[New options for rehabilitation of conductive hearing loss : Tests on normal-hearing subjects with simulated hearing loss]. / Neue Möglichkeiten der Rehabilitation bei Schallleitungsschwerhörigkeit : Tests an normalhörenden Probanden mit simulierter Schwerhörigkeit.

BACKGROUND: Bone conduction hearing aids can be worn as noninvasive devices using a clip or soft band that exerts pressure on the skin, or they can be surgically implanted. ADHEAR (MED-EL GmbH, Innsbruck, Austria) is a novel noninvasive bone conduction hearing aid that is attached behind the ear using an adhesive adapter and does not exert pressure on the skin. ADHEAR is indicated for patients with conductive hearing loss and normal inner ear function. The aim of this study was to evaluate the achievable hearing improvement with ADHEAR. MATERIALS AND METHODS: Twelve subjects with normal hearing participated in this study. To mimic conductive hearing loss, the participants' ear canals were occluded unilaterally with a foam ear plug. The resultant conductive hearing loss was assessed with pure tone air- and bone-conduction threshold audiometry. Hearing ability was tested with and without ADHEAR via free-field tone audiometry, number perception, and monosyllable perception, with the contralateral ear plugged depending on test requirements. RESULTS: Using ADHEAR, the free-field hearing threshold improved by 13.7 dB at 500 Hz, by 17.9 dB at 1 kHz, by 17.2 dB at 2 kHz, and by 9.8 dB at 4 kHz. In the higher frequencies, a significant pure-tone gain of 14.4 dB at 6 kHz and of 16.5 dB at 8 kHz was observed. Number perception with ADHEAR was mean 69.2% at 35 dB, 97.9% at 50 dB, 100% at 65 dB, and 100% at 80 dB. Monosyllable perception with the ADHEAR was mean 35.0% at 35 dB, 72.3% at 50 dB, 93.5% at 65 dB, and 98.8% at 80 dB. CONCLUSION: Hearing performance was significantly better with ADHEAR under all test conditions except those where maximum perception was already achieved without ADHEAR.

Chronic pain in pachyonychia congenita: evidence for neuropathic origin.

BACKGROUND: Pachyonychia congenita (PC) is a rare autosomal dominant skin disease, with chronic pain being the most prominent complaint. Histological studies showing alterations in sensory innervation, along with reports on alterations in mechanical sensitivity, suggest that PC may be a form of neuropathy. OBJECTIVES: Here, for the first time, we aim to evaluate systematically the sensory function of patients with PC vs. controls, in order to investigate the pathophysiology of PC. METHODS: Patients (n = 62) and controls (n = 45) completed the McGill and Douleur Neuropathique-4 (DN4) questionnaires. Sensory testing included detection and pain thresholds, pathological sensations, conditioned pain modulation (CPM) and temporal summation of pain. RESULTS: A moderate-to-severe chronic pain in the feet, throbbing and stabbing in quality, was highly prevalent among patients with PC (86%) and was especially debilitating during weight bearing. In addition, the majority of patients had a DN4 score ≥ 4 (62%), static allodynia (55%) and tingling (53%) in the feet. Compared with controls, patients with PC exhibited thermal and mechanical hypoaesthesia and mechanical hyperalgesia in the feet. CPM was reduced among the patients, and was associated with more enhanced mechanical hyperalgesia in the feet. The specific gene and nature of the causative mutation did not affect any of these features. CONCLUSIONS: Although thermal and mechanical hypoaesthesia may result from thicker skin, its presentation in painful regions, along with mechanical hyperalgesia and allodynia, point towards the possibility of neuropathic changes occurring in PC. The clinical features and DN4 scores support this possibility and therefore neuropathic pain medications may be beneficial for patients with PC.

Auditory cortex activation is modulated by emotion: a functional near-infrared spectroscopy (fNIRS) study.

Visual emotional stimuli evoke enhanced activation in early visual cortex areas which may help organisms to quickly detect biologically salient cues and initiate appropriate approach or avoidance behavior. Functional neuroimaging evidence for the modulation of other sensory modalities by emotion is scarce. Therefore, the aim of the present study was to test whether sensory facilitation by emotional cues can also be found in the auditory domain. We recorded auditory brain activation with functional near-infrared-spectroscopy (fNIRS), a non-invasive and silent neuroimaging technique, while participants were listening to standardized pleasant, unpleasant, and neutral sounds selected from the International Affective Digitized Sound System (IADS). Pleasant and unpleasant sounds led to increased auditory cortex activation as compared to neutral sounds. This is the first study to suggest that the enhanced activation of sensory areas in response to complex emotional stimuli is apparently not restricted to the visual domain but is also evident in the auditory domain.

