bluuebunny/crossref_metadata_2025 huggingface dataset:
Heme oxygenase‐1 and heme oxygenase‐2 have distinct roles in the proliferation and survival of olfactory receptor neurons mediated by cGMP and bilirubin, respectively
Authors: Chen Jijun , Tu Yajun , Moon Cheil , Nagata Eiichiro , Ronnett Gabriele V.
Published: May 2003

Heme oxygenase (HO) is implicated in protection against oxidative stress, proliferation and apoptosis in many cell types, including neurons. We utilized olfactory receptor neurons (ORNs) as a model to define the roles of HO‐1 and HO‐2 in neuronal development and survival, and to determine the mediators of these effects. The olfactory system is a useful model as ORNs display neurogenesis post‐natally and do not contain nitric oxide synthase (NOS) activity, which could confound results. HO isoforms were expressed in ORNs during embryogenesis and post‐natally. Mice null for either HO‐1 or HO‐2 displayed decreased proliferation of neuronal precursors. However, apoptosis was increased only in HO‐2 null mice. Cyclic GMP immunostaining was reduced in ORNs in both genotypes, providing direct evidence that HO mediates cGMP production in vivo. Bilirubin immunostaining was reduced only in HO‐2 null mice. These roles for HO‐1 and HO‐2 were confirmed using detergent ablation of the epithelium to observe increased neurogenesis of ORNs after target disruption in HO null mice. Primary cultures of ORNs revealed that proliferative and survival effects of HO were mediated through cGMP and bilirubin, respectively. These results support a role for HO, the CO‐cGMP signaling system and bilirubin in neurodevelopment and in response to injury.
In vivo neuroprotective role of NMDA receptors against kainate‐induced excitotoxicity in murine hippocampal pyramidal neurons
Authors: Ogita Kiyokazu , Okuda Hiroaki , Yamamoto Yasuhiro , Nishiyama Norito , Yoneda Yukio
Published: May 2003

Activation of NMDA receptors has been shown to induce either neuronal cell death or neuroprotection against excitotoxicity in cultured cerebellar granule neurons in vitro. We have investigated the effects of pretreatment with NMDA on kainate‐induced neuronal cell death in mouse hippocampus in vivo. The systemic administration of kainate (30 mg/kg), but not NMDA (100 mg/kg), induced severe damage in pyramidal neurons of the hippocampal CA1 and CA3 subfields 3–7 days later, without affecting granule neurons in the dentate gyrus. An immunohistochemical study using an anti‐single‐stranded DNA antibody and TdT‐mediated dUTP nick end labeling analysis both revealed that kainate, but not NMDA, induced DNA fragmentation in the CA1 and CA3 pyramidal neurons 1–3 days after administration. Kainate‐induced neuronal loss was completely prevented by the systemic administration of NMDA (100 mg/kg) 1 h to 1 day previously. No pyramidal neuron was seen with fragmented DNA in the hippocampus of animals injected with kainate 1 day after NMDA treatment. The neuroprotection mediated by NMDA was prevented by the non‐competitive NMDA receptor antagonist MK‐801. Taken together these results indicate that in vivo activation of NMDA receptors is capable of protecting against kainate‐induced neuronal damage through blockade of DNA fragmentation in murine hippocampus.
Two modes of exocytosis from synaptosomes are differentially regulated by protein phosphatase types 2A and 2B
Authors: Baldwin Monique L. , Rostas John A. P. , Sim Alistair T. R.
Published: May 2003

The inhibitors okadaic acid (OA), fostriecin (FOS) and cyclosporin A (CsA), were used to investigate the roles of protein phosphatases in regulating exocytosis in rat brain synaptosomes by measuring glutamate release and the release of the styryl dye FM 2‐10. Depolarization was induced by 30 mm KCl, or 0.3 mm or 1 mm 4‐aminopyridine (4AP). OA and FOS produced a similar partial inhibition of KCl‐ and 0.3 mm 4AP‐ evoked exocytosis in both assays, but had little effect upon exocytosis evoked by 1 mm 4AP. In contrast, CsA had no effect upon KCl‐ and 0.3 mm 4AP‐evoked exocytosis, but significantly enhanced glutamate release but not FM 2‐10 dye release evoked by 1 mm 4AP. None of the phosphatase inhibitors changed calcium signals from FURA‐2‐loaded synaptosomes either before or after depolarization. Pretreatment with 100 nm phorbol 12‐myristate 13‐acetate abolished the inhibitory effect of OA on exocytosis induced by 0.3 mm 4AP. Taken together, these results show that exocytosis from synaptosomes has a phosphatase‐sensitive and phosphatase‐insensitive component, and that there are two modes of phosphatase‐sensitive exocytosis that can be elicited by different depolarization conditions. Moreover, these two modes are differentially sensitive to phosphatase 2A and 2B.
Pentylenetetrazole decreases metabolic glutamate turnover in rat brain
Authors: Eloqayli Haytham , Dahl Carl Bredo , Götestam K. Gunnar , Unsgård Geirmund , Hadidi Hakam , Sonnewald Ursula
Published: May 2003

