Biomedical subjects

A Sonnenberg

Publications and source records attributed to A Sonnenberg.

At least 109 records · Page 6Linked to original sources

PubMed1999

A case-control study of the factors associated with spontaneous resolution of hepatitis C viremia.

OBJECTIVE: Infection with the hepatitis C virus (HCV) becomes chronic in 85% of the infected individuals. We studied risk factors that may predict clearance of HCV. METHODS: A case-control study compared the association between risk factors and viral clearance. Viral clearance was defined as presence of a positive HCV antibody test plus negative HCV test by polymerase chain reaction (PCR). Forty-four cases and 214 controls with persistent viremia were identified in a database of patients evaluated at the Gastroenterology Clinic of the University of New Mexico. RESULTS: Of all 258 HCV-antibody-positive patients, 17% had a negative test by PCR. The multivariate logistic regression revealed that a history of parenteral exposure and a long time interval since the most recent exposure were both associated with an increased likelihood of persistent viremia, whereas subjects who had been monogamous for longer time periods were more likely to have cleared HCV from their serum. A low serum level of ferritin also conferred protection against persistent viremia. Case and control subjects did not differ with respect to their demographic characteristics, occurrence of comorbid disease, previous medical history, occurrence of sexually transmitted diseases, blood group, and risky health or sexual practices. CONCLUSIONS: These data suggest that route of exposure and time when exposure occurred are important in the development of persistent HCV infection.

Adult↗

PubMed1999

Exposure to risk factors for ulcerative colitis occurs during an early period of life.

OBJECTIVE: It has been speculated that environmental factors play a role in the etiology of ulcerative colitis. A previous analysis revealed that the time trends of ulcerative colitis in England were shaped by an underlying birth-cohort pattern. We undertook this study to test whether the birth-cohort pattern was a unique feature of the English vital statistics or whether a similar phenomenon could also be ascertained in the mortality statistics from a different country, such as Switzerland. Besides comparing the data of ulcerative colitis from Switzerland and England, the trends of ulcerative colitis were compared with those of gastric and duodenal ulcer. METHODS: Death rates from ulcerative colitis, gastric ulcer, and duodenal ulcer were plotted against the period of death and period of birth. An age-standardized cohort mortality ratio was calculated as a summary statistic of the overall mortality associated with each consecutive birth-cohort. RESULTS: Mortality from ulcerative colitis increased among successive generations born throughout the 19th century. It peaked in individuals born around 1890 and has declined since then. Strikingly similar patterns were found in Switzerland and England. The birth-cohort pattern underlying the time trends of ulcerative colitis applied equally to the data for women and men. In comparison with peptic ulcer, the birth-cohort pattern of ulcerative colitis was almost identical to that of duodenal ulcer. It peaked in both countries 10-20 yr later than gastric ulcer. CONCLUSIONS: The birth-cohort pattern indicates that acquisition of ulcerative colitis is strongly influenced by environmental risk factors and that the exposure to these factors occurs during an early period of life. The similarity in the birth-cohort patterns of duodenal ulcer and ulcerative colitis could hint at a childhood infection or a related mode of transmission in both diseases.

Adult↗

PubMed1999

Outcome of erosive reflux esophagitis after Nissen fundoplication.

OBJECTIVE: The aim of this study was to compare the utilization of health care resources and long term outcome of erosive esophagitis in patients treated with and without open Nissen fundoplication. METHODS: A population of 35,725 patients with erosive esophagitis was extracted from the computerized database of the US Department of Veterans Affairs. Subjects were stratified by severity of disease into erosive esophagitis alone versus erosive esophagitis complicated by esophageal ulcers or peptic strictures. During a mean follow-up period of 4.2 yr (range 1-12 yr), the consumption of health care resources, except for medications, was compared between case and control subjects treated with and without fundoplication, respectively. RESULTS: Among patients with complicated erosive esophagitis, 5,064 control subjects were treated without, and 542 case subjects were treated with, fundoplication. Cases incurred less recurrence of esophageal erosions (controls: 56% vs cases: 46%), esophageal ulcers (38% vs 33%), and peptic strictures (43% vs 32%) during follow-up. Among patients with erosive esophagitis but no complications, 29,514 control subjects were treated without, and 605 case subjects were treated with, fundoplication. Cases did not experience any change in the recurrence of esophageal erosions (controls: 25% vs cases: 24%). Irrespective of treatment type, none of the case or control subjects with erosive esophagitis alone developed esophageal ulcers or peptic strictures during follow-up. Compared with controls, however, after fundoplication in erosive esophagitis alone, cases incurred more dysphagia (2.6% vs 4.6%), postsurgical syndromes (0.8% vs 1.7%), as well as more outpatient visits (34 vs 40 visits/patient) and outpatient procedures (2.7 vs 4.3 procedures/patient). CONCLUSIONS: Fundoplication improves the clinical outcome of erosive esophagitis in patients with concomitant esophageal ulcers and strictures, but not in patients without such complications. Fundoplication does not reduce the consumption of health care resources.

