bluuebunny/crossref_metadata_2025 huggingface dataset:
C-Reactive Protein in Dilated Cardiomyopathy
Authors: Kaneko Katsumi , Kanda Tsugiyasu , Yamauchi Yasuhiko , Hasegawa Akira , Iwasaki Tsutomu , Arai Masashi , Suzuki Tadashi , Kobayashi Isao , Nagai Ryozo
Published: April 2003

The prognosis for patients with idiopathic dilated cardiomyopathy (DCM) is poor, although clinical features are variable. Prediction of outcome has been difficult in individual patients based on laboratory data. In some patients with DCM, myocardial damage secondary to viral or immune-mediated myocardial inflammation may persist. To objectively assess inflammation, we measured plasma concentrations of C-reactive protein (CRP) in 188 patients with idiopathic DCM over 5–8 years. All had dyspnea and fatigue at rest; all patients had a left ventricular ejection fraction less than 40% by echocardiography or by contrast or radionuclide ventriculography. We divided these patients into two groups: patients dying within 5 years following admission (n = 49) and the remainder surviving for at least 5 years (n = 139). CRP concentrations in the patients dying early were significantly higher than in the long-term survivors (1.05 ± 1.37 vs. 0.49 ± 1.04 mg/dl, p < 0.05). Sixty-two percent of the patients with CRP>1.0 died within 5 years. In addition to other laboratory tests including electrocardiography and echocardiography, routine CRP measurements proved to be valuable for identifying high-risk patients who require special treatment strategies.
Ventricular Premature Beats in Triathletes: Still a Physiological Phenomenon?
Authors: Claessens Philip , Claessens Christophe , Claessens Marc , Bloemen Hilde , Verbanck Mieke , Fagard Robert
Published: April 2003

Sudden death is a tragic fact, unexpectedly arising in all age groups. Ventricular arrhythmias are the main cause. At the end of a maximal exercise test more ventricular premature beats were noted in a group of well trained triathletes compared with a similar control group. The etiology is multifactorial. When these ventricular premature beats are associated with specific structural and functional heart adaptations, echocardiographically and electrocardiographically well-documented, then those ‘banal’ ventricular premature beats cannot longer be considered as a physiological phenomenon. In these circumstances the involved subject is a candidate for dangerous arrhythmias and ‘sudden cardiac death’. Purpose: The principal cause of ‘Sudden cardiac death’ is ventricular arrhythmias. We explore the incidence of ventricular premature beats (VPB) in triathletes, who engage in enforced endurance sports. Methods: Fifty-two triathletes were compared with twenty-two control subjects with comparable anthropometric parameters in function of structural and functional cardiac adaptations. Maximal exercise tests were conducted on a stationary bicycle and a treadmill. During the last two minutes of each test, the VPB were registered. Results: Statistically significant differences emerged in the cardiac structure and function between the triathletes and the controls. There were signs of cardiac hypertrophy and arguments for a supernormally diastolic left ventricular function in the triathletes. The performance capacity was also significantly higher in the triathletes. The maximal heart rate was significantly higher in the control group. The number of VPB was significantly higher in the triathletes. The increased risk of VPB in the triathlon group is caused by several factors: the degree of cardiac hypertrophy, the increased diastolic reserve, the duration of the exercise, the existence of an aortic insufficiency jet and some specific electrocardiographic findings. Conclusions: The triathlete has an increased risk of VPB during maximal efforts. We doubt the traditionally accepted view of the physiological nature of those VPB and suspect that the limit of physiological cardiac adaptations to sport efforts is exceeded with the appearance of VPB. The triathlete with VPB and with specific electrocardiographic and echocardiographic findings is a candidate for ‘sudden cardiac death’.
Pain Recollection after Chest Pain of Cardiac Origin
Authors: Everts Bernt , Karlson Björn , Währborg Peter , Abdon Nils-Johan , Herlitz Johan , Hedner Tomas
Published: April 2003

Memory for pain is an important research and clinical issue since patients ability to accurately recall pain plays a prominent role in medical practice. The purpose of this prospective study was to find out if patients, with an episode of chest pain due to suspected acute myocardial infarction could accurately retrieve the pain initially experienced at home and during the first day of hospitalization after 6 months. A total of 177 patients were included in this analysis. The patients rated their experience of pain on a numerical rating scale. The maximal pain at home was retrospectively assessed, thereafter pain assessments were made at several points of time after admission. After 6 months they were asked to recall the intensity of pain and once again rate it on the numerical rating scale. The results from the initial and 6-month registrations were compared. In general, patients rated their maximal intensity of chest pain as being higher at the 6-month recollection as compared with the assessments made during the initial hospitalization. In particular, in patients with a high level of emotional distress, there was a systematic overestimation of the pain intensity at recall.
Acute Myocardical Infarction due toDelirium tremens
Authors: Danenberg Haim D. , Nahir Menachem , Hasin Yonathan
Published: April 2003

A 36-year-old patient with normal-appearing coronary arteries suffered an acute Q-wave myocardial infarction during acute alcohol withdrawal and delirium tremens. Sympathetic hyperactivity with coronary spasm and increased platelet reactivity are probably the underlying mechanisms.
Effects of Angiotensin-Converting Enzyme Gene Polymorphism on the Left-Ventricular Function and Mass in Patients with Acromegaly
Authors: Erbas Tomris , Alikasifoglu Mehmet , Aksöyek Serdar , Unsal Ibrahim , Gedik Olcay , Tuncbilek Ergül
Published: April 2003

