Alpha-1 antitrypsin deficiency is significantly associated with atopy in asthmatic patients.

Background: Although the etiology and disease mechanisms of asthma and alpha-1 antitrypsin deficiency (AATD) are distinct, several reports indicate that asthma is common in AATD patients, however the relationships between asthma and AATD are poorly described in the literature.Objectives: The aim of the study was to investigate in a cohort of outpatients affected by mild to moderate asthma the clinical features that may differentiate asthmatic patients with and without mutation on SERPINA1 gene.Methods: Seven hundred thirty-five asthmatic outpatients underwent quantitative analysis of the serum level of alpha-1antitrypsin. According to the literature only sixty-seven out of seven hundred thirty-five asthmatic patients were submitted to genetic analysis to identify AATD and non-AATD subjects. Fifty-eight patients were studied. Clinical and functional data, including lung function, atopy and bronchial hyperactivity, were recorded.Results: The fifty-eight asthmatic patients were divided in AATD patients (n = 22) and non AATD patients (n = 36), according to genotype. The presence of atopy was significantly higher in patients with AATD than in those without AATD (91% vs. 64%; p = 0.031). AATD patients reported allergic manifestations more than non AATD patients (77% vs. 47%; p = 0.030).Conclusion: Our study shows that the presence of atopy in asthmatic patients with AATD is significantly higher than in asthmatic patients without gene mutation. In addition, a higher percentage of AATD patients self-reported allergic manifestations. No significant differences in respiratory symptoms, physical examination, disease severity or inflammation markers were found between AATD patients and non AATD patients.

Carfilzomib: A Tale of a Heartbreaking Moment: Case Report and Concise Review of the Literature.

BACKGROUND: Carfilzomib, a proteasome inhibitor, known as a therapeutical option for people who have already received one or more previous treatments for multiple myeloma, has well known cardiac and systemic adverse effects. OBJECTIVE: There is evidence supporting that adverse effects are dose dependent, yet there is no known patient phenotype characterized by worse associated consequences, nor are there widely accepted monitoring protocols. RESULTS: In this article we describe two patients with cardiovascular adverse events related to carfilzomib treatment and their clinical course. Our goal was to present two cases of daily practice, which highlighted the complexity of their management and led to underline how baseline evaluation and close follow-up with echocardiography and cardiac biomarkers, including natriuretic peptides, remain an important tool for the cardiotoxicity surveillance. CONCLUSION: These reflections should lead to further studies in order to identify high risk patients for cardiovascular adverse event and clarify the real incidence of cardiotoxicity of this drug and adequate follow-up timing. Finally further research is needed to evaluate strategies for prevention and attenuation of cardiovascular complications of cancer therapy.

Robust method to improve the quality of shearographic phase maps obtained in harsh environments.

This paper presents a new approach to improve the quality of shearographic phase maps acquired in a harsh environment. During in-field nondestructive inspections, the presence of higher disturbances, mainly vibrations, can introduce unknown phase deviations in the sequence of shearographic images. This paper presents a different approach that combines the N-dimensional Lissajous algorithm [Int. J. Optomechatron.8, 340 (2014)1559-961210.1080/15599612.2014.942933] and the concept of phase of differences [Proc. SPIE6345, 634510 (2006)PSISDG0277-786X10.1117/12.693149] to improve the quality of phase maps. The concept is compared with two other methods. Results, advantages, and difficulties of each method are also presented and discussed by using real fringe maps.

Human ileal bile acid transporter gene ASBT (SLC10A2) is transactivated by the glucocorticoid receptor.

