Biomedical subjects

A Sonnenberg

Publications and source records attributed to A Sonnenberg.

At least 19 recordsLinked to original sources

PubMed2002

Medical decision analysis of endoscopic surveillance of Barrett's oesophagus to prevent oesophageal adenocarcinoma.

BACKGROUND: Barrett's oesophagus is associated with an increased risk of the development of oesophageal adenocarcinoma. Endoscopic surveillance every 2-5 years has been recommended to prevent death from adenocarcinoma. AIM: To assess the cost-effectiveness of this strategy. METHODS: The incremental cost-effectiveness of surveillance (as compared to no surveillance) was analysed with a computer model of a Markov process. RESULTS: Compared to no surveillance, the incremental cost-effectiveness of bi-annual endoscopy is 16,695 dollars per life-year saved. Surveillance is less cost-effective if the incidence rate of oesophageal adenocarcinoma is low and the 5-year survival rate is high. For surveillance to be cost-effective, there should be little reduction in health-related quality of life following surgical oesophagectomy to prevent death. Moreover, endoscopic surveillance and oesophagectomy need to be efficacious in reliably diagnosing high-grade dysplasia and preventing deaths from cancer. If such ideal conditions of surveillance are not met, the cost per life-year saved could rise five-fold. CONCLUSIONS: Endoscopic surveillance of patients with Barrett's oesophagus may be a cost-effective means to prevent death from oesophageal adenocarcinoma.

Adenocarcinoma↗

PubMed2002

There are no reliable symptoms for erosive oesophagitis and Barrett's oesophagus: endoscopic diagnosis is still essential.

AIMS: To evaluate the sensitivity and specificity of different symptoms in erosive reflux oesophagitis and Barrett's oesophagus. METHODS: The presence of reflux symptoms was compared between a case population of 306 patients with endoscopically determined erosive reflux oesophagitis, 235 patients with biopsy-proven Barrett's oesophagus and a control population of 198 subjects without reflux disease. RESULTS: Heartburn at any time and heartburn at night represented the only two symptoms to be simultaneously sensitive and specific. Symptoms that were induced by various foods, such as fat, tomato, chocolate, citrus or spices, tended to cluster in the same sub-group of patients. Similarly, heartburn induced by exercise, lying down or bending over tended to occur in the same sub-groups. The frequency of symptoms was influenced more by the presence of mucosal erosions than by the presence of Barrett's oesophagus. Reflux symptoms occurred more frequently in the presence rather than the absence of Barrett's oesophagus, and in long segment rather than short segment of Barrett's mucosa. CONCLUSIONS: Endoscopic inspection of the oesophageal mucosa remains the only certain method by which to reliably diagnose erosive reflux oesophagitis and Barrett's oesophagus.

Barrett Esophagus↗

PubMed2002

General principles to enhance practice patterns in gastrointestinal endoscopy.

AIM: To develop general rules on how to pursue a therapeutic goal of interventional endoscopy without getting lost in abundant details. METHODS: The influences of various medical interventions on the survival of a patient with gastrointestinal haemorrhage are modelled by an influence diagram. Survival is the focal point of multiple influences affecting its overall strength. Any downstream influence can represent the focal point of other preceding upstream influences. The mathematics underlying the influence diagram are similar to those of a decision tree with some notable exceptions. Its formalism allows one to consider inhibitory and additive influences and to include in the same analysis non-commensurable qualities, such as correct diagnosis, haemostasis or survival. RESULTS: The analysis reveals five general rules. First, the large number of factors involved in successful endoscopy render the influence of each individual factor less important. Second, a single factor that exerts its influence on many subsequent factors tends to be associated with an overall greater relevance. Third, remote influences are of lesser relevance than those directly linked to the final outcome. Fourth, factors multiplied by several consecutive probabilities lose their influence. Fifth, endoscopists need to assess the relevance of individual factors with respect to the immediate goals of endoscopy, as well as the general goals of patient well-being. CONCLUSIONS: The influence model of endoscopic haemostasis reveals several general principles that can be utilized as tools in endoscopy training.

