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.

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.

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.

Effects of hypertonic conditions on cytoskeletal and adhesion structures of EUE cells.

The distribution of cytoskeletal structures has been studied by electron and immunofluorescence microscopy in human embryonic epithelial cells (EUE cells) exposed to a hypertonic medium containing 0.274 M NaCl. A first noticeable effect involved an increase of cell size. Microtubules, microfilaments and intermediate filaments were also considerably changed under these experimental conditions. The most marked effect was on intermediate filaments of the keratin type which formed very thick bundles around the nucleus and gave rise to an intracellular cagework which is likely i) to increase mechanical resistance and ii) to avoid cell collapse in conditions of hyperosmolarity. A remarkable increase in complexity of the microfilamentous network was also found: stress fibers became thicker and more densely arranged and vinculin-containing streaks at focal cell-substratum contacts increased in number and size; this indicated improved cellular adhesion. The phenotypic adaptation of EUE cells to conditions of hyperosmolarity is slowly reversible under defined experimental conditions.

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.

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.

Sphenoid wing meningioma progression after placement of a subcutaneous progesterone agonist contraceptive implant.

A causal relationship between sex steroids and meningioma proliferation has long been suspected. We report a case of the clinical progression of a sphenoid wing meningioma after the placement of Norplant, a subcutaneous contraceptive implant containing levonorgestrel, a progesterone agonist. Although not proof of causation, this observation lends further credence to the importance of progesterone receptors in the growth and possible treatment of meningiomas.

PIP: Reported is a female case study of a 40-year-old patient who 4 weeks previous had received a Norplant subcutaneous contraceptive implant. The patient presented at 4 weeks postimplant with blurred vision in her left eye. She further reported never having used hormonal contraceptives. Her vision continued to deteriorate over the next several months to 20/60 visual acuity. After examination by neuro-ophthalmologists at the University of Iowa Hospital and Clinics system, the following abnormalities in the left eye were reported: impaired color vision; a severely reduced critical flicker fusion rating (13 Hz); an abnormality in the temporal field (using Humphrey 30-2 program); and a 3 times greater light sensitivity. The fundus and the optic nerve heads appeared normal. Magnetic resonance imaging revealed a homogeneous mass along the medial sphenoid wing which continued into the left cavernous sinus and sella. Part of this mass crowded the left optic nerve opening (chiasm). During the subsequent 6 weeks, the patient's visual acuity continued to deteriorate to 20/100 despite removal of the Norplant implant. The tumor mass was surgically removed and pathologically examined. It was a meningothelial neoplasm and tested positive for progesterone receptors (125 fmol/mg of protein). It tested negative for estrogen receptors. Authors provide a discussion on the history of hormonal influence/agonist effects on meningiomas. The authors conclude that there is evidence which supports the theory that meningiomas may be subject to hormonal influence and may be stimulated by hormones to grow. They further conclude that their observations do not prove a cause-and-effect relationship and that further research is needed.

Effects of low-power 632 nm radiation (HeNe laser) on a human cell line: influence on adenylnucleotides and cytoskeletal structures.

HeNe (632 nm) irradiation (5, 15 and 30 min) of an embryonal human cell line (EUE) was used to study the short-term effects on energy charge and the rapid, energy-dependent, remodelling processes of cytoskeletal and adhesion structures. The adenosine triphosphate (ATP) concentration, tested by luminometric and high performance liquid chromatography (HPLC) procedures, is constant after 15 and 30 min of HeNe treatment; the lower phosphorylated nucleotides, i.e. adenosine diphosphate (ADP) and adenosine monophosphate (AMP), change after 30 min in opposite directions: the ADP concentration decreases by 39% whilst that of AMP increases about sixfold. The adenylate energy charge (AEC) decreases by 21.7% in treated EUE cells (AEC = 0.65) in comparison with untreated EUE cells (AEC = 0.83). In HeNe-treated cells, the remodelling of cytoskeletal and adhesion molecules becomes evident after 15 min of treatment. The following events are important: (1) modification of stress fibre assembly and increase in vinculin-containing adhesion plaques; (2) assembly and bundling of intermediate filaments; (3) increase in laminin and L-cell adhesion molecules (L-CAM) expression. The lowered energy charge in irradiated cells is related to the increase in AMP production at the expense of ADP. ATP is dynamically constant despite its requirement in short-time remodelling processes of the cytoskeletal network which are enhanced in irradiated cells.

