An Android Application for Estimating Muscle Onset Latency using Surface EMG Signal.

BACKGROUND: Electromyography (EMG) signal processing and Muscle Onset Latency (MOL) are widely used in rehabilitation sciences and nerve conduction studies. The majority of existing software packages provided for estimating MOL via analyzing EMG signal are computerized, desktop based and not portable; therefore, experiments and signal analyzes using them should be completed locally. Moreover, a desktop or laptop is required to complete experiments using these packages, which costs. OBJECTIVE: Develop a non-expensive and portable Android application (app) for estimating MOL via analyzing surface EMG. MATERIAL AND METHODS: A multi-layer architecture model was designed for implementing the MOL estimation app. Several Android-based algorithms for analyzing a recorded EMG signal and estimating MOL was implemented. A graphical user interface (GUI) that simplifies analyzing a given EMG signal using the presented app was developed too. RESULTS: Evaluation results of the developed app using 10 EMG signals showed promising performance; the MOL values estimated using the presented app are statistically equal to those estimated using a commercial Windows-based surface EMG analysis software (MegaWin 3.0). For the majority of cases relative error <10%. MOL values estimated by these two systems are linearly related, the correlation coefficient value ~ 0.93. These evaluations revealed that the presented app performed as well as MegaWin 3.0 software in estimating MOL. CONCLUSION: Recent advances in smart portable devices such as mobile phones have shown the great capability of facilitating and decreasing the cost of analyzing biomedical signals, particularly in academic environments. Here, we developed an Android app for estimating MOL via analyzing the surface EMG signal. Performance is promising to use the app for teaching or research purposes.

3,7,10,14,15-pentaacetyl-5-butanoyl-13,17-epoxy-8-myrsinene a novel compound isolated from Pycnocycla spinosa extract with potent anti-spasmodic and antidiarrheal properties.

Bioassay monitoring of hydroalcoholic extract from the aerial part of Pyconcycla spinosa revealed that it contains components with spasmolytic activity in vitro. In addition, P. spinosa extract at oral dose of 1-5 mg/kg inhibits diarrhoea in animal models. Pharmacological screening of pure compounds isolated from P. spinosa hydroalcoholic extract led to the identification of 3,7,10,14,15-pentaacetyl-5-butanoyl-13,17-epoxy-8-myrsinene (PABEM) which is a new diterpene. In this research, we have investigated antispasmodic and antidiarrheal effects of PABEM for comparison with P. spinosa extract. Aerial parts of P. spinosa were extracted with ethanol. For antispasmodic studies, rat isolated ileum was suspended in Tyrode's solution in an organ bath. The ileum was contracted by acetylcholine (ACh, 0.5 µM), serotonin (5-HT, 5 µM) or electrical field stimulation (EFS). P. spinosa extract in a concentration dependent manner (10-640 µg/ml) inhibited ileum contractions induced by ACh, 5-HT or EFS. The new compound isolated form P. spinosa extract "PABEM" in a similar manner inhibited the contractile response to ACh, 5-HT and EFS. However, the inhibitory effects of PABEM were observed at much lower bath concentrations. The relaxation effect of PABEM was started at 40 ng/ml bath concentration and with 2.5 µg/ml PABEM in the bath, the contractile responses of ileum were completely abolished. Both hydroalcoholic extract of P. spinosa and PABEM reduced intestinal meal transit and castor oil and MgSO4 induced diarrhoea in mice. However, PABEM was about 10 times more potent than its parent extract. This research shows that PABEM is probably the main component responsible for antispasmodic and antidiarrheal actions of P. spinosa extract.

Frequency analysis of HLA class I alleles in Iranian patients with progressive and non-progressive chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is a malignant disorder of B cell origin, with low incidence in Asian populations. In this study we investigated the HLA-class I A and B allele frequencies in 87 Iranian CLL patients and 64 healthy controls using sequence specific primer-polymerase chain reaction (SSP-PCR) technique. Our results showed increased frequencies of HLA-A11:01 (p=0.02) and HLA-B35:01 (p=0.002) alleles and HLA-A11:01/B35:01 haplotype (p=0.036) and decreased frequencies of HLA-A01:01 (p=0.02), HLA-A26:01 (p=0.03), HLA-B65:01 (p=0.03) and HLA-B53:01 (p<0.00001) alleles in CLL patients compared to the control group. Classification of the patients into non-progressive and progressive groups did not reveal significant differences for the frequency of any of the HLA-A and -B alleles or haplotypes between these two subtypes. Comparison between patients with immunoglobulin heavy chain variable region genes (IGHV) mutated (n=56) and unmutated (n=31) subtypes showed a significant increase in HLA-A32:01 (p=0.05) and HLA-A33:01 (p=0.05) alleles in IGHV unmutated patients compared to IGHV mutated patients. Similarly, a higher frequency of HLA-B52:01 (p=0.037) alleles was observed in CD38(+) compared with CD38(-) patients. Our results obtained from an Iranian population indicate that CLL is associated with distinct HLA class I alleles and haplotypes some of which are linked to disease prognostic factors.

