Early prediction of acute pancreatitis: Prospective study comparing computed tomography scans,ranson, glasgow,acute physiology and chronic health evaluation II scores,and various serum markers

The aim of this study was to assess the predictability of the outcome of acute pancreatitis using the Ranson, Glascow, and Acute Physiology and Chronic Health Evaluation (APACHE) II scores, the computed tomography (CT) scan, and several serum markers. Altogether, 137 consecutive patients with acute pancreatitis confirmed by CT scan were prospectively included. Blood samples were obtained daily for 6 days. The predictive value of each parameter was studied by univariate and multivariate analyses comparing mild and severe pancreatitis. A total of 111 attacks were graded as mild (81%) and 26 as severe (19%). Ranson (p = 0.3) and APACHE II (p = 0.049) scores appeared insufficiently predictive in the univariate analysis. Pancreatic imaging by CT scan was insufficiently predictive (p > 0.05), whereas the presence of extrapancreatic fluid collections was more indicative of outcome (p <0.05). With the univariate analysis, the four most reliable serum markers were pancreatic amylase (p <0.001), neutrophil elastase (p <0.05), albumin (p <0.002), and C-reactive protein (p <0.001). Results became homogeneous when the CT results were added; serum albumin plus extrapancreatic fluid collections (negative predictive value 92%-96% and positive predictive value 67%-100%) comprised the best indicator of severity. None of the parameters tested achieved sufficient predictability when used alone. Serum albumin plus extrapancreatic fluid collections comprise the best indicator of severity at the time of admission.     

Oral Squamous Cell Carcinomas Developing from Oral Lichen Planus: A 5–21 year Retrospective Study

Background and AimsThere is insufficient data regarding clinical characteristics, relapse rates, as well as lymph node metastasis of squamous cell carcinomas of the oral cavity (OSCC) developing from oral lichen planus (OLP-OSCC). The aim of this retrospective study was to evaluate clinical characteristics, as well as relapse, recurrence and survival rates of OLP-OSCC. MethodsIn a retrospective monocenter analysis, all consecutive patients with an OSCC treated in the time period 1st January 2000–December 31 2016 were reviewed. All patients with OSCC developing from OLP/OLL (oral lichenoid lesions) were identified and analyzed for epidemiological data, risk profile, location of primary tumor, pTNM classification, lymph node metastasis, primary therapy, recurrence, and outcome.ResultsA total of 103 patients (45%♂/ 55%♀) with an average age of 62 ± 14 year were included in this study. At the time of initial diagnosis, 17% (n = 18) of patients had cervical metastases (CM) whereas only 11% (11 patients) displayed advanced tumor sizes (T > 2). T-status (p = 0.003) and histopathological grading (p = 0.001) had an impact on the incidence of CM. 39.6% of the patients developed a relapse after an average of 24 months with a mean of two recurrences per patient. Advanced tumor size had a significant impact on the 5 year overall survival and was associated with disease-free survival of the patients (p < 0.001, respectively p = 0.004).ConclusionAlthough initial lymph node metastases were not more frequent, more aggressive recurrence patterns compared to OSCC were seen for OLP-OSCC. Therefore, based on the study results, a modified recall for these patients is suggested.     

Discovery of an orally active small-molecule irreversible inhibitor of protein disulfide isomerase for ovarian cancer treatment

Protein disulfide isomerase (PDI), an endoplasmic reticulum chaperone protein, catalyzes disulfide bond breakage, formation, and rearrangement. The effect of PDI inhibition on ovarian cancer progression is not yet clear, and there is a need for potent, selective, and safe small-molecule inhibitors of PDI. Here, we report a class of propynoic acid carbamoyl methyl amides (PACMAs) that are active against a panel of human ovarian cancer cell lines. Using fluorescent derivatives, 2D gel electrophoresis, and MS, we established that PACMA 31, one of the most active analogs, acts as an irreversible small-molecule inhibitor of PDI, forming a covalent bond with the active site cysteines of PDI. We also showed that PDI activity is essential for the survival and proliferation of human ovarian cancer cells. In vivo, PACMA 31 showed tumor targeting ability and significantly suppressed ovarian tumor growth without causing toxicity to normal tissues. These irreversible small-molecule PDI inhibitors represent an important approach for the development of targeted anticancer agents for ovarian cancer therapy, and they can also serve as useful probes for investigating the biology of PDI-implicated pathways.     

