Plasma cysteine, cystine, and glutathione in cirrhosis

Plasma contains three forms of cyst(e)ine: cysteine, cystine, and protein-bound cysteine. The former is a thiol and the latter two are disulfides. The levels of all three types of cyst(e)ine, as well as the cysteinyl tripeptide glutathione, were measured in the plasma of 14 normal and 10 cirrhotic individuals. All subjects ate mixed foods. Some cirrhotic patients were studied during nasogastric hyperalimentation with Vivonex (Norwich Eaton Pharmaceuticals, Norwich, N.Y.) as well as during total parenteral nutrition with FreAmine III (American McGaw, Irvine, Calif.); neither formula contains cyst(e)ine. Regardless of the nature of the diet, cirrhotic patients had significantly subnormal values for cysteine, glutathione, and albumin. In addition, the following significant changes were found to be diet-dependent: (a) elevated methionine during Vivonex, (b) subnormal taurine during mixed foods and total parenteral nutrition, (c) depressed protein-bound cysteine during total parenteral nutrition, (d) depressed cyst(e)ine thiol/disulfide ratio during mixed foods, and (e) depressed total thiol during Vivonex and total parenteral nutrition. The data indicate multiple abnormalities in sulfur metabolism in cirrhosis.     

Significance of false-positive serologic tests for histoplasmosis and blastomycosis in an endemic area

False-positive serologic tests for histoplasmosis (H) and blastomycosis (B) are common in populations from endemic areas. In order to determine the significance of false-positive test results, we reviewed the final diagnoses of all patients whose sera were submitted to our laboratory for radioimmunoassay (RIA) and immunodiffusion (ID) during a 3-yr period. Of the 263 patients whose sera were examined, 29 (11%) had H or B; 41 (17.5%) of the remaining 234 patients had false-positive test results. Of these 41 patients, 31 were positive for H alone, and 10 had antibodies to both H and B. All three patients with false-positive ID tests for histoplasmosis also had positive titers (greater than or equal to 1:16) on RIA. No patient had a false-positive ID result for blastomycosis. The percentage of patients in each of five major diagnostic categories with and without false-positive serologic tests was similar (p greater than 0.05). The majority of patients had pulmonary infections, almost half of which were granulomatous infections other than H or B; this reflects the clinical indications for requesting fungal serologic tests. A positive fungal serology is not useful in suggesting the presence of a pulmonary disease other than H or B in patients from an endemic area suspected of having a pulmonary mycosis.     

Efficacy of Lactulose in Cirrhotic Patients with Subclinical Hepatic Encephalopathy

To investigate the role of lactulose in the treatment of cirrhotic patients with subclinical hepatic encephalopathy (SHE), 40 cirrhotic patients, 33 males and 7 females, were included in the study. The diagnosis of SHE was made by quantitative psychometric tests including the number connection test (NCT), figure connection test (FCT) parts A and B, and two performance subtests of Wechsler adult intelligence scale, ie, picture completion (PC) and block design (BD) tests. SHE was diagnosed in 26 (65%) of 40 patients. Of these 26 patients, 14 patients were randomized to treatment group (lactulose 30–60 ml/day for three months, SHE-L) and 12 patients to no treatment group (no lactulose, SHE-NL). Psychometric tests were repeated in all patients in both groups and in six patients with no SHE (group NSHE, N = 14) after three months. The mean scores and number of the abnormal psychometric tests at entry were significantly higher in patients in groups SHE-L and SHE-NL than in patients in group NSHE; however, there was no significant difference between SHE-L and SHE-NL. The mean number of the abnormal psychometric tests decreased in patients in group SHE-L after three months of treatment with lactulose (2.9 ± 0.9 vs 0.8 ± 1.2; P = 0.004); however, there was no change in patients in group SHE-NL after three months (3.7 ± 1.5 vs 3.5 ± 1.3; P = NS). While SHE improved in 8 of 10 patients in group SHE-L, none of the patients in group SHE-NL improved after three months of follow-up (P < 0.001). Two patients in group SHE-NL also developed overt encephalopathy during the study period. We conclude that lactulose treatment in cirrhotic patients with SHE is effective.     