Seizures were induced in rats by intraperitoneal injection of pentylenetetrazole (PTZ, 70 mg/kg), followed, 30 min later, by injection of [1‐13C]glucose and [1,2‐13C]acetate. Analyses of extracts from cortex, subcortex and cerebellum were performed using 13C magnetic resonance spectroscopy and HPLC. It could be shown that PTZ affected different brain regions differently. The total amounts of glutamate, glutamine, GABA, aspartate and taurine were decreased in the cerebellum and unchanged in the other brain regions. GABAergic neurones in the cortex and subcortex were not affected, whereas those in the cerebellum showed a pronounced decrease of GABA synthesis. However, glutamatergic neurones in all brain regions showed a decrease in glutamate labelling and in addition a decreased turnover in cerebellum. It could be shown that this decrease was in the metabolic pool of glutamate whereas release of glutamate was unaffected since glutamine labelling from glutamate was unchanged. Aspartate turnover was also decreased in all brain regions. Changes in astrocyte metabolism were not detected, indicating that PTZ had no effect on astrocyte metabolism in the early postictal stage.
Proteasome activation and nNOS down‐regulation in neuroblastoma cells expressing a Cu,Zn superoxide dismutase mutant involved in familial ALS
Authors: Aquilano Katia , Rotilio Giuseppe , Ciriolo Maria Rosa
Published: May 2003

Reactive oxygen and nitrogen species have emerged as predominant effectors of neurodegeneration. We demonstrated that expression of the fully active G93A Cu,Zn superoxide dismutase mutant in neuroblastoma cells is associated with an increased level of oxidatively modified proteins, in terms of carbonylated residues. A parallel increase in proteasome activity was detected and this was mandatory in order to assure cell viability. In fact, proteasome inhibition by lactacystin or MG132 resulted in programmed cell death. Nitrosative stress was not involved in the oxidative unbalance, as a decrease in neuronal nitric oxide production and down‐regulation of neuronal nitric oxide synthase (nNOS) level were detected. The nNOS down‐regulation was correlated to increased proteolytic degradation by proteasome, because comparable levels of nNOS were detected in G93A and parental cells upon treatment with lactacystin. The altered rate of proteolysis observed in G93A cells was specific for nNOS as Cu,Zn superoxide dismutase (Cu,Zn SOD) degradation by proteasome was influenced neither by its mutation nor by increased proteasome activity. Treatment with the antioxidant 5,5′‐dimethyl‐1‐pyrroline N‐oxide resulted in inhibition of protein oxidation and decrease in proteasome activity to the basal levels. Overall these results confirm the pro‐oxidant activity of G93A Cu,Zn SOD mutant and, at the same time, suggest a cross‐talk between reactive oxygen and nitrogen species via the proteasome pathway.
Chronic hypoxia potentiates capacitative Ca2+entry in type‐I cortical astrocytes
Authors: Smith I. F. , Plant L. D. , Boyle J. P. , Skinner R. A. , Pearson H. A. , Peers C.
Published: May 2003

Prolonged hypoxia exerts profound effects on cell function, and has been associated with increased production of amyloid β peptides (AβPs) of Alzheimer's disease. Here, we have investigated the effects of chronic hypoxia (2.5% O2, 24 h) on capacitative Ca2+entry (CCE) in primary cultures of rat type‐I cortical astrocytes, and compared results with those obtained in astrocytes exposed to AβPs. Chronic hypoxia caused a marked enhancement of CCE that was observed after intracellular Ca2+stores were depleted by bradykinin application or by exposure to thapsigargin (1 µm). Exposure of cells for 24 h to 1 µmAβP(1−40)did not alter CCE. Enhancement of CCE was not attributable to cell hyperpolarization, as chronically hypoxic cells were significantly depolarized as compared with controls. Mitochondrial inhibition [by FCCP (10 µm) and oligomycin (2.5 µg/mL)] suppressed CCE in all three cell groups, but more importantly there were no significant differences in the magnitude of CCE in the three astrocyte groups under these conditions. Similarly, the antioxidants melatonin and Trolox abolished the enhancement of CCE in hypoxic cells. Our results indicate that chronic hypoxia augments CCE in cortical type‐I astrocytes, a finding which is not mimicked by AβP(1−40)and appears to be dependent on altered mitochondrial function.
Helicobacter pylori Infection and Perforated Peptic Ulcer Prevalence of the Infection and Role of Antimicrobial Treatment
Authors: Gisbert Javier P. , Pajares José María
Published: May 2003

Although the role of Helicobacter pylori infection on noncomplicated peptic ulcer disease has been definitively established, the precise relationship between the organism and complicated ulcer has hardly been studied. The mean prevalence of H. pylori infection in patients with perforated peptic ulcer is of only about 65–70%, which contrasts with the almost 90–100% figure reported in noncomplicated ulcer disease. However, H. pylori infection rates in various studies range markedly from 0% to 100%, suggesting that differences in variables as number and type of diagnostic methods used to diagnose H. pylori infection, or frequency of nonsteroidal anti‐inflammatory drug intake, may be responsible for the low prevalence reported in some studies. Recurrent ulcer disease after peptic ulcer perforation mainly occurs in patients with H. pylori infection, which suggests that the microorganism plays an important role in this complication. All patients with perforated peptic ulcer should be treated by simple closure of the perforation and with therapy aimed at healing of the ulcer and eradicating the H. pylori infection, as disappearance of the organism prevents, or at least decreases, ulcer recurrence and ulcer perforation in patients with H. pylori‐associated perforated ulcers after simple closure. Therefore, H. pylori eradicating treatment should be started during the immediate postoperative period. The patients with intractable recurrent symptoms of peptic ulcer despite adequate medical treatment, but without H. pylori infection (e.g. a patient using nonsteroidal anti‐inflammatory drugs), is probably the only remaining indication for elective definitive surgical treatment of peptic ulcer disease.
Helicobacter pylori and Hepatitis a Virus Infection in School‐Aged Children on Two Isolated Neighborhood Islands in Taiwan
Authors: Chen Liang‐Kung , Hwang Shinn‐Jang , Wu Tzee‐Chung , Chu Chia‐Hsiang , Shaw Cheng‐Kuang
Published: May 2003

Background. The transmission routes of Helicobacter pylori and hepatitis A virus (HAV) infections have been extensively discussed in previous literature. However, whether H. pylori and HAV shared the same transmission pattern or not remains unclear. Lower socioeconomic status was recognized as a consistent risk factor to both infections. However, whether fecal‐oral transmission was a risk factor to both infections is still under debate.