Latent Human Papillomavirus infection is comparable in the larynx and trachea

Recurrent respiratory papillomas are benign airway tumors caused by Human Papillomaviruses (HPVs) types 6 and 11. The disease is characterized by multiple recurrences of papillomas following surgical removal, caused by activation of latent HPV DNA. Most patients have laryngeal disease, while only a small subset has tracheal involvement. We have asked whether the lower frequency of tracheal papillomas was due to reduced prevalence of latent/subclinical tracheal HPV infection or reduced likelihood of activation to clinically apparent disease. A total of 121 biopsies of clinically normal laryngeal and tracheal tissues from 61 patients with laryngeal papillomas were analyzed for HPV DNA by polymerase chain reaction, confirmed by Southern blot hybridization. Patients were followed for 3-18 years (mean = 5.5 +/- 4.4), with only one developing subsequent tracheal disease. There was no significant difference in prevalence of latent HPV DNA between larynx and trachea, analyzing either those patients with a single biopsy or those with more than one biopsy of larynx, trachea, or both. There was also no significant difference between tracheal latency with HPV 6 and HPV 11. We conclude that HPV infects tracheal mucosa and is maintained as a latent infection in the trachea as efficiently as in the larynx. Therefore, we propose that the low frequency of tracheal disease reflects a lower frequency of HPV activation, and postulate that cellular factors that differ between the stratified squamous epithelium of the larynx and the ciliated pseudo-stratified columnar epithelium of the trachea contribute to this difference.     

Improved testing for CMT1A and HNPP using multiplex ligation-dependent probe amplification (MLPA) with rapid DNA preparations: comparison with the interphase FISH method

Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are the two most common peripheral neuropathies, with incidences of about 1 in 2,500. Several techniques can be used to detect the typical 1.5-Mb duplication or deletion associated with these respective conditions, but none combines simplicity with high sensitivity. MLPA is a new technique for measuring sequence dosage. We have assessed its performance for the detection of the specific 1.5-Mb duplication/deletion by prospectively testing 50 patients referred with differential diagnoses of CMT or HNPP. Probes were designed to evaluate the TEKT3, PMP22, and COX10 genes within the CMT1A/HNPP region. We have compared the results with our existing fluorescence in situ hybridization (FISH) assay, which was performed in parallel. There was concordance of results for 49 patients. Of note, one patient showed an intermediate multiplex ligation-dependent probe amplification (MLPA) result with an abnormal FISH result, which is consistent with mosaicism. The assay works equally well with either purified DNA or rapid DNA preparations made by direct cell lysis. The use of the latter significantly reduces the cost of the assay. MLPA is a sensitive, specific, robust, and cost-effective technique suitable for fast, high-throughput testing and offers distinct advantages over other testing methods.     

Constructing a hybrid molecule with low capacity of IgE binding from Chenopodium album pollen allergens

Allergen specific immunotherapy is the only remedy to prevent the progression of allergic diseases. Nowadays, using of recombinant allergens with reduced IgE-binding capacity is an ideal tool for allergen immunotherapy. Therefore, in this study we focused on a hybrid molecule (HM) production with reduced IgE reactivity from Chenopodium album pollen allergens. By means of genetic engineering, a head to tail structure of the three allergens of the C. album pollen was designed. The resulting DNA construct coding for a 46kDa HM was inserted into an expression vector and expressed as hexahistidine tagged fusion protein in Escherichia coli. IgE reactivity of the HM was evaluated by western blotting, inhibition ELISA and in vivo skin prick test and its immunogenic property was tested by proliferation assay. The recombinant HM was expressed and purified by nickel-affinity chromatography. Comparison of the recombinant HM with a mixture of three recombinant allergens, as well as natural allergens in the whole C. album pollen extract via immunological experiments revealed that it has a much lower potential of IgE reactivity. Furthermore, in vivo skin prick tests showed that it has a significantly lower potency to induce cutaneous reactions than the mixture of recombinant wild type allergens and whole extract while, it had been preserved immunogenic properties. Our results have demonstrated that assembling three allergens of C. album in a hybrid molecule can reduce its IgE reactivity.     

Absence of linkage and linkage disequilibrium to chromosome 15q11-q13 markers in 139 multiplex families with autism.

Chromosomal region 15q11-q13 has been implicated to harbor a susceptibility gene or genes underlying autism. Evidence has been derived from the existence of cytogenetic anomalies in this region associated with autism, and the report of linkage in a modest collection of multiplex families. Most recently, linkage disequilibrium with the marker GABRB3-155CA2 in the candidate locus GABRB3, located in this region, has been reported. We searched for linkage using eight microsatellite markers located in this region of chromosome 15 in 147 affected sib-pairs from 139 multiplex autism families. We also tested for linkage disequilibrium in the same set of families with the same markers. We found no evidence for excess allele sharing (linkage) for the markers in this region. Also, we found no evidence of linkage disequilibrium, including for the locus GABRB3-155CA2. Thus, it appears that the role of this region of chromosome 15 is minor, at best, in the majority of individuals with autism.