bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of HBs, HBc, and frCP Virus-Like Particles for Expression of Human Papillomavirus 16 E7 Oncoprotein Epitopes
Authors: Pumpens Paul , Razanskas Raimundas , Pushko Peter , Renhof Regina , Gusars Indulis , Skrastina Dace , Ose Velta , Borisova Galina , Sominskaya Irina , Petrovskis Ivars , Jansons Juris , Sasnauskas Kestutis
Published: April 2003

Objectives: In an attempt to develop virus-like particles (VLPs) as experimental vaccine against human papilloma virus (HPV)-induced tumours, the HPV16 E7 oncoprotein epitopes spanning amino acid (aa) residues 35–98 were expressed on three proteins capable of VLP formation: hepatitis B virus (HBV) surface (HBs) and core (HBc) antigens, and RNA phage fr coats (frCP). Methods: The profile of immunoglobulin isotypes induced in Balb/C mice after immunization with purified chimeric proteins was studied. Results: The HBs*-E7(35–54) protein expressing E7 residues 35–54 between residues 139 and 142 of the HBs carrier formed HBs-like particles in Saccharomyces cerevisiae. The HBcΔ-E7(35–98), but not the frCP-E7(35–98), ensured VLP formation in Escherichia coli. In Balb/C mice, the HBs*-E7(35–54) VLPs predominantly induced an anti-E7 antibody, but not anti-HBs carrier response, whereas the HBcΔ-E7(35–98) VLPs induced a lower anti-E7 compared to anti-HBc carrier response. The frCP-E7(35–98) protein elicited equally high antibody responses to both E7 and frCP carrier. Analysis of the immunoglobulin G isotype profile of the antibodies induced by the E7-carrying chimeras showed that the HBs and frCP derivatives were capable of eliciting the Th1 and Th2 subsets of T helper cells, whereas the HBc-derived chimeras elicited only the Th2 subset. Conclusions: The HBs and HBc, but not frCP carriers support an efficient outcome for VLPs carrying the HPV16 E7 epitopes. All chimeric proteins may be regarded as potential vaccine candidates.
Increased Duodenal Mucosa Infiltration by Mast Cells in Rats with Portal Hypertension
Authors: Diez-Arias J.A. , Aller M.A. , Palma M.D. , Arias J.L. , Muñiz E. , Sánchez M. , Arias J.
Published: April 2003

Background: Enteropathy characterized by vascular and inflammatory alterations in the submucosa and mucosa has been described in patients with portal hypertension. Aims: To verify the theory of inflammatory etiopathogenesis in experimental portal hypertensive duodenopathy, a prehepatic portal hypertension model based on the development of a single and triple partial ligation of the portal vein was used in the rat. Methods: Five rats in each group (male Wistar, 230–255 g) were subjected to single (group II) or triple (group III) partial ligation of the portal vein and then compared to 5 control animals (group I, no operation). The animals were sacrificed 6 weeks later to analyze the histological parameters of the duodenal mucosa and submucosa, i.e., number, diameter and area of submucosal vessels, density of mast cells and mitotic cells. Body, liver and spleen weights and collateral circulation type were also assayed. Results: As was demonstrated by the collateral circulation in all of the animals, the partial portal ligation was successful. Compared to the controls, the number of vessels per microscopic field (25 ± 3.16 vs. 18.60 ± 1.52), their diameter (20.09 ± 2.90 vs. 12.61 ± 3.97 µm, p < 0.05) and consequently their total area (12,749.30 ± 2,298.26 vs. 3,455.82 ± 1,702.33 µm2) were increased in the animals with a single partial ligation (group II) as well as in animals receiving triple partial ligation (group III) (33 ± 12.88, p < 0.05; 22.92 ± 6.72 µm, p < 0.05 and 51,376.95 ± 43,732.24 µm2, p < 0.05, respectively). In addition, the density of mast cells increased from 3.26 ± 1.18 in controls to 10.74 ± 1.47, p < 0.01 and 22.50 ± 6.42, p < 0.01 in single and triple partial portal ligated animals, respectively. Mitosis was significantly induced in crypts of the duodenal mucosa of the single portal ligated animals (25.20 ± 1.78 vs. 17.40 ± 1.14, p < 0.01) but was inhibited in triple partial ligated animals (12.40 ± 5.12, p < 0.05). Compared to controls, both groups of rats developed liver atrophy with a greater decrease in the liver/body weight ratio in the single (2.71 ± 0.50%, p < 0.01) compared to the triple partial ligated animals (3.33 ± 0.09%, p < 0.01). Conclusions: The correlation of the degree of portal hypertension with the vascular changes and mast cell density suggests that both the hypertensive state and inflammation may play a role in the development of portal hypertensive intestinal vasculopathy. The inverse relation of portal hypertension with liver atrophy and mitosis rate in the crypts of the duodenal mucosa has not been clarified and should be investigated in future studies.
How Effective Is Extensive Nonsurgical Treatment of Patients with Clinically Active Crohn’s Disease of the Terminal Ileum in Preventing Surgery?
Authors: Bemelman W.A. , Ivenski M. , van Hogezand R.A. , Hermans J. , Veenendaal R.A. , Griffioen G.
Published: April 2003