BACKGROUND: Patients with Crohn's disease suffer from intestinal bile acid malabsorption. Intestinal bile acid absorption is mediated by the apical sodium dependent bile acid transporter ASBT/IBAT (SLC10A2). In rats, ASBT is induced by glucocorticoids. AIMS: To study whether human ASBT is activated by glucocorticoids and to elucidate the mechanism of regulation. PATIENTS AND METHODS: ASBT expression in ileal biopsies from patients with Crohn's disease and from healthy subjects was quantified by western blot. ASBT promoter function was studied in luciferase assays and by electrophoretic mobility shift assay. RESULTS: In 16 patients with Crohn's disease, ASBT expression was reduced to 69 (7.5)% compared with healthy controls (mean (SEM); p = 0.01). In 10 healthy male volunteers, ASBT protein expression was increased 1.34 (0.11)-fold (mean (SEM); p<0.05) after 21 days' intake of budesonide (9 mg/day) whereas expression of the peptide transporter 1 was unaffected. Reporter constructs of the human ASBT promoter were activated 15-20-fold by coexpression of the glucocorticoid receptor (GR) and exposure to the GR ligands dexamethasone or budesonide. Two glucocorticoid response elements in the ASBT promoter, arranged as inverted hexanucleotide repeats (IR3 elements), conferred inducibility by GR and dexamethasone in a heterologous promoter context and were shown to bind GR in mobility shift assays. CONCLUSIONS: Human ASBT is induced by glucocorticoids in vitro and in vivo. Induction of ASBT by glucocorticoids could be beneficial in patients with Crohn's disease who exhibit reduced ASBT expression. This study identifies ASBT as a novel target of glucocorticoid controlled gene regulation in the human intestine.

[Biliary stents]. / Gallenwegs-Stents.

Endoscopically implantable stents are today the mainstay for therapy of biliary stenoses. It is important to know if a benign or a malignant stenosis is the cause of the biliary obstruction. Generally benign stenoses are treated with plastic-stents whereas malignant stenoses are managed by implantation of a metallic stent. The main indications for plastic stents are postoperative strictures in the biliary tree for example, after biliary tract surgery or liver transplantation, primary sclerosing cholangitis and postoperative biliary leakage. Metallic stents are implanted in palliative circumstances like in stenosing cholangiocarcinoma or in situations where a hepatic metastasis exerts an extrinsic compression on the biliary tract with consecutive cholestasis. The materials used for manufacturing both stent types are biologically inert and thus biocompatible. A current poorly resolved problem is the occlusion of the stent lumen (by sludge, bacterial degradation products etc.) which occurs in both stent types with time. These problems lead to stentocclusion around three to six months after implantation and necessitate endoscopical re-interventions in order to overcome the occlusion. The patency rate for metallic stents is better than for plastic ones. The endoscopic stenttherapy is equivalent to surgical therapy (Intestinal bypass-procedures).

Diagnostic quality of biopsy specimens: comparison between a conventional biopsy forceps and multibite forceps.

BACKGROUND: The endoscopic biopsy is a prerequisite for histopathologic diagnosis. Various types of forceps are used to obtain tissue specimens. The aim of this study was to assess and compare the diagnostic quality of biopsy specimens obtained with a conventional forceps and a Multibite forceps. METHODS: In a prospective, partially blinded, and randomized trial that included 250 patients referred for diagnostic upper and/or lower endoscopy, 510 biopsy specimens obtained with the Multibite forceps were compared with 520 specimens obtained with a conventional forceps. An experienced, blinded pathologist evaluated the specimens for diameter, depth of specimen, artifacts, anatomic orientation, vitality, general histologic quality, and diagnostic quality. Statistical analysis was performed by using the Fisher exact test. A p value of < 0.05 was regarded as significant. RESULTS: There were no statistically significant differences between the specimens obtained with the 2 forceps. The p values for the evaluated parameters were as follows: diameter 0.45, depth of specimen 0.56, artifacts 1.0, pathoanatomic orientation 0.40, vitality 0.45, and histologic diagnostic quality 0.53. CONCLUSION: The quality of biopsy specimens obtained with the Multibite forceps is comparable with that of specimens taken with a conventional forceps. Use of the Multibite forceps saves time in that 4 specimens can be obtained in 1 pass in situations in which a large number of specimens are needed or when the potential for transmission of infection is of concern.

Previous cholecystectomy, gastrectomy, and diabetes mellitus are not crucial risk factors for pancreatic cancer in patients with chronic pancreatitis.