Gastrointestinal Hemorrhage↗

PubMed2002

Inguinal hernia is not a sign of colon cancer: results of a prospective screening trial.

BACKGROUND: It has been suggested that patients with an inguinal hernia harbour an increased risk for colorectal cancer. METHODS: In a prospective clinical trial, we compared the prevalence of colonic neoplasms in 100 cases with inguinal hernia and 100 controls without inguinal hernia. The number, size, histology type, and the location of all colorectal lesions found during a screening flexible sigmoidoscopy were recorded. RESULTS: Not a single case of colorectal cancer was detected in the patients with inguinal hernia pending surgical repair. In the asymptomatic control subjects, one Dukes A and one Dukes B1 colon cancer were detected. Polypectomy was performed in 15% and 17% of the case and control subjects, respectively. During a 5-year period following the initial screening procedure, none of the case or control subjects was diagnosed with colon cancer. CONCLUSIONS: The decision for or against performing an endoscopic procedure in a patient with inguinal hernia should be guided by the general principles of screening for colorectal cancer. The mere presence of an inguinal hernia does not automatically increase the risk of colorectal cancer.

Adenoma↗

PubMed2002

Hospital admissions for peptic ulcer and indigestion in London and New York in the 19th and early 20th centuries.

The occurrence of peptic ulcer increased rapidly in all Western countries from the 19th to the 20th century, attributed to a possible epidemic of Helicobacter pylori, a new pathogenic strain, or a change in host susceptibility. The early trends in hospital admissions for peptic ulcer and dyspepsia in London and New York during the 19th century are reviewed to test these hypotheses.

Duodenal Ulcer↗

PubMed2001

The hemidesmosomal protein bullous pemphigoid antigen 1 and the integrin beta 4 subunit bind to ERBIN. Molecular cloning of multiple alternative splice variants of ERBIN and analysis of their tissue expression.

The bullous pemphigoid antigen 1 (eBPAG1) is a constituent of hemidesmosomes (HDs), cell-substrate adhesion complexes in stratified epithelia. Although its COOH terminus interacts with intermediate filaments, its NH(2) terminus is important for its recruitment into HDs. To identify proteins that interact with the NH(2) terminus of human eBPAG1, we performed a yeast two-hybrid screen, which uncovered a protein belonging to the LAP/LERP (for LRR and PDZ domain) protein family with 16 NH(2)-terminal leucine-rich repeats and a COOH-terminal PDZ domain. The gene for this LAP/LERP protein comprises at least 26 exons located on the long arm of chromosome 5. In most human tissues, several transcripts were detected differing in the coding region situated upstream of or within the PDZ domain. One of the encoded variants was found to correspond to the recently described protein ERBIN. In yeast and in vitro binding experiments, ERBIN was shown to interact not only with eBPAG1 but also with the COOH-terminal region of the cytoplasmic domain of the integrin beta4 subunit, another component of HDs. Antibodies raised against the COOH terminus showed that ERBIN is expressed in keratinocytes. In transfected epithelial cells the protein, however, was not localized in HDs but was either diffusely distributed over the cytoplasm or concentrated at the basolateral plasma membrane. Because ERBIN had been shown previously to interact with the transmembrane tyrosine kinase receptor Erb-B2, which in turn associates with the integrin beta4 subunit, we suggest that ERBIN provides a link between HD assembly and Erb-B2 receptor signaling.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Epithelial development and differentiation in the mammary gland is not dependent on alpha 3 or alpha 6 integrin subunits.