Case-Control Studies↗

PubMed1999

Commonalities in the time trends of Crohn's disease and ulcerative colitis.

OBJECTIVE: The analysis of the time trends of inflammatory bowel disease (IBD) is a powerful research tool to assess the contribution of environmental factors to its etiology and to gain insights about possible causative mechanisms. A previous study revealed a characteristic relationship between the time trends of mortality from Crohn's disease and ulcerative colitis. The present study aimed to test whether the most recent temporal patterns still corroborate the hypothesis of two interacting risk factors in the development of IBD. The time trends of IBD from six countries were checked for common features. METHODS: Mortality data from Australia, Canada, England and Wales, the Netherlands, Sweden, and the United States were analyzed. Age- and sex-specific death rates, as well as total death rates, from Crohn's disease and ulcerative colitis were plotted against the period of death. RESULTS: Mortality from ulcerative colitis decreased continuously during the past 40 years. Mortality from Crohn's disease increased between 1950 and the mid-1970's until reaching a similar level as mortality from ulcerative colitis. Since then the death rates of both diseases have followed a parallel time course. A similar behavior was found, if male and female data were analyzed separately. It could be also discerned in the time trends of each age group. The data from all six countries revealed identical temporal patterns. CONCLUSIONS: The similar time trends of IBD from different countries support the hypothesis that identical causative mechanisms are responsible for the mortality and the occurrence of IBD among populations characterized by different political history and health care systems. The rapidity of the temporal changes implicates environmental agents in the etiology of both diseases. The relationships between the temporal changes of Crohn's disease and ulcerative colitis point at the existence of a shared risk factor responsible for the occurrence of both diseases, and at the existence of at least one additional factor, responsible for the expression of Crohn's disease alone.

Adult↗

PubMed1999

Is virtual colonoscopy a cost-effective option to screen for colorectal cancer?

OBJECTIVE: Computed tomography (CT) or magnetic resonance (MR) colonography is a new technique that uses data generated from CT or MR imaging to create two- and three-dimensional scans of the colon. It has been advocated to become the new primary technique of screening for colorectal cancer. The economic feasibility of such recommendation, however, has not yet been evaluated. METHODS: The cost-effectiveness of two screening strategies using CT colonography or conventional colonoscopy was compared by computer models based on a Markov process. We supposed that a hypothetical population of 100,000 subjects aged 50 yr undergoes a screening procedure every 10 yr. Suspicious findings of CT colonography are worked-up by colonoscopy. After polypectomy, colonoscopy is repeated every 3 yr until no adenomatous polyps are found. RESULTS: Under baseline conditions, screening by CT colonography costs $24,586 per life-year saved, compared with $20,930 spent on colonoscopy screening. The incremental cost-effectiveness ratios comparing CT colonography to no screening and colonoscopy to CT colonography were $11,484 and $10,408, respectively. Screening by colonoscopy remains more cost-effective even if the sensitivity and specificity of CT colonography both rise to 100%. For the two screening procedures to become similarly cost-effective, CT colonoscopy needs to be associated with an initial compliance rate 15-20% better or procedural costs 54% less than colonoscopy. CONCLUSIONS: To become cost-effective and be able to compete with colonoscopy in screening for colorectal cancer, CT or MR colonography would need be offered at a very low price or result in compliance rates much better than those associated with colonoscopy.

