Changes in pulmonary function in patients with ulcerative colitis

OBJECTIVES: Information on the occurrence and frequency of pulmonary involvement in patients with ulcerative colitis (UC) is inconsistent. Some authors reported pulmonary impairment with UC by standard pulmonary function tests (PFTs) and documented a reduced diffusing capacity for carbon monoxide (DLCO) especially in patients with active disease, whereas others could not detect differences in routine PFTs between UC patients and controls. AIM: The aim of this prospective study was to determine the frequency and type of pulmonary dysfunction in patients with UC with respect to disease activity. Furthermore, to evaluate the influence of smoking, nutritional status, sputum cytology and sulphasalazine therapy on PFT parameters. PATIENTS AND METHODS: Twenty-six patients with UC (20 with active disease, 6 inactive) and 16 age and sex matched healthy controls were investigated with respect to the following pulmonary function tests, forced vital capacity (FVC), forced expiratory volume in the 1s (FEV(1)%) and their ratio (FEV(1)/FVC) and forced expiratory flow 25-75% (FEF25-75%) as well as oxygen saturation. For UC patients, colonoscopy and biopsy were done. Disease activity was assessed by Truelove index for UC. Induced sputum was sampled for cytology. Smoking habit, body mass index (BMI) and medications were recorded. RESULTS: Fifteen out of 26 patients with UC (57.6%) exhibited at least one pathological pulmonary function test (<80% of predicted value). Small airway obstruction was reported in the 15 patients, restrictive dysfunction in 30.7% and obstructive dysfunction in 11.5%. The impairment of PFTs was significant and more pronounced in patients with active disease, FVC (-14% of predicted), FEV(1) (-9% of predicted) and FEF25-75% (-32% of predicted), P<0.01, 0.05 and 0.01, respectively. There was no significant influence of smoking and medications on PFTs. CONCLUSIONS: UC patients show significantly decreased lung function tests in comparison to healthy controls. The impairment in active disease exceeded that during the remission. Early recognition is important, as they can be strikingly steroid responsive.     

Prevalence of celiac disease in Tunisia: mass-screening study in schoolchildren

BACKGROUND: Celiac disease is reported to be common among North Africans, particularly Tunisians. Nevertheless, the prevalence of coeliac disease in the general population has not been previously investigated. OBJECTIVE: This study aimed to determine the prevalence of celiac disease among children in Tunisia and to describe the clinical profile of the screened patients. METHODS: A mass screening study based on drawing lots was carried out on schoolchildren in Ariana, a Tunisian district. A participation agreement was obtained from 6286 children (3175 boys, age: 9.7+/-3 years). Two children of known celiac disease were present in this population. All participants were tested for IgA antitissue transglutaminase antibodies (IgA-tTG) by a commercial enzyme-linked immunosorbent assay (ELISA) and total IgA levels. Sera, found positive by the initial screening, were assessed by immunofluorescence for the presence of IgA antiendomysium antibodies (IgA-AE). Positive participants were also called in for serological control, intestinal biopsy, biological exploration (hemoglobin rate, calcemia and albuminemia) and bone mineral densitometry. RESULTS: Among the 6284 participants, 139 (1/45) were positive for IgA-tTG. Forty-two of these had low-level IgA-tTG and no one had IgA deficiency. IgA-AE was detected in 40 participants. One hundred and seven children were called in, 28 had both positive tests (IgA-tTG +/IgA-AE+) and 79 were only positive for IgA-tTG (IgA-tTG +/IgA-AE-). Intestinal biopsy was performed in the 28 participants of the first group (IgA-tTG +/IgA-AE+) and confirmed celiac disease in 26 cases. In the second group (IgA-tTG +/IgA-AE-), intestinal biopsy was performed in 26 children and histological examination was normal in all cases. Among the 26 biopsy-proven celiac disease children, six (23%) had typical clinical symptoms of celiac disease, whereas the others had atypical forms with 11 (42%) asymptomatic. In 23 biopsy-proven celiac disease children, bone mineral density was significantly lower than that of a group of 109 normal children (0.850+/-0.06 g/cm2 versus 0.912+/-0.06 g/cm2, P<0.05). Seven participants (30.4%) among the celiac disease children and six (7.5%) among the controls had a total-body Z score for bone mineral density of <-2 (P<0.001). CONCLUSION: The prevalence of celiac disease in Tunisian schoolchildren, estimated to be about 1/157, is close to the European prevalence. Most of the screened children showed an atypical and asymptomatic form, but even the typical forms were underdiagnosed. Ostopenia was frequently observed in celiac disease patients.     

Teneurin C-terminal associated peptides: an enigmatic family of neuropeptides with structural similarity to the corticotropin-releasing factor and calcitonin families of peptides

The proliferation of genomic sequence data in recent years has led to the identification of numerous orthologous and paralogous genes in a variety of divergent taxa. Phylogenetic comparisons of this sequence information have led not only to the construction of improved evolutionary relationships among genes and species, but also led to greater understanding of how genes and their proteins evolve differently throughout the Metazoa. Our recent characterization of a biologically active corticotropin-releasing factor (CRF)-like sequence at the C-terminal region of the teneurin transmembrane proteins has led to a number of questions of how peptide genes evolve and develop new functions in the Metazoa. The teneurin C-terminal associated peptides show structural similarity to the calcitonin family of peptides as well as the CRF family, and like both peptide families, plays a role in the regulation of stress and anxiety.     