Effects of lead on hepatocyte ultrastructure in Carassius carassius (L.) var. auratus.

Subcellular modifications in hepatocytes of Carassius carassius var. auratus subjected to 24 hr and 48 hr sublethal acute lead (5mg.1-1) exposure were studied by electron microscopy. Cytological alterations were observed after 24 hr of treatment and became more evident after 48 hr. Lead induced an increase in nuclear heterochromatin and alterations in mitochondria, endoplasmic reticulum and Golgi complex ultrastructure. Glycogen granula decreased, and secondary lysosomes and lipid droplets increased. Furthermore, intracytoplasmic lumina with microvilli-bearing surfaces and numerous autophagic vacuola were observed after 48 hr of exposure.

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.

Histochemical research on metabolic pathways of glucose in some species of Mollusca Gastropoda.

The metabolic pathways of glucose were studied by histochemical reactions in some species of gastropods living in different habitats. The glycolytic pathway is histochemically indicated by positive results for glucose-6-phosphate isomerase, fructose-1,6-biphosphate aldolase, glyceraldehyde-3-phosphate dehydrogenase, and D-lactate dehydrogenase. The enzymes of the Krebs cycle gave different responses: isocitrate dehydrogenase and L-malate dehydrogenase were positive, whilst succinate dehydrogenase was constantly negative. Malate synthetase activity was also demonstrated. Despite L-glutamate dehydrogenase is undetectable, the presence of transaminase indicates the gluconeogenetic route. Phosphoglucomutase and glucose-6-phosphate phosphatase appear also positive. The metabolic meaning of our results were discussed.

Histomorphological and cytochemical changes induced in the liver of goldfish Carassius carassius var. auratus by short-term exposure to lead.

The cellular and molecular effects of experimental lead intoxication (5 mg l-1/24 h and 48 h) were studied in hepatocytes of Carassius carassius var. auratus. Significant lead storage was not detected by atomic absorbance spectroscopy after treatment. Cell morphology appeared only poorly impaired. A decrease of glycogen content was observed. Glycolysis, Krebs cycle and pentose shunt were altered in their enzymatic activities. Lysosomal activities were strongly increased. All enzymatic activities tested were altered 24 h after lead treatment.

Biochemical and histochemical features of human cultured cells (EUE) adapted to hypertonic medium.

EUE cells from a human heteroploid line cultured in hypertonic medium (0.274 M NaCl) modify their lipid pattern: sulfolipid concentration reaches 86 to 90 microgram/mg protein whilst it ranges between 19 to 32 microgram/mg in cells cultured in isotonic medium. Ganglioside concentration reaches 2.6 nmoles of sialic acid/mg protein (after 75 days) and 13 (after 85 days) in hypertonic saline medium. Whilst it is 0.5 in isotonic medium. Phospholipid concentration does not show any similar change. Cytoenzymatic analysis reveals that dehydrogenases (lactate, G-6-P dehydrogenases, tetrahydrofolate reductase and NADH diaphorase) appear strongly enhanced in cells grown on hypertonic medium. On the contrary higher acid phosphatase and ATPase activity was demonstrable in cells grown on isotonic medium. These results are similar (except for ATPase activity) to those observed in salt secreting glands involved in strong osmotic work. The results are discussed in relation to the problem of energy supply in cells performing osmotic work.

