing PCI.


Periprosthetic fracture in the elderly with anatomic modular cementless hemiarthroplasty.
The use of an anatomic cementless stem in hemiarthroplasties for femoral intracapsular proximal fracture has been debated, notably because of bone weakness and/or morphological defects related to osteoporosis. We therefore conducted a retrospective study in subjects over 75 years of age who had received an anatomic stem partially coated with hydroxyapatite. The objectives were to determine: 1) the incidence of periprosthetic fractures (PPFs) and, 2) the influence of anatomic factors, including the Cortical Bone Ratio (CBR) (the relation between the endosteal and external diameter of the femoral diaphysis 10cm below the lesser trochanter). The risk of PPF with an anatomic cementless implant is greater than with cemented stems. We retrospectively analyzed 233 patients followed up for 5 years after their surgery. The stem used was an anatomic stem with a modular neck partially coated with hydroxyapatite. The risk factors examined were age, gender, history of osteoporotic fractures, diverse causes of secondary osteoporosis, and proximal bone stock according to various referenced radiological indices such as the CBR. Twenty patients (15%) were lost to follow-up, 74 had died (32%) but did not undergo revision for PPF, 15 of the 139 survivors at the last follow-up (10.8%) had had a PPF, five (3.6%; four females, one male) were early fractures (≤2 months after implantation), ten (7.2%; two females, eight males) were late fractures (>2 months). Male gender was protective for PPF occurrence (RR=0.129; 95%CI (0.04-0.39); P=0.0003), whereas secondary factors of osteoporosis (RR=2.035; 95%CI (1.11-3.72); P=0.0211), and CBR>0.49 (RR=227.42; 95%CI (1.072-48,226.76); P=0.0471) were found as risk factors of PPF. The PPF rate was greater than that related to cemented stems, requiring that morphological and clinical factors of bone weakness (collected with the patient history and related to osteoporosis) be taken into account. A CBR>0.49 requires caution on the use of this type of stem. Level 4. Retrospective study.


Glioblastoma multiforme in a mature ovarian teratoma with recurring brain tumours.
We report a case study to highlight the occurrence of glioblastoma multiforme in an ovarian teratoma. A 10-year-old girl presented with a left frontal lobe primitive neuroectodermal tumour which was successfully treated. After 6 uneventful years, she developed glioblastoma multiforme located posterior to the site of the initial tumour. Six years later, she presented with a mature cystic teratoma containing glioblastoma multiforme. Glioblastoma in an ovarian teratoma is an exceptional event, which might have an initial clinical presentation as a metastatic brain tumour. Alternatively, recurring glial tumours may occur in a genetically predisposed person; the role of radiation and chemotherapy in this context remains to be elucidated.


Differing effect of chenodeoxycholic acid and ursodeoxycholic acid on bile acids in rat colonic wall and contents.
Bile acids may promote experimental colonic cancer. Many studies correlate fecal bile acids and colorectal carcinomas. Little is known on bile acids in the colonic mucosa and their relation to luminal bile acids. We, therefore, studied bile acids in colonic wall and contents of normal female Wistar rats and after 14 days' administration of chenodeoxycholic acid or ursodeoxycholic acid (90 mg/kg daily), two bile acids used in medicamentous cholelitholysis. Both regimens increase total bile acids in colonic contents, ursodeoxycholic acid produces a higher rise in toxic lithocholic acid. In the colonic wall, only ursodeoxycholic acid causes an increase of most nonsulfated bile acids including lithocholic acid. Bile acid patterns do not correlate in colonic wall and contents. We conclude that increased colonic wall bile acids after ursodeoxycholic acid administration warrant control in man. In future colorectal carcinoma studies, not only fecal, but also mucosal bile acid concentrations should be correlated to carcinogenesis.


Experimental and theoretical investigations of evaporation of sessile water droplet on hydrophobic surfaces.
Experiments of sessile water droplet evaporation on both polydimethylsiloxane (PDMS) and Teflon surfaces were conducted. All experiments begin with constant contact area mode (the initial contact angle is greater than 90°), switch to constant contact angle mode and end with mixed mode. Based on the assumptions of spherical droplet and uniform concentration gradient, theoretical analyses for both constant contact area and constant contact angle modes are made and theoretical solutions are derived accordingly, especially a theoretical solution of contact angle is presented first for CCR stage with any value of the initial contact angle. Moreover, comparisons between the theoretical solutions and experimental data of contact angle in CCR stage demonstrate the validity of the theoretical solution and it would help for a better understanding and application of water droplet on solid surfaces, which is quite often encountered in lab-on-a-chip, polymerase chain reaction (PCR) and other micro-fluidics devices.


Effects of imatinib mesylate on renin-angiotensin system (RAS) activity during the clinical course of chronic myeloid leukaemia.
The renin-angiotensin system (RAS) is involved in cell growth, proliferation and differentiation in bone marrow in an autocrine-paracrine manner, and it modulates normal and neoplastic haematopoietic cell proliferation. This study aimed to assess expressions of the RAS components, renin, angiotensinogen and angiotensin-converting enzyme (ACE), during imatinib mesylate treatment of patients with chronic myeloid leukaemia (CML). Expressions of RAS components were studied in patients with CML at the time of diagnosis (n = 83) and at 3, 6 and 12 months after diagnosis (n = 35) by quantitative real-time polymerase chain reaction. De novo CML patients had increased ACE, angiotensinogen and renin mRNA levels and these expression levels decreased following administration of imatinib. The RAS activities were significantly different among Sokal risk groups of CML, highlighting the altered biological activity of RAS in neoplastic disorders. The results of this study confirm that haematopoietic RAS affects neoplastic cell production, which may be altered via administration of tyrosine kinase inhibitors such as imatinib mesylate.


Clotting factors secreted by monocytes and macrophages: analytical considerations.
The secretion of clotting factors by rat spleen macrophages and human peripheral blood monocytes has been studied. The results show that the amount of clotting factors measured depends critically upon the characteristics of the assay system used. The presence of warfarin, salicylic acid or thrombin in the culture medium is shown to decrease the vitamin K dependent clotting factor activity in the supernatant after in vitro culture of rat spleen macrophages and human peripheral blood monocytes.


Canine epitheliotropic cutaneous T-cell lymphoma: an investigation of T-cell receptor immunophenotype, lesion topography and molecular clonality.
Canine epitheliotropic cutaneous T-cell lymphoma (CTCL) is a spontaneous neoplasm of the skin and mucous membranes of aged dogs. The WHO classification of tumours of haematopoietic and lymphoid tissues in human beings recognizes three forms of cutaneous epitheliotropic CTCL: mycosis fungoides (MF), Sézary syndrome and pagetoid reticulosis. In this series of dogs (n = 56), there were 39 cases of MF, 16 cases of pagetoid reticulosis and a single case of Sézary syndrome. Epitheliotropic T cells in CTCL lesions expressed CD8 in 44 of 55 dogs (80%) assessed; neither CD4 nor CD8 was expressed in the remainder. This contrasts with human MF in which alphabeta T-cell receptors (TCR) and CD4 are dominantly expressed. Molecular clonality assessment of canine epitheliotropic CTCL utilizing PCR primers specific for canine TCR gamma (TCRG) was performed. Of the 45 canine cases assessed, TCRG monoclonality was detected in 36 cases (80%). TCR typing of canine epitheliotropic CTCL revealed that TCRgammadelta was expressed in 60% of cases, including all cases of canine pagetoid reticulosis assessed. Either muco-cutaneous junctions or tissues of the oral cavity were the sites of lesions in 32 dogs (57%) with epitheliotropic CTCL. Analysis of the topography of lesions revealed an association with TCR type. If epitheliotropic CTCL lesions occurred in both locations, T cells were more likely to express TCRgammadelta (gammadelta : alphabeta = 2.0). These data establish that canine skin trafficking T cells have a far wider range than previously thought; this includes tongue, gingival, buccal and palatine mucosae.


