Dopamine agonists prevent duodenal ulcer relapse

The present study investigated both the healing rate (after four weeks) and the relapse rate (during six months) following treatment with the dopamine-like drugs bromocriptine (2.5 mg twice daily), amantadine (100 mg nocte), or with the H₂ blockers cimetidine (800 mg nocte), and famotidine (40 mg nocte) in 124 patients with endoscopically proven duodenal ulcer (DU). The ulcer was completely healed in 27 (amantadine), 26 (bromocriptine), 23 (cimetidine), and in 24 (famotidine) patients. Relapse was noted in 34.7% (cimetidine) and 25% (famotidine) versus 11.7% (amantadine) and 7.7% (bromocriptine) DU patients. No significant difference was found in initial healing rates. However, the relapse rate in the cimetidine-treated group was significantly higher than in all the other test groups. Additional comparisons between all the treatment categories showed a significantly lower relapse rate with the dopamine-like agents. These important new results indicate that dopamine-like compounds are equally effective as H₂ blockers in inducing DU healing and may offer a promising advantage over H₂ blockers concerning their efficacy in preventing ulcer relapse in DU patients.     

Identification of protective and broadly conserved vaccine antigens from the genome of extraintestinal pathogenic Escherichia coli

Extraintestinal pathogenic Escherichia coli (ExPEC) are a common cause of disease in both mammals and birds. A vaccine to prevent such infections would be desirable given the increasing antibiotic resistance of these bacteria. We have determined the genome sequence of ExPEC IHE3034 (ST95) isolated from a case of neonatal meningitis and compared this to available genome sequences of other ExPEC strains and a few nonpathogenic E. coli. We found 19 genomic islands present in the genome of IHE3034, which are absent in the nonpathogenic E. coli isolates. By using subtractive reverse vaccinology we identified 230 antigens present in ExPEC but absent (or present with low similarity) in nonpathogenic strains. Nine antigens were protective in a mouse challenge model. Some of them were also present in other pathogenic non-ExPEC strains, suggesting that a broadly protective E. coli vaccine may be possible. The gene encoding the most protective antigen was detected in most of the E. coli isolates, highly conserved in sequence and found to be exported by a type II secretion system which seems to be nonfunctional in nonpathogenic strains.     

Hepatitis B and hepatitis C virus infection and outcome of hemodialysis and kidney transplant patients

AIM: A comparison of the outcome of hepatitis virus-positive and -negative kidney transplant and hemodialysis patients was the aim of this investigation. MATERIALS AND METHODS: The study involved 384 kidney transplant patients (67 HBsAg positive, 39 anti-HCV positive, 278 hepatitis negative), transplanted between 1987 and 2001, and 403 hemodialysis patients (128 HBsAg positive, 83 anti-HCV positive, 192 hepatitis negative) who had started hemodialysis and were referred to the kidney transplant waiting list during the same period. RESULTS: Hemodialysis patients were older than transplant patients. Comparison of the groups' survival rates, adjusted for patient age, showed that all kidney transplant patients survived longer than hemodialysis patients (p < 0.001). HBV infection had a negative impact on patient survival, especially in hemodialysis patients. HCV infection did not have a significant influence on patient survival. Cardiovascular disease was the main cause of death of all hemodialysis- and hepatitis-negative transplant patients. Liver failure was one of the leading causes of death in HBV-positive transplant patients. Mortality risk was higher for older patients, HBV-positive and -negative hemodialysis patients. CONCLUSIONS: Kidney transplantation offers longer survival for hepatitis-positive and -negative hemodialysis patients. HBV but not HCV infection had a negative impact on ESRD patient survival.     

A KEL gene encoding serine at position 193 of the Kell glycoprotein results in expression of KEL1 antigen

BACKGROUND: The KEL2/KEL1 (k/K) blood group polymorphism represents 578C>T in the KEL gene and Thr193Met in the Kell glycoprotein. Anti-KEL1 can cause severe hemolytic disease of the fetus and newborn. Molecular genotyping for KEL*1 is routinely used for assessing whether a fetus is at risk. Red blood cells (RBCs) from a KEL:1 blood donor (D1) were found to have abnormal KEL1 expression during evaluation of anti-KEL1 reagents. STUDY DESIGN AND METHODS: Kell genotyping methods, including KEL exon 6 direct sequencing, were applied. KEL cDNA from D1 was sequenced. Flow cytometry was used to assess KEL1 and KEL2 RBC expression. RESULTS: RBCs from the donor, her mother, and an unrelated donor gave weak or negative reactions with some anti-KEL1 reagents. Other Kell-system antigens appeared normal. The three individuals were homozygous for KEL C578 (KEL*2) but heterozygous for a 577A>T transversion, encoding Ser193. They appeared to be KEL*2 homozygotes by routine genotyping methods. Flow cytometry revealed weak KEL1 expression and normal KEL2, similar to that of KEL*2 homozygotes. CONCLUSION: Ser193 in the Kell glycoprotein appears to result in expression of abnormal KEL1, in addition to KEL2. The mutation is not detected by routine Kell genotyping methods and, because of unpredicted KEL1 expression, could lead to a misdiagnosis.     

