Biomedical subjects

A Sonnenberg

Publications and source records attributed to A Sonnenberg.

At least 55 records · Page 3Linked to original sources

PubMed2001

Gastric surgery is not a risk for Barrett's esophagus or esophageal adenocarcinoma.

BACKGROUND & AIMS: The contribution of duodeno-gastroesophageal reflux to the development of Barrett's esophagus has remained an interesting but controversial topic. The present study assessed the risk for Barrett's esophagus after partial gastrectomy. METHODS: The data of outpatients from a medicine and gastroenterology clinic who underwent upper gastrointestinal endoscopy for any reason were analyzed in a case-control study. A case population of 650 patients with short- segment and 366 patients with long-segment Barrett's esophagus was compared in a multivariate logistic regression to a control population of 3047 subjects without Barrett's esophagus or other types of gastroesophageal reflux disease. RESULTS: In the case population, 25 (4%) patients with short-segment and 15 (4%) patients with long-segment Barrett's esophagus presented with a history of gastric surgery compared with 162 (5%) patients in the control population, yielding an adjusted odds ratio of 0.89 with a 95% confidence interval of 0.54-1.46 for short-segment and an adjusted odds ratio of 0.71 (0.30-1.72) for long-segment Barrett's esophagus. Similar results were obtained in separate analyses of 64 patients with Billroth-1 gastrectomy, 105 patients with Billroth-2 gastrectomy, and 33 patients with vagotomy and pyloroplasty for both short- and long-segment Barrett's esophagus. Caucasian ethnicity, the presence of hiatus hernia, and alcohol consumption were all associated with elevated risks for Barrett's esophagus. CONCLUSIONS: Gastric surgery for benign peptic ulcer disease is not a risk factor for either short- or long-segment Barrett's esophagus. This lack of association between gastric surgery and Barrett's esophagus suggests that reflux of bile without acid is not sufficient to damage the esophageal mucosa.

Adenocarcinoma↗

PubMed2001

Is there a link between cervical inlet patch and Barrett's esophagus?

BACKGROUND: Heterotopic gastric-type mucosa occurs as a flat island or islands of red mucosa in the proximal third of the esophagus where it gives rise to the "cervical inlet patch" (CIP). The aim of the present study was to delineate the clinical epidemiology of the CIP, especially its possible relationship to Barrett's esophagus. METHODS: A case-control study compared 53 case subjects with CIP and 4882 control subjects without CIP. In a multivariate logistic regression, the presence of CIP was chosen as the outcome variable, whereas demographic characteristics, social habits, and presence of other endoscopic diagnoses served as predictor variables. RESULTS: The prevalence of CIP was 1.1%. Its presence was associated with hiatal hernia (odds ratio 2.26: 95% CI [1.12, 4.56]) gastric ulcer (2.93: 95% CI [1.34, 6.40]) and Barrett's esophagus (4.41: 95% CI [2.31, 8.41]). CONCLUSIONS: The coincidence of the cervical inlet patch and Barrett's esophagus could suggest a shared embryonic etiology.

Adult↗

PubMed2001

Risk factors of oesophagitis in arthritic patients.

BACKGROUND: The risk factors that precipitate the occurrence of oesophageal mucosal injury in patients on continuous nonsteroidal anti-inflammatory drug (NSAID) therapy are unknown. METHODS: Outpatients who regularly consumed NSAIDs for osteoarthritis were recruited from a rheumatology clinic into a prospective case-control study. All patients answered a structured interview and underwent upper gastrointestinal endoscopy. RESULTS: Of 450 eligible patients, 195 (43%) consented to be interviewed and undergo upper gastrointestinal endoscopy. Oesophagitis was diagnosed in 41 of these 195 patients (21%). The occurrence of gastric or duodenal ulcer in individual patients did not predict the concomitant damage of the oesophageal mucosa. Young age (odds ratio: 1.79 per decade of life; 95% confidence interval: 1.11-2.86) and hiatus hernia (odds ratio: 3.72; 95% confidence interval: 1.63-8.49) both increased the risk of developing oesophagitis. When questioned, all oesophagitis patients revealed at least one gastrointestinal symptom, heartburn being named most frequently (odds ratio: 4.78; 95% confidence interval: 2.04-11.17). The type of anti-inflammatory medication, the use of alcohol and the use of nicotine were not associated with any significant risk for erosive oesophagitis. CONCLUSIONS: Patients on chronic NSAID therapy for rheumatological disease suffer frequently from erosive oesophagitis. While the risk may be higher in patients with a pre-existing tendency for gastro-oesophageal reflux, any concomitant history of NSAID-induced peptic ulcer disease does not add to the risk. Erosive oesophagitis should be considered especially in patients on NSAIDs who complain of heartburn.

