Poster presentations Vaccine strategies 293 Lung RSV titers were significantly reduced in mice im... more Poster presentations Vaccine strategies 293 Lung RSV titers were significantly reduced in mice immunized with the F/M2: El-95 chimetic peptkte compared to control mice. Conclusion: lntranasal immunization with a synthetic peptide vaccine without adjuvant resulted in induction of cytotoxic T cell responses and in reduction of RSV titer. non-toxic and which will be capable of inducing lifelong protective immunity against all known variants of HBV in humans. Matetlals and Methods: Antibody to the Hepatitis B surface antigen (HB-sAg) provides protective immunity against HBV. with amino acid regions 160-l 71 and 13*147 considered to represent a T-cell and a B-cell epitope. A 46 amino acid peptide (sl21-167) representtna amino acids 121-167 of the Heo-P.4.01.28 atitis B surf& antisen (adw2 sequence) w& selected as a potential syntheic T cell epltopes from the secreted 84. fube~~~/osis 886 antigen (WT59) mapped by antigen specific vaccine candidate and has been synthesised using Fmoc chemistry. Assesshuman T cell lines ment of ~121-167 as an immunogen was carded out in a preliminary in viw~ study using BALB/c mice. Sera collected from the mice was analysed by ELISA
MaterIala and Methods: In order to get more precise information, we have analyzed the intramuscul... more MaterIala and Methods: In order to get more precise information, we have analyzed the intramuscular vaccination with two plasmld DNAs encoding either a mature or a secreted form of the Ag85A protein and compared it to the immunogenicity of an intravenously given live M. bovis BCG vaccine. FteeulB: Significant and comparable Ag85-specific IgG levels of IgGl, IgG2a and IgGPb isotype were detected in sera from mice vaccinated with either mature or secreted Ag85A DNA, whereas BCG-vaccination only induced minimal antibody levels. Vaccination with DNA stimulated comparable levels of IL-2 and IFN-y responses in response to whole BCG culture filtrate and its purtfied Ag85 complex as vaccination with BCG. On the other hand, Thl cytokine production against PPD, BCG cytoplasmic extract and whole BCG bacilli, was cleatiy lower following vaccination with DNA encoding Ag85A than following BCG. A Thl T cell epitope mapping using synthetic 20mer peptides covering the complete mature sequence of Ag85A, indicated that DNA vaccination stimulated a broader IL-2 and IFN-y epitopic repertoire than BCG, albeit that most BCG-triggered epitopes were also recognized following DNA vaccination. The same peptides were recognized following vaccination with DNA encoding the secreted or mature form, and generally responses were strongest against the latter. Moreover, strong CTL activity against Ag85A-transfected P815 cells and peptide-pulsed P815 cells could only be measured following DNA vaccination with ether construct but not after M. bovis BCG infection. Finally, vaccination of guinea pigs with Ag85A encoding DNA induced significant lymphoproliferative responses and antibody production but failed to induce a positive DTH reaction against purified native Ag85, whereas intradermal BCG vaccination did induce a positive DTH reactton but little antibodies or Ag85 specific pmliieration. Conclualon: These results indicate that vaccination with plasmid DNA encoding Ag85A may offer several advantages over classical vaccination with M. bovis BCG by the induction of antibodies of IgGl, IgGPa and lgG2b isotype (which may neutralize the enzymatic mycolyl-transferase activity of Ag85), by the stimulation of a stronger, epitope spreadened but antigenically restricted productton of Thl cytokines, by the absence of DTH induction and by the generation of potent CD8+ CTL responses. 0.4.11.6 Human CD8+ CTL specific for Mycobacterium tlh?rcl4/os/s
Haemoptysis is an alarming symptom, and the management depends upon the aetiology. Emergency mana... more Haemoptysis is an alarming symptom, and the management depends upon the aetiology. Emergency management depends upon localization of the site of bleeding by roentgenogram, computerized chest tompgraphy and bronchoscopy.
Nickel-based superalloys are extensively used in manufacturing hot gas path components in industr... more Nickel-based superalloys are extensively used in manufacturing hot gas path components in industrial gas turbines used for power generation. Specifically, GTD-111DS is one of the widely used alloys used in manufacturing the hot gas path rotating components. These components are subjected to extreme operating environments resulting in creep, oxidation, fatigue of the components during operation. After continued operation, these damage modes need to be repaired and the components go through extensive repair processes, which includes several heat treatments to recover the mechanical properties of the base material (GTD-111DS) lost during operation. The heat treatments used during repair by the different repair vendors can vary a lot in terms of temperature, time and the sequence as well. This study focuses on the understanding the difference in the effects of the heat treatments to the base material (partial solution, full solution, HIP and full solution) in terms of microstructure-mec...
Objectives To examine trends in asthma hospitalisation and mortality rates from 2000 to 2014 in K... more Objectives To examine trends in asthma hospitalisation and mortality rates from 2000 to 2014 in Kuwait according to sex, age and nationality. Methods For this nationwide, retrospective observational study, data from hospital discharge records and death certificates listing asthma as the primary reason for hospitalisation or mortality were obtained from the National Center for Health Information database using International Classification of Diseases, Tenth Revision codes J45 and J46. Trends in sex-adjusted, age-adjusted and nationality-adjusted hospitalisation and mortality rates were examined. Poisson regression models were applied to test for linear trends overtime and estimate adjusted rate ratios and 95% CI. results During the 15-year study period, a total of 43 652 hospitalisations and 484 deaths due to asthma exacerbations were identified. The average annual adjusted rates of asthma hospitalisation and mortality were estimated to be 134.9 (95% CI 131.8 to 138.1) and 2.1 (95% CI 1.8 to 2.4) per 100 000 population, respectively. Hospitalisation rates decreased by 49.5% in the total population (from 180.8 to 91.3 admissions per 100 000 population between 2000 and 2014, p trend <0.001) and by 57.9% in the age group of 5-44 years (from 77.3 to 32.5 admissions per 100 000 population, p trend <0.001). Mortality rates decreased from 4.1 to 0.9 deaths per 100 000 population between 2000 and 2014 in the total population (77.6% decrease, p trend <0.001) and from 0.6 to 0.2 deaths per 100 000 population among those aged 5-44 years (61.9% reduction, p trend =0.005). Kuwaiti compared with non-Kuwaiti subjects had higher risk of asthma hospitalisation and mortality. Among children aged ≤19 years, the risk of hospitalisation was higher in boys compared with girls; however, among adults, women experienced more hospitalisations than men. Conclusions Asthma hospitalisation and mortality rates have substantially decreased between 2000 and 2014 in Kuwait, with persisting differences between genders, age groups and citizens versus non-citizens. The observed decreasing trends in Kuwait are in agreement with global trends.