Background/Aims: The purpose of this study is to determine the effectiveness of extensive nonsurgical management of patients with clinically active Crohn’s disease of the terminal ileum and to identify parameters that could predict failure of this nonsurgical approach. Methods: All consecutive patients hospitalized for the first time because of active Crohn’s disease of the terminal ileum between 1985 and 1994 were included. Two groups of patients were defined. Patients who responded favorably to the extensive treatment protocol (group I), and patients in whom an ileocolic resection had been performed (group II). Treatment and patient characteristics were related to outcome. Results: Twenty-nine (38%) of the 76 patients were treated successfully by nonsurgical management (group I) and did not have surgery until the end of follow-up (mean 8.0 years, range 3–12 years). In total, 47 patients (62%) had ileocolic resection (group II). Logistic regression analysis revealed that a longer time between onset and exacerbation of this disease, the presence of stenosis and extraintestinal manifestations were independent predictors of failure of nonsurgical treatment. Conclusion: Prolonged medical treatment is effective in only one third of the clinically admitted patients. It should be applied with caution particularly in patients exhibiting stenosis, extraintestinal manifestations or a known history of Crohn’s disease of more than 5 years.
Vena cava Stenting and Portorenal Shunt in Budd-Chiari Syndrome: Combination of the ‘Modern’ and the ‘Classical’
Authors: Emre Ali , Özden İlgin , Poyanlı Arzu , Bilge Orhan
Published: April 2003

We have treated a 33-year-old Budd-Chiari patient (due to antiphospholipid syndrome) with a history of myocardial infarction by placing a vascular stent in the inferior vena cava and performing a portorenal shunt with three objectives: (1) to perform a shunt operation on a Budd-Chiari patient with good hepatic functional reserve, (2) to avoid a thoracotomy and manipulation of the heart in a patient with a cardiac thrombus and a history of myocardial infarction and (3) to avoid a synthetic graft in a patient with antiphospholipid syndrome. Vena cava stenting and portorenal shunt make a useful combination which should be included in the armamentarium of the hepatobiliary surgeon.
Single and Multiple Pyogenic Liver Abscesses: Etiology, Clinical Course, and Outcome
Authors: Alvarez José A. , González Juan J. , Baldonedo Ricardo F. , Sanz Lourdes , Carreño Guillermo , Jorge José I.
Published: April 2003

Background: Pyogenic liver abscesses are uncommon but they still carry a high mortality rate when encountered. This study was undertaken to evaluate the differences in the clinical behaviour of patients with single and multiple abscesses. Methods: From January 1985 to December 1997, 133 patients with this disease were treated in the surgical departments of five hospitals, 97 had a single abscess and 36 had multiple abscesses. Clinical features, methods of treatment, and outcome were assessed and compared in both types of abscesses. Results: A biliary origin from ascending cholangitis was most frequently found in multiple abscesses (p = 0.007). Mean age and duration of symptoms were higher in multiple lesions (p = 0.03 and p = 0.001). High levels of alkaline phosphatase were more frequently seen in multiple abscesses than in solitary ones (p = 0.02). They were both most frequently located on the right side. Antibiotic therapy alone was most frequently used in multiple abscesses (p = 0.01). Mortality rate was also higher in this type of patients (p = 0.01). The abscess-related morbidity rate was higher in multiple lesions as well but the statistical difference was not significant. Conclusions: These results suggest that multiple liver abscesses comprise a disease of biliary origin, higher age, longer symptomatic periods, and also higher mortality rate than in single abscess.
Chronic Subdural Hematoma Treated by Burr Holes and Closed Drainage System: A Review of 630 Cases
Authors: Gelabert-González Miguel , López-García Elena , Fernández-Villa Juan
Published: April 2003

Objectives: To study the clinical features and surgical results of patients with chronic subdural hematoma. Methods: A retrospective study of the records of 630 patients treated surgically for chronic subdural hematoma using a burr hole and closed drainage system was conducted. Results: Six hundred and thirty patients (438 males and 192 females) ranging from 12 to 100 years with a mean age of 66.7 years were identified. Upon admission, 242 (38%) patients were in satisfactory condition (grades 0–1), 262 (42%) patients were at grade 2 and 126 (20%) were at grades 3 or 4. In 5.3% of the patients, surgical intervention was required to remove a recurring hematoma. In 77% of the patients, the results achieved could be graded as good (grades 0–1), with mortality being 2.5%. The only factor affecting the outcome was the grade at admission (p < 0.05). Conclusion: A simple and routinely used burr hole procedure either under local or general anesthesia with a closed drainage system is a safe and effective procedure for the treatment of chronic subdural hematoma.
Detection of K19 mRNA Compared with Tumour Markers in Peripheral Blood from Breast Cancer Patients
Authors: Luqmani Yunus A. , Temmim Labiba , Lobo Sharon , Mathew Manoj , Oteifa Medhat , Ali Majda , Parkar Abdul-Hamid
Published: April 2003

Objectives: A rise in peripheral blood of the glycoproteins carcino-embryonic antigen (CEA) and CA15.3 may be indicative of a subsequent clinical relapse and provides a useful adjunct in the management of metastatic breast cancer. We wished to study the relationship of these tumour markers with the expression of keratin 19 (K19) mRNA as a marker of epithelial cancer cells in periodic blood samples taken from patients undergoing postoperative therapy. Methods: CEA and CA15.3 were measured by radio-immunoassay while K19 mRNA was assessed by gel electrophoretic separation after a 40-cycle polymerase chain reaction amplification. Results: Analysis of 395 samples (regardless of patient) showed concurrence in the detection of K19 and CEA and CA15.3 (using positivity cut-offs of 3.2 ng/ml and 32 U/l, respectively) in <20% of cases that were K19+ and in >80% for samples that were K19–. The frequency of CEA and CA15.3 positivity was related to the amount of K19 product. For 65 patients with 2–3 samples collected at 6 monthly intervals, we observed complete agreement for detection of these markers (at each occasion) in about 30% of cases only. Conclusions: These discrepancies may be due partly to the currently qualitative nature of the K19 assessment and emphasize the need for quantification of this but may also reflect a difference in the source of the signals, i.e. K19 originating from circulating cells and CEA/CA15.3 shed from solid tumour deposits. It is likely that K19 detection is more sensitive, but it is less certain which of these markers reflects a significant systemic tumour load and hence is of greater value in predicting relapse.
Prevalence of Dental Fluorosis in Disabled Children and Young Adults in Kuwait
Authors: Shyama Maddi , Al-Mutawa Sabiha A. , Honkala Sisko
Published: April 2003