INTRODUCTION: In the general population, cholecystectomy, diabetes, and chronic pancreatitis seem to be associated with an increased risk of developing pancreatic cancer. AIMS: We assessed whether previous cholecystectomy, gastrectomy, or diabetes mellitus may be risk factors for pancreatic cancer in patients with chronic pancreatitis. METHODOLOGY: We analyzed 853 patients with chronic pancreatitis (110 women, 743 men) with a median follow-up period of 14 years with particular reference to establishing which patients had previously undergone cholecystectomy or distal gastric resection (Billroth II anastomosis) or had diabetes or gallstone disease and the respective time scales involved. RESULTS: Pancreatic cancer developed in 17 patients with chronic pancreatitis after a median period of 8 years from onset of pancreatitis symptoms (range, 3-38 years). Excluding two cholecystectomies performed 1 year before diagnosis of cancer, cholecystectomy was performed in 7/17 (41%) patients with pancreatic cancer and in 381/836 (46%) of the other patients with chronic pancreatitis. Forty-nine (10%) patients with chronic pancreatitis and no pancreatic cancer had undergone cholecystectomy during the years before the onset of chronic pancreatitis, whereas none of the patients in whom a pancreatic malignancy developed had undergone cholecystectomy before the onset of chronic pancreatitis symptoms. Gastrectomies were performed in 116 patients (14%), 47 before the onset of chronic pancreatitis. Only 2/17 patients with pancreatic cancer had undergone previous gastrectomy, though in both cases only shortly before diagnosis of the cancer. Diabetes was diagnosed in 353 patients, but only in 30 (4%) before onset of chronic pancreatitis. Only 1/17 patients (6%) with pancreatic cancer had long-standing diabetes, whereas diabetes developed in 3/17 shortly before diagnosis of pancreatic cancer. CONCLUSIONS: Cholecystectomy, gastrectomy, and diabetes are not major risk factors for the development of pancreatic cancer in patients with chronic pancreatitis.

Safer colonoscopy with patient-controlled analgesia and sedation with propofol and alfentanil.

BACKGROUND: The aim of this study was to assess the efficacy of patient-controlled analgesia and sedation with propofol/alfentanil for colonoscopy compared with continuous drug infusion and conventional nurse-administered medication. METHODS: One hundred fifty patients undergoing colonoscopy on an outpatient basis were randomly assigned to 1 of 3 medication regimens. To maintain blinding, all patients were connected to an infusion pump. Group I patients could self-administer boluses of 4.8 mg propofol and 125 microg alfentanil without restriction. Group II patients received a continuous infusion with 0.048 mg/kg propofol and 0.12 microg/kg alfentanil per minute. Group III patients received intravenous premedication with 0.035 mg/kg midazolam and 0.35 mg/kg meperidine. RESULTS: There were no differences between the groups with respect to pain (visual analogue scale) and procedure time. Patient-controlled analgesia and sedation with propofol/alfentanil (group I) resulted in less of an increase in the transcutaneous partial pressure of carbon dioxide (p = 0.0004) during colonoscopy and less of a decrease in mean arterial blood pressure (p = 0.0021) during recovery, as well as more complete recovery (p = 0.0019) after 45 minutes compared with conventional administration of midazolam/meperidine. Furthermore, patient-controlled analgesia and sedation yielded a higher degree of patient satisfaction than continuous infusion of propofol/alfentanil (p = 0.0033) or nurse-administered midazolam/meperidine (p = 0.0094). CONCLUSIONS: Patient-controlled administration of propofol and alfentanil for colonoscopy may provide a better margin of safety than conventional administration of midazolam and meperidine and results in a higher level of patient satisfaction and shorter recovery.

Cytomegalovirus-induced transient protein-losing hypertrophic gastropathy in an immunocompetent adult.

Transient protein-losing hypertrophic gastropathy with similarity to Ménétrier's disease is described. Acute infection with cytomegalovirus (CMV) could be shown to play a causative role. Immunodeficiency was ruled out. The 34-year-old patient had complete resolution of the disease without antiviral treatment. To our knowledge the present report is the first case of CMV-associated protein-losing hypertrophic gastropathy in an immunocompetent adult. To date, a similar disorder has only been described in children. CMV infection should be considered in patients with acute and symptomatic protein loss of gastrointestinal origin.

Esophageal carcinoma: current staging strategies.