Basal cell carcinoma: what's new under the sun.
Basal cell carcinoma (BCC) is the most common skin cancer in white populations with an increasing incidence worldwide, thereby imposing an important public health problem. Its etiology is still unclear, but existing data indicate that the risk for BCC development is of multifactorial origin and results from the interplay of both constitutional and environmental factors. Yet, UV radiation (UVR) is believed to be the predominant causative risk factor in the pathogenesis of BCC. For years, BCC and squamous cell carcinoma (SCC) have been grouped together as "nonmelanoma skin cancer." However, it seems that there are considerable biologic differences between BCC and SCC, and thus each type of epithelial cancer should be addressed separately. The present review provides an overview of the intriguing etiologic link of BCC with UVR and attempts a comprehensive review of recent epidemiologic and molecular evidence that supports this association.


Vertical jump performance and blood ammonia and lactate levels during typical training sessions in elite 400-m runners.
This study described the effects of 6 typical high-intensity intermittent running training sessions of varying distances (60-300 m) and intensities (80-105% of the individual best 400-m record time) on blood ammonia and lactate concentration changes and on vertical jumping height, in twelve 400-m elite male runners. At the end of the training sessions, similar patterns of extremely high blood lactate (14-23 mmol.L) and ammonia levels (50-100 mumol.L) were observed. Vertical jumping performance was maintained during the initial exercise bouts up to a break zone of further increase in the number of exercise bouts, which was associated, especially in subjects with the highest initial vertical jump, with a pronounced decrease (6-28%) in vertical jumping performance, as well as with blood lactate concentrations exceeding 8-12 mmol.L, and blood ammonia levels increasing abruptly from rest values. This break zone may be related to signs of energetic deficiency of the muscle contractile machinery associated with the ability to regenerate adenosine triphosphate at high rates. It is suggested that replacing some of these extremely demanding training sessions with other intermittent training sessions that preserve muscle generating capacity should allow elite athletes to practice more frequently at competitive intensity with lower fatigue.


The influence of reading direction on hemianopic reading disorders.
Hemianopic reading impairment is a consequence of a visual field defect to either the right or the left side and is characterized by an increased reading time and reduced reading performance. Depending on the side of the visual field defect, reading will be affected differently: Patients suffering from a visual field defect to the right side have noticeable difficulties in reading fluently with slowing. Patients suffering from a visual field defect to the left usually struggle to find the beginning of a line and read more fluently. It was suggested in the literature that changing the reading direction from horizontal to vertical may be a training strategy to reduce reading problems in patients with hemianopia. The aim of the study was to investigate the influence of reading direction on reading speed in patients with left- or right-sided visual field defects and in healthy controls. In 13 patients with hemianopia and in 13 age-matched controls, reading speed was calculated for texts in standard as well as in clockwise rotated orientation of 90, 180, and 270°. In both groups, text rotation reduced reading speed compared to standard reading. Patients with left-sided hemianopia had the greatest reduction after text rotation. Patients with right-sided hemianopia had the smallest speed reduction in 90° vertically rotated texts. Text rotation has different effects in left- or right-sided hemianopia patients. For patients with left-sided heminanopia, rotation of the text may not be a helpful training strategy, for right-sided hemianopia vertical rotation of the text of 90° may be a beneficial training strategy to reduce reading deficits.


Exploring the Utility of Theory-Informed Methodological Approaches in Youth Harassment Research.
In comparison to research on youth bullying, less research has been dedicated to youth harassment experiences in school. This study seeks to illustrate youth harassment experiences in school through three theoretically informed methodological approaches to modeling youth victimization: binary, cumulative risk, and attributional approaches. Data come from the 2015 Vermont School Climate Pilot Survey ( N = 2,589 students). Students with complete harassment information ( N = 2,481) were included. Using theoretically informed methodological approaches, regression models examined the associations between experiencing harassment (binary, attributions, and cumulative) and school connection, safety, and equity. About 16% of the sample experienced some form of harassment during the current school year (2014-2015). The most prominent attributions of harassment include weight (40%), sex (27%), and race (22%). After controlling for sociodemographics, ever experiencing harassment was associated with lower school safety, -0.73 (β), p < .001, lower connection with school, -0.52 (β), p < .001, and lower perceived equity, -0.77 (β), p < .001. Experiencing harassment is negatively related to school climate. The results from these analyses underscore the negative relationship among harassment victimization and several important indicators of school climate including student connection, perceived safety at and to/from school, and perceived equity of school. Theoretically informed methodological approaches in youth harassment research should be advanced to comprehensively assess the relationship between harassment victimization and harassment attributes on the social, academic, and behavioral development of youth.


Autoantibody profiles in juvenile arthritis.
Serologic and correlational testing was performed in a series of 65 patients diagnosed as having juvenile arthritis (JA) and in 21 age matched controls to detect the presence of antinuclear antibodies (ANA), antibodies to ssDNA, IgM and IgG rheumatoid factor (RF), immune complexes (IC) and antibodies to bovine type I and human type II collagen. ANA were found in 51% of the JA patients; the highest incidence (75%) was noted in the pauciarticular onset disease group. Low levels of anti-ssDNA antibodies were detected in 22% of the patients, all of whom had active disease. IgM RF was detected in 35% of the JA patients but only 6% of patients had IgG RF. Similarly, about one fourth of the JA patients had IC detected by the Clq assay. Antibodies to bovine type I and human type II collagen were noted in about 12% of the JA patients.


Clinical characteristics and therapeutic outcomes of elderly patients with chronic myeloid leukemia: A retrospective multicenter study.
We aimed to investigate whether older age leads to limitations in the starting dose of imatinib in daily treatment of chronic myeloid leukemia, and to determine the compliance of elderly patients with tyrosine kinase inhibitors (TKI) therapy. Data including the clinical characteristics, therapeutic outcomes and compliance with TKI therapy of elderly patients with chronic myeloid leukemia aged >65 years were collected from 13 institutions in Turkey, retrospectively. A total of 69 patients (27 [39%] men, 42 [61%] women) were evaluated retrospectively. The median age of the patients was 71 years (range 66-85 years). Of the patients, 66 (96%) were in the chronic phase and three (4.3%) were in the accelerated phase when diagnosed. A total of 63 (91.3%) patients were receiving imatinib as the first-line therapy. The initial dose of imatinib was 400 mg/day in 59 patients (93.6%). Imatinib treatment induced 57 (90.5%) complete hematological responses at 3 months, 29 (46%) complete cytogenetic responses at 6 months and 49 (77.7%) major molecular responses at 12 months. As a result, nilotinib and dasatinib were used in 14 patients as second-line therapy. Second-line TKI induced nine complete hematological responses (64.3%) at 3 months, four complete cytogenetic responses (28.6%) at 12 months and seven major molecular responses (50%) at 18 months. A total of 56 of the patients (81.2%) are still alive. The median overall survival and progression-free survival rates were 35 months (range 1-95 months) and 17 months (range 0.8-95 months), respectively. Elderly patients should receive TKI according to the same guidelines that apply to younger patients.


