Intrahepatic cholangiocarcinoma: indication for transplantation

Background/Purpose. Cholangiocarcinoma (CCC) is a rare malignant tumor of the biliary system with a poor prognosis that frequently presents in advanced unresectable stages. A discussion of the role of liver transplantation (LTx) for intrahepatic (IH)-CCC will be presented, based on a review of the international literature. Methods. A search of the international literature related to the topic was performed in the established online databases and databanks. Only those reports with patient series larger than ten were included. Results. The largest series of patients with IH-CCC (n = 186) was reported in the Data Analysis Booklet of the European Liver Transplant Registry (ELTR), revealing 1-, 3-, 5-, 8-, and 10-year survival rates of 58%, 38%, 29%, 23%, and 21%. Other single-center series had comparable or even worse outcomes. More recent experience identified a certain highly selected group of patients who could benefit from LTx in an otherwise unresectable state of disease. Several single-center studies found tumor stage or size, lymph node involvement, and positive surgical margins/contiguous organ infiltration to be predictors of outcome. The recently published Mayo Clinic protocol uses preoperative chemoirradiation and staging at laparotomy before proceeding to liver transplantation, resulting in an early experience with 100% 1-year survival. Conclusions. Generally speaking, IH-CCC is not a favorable indication for liver transplantation. However, there is a highly selected group of patients with early tumor stages potentially benefitting from LTx. Combination with neoadjuvant chemoirradiation may further improve results after LTx. Living-donation LTx may open new therapeutic possibilities to treat patients at an early stage of disease.     

Central projections of sensory innervation of the rat superficial temporal artery

Elucidating the central sensory projection pathways of extra- and intracranial vessels appears to be of fundamental importance for understanding the pathogenetic mechanisms of primary headaches. In this paper, two kinds of tracers, choleragenoid (cholera toxin subunit b, CTb) and wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP), were used to transganglionically label the central sensory projections of the innervation of the superficial temporal artery (STA). Following either of the tracers applied on the adventitia of the STA, labelled terminations were found mainly in the ipsilateral C1-C3 spinal dorsal horns. Sparse labelling was also found in the interpolar and caudal parts of the spinal trigeminal nucleus. In the spinal cord, CTb labelled profiles were mainly located in laminae III and IV, whereas WGA-HRP labelled profiles were mainly located in laminae I and II. In the medulla, CTb but not WGA-HRP labelled terminals were found in a small dorsolateral extension of the cuneate nucleus. The present results indicate that the primary sensory nervous center of the STA is located in the rostral cervical spinal dorsal horn. The caudal parts of the spinal trigeminal nucleus, which has been demonstrated as a center of pain and temperature sensations of the head and face, transmits limited information from the STA to higher nervous centers.     

Heat nociception is severely reduced in a mutant mouse deficient for the L1 adhesion molecule

Recent findings indicate that the spatial organization of the spinal nociceptive reflex system is adjusted postnatally through experience-dependent mechanisms. The cellular and molecular mechanisms underlying this tuning are not known. Because the adhesion molecule L1 is known to play an important role in neural development and synaptic plasticity, we studied the nociceptive withdrawal reflexes in awake adult mutant mice deficient in L1. Withdrawal reflexes were elicited by a CO(2) laser (heat stimulation) and von Frey monofilaments (tactile stimulation). L1-deficient mice (n=10) had an abnormally high nociceptive heat-reflex threshold compared with wild-type mice (n=11), except for the nose. Other behavioral signs of heat pain, such as vocalization, were either absent or strongly reduced in L1-deficient mice. Tactile thresholds for withdrawal reflexes were increased in L1-deficient mice when compared with wild-types except for the tail. By contrast, the spatial organization of the withdrawal reflexes appeared normal indicating that the L1 adhesion molecule is not essential for the spatial adjustments of reflex connections during development. The termination patterns of thin primary afferent fibers in the superficial dorsal horn, visualized using intra-plantar injections of WGA-HRP, were normal, suggesting that decreased nociceptive heat sensitivity in L1-deficient mice is mainly due to altered central processing. In view of the known interactions between L1 and some of the NMDA-receptor subtypes, and the prominent role of NMDA receptors in nociception and plasticity, it is conceivable that the hypoalgesia seen in L1 mutants is due, in part, to disturbed NMDA-receptor function.     

Delayed complications of endovascular stenting for carotid blowout

Endovascular stents are used in a wide variety of situations including management of acute hemorrhage from a carotid artery blowout. The long-term efficacy of these devices in this setting has not been elucidated. Two cases of carotid stenting for carotid artery blowouts in the face of cervical malignancy and overlying infection were followed over time. In both patients, initial control of carotid bleeding was followed by delayed stent-related complications. Although carotid stents are useful for control of acute carotid blowouts, their long-term efficacy in the setting of head and neck malignancy and overlying infection is suspect.     