Adult↗

PubMed2001

Cause of death in patients with inflammatory bowel disease.

BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) can both result in disease-related mortality. The aim of the present study was to analyze the comorbid medical conditions that contribute to death of patients with inflammatory disease. METHODS: The United States' vital statistics offer the opportunity to study causes of death broken down by primary and contributing secondary conditions. Deaths from UC and CD were retrieved from the 1991-1996 data files of the National Center for Health Statistics. The strengths of individual associations between each comorbid condition and UC or CD were expressed as proportional mortality ratios, adjusted to the age-, gender-, and race-distribution of the general population. RESULTS: Deaths from UC and CD were found to be associated with a similar set of comorbid conditions and complications. Shock, volume depletion, protein/calorie malnutrition, and anemia were the most frequent comorbid conditions in the group of nutritional, fluid, and electrolyte disturbances. Both diseases were frequently associated with peritonitis and septicemia. Lastly, a large number of deaths were associated with complications following medical and surgical interventions. CONCLUSIONS: Deaths due to inflammatory bowel disease appear to be related to complications from multiple medical interventions and surgical procedures. In managing inflammatory bowel disease, the physician must keep in mind the potential for complications that may be associated with aggressive treatment.

Age Factors↗

PubMed2001

Risk factors for erosive reflux esophagitis: a case-control study.

OBJECTIVES: It is presently not fully understood which risk factors contribute to the occurrence of reflux esophagitis and how such factors might influence the severity of the disease. The aim of this study was to delineate the clinical epidemiology of erosive reflux esophagitis. METHODS: Outpatients from a medicine and gastroenterology clinic who underwent upper GI endoscopy were recruited into a case-control study. A total of 1,533 patients with and 3,428 patients without endoscopically diagnosed reflux esophagitis were categorized as case and control subjects, respectively. Using multivariate logistic regressions for statistical analysis, the presence of esophageal erosions, ulcers or strictures, served as three separate outcome variables. Demographic characteristics, intake of nonsteroidal anti-inflammatory drugs (NSAIDs), consumption of alcohol and cigarettes, and the presence of hiatus hernia or peptic ulcer served as predictor variables. RESULTS: Erosive reflux esophagitis tended to occur more frequently in Caucasian male patients. Hiatus hernia was associated with a strong risk for developing esophageal erosions, ulcers, and strictures. Although statistical significance was demonstrated only for esophageal erosions, in all grades of reflux esophagitis alike, gastric and duodenal ulcer exerted a protective influence. Consumption of NSAIDs increased the risk for esophageal ulcers only. Smoking and alcohol were not associated with an increased risk of developing any type of erosive reflux esophagitis. CONCLUSIONS: The results stress the critical role played by hiatus hernia in all grades of erosive reflux esophagitis. NSAIDs may act through a mechanism of topically induced esophageal injury. Our data also suggest that the presence of either gastric or duodenal ulcer exerts a protective influence against the development of reflux disease.

Adult↗

PubMed2001

The diagnostic pursuit of gastrointestinal symptoms.

The present article attempts to model the reasoning underlying the process of diagnostic workup in a patient with GI symptoms. Diagnostic reasoning consists of two consecutive and repetitive steps. Test procedures help to contract a list of multiple competing diagnoses to one focal diagnosis. In a subsequent step, the focal diagnosis again becomes expanded to a second list of new diagnoses that are more precise than those on the first list. In the process of expansion, the focal diagnosis itself serves as a test with its own sensitivity values to generate the second list of associated diagnoses. The process of contraction and expansion repeats itself, until the focal diagnosis of the last contraction is no longer expansible or until diagnostic knowledge gained from further expansion loses therapeutic relevance. The process of contraction and expansion can be formalized by Bayes' formula.