Hepatitis E virus antigen detection as an early diagnostic marker: Report from India

Hepatitis E virus (HEV) is implicated in many outbreaks of viral hepatitis in the Indian subcontinent. The conventional diagnosis of such outbreaks rests on the detection of anti‐HEV IgM antibodies. However, IgM antibodies develop after 4–5 days of infection. An early‐diagnostic marker is imperative for timely diagnosis of the outbreak and also initiation of control measures. This study aimed to determine the use of hepatitis E virus antigen detection as an early diagnostic marker in an outbreak in comparison to anti‐HEV IgM and RT‐PCR analyses. Forty samples were collected during a suspected outbreak of viral hepatitis due to HEV. A total of 36 samples were positive for one or more HEV markers. The positivity for anti‐HEV IgM, HEV antigen, and RT‐PCR was 91.6%, 69.4%, and 47.2% respectively. RT‐PCR and HEV antigen detection gave the highest positive results (100%) in the first 3 days of illness. Positive HEV PCR declined to 54% by Days 4–7, whereas HEV antigen and IgM detection were 88% and 100%, respectively. Sequencing of representative HEV samples indicated that the strains responsible for this outbreak belonged to genotype I, subtype 1a. HEV antigen was found to be an early diagnostic marker of acute infection. HEV antigen was detected in three additional cases in the early phase (1–3 days), and they had no detectable anti‐HEV IgM antibodies. These three samples were also positive for HEV RNA. After Day 7, anti‐HEV IgM was the main diagnostic indicator of infection. J. Med. Virol. 85:823–827, 2013. © 2013 Wiley Periodicals, Inc.     

Antimicrobial peptides derived from growth factors

Growth factors, comprising diverse protein and peptide families, are involved in a multitude of developmental processes, including embryogenesis, angiogenesis, and wound healing. Here we show that peptides derived from HB-EGF, amphiregulin, hepatocyte growth factor, PDGF-A and PDGF-B, as well as various FGFs are antimicrobial, demonstrating a previously unknown activity of growth factor-derived peptides. The peptides killed the Gram-negative bacteria Escherichia coli, Pseudomonas aeruginosa, and the Gram-positive Bacillus subtilis, as well as the fungus Candida albicans. Several peptides were also active against the Gram-positive S. aureus. Electron microscopy analysis of peptide-treated bacteria, paired with analysis of peptide effects on liposomes, showed that the peptides exerted membrane-breaking effects similar to those seen after treatment with the “classical” human antimicrobial peptide LL-37. Furthermore, HB-EGF was antibacterial per se, and its epitope GKRKKKGKGLGKKRDPCLRKYK retained its activity in presence of physiological salt and plasma. No discernible hemolysis was noted for the growth factor-derived peptides. Besides providing novel templates for design of peptide-based antimicrobials, our findings demonstrate a previously undisclosed link between the family of growth factors and antimicrobial peptides, both of which are induced during tissue remodelling and repair.     

Hyperammonemic coma in a post-partum patient with undiagnosed urea cycle defect

Urea cycle disorders (UCD) are common during neonatal period, and it is rarely reported in adults. We are reporting a patient presenting with post-partum neuropsychiatric symptoms rapidly progressing to coma. Markedly raised serum ammonia level on presentation with an initial normal magnetic resonance imaging (MRI) of brain and normal liver function tests led to the suspicion of UCD, which was confirmed on the basis of urine orotic acid and elevated serum amino acid levels. We had to resort to hemodialysis to correct the hyperammonemic coma, which was unresponsive to conventional anti-ammonia measures. She exhibited remarkable improvement with a progressive decline in serum ammonia with repeated hemodialysis and made a full recovery. Timely diagnosis and early institution of hemodialysis in the setting of a poor neurological status maybe considered a suitable treatment option.     

Clinical outcome of living donor kidney transplantation across simultaneous ABO and HLA incompatibility: Single center experience of first ten cases

Background and aimsPreconditioning using different protocols has been tested to prevent antibody mediated rejection (ABMR) individually for ABO and HLA incompatibility. However, simultaneous presence of both barriers is still less explored. The aim of this study was to report outcomes of institutional desensitization protocol in renal transplant recipients with simultaneous ABO and HLA incompatibility.Materials and methodsThis was a retrospective study conducted from October 2015 to December 2018. All patients with a clinical diagnosis of dialysis dependent chronic kidney disease (CKD), who were prospective coexistent HLA and ABO incompatible renal transplant recipients were included in the study. Patients were followed up and graft function and patient survival was assessed at 1 y from the date of transplant.ResultsMedian and mode baseline anti-A titers were 64, while median and mode baseline anti-B titers were 256. All recipients were discharged by tenth postoperative day. None of the patients had any bleeding complications. Post transplant infection rate was found to be 20 %. A total of 54 therapeutic plasma exchange (TPE) procedures were performed before transplant and 8 were performed after transplant. Graft survival and patient survival was 100 % at 3, 6, 9, and 12 months. Range and mean follow-up period was 15–42 months and 23 months respectively. Mean glomerular filtration rate (GFR) at 1 y using the CKD-EPI equation was 85.25 ± 13.76 mL/min. Biopsy proven ABMR was observed in one case only which was managed with TPE and immunosuppression.ConclusionSimultaneous ABO and HLA incompatibility in renal transplant recipients can be managed successfully with adequate preconditioning and careful monitoring.