In this study we have investigated the contribution of the ACE genotype to the development of left-ventricular hypertrophy (LVH) and systolic and diastolic dysfunctions in acromegalic patients. The study group consisted of 30 acromegalic patients (21 women and 9 men, age: 37.9 ± 10.8 years, disease duration: 9.0 ± 6.9 years). The distribution of the DD, ID and II genotypes was 40.0 (n = 12), 46.6 (n = 14) and 13.3% (n = 4), respectively, being similar to frequencies observed in a healthy population. Plasma ACE levels were 55.0 ± 12.0 (45–84), 28.7 ± 15.7 (8–58) and 24.5 ± 12.0 (16–33) U/l in patients with the DD, ID and II genotype, respectively. The mean serum ACE activity in the DD genotype was significantly higher than in the heterozygous group (p < 0.0001). Serum ACE activity showed a significant negative association with the mean growth hormone level (r = –0.52, p = 0.007). The LV early diastolic flow velocity/LV presystolic flow velocity (E/A) ratios were 1.2 ± 0.4 for the DD genotype, 1.3 ± 0.3 for the ID genotype and 0.7 ± 0.1 for the II genotype. The E/A ratio was considerably lower in acromegalic patients with the II genotype compared to the other genotypes (p = 0.03). The LV mass index (LVMI) values were 131.5 ± 4.2 g/m2 for the DD genotype, 141.7 ± 50.3 g/m2 for the ID genotype and 159.6 ± 48.2 g/m2 for the II genotype. However, there was no significant difference in LVMI among allelic groups. All other indices of systolic and diastolic function were not statistically different in the acromegalic patients. The present data fail to support a role of ACE gene polymorphism in determining LVH in acromegalic patients. However, the I allele may prove as a useful marker predicting the development of diastolic dysfunction in acromegalic patients.
Atrial Ejection Force in Systemic Autoimmune Diseases
Authors: Jahns Roland , Naito Johji , Tony Hans-Peter , Inselmann Gerhard
Published: April 2003

Systemic autoimmune disorders may affect several organs, including the heart. We analyzed two-dimensional and pulsed Doppler echocardiograms of patients (n = 37) with systemic lupus erythematosus (SLE, n = 24) or rheumatoid arthritis (RA, n = 13) to determine whether atrial ejection force (AEF) could represent a suitable parameter for detecting left ventricular filling abnormalities in SLE and RA. In both patient subgroups, AEF was significantly higher than in healthy controls (n = 40) matched for gender and age (14.0 ± 5.4 vs. 11.0 ± 3.5 kdyn, p < 0.01). Because conventional echocardiographic parameters of left ventricular function failed to detect such a difference, AEF might serve as an additional sensitive parameter for detecting left ventricular diastolic filling abnormalities early in the course of a systemic autoimmune disease.
Highly Effective Compensatory Mechanisms in a 76-Year-Old Man with a Coarctation of the Aorta
Authors: Miró Òscar , Jiménez Sònia , González Juan , De Caralt Teresa M. , Ordi Jaume
Published: April 2003

We present a man who was diagnosed with coarctation of the aorta (CA) at the age of 76. He had developed an extensive collateral circulation for maintaining the circulation below the CA. This compensatory mechanism was highly effective, since the patient had remained asymptomatic and in good health during most of his life. He died from intrahospitalary pneumonia, unrelated to CA. Long-term survival in patients with untreated CA is exceptional, with only 11 patients living into their 70s being previously reported. A review of these cases is included.
Evaluation of Brain Natriuretic Peptide in the Diagnosis of Heart Failure
Authors: Bettencourt Paulo , Ferreira António , Dias Paula , Castro Alice , Martins Luís , Cerqueira-Gomes Mário
Published: April 2003

A diagnosis of heart failure (HF) can be difficult, especially in patients with mild symptomatology. The purpose of this study was to evaluate the significance of brain natriuretic peptide (BNP) in the diagnosis of HF with systolic or isolated diastolic ventricular dysfunction. One hundred patients and 9 controls were included in the study. Eighty-five patients were diagnosed with HF, based on clinical and echocardiographic findings. BNP levels were accurate for the diagnosis of HF, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.92. In addition, BNP levels showed an excellent accuracy for the diagnosis of isolated diastolic HF (AUC = 0.89). These data suggest that the measurement of BNP levels may be helpful in the diagnosis of HF and in selecting patients for further evaluation. Furthermore, BNP measurement can play an important role in the diagnosis of isolated diastolic HF.
The Problem of Ventricular Dysrhythmias and Sudden Death Mortality in Heart Failure: The Impact of Current Therapy
Authors: Leier Carl V. , Alvarez Rene J. , Binkley Philip F.
Published: April 2003

Congestive heart failure (CHF), one of the few cardiovascular conditions increasing in incidence and prevalence, is characterized by high morbidity and mortality. Up to 50% of the mortality is attributable to dysrhythmic sudden death. Risk stratification to identify those most susceptible to sudden death remains imperfect. The advances in CHF therapeutics and management over the past 16 years have had a favorable impact on CHF mortality including sudden death. The role of amiodarone and implantable cardioverter-defibrillator intervention is evolving and discussed in the context of current CHF management and available trials.
Clinical Symptoms and Myocardial Infarction in Left Bundle Branch Block Patients
Authors: Shlipak Michael G. , Go Alan S. , Lyons William L. , Browner Warren S.
Published: April 2003

In patients with left bundle branch block (LBBB) and acute chest pain, the association between the clinical presentation and the diagnosis of myocardial infarction has not been investigated. We sought to identify features in the clinical history of patients with LBBB and acute cardiopulmonary symptoms that predict myocardial infarction among candidates for reperfusion therapy. We retrospectively studied a consecutive cohort of 75 patients (94 presentations) who presented to a university emergency department from 1994 to 1997 with LBBB on initial electrocardiogram (ECG) and acute chest pain of ≥20 min duration or acute pulmonary edema. Among the 94 presentations meeting criteria for the cohort, 26 (28%) had confirmed myocardial infarction. Coronary heart disease risk factors, past cardiac history, prior LBBB on the ECG, and presenting symptoms did not predict whether patients were having myocardial infarction. The clinical history was not effective at distinguishing LBBB patients with myocardial infarction among patients who appeared to be candidates for acute reperfusion therapy.
Integrated Backscatter for Quantification and Risk Stratification of Blood Stagnation in Left Atrial Appendages of Patients with Rheumatic Mitral Stenosis
Authors: Ho Yi-Lwun , Wu Chau-Chung , Lin Lung-Chun , Chen Ming-Fong , Lee Yuan-Teh , Huang Por-Jau
Published: April 2003