Emergency medical services interval and mortality in significant head injury: a retrospective cohort study.
Recent interest has focused on reorganizing emergency medical services (EMS) for English traumatic brain injury (TBI) patients, with bypass of nonspecialist hospitals and direct transportation to distant neuroscience centres. This may expedite specialist neurocritical care and neurosurgical interventions, but risks harms from prehospital deterioration and delayed resuscitation. We therefore aimed to investigate the effect of EMS interval on outcome following head injury. We performed a multicentre cohort study examining adult patients with significant TBI (head region abbreviated injury scale ≥3) enrolled in the Trauma Audit and Research Network trauma registry between 2005 and 2011. The association between EMS interval and mortality in patients directly admitted to specialist neuroscience centres was explored using bivariate and multivariate logistic regression and propensity score matching analyses. In all, 7149 eligible patients presented directly to specialist neuroscience centres during the study period. Adjusted odds ratios for mortality showed no association between EMS interval and mortality, varying from 0.46 (95% confidence interval 0.1-2.6) for EMS intervals under 20 min to 0.67 (95% confidence interval 0.4-1.2) for EMS intervals more than 120 min (reference EMS interval 40-60 min). This lack of association was also observed following matching using propensity scores, with no significant difference apparent in mortality between EMS intervals less than 60 min and more than 60 min (17.85 vs. 17.0%, P=0.826). These results were unaffected in sensitivity analyses examining missing covariate data or unmeasured outcomes. The lack of observed association between EMS interval and mortality may not preclude bypass of significant TBI patients, with concomitantly prolonged primary transfers from the scene of injury to distant specialist centres. However, given the limitations of registry data, our results should be interpreted with caution.


A human IgG receptor of group A streptococci is associated with tissue site of infection and streptococcal class.
The distribution of receptors for immunoglobulins of several different isotypes was examined for group A streptococcal isolates derived from skin and nasopharyngeal sites. Although human IgG-Fc receptor activity was a variable property of group A streptococci, found among 61% of all isolates tested, it was largely restricted to well-defined subpopulations. Human IgG-binding activity was observed among nearly all impetigo isolates examined. In addition, the expression of the class II M protein molecule (one of two broad antigenic classes of the major virulence factor) and opacity factor (a lipoproteinase) was almost invariably accompanied by human IgG binding, regardless of tissue site of infection. In contrast to class I impetigo isolates, class I nasopharyngeal isolates were relatively devoid of human IgG-binding activity. The data suggest that the presence or absence of human IgG-binding activity correlates with certain diseases caused by group A streptococci.


From function to esthetics: anterior or occlusal compromises to esthetics.
Increased patient expectations together with improved diagnostic, material, and surgical advances have expanded the boundaries of esthetic dentistry. To optimize functional and esthetic success, existing techniques are being enhanced through careful patient selection and management of the occlusion. During the period from 1991 to 1992, several areas relating anterior or occlusal compromises to esthetics have been identified. These include: dental and skeletal malocclusion, periodontal esthetic defects, restorative materials and laboratory techniques, tooth arrangement and maxillomandibular relations, and implant dentistry. This paper reviews some of the literature on these areas during this period.


Anti-dsDNA antibody induces soluble fibronectin secretion by proximal renal tubular epithelial cells and downstream increase of TGF-β1 and collagen synthesis.
The level of anti-dsDNA antibodies correlates with disease activity in lupus nephritis, but their role in pathogenic mechanisms remains to be defined. We investigated the effect of anti-dsDNA antibodies isolated from lupus nephritis patients on fibronectin synthesis and downstream fibrogenesis in proximal renal tubular epithelial cells (PTEC). Kidney biopsies were obtained from patients with active severe proliferative lupus nephritis. In vitro studies with cultured PTEC were performed to investigate the effect of human polyclonal IgG anti-dsDNA antibodies and mycophenolic acid (MPA). The role of IL-6, IL-8, MCP-1, TNF-α, TGF-β1, and MAPK and PKC signaling pathways on soluble and cell-associated fibronectin synthesis was investigated using neutralizing antibodies or specific inhibitors. The effect of exogenous endotoxin-free soluble fibronectin on downstream fibrotic processes was also examined. Fibronectin expression was markedly increased in the tubulo-interstitium of lupus nephritis renal biopsies and it co-localized with IgG deposition. Anti-dsDNA antibodies significantly increased both secreted and cell-associated fibronectin, through prior activation of ERK, p38 MAPK, JNK, PKC-α and PKC-βII. There was downstream induction of IL-6, IL-8, MCP-1, TNF-α and TGF-β1. MPA inhibited the induction of inflammatory and fibrotic processes by anti-dsDNA antibody. Exogenous soluble fibronectin induced TGF-β1 secretion and type I collagen synthesis in PTEC in a dose-dependent manner. Our data demonstrate that anti-dsDNA antibody contributes to tubulo-interstitial fibrosis in lupus nephritis through its action on PTEC. Anti-dsDNA antibody induces both cell-associated and soluble fibronectin secretion in PTEC, the former adds to extracellular matrix deposition while the latter amplifies the fibrotic process through induction of TGF-β1 and collagen type I. The pro-fibrotic effects of anti-dsDNA antibody are ameliorated by MPA.


Psoriasis: symptoms, treatments and its impact on quality of life.
Psoriasis affects between 1% and 3% of the population and there is no cure for this chronic skin disease. This article gives an overview of the condition and available treatments. It focuses on managing symptoms, the range of medications available and the impact this chronic condition can have on a sufferer's quality of life. The article looks at medication non adherence remaining the biggest obstacle to management of the condition and the debilitating effect psoriasis can have on an individual's self-esteem and general well-being. It concludes by considering the role of patient support services such as the touch programme.


Complications after Hypospadias Correction: Prognostic Factors and Impact on Final Clinical Outcome.
The purpose of this study was to analyze the influence of patient and treatment characteristics on the occurrence of complications after hypospadias correction and the impact of complications on final clinical outcome. The study cohort consisted of 205 hypospadias patients who had surgery in the Medical Centre Leeuwarden (1996-2011). Patient and treatment characteristics were hypospadias severity (preoperative meatal location and chordee), number of planned surgeries, reconstruction technique, operation year, and patient's age at the time of surgery. The final clinical outcome was measured with the Hypospadias Objective Scoring Evaluation (HOSE) (maximum score = 16) and compared between patients with and without complications. Sixty-four patients (31%) had complications, most of which were fistulas (n = 40). An increased complication risk was seen in patients with severe hypospadias (preoperative proximal meatus or chordee), multistage reconstruction, reconstruction techniques other than Mathieu, and surgeries performed before 2005. Uncomplicated treatment resulted only in a marginally higher HOSE (15.7) compared with complicated treatment (15.4). Fistulas and multiple complications reduced clinical outcome more (15.3 and 14.9, respectively), while urinary tract infections, wound dehiscence, or prepuce related complications did not (16.0, 16.0, and 15.8, respectively). The complication risk after hypospadias correction is influenced by hypospadias severity and type and year of reconstruction. Certain, but not all complications diminish final clinical outcome.


