When and how to grade Barrett's columnar metaplasia: the Prague system

Barrett's oesophagus (BO), a well-known precursor for oesophageal adenocarcinoma has been generating a great deal of controversy. The initial step in diagnosing BO requires an accurate endoscopic recognition of the columnar lined oesophagus. A reliable diagnosis of BO depends on its effective endoscopic recognition based on the key anatomic landmarks, followed by histological sampling of the columnar-lined epithelium. Precise localisation of the gastrooesophageal junction is pivotal in the endoscopic diagnosis of BO. Multiple ad-hoc grading systems and terminologies of BO have been proposed based on the Z-line appearance, presence or absence of intestinal metaplasia, and the length of Barrett's segment. However, a universally accepted standardised endoscopic grading system of BO is lacking. The Prague C&M criteria, developed by a subgroup of the International Working Group for the Classification of Oesophagitis, are the first explicit, consensus-driven, clinically relevant criteria for the endoscopic recognition and grading of BO that may be useful in both clinical practice and research trials.     

Partial HLA matching and RH incompatibility resulting in graft versus host reaction and Evans syndrome after liver transplantation

We report a case of a 67-year-old male who underwent OLT from a deceased, sex-matched donor. Two months later he developed Evans syndrome and GVHD of the skin. Donor and recipient were matched for HLA-A and -B loci in the direction of rejection but mismatched in the direction of GVHD and fully mismatched for DRB1. These mismatches were permissible for engraftment of donor T-cells but led to GVHD. Chimerism appeared restricted to the T-cell compartment. In this case, partially matched passenger lymphocytes triggered a graft versus host reaction. In addition, alloantibodies caused cytopenias that improved after immunosuppression. HLA typing was critical in confirming this rare diagnosis and elucidating its cause. Recipients of solid organs from donors that are partially matched in the direction of rejection may need to be closely monitored for GVHD.     

Ifosfamide impairs the allostimulatory capacity of human dendritic cells by intracellular glutathione depletion

Ifosfamide, a clinically potent chemotherapeutic agent, causes the depletion of intracellular glutathione (GSH) levels in various cell types. GSH is the major intracellular reductant against oxidative stress. 4-Hydroxyifosfamide (4-OH-IF), the activated form of ifosfamide, depletes GSH levels in T cells and natural killer (NK) cells; this is accompanied by a decrease in T-cell and NK-cell function. Here we demonstrate for the first time that human monocyte-derived dendritic cells (DCs) express higher constitutive levels of GSH and are less sensitive to 4-OH-IF-induced GSH depletion than T cells and NK cells. Treatment of DCs with 4-OH-IF significantly reduced their ability to stimulate allogeneic T-cell proliferation and interferon-gamma (IFN-gamma) production. Ifosfamide also decreased DC interleukin-12p70 (IL-12p70) production after stimulation with lipopolysaccharide (LPS) and IFN-gamma. The decrease in allostimulatory capacity and in IFN-gamma and IL-12 production correlated with a decrease in intracellular GSH in the DCs. The responses could be restored by reconstituting DC GSH levels with glutathione monoethyl ester (GSH-OEt). 4-OH-IF had no inhibitory effect on the ability of DCs to present exogenously added tyrosinase peptide to tyrosinase-specific cytotoxic T lymphocytes (CTLs). These studies suggest that in cancer patients treated with ifosfamide, protection strategies based on glutathione reconstitution may enhance DC function.     

Relationship between caesium (137Cs) load, cardiovascular symptoms, and source of food in 'Chernobyl' children -- preliminary observations after intake of oral apple pectin

Seventeen years after the nuclear power accident at Chernobyl, most of the radio-contamination among the population of Southern Belarus is caused by incorporation of long-lived radioisotopes. The varying levels of 137Cs observed among children in this area are explained by the source of their food, especially by the consumption of contaminated milk produced privately. We stratified children from rural areas of Belarus (caesium [137Cs] contamination >5 Ci/km(2)) by their 137Cs loads into three distinct groups (group 1, <5 Bq/kg body weight [BW]; group 2, 38.4 +/- 2.4 Bq/kg BW; group 3, 122 +/- 18.5 Bq/kg BW). We determined the relationship between the 137Cs load and the children's main source of food and recorded their cardiovascular symptoms. Cardiovascular symptoms, ECG alterations, and arterial hypertension were significantly more frequent in children with high 137Cs burden than in children with very low 137Cs burden. Children with moderate and high 137Cs loads (groups 2 and 3) received apple pectin, a food additive, for 16 days. Apple pectin significantly decreased 137Cs loads in these groups (39% and 28%, respectively). ECG alterations improved, while cardiovascular symptoms and hypertension did not change in any group.     