This study was designed to quantify the blood stagnation in left atrial appendages (LAA) of patients with rheumatic mitral stenosis, and to stratify the risk of spontaneous echo contrast (SEC) for thrombus formation. A total of 45 patients were enrolled in this study. Thirty of the 45 patients had rheumatic mitral stenosis. All the above patients were evaluated for LAA contractility by transesophageal echocardiography. Acoustic density of the stagnant blood was assessed using the integrated backscatter (IBS) mode. Multivariate linear regression analysis showed that the significant independent variables determining relative IBS in LAA were the mitral valve area (p = 0.02) and the atrial fibrillation rhythm (p = 0.0003). In patients with mitral stenosis, the IBS in LAA correlated well with the presence of thrombus (p = 0.004) and SEC (p = 0.002). Using the relative IBS in LAA with 6.8 dB as the cutoff value, the diagnostic sensitivity, specificity, positive predictive value, negative predictive value and accuracy of SEC formation in LAA was 83, 86, 95, 60 and 83%, respectively. Using the relative IBS in LAA with 10.0 dB as the cutoff value, the diagnostic sensitivity, specificity, positive predictive value, negative predictive value and accuracy of SEC with thrombus formation in LAA was 80, 80, 67, 89 and 80%, respectively. In conclusion, the blood stasis in LAA can be objectively quantified using IBS. Utilizing different cutoff values, the acoustic densitometry in LAA enables identification of stagnant blood which represents a risk for the development of either SEC only or SEC with thrombus formation.
Dangerous Impact – Commotio cordis
Authors: Wang Jieh-Neng , Tsai Yu-Chien , Chen Shwu-Ling , Chen Yi , Lin Chia-Shiang , Wu Jing-Ming
Published: April 2003

Sudden death following blunt chest trauma is a frightening occurrence known as ‘commotio cordis’ or ‘concussion of the heart’. It is speculated that commotio cordis could be caused by ventricular fibrillation secondary to an impact-induced energy that was transmitted via the chest wall to the myocardium during its vulnerable repolarization period. We describe a survivor of commotio cordis caused by a baseball. In this patient, an initial ventricular fibrillation was documented and converted by direct current defibrillation. Serial electrocardiographic changes (bifascicular conduction block and T wave inversion in precordial leads) were noticed in this patient. Our case suggested that coronary vasospasm might also play a role in commotio cordis.
Correlation of Predischarge Electrocardiographic Patterns with Left Ventricular Function in Patients with Anterior Wall Myocardial Infarction
Authors: Porter Avital , Mazur Alexander , Solodky Alejandro , Birnbaum Yochai , Sulkes Jacquelin , Imbar Shula , Strasberg Boris
Published: April 2003

The aim of this prospective study was to assess the correlation between different predischarge electrocardiographic patterns and left ventricular function, evaluated by physical examination and echocardiography, in patients with first Q wave anterior acute myocardial infarction. A positive correlation was found between the electrocardiographic pattern and wall motion score assessed by echocardiography, reflecting a gradual worsening in left ventricular function among the different patterns. Patients with an isoelectric ST segment and negative T waves had a 73% decrease in the risk of clinical heart failure compared to those who continued to have ST elevation. Thus, a predischarge electrocardiogram can be used as a simple, noninvasive method for the risk stratification of patients with acute myocardial infarction.
Continuous Infusion of Vancomycin in Methicillin- Resistant Staphylococcus Infection
Authors: Di Filippo A. , De Gaudio A.R. , Novelli A. , Paternostro E. , Pelagatti C. , Livi P. , Novelli G.P.
Published: April 2003

Objective: The aim of the study was to verify the therapeutic response of vancomycin in methicillin-resistant staphylococcus infection (MRSA/MRCNS) administered according to two different methods (intermittent infusion vs. continuous infusion). Method: Experimental plan: retrospective study; study environment: university hospital, two intensive care units. Twenty-five critically ill patients submitted to antibiotic treatment with vancomycin for infection from MRSA/MRCNS were studied. The patients, who were classified according to SAPS II scores, were divided into two groups: group A (n = 14): dose of vancomycin of 0.5 g × 4/day and group B (n = 11): dose of 2 g/day of vancomycin administered in a continuous infusion. Before the antibiotic therapy was started (T1) and prior to its end (T2), the following parameters were evaluated: degree of impairment of the main organs and systems by means of sepsis-related organ failure assessment score (SOFA) and count of the white blood cells (WBC). The length of the hospital stay during intensive care was calculated for both groups (statistics: Student t test). Results: No significant differences were found in the SAPS II scores and in the length of the hospital stay. In a comparison of the T1 and T2 results, we noted that patients of group A had no variations in the SOFA scores (4.84 ± 2.48 vs. 4 ± 3.9) and in the WBC mean values (12,415 ± 5,099 vs. 12,841 ± 6,864 cells/mm3). In contrast, in the patients of group B, we noted significant variations (p < 0.05) in the mean values of the SOFA scores (6.62 ± 2.2 vs. 4.37 ± 3.5) and in the mean values relative to the WBC count (17,242 ± 12,842 vs. 10,757 ± 3,610 cells/mm3). Conclusions: In critically ill patients suffering from MRSA/MRCNS infection, vancomycin administration in continuous infusions improved organ function and leukocyte response, but did not seem to modify the overall evolution of the disease.
Antibiotic Susceptibility Testing (Agar Disk Diffusion and Agar Dilution) of Clinical Isolates of Enterococcus faecalis and E. faecium: Comparison of Mueller-Hinton, Iso-Sensitest, and Wilkins-Chalgren Agar Media
Authors: Traub Walter H. , Geipel Udo , Leonhard Birgit
Published: April 2003