The International Journal of Tuberculosis and Lung Disease, 2002
After several decades of continuous decline, the incidence of tuberculosis (TB) has increased ove... more After several decades of continuous decline, the incidence of tuberculosis (TB) has increased over the last 10 years in several regions of the world. No reports have been published describing the epidemiology of TB in Kuwait. To examine the trend of TB in Kuwait from 1965 to 1999 and analyse the factors associated with this trend. Annual reports of the Kuwait central TB unit were examined. Tuberculosis registers recommended by the World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD), which were available for the years 1998 and 1999, were also examined. The notification rate of TB for the whole population has declined from 259 per 100000 in 1965 to 24/100000 in 1999. There has been a steeper decline among Kuwaiti nationals, from 355/100 000 in 1965 to 14/100000 in 1999. The average annual rate of decline in all cases of TB among Kuwaiti nationals was 11.9% from 1965 to 1976, and 11.0% from 1976 to 1989, but there was a slight rise of 4.3% per year from 1989 to 1999. The average annual rate of decline in all cases of TB among non-nationals was 6.3% from 1965 to 1976, and 8.3% from 1976 to 1989, but there was a rise of 2.3% per year from 1989 to 1999. Tuberculosis in Kuwait declined steadily from 1965 to 1989. Since 1989 there has been a slight rise in TB incidence in Kuwait among both Kuwaiti nationals and non-nationals.
To establish a multiplex polymerase chain reaction for detection of mycobacteria and specific ide... more To establish a multiplex polymerase chain reaction for detection of mycobacteria and specific identification of Mycobacterium tuberculosis complex and to evaluate the test in the diagnosis of tuberculosis. Design: Three sets of primers were used to amplify 383 bp, 240 bp and 131 bp DNA fragments from the genes encoding the 65 kDa, MPB64 and the 19 kDa proteins of M. tuberculosis in a single reaction tube. Reaction conditions were optimized with respect to the requirement of DMSO, concentration of MgCI2, annealing and denaturation temperatures and number of amplification cycles. Inhibitory activity in clinical samples was identified by amplifying a 500 bp DNA fragment of the phage lambda along with the mycobacteriai targets within the same reaction tube. The multiplex PCR was evaluated in differentiating M. tuberculosis complex from other mycobacteria and in the diagnosis of tuberculosis by testing clinical specimens. Results: Amplification of the 383 bp DNA fragment was specific to the genus Mycobacterium. The 240 bp DNA fragment was amplified from M. tuberculosis complex and M. fortuitum and the 131 bp DNA fragment was amplified from the mycobacteria of M. tuberculosis complex and M. scrofulaceum. All the three bands were amplified only from M. tuberculosis complex. Applicability of the multiplex PCR is demonstrated in differentiating M. tuberculosis complex from other mycobacteria by using standard strains and clinical isolates. The multiplex PCR was also useful in the detection of inhibitory activity and in the identification of M. tuberculosis complex directly in clinical samples. Conclusion: The multiplex PCR established in this study could differentiate M. tuberculosis complex from other mycobacteria. This test may also be helpful in the early and specific diagnosis of tuberculosis. R E S U Mf~. Objet: Mise au point d'une r6action de polym~risation en chaine (PCR) multiplexe pour la d~tection de mycobact~ries et pour ridentification precise du eomplexe Mycobacterium tuberculosis, et ~vahier cet essai pour le diagnostic de la tubereulose. Schdma: Trois couples d'amorce ont ~t~ utilis~s afin d'amplifier les fragments d'ADN 383 pb, 240 pb et 131 pb partir des g~nes qui codent pour les prot~ines de 65 kDa, MPB64 et 19kDa de M. tuberculosis dans un m~me essai. Les conditions exp~rimentaies out ~t~ optimis~es, concentration en DMSO et MgCI2, temperatures d'appariement et de d~naturation ainsi que le nombre de cycles d'amplification. L'activit~ inhibitrice dans les ~chantillons cliuiques a ~t~ identifi~e en amplifiant un fragment d'ADN de 500 pb du phage lambda ainsi que les s~queuces mycobact~riennes darts le m~me tube de r~action. La PCR multiplexe a ~t~ ~vaiu~e en montrant la differentiation du complexe M. tuberculosis des antres mycobact~ries et par le diagnostic de ia tubereulose par l'examen des ~chantillons eliuiques. Rdsultats: L'amplifieation du fragment ADN de 383 pb est sp6eifique du genre Mycobacterium. L'amplification du fragment d'ADN de 240 pb a ~t~ recherch~ h partir du complexe M. tuberculosis et de M. fortuitum. De la m~me faqon l'amplification du fragment de 131 pb a ~t~ reeherch~e h partir du complexe M. tuberculosis et de M. scrofulaceum. Les trois s6quenees ont ~t~ amplifi~es seulement h partir du complexe M. tuberculosis. L'applicatiou de la PCR multiplexe est d~montr~e par la differentiation du complexe M. tuberculosis des autres mycobact~ries en utillsant des souches et des isolats cliniques standards. La PCR multiplexe a ~gaiement ~t~ utile pour la d~tection de l'activit~ inhibitrice et pour l'identification directe du complexe M. tuberculosis dans des ~chantillons eliuiques.
