Will a second biopsy sample affect treatment decisions in patients with chronic hepatitis B?

Background and aim

Liver biopsy is the gold standard for assessment of fibrosis in patients with hepatitis B. However, it has some disadvantages, including inter-observer and intra-observer variability in biopsy interpretation and specimen variation. A standard biopsy specimen represents only about 0.0002 % of the whole liver. It has been shown that two biopsy samples collected during a procedure have significant influence on the diagnostic performance of interpretation in patients with hepatitis C or non-alcoholic steatohepatitis. Therefore, we aimed to assess the influence of collecting two liver biopsy samples during a single procedure for staging and grading chronic hepatitis B.

Patients and methods

27 patients were included in the study. The median age of the patients was 43.51 ± 11.69. Fifteen patients were female, 12 patients were male. In the biopsy procedure, two samples of liver lobes were obtained. Grade and stage scores were compared between the two samples. Fibrosis staging and grading were assessed according to the Ishak scoring system.

Results

Numbers of portal tract and biopsy size were equal in the two samples. There was a significant difference between the samples in terms of histological activity index (p value = 0.04). However, the difference was not enough to distinguish the mild and moderate stages. On the other hand, no significant difference in fibrosis staging between the two samples was found.

Conclusions

With this relatively small size of patients, in this study, we showed that a proper liver biopsy size is sufficient to predict treatment decisions in chronic hepatitis B patients. However, further studies are needed to show the association of sampling variability in patients with hepatitis B.

     

The impact of c4d staining as a humoral injury marker

Purpose

Acute and chronic humoral injuries in renal tranplant recipients are the main reasons for graft rejection and failure. Histological and clinical characteristics of humoral rejection and symptoms are variable and not always helpful for differential diagnosis. Clinical monitoring of the allograft, an elevated serum panel-reactive antibody (PRA), and the presence of donor-specific antibody (DSA) during immune monitoring as well as C4d staining of biopsy material can establish the differential diagnosis. Even without a cellular component, humoral rejection reaction is serious because the target tissue is the graft endothelium. Because the kidney graft has a rich vascular structure this attack causes permanent injury to the kidney in the long term. Graft dysfunction in this setting is usually more severe, requiring dialysis therapy, compared with acute cellular reactions. Positive C4d staining of peritubular capillaries in biopsy material represent a hallmark of complement-dependent cytotoxicity, supporting the diagnosis of humoral rejection. We analyzed C4d staining as a hallmark of humoral rejection.

Methods

From 2009 to 2011, we analyzed the relationship between pathological findings of C4d immunohistochemistry staining and the clinical outcomes of 45 kidney transplant recipients who underwent a kidney biopsy because of graft dysfunction due to possible humoral rejection.

Results

Biopsy specimens of 15 patients stained C4d positive; the remaining 30 showed negative results. Intravenous steroids, PP + IVIG with or without antithymocyte globulin (ATG), was administered for treatment. Sixty six percent (n = 10) of patients were C4d positive with 16% (n = 5) of those showing C4d-negative biopsy results, losing their grafts, and returning to hemodialysis.

Conclusions

C4d staining refractory humoral rejection injury was related to poor graft outcomes.     

Transgastric endoscopic pneumoperitoneum versus laparoscopy: effects on host systemic and peritoneal inflammatory responses in a porcine model

Background  

The host systemic and peritoneal immune responses during natural orifice transluminal endoscopic surgery (NOTES) continues to be delineated. The immune response to laparoscopy (LAP) has been favorably depicted. However, the immunologic effects of NOTES are yet to be determined, and the introduction of contaminants via the host orificium may have deleterious effects. The purpose of this study was to characterize the effect that NOTES would have on porcine systemic and peritoneal immune function.     