CYP2C9 gene analysis of some Iranian hypersensitive patients to warfarin.

For the first time in this study, the pharmacogenetic effects of CYP2C9 polymorphism on warfarin sensitivity in some Iranian patients who are on warfarin treatment were shown. The study group consisted of clinically sensitive patients (21 patients) and the control group (37 adult patients). For detection of CYP2C9*2 and CYP2C9*3 variants, a protocol based on restriction fragment length polymorphism based polymerase chain reaction with Eco47I and KpnI was used. In clinically sensitive patients about 81% and in normal response patients about 24.3% carried variant genotypes.

Neutrophil function (innate immunity) during Ramadan.

BACKGROUND: Fasting during the month of Ramadan is one of the essential religious practices of Muslims. The aim of this study was to evaluate opsonisation, phagocytosis, and nitroblue tetrazolium (NBT) reduction by white blood cells in normal, healthy, male subjects under non-fasting (before Ramadan) and fasting (after Ramadan) conditions. METHODS: In this study, 13 Muslim men, aged 28-54 years, whose health was confirmed by health application forms, gave blood samples one week before the beginning of the holy month of Ramadan and during the last week of Ramadan. Blood samples were tested for neutrophil phagocytosis, serum opsonisation power, and NBT reduction. RESULTS: Despite a decline in the neutrophil phagocytic index and serum opsonisation index, the percentage of neutrophils participating in phagocytosis increased with fasting. In addition, there was an increase in the percentage of neutrophils demonstrating NBT reduction. Although there was a decrease in opsonisation of the serum, the increased percentage of opsonisation compensated for this defect. CONCLUSION: This study demonstrates the beneficial effect of fasting during Ramadan on neutrophil phagocytic function.

Assaying of warfarin in Iranian warfarin resistance patients blood by HPLC.

A simple and rapid HPLC method with UV detecting system has been used in determination of warfarin level in plasma of Iranian patients who received different doses of this drug. Six resistance (10-70 mg day(-1)) and 5 sensitive patients (0.5-2.5 mg day(-1)) were selected for this study. Range of warfarin level in plasma was between 0.93 and 22.8. After determination of warfarin level in warfarin sensitive and especially, warfarin resistance patients, we are going to find a relationship between this level and pharmacokinetic or pharmacogenetic factors. In the separate study which was done in our laboratory on the gene that is possibly responsible for warfarin resistance we did not find any mutation in our patient with high warfarin concentration in their blood.

Evaluation of rFVIIa (NovoSeven) in Glanzmann patients with thromboelastogram.

Glanzmann thrombasthenia (GT) is a rare platelet function disorder characterized by a defect in fibrinogen binding to platelet membrane glycoprotein (GP) IIb/IIIa. Recombinant FVIIa (rFVIIa) is a haemostatic agent approved for the treatment of haemophilia patients with inhibitors, patients with acquired haemophilia and in EU also for treatment of factor VII (FVII)-deficient patients and GT patients with antibodies to GPIIb-IIIa. The present study was conducted to evaluate the use of the whole blood test system, rotational thrombelastometry (ROTEM), in measuring the overall haemostasis potential of rFVIIa in 28 GT patients treated with rFVIIa. The correlation of administered rFVIIa and time to start fibrin formation and clot dynamic/stability was assessed and correlation to the clinical response was elucidated. Assessments were performed on predose blood samples spiked with four different concentrations of rFVIIa and whole blood samples taken at 10 and 120 min following dosing. ROTEM parameters clotting time (CT), clot formation time (CFT) and maximum clot firmness (MCF) were measured. Both ex vivo and in vivo data showed beneficial effects on CT in the presence of rFVIIa, but no effect of added rFVIIa was seen on CFT and MCF. In conclusion, the use of thrombelastography at least in the modified form of ROTEM seems to be of limited use in predicting an adequate dose of rFVIIa in GT patients. A good clinical haemostatic response was recorded in spite of the limited changes in the ROTEM pattern supporting the conclusion that ROTEM should not be the method of choice for monitoring rFVIIa therapy in Glanzmann patients.