In recent years, several defined antigens of Mycobacterium tuberculosis have become available eit... more In recent years, several defined antigens of Mycobacterium tuberculosis have become available either by purifying the natural antigens using biochemical procedures, or by producing large quantities of recombinant antigens, using recombinant DNA technology. In this study, we ...
Fiberoptic bronchoscopy is a minimally invasive procedure with a high diagnostic yield. The aim o... more Fiberoptic bronchoscopy is a minimally invasive procedure with a high diagnostic yield. The aim of this study was to document the usefulness of the procedure in the diagnosis of various respiratory disorders in a Middle East country. Data on all bronchoscopies carried out in Chest Diseases Hospital, Kuwait from January 1996 to December 1998 were retrospectively collected. Out of 968 cases, only 620 (64%) patients had a full follow up. Suspected pulmonary tuberculosis (TB) (51.6%), unresolving pneumonia (16.1%), hemoptysis with a normal chest radiograph (8.4%), lung mass (7.7%) and hilar lymphadenopathy (3.2%) were the most common indications. Eleven percent of patients who underwent bronchoscopy had a normal chest radiograph, the reason being hemoptysis in 75.4%, inhalation injury in 21.8% and suspected upper airway obstruction in 2.9%. In smear negative suspected TB cases, 22.5% proved to have active disease. Acid fast bacillus was identified in bronchoalveolar lavage, either by sm...
Though common, the exact incidence and clinical pattern of idiopathic pulmonary fibrosis (IPF) in... more Though common, the exact incidence and clinical pattern of idiopathic pulmonary fibrosis (IPF) in Gulf countries are not known. The results of a four-year prospective study undertaken in two tertiary hospitals in Kuwait are presented. The mean age at diagnosis of the 52 patients studied was 55.40 +/- 11.87 years. Thirty-two (61.5%) patients were male and 22 (42.3%) were smokers. The mean duration of symptoms at diagnosis was 2.1 +/- 0.92 years. Digital clubbing was found in 34 (65%) patients. The mean FVC, TLC and TLCO were 57%, 64.4% and 55% of predicted normal, respectively. The FVC value showed a significant difference between smokers and non-smokers (p < 0.05). HRCT findings were abnormal in all patients. Typical histological and high-resolution computed tomography findings of usual interstitial pneumonia, desquamative interstitial pneumonia and non-specific interstitial pneumonia were observed. This study revealed that IPF is prevalent in Kuwait, with patterns showing some s...
Lobar consolidation in a chest X-ray is often thought to be due to infection. We present the prob... more Lobar consolidation in a chest X-ray is often thought to be due to infection. We present the problem of a 66-year-old female with low grade non-Hodgkin's lymphoma of the mucosa associated lymphoid tissue (MALT) type who had features of lobar consolidation that persisted for years. The different causes, both infectious and non-infectious, of this kind of presentation are discussed.
Tuberculosis is a worldwide health problem of major concern. Direct detection of Mycobacterium tu... more Tuberculosis is a worldwide health problem of major concern. Direct detection of Mycobacterium tuberculosis in clinical specimens is the best approach to identify the causative agent. Identification of M. tuberculosis by culture is the gold standard, but the results are delayed for days to weeks. Microscopic examination of smears is quite fast, but a sample must contain a large number of M. tuberculosis (> 7.5 x 10(3) organisms/ml) for smear positivity. To diagnose tuberculosis specifically within 1 d of receiving clinical specimens, we have established multiplex polymerase chain reaction (MPCR) assays by targeting DNA fragments in the genes present in single or multiple copies in the M. tuberculosis genome. The MPCR results are available within a few hours, and the detection limit for different targets ranges between 2 and 200 organisms. The targets selected in the MPCRs could differentiate between M. tuberculosis complex and other mycobacteria from culture-grown specimens. The ...
Interleukin-8 (IL-8) is considered as the major polymorphonuclear neutrophils (PMNs) chemoattract... more Interleukin-8 (IL-8) is considered as the major polymorphonuclear neutrophils (PMNs) chemoattractant cytokine in lung diseases such as asthma and adult respiratory distress syndrome (ARDS). However, controversial results were obtained regarding the involvement of IL-8 in the pathogenesis of pneumonia. This study examines the role of IL-8 in the recruitment and activation of PMNs in the lung of pneumonia patients. The
Touchdown double-repetitive-element-PCR (DRE-PCR) was carried out for typing 38 consecutive isoni... more Touchdown double-repetitive-element-PCR (DRE-PCR) was carried out for typing 38 consecutive isoniazid-resistant Mycobacterium tuberculosis strains isolated at Chest Diseases Hospital, Kuwait, during 1998-2000. The polymorphism at codon 463 in the katG gene was also determined and correlated with genotypic relationships among the isolates. The isolates exhibited 21 distinct patterns in DRE-PCR. Nearly half of the isolates (18 of 38) exhibited unique patterns. Majority of isolates (16 of 20) yielding multiple DNA fragments in DRE-PCR were unique strains while most of the isolates (16 of 18) yielding a single DNA fragment in DRE-PCR clustered together. The prevalence of L463 in the katG gene was much higher in isolates from Middle Eastern (mostly Kuwaiti) patients than is reported for this ethnic group. The data indicate the possibility of some strains of South Asian/Southeast Asian origin spreading among local populations.