Orientational anisotropy in infant vision.

Infants prefer to look at horizontal and vertical gratings rather than at oblique gratings only when they are at or near threshold spatial frequencies, as would be expected if acuity for oblique edges is lower than that for horizontal and vertical edges. That such a bias exists as early as 6 weeks of age suggests that the orientational asymmetry of the visual system depends on endogenous maturation rathat than exposure to a carpentered world.

Identification and characterization of the fourth single-stranded-DNA binding domain of replication protein A.

Replication protein A (RPA), the heterotrimeric single-stranded-DNA (ssDNA) binding protein (SSB) of eukaryotes, contains two homologous ssDNA binding domains (A and B) in its largest subunit, RPA1, and a third domain in its second-largest subunit, RPA2. Here we report that Saccharomyces cerevisiae RPA1 contains a previously undetected ssDNA binding domain (domain C) lying in tandem with domains A and B. The carboxy-terminal portion of domain C shows sequence similarity to domains A and B and to the region of RPA2 that binds ssDNA (domain D). The aromatic residues in domains A and B that are known to stack with the ssDNA bases are conserved in domain C, and as in domain A, one of these is required for viability in yeast. Interestingly, the amino-terminal portion of domain C contains a putative Cys4-type zinc-binding motif similar to that of another prokaryotic SSB, T4 gp32. We demonstrate that the ssDNA binding activity of domain C is uniquely sensitive to cysteine modification but that, as with gp32, ssDNA binding is not strictly dependent on zinc. The RPA heterotrimer is thus composed of at least four ssDNA binding domains and exhibits features of both bacterial and phage SSBs.

Rfc4 interacts with Rpa1 and is required for both DNA replication and DNA damage checkpoints in Saccharomyces cerevisiae.

The large subunit of replication protein A (Rpa1) consists of three single-stranded DNA binding domains and an N-terminal domain (Rpa1N) of unknown function. To determine the essential role of this domain we searched for mutations that require wild-type Rpa1N for viability in yeast. A mutation in RFC4, encoding a small subunit of replication factor C (RFC), was found to display allele-specific interactions with mutations in the gene encoding Rpa1 (RFA1). Mutations that map to Rpa1N and confer sensitivity to the DNA synthesis inhibitor hydroxyurea, such as rfa1-t11, are lethal in combination with rfc4-2. The rfc4-2 mutant itself is sensitive to hydroxyurea, and like rfc2 and rfc5 strains, it exhibits defects in the DNA replication block and intra-S checkpoints. RFC4 and the DNA damage checkpoint gene RAD24 were found to be epistatic with respect to DNA damage sensitivity. We show that the rfc4-2 mutant is defective in the G(1)/S DNA damage checkpoint response and that both the rfc4-2 and rfa1-t11 strains are defective in the G(2)/M DNA damage checkpoint. Thus, in addition to its essential role as part of the clamp loader in DNA replication, Rfc4 plays a role as a sensor in multiple DNA checkpoint pathways. Our results suggest that a physical interaction between Rfc4 and Rpa1N is required for both roles.

Analysis of a meiosis-specific URS1 site: sequence requirements and involvement of replication protein A.

URS1 is a transcriptional repressor site found in the promoters of a wide variety of yeast genes that are induced under stress conditions. In the context of meiotic promoters, URS1 sites act as repressor sequences during mitosis and function as activator sites during meiosis. We have investigated the sequence requirements of the URS1 site of the meiosis-specific HOP1 gene (URS1H) and have found differences compared with a URS1 site from a nonmeiotic gene. We have also observed that the sequence specificity for meiotic activation at this site differs from that for mitotic repression. Base pairs flanking the conserved core sequence enhance meiotic induction but are not required for mitotic repression of HOP1. Electrophoretic mobility shift assays of mitotic and meiotic cell extracts show a complex pattern of DNA-protein complexes, suggesting that several different protein factors bind specifically to the site. We have determined that one of the complexes of URS1H is formed by replication protein A (RPA). Although RPA binds to the double-stranded URS1H site in vitro, it has much higher affinity for single-stranded than for double-stranded URS1H, and one-hybrid assays suggest that RPA does not bind to this site at detectable levels in vivo. In addition, conditional-lethal mutations in RPA were found to have no effect on URS1H-mediated repression. These results suggest that although RPA binds to URS1H in vitro, it does not appear to have a functional role in transcriptional repression through this site in vivo.