Effect of Ramadan on neutrophil's respiratory burst (innate immunity) and circulating immune complex.

BACKGROUND: The aim of this study was to investigate the effects of Ramadan fasting on neutrophil's respiratory burst and circulating immune complex (CIC) level. METHODS: The effects of Ramadan fasting on neutrophil's respiratory burst and CIC was studied in 21 normal young fasting Muslim individuals using standardized chemiluminescence and poly ethylene glycol methods respectively, the results obtained and statistically analysed. RESULTS: It was shown that in 11 cases out of 21 (52%) both of the chemiluminescence (CL) activity and CIC levels measured before and after Ramadan fasting were in normal range in spite of a insignificant decrease or increase in CL activity or CIC level. Therefore, the changes of the immunological parameters were not significant and the levels remained in the range of normal. In four cases out of 21 (24%), the CL activity and CIC levels were higher than normal range measured just before Ramadan, however after month of Ramadan the CL activity and CIC level decreased reaching to the normal level of these parameters. In four cases out of 21 (24%) there were an increase in CL activity and CIC levels after Ramadan fasting. CONCLUSION: There were no significant changes of CL activity of circulating neutrophils and CIC levels comparing the results obtained before and after Ramadan. More over there was a good correlation between these two immunological parameters measured in the present study.

Analysis of the immunoglobulin heavy chain variable region gene expression in Iranian patients with chronic lymphocytic leukemia.

B-cell chronic lymphocytic leukemia (B-CLL) results from clonal expansion of phenotypically mature but functionally immature B-lymphocytes. The incidence of this type of leukemia is low in Asian countries, whereas it is the most frequent type of leukemia in the West. Previous investigations mainly conducted in Western populations have demonstrated non-random rearrangement of certain immunoglobulin variable region heavy (VH) and/or light (VL) chain genes in different groups of B-CLL patients. Little is known about the profile of VH gene expression in Asian patients. In the present study, we determined the frequency of VH gene family usage in 59 Iranian patients with B-CLL. VH gene family of patients was determined by reverse transcriptase-polymerase chain reaction using VH1-VH7 family specific primers. The most frequently expressed VH gene family was found to be VH3 (45.8%) followed by VH4 (32.2%), VH1 (18.6%), VH5 (1.7%) and VH6 (1.7%), with no expression of VH2 and VH7 gene families. The results indicate a lower representation of the VH1 and VH2 gene families and a higher representation of the VH4 gene family in Iranian B-CLL patients compared to Western patients, suggesting involvement of ethnic and/or environmental factors in B-CLL disease initiation.

Presentation and pattern of symptoms in 382 patients with Glanzmann thrombasthenia in Iran.

Glanzmann thrombasthenia (GT) is a rare autosomal recessive disease characterized by prolonged bleeding time with normal platelet count and morphology. It is caused by the quantitative or qualitative deficiency of the platelet glycoprotein IIb-IIIa. In 382 Iranian patients with GT diagnosed at a single center during the period 1969-2001, consanguinity between parents was 86.6%, in accord with the high frequency of intrafamilial marriages in Iran. Almost all patients had had abnormal mucocutaneous bleeding (epistaxis and gum bleeding); at follow-up, 4/5 of the patients had been transfused at least once to control hemorrhagic episodes. As expected, almost all the patients had a normal platelet count while the leukocyte count was increased in 19.3%. Among women, an unexpected low rate of pregnancies was observed.

Characterization of human hybridoma clones isolated from hemophilia patients with specificity for different domains of coagulating factor VIII.