Aged↗

PubMed2001

Medical diagnoses and procedures associated with clostridium difficile colitis.

OBJECTIVES: The aim of this study was to examine the associations of Clostridium difficile colitis with other comorbid conditions and procedural interventions among hospitalized patients. METHODS: The Patient Treatment File of the Department of Veterans Affairs contains the computerized records of all inpatients treated in 172 Veterans Affairs hospitals distributed throughout the United States. The computerized medical records of 15,091 cases with C. difficile colitis and 61,931 controls without the diagnosis were extracted from the annual files between 1993 and 1998. In a multivariable logistic regression, the occurrence of C. difficile colitis served as outcome variable, whereas the occurrences of other diagnoses or procedures served as predictor variables. RESULTS: The total numbers of diagnoses in the case and control group were 136,840 and 465,972, respectively. The numbers of procedures were 75,479 and 129,612, respectively. C. difficile colitis was significantly associated with HIV infection, candidiasis, malignant neoplasm and chemotherapy, malnutrition, pneumonia, aspiration pneumonitis, intestinal obstruction, diverticulitis, renal failure, urinary tract infection, decubitus, and osteomyelitis. Interventional procedures involving the respiratory tract, bone marrow biopsy, arterial and venous catheterization, urinary catheterization, dialysis, gastrostomy tube, and physical therapy were also frequently associated with the development of C. difficile colitis. CONCLUSIONS: These associations reflect the influence of causal relationships (such as the use of antibiotics and chemotherapy), an increased risk of exposure to C. difficile among immobilized bedridden patients with chronic disease states, or a general system failure in patients with end-stage disease. Knowledge of such associations could help to alert physicians to an increased risk of C. difficile colitis among particular groups of susceptible patients.

Aged↗

PubMed2001

Occupational mortality from inflammatory bowel disease in the United States 1991-1996.

OBJECTIVE: The occupational distribution of inflammatory bowel disease (IBD) may help to shed light on its yet unknown etiology. The U.S. vital statistics offer the opportunity to study cause of death by occupation and industry. METHODS: The numbers of deaths from Crohn's disease and ulcerative colitis were retrieved from the computerized 1991-1996 data files of the National Center for Health Statistics. Deaths were grouped by gender, ethnicity, disease type, occupation, and industry. Mortality by occupation and industry were expressed as proportional mortality ratio (PMR), adjusted for gender and ethnicity. RESULTS: Between 1991 and 1996, 2399 subjects died from Crohn's disease and 2419 subjects died from ulcerative colitis. Significant correlations were found between the PMR values of ulcerative colitis and Crohn's disease regarding their distribution by occupation, r = 0.36 and p < 0.05, as well as by industry, r = 0.37, p < 0.01. IBD mortality by occupation was significantly reduced among farmers (PMR: 70, 95% confidence interval [CI]: 42-97), mining machine operators (31, 95% CI: 0-74), and laborers (71. 95% CI: 45-98). A nonsignificant increase was found among sales persons (117, 95% CI: 95-139) and secretaries (122, 95% CI: 83-161). IBD mortality by industry was significantly reduced in agricultural production of livestock (39, 95% CI: 1-78), mining (46, 95% CI: 9-83), grocery stores (55, 95% CI: 17-94), and work in private households (64, 95% CI: 30-97). A nonsignificant increase was found in food production (128, 95% CI: 74-182), investment and insurance business (137, 95% CI: 77-198), and administration (122, 95% CI: 81-163). CONCLUSIONS: IBD mortality is low in occupations associated with manual work and farming and relatively high in sedentary occupations associated with indoor work. Crohn's disease and ulcerative colitis show a similar distribution.

Aged↗

PubMed2001

Reduced symptoms and need for antisecretory therapy in veterans 3 years after Helicobacter pylori eradication with ranitidine bismuth citrate/amoxicillin/clarithromycin.