Alteration of chromosome positioning during adipocyte differentiation.
Chromosomes are highly restricted to specific chromosome territories within the interphase nucleus. The arrangement of chromosome territories is non-random, exhibiting a defined radial distribution as well as a preferential association with specific nuclear compartments, which indicates a functional role for chromosome-territory organization in the regulation of gene expression. In this report, we focus on changes in adipocyte differentiation that are related to a specific chromosomal translocation associated with liposarcoma tumorigenesis, t(12;16). We have examined the relative and radial positioning of the chromosome territories of human chromosomes 12 and 16 during adipocyte differentiation, and detected a close association between the territories of chromosomes 12 and 16 in differentiated adipocytes, an association not observed in preadipocytes. Although further studies are required to elucidate the underlying reasons for the adipocyte-specific translocation of chromosomes 12 and 16, our observations indicate that alteration of relative chromosome positioning might play a key role in the tumorigenesis of human liposarcomas. In addition, these results demonstrate the potential impact of higher order chromatin organization on the epigenetic mechanisms that control gene expression and gene silencing during cell differentiation.


Genetic studies of familial amyloid polyneuropathy in the Arao district of Japan: I. The genealogical survey.
A genealogical survey of familial amyloid polyneuropathy in the Arao district of Japan was undertaken, and the data were analysed statistically. The survey revealed 92 patients (46 males and 46 females) in 9 families. Thirty-one of the patients (16 males and 15 females) are alive. For 44 patients, the mean age of onset was 34.1 years (range 20-46 years). The penetrance corrected for late onset was 83.5% by Morton's method. The segregation ratio of 18 sibships in which one of the parents was affected was 36 +/- 6% for single ascertainment and 46 +/- 5% for complete ascertainment; the corresponding figures of 14 sibships in which neither parent was affected was 30 +/- 7% for single ascertainment and 40 +/- 6% for complete ascertainment. The results of the analysis were consistent with the assumption of an autosomal dominant mode of inheritance.


Portosystemic arteriovenous fistula. Case report.
A case of the rare portosystemic arteriovenous fistula is presented. This lesion, although basically simple, is not trivial. The predominant cause of death is variceal bleeding. Most often, the fistulas are due to rupture of an aneurysm of the hepatic or splenic artery, gunshot wound of the abdomen, or the use of mass ligature during abdominal surgery. The treatment is excision when possible, reconstruction of the vessels when vessels cannot be sacrificed, and ligation when everything else fails. Angiography is indispensible in defining the fistula. Because of the circulatory strain produced by these fistulas and of the danger of portal hypertension even in the asymptomatic patient, the presence of a portosystemic arteriovenous fistula is sufficient indication for surgical treatment.


Investigating cognitive ability and self-reported driving performance of post-stroke adults in a driving simulator.
Background Safe driving is a complex activity that requires calibration. This means the driver can accurately assess the level of task demand required for task completion and can accurately evaluate their driving capability. There is much debate on the calibration ability of post-stroke drivers. Objectives The aim of this study was to assess the cognition, self-rated performance, and estimation of task demand in a driving simulator with post-stroke drivers and controls. Methods A between-groups study design was employed, which included a post-stroke driver group and a group of similarly aged older control drivers. Both groups were observed driving in two simulator-based driving scenarios and asked to complete the NASA Task Load Index (TLX) to assess their perceived task demand and self-rate their driving performance. Participants also completed a battery of psychometric tasks to assess attention and executive function, which was used to determine whether post-stroke cognitive impairment impacted on calibration. Results There was no difference in the amount of perceived task demand required to complete the driving task. Despite impairments in cognition, the post-stroke drivers were not more likely to over-estimate their driving abilities than controls. On average, the post-stroke drivers self-rated themselves more poorly than the controls and this rating was related to cognitive ability. Conclusion This study suggests that post-stroke drivers may be aware of their deficits and adjust their driving behavior. Furthermore, using self-performance measures alongside a driving simulator and cognitive assessments may provide complementary fitness-to-drive assessments, as well as rehabilitation tools during post-stroke recovery.


Direct evidence that inflammatory multinucleate giant cells form by fusion.
Multinucleate giant cells (MGC) are believed to be formed by fusion of macrophages. In a chimaeric mouse composed of two histoincompatible strains each homozygous for one of the two isoenzymic forms of glucose-6-phosphate isomerase it was found that hybrid enzyme was produced in MGC-rich leucocytic exudates. This hybrid can only occur if nuclei of the two different strains reside within a common syncytial cytoplasm, demonstrating unequivocally that macrophage fusion occurred between cells of the two strains. Since the two strains were histoincompatible it appears that no strain specific recognition is necessary for fusion to occur.


Lectin from Canavalia villosa seeds: A glucose/mannose-specific protein and a new tool for inflammation studies.
With important carbohydrate binding properties, lectins are proteins able to decipher the glycocode, and as such, they can be used in bioassays involving cell-cell communication, protein targeting, inflammation, and hypernociception, among others. In this study, a new glucose/mannose-specific lectin from Canavalia villosa seeds (Cvill) was isolated by a single affinity chromatography step in a Sephadex® G-50 column, with a purification yield of 19.35mg of lectin per gram of powdered seed. Analysis of intact protein by mass spectrometry showed the lectin is composed of three polypeptide chains, including a 25.6kDa α chain, 12.9KDa β, and 12.6 KDa γ fragments, similar to the profile of ConA-like glucose/mannose-specific lectins. Partial sequence of the protein was obtained by MS-MALDI TOF/TOF covering 41.7% of its primary structure. Cvill presented sugar specificity to d-glucose, α-methyl-d-mannoside, d-mannose, and glycoproteins fetuin and ovoalbumin. The lectin characterization showed that Cvill presents high stability within a broad range of pH and temperature, also showing average toxicity against Artemia nauplii. The proinflammatory effect of Cvill was observed by induction of paw edema and hypernociception in mice, with the participation of the carbohydrate binding site, showing its potential to be used as tool in inflammation studies.


Ruthenium-catalyzed α-(hetero)arylation of saturated cyclic amines: reaction scope and mechanism.
Transition-metal-catalyzed sp(3) C-H activation has emerged as a powerful approach to functionalize saturated cyclic amines. Our group recently disclosed a direct catalytic arylation reaction of piperidines at the α position to the nitrogen atom. 1-(Pyridin-2-yl)piperidine could be smoothly α-arylated if treated with an arylboronic ester in the presence of a catalytic amount of [Ru3(CO)12] and one equivalent of 3-ethyl-3-pentanol. A systematic study on the substrate and reagent scope of this transformation is disclosed in this paper. The effect of substitution on both the piperidine ring and the arylboronic ester has been investigated. Smaller (pyrrolidine) and larger (azepane) saturated ring systems, as well as benzoannulated derivatives, were found to be compatible substrates with the α-arylation protocol. The successful use of a variety of heteroarylboronic esters as coupling partners further proved the power of this direct functionalization method. Mechanistic studies have allowed for a better understanding of the catalytic cycle of this remarkable transformation featuring an unprecedented direct transmetalation on a Ru(II)-H species.


Whither autoimmunity: the lessons of anti-CCP and B cell depletion.
The most difficult component to understand in autoimmune disease has been the issue of causation. In contrast, there have been enormous gains in improved diagnostics as well as improved therapy. Indeed, the use of biologics have changed the profile of numerous autoimmune diseases. In this issue, we discuss two such aspects. Firstly, we place in perspective the use of anti-citrullinated protein antibodies in rheumatoid arthritis. Second, we discuss the increasing use of B cell depletion in the treatment of autoimmunity. Clinical Reviews in Allergy and Immunology is a unique venue for these themes because it covers the spectrum of allergy through autoimmunity. Indeed, we also present a special paper on the relationships of the hepatitis B virus and autoimmunity. Although the Th1 to Th2 dichotomy is well known to both murine and human immunologists, it is really in the study of specific inflammatory responses that they are correctly placed in the perspective of the continuum of immunopathology.