LTP-induced depression of response to hypoxia in hippocampus: effects of adenosine receptor activation

Previous work has shown that long-term potentiation (LTP) can reduce the effects of hypoxia in depressing population spikes in rat hippocampal slices. We have now investigated the role of adenosine in this phenomenon. There is no mutual inhibition between the depressant effects of hypoxia and adenosine, but LTP reduces responses to both hypoxia and adenosine, as does application of an A1 receptor antagonist. The effect of LTP is not due to a change in the balance of activation of A1 and A2A adenosine receptors since a selective A2A receptor antagonist did not prevent the interaction. We suggest that LTP may reduce the response to hypoxia by attenuating neuronal sensitivity to adenosine A1 receptors.     

Neuroprotective role of learning in dementia: a biological explanation

Several epidemiological studies have found an association between low educational level (or low cognitively demanding occupations) and dementia. Although other studies have not found evidence to support such an association, there has been a general trend toward a "use it or lose it" concept which attempts to promote a neuroprotective role of intellectual activity against the development of dementia. Formation of amyloid-beta peptide (Abeta) in the brain plays a key role in the development of Alzheimer's disease whilst glutamate has been implicated in the pathophysiology of a number of neurological disorders including Alzheimer's disease and vascular dementia. Abeta can mediate neurodegeneration by a complex interaction of neurodegenerative processes that involve increasing extracellular concentration of glutamate, increasing intracellular Ca2+ concentration, and apoptosis. Long-term potentiation (LTP, a biological correlate of learning and memory) increases the sensitivity of hippocampal neurons to synaptically released glutamate whilst decreasing responses of neurons to bath applied glutamate receptor agonists and to hypoxia/ischemia in vitro. The effects of LTP are likely to involve changes in intracellular Ca2+ concentration. Based on these findings we are proposing that the LTP-induced neuroprotection in vitro may help explain the epidemiological evidence of a possible neuroprotective role of high intellectual activity against dementia.     

Nasal Symptoms Are Associated with School Performance in Adolescents

Children with asthma and allergy have higher school absence rates than others, but little is known about their school performance. In a study of 9538 adolescents, nasal symptoms severe enough to affect daily activity were associated with low-grade sum, particularly in adolescents using anti-allergy medication.     

Influence of diets with cereal grains contaminated by graded levels of two Fusarium toxins on selected enzymatic and histological parameters of liver in gilts.

Feeding experiments with diets containing Fusarium toxin-contaminated wheat were conducted to clarify the pathogenesis of enzymatic and histopathological effects of Fusarium toxins on porcine liver cells. A total of 36 prepuberal gilts were divided into four groups and fed diets with increasing proportions of Fusarium toxin-contaminated wheat at a total wheat proportion of 40% over a period of 35 days. The concentrations of the indicator toxins deoxynivalenol (DON) and zearalenone (ZON) which were analyzed by HPLC methods were 210/4, 3070/88, 6100/235, and 9570/358 microg/kg in the diets fed to groups I-IV, respectively. The feeding of mycotoxin-contaminated diets did not cause gross pathological findings in the livers of the animals. Liver tissues were subjected to enzymatic, histological, and ultrastructural examinations. The percentages of the stained areas in periodic acid-Schiff (PAS), Berlin-Blue, and Masson Goldner's trichrome stainings were calculated using the AnalySIS 3.4-system. Significant histopathological findings of alterations with varying degrees in glycogen reduction and increase of hemosiderin particles were found in the liver cells of groups II, III and IV. The thickness of interlobular connective tissue septum in liver cells was significantly increased in groups III and IV. Qualitative ultrastructural alterations were observed in hepatocytes of gilts in groups III and IV. Dependent upon the mycotoxin concentration in the diet, the hepatocytes developed a dose-dependent, extensive, smooth endoplasmic reticulum, exhibited loss of ribosomes, and acquired an increased number of fatty and autophagic vacuoles. However, liver damage as measured by prominent elevated transaminase activities in serum was not detected. Together, the histopathological results provide evidence of liver dysfunction in the absence of clinical signs, especially in pigs fed higher concentrations of Fusarium toxin-contaminated wheat.     

Frequency of under-corrected refractive errors in elderly Chinese in Beijing

Purpose The aim of the study was to evaluate the prevalence of under-corrected refractive error among elderly Chinese in the Beijing area.Methods The population-based, cross-sectional, cohort study comprised 4,439 subjects out of 5,324 subjects asked to participate (response rate 83.4%) with an age of 40+ years. It was divided into a rural part [1,973 (44.4%) subjects] and an urban part [2,466 (55.6%) subjects]. Habitual and best-corrected visual acuity was measured. Under-corrected refractive error was defined as an improvement in visual acuity of the better eye of at least two lines with best possible refractive correction.Results The rate of under-corrected refractive error was 19.4% (95% confidence interval, 18.2, 20.6). In a multiple regression analysis, prevalence and size of under-corrected refractive error in the better eye was significantly associated with lower level of education (P<0.001), female gender (P<0.001), and age (P=0.001).Conclusions Under-correction of refractive error is relatively common among elderly Chinese in the Beijing area when compared with data from other populations.