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2. A recessive variant in TFAM causes mtDNA depletion associated with primary ovarian insufficiency, seizures, intellectual disability and hearing loss
- Author
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Farid, Ullah, Waqar, Rauf, Kamal, Khan, Sheraz, Khan, Katrina M, Bell, Vanessa Cristina, de Oliveira, Muhammad, Tariq, Shabnam, Bakhshalizadeh, Philippe, Touraine, Nicholas, Katsanis, Andrew, Sinclair, Sijie, He, Elena J, Tucker, Shahid M, Baig, and Erica E, Davis
- Subjects
Male ,Genes, Recessive ,Primary Ovarian Insufficiency ,DNA, Mitochondrial ,Pedigree ,DNA-Binding Proteins ,Mitochondrial Proteins ,Seizures ,Intellectual Disability ,Animals ,Humans ,Female ,Gonads ,Hearing Loss ,Cells, Cultured ,Zebrafish ,Transcription Factors - Abstract
Mitochondrial disorders are collectively common, genetically heterogeneous disorders in both pediatric and adult populations. They are caused by molecular defects in oxidative phosphorylation, failure of essential bioenergetic supply to mitochondria, and apoptosis. Here, we present three affected individuals from a consanguineous family of Pakistani origin with variable seizures and intellectual disability. Both females display primary ovarian insufficiency (POI), while the male shows abnormal sex hormone levels. We performed whole exome sequencing and identified a recessive missense variant c.694C T, p.Arg232Cys in TFAM that segregates with disease. TFAM (mitochondrial transcription factor A) is a component of the mitochondrial replisome machinery that maintains mtDNA transcription and replication. In primary dermal fibroblasts, we show depletion of mtDNA and significantly altered mitochondrial function and morphology. Moreover, we observed reduced nucleoid numbers with significant changes in nucleoid size or shape in fibroblasts from an affected individual compared to controls. We also investigated the effect of tfam impairment in zebrafish; homozygous tfam mutants carrying an in-frame c.141_149 deletion recapitulate the mtDNA depletion and ovarian dysgenesis phenotypes observed in affected humans. Together, our genetic and functional data confirm that TFAM plays a pivotal role in gonad development and expands the repertoire of mitochondrial disease phenotypes.
- Published
- 2021
3. BJS commission on surgery and perioperative care post-COVID-19
- Author
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E. Abahuje, A. Abbas, M. Abd El Aziz Abd El Maksoud, A. Abdelhady, S. Abdelhamid, H. Abdelkarem Ahmed Faraj, B. Abdelqader, T. Abdelrahman, H. Abdou, A. Abdullah, M. Abedua Harrison, E. Abem Owusu, A. Aboalazayem, R. Aboulhosn, S. Abu Oda, A. Abubakar, A. Abutaka, D. Acevedo Fontalvo, S. Acuna, A. Adefemi, S. Adegbola, T. Adenuga, A. Adeyeye, A. Adil Hilmi, A. Adisa, K. Aditya, T. Adjeso, R. Aftab, A. Afzal, V. Aggarwal, A. Aggarwal, R. Aguilera, M. -L. Aguilera-Are´valo, E. J. Aguirre Salamanca, I. Aguirre-Allende, D. Ahari, H. Ahmad, F. Ahmad Rauf, A. Ahmad Zartasht Khan, S. Ahmed, N. Ahmed