In the mammary gland, both laminin and integrins have been shown to be required for normal ductal morphogenesis during development in vivo, and for functional differentiation in culture models. Major integrin receptors for laminins in the mammary gland are alpha 3 beta 1, alpha 6 beta 1, and alpha 6 beta 4. However, the specific subunits that contribute to laminin-mediated mammary cell function and development have not been identified. In this study, we use a genetic approach to test the hypothesis that laminin-binding integrins are required for the function of the mammary gland in vivo. Rudiments of embryonic mammary gland were shown to develop in the absence of these integrin subunits. Postnatal development of the mammary gland was studied in integrin null tissue that had been transplanted into the mammary fat pads of syngeneic hosts. In mammary epithelium lacking alpha 6 integrin, the beta 4 subunit was not apparent and hemidesmosome formation was only rudimentary. However, despite this deficiency, normal ductal morphogenesis and branching of the mammary gland occurred and myoepithelial cells were distributed normally with respect to luminal cells. Mammary alveoli devoid of alpha 3 or alpha 6 integrin formed in pregnancy and were histologically and functionally identical to those in wild-type mammary gland. The tissue underwent full morphological differentiation, and the epithelial cells retained the ability to synthesize beta-casein. This work demonstrates that mammary tissue genetically lacking major laminin-binding integrin receptors is still able to develop and function.

Animals↗

PubMed2001

Structural and functional aspects of filamins.

Filamins are a family of high molecular mass cytoskeletal proteins that organize filamentous actin in networks and stress fibers. Over the past few years it has become clear that filamins anchor various transmembrane proteins to the actin cytoskeleton and provide a scaffold for a wide range of cytoplasmic signaling proteins. The recent cloning of three human filamins and studies on filamin orthologues from chicken and Drosophila revealed unexpected complexity of the filamin family, the biological implications of which have just started to be addressed. Expression of dysfunctional filamin-A leads to the genetic disorder of ventricular heterotopia and gives reason to expect that abnormalities in the other isogenes may also be connected with human disease. In this review aspects of filamin structure, its splice variants, binding partners and biological function will be discussed.

Actins↗

PubMed2001

Cost-effectiveness of endoscopy in irritable bowel syndrome.

BACKGROUND: It is unknown to what extent at what expense flexible sigmoidoscopy and colonoscopy add to the diagnosis of irritable bowel syndrome (IBS). The aim of the study was to assess the incremental cost-effectiveness of endoscopic procedures in the workup for IBS. METHODS: Using the Bayes formula, we calculated the increase in diagnostic certainty for a consecutive number of tests. We also calculated the incremental cost-effectiveness ratio, which corresponds to the test costs divided by the increment in diagnostic certainty. RESULTS: The diagnosis of IBS can be established with a relatively high probability of more than 80% relying on relatively inexpensive and noninvasive tests only. Flexible sigmoidoscopy or colonoscopy constitute the most costly portion of any workup for IBS, which amounts to 50% to 75% of the overall costs. Because of their high incremental cost-effectiveness ratio, endoscopic procedures should not be used at the beginning of the diagnostic workup. This outcome of the analysis remains largely unaffected within reasonable ranges of the sensitivity and specificity of various tests. CONCLUSIONS: In the diagnosis of IBS, inexpensive, noninvasive tests should be used first to rule out other diagnoses. Despite their high incremental cost-effectiveness ratio, flexible sigmoidoscopy and colonoscopy are indicated when a serious organic disease is reasonably likely and needs to be ruled out.

Colonic Diseases, Functional↗

PubMed2001

Function and interactions of integrins.

Integrins are heterodimeric cell adhesion molecules that link the extracellular matrix to the cytoskeleton. The integrin family in man comprises 24 members, which are the result of different combinations of 1 of 18 alpha- and 1 of 8 beta-subunits. Alternative splicing of mRNA of some alpha- and beta-subunits and postranslational modifications of integrin subunits further increase the diversity of the integrin family. In their capacity as adhesion receptors that organize the cytoskeleton, integrins play an important role in controlling various steps in the signaling pathways that regulate processes as diverse as proliferation, differentiation, apoptosis, and cell migration. The intracellular signals that lead to these effects may be transduced via cytoplasmic components, which have been identified as integrin-binding proteins in yeast two-hybrid screens and which could mediate the coupling of integrins to intracellular signaling pathways. In this review an overview is given of the function and ligand-binding properties of integrins as well as of proteins that associate with integrins and may play a role in their signaling function.