Objective: The aim of this study was to determine the prevalence of dental fluorosis in disabled subjects attending the special needs schools in Kuwait. Methods: Eight hundred and thirty-two subjects (442 males, and 390 females) aged 3–29 years, who were visually or hearing impaired or who had physical or developmental disorders, were included in the study. The mean age of the subjects was 12.1 years. The subjects were examined for dental fluorosis using WHO criteria. Dental fluorosis was scored according to Dean’s index. Results: None of the subjects had severe fluorosis; less than 1.0% of them showed moderate fluorosis; 0.7% had mild and 2.5% had very mild fluorosis. There were no subjects with fluorosis up to the age of 7 years, but the prevalence varied from 0 to 10% between 8 and 20 years and only 1 subject above 20 years of age had fluorosis. Non-Kuwaiti nationality was a significant risk factor for the occurrence of dental fluorosis (OR = 2.4; p = 0.027). Conclusion: Fluorosis was less prevalent among these disabled subjects than had been reported among the healthy population in Kuwait.
The Anaerobic Bacteriology of Intrapulmonary Infections in Kuwait
Authors: Panigrahi D. , Rotimi V.O. , Chugh T.D. , Sanyal S.C. , Dhar Rita , Varghese Tina Lis
Published: April 2003

Objective: The primary objective of this study was to ascertain the association of anaerobic bacteria in intrapulmonary infections and their susceptibility pattern to commonly prescribed antibiotics. Methods: One hundred clinical samples (85 broncho-alveolar lavage and 15 lung abscess aspirates) from suspected intrapulmonary infection cases were investigated in order to determine the role of anaerobic bacteria in these infections. The anaerobic bacterial isolates were identified by using the Vitek Anaerobic Card System and conventional methods. Susceptibility of these isolates was determined by Etest method against eight commonly prescribed antibiotics. Results: A total of 42 anaerobes were isolated, of which Prevotella spp. were the commonest isolates, made up of 42.9% (18/42), followed by Peptostreptococcus spp. 33.3% (14/42). Only two Bacteroides fragilis strains were isolated. All the isolates were sensitive to metronidazole, clindamycin, imipenem and meropenem; however, one Prevotella was resistant to piperacillin-tazobactam. The two B. fragilis isolates were susceptible to metronidazole, imipenem, meropenem and piperacillin-tazobactam, and one was found to be resistant to clindamycin. Conclusion: Overall, Prevotella spp. were found to be the predominant anaerobic bacteria associated with intrapulmonary infections in Kuwait. All the commonly prescribed antibiotics had excellent in vitro activities against nearly all the isolates.
Pattern of Intracranial Tuberculomas in Kuwait: A Computed Tomographic Study
Authors: Ramadan Salwa , Prosper Aduh , Al-Muhtaseb Sayeed , Sawhney Sukhpal , Liljana Petkovska
Published: April 2003

Objective: To study the spectrum of computed tomographic (CT) morphologies of intracranial tuberculomas and to show the role of CT in evaluating the response to medical management. Subjects and Methods: The case files and CT scans of 20 patients with proven intracranial tuberculomas over a period of 15 years (1985–1999) were reviewed retrospectively. All the patients had pre- and post-contrast axial CT scans of the brain. Follow-up CT studies were done 2–12 months after starting antituberculous chemotherapy (ATT). Results: There were 15 males and 5 females. Single lesions were seen in 65% of patients. The majority of the lesions (78%) were in the frontal and parietal lobes. Rare sites of presentation included midbrain and basal ganglia. The lesions were isodense in 81% of the precontrast studies and all were enhanced after intravenous administration of the contrast medium. Severe mass effect, hydrocephalus and meningeal enhancement were not common findings. In 80% of the patients the follow-up CT scans showed evidence of response to ATT. Conclusion: CT is a reliable modality in the diagnostic workup and follow-up of patients with intracranial tuberculomas. Administration of contrast medium is mandatory for the evaluation of such patients.
Abdominal Scar Endometrioma Mimicking Incisional Hernia: A Diagnostic Pitfall
Authors: Alabassi Abdulla , Farghaly Medhat M.
Published: April 2003

Objective: Abdominal scar endometriosis is a recognized condition that has been described following a wide variety of gynaecological procedures. We report a case of endometrioma, presenting as a painful subumbilical swelling, mimicking an incarcerated incisional hernia. Clinical Presentation: A 35-year-old woman presented with a painful subumbilical swelling that had been present for 6 months, but had increased in size and become more painful the day prior to admission. Her past medical history included four caesarean sections. Physical examination revealed a firm, tender and irreducible subumbilical nodule with no cough impulses, mimicking a small incarcerated incisional hernia. Intervention: Exploratory laparotomy through the same lower midline incision revealed a subcutaneous swelling resembling an organized chocolate cyst of endometriosis. Apart from intra-abdominal adhesions, no connection to intra-abdominal structures was identified. Histopathology of the specimen was consistent with abdominal scar endometriosis. Conclusion: Endometrioma was diagnosed in this 35-year-old woman following histological examination of a specimen removed during laparotomy. It is recommended that endometrioma should be considered in the differential diagnosis of subcutaneous, scar-related hernias and various abdominal wall masses following gynaecological operations.
Staphylococcus lugdunensis: An Emerging Cause of Ventriculoperitoneal Shunt Infections
Authors: Elliott Sean P. , Yogev Ram , Shulman Stanford T.
Published: April 2003