A multiplex PCR/LDR assay for simultaneous detection and identification of the NIAID category B bacterial food and water-borne pathogens

Enteric pathogens that cause gastroenteritis remain a major global health concern. The goal of this study was to develop a multiplex PCR/ligation detection reaction (LDR) assay for the detection of all NIAID category B bacterial food and water-borne pathogens directly from stool specimens. To validate the PCR/LDR assay, clinical isolates of Campylobacter spp., Vibrio spp., Shigella spp., Salmonella spp., Listeria monocytogenes, Yersinia enterocolitica, and diarrheagenic Escherichia coli were tested. The sensitivity and specificity of the assay were assessed using a large number of seeded culture-negative stool specimens and a smaller set of clinical specimens from Haiti. The overall sensitivity ranged from 91% to 100% (median 100%) depending on the species. For the majority of organisms, the sensitivity was 100%. The overall specificity based on initial testing ranged from 98% to 100% depending on the species. After additional testing of discordant samples, the lowest specificity was 99.4%. PCR/LDR detected additional category B agents (particularly diarrheagenic E. coli) in 11/40 specimens from Haiti that were culture-positive for V. cholerae and in approximately 1% of routine culture-negative stool specimens from a hospital in New York. This study demonstrated the ability of the PCR/LDR assay to detect a large comprehensive panel of category B enteric bacterial pathogens as well as mixed infections. This type of assay has the potential to provide earlier warnings of possible public health threats and more accurate surveillance of food and water-borne pathogens.     

Comparative Pharmacology of Cefaclor and Cephalexin

Two cephalosporin antibiotics, cefaclor and cephalexin, were administered orally to healthy, adult male volunteers for comparison of their pharmacological properties. In doses of 250 mg orally, cefaclor produced a peak serum concentration of 6.01 ± 0.55 (standard deviation [SD]) μg/ml compared with 9.43 ± 2.36 μg/ml for cephalexin (P < 0.01). The half-lives were 0.58 ± 0.07 (SD) h and 0.80 ± 0.12 (SD) h, and elimination constants were 1.22 ± 0.15 and 0.88 ± 0.13 h⁻¹ for cefaclor and cephalexin, respectively (P < 0.001). Neither drug showed accumulation over the dosing period, and both were well tolerated.     

Oxytocin and Social Cognitions in Schizophrenia: A Systematic Review

Schizophrenia is a chronic multifactorial disorder. Over the last years, there has been a growing interest in cognitive deficits in schizophrenia, which is considered by many as the core abnormality of the disease. In the systematic review we focus on the social cognition and its correlation with the neuropeptide oxytocin, which is shown to be involved in the emotion recognizing processes, in the trust behavior and many other aspects of social functioning. The systematic review was performed in order to summarize the data on the liaison of oxytocin with the social cognition impairment in schizophrenia patients. Oxytocin is assumed to be a potential therapeutic agent for schizophrenia, with a special link to social cognitive functions. The oxytocinergic system is a promising neuromodulator of emotion recognition that may have the potential to normalize the social dysfunction seen in schizophrenia. Further studies are required to provide more data on the correlations between oxytocin and socialcognition as well as other schizophrenia symptoms.     

SARS-CoV-2-Induced Pathology—Relevance to COVID-19 Pathophysiology

In spite of intensive studies of different aspects of a new coronavirus infection, many issues still remain unclear. In a screening analysis of histopathology in l200 lethal cases, authors succeeded in performing a wide spectrum of immune histochemical reactions (CD2, CD 3, CD 4, CD 5, CD 7, CD 8, CD14, CD 20, CD 31, CD 34, CD 56, CD 57, CD 68, CD 163, collagen 1,3, spike protein SARS-CoV-2, caspase-3, MLCM; ACE2 receptor, occludin, and claudin-1 and -3) and electron microscopy. The results of the histological and IHC studies of deceased people with varying degrees of severity of coronavirus infection confirmed the ability of these pathogens to cause cytoproliferative changes, primarily in epithelial and endothelial cells. Lesions of various organs are possible, while the reasons for significant differences in organotropy remain unclear. Severe respiratory failure in COVID-19 in humans is associated with a very peculiar viral pneumonia. In the pathogenesis of COVID-19, the most important role is played by lesions of the microcirculatory bed, the genesis of which requires further study, but direct viral damage is most likely. Endothelial damage can be associated with both thrombosis in vessels of various calibers, leading to characteristic complications, and the development of DIC syndrome with maximal kidney damage. Such lesions can be the basis of clinically diagnosed septic shock, while usually there are no morphological data in favor of classical sepsis caused by bacteria or fungi. A massive infiltration of the lung tissue and other organs, mainly by T lymphocytes, including those with suppressor properties, makes it necessary to conduct a differential diagnosis between the morphological manifestation of the protective cellular immune response and direct viral lesions but does not exclude the hypothesis of an immunopathological component of pathogenesis. In many of the deceased, even in the absence of clear clinical symptoms, a variety of extrapulmonary lesions were also detected. The mechanism of their development probably has a complex nature: direct lesions associated with the generalization of viral infection and vascular disorders associated with endothelial damage and having an autoimmune nature. Many aspects of the pathogenesis of coronavirus infection require further comprehensive study.