The Ras GTPase-activating-protein-related human protein IQGAP2 harbors a potential actin binding domain and interacts with calmodulin and Rho family GTPases.

We previously described IQGAP1 as a human protein related to a putative Ras GTPase-activating protein (RasGAP) from the fission yeast Schizosaccharomyces pombe. Here we report the identification of a liver-specific human protein that is 62% identical to IQGAP1. Like IQGAP1, the novel IQGAP2 protein harbors an N-terminal calponin homology motif which functions as an F-actin binding domain in members of the spectrin, filamin, and fimbrin families. Both IQGAPs also harbor several copies of a novel 50- to 55-amino-acid repeat, a single WW domain, and four IQ motifs and have 25% sequence identity with almost the entire S. pombe sar1 RasGAP homolog. As predicted by the presence of IQ motifs, IQGAP2 binds calmodulin. However, neither full-length nor truncated IQGAP2 stimulated the GTPase activity of Ras or its close relatives. Instead, IQGAP2 binds Cdc42 and Racl but not RhoA. This interaction involves the C-terminal half of IQGAP2 and appears to be independent of the nucleotide binding status of the GTPases. Although IQGAP2 shows no GAP activity towards Cdc42 and Rac1, the protein did inhibit both the intrinsic and RhoGAP-stimulated GTP hydrolysis rates of Cdc42 and Rac1, suggesting an alternative mechanism via which IQGAPs might modulate signaling by these GTPases. Since IQGAPs harbor a potential actin binding domain, they could play roles in the Cdc42 and Rac1 controlled generation of specific actin structures.

Proton pump inhibitors reduce cell cycle abnormalities in Barrett's esophagus.

Neoplastic progression in Barrett's esophagus is a multi-step process in which the metaplastic columnar epithelium sequentially evolves through a metaplasia-dysplasia-carcinoma sequence. The expression and DNA copy number of key cell cycle regulatory genes in paired normal and Barrett's esophagus samples was evaluated. Protein levels were evaluated in 60 formalin-fixed, paraffin-embedded human tissues by immunohistochemistry. DNA copy number from 20 fresh tissue pairs was analysed by Southern blot analysis. All normal mucosal samples expressed the p27(kip1) protein, but did not display appreciable nuclear staining for p16(kip4), p21(cip1) or cyclins D1 and E. Barrett's metaplastic specimens displayed increased expression levels of p16(kip4) (74%), p21(cip1) (89%) and cyclins D1 (43%) and E (37%). p27 protein was absent in three cases. There was a significant correlation between the expression of p16(kip4) and cyclin E, and p21(cip1) and p27(kip4) with cyclin D1. DNA analysis did not reveal any amplification or deletion of these genes. Acid suppression, however, was associated with significantly lower expression levels of key cell cycle proteins. Increased expression of key cell cycle regulatory genes appears to occur early in the neoplastic progression associated with Barrett's esophagus. Treatment with proton pump inhibitors appears to alter this increased expression.

Roles of replication protein-A subunits 2 and 3 in DNA replication fork movement in Saccharomyces cerevisiae.

Replication Protein-A, the eukaryotic SSB, consists of a large subunit (RPA1) with strong ssDNA binding activity and two smaller subunits (RPA2 and 3) that may cooperate with RPA1 to bind ssDNA in a higher-order mode. To determine the in vivo function of the two smaller subunits and the potential role of higher-order ssDNA binding, we isolated an assortment of heat-lethal mutations in the genes encoding RPA2 and RPA3. At the permissive temperature, the mutants show a range of effects on DNA replication fidelity and sensitivities to UV and MMS. At the nonpermissive temperature, four out of five RPA2 mutants show a fast-stop DNA synthesis phenotype typical of a replication fork block. In contrast, the fifth RPA2 mutant and all RPA3 mutants are able to complete at least one round of DNA replication at the nonpermissive temperature. The effect of these mutations on the stability of the RPA complex was tested using a coprecipitation assay. At the nonpermissive temperature, we find that RPA1 and RPA2 are dissociated in the fast-stop mutants, but not in the slow-stop mutants. Thus, replication fork movement in vivo requires the association of at least two subunits of RPA. This result is consistent with the hypothesis that RPA functions in vivo by binding ssDNA in a higher-order mode.

Bipartite structure of the SGS1 DNA helicase in Saccharomyces cerevisiae.