Materials and Methods. In 1996, we conducted a cross‐sectional study to evaluate the seroprevalence of antibody to H. pylori and HAV among the randomly selected school‐aged children (age between 13 and 15) on Green Island (n = 91) and Lanyu Island (n = 138) (two isolated neighborhood islands near Taiwan Main Island).

Results. The seroprevalence of H. pylori and HAV on the Green Island were 82.4% and 5.5%, respectively. The seroprevalence of H. pylori and HAV on Lanyu Island were 71.0% and 90.6%, respectively. H. pylori seroprevalence of all children and the subgroup of 13‐year‐olds was significantly lower on Lanyu Island than Green Island. However, it was not significantly different in subgroups of 14‐ and 15‐year‐olds. HAV seroprevalence was significantly higher on Lanyu Island than Green Island among all children and in each age subgroup. The correlation of H. pylori infection and HAV infection did not demonstrate significant linear correlation on both islands.

Conclusions. In conclusion, H. pylori and HAV infections in school‐aged children of 13–15 years of age on Green Island and Lanyu Island did not demonstrate significant correlation. The results of this study imply that H. pylori and HAV may share different transmission routes of infection.
Serologic Prevalence of Antibodies to Helicobacter pylori in Internationally Adopted Children
Authors: Miller Laurie C. , Kelly Natasha , Tannemaat Martijn , Grand Richard J.
Published: May 2003

Background. Helicobacter pylori (H. pylori) infection has been linked to gastritis, diarrhea, peptic ulcers, failure‐to‐thrive, anemia, as well as predisposition to gastric malignancies. Because many internationally adopted children have diarrhea, failure‐to‐thrive, and anemia on arrival to the US, we determined the prevalence of HP antibodies among these children.

Methods. Serum samples from 226 unselected children from 18 countries who were evaluated in the International Adoption Clinic at New England Medical Center were tested for antibodies to H. pylori. The results of serologic screening were analyzed in relation to age at adoption, site of residence prior to adoption, weight and height, and the presence or absence of anemia, diarrhea, or intestinal parasites.

Results. 31% of internationally adopted children had antibodies to H. pylori. The presence of H. pylori‐antibodies was associated with residence in an orphanage (vs. foster care) prior to adoption, older age at adoption, and coinfection with intestinal parasites. No direct effects on height or weight were identified; no associations with diarrhea or anemia were found.

Conclusions. Internationally adopted children have a high incidence of exposure to H. pylori, as diagnosed serologically. Residence in an orphanage (compared with foster care), older age at adoption, and coinfection with intestinal parasites were more common among children seropositive for anti‐H. pylori antibodies.
The Association of Intestinal Parasitosis and H. Pylori Infection in Children and Adults from a Mexican Community with High Prevalence of Parasitosis
Authors: Torres Javier , Perez G. Perez , Ximenez C. , Muñoz L. , Camorlinga‐Ponce M. , Ramos F. , Gomez A. , Muñoz O.
Published: May 2003

Background. ABSTExperimental evidences have suggested that a Th1 response is unable to eliminate H. pylori colonization; whereas a Th2 response, like the one induced by vaccination, reduces H. pylori infection in animal models. Some parasitic infections induce a polarized Th2 response, which theoretically would favor a reduced H. pylori prevalence. The aim of this work was to study the possible association between parasitic infections and H. pylori prevalence.

Materials and Methods. The study population included 120 children and 188 adults from a low socioeconomic level village. H. pylori prevalence was determined in serum by ELISA; parasitic infections were identified in feces by microscopic examination; and total serum IgE levels, as an indirect indicator of some parasitic infections, were determined by ELISA.

Results. In children, H. pylori prevalence was no different between those with and without intestinal parasitic infection. By contrast, adults with intestinal parasitic infection had a significantly lower H. pylori prevalence than adults without parasites (62.6% compared with 80.4%; p = 0.006, OR 2.45). Also in adults, but not in children, total IgE levels were significantly higher in those without H. pylori infection than in those with H. pylori infection (p < 0.001).

Conclusions. Intestinal parasitic infections and serum IgE levels showed an age‐dependent association with H. pylori prevalence. In adults, but not in children, intestinal parasitic infections and increased IgE levels where associated with a reduced H. pylori prevalence.
Is the Recurrence of Helicobacter pylori Infection After Eradication Therapy Resultant from Recrudescence or Reinfection, in Japan
Authors: Okimoto Tadayoshi , Murakami Kazunari , Sato Ryugo , Miyajima Hajime , Nasu Masaru , Kagawa Jiro , Kodama Masaaki , Fujioka Toshio
Published: May 2003

Background. Reinfection of Helicobacter pylori after eradication is rare in developed countries but most often occurs within 1 year. In the present study, we attempted to differentiate between reinfection and recrudescence of H. pylori strains between 6 months and 6 years after successful eradication in Japan, a country with a high prevalence of H. pylori infection.

Materials and Methods. After successful eradication of H. pylori, 274 patients were followed up by endoscopy and urea breath test. In recurrent patients, H. pylori strains isolated initially and after recurrence were compared using PCR‐based restriction fragment length polymorphism (RFLP) analysis.

