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author:("sheer, S.")
1.  Extra-pulmonary primary multidrug-resistant tubercular lymphadenitis in an HIV negative patient 
BMJ Case Reports  2012;2012:bcr0620114337.
A 28-year-old woman without any history of prior antituberculosis treatment presented with cervical lymphadenopathy and a cold abscess near medial end of clavicle of 5 months duration. Pus culture and sensitivity revealed Mycobacterium tuberculosis resistant to rifampicin and isoniazid. Thus she was diagnosed as a case of primary multidrug-resistant tuberculosis and treated with second line drugs according to culture susceptibility pattern. On completion of therapy, patent showed good clinical response. This case highlights the observation that even extra-pulmonary primary multidrug-resistant tuberculosis can be successfully treated with currently available second line drugs.
PMCID: PMC3351637  PMID: 22605844
3.  Swyer–James–MacLeod syndrome with ipsilateral herniation of hyperinflated hyperlucent lung 
BMJ Case Reports  2011;2011:bcr0520114191.
Swyer–James–MacLeod syndrome is characterised by unilateral hyperlucency on chest radiograph with small or normal-sized lung on the affected side and compensatory hyperinflation of opposite lung. Hyperinflation of the affected lung is a very rarely reported entity. An adult female patient, who presented with exertional breathlessness and diagnosed to have hypoplastic left pulmonary artery with hyperlucent, hyperinflated and herniated left lung is described.
PMCID: PMC3176363  PMID: 22679043
4.  Correlation between Phylogroups and Intracellular Proteomes of Propionibacterium acnes and Differences in the Protein Expression Profiles between Anaerobically and Aerobically Grown Cells 
BioMed Research International  2013;2013:151797.
Propionibacterium acnes is one of the dominant commensals on the human skin and also an opportunistic pathogen in relation to acne, sarcoidosis, prostate cancer, and various infections. Recent investigations using housekeeping and virulence genes have revealed that the species consists of three major evolutionary clades (types I, II, and III). In order to investigate protein expression differences between these phylogroups, proteomic profiles of 21 strains of P. acnes were investigated. The proteins extracted from cells cultured under anaerobic and aerobic conditions were analysed using a SELDI-TOF mass spectrometer, high-resolution capillary gel electrophoresis, and LC-MS/ MS. The SELDI spectral profiles were visualised as a heat map and a dendrogram, which resulted in four proteomic groups. Strains belonging to type I were represented in the proteome Group A, while Group B contained type III strains. Groups C and D contained mixtures of types I and II. Each of these groups was not influenced by differences in culture conditions. Under anoxic growth conditions, a type IB strain yielded high expressions of some proteins, such as methylmalonyl-CoA epimerase and the Christie-Atkins-Munch-Petersen (CAMP) factor. The present study revealed good congruence between genomic and proteomic data suggesting that the microenvironment of each subtype may influence protein expression.
PMCID: PMC3708387  PMID: 23878795
5.  Bilateral nodular pulmonary tuberculomas simulating metastatic disease 
BMJ Case Reports  2011;2011:bcr1120103539.
A 62-year-old lady presented with bilateral nodular lung opacities suspicious of metastatic disease on chest radiography and high-resolution CT. Histopathology, however, revealed caseating granulomas. The correct diagnosis of tuberculosis (TB) was confirmed when she responded clinically and radiologically to antitubercular treatment. TB should be considered in the differential diagnosis of bilateral nodular opacities which is the usual presentation of secondary malignancies of lung.
PMCID: PMC3079501  PMID: 22701010
6.  Pyopneumothorax Secondary to Aspergillus Infection: A Case Report 
Oman Medical Journal  2012;27(6):494-496.
A 32 -year- old male presented with complaints of fever, dry cough, breathlessness and right sided chest pain of two months duration. Chest radiograph showed right sided hydropneumothorax which revealed frank pus on diagnostic thoracocentesis, for which tube thoracostomy was done. Despite vigorous broad spectrum antibiotic coverage, postural drainage and chest physiotherapy, there was no clinical improvement. Further work up included serology, pleural fluid culture, closed as well as thoracoscopic guided pleural biopsy revealed growth of Aspergillus fumigatus. Patient was prescribed antifungal medication (Voriconazole) and subsequent thoracotomy with right sided pneumonectomy showed good clinical recovery.