SGS1 in yeast encodes a DNA helicase with homology to the human BLM and WRN proteins. This group of proteins is characterized by a highly conserved DNA helicase domain homologous to Escherichia coli RecQ and a large N-terminal domain of unknown function. To determine the role of these domains in SGS1 function, we constructed a series of truncation and helicase-defective (-hd) alleles and examined their ability to complement several sgs1 phenotypes. Certain SGS1 alleles showed distinct phenotypes: sgs1-hd failed to complement the MMS hypersensitivity and hyper-recombination phenotypes, but partially complemented the slow-growth suppression of top3 sgs1 strains and the top1 sgs1 growth defect. Unexpectedly, an allele that encodes the amino terminus alone showed essentially complete complementation of the hyper-recombination and top1 sgs1 defects. In contrast, an allele encoding the helicase domain alone was unable to complement any sgs1 phenotype. Small truncations of the N terminus resulted in hyper-recombination and slow-growth phenotypes in excess of the null allele. These hypermorphic phenotypes could be relieved by deleting more of the N terminus, or in some cases, by a point mutation in the helicase domain. Intragenic complementation experiments demonstrate that both the amino terminus and the DNA helicase are required for full SGS1 function. We conclude that the amino terminus of Sgs1 has an essential role in SGS1 function, distinct from that of the DNA helicase, with which it genetically interacts.

Requirement for three novel protein complexes in the absence of the Sgs1 DNA helicase in Saccharomyces cerevisiae.

The Saccharomyces cerevisiae Sgs1 protein is a member of the RecQ family of DNA helicases and is required for genome stability, but not cell viability. To identify proteins that function in the absence of Sgs1, a synthetic-lethal screen was performed. We obtained mutations in six complementation groups that we refer to as SLX genes. Most of the SLX genes encode uncharacterized open reading frames that are conserved in other species. None of these genes is required for viability and all SLX null mutations are synthetically lethal with mutations in TOP3, encoding the SGS1-interacting DNA topoisomerase. Analysis of the null mutants identified a pair of genes in each of three phenotypic classes. Mutations in MMS4 (SLX2) and SLX3 generate identical phenotypes, including weak UV and strong MMS hypersensitivity, complete loss of sporulation, and synthetic growth defects with mutations in TOP1. Mms4 and Slx3 proteins coimmunoprecipitate from cell extracts, suggesting that they function in a complex. Mutations in SLX5 and SLX8 generate hydroxyurea sensitivity, reduced sporulation efficiency, and a slow-growth phenotype characterized by heterogeneous colony morphology. The Slx5 and Slx8 proteins contain RING finger domains and coimmunoprecipitate from cell extracts. The SLX1 and SLX4 genes are required for viability in the presence of an sgs1 temperature-sensitive allele at the restrictive temperature and Slx1 and Slx4 proteins are similarly associated in cell extracts. We propose that the MMS4/SLX3, SLX5/8, and SLX1/4 gene pairs encode heterodimeric complexes and speculate that these complexes are required to resolve recombination intermediates that arise in response to DNA damage, during meiosis, and in the absence of SGS1/TOP3.

PAIN OUT: the making of an international acute pain registry.

BACKGROUND: About 240 million patients undergo surgery every year, worldwide. Roughly 50% of these patients report clinically significant pain. Numerous barriers impede provision of adequate management. Lack of evidence about appropriateness and effectiveness of interventions is one. A registry can provide such information, eventually facilitating better management. This paper reports the development and feasibility of PAIN OUT, the first international acute pain registry, established with funds from the European Commission, and presents preliminary analysis to illustrate the nature of investigations that registry data make possible. METHODS: On the first postoperative day, 6347 adult patients undergoing orthopaedic or general surgery, in 11 medical centres in Europe and Israel, provided Patient Reported Outcomes (PROs) using a validated questionnaire. Clinical data were abstracted from the patient's chart. RESULTS: Feasibility worked well. Over a period of 1 year, surveyors accrued targeted data sets and entered them into an online browser. Collaborators could receive online feedback comparing their findings about PROs against anonymized findings from other centres. Missing data for the majority of variables were low. Despite considerable variability between institutions, a large number of patients were treated according to the generic, evidence-based recommendations we assessed. However, this was not sufficient to result in acceptable outcomes for the majority of patients. CONCLUSION: The initial development of PAIN OUT has been achieved. From 2013, it continues as a not-for-profit academic project, open to clinicians and researchers worldwide. The International Association for Study of Pain and PAIN OUT will work together to maintain, disseminate and develop the registry.