Results. Recurrence of H. pylori occurred in 15 of 274 patients (5.5%) at 6 months after eradication and the annual recurrence rate was 2.0% per patient year (between 1 and 6 years). PCR‐based RFLP analysis of H. pylori strains isolated initially and after recurrence showed that 62.5% (at 6 months) and 100% (after 1 years) of bacteria were of different strains.

Conclusion. Reinfection of H. pylori was not as rare at 6 months after eradication as reported previously, and up to 6 years after eradication, the annual reinfection rate is 2.0% per patient year in Japan.
Prevention and Suppression of Helicobacter felis Infection in Mice Using Colostral Preparation with Specific Antibodies
Authors: Marnila Pertti , Rokka Susanna , Rehnberg‐Laiho Leena , Kärkkäinen Päivi , Kosunen Timo U. , Rautelin Hilpi , Hänninen Marja‐Liisa , Syväoja Eeva‐Liisa , Korhonen Hannu
Published: May 2003

Background. Specific antibodies against Helicobacter were enriched from the colostra of hyperimmunized cows. Efficacies of colostral control preparation and immune preparation containing specific antibodies against Helicobacter felis were studied in the prevention and treatment of experimental H. felis infection in mice.

Materials and Methods. H. felis‐infected mice were given either immune or control preparation with or without complement or amoxicillin orally in four different trials. H. felis status was assessed on the basis of bacterial stainings, gastric histology and serum antibodies.

Results. Immune, but not control preparation, prevented H. felis infection (p > 0.01), the efficacy being dependent on the presence of specific antibodies. In the trial on infected Balb/c mice treatment with immune preparation (p = 0.029) but not control preparation decreased the colonization of gastric antrum by H. felis. In the further trials with infected SJL‐mice, treatments with colostral preparations did not decrease colonization. Amoxicillin treatment decreased the colonization with trend‐setting significance (p = 0.056; infected mice as controls), whereas amoxicillin combined with immune preparation had a significant effect (p < 0.0005).

Conclusions. Specific colostral antibodies were useful in the prevention of Helicobacter infection in a mouse model. The results of the treatment trials were controversial but a similar colostral immune preparation against H. pylori could be effective and useful in preventing infections in humans and during antibiotic treatment.
Mixed‐Infection of Antibiotic Susceptible and Resistant Helicobacter pylori Isolates in a Single Patient and Underestimation of Antimicrobial Susceptibility Testing
Authors: Kim Jae J. , Kim Jong G. , Kwon Dong H.
Published: May 2003

Antibiotic resistance among Helicobacter pylori has been increasing worldwide and has begun to affect the overall efficacy of current antibiotic regimens adversely. We examined 220 pairs of H. pylori isolates obtained from both the antrum and corpus of separate patients; 109 (50%) harbored antibiotic‐resistant H. pylori: amoxicillin (0.5%), clarithromycin (5.9%), furazolidone (1.4%), metronidazole (45.5%), nitrofurantoin (1.4%), and tetracycline (6.8%). Heteroresistance among the two biopsy sites from each patient was present in 41 of the 109 patients (38%) with antibiotic resistant H. pylori (e.g. 34% with resistant strains would be misclassified as susceptible if a biopsy of the antrum alone used for antimicrobial susceptibility testing). DNA fingerprinting genotype analysis was carried out on the 41 pairs of isolates with heteroresistance. While different patients had different fingerprinting patterns, each pair of isolates showed identical or similar fingerprinting patterns. These results suggest that antibiotic‐resistant H. pylori typically develop from pre‐existing susceptible strain rather than coinfection with a different strain. The minor differences in genotype (degeneration of genotype) seen reflect one of the processes for development of genetic diversity in H. pylori. No biopsy single site can be considered representative for antimicrobial susceptibility testing.
Antimicrobial Activity of Essential Oils against Helicobacter pylori
Authors: Ohno Tomoyuki , Kita Masakazu , Yamaoka Yoshio , Imamura Shigeyoshi , Yamamoto Toshiro , Mitsufuji Shoji , Kodama Tadashi , Kashima Kei , Imanishi JirO
Published: May 2003

Background. Helicobacter pylori is an important pathogen responsible for gastroduodenal diseases in humans. Although the eradication of H. pylori using antibiotics often improves gastroduodenal diseases, resistance to the antibiotics is emerging.

Materials and Methods. The antimicrobial effect of essential oils and the development of resistance to the essential oils were evaluated in vitro and in vivo.

Results. Thirteen essential oils used in this study completely inhibited the growth of H. pylori in vitro at a concentration of 0.1% (v/v). Cymbopogon citratus (lemongrass) and Lippia citriodora (lemon verbena) were bactericidal against H. pylori at 0.01% at pH 4.0 and 5.0. Resistance to lemongrass did not develop even after 10 sequential passages, whereas resistance to clarithromycin developed under the same conditions. In in vivo studies, the density of H. pylori in the stomach of mice treated with lemongrass was significantly reduced compared with untreated mice.

Conclusions. These results demonstrate that the essential oils are bactericidal against H. pylori without the development of acquired resistance, suggesting that essential oils may have potential as new and safe agents for inclusion in anti‐H. pylori regimens.
Helicobacter pylori Modulation of Gastric and Duodenal Mucosal T Cell Cytokine Secretions in Children Compared with Adults
Authors: Bontems Patrick , Robert Fabienne , Van Gossum André , Cadranel Samy , Mascart Françoise
Published: May 2003

Background. In contrast to adults, ulcers are un‐common in Helicobacter pylori‐infected children. Since immunological determinants influence the outcome of H. pylori infection, we have investigated mucosal T cell responses in H. pylori‐infected children and compared them with those of adults and negative controls.

