Connectionist networks in auditory system modeling

Understanding how complex sounds, such as speech, are processed and eventually perceived in the brain is essential for building more effective speech processors. The echolocating bat provides an animal model for complex-sound processing of identified stimulus features at higher levels of the auditory pathway. In this paper, we present the use of connectionist models for modeling cortical neurons that play a key role in our auditory system model of a species of FM bat, Myotis lucifugus. The influence of network related parameters on modeling accuracy is presented, and the response of these models is explained in a behavioral context.     

Computational Tools for Quantitative Breast Morphometry Based on 3D Scans

Quantitative analysis of breast morphometry is critical to breast plastic surgery. Recently, three-dimensional (3D) photography has emerged as a strong new alternative for breast morphometry analysis in comparison to other existing techniques. 3D photography enables the capture of the entire breast surface topology virtually in a single snapshot and without any direct contact with the patient, thus causing minimal discomfort. In this paper, we present a set of computational tools for the quantitative analysis of two key morphological properties of the breast that are of interest to breast plastic surgery based on 3D scans, namely breast shape and volume. The breast shape is modeled using a compact geometric model capable of capturing the global shape of the breast with very few parameters. Specifically, the shape model is deduced by applying a set of five global deformations to a geometric primitive. These deformations, defined using very intuitive parameters, closely model the key shape variables that surgeons inherently use to describe the overall shape of the breast. Patient-specific parameters of the breast shape model are automatically recovered by fitting a generic breast shape model to the 3D scan of the patient’s breast using a physics-based deformable model framework. The mean error of fit between the automatically fitted shape model and the actual breast surface for 12 subjects varied between 0.9 and 2.6 mm. These results are very encouraging considering the fact that only 17 parameters are used to determine the shape of the breast. The breast volume is estimated automatically by first localizing the breast on a 3D scan of the patient’s torso and then computing the volume enclosed between an interpolated breast-less torso surface and the actual breast. The volume estimated by the proposed method was found to be within the intra-operator variability among five segmentation trials performed manually by an expert on 3D torso scans of three subjects.     

Detection of Helicobacter pylori infection of the gastric mucosa by measurement of gastric aspirate ammonium and urea concentrations.

Helicobacter pylori possesses unusually high urease activity that lowers the urea concentration and raises the ammonium concentration of the gastric juice in infected people. The value of measuring urea and ammonium concentrations in gastric juice obtained during upper gastrointestinal endoscopy as a means of diagnosing the presence and eradication of the infection was assessed. Twenty four subjects with the infection and 14 in whom it had been eradicated were examined. Their H pylori status was confirmed by antral biopsy and 14C urea breath test. The median (range) gastric juice urea concentration in infected subjects was 0.8 mmol/l (0.5-2.9 mmol/l), which was lower than that in the uninfected subjects (2.1 mmol/l (1.0-3.7 mmol/l)) (p less than 0.001). The median gastric juice ammonium concentration in infected subjects was 3.4 mmol/l (1.0-13.0 mmol/l), which was higher than that in the uninfected subjects (0.64 mmol/l (0.02-1.4 mmol/l)) (p less than 0.001). Though the two groups overlapped in respect of their urea and ammonium concentrations, they were completely different when the urea: ammonium ratios were calculated--the ratios ranged from 0.04-0.7 (median 0.26) and from 1.1-113 (median 3.4) in infected and uninfected subjects respectively (p less than 0.001). Treatment with H2 antagonists did not change the concentrations of urea and ammonium or their ratio in gastric juice. Measurement of the urea: ammonium ratio in aspirated gastric juice obtained during routine upper gastrointestinal endoscopy may provide a rapid method of detecting H pylori infection and of confirming its eradication.     

Surveillance of patients with Barrett's esophagus for dysplasia and cancer with balloon cytology

BACKGROUND & AIMS: A less costly cancer surveillance method for Barrett's esophagus is desirable. The aim of this study was to compare nonendoscopic balloon cytology with biopsy and brush cytology for detecting dysplasia and carcinoma in patients with Barrett's esophagus. METHODS: Patients in a surveillance program underwent balloon cytology before endoscopy with biopsy and brush cytology. Results of cytology were compared with those of histology. RESULTS: Adequate columnar epithelium was obtained in 52 of 63 (83%) patients with balloon cytology and 59 of 61 (97%) with brush cytology. Balloon cytology obtained abnormal cells in 6 of 8 patients with adenocarcinoma, 2 of 2 patients with high-grade dysplasia, and 2 of 8 patients with low-grade dysplasia. Sensitivity of balloon cytology for high-grade dysplasia or carcinoma was 80% but only 25% for low-grade dysplasia. No patients without dysplasia or carcinoma had abnormal cells. Brush cytology was abnormal in all 11 patients with high-grade dysplasia or carcinoma but only 2 of 9 patients with low-grade dysplasia (sensitivity, 22%). Two of 39 patients without dysplasia had abnormal cells (specificity, 95%). Balloon cytology cost was sixfold less than endoscopy with biopsy. CONCLUSIONS: Balloon cytology detected 80% of patients with high-grade dysplasia or carcinoma when sampling was adequate. Brush cytology data suggest that a more abrasive balloon may improve balloon cytology sensitivity. The potential cost savings of balloon cytology compared with endoscopic cancer surveillance in Barrett's esophagus support further studies of this technique. (Gastroenterology 1997 Jun;112(6):1787-97)     

Effect of inhibition of Helicobacter pylori urease activity by acetohydroxamic acid on serum gastrin in duodenal ulcer subjects.