Decompression and distraction-derotation arthrodesis for degenerative spondylolisthesis.
Degenerative spondylolisthesis is the result of chronic disc degeneration with secondary segmental spinal instability. Localized collapse and translational and rotational vertebral subluxation result in low back pain and radiculopathy. Twenty patients with L4-5 degenerative spondylolisthesis having back pain and radiculopathy were treated with a combination of decompressive laminectomy and distraction arthrodesis with short parallel Harrington rods. Patients were ambulated immediately after operation. Minimum follow-up was 2 years (average, 31.6 months). Satisfactory results were obtained in 17 patients (85%). No intraoperative complications occurred. The spondylolisthesis progressed significantly in one patient and the Harrington rods loosened in another. The procedure appears to assist in reducing pathologic motion contributing to low back pain and to relieve traction or compression forces on neural structures by restoring spinal canal anatomy.


[Effect of acupoint-catgut-embedding intervention on type II diabetic rats].
To observe the effect of acupoint-catgut-embedding therapy on blood lipid and insulin levels in type I diabetes mellitus rats;s as to reveal its mechanism underlying improvement of pancreatic functions. Thirty SD rats were divided into normal, model and treatment group. The type I diabetes model was established by feeding the rats with high-fat diet and intraperitodneal injection of streptozotocin (STZ). Catgut-embedment was performed in acupoint "Zhongwan" (CV 12)-"Xiawan" (CV 10), "Yishu"-"Ganshu" (BL 18), etc., once every 20 days, twice altogether. Fasting blood glucose (FBG) content was assayed by glucose oxidase method; glycosylated hemoglobin A 1 c (HbA 1 c) assayed by ELISA, and serum fasting C-peptide(FC-p) deterriined by chemiluminescence method; and the triglyceride (TG), total cholesterol (TC), and serum insulin (INS) levels were detected by enzymatic method, separately. The rat's pancreas tissues were fixed with 4% paraformaldehyde and cut into sections (4 Im in thickness) and stained with H. E. method. After modeling, the levels of FBG, HbA 1 c, INS and FC-p, TG, TC were significantly increased in the model group in comparison with those of the normal group (P<0.05), while INS sensitive. index was apparently decreased in the model group (P<0.05). Following catgut-embedding treatment, changes of the above-mentioned indexes were all remarkably reversed (P<0.05), and H.E. staining showed an improvement of the injured pancreatic tissue and islet cells. Catgut-embedding therapy can reduce fasting blood glucose and insulin resistance, and improve lipid metabolism in type I diabetic rats, which may contribute to its effect in protecting pancreatic islet cells.


Alcohol use and reported physician visits in older adults.
In general, older adults use a greater proportion of health care services than other age segments of the population. Alcohol abusers also use a greater proportion of health care services than alcohol nonabusers. Therefore we expected that among older adults, alcohol consumption would be positively related to health service use. In a sample of older adults, this study examined the relationship between alcohol consumption and an indicator of health service use--the self-reported number of physician visits. Data obtained on adult participants in the 1990 National Health Interview Survey, age 60 and older (n = 10,522), were examined. The number of physician visits was regressed on health status and alcohol consumption measures. Counter to a priori expectations, alcohol consumption was negatively associated with physician visits. This finding was obtained after adjusting for respondent sex and health status measures. Other research suggests that the rates of alcohol-related hospital admissions among older adults are on par with those of myocardial infarctions--an indication that harmful use of alcohol in older adults is going undetected. We found heavier alcohol consumption associated with fewer physician visits. This underscores the need for a better understanding of the role alcohol serves in the health perceptions of older adults. Broadening our knowledge in this area would be of benefit not only to the well-being of individuals also for health services policy considerations.


A comparative study of the effect of vitamin E-nicotinate and the combination of vitamin E and nicotinic acid on the hydrogen peroxide-induced platelet aggregation.
The inhibitory effect of vitamin E-nicotinate upon the hydrogen peroxide (H2O2)-induced platelet aggregation was found to be greater than that of either vitamin E alone or the combination of vitamin E and nicotinic acid. Nicotinic acid showed no inhibitory effect. It was suggested that the effect of vitamin E-nicotinate was not due to the additive effect of vitamin E and nicotinic acid produced by hydrolysis, but to the unique and distinctive property of vitamin E-nicotinate itself.


Temperature and bacterial profile of post chill poultry carcasses stored in processing combo held at room temperature.
Post chill whole poultry carcasses from a commercial processing plant were stored in a processing combo at room temperature (70 °F/21 °C) for 54 h to mimic the scenario of temperature abuse before further processing. Temperature data were collected in 1-min intervals and averaged each hour by 9 temperature data loggers. Two linear regressions were developed for the combo and internal breast temperature and slopes were nearly identical. Microbial data was collected by performing whole bird carcass rinses that were enumerated for aerobic plate count (APC), Enterobacteriaceae, Escherichia coli, and total coliform. Samples were collected from the chiller chute at time zero for initial bacterial counts. Carcass sampling continued once the internal breast temperature achieved 45 °F (7 °C 10 h) and continued every 2 h until the final internal breast temperature was 63 °F (17 °C 54 h). Linear regressions were developed for the first 26 h, which exhibited no statistically significant growth except for Enterobacteriaceae. A 2nd linear regression (28 to 54 h) exhibited significant growth for all analyses. Overall, APC increased from a log(10) colony forming unit (CFU)/mL count of 2.86 to 7.02, Enterobacteriaceae increased from 0.66 to 6.64, coliform increased from 0.72 to 4.81, and E. coli increased from 0.53 to 4.45. Denaturing gradient gel electrophoresis was performed to detect changes in the bacterial populations, which indicated 95% similarity within sampled groups, but the overall percent similarity among samples collected over 54 h was 8%. From the data, microbial growth demonstrates a period of 26 h for minimal growth; therefore, the product could be further processed rather than designated as waste.


Characterization of regulatory T cells in tumor suppressive microenvironments.
Increasing evidence suggests that immunotherapy is a promising strategy for treating patients with invasive and metastatic cancers, but clinical trails are discouraging so far. Recent studies showed that several subsets of regulatory tumor-infiltrating lymphocytes (TILs), such as naturally occurring CD4(+)CD25(+) regulatory T cells (Treg), and adaptively induced Treg cells of Tr1, Th3, CD8(+), as well as gammadelta Treg cells, have been identified in human cancers. These Treg-cell subsets form a tumor suppressive microenvironment that presents a major barrier to successful anti-tumor immunotherapy. Thus, how to modulate the Treg-cell function in tumor microenvironments is essential for cancer treatment and elimination. To date, there is no unique and selective marker for all subsets of Treg cells, and a combination of assays for Treg-associated markers and suppressive activity is still the most common way used to define these tumor-associated Treg cells. In this chapter, we describe protocols to purify and characterize tumor-associated Treg cells from peripheral blood and TILs of cancer patients, which is critical for predicting clinical outcomes and monitoring the effects of tumor immunotherapy.