Staphylococcus lugdunensis, a coagulase-negative staphylococcus first described in 1988, has gained recognition as an organism with considerable pathogenic capability in adults. In contrast to the indolent presentation characteristic of other coagulase-negative staphylococci, S. lugdunensis infections resemble the aggressive behavior of Staphylococcus aureus. Although the organism has been isolated from a wide variety of infections in adults, it is a very rare cause of pediatric infections. We describe the first two pediatric patients who developed ventriculoperitoneal shunt infections caused by S. lugdunensis. These cases suggest that coagulase-negative staphylococci should be identified to the species level and that, if S. lugdunensis is identified, greater morbidity compared to that associated with other coagulase-negative staphylococcal shunt infections should be anticipated. A longer course of therapy is recommended for S. lugdunensis infections.
Clinical Significance of Cervicomedullary Deformity in Chiari II Malformation
Authors: Narayan Prithvi , Mapstone Timothy B. , Tubbs R. Shane , Grabb Paul A. , Frye Timothy
Published: April 2003

Objective: The purpose of this study was to determine if there is a difference in the caudal extent of brain stem herniation and the degree of cervicomedullary deformity between symptomatic and asymptomatic Chiari II patients. Methods: Magnetic resonance imaging and the clinical presentation of 14 symptomatic and 59 asymptomatic patients were analyzed. The level of the cervicomedullary deformity below the foramen magnum was measured in both groups. The level of the deformity was identified by the cervical vertebral body or disc space level. Results and Conclusion: Review of our results shows no obvious relationship between the level of cervicomedullary deformity and the presenting symptoms or the outcome after surgical decompression. We conclude that the level of herniation and the cervicomedullary deformity is not a reliable marker to determine which patients may become symptomatic and require decompression or to determine prognosis.
Endovascular Particulate and Alcohol Embolization for Near-Fatal Epistaxis from a Skull Base Vascular Malformation
Authors: Koebbe Christopher J. , Horowitz Michael , Levy Elad I. , Adelson David , Jungries Charles
Published: April 2003

A three-year old girl who initially presented at 16 months with epistaxis from an anterior skull base vascular anomaly returned with near-fatal epistaxis despite embolization of the internal maxillary artery at the time of initial presentation. Repeat angiography demonstrated blood supply to the vascular lesion coming from branches of both the external and internal carotid arteries. The patient underwent four sessions of endovascular embolization with polyvinyl alcohol, alcohol, and gelatin microspheres. At the conclusion of treatment, her epistaxis had resolved and the only residual blood supply to the lesions came from bilateral ophthalmic arteries intentionally not sacrificed to prevent loss of vision. Endovascular embolization of both the internal and external carotid arteries is a challenging but important treatment option for life-threatening epistaxis resulting from vascular lesions of the skull base.
Early Treatment of Posthemorrhagic Hydrocephalus in Low-Birth-Weight Infants with Valveless Ventriculoperitoneal Shunts
Authors: Vinchon Matthieu , Lapeyre Fabrice , Duquennoy Chantal , Dhellemmes Patrick
Published: April 2003

The surgical treatment of posthemorrhagic hydrocephalus (PHH) in low-birth-weight infants (LBWI) is debated. In a few cases, hydrocephalus progresses rapidly and requires early drainage, but valves and ventriculostomy have a high rate of complications in the early phase. Temporary valveless shunt (VLS) is proposed as an alternative treatment of acute PHH in LBWI. Thirteen infants with PHH, weighing less than 2,000 g at birth, were treated with VLS, which was systematically converted into a valve-regulated shunt (VRS) after a few weeks; during the same period, 27 others were treated with VRS initially. The use of VLS presented significantly more shunt obstructions, but not more shunt infections, than VRS. Although placement of VLS was performed earlier, and in smaller babies than VRS, the outcome after a mean 9.1-year follow-up period was comparable in both groups, and only shunt infection was correlated with a poor outcome. We conclude that VLS is a valuable treatment of rapidly evolving PHH in LBWI.
Measurement of Gastric PCO2 as an Index of Tissue Hypoxia during Obstructive Sleep Apnea
Authors: Epstein Lawrence J. , Jervis Jr. Oliver J. , Henderson, II James H. , Sullivan Marjorie , Mohsenifar Zab
Published: April 2003

Background: Gastric mucosal ischemia develops in critically ill patients in a number of clinical settings due to diversion of blood flow from the splanchnic bed to more vital organs, and can be detected by the measurement of gastric intramucosal pH (pHi). Study Objective: We hypothesized that similar changes would occur during obstructive sleep apnea (OSA) due to increased respiratory work during the periods of apnea. Methods: Gastric Pco2, pHi and arterial blood gases were measured during 3 conditions in 8 patients with severe OSA: at baseline awake, while asleep with ≧30 obstructive apneas or hypopneas per hour, and asleep after elimination of apneas with continuous positive airway pressure (CPAP). Results: Significant changes between the baseline and apnea conditions were detected using ANOVA for repeated measures for gastric PCO2, 40.2 ± 5.3 vs. 85.4 ± 34.0 (p < 0.001), pHi, 7.41 ± 0.06 vs. 7.11 ± 0.17 (p < 0.005), and the gastric-arterial PCO2 difference (DCO2), –2.3 ± 5.5 vs. 44.3 ± 36.21 (p < 0.006). Nasal CPAP returned all measures back to baseline values. Conclusions: Gastric tissue hypoxia develops in patients with severe OSA and may be a marker of disease severity. Treatment of OSA with CPAP eliminates the regional tissue hypoxia.
Radicular Involvement and Medullary Invasion from a Malignant Mesothelioma
Authors: Rojas Jose-Luis , Alfageme Inmaculada , de la Cruz Inés , Reyes Nuria , Muñoz Jesús
Published: April 2003