Adult↗

PubMed1999

The effect of antibiotic therapy on bleeding from duodenal ulcer.

OBJECTIVE: We conducted this study to test whether eradication of Helicobacter pylori (H. pylori) infection prevents hemorrhage related to duodenal ulcer. METHODS: Patients with H. pylori infection and endoscopically proven duodenal ulcers without ulcer-related hemorrhage were enrolled into four randomized, double-blind, multicenter studies using the same study protocol. They were treated with clarithromycin plus omeprazole (441 patients), omeprazole alone (447 patients), or ranitidine alone (263 patients). Success of H. pylori eradication was evaluated by the 13C-urea breath test 4-6 wk after the last dose of study drug. Follow-up continued at monthly intervals up to 1 yr after the last dose of study drug. RESULTS: Bleeding due to duodenal ulcer was not observed in any patients who received clarithromycin plus omeprazole, whereas five patients in the omeprazole treatment group and six patients in the ranitidine treatment group experienced an episode of ulcer-related hemorrhage during follow-up. All patients who experienced ulcer-related bleeding were male. When compared by bleeding, there were no significant differences with respect to ethnicity, alcohol consumption, or tobacco use. H. pylori infection was no longer detectable in 68% of patients after treatment with clarithromycin plus omeprazole, compared with 5% after treatment with omeprazole alone or 4% after treatment with ranitidine alone. CONCLUSION: In a population of duodenal ulcer patients without predisposing risk factors for ulcer bleeding, antibiotic eradication or suppression of H. pylori infection prevented the occurrence of ulcer-related hemorrhage for up to 1 yr after therapy.

Adult↗

PubMed1999

Corpus gastritis is protective against reflux oesophagitis.

BACKGROUND: Gastric acid is important in the pathogenesis of reflux oesophagitis. Acid production by the gastric corpus is reduced in corpus gastritis. AIMS: To determine whether corpus gastritis protects against reflux oesophagitis. METHODS: Patients presenting for elective oesophagogastroduodenoscopy were studied. Two biopsy specimens were taken from the antrum, corpus, and cardia and stained with haematoxylin/eosin and Diff-Quick II stains. The presence and severity of gastritis were graded according to a modified updated Sydney classification. RESULTS: Of 302 patients, 154 had endoscopic signs of reflux oesophagitis. There was no difference between patients with and controls without oesophagitis in the overall infection rates with Helicobacter pylori. Acute or chronic corpus gastritis occurred less often in patients with than those without reflux oesophagitis. Compared with controls, corpus gastritis was less severe in patients with reflux oesophagitis. The presence of acute or chronic gastritis in the corpus was significantly correlated with either type of gastritis in other areas of the stomach. In a multivariate logistic regression, age, sex, smoking status, and the presence of chronic corpus gastritis all exerted a significant influence on the presence of reflux oesophagitis. Chronic corpus gastritis was associated with a 54% reduced risk for reflux oesophagitis. CONCLUSIONS: While infection with H pylori alone may not affect the occurrence of reflux oesophagitis, the development of chronic corpus gastritis seems to be protective.

Acute Disease↗

PubMed1999

The unsolved problem of surveillance for colorectal cancer in ulcerative colitis.

The association between long standing extensive ulcerative colitis and the increased risk for developing colorectal cancer suggests that surveillance by frequent and regular colonoscopies may provide a means for reducing cancer-related morbidity and mortality. A crude calculation suggests that such a surveillance program would also be cost effective. None of several clinical trials, however, has been able to provide unequivocal evidence in favour of surveillance. The major reason for this failure relates to the prohibitively large number of patients with ulcerative colitis who need to be followed over a prolonged time period before statistically sound results would be obtained. Because models of decision analyses themselves have to rely on medical evidence, they cannot provide a substitute for deficient clinical data. The issue of surveillance colonoscopy cannot be resolved by the available knowledge or analytical tools. Hopefully, new techniques of surveillance or even a cure for ulcerative colitis will render the question mute of whether or not to screen patients with ulcerative colitis by frequent colonoscopy.

Colitis, Ulcerative↗

PubMed1999

Partial rescue of epithelial phenotype in integrin beta4 null mice by a keratin-5 promoter driven human integrin beta4 transgene.