We have used a synthetic-peptide approach to map epitope regions of the Mycobacterium tuberculosi... more We have used a synthetic-peptide approach to map epitope regions of the Mycobacterium tuberculosis ESAT-6 antigen recognized by human T cells in relation to major histocompatibility complex (MHC) restriction. ESAT-6-specific CD4+ T-cell lines were established by stimulating peripheral blood mononuclear cells from 25 HLA-DR-typed tuberculosis patients with complete antigen in vitro. The established T-cell lines were then screened for proliferation and interferon-gamma (IFN-gamma) secretion in response to eight overlapping 20-mer peptides covering the ESAT-6 sequence. The response of the T-cell lines to ESAT-6 and peptides from a human leucocyte antigen (HLA)-heterogeneous group of donors suggested the presence of multiple epitopes and promiscuous recognition of the antigen. Analysis of antigen and peptide recognition in the presence of anti-HLA class I and class II antibodies suggested that the T-cell lines recognized ESAT-6 in association with HLA-DR and -DQ molecules. Furthermore, testing of selected T-cell lines with ESAT-6 and the peptides in the presence of autologous and allogeneic HLA-DR- and -DQ-typed antigen-presenting cells identified HLA-DR2, -DR52 and -DQ2 amongst the HLA molecules involved in the presentation of ESAT-6 and its peptides to human Th1 cells. In addition, the T-cell lines were cytotoxic for monocytes and macrophages pulsed with ESAT-6 and peptides. In conclusion, the recognition of ESAT-6 by IFN-gamma-secreting and cytotoxic CD4+ T cells in association with frequently expressed HLA class II molecules supports the application of this antigen to either specific diagnosis or subunit vaccine design.
We have screened peripheral blood mononuclear cells (PBMC) from tuberculosis (TB) patients for pr... more We have screened peripheral blood mononuclear cells (PBMC) from tuberculosis (TB) patients for proliferative reactivity and interferon-gamma (IFN-gamma) secretion against a panel of purified recombinant (r) and natural (n) culture filtrate (rESAT-6, nMPT59, nMPT64 and nMPB70) and somatic-derived (rGroES, rPstS, rGroEL and rDnaK) antigens of Mycobacterium tuberculosis. The responses of PBMC to these defined antigens were compared with the corresponding results obtained with complex antigens, such as whole-cell M. tuberculosis, M. tuberculosis culture filtrate (MT-CF) and cell wall antigens, as well as the vaccine strain, Mycobacterium bovis bacillus Calmette-Guerin (BCG). In addition, M. tuberculosis and MT-CF-induced T-cell lines were tested in the same assays against the panel of purified and complex antigens. The compiled data from PBMC and T-cell lines tested for antigen-induced proliferation and IFN-gamma secretion showed that the most frequently recognized antigen was ESAT-6, followed by MPT59, GroES, MPB70, MPT64, DnaK, GroEL and PstS. The frequency of ESAT-6 responders, as measured both by proliferation (18/19) and secretion of IFN-gamma (16/19) was comparable to the results obtained with whole-cell M. tuberculosis, MT-CF and M. bovis BCG. We also observed that most of the high responders to complex antigens recognized all of the antigens tested (covariation), demonstrating that the repertoire of human T-cell specificities induced by natural infection is directed towards several unrelated culture filtrate as well as somatic-derived protein antigens. In conclusion, the results obtained suggest that the cellular immune response in humans is directed against several important target antigens of M. tuberculosis and that some antigens, such as ESAT-6, are recognized by a high number of individuals. Such antigens represent candidates to be used for development of specific diagnostic reagents or in subunit vaccines.
This article is concerned with the liability of search engines for algorithmically produced searc... more This article is concerned with the liability of search engines for algorithmically produced search suggestions, such as through Google's 'autocomplete' function. Liability in this context may arise when automatically generated associations have an offensive or defamatory meaning, or may even induce infringement of intellectual property rights. The increasing number of cases that have been brought before courts all over the world puts forward questions on the conflict of fundamental freedoms of speech and access to information on the one hand, and personality rights of individualsunder a broader right of informational self-determination-on the other. In the light of the recent judgment of the Court of Justice of the European Union (EU) in Google Spain v AEPD, this article concludes that many requests for removal of suggestions including private individuals' information will be successful on the basis of EU data protection law, even absent prejudice to the person concerned. K E Y W OR D S : ISP liability; defamation; data protection; trade mark infringement; intellectual property; freedom of speech; false light; right to be forgotten
Tuberculin test (purified protein derivative) is currently accepted as a standard investigation u... more Tuberculin test (purified protein derivative) is currently accepted as a standard investigation used in the diagnosis of tuberculosis (TB). Although the sensitivity of the test is reliable, a substantial number of those subjected to screening for TB by such test are cigarette smokers. This study is designed to investigate the effect of smoking on cellmediated delayed-type cellular hypersensitivity (DTH) reaction by PPD.Prospective, case-control study was conducted at the Chest and TB unit of Chest Hospital Kuwait.The study population consisted of 357 healthy volunteers serving as controls and 200 in-patients under direct medical supervision and treatment for tuberculosis as cases.The mean age was 33.69 7 8.6 SD; 286 were current smokers and 271 were lifetime non-smokers. PPD test was done using 2TU RT23 SSIFDenmark on all subjects. Median PPD was significant among the cases (P=0.03) between smokers and non-smokers and was highly significant among the healthycontrols (Po0.001).No significantdifference was seen between median pack years of smoking and PPD levels among the patient group (P=0.264), but the difference was significant among the controlgroup (Po0.001).Univariate analysis of variance (ANOVA) on PPD, takinginto account age, pack years of smoking, ethnic groups and BCG scar showed sufficient response but was not statistically significant to all these factors. Smoking habit does not appear to influence the cutaneous delayed type hypersensitivity reaction by tuberculin skin test.