The mechanism of the hypergastrinaemia associated with Helicobacter pylori infection is unknown. It may be an effect of the ammonia produced by the bacterium near the antral epithelial surface. We have examined the effect on serum gastrin of inhibiting H pylori urease activity with acetohydroxamic acid in six duodenal ulcer patients. On day 1 the fasted patients received placebo tablets at 8 am, a peptide meal at 10 am, and a 14C urea breath test at 11.30 am. The next day 750 mg acetohydroxamic acid was administered orally in place of the placebo. The median (range) 30 minute breath test value (dose/mmol CO2 X kg body wt X 100) was 152 (111-335) on day 1, but only 22 (14-95) the next day (p less than 0.03). Further studies performed in one subject confirmed that acetohydroxamic acid lowered the ammonium concentration and raised the urea concentration in gastric juice. The inhibition of urease activity and ammonia production did not result in a fall in the basal gastrin concentration or in the median integrated gastrin response to the peptide meal, which was 78 ng/1.h (range 21-222) on day 1 and 79 ng/1.h (33-207) the next day. Ten days after acetohydroxamic acid, the urea breath test values were similar to those before treatment. This study shows that the raised gastrin concentration in patients with H pylori infection is not directly related to the organism's urease activity. It also shows that temporary suppression of H pylori urease activity does not clear the infection.     

Expression of the green fluorescent protein in the oligodendrocyte lineage: a transgenic mouse for developmental and physiological studies

We generated a transgenic mouse expressing the enhanced green fluorescent protein (EGFP) under the control of the 2'-3'-cyclic nucleotide 3'-phosphodiesterase (CNP) promoter. EGFP(+) cells were visualized in live tissue throughout embryonic and postnatal development. Immunohistochemical analysis in brain tissue and in sciatic nerve demonstrated that EGFP expression was restricted to cells of the oligodendrocyte and Schwann cell lineages. EGFP was also strongly expressed in "adult" oligodendrocyte progenitors (OPs) and in gray matter oligodendrocytes. Fluorescence-activated cell sorting allowed high-yield purification of EGFP(+) oligodendrocyte-lineage cells from transgenic brains. Electrophysiological patch clamp recordings of EGFP(+) cells in situ demonstrated that OP cells displayed large outward tetraethylammonium (TEA)-sensitive K(+) currents and very small inward currents, whereas mature oligodendrocytes were characterized by expression of large inward currents and small outward K(+) currents. The proliferation rate of EGFP(+) cells in developing white matter decreased with the age of the animals and was strongly inhibited by TEA. Oligodendrocyte development and physiology can be studied in live tissue of CNP-EGFP transgenic mice, which represent a source of pure EGFP(+) oligodendrocyte-lineage cells throughout development.     

In vitro and in vivo evaluation of the efficacy of nanoformulation of siRNA as an adjuvant to improve the anticancer potential of cisplatin

With the advent of advanced tools in molecular biology, understanding on cancer etiology has improved. siRNA can be considered as an effective tool in cancer therapy through silencing overexpressed genes responsible for cell proliferation or preventing apoptosis. However, some contentious issues such as stability and delivery of siRNA are to be resolved. Bcl-2, an anti-apoptotic gene, is overexpressed in a wide variety of cancers and responsible for drug resistance tumors. In our earlier studies, we developed a nanoformulation of siRNA targeting the Bcl-2 and achieved successful delivery in vitro and in vivo. To extend the scope of the study further, in the present work, we studied the role of nanoformulation of siRNA as adjuvant in chemotherapy with cisplatin. Dose dependant nephrotoxicity is a serious concern apart from other adverse effects of cisplatin. The IC₅₀ value for cisplatin was decreased from 9.83 μmol/l to 7.43 μmol/l in HeLa cells and from 8.54 μmol/l to 6.68 μmol/l in HEp-2 cells, when it was given with siRNA nanoformulation. Cisplatin at the dose of 1.7 mg/kg in combination with siRNA nanoformulation was effective in improving the lifespan of tumor bearing mice with significant decrease in nephrotoxicity.     

Formulation,characterization, in vitro and in vivo evaluation of castor oil based self-nano emulsifying levosulpiride delivery systems

Context: Levosulpiride (LSP) is a hydrophobic benzamide derivative used in the treatment of schizophrenia. SNEDDS were extensively practiced for systemic delivery of poorly aqueous soluble drugs to achieve maximum bioavailability.

Objective: The present study was focussed on the formulation, optimisation and evaluation of LSP SNEDDS using castor oil, for enhancement of drug absorption and bioavailability.

Materials and methods: Pseudo-ternary phase diagram was plotted to identify the range of SNEDDS components. Twenty formulations were designed, prepared and characterised by its particle size, zeta potential, viscosity, and stability. In vitro dissolution data modelling was performed. Microscopy, FTIR and in vivo bioavailability studies were conducted for optimum formulation.

Results, discussion and conclusion: F18 containing castor oil, 0.9?mL; PEG 600, 1.36?mL and Tween 80, 2.74?mL was found to be optimum. The optimised formulation had shown uniform globule size, no interactions of LSP with SNEDDS components and higher pharmacokinetic parameters than that of commercial preparation.