Integrin beta4 null mice exhibit extensive epidermal detachment, reminiscent of the human skin blistering disease junctional epidermolysis bullosa associated with pyloric atresia. Hemidesmosomes, the stable adhesion structures of squamous epithelia, are not formed in the absence of alpha6beta4. Null mutant mice die shortly after birth, but apart from their striking epithelial phenotype, no obvious developmental defects have been observed. To elucidate the cause of death in these mice, we generated transgenic mice with a heterologous construct consisting of the squamous epithelial-specific keratin-5 promoter and a human integrin beta4 subunit cDNA. The transgene was not expressed in the presence of endogenous beta4, probably as a result of competition for a limited pool of alpha6 subunits. In a beta4 null background, however, the transgene was expressed, and its expression pattern followed that of squamous epithelial-specific keratins. These rescued pups appeared healthy and ultrastructural analysis revealed that the interspecies heterodimer alpha6(mouse)/beta4(human) was sufficient to trigger the assembly of hemidesmosomes. After a variable period of up to 48 hours after birth these animals began to exhibit haemorrhages at the plantar and palmar areas. We observed the formation of small blisters and found that the transgene was not detectably expressed in this region, which is devoid of hair follicles. The rescued neonates became increasingly cyanotic and died soon after the onset of this phenomenon. We performed a developmental study of the expression of beta4 in the complete respiratory tract, but we found no correlation between the spatiotemporal distribution of beta4 and the onset of the respiratory insufficiency. It became clear, however, that there was a gradual detachment of squamous epithelia in the oral and nasal cavities which led to obstruction of the respiratory tract, suggesting that in beta4 null and rescued mice, neonatal death was a direct consequence of decreased adhesion properties of hairless squamous epithelia, rather than a developmental defect of the lungs.

Animals↗

PubMed1999

Antibiotic therapy of Helicobacter pylori infection reduces healthcare expenditures related to duodenal ulcer.

OBJECTIVE: To test whether eradication of Helicobacter pylori saves costs in the treatment of duodenal ulcer disease, compared with conventional antisecretory therapy. STUDY DESIGN: A prospective, double-blind clinical trial was conducted at 132 sites in the United States. PATIENTS AND METHODS: Adult patients with active duodenal ulcer and confirmed H pylori infection were randomized to receive treatment with clarithromycin plus omeprazole, omeprazole alone, or ranitidine alone. Utilization of ulcer-related healthcare resources was documented during 1 year following therapy. Costs were calculated by multiplying the number of health resources utilized by the cost of each resource. Resource costs were obtained from a database containing actual average costs spent by managed care organizations on outpatient and inpatient treatment. RESULTS: Of the 819 patients enrolled, 727 completed the study: 243 received clarithromycin plus omeprazole, 248 omeprazole alone, and 236 ranitidine alone. Ulcer-related health resource utilization and total ulcer-related healthcare costs were decreased after treatment with clarithromycin plus omeprazole, compared to treatment with omeprazole or ranitidine alone. In multivariate linear regression analyses, type of treatment was found to be a significant predictor of total costs. Specific costs associated with endoscopic examinations, clinic visits, and medications were also significantly reduced by treatment with clarithromycin plus omeprazole as compared to other treatment forms. CONCLUSIONS: In a managed care environment, therapy with clarithromycin and omeprazole to eradicate H pylori in patients with duodenal ulcer disease would result in significant cost savings secondary to a reduction in the utilization of healthcare resources.

Adolescent↗

PubMed1999

Limitations of the faecal occult blood test in screening for colorectal cancer.