OBJECTIVE: The most effective combination therapy to eradicate Helicobacter pylori has not yet been found. The perfect combination would be effective, relatively free of side effects, and easy to comply with. We studied a 14-day course of three medications taken twice daily by H. pylori-infected patients who were enrolled in the outpatient Veterans Affairs (VA) clinics. The two major objectives were 1) to determine the effectiveness of the combination therapy and 2) to determine the compliance of patients in a VA population. METHODS: Fifty-two male patients were identified with H. pylori infection by positive CLO (Rapid Urease Test) test, positive Giemsa stain, or positive serology. Active infection was confirmed by a positive 13C urea breath test (UBT). Patients were treated for 14 days with open-label triple-combination therapy of ranitidine bismuth citrate (RBC; 400 mg b.i.d.), amoxicillin (1000 mg b.i.d.), and clarithromycin (500 mg b.i.d.). Successful eradication of H. pylori was confirmed by repeat UBT at 6-8 wk after the final dose of therapy. RESULTS: Of the 52 enrolled patients, 49 (94.2%) met the criteria for successful completion of the study (per protocol analysis based on compliance with at least 80% of medication and performance of both UBTs). Of the three patients who did not successfully complete, one was cured (after 6 days of treatment), and two remained infected (after 3 days and 9 days of treatment). Of the 49 completed patients, 45 (91.8%) were cured, and four remained infected. Overall, regardless of compliance (intent-to-treat analysis), 46 of the 52 (88.4%) patients had documented cure of H. pylori infection as determined by the posttreatment UBT. By 3 yr after H. pylori eradication, two of 15 (13.3%) patients who were not on baseline medications had developed the need for antisecretory therapy, but 18 of 31 (58.1%) who were on baseline medications were able to stop therapy. Thus, at 3 yr, successful H. pylori eradication decreased the need for antisecretory therapy from 67.4% of the H. pylori-infected population to 43% of the H. pylori-eradicated population. The effect of H. pylori eradication in improving symptoms at 3 yr was statistically significant in both the ulcer population and the nonulcer population. Adverse events were mild, and included diarrhea (26 patients), bad taste in mouth (24 patients), nausea/upset stomach (nine patients), and headache (two patients). The diarrhea was self-limiting in 25 of the 26 patients. Only two patients discontinued medication because of adverse events. CONCLUSION: The RBC/amoxicillin/clarithromycin combination was, in our VA population, an easily complied with, highly effective, and safe triple therapy with a 90% H. pylori eradication rate. Successful eradication of H. pylori leads to a dramatic decrease in upper-gut symptoms and decreased need for antisecretory therapy.

Aged↗

PubMed2001

Gastroesophageal reflux disease is a risk factor for laryngeal and pharyngeal cancer.

OBJECTIVE: Gastroesophageal reflux disease (GERD) is a proposed risk factor for developing laryngeal and pharyngeal cancers. No controlled study has examined this association. METHODS: A case-control-study was performed using the computerized hospitalization and outpatient databases of the US Department of Veterans Affairs. All patients, who were veterans, had been identified as being hospitalized with laryngeal or pharyngeal during 1991 to 1997. In addition, all persons diagnosed with laryngeal or pharyngeal cancer in 1999 in the outpatient files were identified. From the same patient populations, four nonmatched control subjects were randomly assigned for each case. The medical history for cases and controls was retrospectively searched for GERD diagnoses, tobacco use, and alcohol dependence. Multivariable logistic regression analyses were performed to assess the risk factors for laryngeal and pharyngeal cancers. RESULTS: A total of 8,228 hospitalized patients with laryngeal cancers and 1,912 with pharyngeal cancers were compared to 32,912 and 7,648 hospitalized controls, while 9,292 outpatients with laryngeal cancer and 2,769 outpatients with pharyngeal cancer were compared with 37,168 and 11,076 outpatient controls without cancer. Among hospitalized persons, the prevalence of GERD was higher among patients with laryngeal cancer (8.9 vs 4.0%, p < 0.0001) and pharyngeal cancer (6.2 vs 3.8%, p < 0.0001). In a multivariable logistic regression analysis that was controlled for age, gender, ethnicity, smoking, and alcohol, GERD was associated with an adjusted odds ratio (OR) of 2.40 for laryngeal cancer among hospitalized patients (95% CI 2.15-2.69, p < 0.0001) and an adjusted OR of 2.38 (95% CI 1.87-3.02, p < 0.0001) for pharyngeal cancer. For outpatients, GERD was associated with an adjusted OR = 2.31 (95% CI 2.10-2.53) for laryngeal cancer and adjusted OR = 1.92 (95% CI 1.72-2.15). CONCLUSIONS: Among US veterans, the risk for laryngeal or pharyngeal cancers is modestly increased in the presence of GERD. This effect seems to be independent of age, gender, smoking, and alcohol intake.