A patient with suspected esophageal carcinoma represents a challenge to the treating physicians. Most patients present with an advanced stage of disease, and in the majority of cases only palliative treatment can be offered. Various treatment modalities are available, which are applied according to the TNM stage of the disease and the performance status of the patient. A precise histological diagnosis and highly accurate tumor staging of a patient with esophageal carcinoma is a prerequisite for the selection of the most suitable treatment option. Endoscopic ultrasound (EUS) has emerged as the most accurate diagnostic modality for locoregional staging. Problems in identifying early tumor stages or tumor strictures can be generally overcome by using miniprobe sonography (MPS). EUS/fine-needle aspiration biopsy (FNA) technology provides a valuable means of identifying suspicious locoregional lymph nodes. Patients with a proximal tumor (trachea bifurcation) should undergo bronchoscopy to rule out infiltration of the tracheobronchial system. Ultrasound (US), computed tomography (CT), and possibly magnetic resonance imaging (MRI) are the diagnostic tools of choice for extended tumor staging. After excluding extended tumor stage and severe concomitant diseases, diagnostic laparoscopy with intra-abdominal ultrasound should be performed in patients with adenocarcinoma of the esophagus prior to esophagectomy. Intra-abdominal metastases which can be missed preoperatively in some cases have to be ruled out in order to avoid unnecessary surgery.

Gill endocrine cells in the goldfish Carassius carassius var. auratus and their impairment following experimental lead intoxication.

The presence of endocrine cells in the gills of the goldfish Carassius carassius and the effects of lead intoxication (5 mg l(-1)) on their relative abundance and secretory activity were studied. Endocrine cells synthesizing peptido-like (met and leu-enkephalin and neuropeptide Y) and serotonin-like substances were detected in gill filaments by immunocytochemical procedures. Decreased immunoreactivity for two enkephalins and neuropeptide Y was observed after 48 and 96 h lead exposure. In contrast, increased serotonin immunoreactivity was evident after a one-week treatment. A search for Ca++-binding proteins was also carried out by immunocytochemical methods. Calbindin D-28K and S-100-like molecules were detected in gill epithelium, and their expression appeared enhanced after lead exposure.

Attitude to Helicobacter pylori infection among Swiss gastroenterologists.

OBJECT: To assess the current attitude to Helicobacter pylori infection in Switzerland, since a review of the literature reveals few publications dealing with application of therapeutic recommendations. METHODS: The initial diagnostic methods, the indications for eradication therapy, the therapeutic regimen and its duration, together with eradication control, were indicated in questionnaires sent out to the members of the Swiss Society for Gastroenterology and Hepatology at the beginning of 1997. RESULTS: Helicobacter pylori was diagnosed mainly with a rapid urease test and/or histology. Peptic ulcer disease (100%), mucosa associated lymphoid tissue (MALT) lymphoma (94.5%) and therapy-resistant dyspepsia (78.7%) were clear indications for Helicobacter pylori eradication. Only a minority eradicated Helicobacter pylori in all positive subjects. 7-day triple therapy (with proton pump inhibitors, a macrolide antibiotic and an imidazole derivative) is the preferred first line treatment. CONCLUSIONS: The eradication of Helicobacter pylori in ulcer disease is established practice. Non-ulcer dyspepsia remains a controversial but often used indication. Two antibiotics together with proton pump inhibitors constitute the mostly widely used eradication therapy.

Argon beam coagulation for treatment of symptomatic radiation-induced proctitis.

BACKGROUND: Radiation proctitis is a complication of radiotherapy for malignant pelvic disease. Argon beam coagulation is a new and rapidly evolving technology that permits a "no-touch" electrocoagulation of diseased tissue. METHODS: We analyzed retrospectively the records of 7 patients with prostatic and endometrial cancers treated with irrradiation (median radiation dose was 6840 cGy, range 2400 to 7200 cGy). The median time to onset of symptoms after the conclusion of radiotherapy was 20 months (range 16 to 48 months); symptoms consisted of rectal bleeding and tenesmus in all patients. The patients underwent argon beam coagulation after colonoscopic evaluation. The usual treatment interval was 3 weeks (range 1 to 3 weeks). RESULTS: A median of 2 treatment sessions (range 2 to 4) was necessary for complete symptom relief. All interventions were well tolerated without complications. During follow-up (median 24 months, range 18 to 24 months), there was no recurrence of symptoms (bleeding, tenesmus). CONCLUSIONS: Argon beam coagulation is a safe, well tolerated, and effective treatment option in symptomatic radiation proctitis.

[Diarrhea as initial manifestation of medullary thyroid carcinoma]. / Diarrhoe als Erstmanifestation eines medullären Schilddrüsenkarzinoms.