BACKGROUND: A screening test should be acceptable, safe, simple, accurate, reliable, effective, and inexpensive. Screening for colorectal cancer with the faecal occult blood test is done to reduce the incidence and mortality from colorectal cancer. How does this test measure up to these requirements? METHODS: The characteristics of faecal occult blood test are described by means of clinical epidemiology, analysing its compliance, sensitivity, specificity, positive predictive value, and its test performance in Bernoulli trials. A decision tree and a Markov model are used to compare the cost-effectiveness of screening strategies involving faecal occult blood test and colonoscopy. RESULTS: After 5-10 years, patient compliance in a faecal occult blood test screening programme falls below 50%. Over 80% of the patients are likely to leave the programme before its completion. Although the test itself may seem safe and simple, the high rate of false-positive outcomes exposes many subjects to the potential complications of colonoscopy. The high rate of false-negative tests gives patients with colorectal cancer a false sense of security and delays their proper diagnostic work-up. In populations with low prevalence rates of colorectal cancer, faecal occult blood test becomes very inaccurate in diagnosing colorectal cancer, as its positive predictive value falls below 5%. Its long-term test performance is unreliable in that it comes to depend on the frequency, with which the test is repeated. Any negative or positive test result can be achieved by varying the frequency of test repetition. Screening by colonoscopy every five or ten years is more cost-effective than screening by annual faecal occult blood test in preventing the occurrence of colorectal cancer and its associated mortality. CONCLUSIONS: Screening strategies for colorectal cancer involving faecal occult blood test should be abandoned.

Colonoscopy↗

PubMed1998

Determinants in the cytoplasmic domain of P-selectin required for sorting to secretory granules.

P-selectin is a granule membrane protein of platelets and endothelial cells that is expressed at the plasma membrane after cell activation. To determine which residues in its cytoplasmic tail are important for sorting to storage granules during biosynthesis, we expressed P-selectin mutants in AtT-20, a murine cell line with secretory granules that contain the hormone corticotropin ('ACTH'). Immunofluorescence microscopy of permeabilized cells revealed that wild-type P-selectin and mutants with alanine substitutions at 14 different positions in the cytoplasmic tail were concentrated in the tips of the cellular processes, which contain the majority of corticotropin granules. However, targeting to the cell tips was greatly decreased for Tyr777-->Ala, Tyr777-->Phe, Gly778-->Ala, Phe780-->Ala and Leu768/Asn769-->Ala/Ala mutants. The reduced presence of these mutants in corticotropin granules was confirmed by immunoelectron microscopy. Stimulation of AtT-20 transfectants with 8-Br-cAMP resulted in a significant increase in membrane expression of wild-type P-selectin, but in only a marginal increase in the surface expression of the five mutants. Antibody binding studies with intact and permeabilized cells demonstrated that the percentage of P-selectin that is expressed on the surface of the cells was considerably higher for these mutants than for wild-type P-selectin (6%), ranging from approximately 20% for the Gly778 and Phe780 mutants to 63% for the Leu768/Asn769 mutant. Taken together, these results indicate that Tyr777, Gly778 and Phe780 form part of an atypical tyrosine-based motif, which also requires the presence Leu768 and/or Asn769 to mediate sorting of P-selectin to secretory granules.

Amino Acid Sequence↗

PubMed1998

Cre-loxP-mediated inactivation of the alpha6A integrin splice variant in vivo: evidence for a specific functional role of alpha6A in lymphocyte migration but not in heart development.

Two splice variants of the alpha6 integrin subunit, alpha6A and alpha6B, with different cytoplasmic domains, have previously been described. While alpha6B is expressed throughout the development of the mouse, the expression of alpha6A begins at 8.5 days post coitum and is initially restricted to the myocardium. Later in ontogeny, alpha6A is found in various epithelia and in certain cells of the immune system. In this study, we have investigated the function of alpha6A in vivo by generating knockout mice deficient for this splice variant. The Cre- loxP system of the bacteriophage P1 was used to specifically remove the exon encoding the cytoplasmic domain of alpha6A in embryonic stem cells, and the deletion resulted in the expression of alpha6B in all tissues that normally express alpha6A. We show that alpha6A-/- mice develop normally and are fertile. The substitution of alpha6A by alpha6B does not impair the development and function of the heart, hemidesmosome formation in the epidermis, or keratinocyte migration. Furthermore, T cells differentiated normally in alpha6A-/- mice. However, the substitution of alpha6A by alpha6B leads to a decrease in the migration of lymphocytes through laminin-coated Transwell filters and to a reduction of the number of T cells isolated from the peripheral and mesenteric lymph nodes. Lymphocyte homing to the lymph nodes, which involves various types of integrin-ligand interactions, was not affected in the alpha6A knockout mice, indicating that the reduced number of lymph node cells could not be directly attributed to defects in lymphocyte trafficking. Nevertheless, the expression of alpha6A might be necessary for optimal lymphocyte migration on laminin in certain pathological conditions.