Hemophilia A patients treated with human coagulating factor VIII (FVIII) may develop inhibitory antibodies (inhibitors). Characterization of the inhibitors at the clonal level may help exploring new therapeutic strategies. We have generated lymphoblastoid cell lines (LCLs) producing anti-FVIII antibodies from peripheral blood lymphocytes of hemophilia A patients with high inhibitor titers. We fused the anti-FVIII-positive LCLs with a heteromyeloma, to produce FVIII specific hybridomas. We determined the specificity, isotype, idiotypic and immunoglobulin (Ig) variable region heavy (VH) chain gene family profiles of the secreted antibodies (Ab) by ELISA, immunoblotting and RT-PCR. We established eight hybridomas which produced high titers of anti-FVIII Ab. All hybridomas secreted IgM Ab, associated with either kappa(5/8) or lambda(3/8) light chain. Analysis of the expressed VH genes by RT-PCR revealed that the hybridomas utilized only the VH1 (63%) or the VH3 (37%) gene families. Among the cross-reactive idiotypes (CRIs) we tested, only the VH1 and VK3b-associated CRIs were expressed by 3 hybridomas. Immunoblotting of thrombin-digested FVIII demonstrated distinct patterns of reactivity of the monoclonal Ab (MAb) secreted by the hybridomas, which recognized either the A2 domain of the Fvm heavy chain, or the light chain, or both. Our findings suggest that: a) the isotype of the anti-FVIII Ab secreted by LCLs and hybridoma clones (IgM) differs from that of anti-FVIII Ab in vivo, which are predominantly IgG4: this suggests a negative selection of the isotype-switched FVIII-specific B-cells in the periphery of these patients; b) the anti-FVIII Ab have a biased representation of the VH1 gene family, and c) somatic mutations in the VH genes coding for FVIII specificity occur in the anti-FVIII Ab response, as evidenced by lack of expression of the VH-associated CRI.

Analysis of the expressed immunoglobulin variable region heavy chain gene products in paraproteins from Iranian patients with multiple myeloma.

The frequency of expression of immunoglobulin (Ig) variable region heavy (VH ) chain gene products was studied in 43 Iranian patients with mutiple myeloma (MM). The expressed VH gene families and associated cross-reactive idiotypes (CRI) were analysed by immunoblotting and ELISA, using peptide-induced polyclonal antibodies specific for VH 1-VH 6 gene families and monoclonal antibodies (MAb) recognising CRI linked to theVH 1, VH 3, VH 4 and VH 6 gene families. The results revealed that the VH 3 family (60. 5%) was the most predominant gene family. In contrast, no paraproteins were encoded by genes from the VH 2 gene family and only 2.3% were encoded by the VH 5 family. The panel of paraproteins tested rarely expressed the probed VH -associated CRI. Our results suggest that: 1-The Ig VH genes, may not be randomly expressed in the malignant plasma cells from Iranian patients with MM. 2- Some of the genes seem to be negatively selected or highly mutated, as evidenced by the lack of expression of the probed CRI.

Congenital factor X deficiency: spectrum of bleeding symptoms in 32 Iranian patients.

The spectrum of the clinical manifestations of congenital factor X deficiency was studied in 32 Iranian patients. The most frequent symptom was epistaxis, which occurred in 72% of patients, with all degrees of deficiency. Other mucosal haemorrhages (e.g. haematuria, gastrointestinal bleeding) were less frequent and occurred mainly in patients with unmeasurable factor X. Menorrhagia occurred in half of the women of reproductive age. Soft tissue bleeding occurred in two-thirds of the patients; spontaneous haematomas and haemarthroses led to severe arthropathy in five patients. Bleeding from the umbilical stump was an unexpected finding in nine patients. This study demonstrated that the bleeding tendency of factor X deficiency is severe and correlates with factor levels.

Symptoms of inherited factor V deficiency in 35 Iranian patients.

The type of bleeding symptom has been evaluated in 35 Iranian patients with an inherited deficiency of factor V, with plasma levels between 1% and 10%. The most frequent symptoms included epistaxis and excessive bleeding after surgery. Haemarthroses and muscle haematomas were less common, even in severely deficient patients. More severe symptoms such as gastrointestinal and central nervous system bleeding were rare. The severity of bleeding symptoms was only partially related to the degree of factor V deficiency in plasma. On the whole, human factor V deficiency is characterized by a moderately severe bleeding phenotype.

Clinical manifestations in 28 Italian and Iranian patients with severe factor VII deficiency.

There has been wide variation in the reported haemorrhagic manifestations of factor VII deficiency. We examined type and frequency of clinical manifestations in 28 Iranian and Italian patients with severe deficiency (factor VII coagulant activity 2% or less). The most frequent symptoms were epistaxis and menorrhagia, whereas soft tissue bleeding such as haemarthrosis and muscle haematoma was less frequent. Only 5 of 9 patient who underwent surgery without factor VII replacement therapy had postoperative bleeding severe enough to require blood transfusion. No thrombotic manifestation occurred. A factor VII functional assay based on the use of human thromboplastin was a better predictor of the bleeding tendency of these patients than a rabbit thromboplastin-based functional assay or immunoassay. On the whole, this study shows that in severe factor VII deficiency bleeding in mucosal tracts is not uncommon. Surgery can sometimes be performed without replacement therapy and without haemorrhagic complications.