Animals↗

PubMed2001

Hospitalization with respiratory disease following hiatal hernia and reflux esophagitis in a prospective, population-based study.

PURPOSE: Hiatal hernia and reflux esophagitis have been associated with respiratory manifestations, though the temporal sequence of this relationship is uncertain. This study examined prospectively the relationship of hiatal hernia and reflux esophagitis with respiratory outcomes in a representative sample of the United States population. METHODS: 6928 participants in the first National Health and Nutrition Examination Survey, a population-based sample initially examined in 1971-1975, who were hospitalized during follow-up through 1992-1993 composed the study population. The relationship between hiatal hernia and reflux esophagitis hospitalization and a subsequent hospitalization with respiratory outcomes was measured in persons free of respiratory disease at baseline and at first hospitalization. RESULTS: Multivariable survival analysis showed higher rates of hospitalization with any respiratory diagnosis [rate ratio (RR) = 1.4, 95% confidence interval (CI) 1.2-1.7] in persons with preceding hiatal hernia or reflux esophagitis hospitalization. Individually, rate ratios of pharyngitis (RR = 5.6, CI 2.0-15.7), tonsillitis (RR = 8.0, CI 2.5-25.8), bronchitis (RR = 1.8, CI 1.2-2.7), pneumonia (RR = 1.3, CI 1.0-1.7), emphysema (RR = 2.9, CI 1.5-5.5), asthma (RR = 2.1, CI 1.1-4.2), bronchiectasis (RR = 6.2, CI 1.1-34.3), and empyema or abscess (RR = 7.4, CI 1.3-42.3) were all higher following hiatal hernia and reflux esophagitis. Rate ratios were similar when reflux esophagitis and hiatal hernia were examined separately. CONCLUSIONS: A prior hiatal hernia or reflux esophagitis hospitalization increased risk of respiratory disease hospitalization.

Adult↗

PubMed2001

Truncated typeXVII collagen expression in a patient with non-herlitz junctional epidermolysis bullosa caused by a homozygous splice-site mutation.

SUMMARY: Type XVII collagen (180-kDa bullous pemphigoid antigen) is a structural component of hemidesmosomes. Mutations in the type XVII collagen gene (COL17A1) have been established to be the molecular basis of non-Herlitz junctional epidermolysis bullosa (JEB-nH), an inherited skin blistering disorder. Here we report for the first time truncated type XVII collagen expression, caused by homozygosity for a COL17A1 donor splice-site mutation (4261+1 g --> c), which was identified by PCR amplification on genomic DNA. By RT-PCR and sequencing of cDNA derived from mRNA from the patient's cultured keratinocytes, we provide evidence of cryptic splicing and exon skipping, most abundantly of exon 52. JEB-nH patients with COL17A1 splice-site mutations resulting in an exon skip often have no immunologically detectable type XVII collagen. However, in our patient with the generalized atrophic benign epidermolysis bullosa subtype, a small amount of type XVII collagen was detectable in the skin, and immunoblotting of cultured keratinocytes revealed that the 180-kDa protein was 10 kDa shorter. We hypothesize that the function of this truncated type XVII collagen polypeptide, which is expressed at low levels, is impaired, explaining the JEB-nH phenotype.

Aged↗

PubMed2001

Two different mutations in the cytoplasmic domain of the integrin beta 4 subunit in nonlethal forms of epidermolysis bullosa prevent interaction of beta 4 with plectin.