Forty-two isolates of Enterococcus faecalis and 56 isolates of Enterococcus faecium, including 8 vancomycin-resistant strains, were examined for comparative susceptibility to 27 antimicrobial drugs with the agar dilution method, employing Mueller-Hinton (MHA), Iso-Sensitest (ISTA), and Wilkins-Chalgren (WCA) agar. The Bauer-Kirby agar disk diffusion method was used to comparatively test 24 of the agents in parallel. The enterococci yielded better growth on ISTA and WCA. However, WCA completely antagonized co-trimoxazole and, though less, fosfomycin. Importantly, WCA slightly reduced the activities of teicoplanin (minimal inhibitory concentrations, MICs, raised up to twofold) and vancomycin (MICs raised two- to fourfold) against enterococci and staphylococcal quality control strains. Therefore, WCA was judged unsuitable for susceptibility testing of enterococci. For E. faecalis no discrepancies between agar dilution MICs and inhibition zone diameters were encountered with augmentin, ampicillin, ampicillin-sulbactam, chloramphenicol, mupirocin, oxacillin, teicoplanin, and co-trimoxazole. Overall, MHA yielded fewer very major (category I) and major (category II) discrepancies than ISTA. However, numerous minor (category III), slight (category IV), minimal (category V), and/or negligible (category VI) discrepanices were encountered with ciprofloxacin, doxycycline, erythromycin, fosfomycin, fusidic acid, meropenem, ofloxacin and rifampin. With respect to E. faecium, only cefotaxime, mupirocin, oxacillin, and teicoplanin yielded nondiscrepant results. Several very major (I) and major (II) discrepancies were observed with augmentin, ampicillin, ampicillin-sulbactam, doxycycline, fusidic acid, imipenem, and penicillin G. Minor discrepancies (categories III–VI) were particularly numerous with augmentin, chloramphenicol, ciprofloxacin, doxycycline, and piperacillin. The largest numbers of negligible (VI) discrepancies were noted with fosfomycin, fusidic acid, and ofloxacin. It is recommended to test one cephalosporin (cefuroxime or the like) in parallel for educational purposes and to exclude fosfomycin, fusidic acid, and rifampin from test batteries because of the wide scatter of test results. The large number of minimal (V) discrepancies of ciprofloxacin against E. faecalis, the numerous minor (III) and slight (IV) discrepancies of chloramphenicol against E. faecium, and the not insignificant number of very major (I) and minor (III) discrepancies observed with meropenem against isolates of E. faecalis necessitated proposals for new disk intermediate susceptibility criteria.
Inhibitory Action of Natural Carrageenans on Herpes simplex Virus Infection of Mouse Astrocytes
Authors: Carlucci M.J. , Scolaro L.A. , Damonte E.B.
Published: April 2003

The effects of the carrageenans 1T1 (λ-type), 1C1 (κ/ι-type) and 1C3 (ιι/ν-type), isolated from the red seaweed Gigartina skottsbergii, on herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infection of murine astrocytes were investigated. The three compounds were effective inhibitors of virus replication, as determined by a virus yield inhibition assay, in astrocytes as well as in Vero cells. The 50% inhibitory concentration was in the range of 0.9–3.6 and 0.4–3.2 μg/ml for astrocytes and Vero cells, respectively, whereas the 90% inhibitory concentration ranged from 6.5 to 17.0 μg/ml in astrocytes and from 3.5 to 22.2 μg/ml in Vero cells. No cytotoxicity was detected at concentrations of up to 1,000 μg/ml, indicating high selectivity indices for these compounds. Inhibition of viral cytopathology and antigen expression was also detected in the presence of the carrageenans. The increase in the expression of glial fibrillary acidic protein (GFAP), an activated astrocyte marker, produced during the course of HSV-1 infection in astrocytes, was reversed in the presence of 1C1 and 1C3. By contrast, the λ-carrageenan 1T1 increased the expression of GFAP, independently of HSV-1 infection.
K-Ras Mutations at Codon 12 Are Rare Events in Chronic Pancreatitis
Authors: Orth Martina , Gansauge Frank , Gansauge Susanne , Beger Hans-Günther , Adler Guido , Schmid Roland M.
Published: April 2003

Background/Aims: The activation of the K-ras gene at codon 12 is thought to be an early genetic event in the multistep pathogenesis of pancreatic cancer. Since the risk of pancreatic cancer is significantly elevated in subjects with chronic pancreatitis, the aim of the present study was to determine the frequency of K-ras mutations in chronic pancreatitis. Methods: Pancreatic DNA from intraoperatively resected tissues of 60 patients with chronic pancreatitis and 11 patients with histologically confirmed pancreatic carcinoma was evaluated by PCR amplification and restriction fragment length polymorphism analysis. Results: In none of the 60 samples of chronic pancreatitis could K-ras mutations be identified using two independent PCR assays. In 5 of 11 patients with pancreatic carcinoma, K-ras mutations in codon 12 were detected. Conclusion: These data indicate that K-ras mutations are rare events in chronic pancreatitis. Alternatively, it is possible that the time span between the occurrence of K-ras mutations and malignant transformation is rather short.
Helicobacter pylori Infection Decreases Gastric Alcohol Dehydrogenase Activity and First-Pass Metabolism of Ethanol in Man
Authors: Simanowski Ulrich A. , Egerer Gerlinde , Oneta Carl , Keil Thomas , Parés Xavier , Conradt Christian , Arce Luis , Waldherr Rüdiger , Stickel Felix , Russell Robert M. , Aderjan Rolf , Klee Fritz , Seitz Helmut K.
Published: April 2003