In vivo metabolite profile of adult zebrafish brain obtained by high‐resolution localized magnetic resonance spectroscopy

Purpose

To optimize high‐resolution MR spectroscopy (MRS) for obtaining neurochemical composition of adult zebrafish brain in vivo.

Materials and Methods

A flow‐through setup for supporting MRS of living zebrafish has been designed. In vivo MR microscopy (MRM) images were obtained using a rapid acquisition with relaxation enhancement (RARE) sequence to select a volume of interest. In vivo MR spectra from zebrafish brain were obtained using an optimized point‐resolved spectroscopy (PRESS) sequence preceded by a variable pulse power and optimized relaxation delays (VAPOR) sequence for global water suppression interleaved with outer volume suppression (OVS). In vitro MR spectra in the brain extract were obtained by using correlated spectroscopy (COSY) sequences.

Results

Optimized high‐resolution localized MRS at 9.4T in conjunction with a strong gradient system, efficient shimming, and the water suppression scheme resulted in a reasonable separation of resonances from various metabolites in vivo from a voxel as small as 3.3 μL placed in the zebrafish brain. In addition, more than 14 metabolites were identified in adult zebrafish brain extracts.

Conclusion

We have successfully optimized a high‐resolution localized in vivo MRS technique to get access to the zebrafish brain, and obtained for the first time the neurochemical composition of the zebrafish brain. J. Magn. Reson. Imaging 2009;29:275–281. © 2009 Wiley‐Liss, Inc.     

High resolution localized two‐dimensional MR spectroscopy in mouse brain in vivo

Localized two‐dimensional MR spectroscopy (2D MRS) is impacting the in vivo studies of brain metabolites due to improved spectral resolution and unambiguous assignment opportunities. Despite the large number of transgenic mouse models available for neurological disorders, localized 2D MRS has not yet been implemented in the mouse brain due to size constraints. In this study we optimized a localized 2D proton chemical shift correlated spectroscopic sequence at field strength of 9.4T to obtain highly resolved 2D spectra from localized regions in mouse brains in vivo. The combination of the optimized 2D sequence, high field strength, strong gradient system, efficient water suppression, and the use of a short echo time allowed clear detection of cross‐peaks of up to 16 brain metabolites, allowing their direct chemical shift assignments in vivo. To our knowledge this is the first in vivo 2D MRS study of the mouse brain, demonstrating its feasibility to resolve and simultaneously assign several metabolite resonances in the mouse brain in vivo. Implementation of 2D MRS will be invaluable in the identification of new biomarkers during disease progression and treatment using the various available mouse models. Magn Reson Med 60:449–456, 2008. © 2008 Wiley‐Liss, Inc.     

Neuroendocrine differentiation in basal cell carcinoma

Basal cell carcinoma (BCC) is the prototypical basaloid tumor of the skin. It may show various patterns simulating other cutaneous tumors due to its pleomorphism. It may have an unusal pattern of differentiation such as squamous, sebaceous, apocrine, eccrine, pilar, and endocrine differentiation. In order to establish the relative frequency of neuroendocrine differentiation in BCC, we performed a retrospective study of 33 consecutive BCCs using conventional immunohistochemistry with two neuroendocrine antibodies: Chromogranine A and synaptophysine. The age of the patients ranged from 17–83 years with mean of 65 years. The male to female ratio was 16:17. In immunohistochimestry, Chromogranine A was seen in 72.2% (24/33) while Synaptophysine was positive in 9.09% (3/33). Their expression was cytoplasmic and membranous and was seen in the periphery of these tumors in the overlying cells. Positive staining of chromogranine A was high (75–100% of tumors cells) in 9%, intermediate (25–75% of tumors cells) in 33% of cases and relatively low (<25%) in 30.3% of cases.     

Targeting of HER2 antigen for the treatment of disseminated peritoneal disease.

The studies reported herein demonstrate the efficacy of alpha-particle-targeted radiation therapy of peritoneal disease with Herceptin as the targeting vehicle. Using the CHX-A-DTPA linker, Herceptin was radiolabeled with indium-111 and bismuth-213 with high efficiency without compromising immunoreactivity. A pilot radioimmunotherapy study treating mice bearing 5-day LS-174T (i.p.) xenografts, a low but uniform HER2 expressing, human colon carcinoma, with a single dose of (213)Bi-CHX-A"-Herceptin, proved disappointing. This defined the effect of tumor burden/size on tumor response to radioimmunotherapy with alpha-radiation. A more successful experiment with a lower tumor burden (3 days) in mice followed. A specific dose-response (P = 0.009) was observed, and although a maximum-tolerated dose was not determined, a dose of 500 to 750 muCi was selected as the operating dose for future experiments based on changes in animal weight. Median survival was increased from 20.5 days for the mock-treated mice to 43 and 59 days with 500 and 750 muCi, respectively. The therapeutic effectiveness of (213)Bi-CHX-A"-Herceptin was also evaluated in a second animal model for peritoneal disease with a human pancreatic carcinoma (Shaw). The results of this study were not as dramatic as with the former model, and higher doses were required to obtain an increase in survival of the mice (P = 0.001).