Poster presentations Vaccine strategies 293 Lung RSV titers were significantly reduced in mice im... more Poster presentations Vaccine strategies 293 Lung RSV titers were significantly reduced in mice immunized with the F/M2: El-95 chimetic peptkte compared to control mice. Conclusion: lntranasal immunization with a synthetic peptide vaccine without adjuvant resulted in induction of cytotoxic T cell responses and in reduction of RSV titer. non-toxic and which will be capable of inducing lifelong protective immunity against all known variants of HBV in humans. Matetlals and Methods: Antibody to the Hepatitis B surface antigen (HB-sAg) provides protective immunity against HBV. with amino acid regions 160-l 71 and 13*147 considered to represent a T-cell and a B-cell epitope. A 46 amino acid peptide (sl21-167) representtna amino acids 121-167 of the Heo-P.4.01.28 atitis B surf& antisen (adw2 sequence) w& selected as a potential syntheic T cell epltopes from the secreted 84. fube~~~/osis 886 antigen (WT59) mapped by antigen specific vaccine candidate and has been synthesised using Fmoc chemistry. Assesshuman T cell lines ment of ~121-167 as an immunogen was carded out in a preliminary in viw~ study using BALB/c mice. Sera collected from the mice was analysed by ELISA
MaterIala and Methods: In order to get more precise information, we have analyzed the intramuscul... more MaterIala and Methods: In order to get more precise information, we have analyzed the intramuscular vaccination with two plasmld DNAs encoding either a mature or a secreted form of the Ag85A protein and compared it to the immunogenicity of an intravenously given live M. bovis BCG vaccine. FteeulB: Significant and comparable Ag85-specific IgG levels of IgGl, IgG2a and IgGPb isotype were detected in sera from mice vaccinated with either mature or secreted Ag85A DNA, whereas BCG-vaccination only induced minimal antibody levels. Vaccination with DNA stimulated comparable levels of IL-2 and IFN-y responses in response to whole BCG culture filtrate and its purtfied Ag85 complex as vaccination with BCG. On the other hand, Thl cytokine production against PPD, BCG cytoplasmic extract and whole BCG bacilli, was cleatiy lower following vaccination with DNA encoding Ag85A than following BCG. A Thl T cell epitope mapping using synthetic 20mer peptides covering the complete mature sequence of Ag85A, indicated that DNA vaccination stimulated a broader IL-2 and IFN-y epitopic repertoire than BCG, albeit that most BCG-triggered epitopes were also recognized following DNA vaccination. The same peptides were recognized following vaccination with DNA encoding the secreted or mature form, and generally responses were strongest against the latter. Moreover, strong CTL activity against Ag85A-transfected P815 cells and peptide-pulsed P815 cells could only be measured following DNA vaccination with ether construct but not after M. bovis BCG infection. Finally, vaccination of guinea pigs with Ag85A encoding DNA induced significant lymphoproliferative responses and antibody production but failed to induce a positive DTH reaction against purified native Ag85, whereas intradermal BCG vaccination did induce a positive DTH reactton but little antibodies or Ag85 specific pmliieration. Conclualon: These results indicate that vaccination with plasmid DNA encoding Ag85A may offer several advantages over classical vaccination with M. bovis BCG by the induction of antibodies of IgGl, IgGPa and lgG2b isotype (which may neutralize the enzymatic mycolyl-transferase activity of Ag85), by the stimulation of a stronger, epitope spreadened but antigenically restricted productton of Thl cytokines, by the absence of DTH induction and by the generation of potent CD8+ CTL responses. 0.4.11.6 Human CD8+ CTL specific for Mycobacterium tlh?rcl4/os/s
Haemoptysis is an alarming symptom, and the management depends upon the aetiology. Emergency mana... more Haemoptysis is an alarming symptom, and the management depends upon the aetiology. Emergency management depends upon localization of the site of bleeding by roentgenogram, computerized chest tompgraphy and bronchoscopy.
Nickel-based superalloys are extensively used in manufacturing hot gas path components in industr... more Nickel-based superalloys are extensively used in manufacturing hot gas path components in industrial gas turbines used for power generation. Specifically, GTD-111DS is one of the widely used alloys used in manufacturing the hot gas path rotating components. These components are subjected to extreme operating environments resulting in creep, oxidation, fatigue of the components during operation. After continued operation, these damage modes need to be repaired and the components go through extensive repair processes, which includes several heat treatments to recover the mechanical properties of the base material (GTD-111DS) lost during operation. The heat treatments used during repair by the different repair vendors can vary a lot in terms of temperature, time and the sequence as well. This study focuses on the understanding the difference in the effects of the heat treatments to the base material (partial solution, full solution, HIP and full solution) in terms of microstructure-mec...
Objectives To examine trends in asthma hospitalisation and mortality rates from 2000 to 2014 in K... more Objectives To examine trends in asthma hospitalisation and mortality rates from 2000 to 2014 in Kuwait according to sex, age and nationality. Methods For this nationwide, retrospective observational study, data from hospital discharge records and death certificates listing asthma as the primary reason for hospitalisation or mortality were obtained from the National Center for Health Information database using International Classification of Diseases, Tenth Revision codes J45 and J46. Trends in sex-adjusted, age-adjusted and nationality-adjusted hospitalisation and mortality rates were examined. Poisson regression models were applied to test for linear trends overtime and estimate adjusted rate ratios and 95% CI. results During the 15-year study period, a total of 43 652 hospitalisations and 484 deaths due to asthma exacerbations were identified. The average annual adjusted rates of asthma hospitalisation and mortality were estimated to be 134.9 (95% CI 131.8 to 138.1) and 2.1 (95% CI 1.8 to 2.4) per 100 000 population, respectively. Hospitalisation rates decreased by 49.5% in the total population (from 180.8 to 91.3 admissions per 100 000 population between 2000 and 2014, p trend <0.001) and by 57.9% in the age group of 5-44 years (from 77.3 to 32.5 admissions per 100 000 population, p trend <0.001). Mortality rates decreased from 4.1 to 0.9 deaths per 100 000 population between 2000 and 2014 in the total population (77.6% decrease, p trend <0.001) and from 0.6 to 0.2 deaths per 100 000 population among those aged 5-44 years (61.9% reduction, p trend =0.005). Kuwaiti compared with non-Kuwaiti subjects had higher risk of asthma hospitalisation and mortality. Among children aged ≤19 years, the risk of hospitalisation was higher in boys compared with girls; however, among adults, women experienced more hospitalisations than men. Conclusions Asthma hospitalisation and mortality rates have substantially decreased between 2000 and 2014 in Kuwait, with persisting differences between genders, age groups and citizens versus non-citizens. The observed decreasing trends in Kuwait are in agreement with global trends.