Predictors of milk consumption in a population of 17- to 35-year-old military personnel.
The purpose of this investigation was to survey an entire population of Air Force recruits (N = 32,144) regarding milk consumption and demographic and health-related factors that may predict milk consumption. All subjects were required to fill out a 53-item health survey at the start of basic military training. All recruits who entered the US Air Force from August 1995 to August 1996 participated in this study (N = 32,144). Potential correlates of milk intake were analyzed using Spearman rank order correlations and multiple linear regression. Variables were removed if they did not make a meaningful contribution to variance in milk intake. Because of skewed distributions, several variables were dichotomized (e.g., age: 17 to 24 vs 25 to 35 years). In terms of milk consumption, 51.7% of the respondents reported intake of fewer than 1 serving per day; only 17.9% reported intake of 3 servings or more per day. Milk intake was positively associated with body weight and fruit/vegetable intake and negatively associated with age, education level, reported milk-related gastric distress, physical activity level, dieting frequency, and concern about weight. Gender (women reported lower intake) and ethnicity (minorities reported lower intake) were independently related to milk consumption. Of all respondents, 16.1% reported themselves to have milk-related gastric distress, but rates varied depending on age, gender, and ethnicity (ranging from 10.2% for younger non-Hispanic white men to 60.4% for older Asian men). Despite the efforts of large, costly campaigns designed to increase milk consumption, self-reported milk consumption in young adults is extremely low. Given the importance of dairy products as a major source of calcium in the American diet, dietetics practitioners should assess milk consumption among young adults to ensure sufficient calcium intake to maximize peak bone mass in this group.


Fluorescence line narrowing and Δ-FLN spectra in the presence of excitation energy transfer between weakly coupled chromophores.
The results of simulations of fluorescence line narrowed (FLN) and Δ-FLN spectra of weakly coupled chromophore dimers and trimers, connected by slow (hundreds of picoseconds) excitation energy transfer and embedded in amorphous solids such as proteins, are presented. The model includes wavelength-dependent excitation energy transfer (EET) rate distributions converted to nonidentical sub- site distribution function (sub-SDF) (one for each EET rate), as well as spectral hole burning in pigments excited via EET. Emission of the donor molecules and realistic EET probability dependence on the donor-acceptor energy gap are also included. The shapes of the FLN and Δ-FLN spectra are very sensitive to even small variations of interpigment coupling in this weak-coupling regime, and proper modeling is essential for extracting correct parameters from the experimental spectra. Applications of the model to the trimeric FMO complex and the dimeric cytochrome b6f are demonstrated.


Corrigendum.
Hubbard MA, Khalil AA, Schoeff SS, et al. Nanoimmunoassay to detect responses in head and neck cancer: feasibility in a mouse model. Otolaryngol Head Neck Surg. 2014;151:92-99. (Original DOI: 10.1177/0194599814528302 ).


A cytogenetic study on the teaching staff of a polluted school with a questionable increased incidence of malignancies.
Exposure to pollutants, in particular polychlorinated biphenyls (PCB), was established at a school built in 1966. Because of a statistically conspicuous increased frequency of breast cancer observed in the teachers of the school this study was performed to ascertain whether the teachers in the polluted school have an increased level of micronucleated cells (MN) or sister chromatid exchanges (SCE) as an expression of a raised cytogenetic risk. Teachers in a directly adjacent school served as one control group and those from a school about 30 km away as a second one. Each teacher had to answer a questionnaire and after venous blood samples had been taken, the number of MN and SCE in peripheral lymphocytes were determined. For the teachers in the polluted school, in addition, the length of stay in the building during the last month and year was recorded. Thereby no correlation with the number of MN and SCE was proven. In comparison with the two control groups, neither the number of MN nor SCE was increased in the teachers of the polluted school. Even if their predictive value for cancer risk assessment is disputed, MN and SCE have a high rating as standard procedures in the proof of an exposure to genotoxic agents. This study thus does not provide any evidence that, for the teachers in the polluted school, a relevant exposure to genotoxic agents exists.


Assessment of urea removal in haemodialysis and the impact of the European Best Practice Guidelines.
Dialysis adequacy, assessed by urea kinetics, is an important determinant of patient outcome, and is therefore an important clinical performance indicator. In this perspective, renal registry data may be useful to compare practices across countries. To serve that purpose available data should be comparable and preferably collected using a standardized procedure. The aim of this study, initiated by the European Renal Association-European Dialysis and Transplantation Association (ERA-EDTA) QUality European STudies (QUEST) initiative, was to make an inventory of the different methods used to determine urea kinetic measurements in the light of the European Best Practice Guidelines. Via their national and regional registries, European haemodialysis centres were invited to complete a questionnaire regarding their practice of measuring dialysis adequacy. Fourteen regional or national registries among 51 sent back 255 questionnaires. Great variability in the methodology to assess Kt/V was observed. The urea reduction ratio (URR) was used alone by 37% (in association 46%) of dialysis centres, spKt/V by 25% (35%) and on-line clearance by 4% (12%), whereas only 10% (13%) used eKt/V, as recommended by EBPG. Forty percent of centres measured urea removal less than once a month, 6% of which never measured urea removal and 9% only every 6 months or less frequently. Despite the fact that the use of URR is not recommended by EBPG, it was the most commonly used indicator to measure urea removal, whereas eKt/V was only used by a small minority of centres. This study allowed us to point out the need to standardize definitions and procedures and to develop an effective plan for implementation of the guidelines.


Transient IgG subclass deficiencies in newly diagnosed diabetic children.
In 27 children (15 males and 12 females) with insulin-dependent diabetes mellitus (IDDM), aged 1.2-13.5 years (mean 9.9 +/- 3.6 years) we investigated immunoglobulins (IgG, IgA, IgM), IgG subclass levels and islet-cell antibodies (ICA) at diagnosis and at 6 and 12 months after disease onset. At diagnosis, IgG levels were lower than -2SD in 7 patients (26%), IgA in 1 (3.7%), IgM in 1 (3.7%). IgG subclass levels were below the 3rd percentile in 13 patients (48.1%); in particular IgG1 in 7 (26%), IgG2 in 3 (11.1%), IgG3 in 2 and IgG4 undetectable in 1 case. In 3 out of the 13 patients combined IgG1-IgG3, IgG1-IgG2 and IgG1-IgG4-IgA deficiencies were observed. ICA were greater than 20 Juvenile Diabetes Foundation units in 17/27 patients. The HLA-DR2 frequency was higher in patients with IgG subclass deficiency than in patients with normal IgG subclass levels. During follow up, IgG levels normalized in 6 patients while IgA and IgM did not change. IgG1 normalized in 5 out of the 7 patients, IgG2 in all patients while IgG3 and IgG4 did not change. One year later ICA were still present in 8/27 patients. The hypogammaglobulinaemia and IgG subclass deficiencies observed in our patients could have either a genetic or an acquired basis.