Material and Methods. Mucosal biopsies were obtained from 43 patients undergoing an upper GI endoscopy for dyspeptic symptoms. The concentrations of released cytokines and the density of CD3+, CD25+ and CD69+cells were evaluated by flow cytometry, and the numbers of cytokine‐secreting cells were measured by ELISPOT.

Results. The numbers of isolated antral CD3+ lymphocytes were only significantly raised in infected adults compared with noninfected controls (p < 0.05), whereas the proportion of CD3+ cells expressing activation markers (CD25 or CD69) remained low. In the stomach, IFN‐γ concentrations increased in infected children and infected adults compared with controls (p < 0.05), but IFN‐γ concentrations were tenfold lower in children than in adults (p < 0.01). IL‐2, IL‐4, IL‐10 and TNF‐α concentrations were similar in infected and in uninfected children and adults. In contrast, in the duodenum, IFN‐γ, as well as IL‐4 and IL‐10 concentrations were only increased in infected children compared with controls (p < 0.05). The concentrations of these cytokines were similar in both groups of adults who, however, like children, displayed a higher number of duodenal IL‐4‐secreting cells compared to controls (p < 0.05).

Conclusion. These results suggest that IFN‐γ secretion in the stomach of H. pylori‐infected patients is lower in children than in adults. This could protect children from development of severe gastro‐duodenal diseases such as ulcer disease. In addition, infected patients are characterised by a dysregulation of the mucosal cytokine secretion at distance from the infection site.
CagA Tyrosine Phosphorylation in Gastric Epithelial Cells Caused by Helicobacter pylori in Patients with Gastric Adenocarcinoma
Authors: Lai Yo‐Ping , Yang Jyh‐Chin , Lin Tzu‐Zung , Wang Jin‐Town , Lin Jaw‐Town
Published: May 2003

Background. Tyrosine phosphorylation of Helicobacter pylori cytotoxin‐associated protein of in gastric epithelial cells is reported. The goals of this study are first to examine the occurrence of CagA tyrosine phosphorylation in H. pylori strains isolated from patients with gastric adenocarcinoma and gastritis, and second to clarify the relationship between the diversity of tyrosine phosphorylation motifs and the presence of CagA tyrosine phosphorylation.

Methods. Fifty‐eight clinical isolates of H. pylori from patients with gastric adenocarcinoma (29 cases) and gastritis (29 cases) were studied for CagA tyrosine phosphorylation by Western blotting. Sequence diversity of tyrosine phosphorylation motifs was analysed among positive‐ or negative‐CagA tyrosine phosphorylation isolates.

Results. Positive CagA tyrosine phosphorylation was found in 93.1% (27 of 29) of strains from gastric adenocarcinoma patients and 51.7% (15 of 29) of strains from gastritis patients (p < 0.001). Intact motifs were found in H. pylori isolates with CagA tyrosine phosphorylation. Of the 16 negative CagA tyrosine phosphorylation isolates, intact tyrosine phosphorylation motifs were found in 15 isolates.

Conclusions. CagA tyrosine phosphorylation, which is significantly greater in strains from gastric adenocarcinoma patients, may play a role in gastric carcinogenesis, and could be a better marker of more virulent strains than the cag pathogenicity island in Asia, where the cag pathogenicity island is present in nearly all H. pylori strains. Sequence diversity of tyrosine phosphorylation motifs on CagA was not related to the presence of tyrosine phosphorylation. The absence of tyrosine phosphorylation motif might result in negative tyrosine phosphorylation phenotypes, but such motifs are not the sole factors associated with CagA tyrosine phosphorylation.
Helicobacter pylori CagA Status, Mucosal Oxidative Damage and Gastritis Phenotype: A Potential Pathway to Cancer?
Authors: Farinati Fabio , Cardin Romilda , Russo Valentina M. , Busatto Graziella , Franco Monica , Rugge Massimo
Published: May 2003

Background. Oxidative DNA damage is associated with Helicobacter pylori infection, atrophy and intestinal metaplasia. H. pylori‐cagA‐positive strains are associated with the highest risk of gastric cancer.

Aims. To ascertain whether cagA‐positive H. pylori infection correlates with higher concentrations of 8OHdG and the presence of precancerous changes.

Patients and Methods. 118 patients were studied (65M/53F, age 61 ± 14 years). Twelve were H. pylori‐negative. Among the H. pylori‐positive patients, 34 were cagA‐positive and 40 were cagA negative. In 32 patients H. pylori had been eradicated at least 6 months before endoscopic sampling.

The phenotype of the gastritis (atrophic compared with nonatrophic, with and without intestinal metaplasia) was scored in biopsy samples obtained from the antrum, corpus, and angularis incisura. In antral biopsy samples, 8‐hydroxydeoxyguanosine was assessed by HPLC (electrochemical detector). CagA status was determined by PCR.

Results. The highest scores for both mononuclear inflammation and activity of gastritis were significantly associated with cagA status (p = 0.036 antrum and p = 0.02 corpus). cagA‐positive infection significantly correlated with a higher prevalence of atrophic‐metaplastic lesions (p = 0.04). cagA‐positive patients had higher 8‐hydroxydeoxyguanosine levels than both cagA‐negative and H. pylori‐negative cases (p = 0.01). The 8‐hydroxydeoxyguanosine levels were significantly higher in multifocal atrophic gastritis (p = 0.04). The odds ratio for cagA‐positive patients having 8OHdG levels above a cut‐off calculated on the basis of the ROC curves were 7.12, overall, reaching 11.25 when only patients younger than 50 were considered.