We present the case of a 57-year-old patient who had worked at a fiber-cement factory for 28 years. The patient developed an epithelioid-type pleural mesothelioma 5 years after retiring, after he was diagnosed with asbestosis. Only 5 months after the diagnosis of mesothelioma, a medullar section appeared to be totally invaded by a tumor in the medullar canal, thus causing paraplegia and affecting the bladder and anal sphincters. The patient underwent radiotherapy and chemotherapy, and achieved partial recovery, but died 9 months after the diagnosis.
Acute Effect of Nasal Continuous Positive Air Pressure on the Ventilatory Control of Patients with Obstructive Sleep Apnea
Authors: Moura Sônia M.T. , Bittencourt Lia R. , Bagnato Maurício C. , Lucas Sandra R. , Tufik Sérgio , Nery Luiz E.
Published: April 2003

Background: Sleep fragmentation can decrease the awake ventilatory control. Since patients with obstructive sleep apnea (OSA) patients exhibit sleep fragmentation linked to respiratory events, their ventilatory control could be impaired. However, most of these patients are also obese, which could conversely increase the ventilatory control. The effect of nasal continuous positive airway pressure (CPAP) on the awake ventilatory control in normocapnic OSA patients is unclear. Objectives: To study the acute effect of nasal CPAP on the awake ventilatory control in normocapnic OSA patients. Methods: 12 normocapnic OSA patients, with an apnea/hypopnea index (AHI) >15 with moderate obesity (body mass index: 33.5 kg/m2) and normal pulmonary function tests were submitted to two polysomnography studies (diagnostic and for CPAP titration). Before and after 3 consecutive nights of nasal CPAP we analyzed the hypersomnia score and the ventilatory and the mouth occlusion pressure (P.1) responses at rest (breathing room air and a mixture of 8% CO2 + 40% O2). Results: The respiratory drive of OSA patients as evaluated by P.1 was in the range of the controls of our laboratory. After nasal CPAP, a significant decrease in AHI (mean: 51.9–9.4/h) and arousal (mean: 88.7–43/h) occurred, as well as improvement in nocturnal oxyhemoglobin. There was a marginal increase in ΔVE/ΔPETCO2 (mean: 1.41–1.87 liters/min/ mm Hg, p = 0.09) and a significant rise in P.1/ΔPETCO2 (mean: 0.29–0.43 cm H2O/mm Hg), a better indicator of ventilatory drive. Conclusions: Normocapnic OSA patients increased their awake ventilatory drive response to a hypercapnic and hyperoxic mixture with the use of 3 consecutive nights of nasal CPAP.
Update on the Pathology and Genetics of Exocrine Pancreatic Tumors with Ductal Phenotype: Precursor Lesions and New Tumor Entities
Authors: Lüttges J. , Klöppel G.
Published: April 2003

The majority of pancreatic neoplasms show a ductal phenotype and can be classified as ductal adenocarcinomas. Pancreatic duct lesions have been discussed as tumor precursors. This review presents a recently adopted standard system for these lesions which distinguishes among three grades of pancreatic intraepithelial neoplasia (PanIN). Molecular studies revealed that PanIN-2 and PanIN-3 lesions represent a distinct step towards invasive carcinoma. Another focus of the review is the advances that have been made in the further immunohistochemical and molecular characterization of special pancreatic neoplasms showing a ductal phenotype, such as undifferentiated carcinoma, mucinous noncystic (colloid) carcinoma, intraductal papillary mucinous neoplasm, mucinous cystic neoplasm, medullary carcinoma, and other rare tumors.
Helicobacter pylori Infection as a Model for Gastrointestinal Immunity and Chronic Inflammatory Diseases
Authors: Ernst Peter B. , Takaishi Hiromasa , Crowe Sheila E.
Published: April 2003

Approximately 50% of humanity is infected with Helicobacter pylori. It is a life-long infection that elicits a marked host inflammatory response; however, natural infection fails to yield protective immunity. Rather than providing protection, the chronic inflammatory response associated with natural infection contributes to tissue damage and the pathogenesis of gastroduodenal disease, including atrophic gastritis, peptic ulcer, and gastric cancer. While bacterial factors are important triggers of inflammation, many subjects infected with strains bearing putative virulence factors remain free from disease. Recent genetic studies have implicated the host’s immune and inflammatory responses, suggesting that disease results from an interaction between bacterial and environmental factors in genetically susceptible hosts. Other digestive diseases, including celiac disease and inflammatory bowel disease, mimic this paradigm, where it appears that luminal triggers only manifest disease in subjects with the right combination of host and environmental factors. Since infection with H. pylori is relatively common, it is possible to study the impact of a specific etiologic agent on the pathogenesis of disease in humans. This approach has illuminated the complexity of the pathogenic mechanisms, but the advances achieved to date may provide some hints regarding the pathogenesis of chronic inflammatory diseases elsewhere in the digestive tract.
Current Standards in the Diagnosis of Helicobacter pylori Infection
Authors: Leodolter A. , Wolle K. , Malfertheiner P.
Published: April 2003