Aged↗

PubMed2001

Comorbid occurrence of liver and pancreas disease in United States military veterans.

OBJECTIVE: The clinical epidemiology of the comorbidity between liver and pancreas disease is unknown. The Patient Treatment File of the Department of Veterans Affairs contains the computerized records of all inpatients treated in 172 Department of Veterans Affairs hospitals distributed throughout the United States. This large database offers a unique opportunity to study the epidemiology of liver-pancreas comorbidity (LPC). METHODS: In a case-control study, 6,393 LPC cases were compared to 34,513 controls with alcoholic liver disease and liver cirrhosis alone and 68,038 controls without liver or pancreas disease. Multivariate logistic regression analysis was used to assess the joint influence of multiple risk factors on the occurrence of LPC. RESULTS: LPC occurred in 15.6% of patients with alcoholic liver disease and liver cirrhosis identified in the Patient Treatment File between 1990 and 1993. Compared to controls with liver disease alone, LPC cases were characterized by younger age (odds ratio = 0.88 per age decade, CI = 0.86-0.90) and African American (2.33, 2.18-2.48) or Hispanic (1.24, 1.12-1.38) ethnicity. Compared to controls with neither liver nor pancreas disease, LPC cases were characterized by male gender (1.67, 1.28-2.17), African American (1.41, 1.32-1.50) or Hispanic (2.04, 1.82-2.30) ethnicity, more frequent history of alcoholism (29.5, 26.7-32.6), and being divorced (1.35, 1.26-1.44). CONCLUSIONS: Comorbidity of liver and pancreas disease is relatively common in the veteran population. Such patients are more frequently divorced and of African American or Hispanic ethnicity, and present with a history of excessive alcoholism at a relatively young age.

Case-Control Studies↗

PubMed2001

The comorbid occurrence of other diagnoses in patients with ulcerative colitis and Crohn's disease.

OBJECTIVES: The comorbidity between inflammatory bowel disease (IBD) and other diagnoses may help to shed light on the etiology and pathophysiology of IBD. The US Vital Statistics offer the opportunity to study causes of death broken down by comorbid disease associations. The aim of this study was to analyze the presence of comorbid conditions in persons who died from ulcerative colitis or Crohn's disease. METHODS: The numbers of deaths from ulcerative colitis and Crohn's disease were retrieved from the computerized 1991-1996 data files of the National Center for Health Statistics. Comorbid associations between other diagnosis and ulcerative colitis or Crohn's disease were expressed as age-, gender-, and race-standardized proportional mortality ratios. RESULTS: Ulcerative colitis and Crohn's disease showed, in general, similar patterns of comorbidity. Both diseases were associated with similar sets of GI complications, such as intestinal obstruction and stasis, mucosal inflammation and infection, vascular complications, and complications related to fistula and abscess formation. Extraintestinal complications of both IBD involved disorders of the hepatobiliary system, urinary system, and various coagulopathies. Ulcerative colitis alone was found to be associated with Hirschsprung's disease and schizophrenia, whereas Crohn's disease alone was found to be related with osteoporosis and amyloidosis. CONCLUSIONS: No completely unexplained or hitherto undescribed association was revealed. The numerous intestinal and extraintestinal complications associated with IBD serve as a reminder of the systemic nature and the resultant clinical severity of both ulcerative colitis and Crohn's disease.