Conclusions. cagA‐positive patients were characterized: first, for higher scores for gastritis, activity and atrophic and metaplastic lesions; and second for greater oxidative DNA damage overall, at younger age and in the presence of multifocal atrophy. This setting may represent a cancer‐prone biological context.
Editorials: Are HMG‐CoA Reductase Inhibitors Underutilized in Dialysis Patients?
Authors: Seliger Stephen L. , Stehman‐Breen Catherine O.
Published: May 2003

ABSTRACT Patients with end‐stage renal disease (ESRD) treated with dialysis have a dramatically elevated rate of cardiovascular disease (CVD) compared to the general population. Lipid‐lowering therapy with 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase inhibitors (“statins”) has been shown to markedly reduce cardiovascular risk in patients without renal failure, but their effect has not been fully studied in the dialysis population. In this article we will first discuss the known benefits of statin therapy in the general population and summarize the current guidelines for such therapy. We will then examine the evidence linking dyslipidemia and cardiac disease in the dialysis population and discuss possible pathophysiologic mechanisms by which statins could prevent cardiac disease in these patients. We will also review prior clinical studies of the effects of statins in patients on dialysis, with particular attention to the safety and efficacy of these drugs in this population. Finally, we will review how statins are currently being used in the care of dialysis patients and suggest whether an expanded utilization of these drugs could help reduce the enormously high rates of cardiac disease in this patient population.
Hidden Sources of Phosphorus in the Typical American Diet: Does it Matter in Nephrology?
Authors: Uribarri Jaime , Calvo Mona S.
Published: May 2003

ABSTRACT Elevated serum phosphorus is a major, preventable etiologic factor associated with the increased cardiovascular morbidity and mortality of dialysis patients. An important determinant of serum phosphorus is the dietary intake of this mineral; this makes dietary restriction of phosphorus a cornerstone for the prevention and treatment of hyperphosphatemia. The average daily dietary intake of phosphorus is about 1550 mg for males and 1000 mg for females. In general, foods high in protein are also high in phosphorus. These figures, however, are changing as phosphates are currently being added to a large number of processed foods including meats, cheeses, dressings, beverages, and bakery products. As a result, and depending on the food choices, such additives may increase the phosphorus intake by as a much as 1 g/day. Moreover, nutrient composition tables usually do not include the phosphorus from these additives, resulting in an underestimate of the dietary intake of phosphorus in our patients. Our goal is to convey an understanding of the phosphorus content of the current American diet to better equip nephrologists in their attempt to control hyperphosphatemia.
Overcoming Barriers to Arteriovenous Fistula Creation and Use
Authors: Lok Charmaine E. , Oliver Matthew J.
Published: May 2003

ABSTRACT National guidelines advocate the placement of arteriovenous fistulas (AVFs) as the preferred vascular access for hemodialysis (HD) patients because of their low complication rate, lower costs, and prolonged patency, once matured. The current Dialysis Outcomes Quality Initiative (DOQI) guidelines aim for an AVF incidence of 50% and a 40% prevalence in the United States. Although patients currently starting dialysis do so at an increasingly older age and with more comorbidity, they should be given every opportunity to receive an AVF. Meeting this challenge is facilitated by a multidisciplinary approach with early referral to the nephrologist in the predialysis period for access planning. Key components of a vascular access program may include the coordination by a dedicated access coordinator and outcome tracking via a prospective database. Preoperative vessel evaluation and careful selection of an appropriate surgical site, along with an experienced surgeon, improve surgical outcomes. Transposed brachiobasilic or other tertiary fistulas should be offered to patients who cannot receive a native radiocephalic or brachiocephalic fistula. The ability to routinely monitor and salvage failing AVFs is important to achieving successful AVF outcomes. Standardized definitions of AVF outcomes are important to allow individual centers and continuous quality assurance (CQA) programs to track and benchmark their outcomes against local and national standards to help them meet recommended targets.
The Challenges of Diabetes Care in the Dialysis Unit
Authors: McMurray Stephen D.
Published: May 2003

ABSTRACT Nephrologists, dialysis facilities, and payers are confronted with a new and more difficult set of challenges to effectively care for the steadily increasing number of patients with diabetes mellitus (DM) developing end‐stage renal disease (ESRD). U.S. Renal Data System (USRDS) data suggest that the current care of patients with DM on dialysis is suboptimal. Recently published reports have confirmed the value of HbA1C measurements in the diabetic dialysis population, that control of blood glucose lowers mortality, and that a program of care management and diabetes education can have a significant impact on patient outcomes. As leader of the nephrology team, the nephrologist should, at a minimum, be accountable for defining who is managing the diabetes. A more systematic and educated approach to DM and its complications needs to be developed by the renal community.
A Time for Rediscovery: Chronic Hemofiltration for End‐Stage Renal Disease
Authors: McCarthy James T. , Moran John , Posen Gerald , Leypoldt John K. , Hull Alan R. , Jaber Bertrand L. , Correa‐Rotter Ricardo
Published: May 2003