PMCID: PMC3515036  PMID: 23226822
Aspergillosis; Aspergillus fumigatus; Aspergillus pyopneumothorax
7.  Poland sequence: Series of two cases and brief review of the literature 
Annals of Thoracic Medicine  2012;7(2):110-112.
Poland sequence is a rare congenital anomaly involving the chest wall and arm, displaying differing degrees of severity, functional and aesthetic impairments. Here we report a series of two cases that presented to us with this anomaly. These cases illustrate, for physicians, the importance of physical diagnosis and reinforce the practice of looking for additional anomalies when one is discovered.
PMCID: PMC3339202  PMID: 22558018
Aesthetic impairments; congenital anomalies; Poland sequence; Poland syndrome
8.  Spontaneous Resolution of Massive Spontaneous Tubercular Pneumothorax 
Case Reports in Pulmonology  2012;2011:502639.
A 29-year-old female presented with complaints of fever and productive cough of three weeks duration. Pulmonary tuberculosis was diagnosed bacteriologically and she was prescribed antituberculosis drugs. During follow-up she developed massive pneumothorax, for which patient refused surgical management and was managed conservatively. After six months there was complete spontaneous resolution of pneumothorax. The unusual presentation and unexpected outcome prompted us to report this case.
PMCID: PMC3420441  PMID: 22937428
9.  A comparative study on the clinical and polysomnographic pattern of obstructive sleep apnea among obese and non-obese subjects 
Annals of Thoracic Medicine  2012;7(1):26-30.
This study was designed to compare the pattern of obstructive sleep apnea (OSA) among obese and nonobese subjects regarding clinical and polysomnographic data obtained for a polysomnographic study.
A cross-sectional retrospective descriptive study was conducted by analyzing polysomnographic data in 112 consecutive patients underwent a sleep study at our sleep laboratory from January 2009 to July 2010. Out of them, 81 were diagnosed to have OSA (apnea-hypopnoea Index ≥5). These patients were classified in two groups with body mass index (BMI) < 27.5 kg/m2 as nonobese and BMI≥27.5 kg/m2 as obese. Clinical as well as polysomnographic data were evaluated and compared between the two groups. Patients were also evaluated for other risk factors such as smoking, alcoholism, and use of sedatives. Data were subjected to statistical analysis (χ2-test, P value <0.05 considered to be significant). The Fisher Exact test was applied wherever the expected frequency for a variable was ≤5.
Of 81 patients with OSA, 36 (44.4%) were nonobese with a mean BMI of 26.62 ± 2.29 kg/m2 and 45 (55.6%) were obese with a mean BMI of 35.14 ± 3.74 kg/m2. Mean AHI per hour was significantly more in the obese than in the nonobese group (50.09 ± 29.49 vs. 24.36 ± 12.17, P<0.001). The use of one or more sedatives was more in nonobese as compared to obese (58.3% vs. 24.4%, P=0.002). The obese group had significantly higher desaturation and arousal index (P<0.001). The minimal oxygen saturation was lower in the obese than the nonobese group (68.5 ± 13.00 vs. 80.3 ± 7.40, P<0.001) and was well below 90% in both groups. Overall, the OSA in nonobese patients was mild-to-moderate as compared to that of the obese and no significant differences were observed between them as regard to age, gender, mean neck circumference, excessive daytime sleepiness, adenoid or tonsillar enlargement, smoking, and remaining polysomnographic parameters.
Obstructive sleep apnea can occur in nonobese persons though with less severity as compared to obese leading to a concept that OSA is not restricted to obese persons only and there is a high demand of its awareness regarding evaluation, diagnosis, and management in such individuals.
PMCID: PMC3277037  PMID: 22347347
Body mass index; obesity; obstructive sleep apnea
10.  Ewing’s Sarcoma Presenting as Pleural Effusion 
Oman Medical Journal  2011;26(5):362-364.
A 20-year-old female presented to the Pulmonary Medicine Department with complaints of fever, left sided chest pain and progressive dyspnoea of four months duration. Radiological examination revealed a mass lesion with massive pleural effusion and rib erosion. Histopathology showed neoplastic cells with scanty cytoplasm, hyperchromatic nuclei and rosette formation suggestive of Ewing sarcoma. The rarity of this tumor and its unusual presentation prompted this report.