Alternative Splicing↗

PubMed1998

Genomic organization of the human alpha 3 integrin subunit gene.

The alpha 3 beta 1 integrin is a receptor for various laminin isoforms and plays an important role in the maintenance of tissue integrity. We have characterized the genomic structure of the complete gene for the human alpha 3 integrin subunit. The gene contains 26 exons spanning a region of 36.3 kb of genomic DNA. Its structure closely resembles that of alpha 6, another of the three integrin alpha-subunits that are part of laminin receptors, except that it lacks the corresponding exon 5A, which encodes an X1 region in the extracellular domain of alpha 6. However, the alpha 3 gene contains the equivalent of an exon 5B for an X2-like region, which in alpha 6 and alpha 7 is present only in certain tissue-specific alternative transcripts. The two A and B cytoplasmic variants of alpha 3, which are common to the three laminin receptor integrin alpha-subunits, are encoded by separate exons.

Alternative Splicing↗

PubMed1998

Hemidesmosome formation is initiated by the beta4 integrin subunit, requires complex formation of beta4 and HD1/plectin, and involves a direct interaction between beta4 and the bullous pemphigoid antigen 180.

Hemidesmosomes (HDs) are stable anchoring structures that mediate the link between the intermediate filament cytoskeleton and the cell substratum. We investigated the contribution of various segments of the beta4 integrin cytoplasmic domain in the formation of HDs in transient transfection studies using immortalized keratinocytes derived from an epidermolysis bullosa patient deficient in beta4 expression. We found that the expression of wild-type beta4 restored the ability of the beta4-deficient cells to form HDs and that distinct domains in the NH2- and COOH-terminal regions of the beta4 cytoplasmic domain are required for the localization of HD1/plectin and the bullous pemphigoid antigens 180 (BP180) and 230 (BP230) in these HDs. The tyrosine activation motif located in the connecting segment (CS) of the beta4 cytoplasmic domain was dispensable for HD formation, although it may be involved in the efficient localization of BP180. Using the yeast two-hybrid system, we could demonstrate a direct interaction between beta4 and BP180 which involves sequences within the COOH-terminal part of the CS and the third fibronectin type III (FNIII) repeat. Immunoprecipitation studies using COS-7 cells transfected with cDNAs for alpha6 and beta4 and a mutant BP180 which lacks the collagenous extracellular domain confirmed the interaction of beta4 with BP180. Nevertheless, beta4 mutants which contained the BP180-binding region, but lacked sequences required for the localization of HD1/plectin, failed to localize BP180 in HDs. Additional yeast two- hybrid assays indicated that the 85 COOH-terminal residues of beta4 can interact with the first NH2-terminal pair of FNIII repeats and the CS, suggesting that the cytoplasmic domain of beta4 is folded back upon itself. Unfolding of the cytoplasmic domain may be part of a mechanism by which the interaction of beta4 with other hemidesmosomal components, e.g., BP180, is regulated.

Animals↗

PubMed1998

Cost savings in duodenal ulcer therapy through Helicobacter pylori eradication compared with conventional therapies: results of a randomized, double-blind, multicenter trial. Gastrointestinal Utilization Trial Study Group.