Psychometric validation of the neuropathic pain symptom inventory for its use in Spanish.
Clinical instruments are required for the assessment of neuropathic pain (NP). The primary aim of this study was to perform a complete psychometric validation of the Neuropathic Pain Symptom Inventory (NPSI) in Spanish patients. A linguistically validated version in Spanish of the NPSI and other clinical instruments for NP were administered on two occasions separated by at least one month to 548 patients suffering from chronic NP. The authors evaluated the responsiveness, the construct validity, and the internal structure of the NPSI by means of, respectively, receiver operating characteristic (ROC) curves analysis and calculation of reliable change indices, a multitrait-multimethod (MTMM) design, and primary component analysis. Internal consistency and test-retest reliability were evaluated, respectively, by calculating several Cronbach's alpha coefficients and intraclass correlation coefficients of some scores selected appropriately. The areas under the ROC curves were greater than 0.85. The MTMM design found convergent-discriminant correlations correctly aligned for all NPSI subscores in the first assessment, and for all but paresthesia/dysesthesia subscores in the second assessment. The five components of the NPSI described by its authors were confirmed on one occasion, but the "electric shocks" and "stabbing" items did not associate consistently, as in the original version, the first time the NPSI was administered. All reliability coefficients were above 0.70. The Spanish NPSI has good concurrent and construct validity and is reliable for a wide range of patients with NP. One exception to the original structure was found affecting one item, presumably relating to a cultural feature.


[Relation between prognosis and the Su-PS skin reaction in patients with non-resected primary lung cancer receiving OK-432].
Chemotherapy and administration of OK-432 were performed concomitantly in 49 cases of inoperable primary lung cancer, and the Su-PS skin reaction was measured. In the group of patients under 60 years of age, the maximum diameter of the reaction after chemotherapy tended to be large, and evaluation of the results showed that the maximum diameter tended to be large in the group showing tumor contraction effects. In a comparison of the prognosis between the group which survived for less than 6 months and that which survived for 6 months or longer, there was no significant difference between them before administration of OK-432, but when the maximum reaction diameter after chemotherapy was compared, that in the group which survived for 6 months or longer was significantly stronger (p less than 0.05). The Su-PS skin reaction at the time of administration of OK-432 is therefore considered to be a useful immunological parameter for predicting the results of treatment and also for prognosis.


Adaptive Fuzzy Tracking Control for Strict-Feedback Markov Jumping Nonlinear Systems With Actuator Failures and Unmodeled Dynamics.
In this paper, an adaptive fuzzy tracking controller is developed for a class of strict-feedback Markovian jumping systems subjected to multisource uncertainties. The unpredictable actuator failures, the unknown nonlinearities, and the unmodeled dynamics are simultaneously taken into consideration, which evolve according to the Markov chain. It is noted that the elements in the transition rate matrix of the Markov chain are not fully available. In virtue of the norm estimation approach, the challenges caused by the complex multiple uncertainties and actuator failures are effectively handled. Furthermore, to compensate for the unavailable switching nonlinearities, the fuzzy logic systems are employed as online approximators. As a result, a novel adaptive fuzzy fault-tolerant tracking control structure is constructed. The sufficient condition is provided to guarantee that the studied system is stochastically stable. Finally, a number of illustrative examples are employed to demonstrate the effectiveness of the proposed methodology.


Novel evidence for paternal dietary influences on cognitive and neural functions in offspring mice.


Tardive dyskinesia.
The basic pathogenesis of tardive dyskinesia appears to relate to chronic pharmacologic denervation of specific dopaminergic receptor sites in the striatum. The pathophysiology of the disorder relates to the resultant denervation hypersensitivity. The mainstay of treatment includes withdrawal of neuroleptics where feasible and the use of dopamine-depleting agents. Enhancement of the striatal cholinergic input offers potential ancillary benefit to the alleviation of abnormal movements. The benefit of manipulating other neurotransmitters remains experimental. Treatment of tardive dyskinesia with neuroleptics themselves is clearly treatment with the presumed offending agent, and should be avoided. This shortsighted therapy may temporarily abate the pathophysiology of the condition but serves to aggravate its pathogenesis.


Whole-cell patch-clamp recordings from identified spinal neurons in the zebrafish embryo.
We describe a preparation for obtaining patch-clamp recordings from identified embryonic spinal cord interneurons, motoneurons and sensory neurons in an in vivo zebrafish preparation. This preparation is used to study the spatial and temporal patterns of spontaneous and touch-evoked electrical activity during the initial development of circuitry in the spinal cord. The combination of these physiological techniques with the powerful genetic and molecular tools available in the zebrafish has the potential to increase our understanding of the complex interactions between genes and electrical activity during the development of the vertebrate nervous system.


Design of a slow-release capsule using laser drilling.
Conventional hard gelatin capsules were made GI-tract resistant by formalin vapor treatment. The residual formalin content was 80 micrograms/capsule 24 h after treatment, which decreased with increased storage time. An in vitro GI-tract resistance test was performed by exposing the capsules to simulated gastric fluid for 4 h and then to simulated intestinal fluid for 4 h at 37 degrees C. The resistance was further confirmed by in vivo X-ray studies in human volunteers. Minute pores were drilled on the hardened shells of the capsules with a carbon dioxide gas laser. This permitted the slow passage of the encapsulated tetracycline hydrochloride when subjected to 0.1 M HCl in in vitro dissolution studies. In vitro drug release from these capsules followed zero-order kinetics after an initial lag period of 30 min. The factors influencing the in vitro release rate of tetracycline hydrochloride from these capsules are discussed.


Mitral valve prolapse in women with oral contraceptive-related cerebrovascular insufficiency. Associated persistent hypercoagulable state.
We examined a group of former oral contraceptive (OC) users, who had experienced cerebrovascular insufficiency, for the presence of hypercoagulable states. We found hypercoagulability in this group in the form of decreased plasma antithrombin III activity, increased platelet coagulant activity, and elevated plasma beta-thromboglobulin level. Certain characteristics (cigarette smoking, vascular headache, hyperlipidemia, and mitral valve prolapse) were encountered with increased frequency among former OC users who had experienced cerebrovascular insufficiency. The association of mitral valve prolapse with OC-related cerebrovascular insufficiency was particularly striking. We propose that preexisting hypercoagulable states, such as may exist in a subset of individuals with mitral valve prolapse, will magnify the risk of OC-related cerebrovascular morbidity.


High incidence of symptomatic incisional hernia after midline extraction in laparoscopic colon resection.
The incidence of incisional hernia has not decreased despite the use of laparoscopy for colon resections. The objective of this study is to evaluate the impact of the incision used for specimen extraction on the incidence of incisional hernia after laparoscopic colectomy. Patients who underwent laparoscopic colectomy without stoma at a single university tertiary-care centre from 2003 to 2009 were identified from an operating room database. Patients were contacted by telephone for participation, and underwent physical examination ± ultrasonography for incisional hernia at the specimen extraction site and completed the Body Image Questionnaire. Specimen extraction incisions were classified into midline, transverse and Pfannenstiel groups. Out of a total of 251 patients, 99 patients agreed to participate (68 midline, 7 transverse, 24 Pfannenstiel), while 73 patients refused consent and 79 patients could not be contacted. Patients who refused consent were older (69.8 vs 62.4 years, p = 0.001) but otherwise were similar to participants with respect to gender, malignant disease, postoperative complications and extraction site. Mean length of follow-up was 37.0 months. The overall incidence of incisional hernia was 21% (21/99), being 29 % (20/68) after midline incision compared with 14 % (1/7) after transverse and 0 % (0/24) after Pfannenstiel incisions (p = 0.002). Of patients with incisional hernia, 47 % (10/21) were symptomatic. Patients with incisional hernia had lower cosmetic score (14.4 vs 17.7, p = 0.02) compared with those without, but there was no difference in body image score. There were no differences in body image or cosmesis between the three incisions. There is a high incidence of symptomatic incisional hernia after midline specimen extraction in laparoscopic colectomy, which negatively impacts cosmesis. The risk of hernia may be lower with the use of a transverse or Pfannenstiel incision for specimen extraction.