The International Journal of Tuberculosis and Lung Disease, 2002
After several decades of continuous decline, the incidence of tuberculosis (TB) has increased ove... more After several decades of continuous decline, the incidence of tuberculosis (TB) has increased over the last 10 years in several regions of the world. No reports have been published describing the epidemiology of TB in Kuwait. To examine the trend of TB in Kuwait from 1965 to 1999 and analyse the factors associated with this trend. Annual reports of the Kuwait central TB unit were examined. Tuberculosis registers recommended by the World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD), which were available for the years 1998 and 1999, were also examined. The notification rate of TB for the whole population has declined from 259 per 100000 in 1965 to 24/100000 in 1999. There has been a steeper decline among Kuwaiti nationals, from 355/100 000 in 1965 to 14/100000 in 1999. The average annual rate of decline in all cases of TB among Kuwaiti nationals was 11.9% from 1965 to 1976, and 11.0% from 1976 to 1989, but there was a slight rise of 4.3% per year from 1989 to 1999. The average annual rate of decline in all cases of TB among non-nationals was 6.3% from 1965 to 1976, and 8.3% from 1976 to 1989, but there was a rise of 2.3% per year from 1989 to 1999. Tuberculosis in Kuwait declined steadily from 1965 to 1989. Since 1989 there has been a slight rise in TB incidence in Kuwait among both Kuwaiti nationals and non-nationals.
To establish a multiplex polymerase chain reaction for detection of mycobacteria and specific ide... more To establish a multiplex polymerase chain reaction for detection of mycobacteria and specific identification of Mycobacterium tuberculosis complex and to evaluate the test in the diagnosis of tuberculosis. Design: Three sets of primers were used to amplify 383 bp, 240 bp and 131 bp DNA fragments from the genes encoding the 65 kDa, MPB64 and the 19 kDa proteins of M. tuberculosis in a single reaction tube. Reaction conditions were optimized with respect to the requirement of DMSO, concentration of MgCI2, annealing and denaturation temperatures and number of amplification cycles. Inhibitory activity in clinical samples was identified by amplifying a 500 bp DNA fragment of the phage lambda along with the mycobacteriai targets within the same reaction tube. The multiplex PCR was evaluated in differentiating M. tuberculosis complex from other mycobacteria and in the diagnosis of tuberculosis by testing clinical specimens. Results: Amplification of the 383 bp DNA fragment was specific to the genus Mycobacterium. The 240 bp DNA fragment was amplified from M. tuberculosis complex and M. fortuitum and the 131 bp DNA fragment was amplified from the mycobacteria of M. tuberculosis complex and M. scrofulaceum. All the three bands were amplified only from M. tuberculosis complex. Applicability of the multiplex PCR is demonstrated in differentiating M. tuberculosis complex from other mycobacteria by using standard strains and clinical isolates. The multiplex PCR was also useful in the detection of inhibitory activity and in the identification of M. tuberculosis complex directly in clinical samples. Conclusion: The multiplex PCR established in this study could differentiate M. tuberculosis complex from other mycobacteria. This test may also be helpful in the early and specific diagnosis of tuberculosis. R E S U Mf~. Objet: Mise au point d'une r6action de polym~risation en chaine (PCR) multiplexe pour la d~tection de mycobact~ries et pour ridentification precise du eomplexe Mycobacterium tuberculosis, et ~vahier cet essai pour le diagnostic de la tubereulose. Schdma: Trois couples d'amorce ont ~t~ utilis~s afin d'amplifier les fragments d'ADN 383 pb, 240 pb et 131 pb partir des g~nes qui codent pour les prot~ines de 65 kDa, MPB64 et 19kDa de M. tuberculosis dans un m~me essai. Les conditions exp~rimentaies out ~t~ optimis~es, concentration en DMSO et MgCI2, temperatures d'appariement et de d~naturation ainsi que le nombre de cycles d'amplification. L'activit~ inhibitrice dans les ~chantillons cliuiques a ~t~ identifi~e en amplifiant un fragment d'ADN de 500 pb du phage lambda ainsi que les s~queuces mycobact~riennes darts le m~me tube de r~action. La PCR multiplexe a ~t~ ~vaiu~e en montrant la differentiation du complexe M. tuberculosis des antres mycobact~ries et par le diagnostic de ia tubereulose par l'examen des ~chantillons eliuiques. Rdsultats: L'amplifieation du fragment ADN de 383 pb est sp6eifique du genre Mycobacterium. L'amplification du fragment d'ADN de 240 pb a ~t~ recherch~ h partir du complexe M. tuberculosis et de M. fortuitum. De la m~me faqon l'amplification du fragment de 131 pb a ~t~ reeherch~e h partir du complexe M. tuberculosis et de M. scrofulaceum. Les trois s6quenees ont ~t~ amplifi~es seulement h partir du complexe M. tuberculosis. L'applicatiou de la PCR multiplexe est d~montr~e par la differentiation du complexe M. tuberculosis des autres mycobact~ries en utillsant des souches et des isolats cliniques standards. La PCR multiplexe a ~gaiement ~t~ utile pour la d~tection de l'activit~ inhibitrice et pour l'identification directe du complexe M. tuberculosis dans des ~chantillons eliuiques.