The hematopoietic cell transplantation comorbidity index is a predictor of early death and survival in adult acute myeloid leukemia patients

The hematopoietic cell transplantation comorbidity index (HCT-CI) is predictive of early death and survival in elderly patients with acute myeloid leukemia (AML). The aim of this study was to determine the prognostic role of the HCT-CI for early death and survival in adult AML patients. In the single-center retrospective study, we analyzed the outcome of 233 adult AML patients. The results indicated that the HCT-CI score is an independent predictor of early death in entire cohort of adult patients with AML. In subgroup analysis, HCT-CI is an independent predictor for early death in elderly patients but not in patients younger than 60 years. A high HCT-CI score predicts shorter survival in adult patients with AML.     

Inducibility of metallothionein biosynthesis in the whole soft tissue of zebra mussels Dreissena polymorpha exposed to cadmium,copper, and pentachlorophenol

Freshwater mussels Dreissena polymorpha (Pallas, 1771) were exposed to the elevated concentrations of Cd (10, 50, 100, and 500 μg/L), Cu (10, 30, 50, and 80 μg/L), and an organochlorinated pesticide, pentachlorophenol (PCP) (1, 10, and 100 μg/L). Induced synthesis of biomarker metallothionein (MT) and changes in concentrations of cytosolic Cd, Cu, and Zn in the whole soft tissue of mussels were monitored after a 7‐day laboratory exposure to the contaminants. A clear dose‐dependent elevation in the MT concentration was observed after exposure to Cd at doses of 10–100 μg/L, and this increase of MT content was accompanied with a linear increase of cytosolic Cd. Cd concentration of 500 μg/L caused no additional increase of MT and Cd in mussel cytosol, suggesting possible toxic effects due to exceeding cellular inducible/defense capacity. Cu exposure resulted with variable changes in MT concentrations, with no clear linear relationship between MT and Cu concentrations in water, although a progressive dose‐dependent accumulation of Cu in the soluble fraction of mussel tissues was recorded. A decrease of cytosolic Zn was evident at higher exposure concentrations of both metals used. PCP in concentrations applied was unable to induce MT synthesis, but the higher concentrations of PCP influenced the cytosolic metal concentrations. In conclusion, the results obtained confirm the specificity of MT induction in D. polymorpha as an biological response on metal stimulation, especially by cadmium, being more closely correlated to MT than copper within the ecologically relevant concentration range. The strong induction potential of cadmium as well as an absence of MT induction following exposure to PCP as an organic chemical contaminant are supporting evidences for usage of zebra mussel MT as a specific biomarker of Cd exposure in biomonitoring programs. © 2009 Wiley Periodicals, Inc. Environ Toxicol, 2010.     

Vascular Access in Patients Treated With Chronic Hemodialysis for 30 Years or More

The aim of our study was to evaluate vascular access in patients treated with chronic hemodialysis for 30 years or more. Patients who had started dialysis in 1978 or earlier were identified from the Slovenian Renal Replacement Therapy Registry. The data on vascular access on April 2008 are presented. Sixteen patients were still alive, seven men and nine women aged 62 ± 12 years (46–84), and they had been treated for 32 ± 1.7 years (30–35), mainly with chronic HD. They had started HD at the age of 30 ± 12 years (13–50), and none had diabetes. The vascular access in nine was a native arteriovenous (AV) fistula, on the forearm in eight patients, and a brachiobasilic fistula in one patient. Four patients had their primary AV fistulas still in use (maximum 35 years). In the remaining five patients, multiple salvage procedures had been performed or new AV fistulas created. The vascular access in four patients was the polytetrafluoroethylene (PTFE) graft, functioning for 1–8 years. In three patients, a non‐cuffed, single‐lumen hemodialysis catheter (a precurved jugular in two patients and a subclavian in one) locked with 30% citrate, with mupirocin at the exit site, was used for 5–12 years. The catheters were exchanged approximately once every two years over a guide‐wire because of mechanical damage. None of these three patients had had catheter‐related sepsis or exit‐site infection. Before catheters, these patients had had multiple AV fistulas and PTFE grafts. Although native AV fistula is the predominant type of vascular access, a greater than 30‐year survival on hemodialysis is possible with the combined use of AV fistula, PTFE graft, and a non‐cuffed hemodialysis catheter locked with citrate.     