Recurrent hepatitis C following liver transplant: diagnosis, natural history, and therapeutic options.
Hepatitis C virus (HCV) related cirrhosis is the most common indication for orthotopic liver transplantation (OLT). Updated data suggest worse long-term outcomes for those transplanted with HCV than those transplanted for other indications. Re-infection with HCV post-OLT is universal, therefore diagnosis of recurrence should be based on histological findings in the setting of persistent viremia. Variables associated with worse outcome of recurrent disease include early recurrence, degree of immunosuppression, and donor age. Antiviral therapy has been used in the prevention and treatment of recurrent disease, and can be initiated prior to transplantation, prophylactically after transplantation, and during recurrence. Preliminary studies of pre-transplantation treatment demonstrate virological responses, but tolerance is common. Higher efficacy has been associated with combination therapy for recurrent disease. Adverse effects limit its widespread use.


Rift Valley fever surveillance in mobile sheep flocks in the Nile Delta.
Rift Valley fever (RVF) surveillance was carried out in the Nile Delta by monitoring mobile and stationary sheep flocks for antibodies to RVF virus. Sheep are known to be susceptible to RVF virus infection and experienced severe morbidity in 1977 and 1978 when RVF was epidemic in Egypt. Four hundred six sheep in 32 flocks were surveyed during 1984. Twenty-four sheep from 7 flocks had antibodies to RVF virus detected by hemagglutination inhibition and plaque reduction neutralization tests. Antibodies were found primarily in sheep greater than 3 years of age, although 1- and 2-year-old sheep were included in the sample. No seroconversion was observed among 177 seronegative sheep that were bled successively for a period of 10 months. These results indicate that epizootic RVF was probably not present in the Nile Delta during 1984.


[Ultrathin bronchoscopy].
To evaluate the clinical benefits of ultrathin bronchoscope in the pathological diagnosis of peripheral lung lesions, we routinely used a 2.8 mm outer diameter ultrathin for the peripheral lesions with fluoroscopic guidance. A retrospective analysis was performed on the pathological diagnoses, their accuracy, the optimal number of biopsy specimens. In the final diagnoses of 209 malignancies, 132 patients (63%) obtained their results at first examinations. The diagnostic rates were not different as to the size of the tumor of less than 2.0 cm or more. We have tried to obtain 10 biopsy specimens. The diagnostic rate was 46% at the first biopsy, and reached 90% cumulatively on the 6th attempt. In the final diagnoses of benign lesions 39% received pathological diagnosis at the first bronchoscopy. Pneumothorax was experienced in 6 patients (1.5%). All improved by observation only (4) or by tube drainage (2). In 2 patients, ultrathin scope penetrated visceral pleura. No major bleeding was observed. Ultrathin bronchoscopy is a safe and reliable method to obtain the pathological specimen in the diagnosis of peripheral lesions under fluoroscopic guidance. Pneumothorax was the only complication so far. Ultrathin bronchoscopy may be the procedure of choice for peripheral lesions.


Molecular identification of the Sporothrix schenckii complex.
Sporothrix schenckii, an ascomycetous dimorphic organism that for over a century was recognized as the sole agent of sporotrichosis, a subcutaneous mycosis with a worldwide distribution. However, it has been proposed, based on physiologic and molecular aspects, that S. schenckii is a complex of distinct species: Sporothrix brasiliensis, Sporothrix mexicana, Sporothrix globosa, S. schenckii sensu strictu, Sporothrix luriei, and Sporothrix albicans (formerly Sporothrix pallida). Human disease has a broad range of clinical manifestations and can be classified into fixed cutaneous, lymphocutaneous, disseminated cutaneous, and extracutaneous sporotrichosis. The gold standard for the diagnosis of sporotrichosis is the culture; however, serologic, histopathologic and molecular approaches have been recently adopted for the diagnosis of this mycosis. Few molecular methods have been applied to the diagnosis of sporotrichosis to detect S. schenckii DNA from clinical specimens, and to identify Sporothrix spp. in culture. Until now, Sporothrix is the unique clinically relevant dimorphic fungus without an elucidated genome sequence, thus limiting molecular knowledge about the cryptic species of this complex, and the sexual form of all S. schenckii complex species. In this review we shall focus on the current diagnosis of the sporotrichosis, and discuss the current molecular tools applied to the diagnosis and identification of the Sporothrix complex species. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012).


Loss of metacarpal bone density predicts RA development in recent-onset arthritis.
Serum samples taken before the onset of RA suggest that one of the first features of RA is BMD loss. We determined the ability of radiographic BMD loss to predict RA development and arthritis persistency in patients with early undifferentiated arthritis (UA). Five hundred and seventeen patients with early UA, included in the Leiden Early Arthritis Clinic, were assessed. Of these, 101 had hand radiographs made at first visit as well as after 6 months. BMD loss was measured using digital X-ray radiogrammetry (DXR) online. The outcome measures fulfilled the 1987 ACR criteria for RA after 1 year and arthritis persistency during a mean follow-up of 7 years. Additionally, it was assessed whether BMD measurements improved predictions compared with a validated prediction rule. A total of 53.8% of UA patients developed RA and 67.5% had persistent disease after 7 years follow-up. Highly elevated BMD loss (≥2.5 mg/cm2/month) was present in 16.3% of patients and associated with RA development [odds ratio (OR) 6.1, 95% CI 1.2, 29.2, positive predictive value (PPV) 85%, negative predictive value (NPV) 52%, sensitivity 26%, specificity 95%]. BMD loss may have an independent effect of anti-CCP when tested in a logistic regression analysis (OR 4.1, 95% CI 0.8, 21.2), although the CI is large. All UA patients that were unclassified with the prediction rule and had highly elevated BMD loss progressed to RA. BMD loss was not significantly associated with arthritis persistency (HR = 0.56, 95% CI 0.14, 2.29). Present data suggest that BMD loss predicts RA development. These findings need to be verified in larger studies.


Hemicrania continua-like headache with leprosy: casual or causal association?
Hemicrania continua is a strictly unilateral, moderate to severe, continuous, indomethacin-responsive primary headache disorder with ipsilateral autonomic cranial symptoms at the time of exacerbations. We describe a 30-year-old woman with a 4-month history of indomethacin-responsive hemicrania continua-like headache and one-month history of mononeuritis multiplex due to leprosy. Indomethacin was successfully weaned off after completion of antileprotic therapy.


Novel UHPLC-MS/MS method for the determination of rotigotine in the plasma of patients with Parkinson's disease.
A novel ultra-high-pressure liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of the dopamine receptor agonist rotigotine in human plasma. Following liquid-liquid extraction with tert-butyl methyl ether from 500 μL plasma, the chromatographic analysis was performed on a Gemini NX3 column using 5 mm pH 5.0 ammonium acetate-5 mm ammonium acetate in methanol as binary gradient mobile phase, at a flow rate of 0.3 mL/min. The MS/MS ion transitions were 316.00 → 147.00 for rotigotine and 256.10 → 211.00 for the internal standard (lamotrigine). The lower limit of quantitation was 50 pg/mL and the linearity was determined from 50 to 2500 pg/mL. The mean recovery was 96.9%. Both intra- and interassay imprecision and inaccuracy were ≤15% at all quality control concentrations. The method was successfully applied to measure morning trough plasma rotigotine concentrations in a series of patients with Parkinson's disease on chronic treatment. The present study describes the first fully validated method for rotigotine determination in human plasma.