In recent years, several defined antigens of Mycobacterium tuberculosis have become available eit... more In recent years, several defined antigens of Mycobacterium tuberculosis have become available either by purifying the natural antigens using biochemical procedures, or by producing large quantities of recombinant antigens, using recombinant DNA technology. In this study, we ...
Fiberoptic bronchoscopy is a minimally invasive procedure with a high diagnostic yield. The aim o... more Fiberoptic bronchoscopy is a minimally invasive procedure with a high diagnostic yield. The aim of this study was to document the usefulness of the procedure in the diagnosis of various respiratory disorders in a Middle East country. Data on all bronchoscopies carried out in Chest Diseases Hospital, Kuwait from January 1996 to December 1998 were retrospectively collected. Out of 968 cases, only 620 (64%) patients had a full follow up. Suspected pulmonary tuberculosis (TB) (51.6%), unresolving pneumonia (16.1%), hemoptysis with a normal chest radiograph (8.4%), lung mass (7.7%) and hilar lymphadenopathy (3.2%) were the most common indications. Eleven percent of patients who underwent bronchoscopy had a normal chest radiograph, the reason being hemoptysis in 75.4%, inhalation injury in 21.8% and suspected upper airway obstruction in 2.9%. In smear negative suspected TB cases, 22.5% proved to have active disease. Acid fast bacillus was identified in bronchoalveolar lavage, either by sm...
Though common, the exact incidence and clinical pattern of idiopathic pulmonary fibrosis (IPF) in... more Though common, the exact incidence and clinical pattern of idiopathic pulmonary fibrosis (IPF) in Gulf countries are not known. The results of a four-year prospective study undertaken in two tertiary hospitals in Kuwait are presented. The mean age at diagnosis of the 52 patients studied was 55.40 +/- 11.87 years. Thirty-two (61.5%) patients were male and 22 (42.3%) were smokers. The mean duration of symptoms at diagnosis was 2.1 +/- 0.92 years. Digital clubbing was found in 34 (65%) patients. The mean FVC, TLC and TLCO were 57%, 64.4% and 55% of predicted normal, respectively. The FVC value showed a significant difference between smokers and non-smokers (p < 0.05). HRCT findings were abnormal in all patients. Typical histological and high-resolution computed tomography findings of usual interstitial pneumonia, desquamative interstitial pneumonia and non-specific interstitial pneumonia were observed. This study revealed that IPF is prevalent in Kuwait, with patterns showing some s...
Lobar consolidation in a chest X-ray is often thought to be due to infection. We present the prob... more Lobar consolidation in a chest X-ray is often thought to be due to infection. We present the problem of a 66-year-old female with low grade non-Hodgkin's lymphoma of the mucosa associated lymphoid tissue (MALT) type who had features of lobar consolidation that persisted for years. The different causes, both infectious and non-infectious, of this kind of presentation are discussed.
Tuberculosis is a worldwide health problem of major concern. Direct detection of Mycobacterium tu... more Tuberculosis is a worldwide health problem of major concern. Direct detection of Mycobacterium tuberculosis in clinical specimens is the best approach to identify the causative agent. Identification of M. tuberculosis by culture is the gold standard, but the results are delayed for days to weeks. Microscopic examination of smears is quite fast, but a sample must contain a large number of M. tuberculosis (> 7.5 x 10(3) organisms/ml) for smear positivity. To diagnose tuberculosis specifically within 1 d of receiving clinical specimens, we have established multiplex polymerase chain reaction (MPCR) assays by targeting DNA fragments in the genes present in single or multiple copies in the M. tuberculosis genome. The MPCR results are available within a few hours, and the detection limit for different targets ranges between 2 and 200 organisms. The targets selected in the MPCRs could differentiate between M. tuberculosis complex and other mycobacteria from culture-grown specimens. The ...
Interleukin-8 (IL-8) is considered as the major polymorphonuclear neutrophils (PMNs) chemoattract... more Interleukin-8 (IL-8) is considered as the major polymorphonuclear neutrophils (PMNs) chemoattractant cytokine in lung diseases such as asthma and adult respiratory distress syndrome (ARDS). However, controversial results were obtained regarding the involvement of IL-8 in the pathogenesis of pneumonia. This study examines the role of IL-8 in the recruitment and activation of PMNs in the lung of pneumonia patients. The
Touchdown double-repetitive-element-PCR (DRE-PCR) was carried out for typing 38 consecutive isoni... more Touchdown double-repetitive-element-PCR (DRE-PCR) was carried out for typing 38 consecutive isoniazid-resistant Mycobacterium tuberculosis strains isolated at Chest Diseases Hospital, Kuwait, during 1998-2000. The polymorphism at codon 463 in the katG gene was also determined and correlated with genotypic relationships among the isolates. The isolates exhibited 21 distinct patterns in DRE-PCR. Nearly half of the isolates (18 of 38) exhibited unique patterns. Majority of isolates (16 of 20) yielding multiple DNA fragments in DRE-PCR were unique strains while most of the isolates (16 of 18) yielding a single DNA fragment in DRE-PCR clustered together. The prevalence of L463 in the katG gene was much higher in isolates from Middle Eastern (mostly Kuwaiti) patients than is reported for this ethnic group. The data indicate the possibility of some strains of South Asian/Southeast Asian origin spreading among local populations.