ABSTRACT Provision of maintenance renal replacement therapy (MRRT) is becoming increasingly challenging. The number of patients requiring MRRT is growing rapidly, while the number of nephrologists, nurses, and other staff available to provide therapy is not increasing at a similar rate. Patients are now older and have more comorbid conditions, which magnifies the complexity of their RRT and makes it increasingly difficult to maintain the quality of care within the limitations of constrained economic resources. The two most commonly used MRRTs are hemodialysis (HD) and peritoneal dialysis (PD). A third modality of MRRT, hemofiltration, is not currently in widespread use in North America. In hemofiltration, plasma is filtered through a highly permeable, biocompatible synthetic membrane and waste products are removed by convection and solvent drag as the filtrate moves across the membrane. Hemofiltration equipment constantly monitors the rate of plasma removal and administers a sterile, nonpyrogenic replacement solution at an appropriate rate to replace the waste‐laden ultrafiltrate and avoid vdume depletion in the patient. Hemofiltration may offer some potential clinical advantages to the MRRT patient, including better hemodynamic and cardiovascular stability, enhanced removal of middle molecular weight toxins, increased comfort, and therapy preference. Some reports indicate possible reduced morbidity and mortality and reduced risk of bacterial contamination and inflammation as a result of the use of sterile, ultrapure replacement fluids. Chronic hemofiltration is a relatively simple MRRT option that may offer significant benefits for many patients who have end‐stage renal disease (ESRD) and deserves closer consideration for these patients.
Systolic Hypertension in Hemodialysis Patients
Authors: Agarwal Rajiv
Published: May 2003

ABSTRACT Systolic hypertension with or without diastolic hypertension is a major problem in hemodialysis (HD) patients; isolated diastolic hypertension is uncommon. Accelerated age‐related changes in vascular stiffness, together with factors peculiar to uremia, lead to loss of large and small vessel distensibility and profound changes in circulatory function that includes an increase in systolic pressure and widening of the pulse pressure. Epidemiologic studies show a direct relationship of mortality with systolic blood pressure (BP) and an inverse relationship with diastolic BP. Thus systolic BP should be the focus of treatment. In HD patients with systolic hypertension, diastolic BP is inversely related to cardiovascular risk. An accurate diagnosis of hypertension followed by nonpharmacologic measures (sodium restriction, exercise, dry weight) should be the initial steps in BP reduction. The second step should be the use of antihypertensive agents, particularly the use of angiotensin converting enzyme (ACE) inhibitors and/or β‐blockers. The use of these agents has been associated with better outcomes in observational studies in HD patients. Furthermore, the administration of atenolol and lisinopril can be supervised three times a week to achieve improved BP control. Daily dialysis may improve BP and cardiovascular risk factors. Although more difficult to implement, it may emerge as a feasible alternative to conventional dialysis. Adequate systolic BP control with these available and emerging techniques should help stem the tide of cardiovascular mortality and mortality in HD patients.
Review Articles: Uremic Malnutrition: New Insights Into an Old Problem
Authors: Pupim Lara B. , Ikizler T. A.
Published: May 2003

ABSTRACT Uremic malnutrition is highly prevalent and is associated with poor clinical outcomes in end‐stage renal disease (ESRD) patients. Inadequate diet and a state of persistent catabolism play major roles in predisposing these patients to uremic malnutrition and appear to have an additive effect on overall outcome. Recent studies highlight the existence of a complex syndrome involving chronic inflammation, metabolic abnormalities, and hormonal derangements contributing to the increased morbidity and mortality observed in ESRD patients. Novel strategies such as appetite stimulants, anti‐inflammatory drugs, and anabolic hormones along with conventional nutritional supplementation may provide potential interventions to improve clinical outcome in ESRD patients.
Human Immunodeficiency Virus Infection in End‐Stage Renal Disease Patients
Authors: Rao T. K. Sreepada
Published: May 2003

ABSTRACT Human immunodeficiency virus (HIV) infection in patients with end‐stage renal disease (ESRD) offers many diagnostic and therapeutic challenges to nephrologists. Renal failure may be a direct consequence of viral infection (HIV‐associated nephropathy), or intrinsic renal diseases may occur in previously infected individuals. Patients receiving renal replacement therapy (RRT) may acquire HIV infection from blood transfusions, renal allografts, sexual contacts, or needle sharing by drug addicts. In the early 1980s, the overall prognosis of patients with the acquired immunodeficiency syndrome (AIDS) was very poor, and survival of those with ESRD was dismal. Consequently many even questioned the value of providing maintenance dialysis to patients with AIDS. With advances in diagnostic techniques in serologic and viral markers of disease, and deployment of highly effective antiretroviral agents, the prognosis of HIV‐infected patients has dramatically improved. Over the past two decades, experiences in the management of HIV patients with ESRD is accumulating. Both peritoneal dialysis and hemodialysis are effective modes of therapy and many centers are now beginning to perform renal transplantation in HIV‐infected patients. This article deals with various aspects of HIV infection in patients with ESRD.
Thrombosis in End‐Stage Renal Disease
Authors: Casserly Liam F. , Dember Laura M.
Published: May 2003

ABSTRACT Although renal failure has classically been associated with a bleeding tendency, thrombotic events are common among patients with end‐stage renal disease (ESRD). A variety of thrombosis‐favoring hematologic alterations have been demonstrated in these patients. In addition, “nontraditional” risk factors for thrombosis, such as hyperhomocysteinemia, endothelial dysfunction, inflammation, and malnutrition, are present in a significant proportion of chronic dialysis patients. Hemodialysis (HD) vascular access thrombosis, ischemic heart disease, and renal allograft thrombosis are well‐recognized complications in these patients. Deep venous thrombosis and pulmonary embolism are viewed as rare in chronic dialysis patients, but recent studies suggest that this perception should be reconsidered. Several ESRD treatment factors such as recombinant erythropoietin (EPO) administration, dialyzer bioincompatibilty, and calcineurin inhibitor administration may have prothrombotic effects. In this article we review the pathogenesis and clinical manifestations of thrombosis in ESRD and evaluate the evidence that chronic renal failure or its management predisposes to thrombotic events.
Complications of Percutaneous Treatment of Thrombosed Hemodialysis Access Grafts
Authors: Ash Stephen , Weng Francis L. , Berns Jeffrey S.
Published: May 2003