A large number of diagnostic tests are available for the diagnosis of Helicobacter pylori infection. These diagnostic methods include invasive and noninvasive methods. Culture yields the highest specificity and moreover allows the determination of strain resistance against antibiotics. Histology besides detection of H. pylori allows to assess morphological changes of the gastric mucosa. In clinical practice, the rapid urease test is very convenient and highly accurate. The 13C-urea breath test and the recently developed stool antigen test are reliable noninvasive tests with a high diagnostic accuracy in pre- and posttreatment conditions. Serological tests have a lower diagnostic accuracy and should only be used for screening of H. pylori infection or after careful local validation.
Helicobacter pylori Treatment: A Role for Probiotics?
Authors: Cremonini Filippo , Canducci Filippo , Di Caro Simona , Santarelli Luca , Armuzzi Alessandro , Gasbarrini Giovanni , Gasbarrini Antonio
Published: April 2003

Many new therapeutic strategies are studied to improve Helicobacter pylori eradication rate. Probiotics are live microorganisms which, upon administration, may interact with the human microflora and positively affect the health status. The use of probiotics in the field of H. pylori infection has been proposed for improving eradication rate and tolerability and for compliance of multiple antibiotic regimens used for the infection. Results from laboratory studies and from clinical trials seem to confirm the expectancies, but there is lack of standardization in terms of type of probiotic strain used, dosage and timing of supplementation. Before further ongoing trials and future studies will clarify these points, probiotics could remain a useful adjunct to standard anti-H. pylori therapies, but cannot take the place of other validated options.
The Prevalence of Helicobacter pylori Infection and the Pattern of Gastritis in Barrett’s Esophagus
Authors: Peitz Ulrich , Hackelsberger Andreas , Günther Thomas , Clara Lucia , Malfertheiner Peter
Published: April 2003

Background/Aim: Acid output is related to the gastritis pattern in Helicobacter pylori infection. The hypothesis to be tested is that gastritis in patients with Barrett’s esophagus, defined as columnar epithelia lined lower esophagus (CELLO) with intestinal metaplasia (IM), is antrum predominant. Patients and Methods: Patients undergoing esophagogastroduodenoscopy were investigated for CELLO. The gastritis parameters H. pylori density, activity, and chronicity were graded in biopsy specimens of antrum and corpus. IM was assessed in biopsies from CELLO patients. In a prospective part, 19 patients with CELLO with IM were compared with 38 age-matched control patient with dyspepsia. Results: Of 200 patients with CELLO, 85% had a short segment (<3 cm), 15% a segment of ≧3 cm. IM was present in 36% of cases with a short CELLO and in 84% of patients with a long segment. The H. pylori prevalence was 50%, independent of the length of CELLO or the presence of IM. The gastritis phenotype was minimally antrum predominant. The antrum/corpus distribution was not related to the length of CELLO or the presence of IM and not different from controls. The activity in corpus and antrum was lower in patients with CELLO with IM as compared with patients with CELLO without IM or controls. Conclusions: A high proportion of patients with CELLO are H. pylori infected. The pattern of H. pylori gastritis is characterized by a pangastritis with low activity which is not likely to predispose to an increase in acid output after eradication.
H. pylori Infection and Visceral Hypersensitivity in Patients with Irritable Bowel Syndrome
Authors: Gerards C. , Leodolter A. , Glasbrenner B. , Malfertheiner P.
Published: April 2003

Background/Aim: Irritable bowel syndrome (IBS) is characterized by abdominal pain and changes in stool habits. Visceral hypersensitivity (VH) is a key factor in the pathophysiology of IBS. The role of Helicobacter pylori infection in the induction of VH in the upper gastrointestinal tract is controversially discussed. The aim of this study is to evaluate the value of rectal barostat in eliciting abdominal symptoms in patients with IBS in relation to H. pylori infection. Patients and Methods: 31 patients (19 female, 12 male, mean age 45.6 ± 10 years) with normal colonoscopy and clinical signs of IBS were examined by rectal barostat (pressure-controlled balloon distension in the rectum). Induction of typical abdominal discomfort (far from the balloon) defined the examination positive. Level of nonpainful perception (L1), feeling of defecation (L2), and pain or stool urgency (L3) were registered in comparison with a healthy control group (CG; n = 15, 9 female, 6 male). The H. pylori status was defined by 13C-urea breath test (n = 46). Results: Typical abdominal discomfort was induced in 9 patients (pain group, PG) by pressure-controlled rectal distension (H. pylori status: 8 positive, 1 negative). Patients not presenting with abdominal pain to rectal distension (nonpain group, NPG) were all H. pylori negative (p < 0.001). L3 as an indicator of VH was reached at a lower pressure threshold in PG than in NPG or CG (p < 0.05). The perception was not different between NPG and CG (p > 0.05). Conclusions: The induction of typical abdominal discomfort in patients with IBS by the use of rectal barostat occurred predominantly in H. pylori infected patients and suggests that H. pylori infection may be involved in triggering VH in patients with IBS. Further studies in larger patient groups and after H. pylori eradication therapy are needed to confirm and extend this observation.
Role of Stress in Functional Gastrointestinal Disorders
Authors: Mönnikes H. , Tebbe J.J. , Hildebrandt M. , Arck P. , Osmanoglou E. , Rose M. , Klapp B. , Wiedenmann B. , Heymann-Mönnikes I.
Published: April 2003