Background/Aims: Ethanol is metabolized by alcohol dehydrogenase in the human stomach. This metabolism contributes to the so-called first-pass metabolism of ethanol which is affected by gender, medication, and morphological alterations of the gastric mucosa. Recently, it has been shown that Helicobacter pylori is capable to oxidize ethanol to acetaldehyde in vitro. Since H. pylori also injures gastric mucosa, the present study examines the effect of this bacterium on gastric alcohol dehydrogenase activity and systemic availability of ethanol in vivo. Methods: Thirteen volunteers (7 men and 6 women, aged 18–52 years) with gastric H. pylori infection diagnosed by a positive CLO test and positive gastric histology received ethanol (0.225 g/kg) either orally or intravenously before and after H. pylori elimination to determine systemic availability of ethanol. In addition, gastric biopsy specimens were taken from all subjects before and after H. pylori elimination for histological assessment of mucosal alterations and determinations of gastric alcohol dehydrogenase activity and phenotype of the enzyme. Results: In the presence of H. pylori the first-pass metabolism of ethanol was found to be significantly reduced (625 ± 234 vs. 1,155 ± 114 mg/dl/min, p = 0.046). This reduction of first-pass metabolism of ethanol was associated with a significant decrease in alcohol dehydrogenase activity (4.8 ± 1.5 vs. 12.1 ± 2.3 nmol/mg protein × min, p < 0.05) and an increase in the severity of mucosal damage as determined by a histological score (p < 0.05). Conclusions: H. pylori infection leads to gastric mucosal injury which is associated with a decrease in gastric alcohol dehydrogenase activity and first-pass metabolism of ethanol. Ethanol metabolism by H. pylori does not play an important role in vivo. However, gastric morphology is one important factor determining systemic availability of ethanol in man.
Genetics of Colonic Cancer
Authors: Lynch Henry T. , Lynch Jane F.
Published: April 2003

Research in hereditary forms of colorectal cancer (CRC) has increased almost logarithmically thanks in a major way to momentous discoveries in molecular genetics during the past decade. Between 10 and 20% of the total CRC burden is due to Mendelian-inherited CRC syndromes. The paradigm for hereditary CRC is familial adenomatous polyposis (FAP), wherein the APC germ-line mutation has been identified. This has contributed to the elucidation of genomic and clinical heterogeneity within the syndrome, wherein an attenuated form of FAP has been identified as a result of intragenic mutations within this large APC gene. The most common form of hereditary CRC is hereditary nonpolyposis colorectal cancer (HNPCC). Several mutator genes, namely hMSH2, hMLH1, hPMS1, hPMS2 and, more recently, hMSH6/GTBP, have been identified. These molecular genetic discoveries are providing new insights into the pathogenesis of CRC. Individuals within these kindreds who are harbingers of these germ-line mutations will benefit from screening and, one day, chemoprevention.
Schistosomiasis
Authors: El-Garem Ahmed Ali
Published: April 2003

Schistosomiasis is a man-made disease related to water contact in the agricultural fields and affecting millions of people in developing countries in the tropical and subtropical parts of Africa, Asia and South America. It is a bisexual trematode living in the portal blood and perivesical venous plexus. Its life cycle necessitates the presence of an intermediate host – a fresh water mollusc – that differs according to place. The pathogenetic stage is the ova that initiate an immunologically delayed hypersensitivity cell-mediated reaction in the organs where they are deposited. The liver, colon, urinary bladder and ureter are the main organs affected; however, any organ can be affected, even the skin and the brain. The review discusses the pathogenesis, pathology, diagnosis: parasitological and immunological, the clinical picture, treatment and control. The present status of the research work on vaccination is also presented.
Comparison of Omeprazole, Metronidazole and Clarithromycin with Omeprazole/Amoxicillin Dual-Therapy for the Cure of Helicobacter pylori Infection
Authors: Miehlke Stephan , Meining Alexander , Lehn Norbert , Höchter Wilhelm , Weingart Josef , Simon Thomas , Krämer Walter , Klann Hermann , Bolle Karl-Heinz , Sommer Albrecht , Stolte Manfred , Bayerdörffer Ekkehard
Published: April 2003

In this randomized, multicenter trial, we evaluated the effectiveness and side effect profile of a modified omeprazole-based triple therapy to cure Helicobacter pylori infection. The control group consisted of patients treated with standard dual therapy comprising omeprazole and amoxicillin. One hundred and fifty-seven H. pylori infected patients with duodenal ulcers were randomly assigned to receive either a combination of omeprazole 10 mg, clarithromycin 250 mg and metronidazole 400 mg (OCM) given three times daily for 10 days (n = 81), or a combination of omeprazole 20 mg and amoxicillin 1 g (OA) given twice daily for 14 days (n = 76). Prior to treatment and after 2 and 6 weeks, gastric biopsies from the antrum and corpus were obtained for histology and H. pylori culture. H. pylori infection was cured in 97.4% after OCM and in 65.8% after OA in the per-protocol analysis (p < 0.001) (intention-to-treat analysis: 93.4% and 63.2%, respectively). H. pylori was successfully cultured in 122 patients (77%). The overall rate of metronidazole resistance was 19.7% (24/122), no primary resistance to clarithromycin or amoxicillin was found. In the OCM group, all patients infected with metronidazole-sensitive H. pylori strains (n = 51) and those infected with strains of unknown susceptibility to metronidazole (n = 14) were cured (100%), while 77% (10/13) of those harboring metronidazole-resistant strains were cured of the infection (p = 0.36). Side effects leading to premature termination of treatment occurred in 2.5% of the patients in the OCM group and in 1.4% of the OA group. We conclude that combined treatment with omeprazole, clarithromycin and a higher dose of metronidazole is highly effective in curing H. pylori infection, and that this regimen remains very effective in the presence of metronidazole-resistant strains.
Omeprazole for Peptic Ulcer Disease in Pregnancy
Authors: Brunner G. , Meyer H. , Athmann C.
Published: April 2003