ABSTRACT Percutaneous catheter‐based thrombolysis is commonly used in association with angioplasty to treat thrombosed hemodialysis arteriovenous grafts. Although major complications of these percutaneous procedures are relatively uncommon, they can result in several potentially serious complications, including pulmonary embolism, cerebral embolism, arterial embolism, bleeding with perigraft hematoma or hemorrhage, and vein rupture. This article reviews the epidemiology, clinical significance, and management of these complications.
Hemodialysis Catheter‐Associated Endocarditis: Clinical Features, Risks, and Costs
Authors: Sandroni Stephen , McGill Rita , Brouwer Deborah
Published: May 2003

ABSTRACT Endocarditis associated with vascular access catheters for hemodialysis (HD) is a catastrophic but not widely appreciated phenomenon. Its current incidence, clinical outcome, and associated costs are not easily ascertained. Increasing use of tunneled catheters for HD access may result in a larger pool of patients at risk for endocarditis. We present two representative cases, review recent trends, and assess the current potential for additional cases.
Peritoneal Dialysis Underutilization: The Impact of an Interventional Nephrology Peritoneal Dialysis Access Program
Authors: Asif Arif , Byers Patricia , Gadalean Florin , Roth David
Published: May 2003

Peritoneal dialysis (PD) is an underutilized form of renal replacement therapy. Recent data have emphasized that only 12% of end‐stage renal disease (ESRD) patients are initiated on this form of therapy in the United States. Patients requiring PD have most often been referred to general surgeons for catheter placement. This has incurred additional delays in starting treatment and loss of decision‐making control by the referring nephrologist. To address this issue, we developed and incorporated our own PD access placement program into the preexisting chronic kidney disease (CKD) education program. To date, 46 patients have undergone 71 procedures. These included 51 (72%) PD catheter insertions, 14 (20%) removals, and 6 (8%) repositioning procedures for poor drainage. PD catheter insertion was performed peritoneoscopically under local anesthesia and a Fogarty catheter was used to reposition a migrated catheter. All of the procedures were performed by nephrologists in a dedicated interventional nephrology (IN) laboratory. All six repositioning procedures failed to restore optimal drainage. Five of these patients had the catheter removed and a new catheter placed during the same procedure. Of these five patients, one had recurrence of poor drainage and opted for hemodialysis (HD). The sixth patient declined reinsertion and chose HD. Of the remaining seven removal procedures, three were due to fungal peritonitis, one due to bowel perforation, one due to severe depression, one due to transplant, and one catheter was removed at the request of the primary physician in a terminally ill patient. Eight of the 51 catheter insertions were during the initial admission of a catastrophic dialysis start. Two of these patients started acute PD and avoided catheter placement for HD. Thirty‐seven of 46 patients have a functional PD catheter with a follow‐up of 8.6 ± 0.8 (mean ± SE) months. During an 18‐month period our PD population has increased from 43 to 80 patients. We conclude that a dedicated PD access placement program coupled with a CKD education program can have a dramatic impact on patient choice and PD growth.
Pharmacomechanical Thrombolysis of Natural Vein Fistulas: Reduced Dose of TPA and Long‐Term Follow‐Up
Authors: Schon Donald , Mishler Rick
Published: May 2003

ABSTRACT Twenty‐five episodes of pharmacomechanical thrombolysis of 20 clotted arteriovenous fistulas (AVFs) are reported. The technique presented utilizes the local instillation of tissue plasminogen activator (TPA) in small doses together with manual maceration to dissolve clot and balloon angioplasty to correct the underlying stenoses. Since the minimum dose of TPA necessary to successfully perform thrombolysis of a natural vein fistula had never been determined, an attempt to use as minimal a dose of TPA as possible was made. Five procedures were performed in fistulas which had previously undergone a thrombolysis procedure with TPA. The procedures were successful in 92% of cases with an average dose of TPA required of 2.3 ± 0.32 mg/procedure. In addition to the 20 accesses in this article, we offer follow‐up life table data on 15 fistulas that were previously reported for a total of 35 accesses salvaged with pharmacomechanical thrombolysis. Primary patency was 11.2 months and secondary patency was 25 months. Fifty‐five percent of fistulas required repeat angioplasty procedures at an average of 3.6‐month intervals. In addition, more than half of the fistulas that presented with clotting required repeat interventions for continued patency. This report demonstrates the effectiveness of small doses of TPA in successful pharmacomechanical thrombolysis of clotted fistulas.
Nephrogenic Fibrosing Dermopathy: An Unusual Skin Condition Associated with Kidney Disease
Authors: Perazella Mark A. , Ishibe Shuta , Perazella Mark A. , Reilly Robert F.
Published: May 2003

ABSTRACT We report the case of a patient who, while on long‐term hemodialysis (HD), developed nephrogenic fibrosing dermopathy, a newly described sclerosing skin disorder. This disorder is characterized by thickened, hardened skin with brawny hyperpigmentation and raised plaques. The most common patient complaints are pruritus and dysesthesia. The extremities are predominantly involved with sparing of the torso and face. Dysfunction of internal organs has not been described, distinguishing it from other fibrosing conditions such as scleroderma. The skin biopsy is characterized by haphazardly arranged dermal collagen spindle cells in the reticular dermis. Extensive mucin deposits are interposed between collagen bundles and there are an increased number of fibroblast‐type cells. In contrast to scleroderma, inflammatory cells are generally absent. Corticosteroid therapy can be tried, but in our patient was of no benefit.