Restricted tissue expression pattern of a novel human rasGAP-related gene and its murine ortholog.

The mammalian rasGAPs constitute a group of widely expressed proteins involved in the negative regulation of ras-mediated signaling. In this study we have isolated a novel human gene, RASAL (Ras GTPase-activating-like) and its murine ortholog, MRASAL which are most similar to the GAP1 family of rasGAP proteins, based upon the presence and organization of specific conserved domains. Full-length human and murine mRNA sequences are predicted to encode 804 and 799 amino acid polypeptides, respectively. Sequence analysis of these two proteins revealed the presence of two N-terminal calcium-dependent phospholipid binding C2 domains, a conserved GAP related domain (GRD) and a C-terminal pleckstrin homology (PH) domain. Northern blot and mRNA in situ hybridization analyses indicate that RASAL, in contrast to other mammalian rasGAP proteins, has a limited expression pattern; RASAL is highly expressed in the follicular cells of the thyroid and the adrenal medulla and expressed at lower levels in brain, spinal cord and trachea. Human RASAL has been localized by radiation hybrid mapping to chromosome 12q23-24.

Individual changes in T lymphocyte parameters of old human subjects.

Parameters of peripheral blood T lymphocytes were determined repeatedly (twice, 2-4 weeks apart), in ten old (78 + 5) and compared to nine young (31 + 5) human subjects. Assays included percentage of total, helper, and suppressor, T lymphocytes, and the reaction to PHA stimulation for 24, 48, 72, and 96 h, as assessed by levels of proliferation and IL-2 production. A lower response to PHA was observed in the old as compared to the young, with no significant changes in T cell subsets. A marked variability was noted between the results of the first and second determinations of the response to PHA in each individual. The lack of correlation between the two determinations was more prominent in the old. Unresponsiveness to PHA throughout the incubation period, was noted in two old subjects, but, in only one of the two determinations. This transient unresponsiveness was not accompanied by any changes in their clinical state. Thus, establishments of the immune status of the aged should be based on at least two repeated determinations.

The development of visual acuity in infant astigmats.

Acuity for vertical, horizontal, and oblique gratings was measured in 77 infant astigmats using a preferential looking procedure. Measurements were made with the refractive error uncorrected. Most of the infant astigmats were slightly to moderately hyperopic with respect to the test distance of 50 cm. Their acuity was not significantly different from that of a group of non-astigmatic infants. Average acuity for vertical and horizontal gratings increased from 6/200 at 1 month of age to 6/24 at 1 yr. Average acuity for oblique gratings increased more slowly, so that by 1 yr of age it was only 6/33. The only infants to show reductions in acuity were those with a strong myopic focus and one infant with a very strong hyperopic focus. When this infant was tested with optical correction, acuity improved to normal levels. This suggests that meridional amblyopia develops sometime after the first year of life or that it is confined to high spatial frequencies.

Treatment of human ulcers by application of macrophages prepared from a blood unit.

Decubital ulcers contribute to morbidity and mortality in elderly patients. Macrophages play a major role in the process of wound healing. We compared the efficacy of local treatment of decubital ulcers in elderly patients using macrophages prepared from a blood unit, vs. conventional treatments. Patients with decubital ulcers (n = 199) hospitalized during one year in a Geriatric Hospital in Israel, were included in the study. The ulcers of 72 patients (average age 82), who provided informed consent, by themselves or by family, were treated by local injection of macrophages prepared from a blood unit in a closed sterile system. The remaining 127 patients (average age 79) were treated conventionally and served as controls. No exclusion criteria were applied. Only a completely healed ulcer was considered a positive outcome of treatment. In the macrophage-treated group 27% (36 out of 131 ulcers) were healed compared to 6% (15 out of 248) in the control group (p < 0.001). There was also a significantly faster healing in the experimental group (p < 0.02). No side effects were noted. We conclude that Macrophages prepared from a blood unit, in cost-effective, closed, sterile system, are significantly more effective than conventional methods for the treatment of ulcers in elderly patients.

Characterization of lympho-myeloid-erythroid-megakaryocytic stem cells in peripheral blood of hairy cell leukemia patients.