This report contains the observations of 9 women who received omeprazole for severe reflux disease during different stages of pregnancy. Four patients took omeprazole at the time of conception, and 3 of these patients continued omeprazole therapy without interruption until delivery. One patient discontinued therapy in the 8th week of pregnancy but had to take the drug again from the 28th week to delivery. The other 5 patients started therapy in weeks 24, 30, 33, 34 and 36 of pregnancy because of bleeding in 2 patients and unbearable H2 receptor refractory reflux symptoms in the other 3 patients. All patients were carefully monitored. In all cases omeprazole was well tolerated. No severe side effects were observed in any of the mothers or their newborns. No malfunctions or malformations were observed in the newborns. Follow-up of the children between 2 and 12 years showed normal development in all children. These data together with the data on 8 such pregnancies published by other authors suggest that omeprazole is safe when given during pregnancy at whatever phase.
Pancreatic Tumour Marker Anti-Mucin Antibody CAM 17.1 Reacts with a Sialyl Blood Group Antigen, Probably I, Which Is Expressed throughout the Human Gastrointestinal Tract
Authors: Eccleston D.W. , Milton J.D. , Hoffman J. , Bara J. , Rhodes J.M.
Published: April 2003

CAM 17.1 is an antimucin monoclonal antibody which has recently been proven valuable as a reagent for serological diagnosis of pancreatic cancer. A series of studies have been performed to characterise its epitope. First it was screened immunohistochemically against a wide range of formalin-fixed normal and neoplastic human tissues and showed widespread binding to mucin throughout the gastro-intestinal tract, in both normal and malignant tissues. In pancreas, strong intracellular staining of acinar and ductal cells was found in normal tissue and in carcinoma cells in tumours. Normal stomach showed only weak staining (n = 6), but gastritis with metaplasia showed strong staining (n = 4). Staining of colonic mucosa from patients of known Lewis phenotype showed Le(a+b–) (7/8) and Le(a–b+) (4/6) samples to be positive, but not Le(a–b–) (0/3) samples. CAM 17.1 agglutinated all donor erythrocytes tested at 4°C regardless of blood group, whereas cord blood red cells were not agglutinated. Since I antigen is the only antigen known to be present on all adult red blood cells but absent from cord blood, this suggests probable involvement of this antigen in the binding site. The agglutination was abolished by sialidase treatment of the red cells and immunoblotting with slot-blotted mucin showed that binding was both acid and sialidase sensitive indicating the involvement of sialic acid in the binding site. These studies show that CAM 17.1 binds to a sialic-acid-containing determinant of mucin, probably sialyl-I, which epitope shows wide distribution throughout the gastro-intestinal tract.
Lipopolysaccharide Exhibits Synergistic Enhancement of Butyrate-Induced and Retinoic Acid-Mediated Alkaline Phosphatase Activity on Small Intestinal Epithelial Cell Line, IEC-6
Authors: Fukushima Kouhei , Sasaki Iwao , Takahashi Ken-ichi , Naito Hiroo , Ogawa Hitoshi , Sato Shun , Matsuno Seiki
Published: April 2003

Although both lipopolysaccharide (LPS) and sodium butyrate are major bacterial products and bioactive chemicals with multiple functions on mucosal cells in the gut, their interaction effects on epithelial cells are not well understood. The purpose of the present study was to investigate whether LPS modulates butyrate-induced and retinoic acid-mediated alkaline phosphatase (ALP) activity of IEC-6 cells – a rat nontransformed small intestinal epithelial cell line. When cells reached confluency, various combinations of sodium butyrate, retinoic acid and LPS were added to the cultures. Cells were then harvested for the measurement of ALP activities. Sodium butyrate, but not retinoic acid or LPS alone, enhanced ALP activity. When LPS was additionally used with butyrate or retinoic acid, synergistic induction of ALP activities was demonstrated. No additive effect for ALP activity was observed when muramyl peptides or N-formylmethionyl-leucyl-phenylalanine was used with these acids. The present study clearly demonstrated that the specific combination of butyrate and LPS synergistically increased ALP activity, an epithelial differentiation-associated marker, of an intestinal epithelial cell line.
A Continuous Automated Method for the Determination of Intestinal Disaccharidase Activities
Authors: Sall I. , Férard G.
Published: April 2003

A reliable method for the measurement of various disaccharidase activities such as maltase, isomaltase and sucrase is introduced. It is based on the continuous measurement of liberated glucose by a commercially available glucose dehydrogenase reagent. The procedures were first optimized for enzymes from rat intestinal mucosa. The pH optima were similar (6.3–6.7) for the three enzymes tested, and the apparent Kms were estimated to be 18, 12 and 19 mmol/l for maltase, isomaltase and sucrase, respectively. The procedures were adapted on a Cobas Mira automated analyzer. The assays correlated strongly with the conventional method of Dahlqvist. They were reliable, rapid, easy to perform and validate because the progress curve of each reaction rate can be continuously monitored. The method described has also been applied to human intestinal mucosa (Caco-2 cells).
Augmentation of Water-Immersion Stress- Induced Gastric Mucosal Lesions in BALB/c Mice Infected with Helicobacter felis
Authors: Matsushima Yumi , Kinoshita Yoshikazu , Watanabe Makoto , Hassan Sazzad , Fukui Hirokazu , Maekawa Toru , Okada Akihiko , Kawanami Chiharu , Kishi Kiyohiko , Watanabe Norihiko , Nakao Masafumi , Chiba Tsutomu
Published: April 2003