The integrin alpha 6 beta 4 plays a crucial role in the assembly and maintenance of hemidesmosomes. Previous work has shown that the recruitment of plectin into hemidesmosomes is dependent on beta 4 and involves a region of the beta 4 cytoplasmic domain, which contains the first two fibronectin (FNIII) repeats and a short region of the connecting segment. Two missense mutations (R1225H and R1281W) in beta 4 that are responsible for nonlethal forms of epidermolysis bullosa are located in the second FNIII repeat. One of them is confined to a loop region that connects two beta strands (EC') whereas the other is located at the N-terminal end of the second FNIII repeat. We here report that these mutations render beta 4 unable to interact with plectin and prevent the localization of plectin in hemidesmosomes. Substitution of a lysine residue (K1279W) that forms part of the same loop as R1281 had no effect on the ability of beta 4 to recruit plectin. Furthermore, we show that an extended loop structure in beta 4, composed of the amino acids DDN (1262--1264), which resembles the RGD integrin-binding loop in fibronectin, is not involved in the binding to plectin. These results further demonstrate that binding of beta 4 to plectin is essential for the proper formation and function of hemidesmosomes and that loss of the interaction between beta 4 and plectin is associated with a mild form of epidermolysis bullosa.

Animals↗

PubMed2001

Walking and chewing reduce postprandial acid reflux.

BACKGROUND: Gastro-oesophageal reflux is worse after meals, and antacids are usually consumed after dietary indiscretion. AIM: To investigate whether walking or gum chewing affect meal-induced gastro-oesophageal reflux. METHODS: The study population comprised 12 case subjects with gastro-oesophageal reflux disease and 24 healthy controls. Each subject was studied using pH-metry for 5 h on 3 separate days. After baseline recording of pH for 1 h, all subjects were fed a standard breakfast over a 20-min period. On one of the days, oesophageal pH was recorded after the 20-min eating period for an additional 4 h in the sitting position. On another day, postprandial oesophageal pH was recorded for the first hour whilst walking, and for 3 subsequent hours whilst sitting. During a third day, oesophageal pH was recorded for the first postprandial hour whilst gum-chewing, followed by 3 h of sitting. RESULTS: Food intake promoted gastro-oesophageal reflux in case subjects with GERD as well as in healthy controls, although postprandial reflux was more pronounced amongst the refluxers than amongst the controls. Chewing gum for 1 h after the meal reduced the acid contact time in both groups, with a more profound effect in refluxers than in controls. Whilst the beneficial effect of 1-h of gum-chewing lasted for up to 3 h in both groups, the beneficial effect of 1-h of walking was apparent only in refluxers, only to a mild degree, and only for a short duration. CONCLUSIONS: Chewing gum after a meal helps to reduce postprandial oesophageal acid exposure.

Female↗

PubMed2001

Healthcare resource utilization in the management of oesophageal adenocarcinoma.

OBJECTIVE: To study the natural history of oesophageal adenocarcinoma in terms of utilization of the healthcare resources and associated medical costs. METHODS: All 29 patients treated at the University of New Mexico Health Center between 1 January 1992 and 1 December 1998 for an oesophageal adenocarcinoma were included in the study. For each individual patient, all medical resources utilized, facility costs, and physician fees were retrieved from the computerized databases of the collection departments. RESULTS: During the progress of the disease, the same type of diagnostic or therapeutic procedure became necessary a number of times, and patients underwent, on average, three (range one to eight) upper gastrointestinal endoscopies, five (range one to 11) computerized tomography scans, 35 (five to 143) X-ray examinations, and 28 (three to 46) radiation therapies or 39 (10 to 74) chemotherapies. The large variation in the numbers of resources utilized was also reflected by a corresponding variation in total healthcare costs. The mean cost per patient was $48 127, ranging between $13 454 and $139 721. Facility costs comprised 88% of all costs compared to physician fees which comprised 12%. The largest cost items, in declining order, were physician encounters ($16 916), radiation plus chemotherapy ($9909 plus $4891, respectively), and pharmacy prescriptions ($7565). CONCLUSIONS: The prolonged disease process and the many diagnostic and therapeutic procedures result in complications, side-effects, inconclusive tests, or failed therapies that all markedly increase the use of healthcare resources. Because such outcomes are the rule rather than the exception, the management of oesophageal adenocarcinoma is expensive.

