Effects of topical application of methotrexate on nasal mucosa in rats: a preclinical assessment study.

OBJECTIVE: The aim of this study is to investigate dose-dependent effect of the topical application of methotrexate (MTX) in rats on the normal nasal mucosa, liver tissue, liver enzymes, and hemoglobin levels. STUDY DESIGN: Preclinical animal study. SETTING: Twenty male adult wistar albino rats were randomly divided into 4 groups (n=5). A single puff of MTX (2.5 microg) was applied to both nasal cavities 2 times a day. The animals were given MTX 1 day a week in group 1, 3 days a week in group 2, and 5 days a week in group 3. Control group animals were given 1 puff of physiologic saline to both nasal cavities 5 days a week and 2 times a day. After 28 days, liver biopsies, blood samples, and 5 nasal mucosal biopsies were taken. Histological examination was made with respect to certain parameters semiquantitatively (grade 0-3). The aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and hemoglobin counts were studied from blood samples. RESULTS: There are no statistically significant differences with respect to histopathological parameters between the control group and the groups 1-3 (P>0.05). Histopathological examination of liver tissue did not reveal any evident difference between the control and study groups. Mean AST and ALT as liver function tests and hemoglobin counts were within normal limits. Topical application of MTX at these doses has no toxic effect on the nasal mucosa, the liver tissue, AST and ALT levels, and hemoglobin level. CONCLUSIONS: These results have been encouraging to investigate use of the topical application of MTX in nasal manifestation of autoimmune disease or addition of the topical application of MTX to the steroid treatment in cases with massive nasal polyposis resistant to steroids and prone to recurrence.     

The role of gastric Helicobacter pylori infection in laryngopharyngeal reflux disease.

OBJECTIVES: To investigate the role of Helicobacter pylori (H pylori) infection in laryngopharyngeal reflux (LPR). STUDY DESIGN: A prospective multidisciplinary clinical study. METHODS: Forty-four adult patients who applied to our ENT clinic with LPR symptoms were evaluated. Then these patients underwent upper gastrointestinal system endoscopy and double probe pH monitoring. In addition, during the endoscopy multiple biopsies from the stomach were obtained to detect H pylori. RESULTS: Results from 32 LPR positive patients were assessed (10 male and 22 female). There were no statistically significant differences between the presence of H pylori and sex, age, degree of gastritis and esophagitis, and also the number of reflux, fractional acid exposure time regarding proximal probe readings. Similarly for both proximal and distal probe readings, the average score of esophageal acid clearance was not statistically significant (P > 0.05). In addition, no statistically significant difference was found between the presence of H pylori and GERD (P > 0.05). CONCLUSIONS: The results of this study demonstrated that there is no relationship between gastric H pylori infection and LPR. EBM rating: B-3b.     

Knowledge and attitudes of primary health care personnel concerning mental health problems in developing countries: a follow-up study

Within the context of a World Health Organization coordinated collaborative study health workers in six developing countries were assessed 18 months after their training for improvement in their knowledge and attitude towards mental health problems and their management. The approaches to training varied between study areas, but the degree of improvement following the training, was of equal magnitude in all countries. The training process has formalized the recognition by the health workers that treatment of mental health problems is an integral part of their work.     

Amplification and restriction endonuclease digestion of a large fragment of genes coding for rRNA as a rapid method for discrimination of closely related pathogenic bacteria.

By use of primers specific to conserved regions of the rRNA gene cluster, a discrete amplicon of approximately 5 kb was amplified by PCR from all 21 bacterial genera investigated. Subsequent endonuclease digestion of the PCR product with HaeIII distinguished between the three species of the human pathogen Francisella spp. on the one hand and four clinically relevant genomic groups of Acinetobacter spp. on the other hand. The described technique has the potential as a rapid method for discriminating between closely related species that are of clinical importance.     

Rescue of lethal molybdenum cofactor deficiency by a biosynthetic precursor from Escherichia coli

Substitution therapies for orphan genetic diseases, including enzyme replacement methods, are frequently hampered by the limited availability of the required therapeutic substance. We describe the isolation of a pterin intermediate from bacteria that was successfully used for the therapy of a hitherto incurable and lethal disease. Molybdenum cofactor (Moco) deficiency is a pleiotropic genetic disorder characterized by the loss of the molybdenum-dependent enzymes sulphite oxidase, xanthine oxidoreductase and aldehyde oxidase due to mutations in Moco biosynthesis genes. An intermediate of this pathway-'precursor Z'-is more stable than the cofactor itself and has an identical structure in all phyla. Thus, it was overproduced in the bacterium Escherichia coli, purified and used to inject precursor Z-deficient knockout mice that display a phenotype which resembles that of the human deficiency state. Precursor Z-substituted mice reach adulthood and fertility. Biochemical analyses further suggest that the described treatment can lead to the alleviation of most symptoms associated with human Moco deficiency.     