Background and Aims: Inoculation of Helicobacter felis into the murine stomach has been reported to induce chronic gastric inflammation and may be a model of Helicobacter pylori-induced chronic gastritis. In this study, to characterize H. felis-induced gastritis, the gastric production of interleukin-1β (IL-1β) and hepatocyte growth factor (HGF) was measured in mice. Methods: Gastric mucosal lesions were induced in H. felis-infected BALB/c mice by water-immersion stress. The severity score of gastric erosions per stomach was measured as the sum of the length of erosions. Gene expression of IL-1β and HGF were analyzed by Northern blot analysis and production of HGF was examined using the enzyme immunoassay method. Results: Water-immersion stress induced gastric mucosal lesions accompanied by increased expression of IL-1β mRNA. H. felis infection evoked enhanced expression of IL-1β and HGF genes. When H. felis-infected mice were stressed by water immersion, the mucosal lesions were more severe than those in non-infected mice. Moreover, IL-1β gene expression as well as HGF production was further increased. Conclusions: Although H. felis inoculation did not cause gastric mucosal erosions by itself, it augmented the stress-induced erosions.
p38 Map Kinase Is Expressed in the Pancreas and Is Immediately Activated following Cerulein Hyperstimulation
Authors: Wagner Andreas C.C. , Metzler Wolfgang , Höfken Thomas , Weber H. , Göke Burkhard
Published: April 2003

Background: The pathophysiology of pancreatitis and the pancreatic stress response are not well understood. In the pancreas, mitogen-activated protein kinase (MAPK) and stress-activated protein kinase (SAPK) are reportedly regulated by secretagogue stimulation and hyperstimulation. However, no data exist on the expression and regulation of pancreatic p38 Map kinase. Aims: Pancreatic expression of p38 Map kinase and MAPK, SAPK and p38 regulation during pancreatic stress were investigated. Methods: For hyperstimulation and secretory stress, cerulein was given intravenously, while hyperthermia preconditioning stress was induced by whole body hyperthermia (42°C). Results: In addition to MAPK and SAPK, p38 Map kinase was found to be expressed in the rat pancreas. Cerulein regulated all kinases time- and dose-dependently. MAPK and p38 Map kinase showed basal activity and were further activated at low cerulein doses. SAPK had no basal activity and its activation required maximal secretory to supramaximal amounts of cerulein. Cerulein hyperstimulation, inducing pancreatitis, activated p38 more rapidly than SAPK and more strongly than MAPK. In contrast to cerulein hyperstimulation stress, hyperthermia stress only activated p38 Map kinase. Conclusions: p38 Map kinase is expressed in the pancreas and is most rapidly activated following cerulein hyperstimulation. Both SAPK and p38 Map kinase are possibly important regulators during the onset of cerulein pancreatitis.
Role of Circulating Gastrin in Colorectal Adenomas and Carcinomas
Authors: Lamberts Regina , Wartenberg Tanja , Creutzfeldt Werner
Published: April 2003

Background/Aims: A trophic role of gastrin has been convincingly demonstrated in the oxyntic mucosa of the stomach, but is still a matter of debate in the lower gastrointestinal tract. Methods: In order to examine the role of circulating gastrin in colorectal adenoma and carcinoma fasting serum gastrin concentrations were determined in 351 patients undergoing complete colonoscopy. Results: In comparison to controls (n = 145) more patients with either polyps (n = 125) or colorectal carcinoma (n = 81) have slightly increased serum gastrin concentrations, leading to an increased mean, but no change in median serum gastrin levels. In 3 patients preoperatively increased serum gastrin concentrations were normalized after surgical removal of the polyp and/or tumor, suggesting a local release of gastrin from the polyp/tumor. Gastrin concentrations do not correlate with the histopathological classification or malignant potential of adenomatous polyps. Conclusion: In view of these findings a significant role of circulating endogenous gastrin in human colorectal carcinogenesis seems to be unlikely.
Hyperglycemia Reduces Pancreaticobiliary Secretion in Response to Modified Sham Feeding in Humans
Authors: Lam W.F. , Lindeboom M.E. , Lamers C.B.H.W. , Masclee A.A.M.
Published: April 2003

Background/Aims: We have investigated the effect of acute hyperglycemia on pancreaticobiliary secretion and pancreatic polypeptide (PP) release. Methods: Duodenal outputs of bilirubin, trypsin, lipase, amylase and bicarbonate were measured using a recovery marker under basal conditions and in response to modified sham feeding (MSF) in 6 healthy subjects on two separate occasions: during normoglycemia and during acute hyperglycemia (15 mmol/l). Results: During hyperglycemia the basal pancreaticobiliary output was significantly (p < 0.05) reduced. During normoglycemia MSF significantly (p < 0.05) increased the output of bilirubin and pancreatic enzymes; during hyperglycemia only the output of pancreatic enzymes increased significantly (p < 0.05) over basal. During MSF the outputs of bilirubin (16 ± 4 vs. 4 ± 2 µmol/30 min), trypsin (26 ± 7 vs. 7 ± 4 U/30 min), lipase (36 ± 11 vs. 15 ± 6 kU/30 min), amylase (3.4 ± 0.7 vs. 1.4 ± 0.7 kU/30 min) and bicarbonate (0.8 ± 0.1 vs. 0.5 ± 0.1 mmol/30 min) were significantly (p < 0.05) reduced during hyperglycemia compared to normoglycemia. During hyperglycemia basal and MSF-stimulated PP levels were significantly (p < 0.05) reduced compared to normoglycemia. MSF did not significantly influence plasma cholecystokinin levels in both experiments. Conclusions: This study indicates (1) that the blood glucose levels affect basal and cephalic stimulated pancreaticobiliary secretion and (2) that the PP secretion during hyperglycemia is reduced, suggesting impaired vagal cholinergic activity during hyperglycemia.
Effect of Whey-Based Culture Supernatant of Lactobacillus acidophilus (johnsonii) La1 on Helicobacter pylori Infection in Humans
Authors: Michetti P. , Dorta G. , Wiesel P.H. , Brassart D. , Verdu E. , Herranz M. , Felley C. , Porta N. , Rouvet M. , Blum A.L. , Corthésy-Theulaz I.
Published: April 2003