Circulating stem cells with lympho-myeloid-erythroid differentiative capacity have been described in the peripheral blood of hairy cell leukemia (HCL) patients (Michalevicz R. & Revel M. (1987) Interferons regulate the in vitro differentiation of multilineage lympho-myeloid stem cells in Hairy Cell Leukemia. Proc. natn. Acad. Sci. U.S.A. 84, 2307.) The aim of the present work was to enrich the progenitors and characterize their antigenic and growth properties. Peripheral blood (PB) from HCL patients was stained with antibodies (BI3C5 (CD34) and/or My10 as well as RFB7 (CD20) and RFT12 (CD7) and sorted using flow cytometry (FCM) into positive and negative fractions. Peripheral blood cells from several patients showed 4-16% cells positive for the BI3C5/My10. The positive fraction contained all the colony-forming cells and LGEM/LG/LGM colonies were enriched approximately ten-fold as compared to the unsorted population. No colony was found in the negative fraction. All colony forming cells were in the RFB7 and RFT12-negative fractions. Thus, circulating stem cells with lymphoid/myeloid potential can be isolated from PB of HCL patients.

The absorption of low-dose methotrexate in patients with inflammatory bowel disease.

BACKGROUND: Recent clinical trials have demonstrated that methotrexate may have an important therapeutic role in the treatment of patients with inflammatory bowel disease, who are either refractory or intolerant to traditional medical therapy. The aim of this study was to evaluate the pharmacokinetics of low-dose oral methotrexate in patients with inflammatory bowel disease. METHODS: Methotrexate (12.5 mg) was given orally to nine patients with inflammatory bowel disease: five with Crohn's disease, and four with ulcerative colitis, and to six patients with rheumatoid arthritis who served as a control group. Blood samples were drawn at specific intervals to evaluate methotrexate plasma levels. RESULTS: Methotrexate was rapidly absorbed in all patients. Peak concentrations (Cmax) varied considerably, ranging from 0.25-0.87 micro M. The mean Cmax values were similar in all patient groups (0.59 +/- 0.12, 0.69 +/- 0.16 and 0.54 +/- 0.18 micro M, P not significant) for Crohn's disease, ulcerative colitis and rheumatoid arthritis, respectively. The mean area under curve in 120 min (AUC0-120) was also similar in all patient groups (32.9 + 11.3, 43.6 + 9.9 and 41.8 + 14.9 ng.min/mL, P not significant) for Crohn's disease, ulcerative colitis and rheumatoid arthritis, respectively. The mean time to reach Cmax, (tmax), varied between patient groups (84, 112 and 95 min, respectively, with a significant difference, P < 0.02, between the Crohn's disease and ulcerative colitis groups. A negative correlation was found between methotrexate dosage/kg and Cmax (r = -0.74) only in Crohn's disease patients but not in the other patient groups. CONCLUSIONS: Orally administered methotrexate is well absorbed in patients with inflammatory bowel disease including those with severe small bowel disease or resection. If methotrexate is proven to be effective in inflammatory bowel disease, it should be administered orally.

One week triple therapy with omeprazole, clarithromycin and tinidazole for Helicobacter pylori: differing efficacy in previously treated and untreated patients.

BACKGROUND: Triple therapy with omeprazole, clarithromycin, and tinidazole (OCT) has been found to be highly effective against Helicobacter pylori infection. However, its efficacy as a second line regimen for patients who failed metronidazole-based triple therapy has not been evaluated. AIM: The aim of this study was to evaluate the efficacy of low-dose, short-term OCT therapy in an Israeli population, and to compare results obtained in previously treated and untreated patients. METHODS: Patients with duodenal or gastric ulcers and chronic antral gastritis with H. pylori infection as assessed by rapid urease test and/or 14C urea breath test (14C-UBT), were studied. All patients received omeprazole 20 mg b.d., clarithromycin 250 mg b.d. and tinidazole 500 mg b.d. for 7 days. Eradication was assessed by 14C-UBT 4 weeks after treatment. RESULTS: One hundred and fourty-four patients (M/F = 81/63) were enrolled (mean age 48.1 years, range 12-78). Eradication of H. pylori was significantly different between patients who were initially treated with this regimen (90/94, 96%) and patients who had previously failed to eradicate H. pylori with standard triple therapy (27/50, 54%). Moreover, the eradication rate was significantly decreased in patients with more than one previous failure (9/22, 41%) compared to that in patients with only one failure (18/29, 62%). No other differences such as age, gastric pathology, ethnic origin, smoking habits, or pre-treatment urease activity were found to influence the eradication rate. CONCLUSIONS: One-week low-dose triple therapy with OCT is highly effective as an initial therapy in eradicating H. pylori infection. The efficacy is significantly lower when given as a second line treatment in patients who have previously failed to eradicate H. pylori with bismuth-based standard triple therapy.