Tyrosine kinase inhibitors suppress prostaglandin F2α-induced phosphoinositide hydrolysis, Ca elevation and contraction in iris sphincter smooth muscle

We investigated the effects of the protein tyrosine kinase inhibitors, genistein, tyrphostin 47, and herbimycin on prostaglandin F_2α- and carbachol-induced inositol-1,4,5-trisphosphate (IP₃) production, [Ca²⁺]_i mobilization and contraction in cat iris sphincter smooth muscle. Prostaglandin F_2α and carbachol induced contraction in a concentration-dependent manner with EC₅₀ values of 0.92×10⁻⁹ and 1.75×10⁻⁸ M, respectively. The protein tyrosine kinase inhibitors blocked the stimulatory effects of prostaglandin F_2α, but not those evoked by carbachol, on IP₃ accumulation, [Ca²⁺]_i mobilization and contraction, suggesting involvement of protein tyrosine kinase activity in the physiological actions of the prostaglandin. Daidzein and tyrphostin A, inactive negative control compounds for genistein and tyrphostin 47, respectively, were without effect. Latanoprost, a prostaglandin F_2α analog used as an antiglaucoma drug, induced contraction and this effect was blocked by genistein. Genistein (10 μM) markedly reduced (by 67%) prostaglandin F_2α-stimulated increase in [Ca²⁺]_i but had little effect on that of carbachol in cat iris sphincter smooth muscle cells. Vanadate, a potent inhibitor of protein tyrosine phosphatase, induced a slow gradual muscle contraction in a concentration-dependent manner with an EC₅₀ of 82 μM and increased IP₃ generation in a concentration-dependent manner with an EC₅₀ of 90 μM. The effects of vanadate were abolished by genistein (10 μM). Wortmannin, a myosin light chain kinase inhibitor, reduced prostaglandin F_2α- and carbachol-induced contraction, suggesting that the involvement of protein tyrosine kinase activity may lie upstream of the increases in [Ca²⁺]_i evoked by prostaglandin F_2α. Further studies aimed at elucidating the role of protein tyrosine kinase activity in the coupling mechanism between prostaglandin F_2α receptor activation and increases in intracellular Ca²⁺ mobilization and identifying the tyrosine-phosphorylated substrates will provide important information about the role of protein tyrosine kinase in the mechanism of smooth muscle contraction, as well as about the mechanism of the intraocular pressure lowering effect of the prostaglandin in glaucoma patients.     

Logical functional analysis in the assessment and treatment of eating disorders

Cognitive behaviour therapy (CBT) is now suggested to be the treatment of choice for bulimia nervosa. However, it is also known than no more than approximately 50% of patients recover after receiving CBT. When the first-line manual-based treatment fails, the therapist should use other empirically supported treatments, and if they do not work or are not available, then the therapist should resort to the problem-solving (hypothesis-testing) approach that characterises CBT. However, using problem-solving strategies demands a thorough analysis and understanding of the variables maintaining the problems. Behavioural functional analysis, which lies at the core of behaviour therapy and applied behaviour analysis, helps the therapist to gain the understanding needed for using relevant cognitive and behavioural treatment strategies and methods. However, functional analysis has been criticised for lack of replicability and cost-ineffectiveness. Logical functional analysis (LFA) is a recent development that seems to be both replicable and useful for treatment planning. In this paper, an LFA of eating disorders that helps to guide the CBT treatment and makes it more individualised is described, discussed, and illustrated by a case example.     