Background: Specific strains of Lactobacillus acidophilus are known to inhibit intestinal cell adhesion and invasion by enterovirulent bacteria. As L. acidophilus can survive transiently in the human stomach, it may downregulate Helicobacter pylori infection. Methods: The ability of L. acidophilus (johnsonii) La1 supernatant to interfere with H. pylori bacterial growth, urease activity, and adhesion to epithelial cells was tested in vitro. Its effect on H. pylori infection in volunteers was monitored in a randomized, double-blind, controlled clinical trial, using a drinkable, whey-based, La1 culture supernatant. H. pylori infected volunteers were treated 14 days with 50 ml of La1 supernatant four times a day combined with either omeprazole 20 mg four times a day or with placebo. Infection was assessed by breath test, endoscopy, and biopsy sampling, performed at inclusion, immediately at the end of the treatment (breath test only), and 4 weeks after the end of the treatment. Results: La1 supernatant inhibited H. pylori growth in vitro, regardless of previous binding of H. pylori to epithelial cells. In 20 subjects (8 females, 12 males, mean age 33.1 years) a marked decrease in breath test values was observed immediately after treatment with La1 supernatant, both in the omeprazole and in the placebo group (median 12.3 vs. 28.8 and 9.4 vs. 20.4, respectively; p < 0.03). In both treatment groups, breath test values remained low 6 weeks after treatment (omeprazole treated 19.2, placebo treated 8.3; p < 0.03 vs. pretreatment), but the persistence of H. pylori infection was confirmed in gastric biopsies. Conclusion: La1 culture supernatant shown to be effective in vitro has a partial, acid-independent long-term suppressive effect on H. pylori in humans.
Helicobacter pylori and the Risk of Colonic Adenomas
Authors: Breuer-Katschinski B. , Nemes K. , Marr A. , Rump B. , Leiendecker B. , Breuer N. , Goebell H.
Published: April 2003

Aims: Previous studies have found a positive association between Helicobacter pylori infection and colorectal adenomas. The aim of the present study was to examine this association while taking possible confounding factors into account. Methods: 98 serum samples were available from 182 patients with colorectal adenomas who entered a case-control study of colorectal adenomas and diet. The H. pylori status in patients was compared with a hospital control group and a population control group. Results: H. pylori IgG antibodies were more common in colorectal polyp patients compared with either control group, the prevalence being 79% in cases compared with 62% in both control groups. The corresponding RR was 1.4 (0.76–2.6) compared with hospital controls and 2.1 (1.1–3.9) compared with population controls. After adjusting for possible confounding variables the association between H. pylori status and adenoma risk was even more marked. There was an RR of 1.6 (0.80–3.4) compared with hospital controls and an RR of 2.6 (1.3–5.4) compared with population controls, the latter association being statistically significant. Conclusion: These findings suggest a statistically significant association between H. pylori infection and colorectal polyps. A possible mechanism might be increased gastrin levels in H. pylori-infected subjects which exhibit a trophic effect on colonic mucosa.
Fragmentation Pattern of Mucins in Normal and Diseased Gastric Mucosae: A Glycoprotein Fractionates with Gastric Mucins Purified from Mucosal Scrapings of Cancer and Peptic Ulcer Patients
Authors: Mall Anwar S. , McLeod Heather A. , Hickman Rosemary , Kahn Delawir , Dent David M.
Published: April 2003

Background/Aims: Gastric cancer, a fatal malignancy, is prevalent in the Western Cape region of South Africa. The aim of this study was a biochemical characterisation of gastric mucins in this disease, compared with gastric ulceration and controls from transplant donors. Methods: Mucins were extracted in a denaturing medium (to prevent endogenous proteolysis) and purified by caesium chloride density gradient ultracentrifugation. Analysis of mucin was by gel filtration, SDS-PAGE and Western blotting methods. Results: All samples of mucin when analysed by gel filtration were found to contain polymeric glycoprotein together with varying amounts of lower-molecular-weight glycoprotein. SDS-PAGE and Western blot analysis showed that diseased stomachs had glycopeptides of a wider range in size and antigenicity with a greater number of smaller fragments immunoreactive to monoclonal antibodies 2–12M1 and 9–13M1. We identified by SDS-PAGE a glycoprotein which co-fractionates in a caesium chloride density gradient with mucins isolated from gastrectomy specimens resected for carcinoma and peptic ulceration and which was absent from mucins of the transplant donor control group. This neuraminidase-sensitive glycoprotein resisted dissociation from mucin during purification in a 3.5 M CsCl density gradient but was partially separable by Sepharose 2B gel chromatography and heat treatment (100°C, 2.0 min) in SDS. Chemical analysis of the glycoprotein by HPLC favours it being an N-linked glycoprotein. Its non-ideal electrophoretic properties make its exact size estimation difficult and we ascribe to it a broad size range of Mr ∼55–65 kD. Conclusion: We conclude that mucins from diseased stomachs were more degraded than those from donors and that the diseased mucosa reproducibly secretes a Mr ∼55–65 kD glycoprotein, the role of which needs to be established.