Aged↗

PubMed2001

No association between gallstones and gastroesophageal reflux disease.

OBJECTIVES: Gallstones and hiatal hernia reportedly have been linked to similar dietary factors prevalent in western countries, and patients with cholelithiasis or previous cholecystectomy have been reported to have more duodenogastric reflux than healthy controls. Nonetheless, the contribution of duodenogastric reflux to the development of gastroesophageal reflux disease (GERD) remains controversial. The present study was aimed to assess the association between gallstone disease and GERD. METHODS: Outpatients from general medical clinics who underwent upper GI endoscopy and abdominal ultrasonography were recruited into a case-control study. A case population of 790 patients with various grades of GERD was compared to a control population of 407 patients without GERD. In a multivariate logistic regression, the presence of GERD served as the outcome variable, whereas the presence of gallstones, hiatal hernia, social habits, and demographic characteristics served as predictor variables. RESULTS: No associations were found between the presence of cholelithiasis or previous cholecystectomy and GERD or between the presence of cholelithiasis or previous cholecystectomy and hiatal hernia. The severity of GERD also remained unaffected by the presence of gallstones. The occurrence of GERD was influenced only by hiatal hernia (odds ratio [OR] = 3.15, 95% CI = 2.44-4.08), alcohol consumption (OR = 1.47, CI = 1.08-1.99), and not by cholelithiasis (OR = 1.02, CI = 0.68-1.51), or cholecystectomy (OR = 0.90, CI = 0.64-1.28). The frequency of GERD among hiatus hernia patients with gallstones (437/592 = 74%) was similar to the frequency of GERD among hiatus hernia patients without gallstones (168/220 = 76%, p = 0.516). CONCLUSIONS: Neither cholelithiasis nor cholecystectomy poses a risk for the occurrence of GERD or hiatal hernia. Gallstone disease does not seem to influence the integrity of the esophageal mucosa through GERD.

Aged↗

PubMed2001

Period- and cohort-age contours of deaths from gastric and duodenal ulcer in New York 1804-1998.

OBJECTIVES: Mortality data of peptic ulcer are mostly national and limited to the 20th century. The New York City data from 1804 have therefore been examined by both year of death and year of birth (cohort analysis), to consider whether the increases and subsequent decreases in deaths from gastric, followed by duodenal ulcer, can be attributed to Helicobacter pylori. METHODS: The annual mortality reports of New York City described gastric ulcer from 1838 and duodenal ulcer from 1931. The age-specific death rates per 100,000 population were calculated in 10-yr periods both by year of death and by year of birth for each disease according to age and sex. RESULTS: For gastric ulcer the period-of-death-age contours from the 1850s to the 1990s showed an increase to a mid-19th century plateau, but the cohort-age contours revealed a peak mortality for those born in the 1870s. Women born between about 1770 and 1880 showed a faster increase in mortality. For duodenal ulcer the period of birth contours showed a decline from a peak for those born in the 1880s and 1890s, with no sex difference. CONCLUSIONS: This urban study with data regarding deaths from gastric ulcer registered from 1838 and in those born from the 1770s, revealed by cohort analysis a peak in the 1870s, and for duodenal ulcer in the 1880s, comparable to national data worldwide. These time changes in fatalities are compatible with a change in the environment of children born in these decades, as, for example infection by a pathogenic strain of H. pylori.

Cohort Studies↗

PubMed2001

A medical uncertainty principle.

Acquisition of diagnostic knowledge and improvement of patient health often are mutually exclusive goals. A perfect understanding of a disease process is only obtained through unrestricted testing that exposes the patient to adverse events and discomfort. In a patient completely undisturbed by test procedures, the physician remains ignorant about the nature of the disease. The interplay of diagnostic knowledge and patient health can be formulated in terms of an uncertainty principle, which allows one to mathematically derive the parameters that influence the balance between the two competing goals. The majority of clinical conditions permit the pursuit of perfect diagnostic knowledge. Occasional medical disasters occur because physicians underestimate the patient's functional reserve or the cumulative toll exerted by multiple tests. Especially in emergency situations or serious illness, the maximum amount of knowledge that can be achieved is far less than perfect. Under such circumstances, the best management option takes into account a "calculated" amount of diagnostic uncertainty.