We have used a synthetic-peptide approach to map epitope regions of the Mycobacterium tuberculosi... more We have used a synthetic-peptide approach to map epitope regions of the Mycobacterium tuberculosis ESAT-6 antigen recognized by human T cells in relation to major histocompatibility complex (MHC) restriction. ESAT-6-specific CD4+ T-cell lines were established by stimulating peripheral blood mononuclear cells from 25 HLA-DR-typed tuberculosis patients with complete antigen in vitro. The established T-cell lines were then screened for proliferation and interferon-gamma (IFN-gamma) secretion in response to eight overlapping 20-mer peptides covering the ESAT-6 sequence. The response of the T-cell lines to ESAT-6 and peptides from a human leucocyte antigen (HLA)-heterogeneous group of donors suggested the presence of multiple epitopes and promiscuous recognition of the antigen. Analysis of antigen and peptide recognition in the presence of anti-HLA class I and class II antibodies suggested that the T-cell lines recognized ESAT-6 in association with HLA-DR and -DQ molecules. Furthermore, testing of selected T-cell lines with ESAT-6 and the peptides in the presence of autologous and allogeneic HLA-DR- and -DQ-typed antigen-presenting cells identified HLA-DR2, -DR52 and -DQ2 amongst the HLA molecules involved in the presentation of ESAT-6 and its peptides to human Th1 cells. In addition, the T-cell lines were cytotoxic for monocytes and macrophages pulsed with ESAT-6 and peptides. In conclusion, the recognition of ESAT-6 by IFN-gamma-secreting and cytotoxic CD4+ T cells in association with frequently expressed HLA class II molecules supports the application of this antigen to either specific diagnosis or subunit vaccine design.
We have screened peripheral blood mononuclear cells (PBMC) from tuberculosis (TB) patients for pr... more We have screened peripheral blood mononuclear cells (PBMC) from tuberculosis (TB) patients for proliferative reactivity and interferon-gamma (IFN-gamma) secretion against a panel of purified recombinant (r) and natural (n) culture filtrate (rESAT-6, nMPT59, nMPT64 and nMPB70) and somatic-derived (rGroES, rPstS, rGroEL and rDnaK) antigens of Mycobacterium tuberculosis. The responses of PBMC to these defined antigens were compared with the corresponding results obtained with complex antigens, such as whole-cell M. tuberculosis, M. tuberculosis culture filtrate (MT-CF) and cell wall antigens, as well as the vaccine strain, Mycobacterium bovis bacillus Calmette-Guerin (BCG). In addition, M. tuberculosis and MT-CF-induced T-cell lines were tested in the same assays against the panel of purified and complex antigens. The compiled data from PBMC and T-cell lines tested for antigen-induced proliferation and IFN-gamma secretion showed that the most frequently recognized antigen was ESAT-6, followed by MPT59, GroES, MPB70, MPT64, DnaK, GroEL and PstS. The frequency of ESAT-6 responders, as measured both by proliferation (18/19) and secretion of IFN-gamma (16/19) was comparable to the results obtained with whole-cell M. tuberculosis, MT-CF and M. bovis BCG. We also observed that most of the high responders to complex antigens recognized all of the antigens tested (covariation), demonstrating that the repertoire of human T-cell specificities induced by natural infection is directed towards several unrelated culture filtrate as well as somatic-derived protein antigens. In conclusion, the results obtained suggest that the cellular immune response in humans is directed against several important target antigens of M. tuberculosis and that some antigens, such as ESAT-6, are recognized by a high number of individuals. Such antigens represent candidates to be used for development of specific diagnostic reagents or in subunit vaccines.
This article is concerned with the liability of search engines for algorithmically produced searc... more This article is concerned with the liability of search engines for algorithmically produced search suggestions, such as through Google's 'autocomplete' function. Liability in this context may arise when automatically generated associations have an offensive or defamatory meaning, or may even induce infringement of intellectual property rights. The increasing number of cases that have been brought before courts all over the world puts forward questions on the conflict of fundamental freedoms of speech and access to information on the one hand, and personality rights of individualsunder a broader right of informational self-determination-on the other. In the light of the recent judgment of the Court of Justice of the European Union (EU) in Google Spain v AEPD, this article concludes that many requests for removal of suggestions including private individuals' information will be successful on the basis of EU data protection law, even absent prejudice to the person concerned. K E Y W OR D S : ISP liability; defamation; data protection; trade mark infringement; intellectual property; freedom of speech; false light; right to be forgotten
Tuberculin test (purified protein derivative) is currently accepted as a standard investigation u... more Tuberculin test (purified protein derivative) is currently accepted as a standard investigation used in the diagnosis of tuberculosis (TB). Although the sensitivity of the test is reliable, a substantial number of those subjected to screening for TB by such test are cigarette smokers. This study is designed to investigate the effect of smoking on cellmediated delayed-type cellular hypersensitivity (DTH) reaction by PPD.Prospective, case-control study was conducted at the Chest and TB unit of Chest Hospital Kuwait.The study population consisted of 357 healthy volunteers serving as controls and 200 in-patients under direct medical supervision and treatment for tuberculosis as cases.The mean age was 33.69 7 8.6 SD; 286 were current smokers and 271 were lifetime non-smokers. PPD test was done using 2TU RT23 SSIFDenmark on all subjects. Median PPD was significant among the cases (P=0.03) between smokers and non-smokers and was highly significant among the healthycontrols (Po0.001).No significantdifference was seen between median pack years of smoking and PPD levels among the patient group (P=0.264), but the difference was significant among the controlgroup (Po0.001).Univariate analysis of variance (ANOVA) on PPD, takinginto account age, pack years of smoking, ethnic groups and BCG scar showed sufficient response but was not statistically significant to all these factors. Smoking habit does not appear to influence the cutaneous delayed type hypersensitivity reaction by tuberculin skin test.
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