Psychological stress is widely believed to play a major role in functional gastrointestinal (GI) disorders, especially irritable bowel syndrome (IBS), by precipitating exacerbation of symptoms. The available data clearly demonstrate that inhibition of gastric emptying and stimulation of colonic transit is the most consistent pattern in the motility response of the GI tract to acute or short-term stress. Thus, one might propose that these alterations might play a pathophysiological role in dyspeptic symptoms and alterations in stool frequency and consistency in patients with stress-related functional GI disorders. Taken together, the above-mentioned studies suggest that the colonic motor response to stress is exaggerated in IBS. There is evidence that an increased emotional response is associated with this difference in colonic, and perhaps also gastric motor responses to certain stressors. However, almost no valid data are available so far from human studies addressing the question if differences in motility responses to stress between patients with functional GI disorders and healthy subjects are due to an altered stress response associated with an imbalance of the autonomic nervous system or increased stress susceptibility. We can summarize that in experimental animals the most consistent pattern of GI motor alterations induced by various psychological and physical stressors is that of delaying gastric emptying and accelerating colonic transit. Endogenous corticotropin-releasing factor (CRF) in the brain plays a significant role in the central nervous system mediation of stress-induced inhibition of upper GI and stimulation of lower GI motor function through activation of brain CRF receptors. The inhibition of gastric emptying by CRF may be mediated by interaction with the CRF-2 receptor, while CRF-1 receptors are involved in the colonic and anxiogenic responses to stress. Endogenous serotonin, peripherally released in response to stress, seems to be involved in stress- and central CRF-induced stimulation of colonic motility by acting on 5HT-3 receptors. Taken together, the limited data available from investigations in healthy subjects and patients with functional GI disorders provide some evidence that stress affects visceral sensitivity in humans. Acute psychological stress seems to facilitate increased sensitivity to experimental visceral stimuli, if the stressor induces a significant emotional change. In summary, studies in experimental animals suggest that stress-induced visceral hypersensitivity is centrally mediated by endogenous CRF and involvement of structures of the emotional motor system, e.g. the amygdala. Stress-induced activation or sensitization of mucosal mast cells in the GI tract seem to be involved in stress-associated alterations of visceral sensitivity.
How Valuable Is the Application on Consensus Guidelines in the Management of Functional Gastrointestinal Disorders?
Authors: Vaira D. , Gatta L. , Ricci C. , D’Anna L. , Miglioli M.
Published: April 2003

When patients complain of problems, physicians are used to look for some physical or physiological abnormality ruling out infections, inflammatory or cancer. Unfortunately, when we talk about functional disorders we usually cannot observe any defects and it is only possible for us to know of them through the words of our patients. Developing criteria and guidelines is not an easy process, in particular for functional gastrointestinal diseases, when no disease-based biological markers exist. It is difficult to define a medical disorder in the absence of a biological ‘gold standard’. The Rome II classification is based on the assumption that for each disorder there are symptom custers. Symptoms have in common disturbances in sensory and/or motor gastrointestinal function, which sometimes may overlap across anatomic regions. Nevertheless, several studies provide evidence for site-specific syndromes.
Current Status of Liver Transplantation for Treatment of Hepatocellular Carcinoma
Authors: Frilling Andrea , Malago Massimo , Broelsch Christoph Erich
Published: April 2003

Hepatocellular carcinoma accounts for more than 5% of all malignancies with a continuous increase worldwide. The most important risk factor is liver cirrhosis, frequently associated with hepatitis B virus or hepatitis C virus infection. Liver resection is the only treatment that can potentially achieve cure. In carefully selected patients with a tumor smaller than 5 cm the 5-year survival is around 50%. The presence of liver cirrhosis and portal hypertension limits the feasibility of hepatic resection. Child-Pugh A patients without major associated risk factors may be considered as the ideal target group for resection. A significant local disease recurrence rate of more than 70% at 5 years is the main problem of hepatic resection. Orthotopic liver transplantation offers the possibility of removing a potentially multicentric tumor and the underlying end-stage liver disease. Due to pure selection of suitable candidates the initial reports on the efficacy of liver replacement in a cohort of patients with hepatocellular carcinoma were disappointing. Taking the shortness of donor organs and the high posttransplant tumor recurrence rate into account, several groups developed criteria qualifying transplantation. A tumor size of >6 cm and gross intrahepatic portal vein involvement seem to be of significant prognostic importance. Patients with smaller solitary tumors or less than 3 tumors with a total tumor diameter of <8 cm have the same survival after transplantation as those with benign liver disease. Living donor liver transplantation offers a new approach to overcome the organ shortage and to theoretically extend the indication for transplantation in hepatocellular carcinoma.
Observation of Psychoactive Substance Consumption: Methods and Results of the French OPPIDUM Programme
Authors: Thirion Xavier , Micallef Joelle , Barrau Karine , Djezzar Samira , Sanmarco Jean Louis , Lagier Georges
Published: April 2003

This study presents a French programme designed to observe and evaluate psychoactive substance dependence and abuse. Annual surveys lasting 4 weeks are performed with drug users in drug centres. Its usefulness is discussed using examples from the study: potential for antidepressant dependence (amineptine), monitoring benzodiazepine use and consumption associated with maintenance treatments. Flunitrazepam is the most consumed benzodiazepine and often got by deal (29%). There are important differences between buprenorphine consumption in a maintenance treatment context (9/10) and beyond this context (1/10). The main methodology problems encountered are representativeness and validity of data. The limits of the programme and its role in the French health care system are discussed.
Homonymous Defect of Macular Vision in Ischemic Stroke
Authors: Isa Katsunori , Miyashita Kotaro , Yanagimoto Shoko , Nagatsuka Kazuyuki , Naritomi Hiroaki
Published: April 2003