Delivery of Health Care↗

PubMed2001

Temporal associations between coughing or wheezing and acid reflux in asthmatics.

BACKGROUND AND AIMS: The pulmonary symptoms of patients with lung disease may be ascribed to gastro-oesophageal reflux although a causal relationship between acid reflux and coughing or wheezing has not been proved. Does cough cause reflux or does reflux cause cough? The aim of this study was to evaluate 24 hour oesophageal pH tracings of asthmatics with gastro-oesophageal reflux to determine the temporal association between acid reflux and coughing or wheezing. METHODS: The oesophageal tracings of 128 asthmatics from the outpatient clinics who underwent oesophagogastroduodenoscopy, oesophageal manometry, and 24 hour oesophageal pH monitoring were analysed. Three possible temporal relationships between the occurrence of acid reflux and the occurrence of coughs or wheezes were evaluated: (1) pulmonary symptoms preceding reflux; (2) reflux preceding pulmonary symptoms; and (3) unrelated occurrence of both events. RESULTS: Of 128 asthmatics, 53 recorded five or more coughs and 19 recorded three or more wheezes during the 24 hour recording period. Mean acid contact time was similar in asthmatics with and without pulmonary symptoms (12.2 (1.2)% v 10.4 (0.6)%). Of all coughs and wheezes, 46% and 48%, respectively, were associated with acid reflux. For the individual asthmatic, the likelihood of reflux induced coughing increased as the number of coughs increased. CONCLUSIONS: Half of all coughs and wheezes in asthmatics are associated with acid reflux into the oesophagus. While an occasional coughing episode can lead to reflux, it is rather the reflux episode in the vast majority of instances that leads to cough.

Asthma↗

PubMed2001

The interaction of plectin with actin: evidence for cross-linking of actin filaments by dimerization of the actin-binding domain of plectin.

Plectin is a major component of the cytoskeleton and is expressed in a wide variety of cell types. It plays an important role in the integrity of the cytoskeleton by cross-linking the three filamentous networks and stabilizing cell-matrix and cell-cell contacts. Sequence analysis showed that plectin contains a highly conserved actin-binding domain, consisting of a pair of calponin-like subdomains. Using yeast two-hybrid assays in combination with in vitro binding experiments, we demonstrate that the actin-binding domain of plectin is fully functional and preferentially binds to polymeric actin. The sequences required for actin binding were identified at the C-terminal end of the first calponin homology domain within the actin-binding domain of plectin. We found that the actin-binding domain of plectin is able to bundle actin filaments and we present evidence that this is mediated by the dimerization of this domain. In addition we also show that plectin and another member of the plakin family, dystonin, can heterodimerize by their actin-binding domains. We propose a new mechanism by which plectin and possibly also other actin-binding proteins can regulate the organization of the F-actin network in the cell.

Actins↗

PubMed2000

Dual stimulation of Ras/mitogen-activated protein kinase and RhoA by cell adhesion to fibronectin supports growth factor-stimulated cell cycle progression.

In cellular transformation, activated forms of the small GTPases Ras and RhoA can cooperate to drive cells through the G1 phase of the cell cycle. Here, we show that a similar but substrate-regulated mechanism is involved in the anchorage-dependent proliferation of untransformed NIH-3T3 cells. Among several extracellular matrix components tested, only fibronectin supported growth factor-induced, E2F-dependent S phase entry. Although all substrates supported the mitogen-activated protein kinase (MAPK) response to growth factors, RhoA activity was specifically enhanced on fibronectin. Moreover, induction of cyclin D1 and suppression of p21(Cip/Waf) occurred specifically, in a Rho-dependent fashion, in cells attached to fibronectin. This ability of fibronectin to stimulate both Ras/MAPK- and RhoA-dependent signaling can explain its potent cooperation with growth factors in the stimulation of cell cycle progression.

3T3 Cells↗