PMCID: PMC3215445  PMID: 22125734
Ewing's sarcoma; Pleural effusion; Rib
11.  Coherent pipeline for biomarker discovery using mass spectrometry and bioinformatics 
BMC Bioinformatics  2010;11:437.
Robust biomarkers are needed to improve microbial identification and diagnostics. Proteomics methods based on mass spectrometry can be used for the discovery of novel biomarkers through their high sensitivity and specificity. However, there has been a lack of a coherent pipeline connecting biomarker discovery with established approaches for evaluation and validation. We propose such a pipeline that uses in silico methods for refined biomarker discovery and confirmation.
The pipeline has four main stages: Sample preparation, mass spectrometry analysis, database searching and biomarker validation. Using the pathogen Clostridium botulinum as a model, we show that the robustness of candidate biomarkers increases with each stage of the pipeline. This is enhanced by the concordance shown between various database search algorithms for peptide identification. Further validation was done by focusing on the peptides that are unique to C. botulinum strains and absent in phylogenetically related Clostridium species. From a list of 143 peptides, 8 candidate biomarkers were reliably identified as conserved across C. botulinum strains. To avoid discarding other unique peptides, a confidence scale has been implemented in the pipeline giving priority to unique peptides that are identified by a union of algorithms.
This study demonstrates that implementing a coherent pipeline which includes intensive bioinformatics validation steps is vital for discovery of robust biomarkers. It also emphasises the importance of proteomics based methods in biomarker discovery.
PMCID: PMC2939613  PMID: 20796299
12.  Replacing Reverse Line Blot Hybridization Spoligotyping of the Mycobacterium tuberculosis Complex ▿ † ‡  
Journal of Clinical Microbiology  2010;48(5):1520-1526.
Spoligotyping is a tool for the molecular characterization/typing of Mycobacterium tuberculosis complex (MTBC) strains based on target sequences (spacers) in the direct repeat (DR) region (14). The standard spoligotyping assay involves the hybridization of amplified sample DNA to nylon membrane-immobilized oligonucleotides whose sequences are representative of 43 spacer regions. Variations in the number of spacers as a result of deletions of adjacent blocks of repetitive units allow the differentiation of clinical isolates. In the present study, we developed a new multiplexed primer extension-based spoligotyping assay using automated matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) that improves the classical reverse line blot hybridization assay with respect to reproducibility, throughput, process flow, ease of use, and data analysis. Validation of the MALDI-TOF MS-based spoligotyping assay with two sample sets with a total of 326 samples resulted in 96.6% concordance (315/326) when the full spoligotype patterns were compared with the results of standard spoligotyping and 99.9% concordance when the results were compared with those of individual primer extension assays. Ten strains (including two Mycobacterium canettii strains) showed discordant results with one or two spacer differences from the membrane-based spoligotyping result. Most discordant samples were identified to be the result of ambiguities in the interpretation of weak hybridization signals in the reverse line blot assay and sequence variations in the spacer regions. We established a new automated primer extension assay and successfully validated it for use for the routine typing of MTBC strains in the research and public health laboratory environments. The present multiplex levels of up to 30 are extendable and allow the additional incorporation of controls and antibiotic resistance markers.
PMCID: PMC2863940  PMID: 20200291
13.  Multispacer Sequence Typing for Mycobacterium tuberculosis Genotyping 
PLoS ONE  2008;3(6):e2433.
Genotyping methods developed to survey the transmission dynamics of Mycobacterium tuberculosis currently rely on the interpretation of restriction and amplification profiles. Multispacer sequence typing (MST) genotyping is based on the sequencing of several intergenic regions selected after complete genome sequence analysis. It has been applied to various pathogens, but not to M. tuberculosis.