Histochemical and biochemical research on the pallial gland of Lithophaga (Lithodomus) lithophaga L.

Histomorphological staining demonstrated 2 types of cells in the pallial gland of the mantle of Lithodomus lithophaga: gland cells containing glycolipoprotein and interstitial cells, containing lipid droplets. Biochemical analysis aiming at separate and evaluate lipidic and peptidic components were carried out by lipid extraction, T.L.C. separation and colorimetric assays. Phospho- and sulfolipids were separated from non-polar lipids. Sialo-cerebrosides (gangliosides) are missing. Hydrophobic peptide component was extracted and aminoacid analysis was made. The presence of acid (phosphate) group in the gland secretion is discussed in relation to the function of the secretion (Ca uptake and rock boring). The prominent glycogen storage is considered as an important energy source to be used for osmotic work and to synthesize glycosidic stones for glycolipo-protein secretion.

Enzymatic characterization of E.U.E. (embryonal human explants) cells adapted to hypertonic media.

E.U.E. cells (general population) were submitted to biochemical and cytoenzymatic tests to compare the enzymatic profile of E.U.E. cells (controls) with that of E.U.E. adapted to hypertonic medium. The adapted cells are characterized by very high oxoreductase activity (LDH, HBDH, G-6-P DH) and very high alkaline-phosphatase activity. Clones derived from general population were also submitted to biochemical tests to characterize those more strictly related to the enzymatic profile of adapted cells. The profile of clone N. 13 resembles on this respect that of the adapted cells. The high redox activity is a prerequisite supporting energy supply for osmotic work. The increased activity of plasma membrane enzymes of the adapted cells is also demonstrable in cells exposed for short time to salinity.

Immunocytochemical detection of endocrine cells in the gut of Viviparus ater (Mollusca, Gastropoda).

The presence of endocrine cells was investigated by immunocytochemical procedures in the gut and salivary gland of Viviparus ater, a freshwater prosobranch gastropod. The endocrine cells were scanty and both of closed and open cell type. Most of them were located in the esophagus (immunostaining with anti-gastrin, anti-insulin, anti-serotonin and anti-substance P antisera), very few in the stomach (immunoreactive only to anti-gastrin antibody) and in proximal part of the intestine (immunoreactive to anti-serotonin and anti-substance P antibodies). In the salivary glands, occasional endocrine cells scattered among the glandular cells in the adenomera stained with anti-neuropeptide Y, anti-pancreatic polypeptide and anti-somatostatin sera were detected.

Immunocytochemical study of endocrine cells in the gut of goldfish Carassius carassius (L.) var. auratus submitted to experimental lead intoxication.

In the present study, the effects of experimental lead pollution on gut endocrine cells have been determined in the goldfish Carassius carassius (L.) var.auratus by immunocytochemical reactions. In the mucosa and submucosa, only vasoactive intestinal polypeptide- and 5-HT-like immunoreactive nerve fibers were observed. Endocrine cells displaying immunoreactivity against gastrin, CCK8, metenkephalin, bombesin, neuropeptide Y, pancreatic polypeptide, substance P, secretin, somatostatin and vasoactive intestinal polypeptide antibodies were detected. No immunoreactivity against glucagon, insulin and 5-HT antibodies was revealed in the endocrine cells. Some modifications appeared evident in the endocrine cells 48-96 h after lead intoxication, and can be summarized as follows: 1) discharge of secretory granules (secretin- and vasoactive intestinal polypeptide-like peptides), up to the extent that the cells appeared to be depleted of secretory material; 2) increase of immunoreactivity in the endocrine cells (met-enkephalin- and pancreatic polypeptide-like peptides) or in the frequency of positive cells (met-enkephalin-like peptide); 3) no variations (gastrin-, CCK8, bombesin-, somatostatin- and substance P-like peptides). The alterations were not enhanced by long term treatment. Nerve fibers did not show modifications.

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.

[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).