A gene for autosomal recessive limb-girdle muscular dystrophy maps to chromosome 2p

The limb-girdle muscular dystrophies are a clinically and geneticallyheterogeneous group of disorders. We have ostudied two largeinbred families of different ethnic origin and excluded linkageto LGMD2 on chromosome 15q and SCARMD on chromosome 13. Proceedingto a genomic linkage search, we have now identified linkageto markers D2S134 and D2S136 on chromosome 2p (maximum lod score3.57 at zero recombination). The phenotype in the two familieswas similar, with onset in the pelvic girdle musculature inthe late teens and usually relatively slow progression. Thiswork Identifies a second locus for autosomal recessive limb-girdlemuscular dystrophy.     

Phenotype, activation and lymphokine secretion by gamma/delta T lymphocytes from schistosomiasis and carcinoma of the urinary bladder.

In humans the majority of the CD3+ T cells usually express an alpha/beta T cell receptor (TcR) and a minority express a gamma/delta TcR. The CD3+ TcR alpha/beta and CD3+ TcR gamma/delta cells from blood of the patients with schistosomiasis with carcinoma of the urinary bladder (SCB) were analyzed for phenotype, activation, secretion of interleukin 2 (IL 2). B cell growth factor (BCGF) and B cell differentiation factor (BCDF), as well as for autologous (AMLR) and allogeneic (MLR) mixed lymphocyte reaction. Patients with SCB had a highly increased percentage of CD3+ TcR gamma/delta and a decreased percentage of CD3+ TcR alpha/beta T cells in their circulation. These CD3+ TcR gamma/delta T cells expressed the CD25 (IL 2 receptor), CD38, CD71 (transferrin receptor) and HLA-DR activation antigens at a higher intensity after in vitro stimulation with recombinant IL 2, phytohemagglutinin and soluble egg antigen (from Schistosoma haematobium). The SCB patients' CD3+ TcR gamma/delta T cells were highly deficient in secretion of IL 2 but produced highly elevated levels of BCGF and BCDF. On the contrary, both BCGF and BCDF activities of the CD3+ TcR alpha/beta T cells were decreased. Moreover, CD3+ TcR gamma/delta T cells demonstrated highly deficient AMLR and MLR activity. These observations suggest a possible role of CD3+ TcR gamma/delta T cells in the immune response and the disease pathogenesis in human schistosomiasis infections.     

Mechanisms by which Candida albicans induces endothelial cell prostaglandin synthesis.

One strategy for improving resistance to opportunistic pathogens is to determine host cellular responses during the invasion process and upregulate those responses that are relevant to host defense mechanisms. Within this context, we have shown previously that invasion of endothelial cells by Candida albicans in vitro causes increased production of prostaglandins. As a prerequisite for modulating endothelial cell prostaglandin production, we now characterize the mechanisms through which this process occurs. Endothelial cell invasion by C. albicans appeared to stimulate the conversion of arachidonic acid into prostaglandins by upregulating the synthesis of endothelial cell cyclooxygenase and increasing the activity of the endothelial cell phospholipase. The enhanced activities of these two enzymes were independent of calphostin C-sensitive protein kinase C and resulted in the increased production and extracellular secretion of prostaglandin I2 (PGI2), PGF2 alpha, and PGE2. The secretion of these prostaglandins had no effect on the amount of endothelial cell injury induced by C. albicans. The role of the increased prostaglandin secretion by endothelial cells is likely related to modulation of the leukocyte response at the candida-leukocyte-endothelial cell interface.     

An intelligent system for diagnosis of the heart valve diseases with wavelet packet neural networks

In this paper, an intelligent system is presented for interpretation of the Doppler signals of the heart valve diseases based on the pattern recognition. This paper especially deals with combination of the feature extraction and classification from measured Doppler signal waveforms at the heart valve using the Doppler Ultrasound. Because of this, a wavelet packet neural network model developed by us is used. The model consists of two layers: wavelet and multi-layer perceptron. The wavelet layer is used for adaptive feature extraction in the time-frequency domain and is composed of wavelet packet decomposition and wavelet packet entropy. The multi-layer perceptron used for classification is a feed-forward neural network. The performance of the developed system has been evaluated in 215 samples. The test results showed that this system was effective in detecting Doppler heart sounds. The correct classification rate was about 94% for abnormal and normal subjects.