HISTORY AND CLINICAL FINDINGS: For 15 months a 52-year-old business man had been suffering from chronic diarrhoea which had persisted even after exophthalmic hyperthyroidism (Grave's disease) had been diagnosed and adequately treated. Physical examination on admission revealed no abnormalities, in particular no sign of hyperthyroidism. INVESTIGATIONS AND DIAGNOSIS: Repeated stool examinations failed to demonstrate any infectious organisms. Upper gastrointestinal endoscopy and ileaocoloscopy were normal, as were biopsies. Persistence of the diarrhoea during a fasting test and the bulky stools suggested a secretory cause. Among various hormonal tests the calcitonin concentration was found to be greatly raised (4572 ng/l, normal 10 < ng/l). Ultrasound demonstrated a thyroid tumour and cytological examination of a fine-needle biopsy revealed a medullary carcinoma. TREATMENT AND COURSE: After total thyroidectomy with bilateral neck dissection the patient was free of any symptoms: the diarrhoea ceased immediately after the operation and the calcitonin concentration became nearly normal. CONCLUSIONS: Signs of chronic secretory diarrhoea suggest the possibility of an endocrinally active tumour. Search for a medullary carcinoma of the thyroid with measurement of the serum calcitonin level should be among the diagnostic procedures.

Glycoconjugate and adhesion molecule changes during the cell cycle in a human embryonic epithelial cell line.

The changes in the expression of glycoconjugates and adhesion molecules were studied by selective lectin binding and immunocytochemical reactions in a human embryonic epithelial cell line (EUE cells), synchronized in the cell phases. The results can be summarized as follows: most of the tested lectins display a more diffuse binding for the cytoplasm in G1 than S and G2 phases; in the S and particularly in G2 phases the cytoplasm glycoconjugates are arranged around the nucleus; cells in mitosis always show a strong binding towards all tested lectins. Cellular fibronectin and its receptor beta 1 integrin are well expressed in G1, but the strongest reaction is observed in the S phase. The immunoreactions for laminin and uvomorulin (L-CAM) are poorly positive in all cell cycle phases. The immunocytochemical reaction for heparan sulfate is positive, with a stronger reaction in S and G2 than G1; on the contrary a diffuse staining with the anti-dermatan sulfate proteoglycan antibody appears unchanged during the cell cycle.

Neonatal asteroid hyalosis.

Asteroid hyalosis, noted in 0.83% of routine eye examinations, is uncommon in younger patients and is more frequently seen in patients more than 60 years old. It has been considered to be related to an aging process, and when it occurs in younger patients, ocular disease is typically associated. We report a 4-week-old patient with Down syndrome and bilateral congenital cataracts who had unilateral asteroid hyalosis.

The digestive gland of Viviparus ater (Mollusca, Gastropoda, Prosobranchia): an ultrastructural and histochemical study.

The digestive gland of Viviparus ater was studied using histochemical and ultrastructural methods. Only one cell type was observed in the tubule epithelium of the gland. The cells are involved in an endocytotic process mediated by clathrin-coated vesicles and in the intracellular digestion of food materials (thus they can be regarded as digestive cells). The different stages of digestion and exocytotic extrusion of residual bodies into the tubule lumen were shown by electron microscopy. Very few, small mucocytes are scattered among the digestive cells. Calcium concretions, glycogen-containing cells and endocrine cells are scattered in the area of connective tissue present among the digestive tubules.

Bleeding anorectal varices: successful treatment with transjugular intrahepatic portosystemic shunting (TIPS).

A patient with severe recurrent rectal bleeding from anorectal varices due to portal hypertension because of hepatitis C virus related liver cirrhosis is presented. As illustrated by the report, it is essential to differentiate bleeding anorectal varices from bleeding haemorrhoids because treatment is different. In our patient, implantation of a transjugular intrahepatic portosystemic shunt (TIPS) led to an impressive regression of the anorectal varices, which could be demonstrated by sigmoidoscopy, endosonography, and magnetic resonance imaging. Recurrent rectal bleeding in a patient with portal hypertension should alert the physician to consider anorectal varices. Endoscopic ultra-sound and magnetic resonance imaging are new and non-invasive modalities for diagnosis and post-treatment control.