It is generally believed that a homonymous defect of macular vision (HMV) is caused by a small lesion restricted to the occipital lobe tip and rarely results from ischemic stroke. The incidence of HMV was studied retrospectively in 54 patients with infarction of the posterior cerebral artery territory who underwent Goldmann’s visual field test. HMV was found in 6 patients (11%). In all of them, HMV was first dismissed due to a confrontation test of visual fields at the bedside and later detected by Goldmann’s visual field test. All had a relatively large infarction extending from the occipital lobe tip to the posterior part of the calcarine cortex and/or the neighboring subcortical regions. Stroke-induced HMV can be caused by a large lesion involving the occipital pole and may not be so rare as generally considered.
Blood Flow in the Left Atrial Appendage and Embolic Stroke in Nonvalvular Atrial Fibrillation
Authors: Takada Tatsuro , Yasaka Masahiro , Nagatsuka Kazuyuki , Minematsu Kazuo , Yamaguchi Takenori
Published: April 2003

It is unclear if low flow velocity in the left atrial appendage (LAA) is a predisposing factor to stroke in patients with nonvalvular atrial fibrillation (NVAF). We investigated flow velocity in the LAA in NVAF patients in relation to a past history of stroke and other potential embolic sources. We measured and analyzed peak flow velocities into (FV-in) and out of (FV-out) the LAA in a middle portion of the LAA in 35 NVAF patients by transesophageal echocardiography (TEE). We divided the NVAF patients into 3 groups: the Eaf group had a history of embolic stroke without any other potential embolic sources; the Emulti group had other potential embolic sources, and the control group had no embolic history. FV-in and FV-out in the Eaf group (12.3 ± 6.7 and 10.2 ± 7.3 cm/s) were significantly lower than those in the control group (24.3 ± 11.3 and 19.9 ± 8.8 cm/s; multicomparison Scheffé’s test, p = 0.0123 and 0.0395, respectively). The Emulti group varied in those values from less than 5 to above 35. Low flow velocity in the LAA seems to be a predisposing factor for stroke in NVAF patients without any other sources of emboli.
The Importance of the Intrathecal Infusion Test in the Diagnostic of Normal-Pressure Hydrocephalus
Authors: Meier Ullrich , Bartels Philip
Published: April 2003

Objective: The intrathecal infusion test is a reliable method for diagnosing normal-pressure hydrocephalus (NPH). Methods: Between May 1982 and January 1997, we investigated 200 patients suspected of having NPH by carrying out an intrathecal infusion test with a constant-flow technique. The resistance to cerebrospinal fluid outflow in the intrathecal infusion test was the main criterion for grouping patients into those with NPH or those with cerebral atrophy. A further differentiation into early stage and advanced stage was made by measuring the compliance, this being the secondary criterion. Results: In 107 patients (54%), the diagnosis of NPH could be confirmed. Of these, 102 patients (95%) underwent a shunt operation. Graduation of NPH and cerebral atrophy following the results of the infusion test at an early stage and an advanced stage allows prognostic evaluations about the course of disease to be made. Patients with NPH at an early stage reported an improvement of their symptoms in the follow-up after a shunt operation in 65% of cases, while 50% of those with advanced-stage NPH reported improvement. Conclusion: The computer- aided infusion test allows a reliable differentiation between patients with NPH and those with cerebral atrophy.
Neurologic Sequelae after Severe Falciparum Malaria in Adult Travelers
Authors: Roze E. , Thiebaut M.M. , Mazevet D. , Bricaire F. , Danis M. , Deseilligny C. Pierrot , Caumes E.
Published: April 2003

Severe falciparum malaria usually occurs in nonimmune patients, namely children in endemic areas or travelers returning from tropical areas. It generally has one of two outcomes: rapid death or cure without sequelae. Neurologic sequelae have been reported in children but have not been described in detail in adults. The purpose of this study was to determine the clinical spectrum, neuroimaging aspects and long-term outcome of these sequelae. We describe six imported cases of severe malaria with neurologic sequelae in adults, seen in a Parisian university hospital over a 10-year period. The most striking findings were neuropsychological disorders, in particular memory impairment and diffuse white matter damage on magnetic resonance imaging. Only three of the patients had made a full recovery after 6 months.
The Masseter Reflex: Postprocessing Methods and Influence of Age and Gender
Authors: Fitzek Sabine , Fitzek Clemens , Hopf Hanns Christian
Published: April 2003

Objectives: Normative values of the masseter reflex are scarce. We studied the latencies, amplitudes and side differences of the masseter reflex in 105 healthy volunteers between the ages of 5 and 78 years. Methods: Latencies were calculated as the mean of 10 single sweeps and, simultaneously, measured from the summation curve. Short-term reproducibility was determined in 33 volunteers by retesting the reflex after 1 week. Results: There was a positive correlation between age and latencies and a negative correlation between age and amplitude. Maximal normal latencies were 8.3 ms for men and 7.9 ms for women in the age group below 50 years and 9.1 and 9.2 ms for the age group above 50 years. Latency differences between the right and left sides of >0.4 ms for subjects aged below 50 years and >0.5 ms for subjects aged above 50 years exceeded the 95% confidence interval. Amplitudes did not depend on gender. Calculated as a percentage of the side with higher amplitude, differences above one third could be accepted as abnormal. Conclusion: The masseter reflex appears to be a stable and robust clinical test, if age and gender differences are taken into account.