Methods and Findings
In M. tuberculosis, the MST approach yielded eight variable intergenic spacers which included four previously described variable number tandem repeat loci, one single nucleotide polymorphism locus and three newly evaluated spacers. Spacer sequence stability was evaluated by serial subculture. The eight spacers were sequenced in a collection of 101 M. tuberculosis strains from five phylogeographical lineages, and yielded 29 genetic events including 13 tandem repeat number variations (44.82%), 11 single nucleotide mutations (37.93%) and 5 deletions (17.24%). These 29 genetic events yielded 32 spacer alleles or spacer-types (ST) with an index of discrimination of 0.95. The distribution of M. tuberculosis isolates into ST profiles correlated with their assignment into phylogeographical lineages. Blind comparison of a further 93 M. tuberculosis strains by MST and restriction fragment length polymorphism-IS6110 fingerprinting and mycobacterial interspersed repetitive units typing, yielded an index of discrimination of 0.961 and 0.992, respectively. MST yielded 41 different profiles delineating 16 related groups and proved to be more discriminatory than IS6110-based typing for isolates containing <8 IS6110 copies (P<0.0003). MST was successfully applied to 7/10 clinical specimens exhibiting a Cts ≤ 42 cycles in internal transcribed spacer-real time PCR.
These results support MST as an alternative, sequencing-based method for genotyping low IS6110 copy-number M. tuberculosis strains. The M. tuberculosis MST database is freely available (
PMCID: PMC2413405  PMID: 18560597
14.  Proteome analysis of serovars Typhimurium and Pullorum of Salmonella enterica subspecies I 
BMC Microbiology  2005;5:42.
Salmonella enterica subspecies I includes several closely related serovars which differ in host ranges and ability to cause disease. The basis for the diversity in host range and pathogenic potential of the serovars is not well understood, and it is not known how host-restricted variants appeared and what factors were lost or acquired during adaptations to a specific environment. Differences apparent from the genomic data do not necessarily correspond to functional proteins and more importantly differential regulation of otherwise identical gene content may play a role in the diverse phenotypes of the serovars of Salmonella.
In this study a comparative analysis of the cytosolic proteins of serovars Typhimurium and Pullorum was performed using two-dimensional gel electrophoresis and the proteins of interest were identified using mass spectrometry. An annotated reference map was created for serovar Typhimurium containing 233 entries, which included many metabolic enzymes, ribosomal proteins, chaperones and many other proteins characteristic for the growing cell. The comparative analysis of the two serovars revealed a high degree of variation amongst isolates obtained from different sources and, in some cases, the variation was greater between isolates of the same serovar than between isolates with different sero-specificity. However, several serovar-specific proteins, including intermediates in sulphate utilisation and cysteine synthesis, were also found despite the fact that the genes encoding those proteins are present in the genomes of both serovars.
Current microbial proteomics are generally based on the use of a single reference or type strain of a species. This study has shown the importance of incorporating a large number of strains of a species, as the diversity of the proteome in the microbial population appears to be significantly greater than expected. The characterisation of a diverse selection of strains revealed parts of the proteome of S. enterica that alter their expression while others remain stable and allowed for the identification of serovar-specific factors that have so far remained undetected by other methods.
PMCID: PMC1181816  PMID: 16026608
15.  Towards the development of a DNA-sequence based approach to serotyping of Salmonella enterica 
BMC Microbiology  2004;4:31.
The fliC and fljB genes in Salmonella code for the phase 1 (H1) and phase 2 (H2) flagellin respectively, the rfb cluster encodes the majority of enzymes for polysaccharide (O) antigen biosynthesis, together they determine the antigenic profile by which Salmonella are identified. Sequencing and characterisation of fliC was performed in the development of a molecular serotyping technique.
FliC sequencing of 106 strains revealed two groups; the g-complex included those exhibiting "g" or "m,t" antigenic factors, and the non-g strains which formed a second more diverse group. Variation in fliC was characterised and sero-specific motifs identified. Furthermore, it was possible to identify differences in certain H antigens that are not detected by traditional serotyping. A rapid short sequencing assay was developed to target serotype-specific sequence motifs in fliC. The assay was evaluated for identification of H1 antigens with a panel of 55 strains.
FliC sequences were obtained for more than 100 strains comprising 29 different H1 alleles. Unique pyrosequencing profiles corresponding to the H1 component of the serotype were generated reproducibly for the 23 alleles represented in the evaluation panel. Short read sequence assays can now be used to identify fliC alleles in approximately 97% of the 50 medically most important Salmonella in England and Wales. Capability for high throughput testing and automation give these assays considerable advantages over traditional methods.
PMCID: PMC514894  PMID: 15298703

Results 1-15 (15)