Preoperative Ultrasonographic Mapping of Blood Vessels Before Arteriovenous Fistula Construction in Elderly Patients With End‐stage Renal Disease

The aim of our retrospective study was to evaluate the ultrasonographic mapping of both arm and forearm vessels before primary arteriovenous fistula (AVF) construction in elderly patients with end‐stage renal disease. There were 129 patients aged 75 ± 6 (65–93) years, 58% men, 37% diabetics, who participated in the study. The inner diameter of veins (under compression) and arteries, and the arterial peak systolic velocity (PSV) were measured. The presence of arterial calcifications was noted. The positions for possible native AVF construction (radiocephalic and brachiocephalic) were suggested and an AVF was constructed by a trained nephrologist. An adequate cephalic vein was present in 76 (59%) patients (diameter 4.9 ± 1.1 mm) in the right arm, and in 83 (64%) patients (4.7 ± 1.2 mm) in the left arm. Suitable veins in the forearm were recorded in 73 (57%) patients on the right (3.7 ± 0.7 mm) and in 76 (59%) patients on the left (3.5 ± 1.0 mm) side. The inner arterial diameter was: brachial—right 4.6 ± 0.6 mm (calcifications in 26%), left 4.6 ± 0.7 mm (calcifications in 20%); radial—right 2.3 ± 0.4 mm (calcifications in 36%), left 2.3 ± 0.5 mm (calcifications in 29%). In 32% of patients, one native AVF was possible, in 17% two, in 23% three and in 18% four, while in 10% no AVF was possible. In 84% of patients an AVF was constructed, with no significant difference in non‐diabetic vs. diabetic patients (88% vs. 80%) or females vs. males (87% vs. 83%). Native AVF can be constructed in the majority of elderly patients, often in multiple positions, with no significant differences in terms of sex or diabetic status.     

Two MER2-negative individuals with the same novel CD151 mutation and evidence for clinical significance of anti-MER2

BACKGROUND: MER2 (RAPH1), the only antigen of the RAPH blood group system, is located on the tetraspanin CD151. Only four examples of alloanti‐MER2 are known. We report here two new examples of alloanti‐MER2, in women of Pakistani and Turkish origin, one of whom showed signs of a hemolytic transfusion reaction (HTR) after transfusion of 3 units of red cells (RBCs). STUDY DESIGN AND METHODS: Standard serologic methods were used. A monocyte monolayer assay (MMA) was used to assess the potential clinical significance of one of the antibodies. All exons and flanking intronic sequences of CD151 were amplified and sequenced. A homology model for CD151 second extracellular loop (EC2) was constructed based on the crystal structure of CD81. RESULTS: RBCs of both patients did not react with alloanti‐MER2, and neither of their antibodies reacted with MER2‐negative RBCs. The MMA results suggested that the antibody that appeared to have caused an HTR had the potential to be clinically significant. Both patients were homozygous for a 511C>T mutation in CD151 encoding an Arg171Cys change. This change did not result in any significant structural rearrangement in the protein model. CONCLUSIONS: Two MER2‐negative patients with anti‐MER2 are homozygous for the same novel mutation encoding an amino acid substitution in the EC2 of CD151. One of the antibodies may have been responsible for an HTR, and crossmatch‐compatible RBCs should be recommended for transfusion to patients with anti‐MER2.     

Pro-inflammatory and anti-inflammatory cytokines in acute ischemic stroke and their relation to early neurological deficit and stroke outcome

ObjectivesOur aim was to explore (i) the difference in concentration of IL-6, TNF-α and IL-10 between acute ischemic stroke patients and control individuals; (ii) the association of plasma cytokine concentration with stroke severity at admission assessed by NIHSS and stroke outcome in 90 days assessed by Barthel index (BI) and modified Rankin scale (mRS).Materials and methodsStudy included 68 stroke patients admitted within 12 h of symptoms onset and 71 controls.ResultsIL-6 was increased in patients relative to controls (P = 0.035) and this increase was associated with severe stroke (P = 0.007) and worse outcome (P = 0.030 and 0.019; assessed by BI and mRS, respectively), whereas IL-10 was decreased (P = 0.044) and associated with better outcome (P = 0.043). TNF-α did not differ between studied groups (P = 0.302).ConclusionsIncreased IL-6 and reduced IL-10 concentrations are present in early stroke period and are associated with a degree of neurological deficit and/or stroke outcome.