BACKGROUND: We hypothesized that treatment of duodenal ulcer disease with antibiotic therapy directed toward Helicobacter pylori infection is more cost-effective than therapy with antisecretory agents. METHODS: A randomized, double-blind, multicenter clinical trial of adult patients with active duodenal ulcer and H. pylori infection was conducted. Patients were randomized to receive 500 mg of clarithromycin 3 times a day plus 40 mg of omeprazole daily for 14 days followed by 20 mg of omeprazole daily for an additional 14 days (group 1), 20 mg of omeprazole daily for 28 days (group 2), or 150 mg of ranitidine hydrochloride twice a day for 28 days (group 3). The use of ulcer-related health care resources was documented during monthly interviews for 1 year after the initial therapy. Clinical success was evaluated 4 to 6 weeks and 1 year after the end of therapy. RESULTS: Of the 819 patients enrolled, 727 completed the study. Group 1 included 243 patients; group 2, 248 patients; and group 3, 236 patients. Patients in group 1 used fewer ulcer-related health care resources during the 1 year after therapy compared with groups 2 and 3 (comparisons are given as group 1 vs group 2 and group 1 vs group 3, respectively): the number of endoscopies performed, 28 vs 76 (P<.001) and vs 71 (P<.001); patients receiving drugs to treat an ulcer, 118 vs 180 (P<.001) and vs 168 (P<.001); clinic visits, 83 vs 135 (P=.05) and vs 161 (P<.001); hospitalizations, 0 vs 5 (P=.045) and vs 6 (P=.02); and length of hospital stay, 0 vs 24 days (P=.04) and vs 37 (P=.04). When ulcer-related costs were defined as the outcome variable in a multivariate linear regression analysis, therapy was determined to have a significant influence on costs (group 1 vs group 2, P<.001; group 1 vs group 3, P=.008). Clinical success rates at the end of the study and cure of H. pylori infection were significantly greater in group 1 compared with groups 2 and 3 (P<.001). Therapy with clarithromycin plus omeprazole provided savings of $1.94 and $2.96 (compared with therapy with omeprazole and with ranitidine hydrochloride, respectively) per dollar spent within the first year after therapy. This incremental cost-benefit translates to savings of $547 or $835 per patient in group 1 (compared with patients in group 2 or group 3, respectively) during the first year after therapy. CONCLUSIONS: Combination therapy with clarithromycin and omeprazole resulted in significantly fewer uses of ulcer-related health care resources than conventional antisecretory therapy during a 1-year follow-up and significant savings in associated costs during the same period. Patients who received clarithromycin plus omeprazole also showed a significantly improved clinical outcome compared with patients who received only omeprazole or ranitidine.

Adult↗

PubMed1998

Knockout and knockin of the beta1 exon D define distinct roles for integrin splice variants in heart function and embryonic development.

The beta1D integrin is a recently characterized isoform of the beta1 subunit that is specifically expressed in heart and skeletal muscle. In this study we have assessed the function of the beta1D integrin splice variant in mice by generating, for the first time, Cre-mediated exon-specific knockout and knockin strains for this splice variant. We show that removal of the exon for beta1D leads to a mildly disturbed heart phenotype, whereas replacement of beta1A by beta1D results in embryonic lethality with a plethora of developmental defects, in part caused by the abnormal migration of neuroepithelial cells. Our data demonstrate that the splice variants A and D are not functionally equivalent. We propose that beta1D is less efficient than beta1A in mediating the signaling that regulates cell motility and responses of the cells to mechanical stress.

Animals↗

PubMed1998

An endo-1,4-beta-xylanase-encoding gene from Agaricus bisporus is regulated by compost-specific factors.

Compost is the preferred substrate for growth of the edible fungus Agaricus bisporus. Utilization of compost requires the production of enzymes involved in degradation of lignocellulolytic components. For molecular characterization of these processes we are isolating the encoding genes. By applying heterologous screening techniques, we have cloned such a gene, which is specifically induced on compost encoding an endo-1,4-beta-xylanase (xlnA) belonging to glycosyl hydrolase family 10. The gene encodes a pre-protein of 333 amino acid residues with a predicted molecular mass of 34,946 for the mature protein. The open reading frame is interrupted by ten introns of which introns 5 and 6 are separated by an exon of only two base-pairs. High expression of the xlnA gene was observed in vegetative mycelium grown on sterilized compost while xlnA messengers were not detected in fruit bodies. Addition of glucose or xylose to compost repressed xlnA expression. When glucose-grown colonies were transferred to a medium containing cellulose, xylan or xylose as sole carbon source, the organism responded by expressing xlnA at a high level for a short period. Transfer from glucose to compost yielded a much stronger and constant xlnA induction. A similar pattern of expression was found for the cel3 gene encoding a cellulase, suggesting that these genes are induced by compost-specific factors rather than by the substrates they act upon. Antiserum raised against XLNA protein, which was heterologously expressed in Escherichia coli, detected, when the fungus was grown on compost, an extracellular protein of 33 kDa with endo-xylanase activity.

Agaricus↗