Environmental and health monitoring study in dry cleaning departments

The aim of the present work is to evaluate the potential exposures to perchloroethylene in the dry cleaning departments in a group of seven first‐class Egyptian hotels; conditions which contribute to excessive levels and possible health effects in the exposed workers. Environmental monitoring of the workplaces was done through air samples, being collected from the breathing zones in the dry cleaning departments, carried out in different stages during washing process: close to press machine, flat iron, mannequin, spotting table and while charging the cleaning machine with the solvent. Atmospheric samples were analyzed by gas chromatography technique. The environmental study showed that the PCE levels were much exceeded in many workplaces, compared to the recommended TLV‐TWA. A group of 53 dry cleaners are included in the present work, in addition to 30 unexposed office workers, served as a control group. Both groups were thoroughly interviewed and examined clinically stressing on the condition of their CNS and PNS. Blood samples were collected and analyzed (spectrophotometrically) for the measurement of liver and renal function tests. Urine samples were collected and analyzed for the determination of the urinary trichloroacetic acid. Headache, nervousness, dizziness and vertigo were the most prevalent symptoms elicited in the exposed workers, followed by symptoms of respiratory and gastrointestinal irritation and skin and mucous membranes’ reactions. Gloves and stokings’ hypoaesthesia affected about l/4th of the exposed workers, followed by tremors (22.64%), first cranial nerve affection (11.32%), and disturbed reflexes (5.66%). Other signs elicited in the exposed workers were in the form of skin manifestations (16.98%), pallor (7.55%), and jaundice (2 cases). Insignificant systolic and diastolic high blood pressures were elicited in the exposed workers compared to the controls. Higher values of blood urea, serum creatinine, SGOT, total proteins, and urinary trichloroacetic acid were elicited in the exposed workers compared to the controls, whereas, lower figures of albumin were elicited in the exposed workers than in the controls. However, in spite of such differences, there was no statistical significance for those differences except for the urinary trichloroacetic acid (t = 3.6, ρ < 0.05). Duration of exposure proved to have no significant effect on most of the bioindicators, being examined in the present study. The study recommended a pre employment medical examination for the subjects recommended to work in dry cleaning, as well as a periodic medical examination to elicit the early manifestations due exposure to PCE. Various engineering control measures must be taken into consideration, when we try to improve the workplaces being studied. Personal protective measures could be considered the last effective line of defense against the various health hazards being faced by the working population in such an important economic activity.     

The location of photodegradable nitric oxide store in the mouse stomach fundus

The aim of this study was to investigate the location of photodegradable nitric oxide (NO) store using a pharmacological approach in mouse gastric fundus. The ultraviolet light irradiation (UV; 360 nm, 60 s), electrical field stimulation (EFS; 4 Hz, 25 V, 1 ms, 15s-train), exogenous nitric oxide (NO; 10 microM), nitroglycerin (100 microM) and isoproterenol (5 nM) induced relaxation in mouse gastric fundus preparations in the absence or presence of an intact mucosa. The NO scavenger, haemoglobin (20 microM), significantly inhibited the relaxation of intact and denuded mucosa stomach fundus to UV light irradiation, EFS and NO, but not to nitroglycerin and isoproterenol. The superoxide anion generator, pyrogallol (50 microM), inhibited relaxation of intact and denuded mucosa stomach fundus induced by UV light irradiation, EFS, NO, but not to nitroglycerin and isoproterenol. The inhibition observed with pyrogallol was prevented by exogenous Cu/Zn superoxide dismutase (SOD; 100 U/ml), a membrane impermeable antioxidant. The Cu/Zn SOD inhibitor, diethyldithiocarbamic acid (DETCA; 8 mM), inhibited the relaxation of intact and denuded mucosa stomach fundus to UV light irradiation, EFS, NO and nitroglycerin but not those to isoproterenol. Exogenous SOD (100 U/ml) partially prevented the inhibitory effect of DETCA on relaxation to UV light irradiation, EFS, NO but not to nitroglycerin. DETCA-induced inhibition of the nitroglycerin-induced relaxation was partially prevented by the cell-permeable polyethylene-glycol-superoxide dismutase (100 U/ml). These results indicate that photodegradable NO store is, at least in part, unlikely to be within smooth muscle cells, and furthermore, that UV light-induced relaxation is not dependent on gastric mucosal layer.     

Attrition and outcome in self-help treatment for bulimia nervosa and binge eating disorder: a constructive replication

The aim of the study was to assess the efficacy of a 12-week CBT-based pure and guided self-help among 29 patients with full and subthreshold bulimia nervosa, and binge eating disorder. In the intention-to-treat analyses, self-help had a moderately positive and sustained effect on the patients' eating problems. The patients reduced their mean number of objective bulimic episodes and purging behavior by 26% and 22% over the course of treatment. The corresponding reduction levels for the treatment completers (n=21) were 41% and 34%, respectively. As in the previous study, there were no significant differences between the pure and guided self-help mode in terms of outcome, and the results were sustained 6 months after the end of the treatment. The findings are discussed in relation to the shorter duration of the self-help, the lower rate of attrition, and the characteristics of the sample compared to the earlier trial.