Adenocarcinoma↗

PubMed2001

When William of Ockham meets Thomas Bayes: finding a few diagnoses among a great many symptoms.

Bayes' formula is a means to estimate disease probability based on the presence of symptoms and the outcome of clinical tests. The probability helps to decide among competing diagnostic options. If, however, several diseases present with similar symptoms, they may appear equally probable, and Bayes' formula will fail as an aid to reach a diagnostic decision. The aim of this study is to show how a merger of Bayes' principle with that of Ockham can help to decide in favour of one diagnosis among multiple, seemingly equally probable diagnostic hypotheses. The hypotheses are compared to each other with respect to those tests and symptoms which they fail to explain. The unexplained tests and symptoms are used to estimate the probabilities for a set of secondary diagnoses that match each one of the primary diagnoses. The more likely a secondary diagnosis appears, the less likely its corresponding primary diagnosis will remain as the sole diagnosis to explain all the clinical findings. Even without a detailed calculation, the proposed concept of using unexplained tests and symptoms to rate competing differential diagnoses could help the clinician to select the most probable diagnosis.

Aged↗

PubMed2001

Reflux symptoms are associated with psychiatric disease.

AIMS: To evaluate the frequency of reflux symptoms in patients with a diagnosed psychiatric disorder and to assess potential risk factors for symptom occurrence. METHODS: The presence of reflux symptoms was compared between a case population of 94 psychiatric patients and a control population of 198 non-psychiatric patients. RESULTS: Heartburn, exercise-induced heartburn, cough and dysphagia were all reported significantly more frequently by subjects with psychiatric disorders than by control subjects. The presence of any psychiatric diagnosis exerted an increased risk for both heartburn (odds ratio, 2.71; 95% confidence interval, 1.01-7.30) and exercise-induced heartburn (3.34; 1.12-9.96). The type of psychiatric disorder, the type of psychotropic medication and the lifestyle did not influence the presence of reflux symptoms. CONCLUSIONS: Reflux symptoms occur more frequently in patients with than without a diagnosed psychiatric disorder. The reflux symptoms are not associated with any specific type of medication and may reflect a generally reduced threshold for or distorted perception of symptoms.

Adult↗

PubMed2001

Long-term nonsurgical management of Barrett's esophagus with high-grade dysplasia.

BACKGROUND & AIMS: Surgical resection of the esophagus is frequently recommended for Barrett's high-grade dysplasia (HGD) without cancer. METHODS: During a 20-year period, patients were diagnosed and observed through an organized surveillance program at the Hines Veterans Affairs Hospital. The program was supported by Hines VA and organized and managed by 2 endoscopists using preestablished endoscopic criteria. RESULTS: Barrett's esophagus was diagnosed in 1099 patients, and 36,251 esophageal mucosal specimens were reviewed. Seventy-nine of 1099 patients (7.2%) initially had HGD (34 prevalent) or subsequently developed HGD (45 incident) without evidence of cancer. Of the 75 HGD patients who remained without detectable cancer after the 1 year of intensive searching, 12 developed cancer (16%) during a mean 7.3-year surveillance period: 11 of the 12 who were compliant were considered cured with surgical or ablation therapy. Cancer did not develop in the remaining 63 HGD patients during the surveillance period. CONCLUSIONS: HGD without cancer in Barrett's esophagus follows a relatively benign course in the majority of patients. In the patients who eventually progress to cancer during regular surveillance, surgical resection is curative. Surveillance endoscopies with biopsy is a valid and safe follow-up strategy for Barrett's patients who have HGD without cancer.

Adenocarcinoma↗