Fieturi, S. Ahmed Mohamed, Z. Ahmed-Bakhsh, M. Ahsan Javed, L. Akano, A. Akbar, M. Akhbari, P. Akhmedov, G. Aksit, Y. Akula, A. S. Alagaratnam, S. Al Majid, O. Al Mukhtar, H. Al Omran, N. AlAsali, M. Al-Azzawi, R. Al-Habsi, H. Al-Iraqi, H. Al-Naggar, E. Alameer, H. Albirnawi, D. Alderson, F. Aldulaijan, R. Alejandro Miranda Ojeda, A. AlHasan, S. Ali, A. Ali, M. Ali Khan, Y. Alimova, F. Aljanadi, R. Aljubure, N. Allopi, H. Almedbal, M. Almubarak, Z. Alqaidoom, N. Alselaim, M. Alshaar, R. Alshammari, K. Altaf, S. Altıner, B. Altunpak, L. A. Alvarez Lozada, E. Amal Nahal, A. Amer, K. Amin, U. Aminu, N. Amisi Numbi, T. Amjad, R. Amoah, Y. An, N. -A. Anastasopoulos, J. Andre´s Urrutia, F. Angarita, K. -L. Angarita, M. A´ ngel FreirI´a Eiras, A. Antypas, M. A. Anwar, H. Anwar, T. O. Apampa, K. Apostolou, C. Aquina, R. Arachchige Adithi Himika Randeni, M. I. Archila Godı´nez, O. Arez, A. A. Arezzo, P. Armonis, S. Arshad, M. Arshad Salman, A. Arshid, P. C. Arteaga Asensio, T. Arthur, A. Arumuga Jothi, F. Aryo Damara, L. Asensio Gomez, J. Ashcroft, S. Ashraf, A. Asif, M. Atif, M. Attaullah Khan, N. Avellaneda, S. Awad, M. Awadh, A. Axiaq, A. Ayad Mohammed Shuwayyah, D. Ayalew, E. Aytac, F. Azam, J. Azevedo, B. Azhar, J. Aziz, A. Aziz, A. Azzam, A. Baba Ndajiwo, M. Baig, D. Baker, F. Bakko, R. Balachandran, G. Balachandran, J. Balagizi Mudekereza, E. Balai, B. Balci, A. 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Costa, D. Couch, S. Cowper, B. Creavin, B. Crook, A. Curell, R. D’alessio, J. Dale, J. Damgaard Eriksen, I. Dario Martin Gonzalez, A. Darwish, M. Das, R. Das, K. Das, R. Dave, S. O. David, T. Davies, C. Davis, S. Davison, V. Davletshina, A. Dawidziuk, A. Dawson, M. de Andres Crespo, H. de Berker, P. de Dieu Ngo, E. Dekker, R. de la Caridad Espinosa Luis, B. de Lacy, N. Demartines, A. de Montserrat Medina Sifuentes, S. De Silva, C. del Rio, V. Delaune, A. Dell, I. Demirbas¸, S. Demirli Atici, M. Deniz Tepe, M. Derebey, G. Desai, M. Desai, S. Devarakonda, N. Deveras, G. Di Franco, M. Di Martino, F. Di Marzo, A´ . Dı´az, G. Diaz del Gobbo, C. DiazCastrillon, L. Dick, K. Dickinson, E. Diego, I. Dimasi, A. Ding, S. Dingemans, L. Dixon, B. Dixon, W. Doherty, D. Dooreemeah, C. Donohue, M. Dornseifer, F. Dossa, W. Dossou, T. Drake, I. Drami, G. Drevin, M. C. du Plessis, N. Dudi-Venkata, R. Dudley, S. Duffy, D. Duklas, B. -D. Dumbrava, F. Duygu Avlar, A. Dworzynska, W. Ebrahim, A. Ebrahim, E. Efre´n Lozada Herna´ ndez, N. Ehigie, M. El Boghdady, C. El Hasnaoui, M. El Sheikh, A. El-Hussuna, O. Eldurssi, H. Elfeki, M. Elhadi, M. Elhassan, A. Elhissi, B. Elliot, C. Elsenbroek, B. Elsolh, N. Elson, H. Eltyeb, H. Emerson, S. H. Emile, G. Endalle, W. English, C. Ercisli, G. Espinosa, M. Essam Abdelraheem, H. Essangri, P. Etienne, M. D. Evans, T. Evans, C. Ezeme, F. Ezzahraa, T. Fadalla, J. Fagan, M. Fahmy, C. Fairfield, O. Falade, S. Famularo, F. Faqar-Uz-Zaman, Y. Farid, A. Farooq, H. Farooq, F. Farooqui, B. Farquharson, A. Faruqi, R. Faulder, M. Faut, K. Fechner, T. Feenstra, M. Fehervari, L. Fernandez, J. Ferna´ ndez Alberti, L. Ferrario, D. Field, L. Fiore, S. Fingerhut, S. Finlayson, N. Fleming, C. Fleming, E. Florial, M. Fok, D. Fokin, M. Foley, M. P. Forero, T. Forgan, M. Fornasiero, H. Fowler, G. Fowler, E. Franchi, L. Franklin, A˚ . Fredriksson, P. Fruhling, G. Fuentes Navarrette, A. Fu¨ lo¨ p, M. Furtado, T. Gaarder, N. Galbraith, I. T. K. Gallagher, G. Gallo, T. Gana, E. Gaskin, M. Gasparini, R. G. Gatan, E. Geary, K. Gelaye Wudineh, G. Gemenetzis, M. Georgi, H. Ghalige, W. Ghareeb, T. Ghatwary Tantawy, C. Ghomsi, A. Ghuman, P. Giannakis, F. Giron, K. Gjengedal, E. Gkotsis, J. Glasbey, S. Godahewa, D. Godula, P. Goffredo, S. Goh, M. Golriz, L. Gomez, D. Gomez Gomez, R. Gonzalez, D. Gonzalez, E. Gonzalez Gutierrez, D. Gopar, L. Gordini, A. Gori, S. Gorta´ zar, N. Gousy, R. Gowda, M. Gowda, J. Gqada, M. Grechenig, J. Greer, L. Grego´ rio, A. Grigorova, H. Grimes, V. Groot, R. C. Grossman, R. Gruber, A. Gru¨ ter, R. Guest, R. Gujjuri, E. Gu¨ lc¸ek, B. Gulcu, K. Gull, M. Gulmez, V. Gupta, A. Gutlic, T. Guven, T. Gwatirisa, G. Gwini, P. Gwodog, S. Gysling, M. Habib, A. B. Hafeez Bhatti, J. Hallesmith, S. Halloran, M. Hamza Sadiq, C. Haney, N. Hanna, L. Hanna, M. Hannington, J. Harbjerg, D. Haribaskaran, N. Harran, B. Harrington, E. Harrison, R. Hasan, S. Hashmi, M. Hassan, A. Hassan, L. Haverkamp, S. Hazen, B. Heer, J. Heil, J. Helliwell, N. Henriksen, D. Henshall, M. Hermanson, S. Hermena, D. Hettiarachchi, C. Hextall, M. Hidalgo, H. Hidayat, A. Hider, P. Higgins, R. Hinchliffe, D. Hirani, D. Hirpara, I. Hisham, M. Hite, S. M. Hoh, C. Holmberg, E. Ho¨ lmich, F. Holst, A. Hossam, A. Hossam Elfallal, P. Howard, E. Huaman, Y. Huang, L. Huang, D. Huang, T. Huber, J. Hugh, J. Hughes, F. Hu¨ ttner, R. Huynh, A. Hylands, J. Iannuzzi, B. Ielpo, A. Iftikhar Talib, J. Ignacio, P. Ignatavicius, S. Ike, C. Ikwu, M. Inama, A. Ing, A. Ingels, A. Isik, N. Islam, I. J. Ives, A. J. M. S. AlHasan, C. J. Perez Rivera, F. Ja´ come, T. Jaffer, O. Jagiella-Lodise, M. Jain, K. Jain, M. Jakubauskas, M. Jalal, H. James, Y. Jang, B. Janssen, H. Jansson, U´ . Jariod-Ferrer, H. Javanmard, S. Javed, U. Jayarajah, I. Jayasuriya, J. Je, Z. Jessop, E. Jia Lin Tang, H. Jiang, Y. Jiayan, T. Jih Huei, R. Jimenez-Rodriguez, D. Joh, A. Johnson, N. Jones, C. Jones, C. Jordan, J. Jose´ Nu´ nez Ju, ~ M. Jose´ Pizarro, C. Jose Salazar J. Joseph, C. Justiniano, T. Kabir, M. Kadhum, C. Kalfountzos, E. Kalogiannaki, K. Kalyanasundaram, S. Kamarajah, M. Kamil Quraishi, Y. Kanemitsu, A. Kapila, V. Kapila, G. Karagiannidis, M. Kashif, S. Kathiravelupillai, A. Kathiravelupillai, E. Katsogridakis, K. Kaur, H. Kaur Sekhon Inderjit Singh, N. Kausur, M. Kawka, G. Keehan, S. Kehlet Watt, M. Kelly, M. E. Kelly, I. Kelvin Egbuchulem, G. Kembuan, E. Khajeh, A. Khaled Elfaitur, M. F. Khan, S. Khan, M. Khan, D. Khan, H. Khan, H. Khatkar, E. Khatkov, R. Khaw, B. Kim, K. Kishore Siddiraju, D. Kitua, B. Kırımtay, S. Kmezic, S. Knight, T. Koe¨ter, A. Koh, F. Koh Hong Xiang, T. Kojo Anyomih, A. I. N. Kok, R. Kokelaar, I. Koliarakis, S. Kolli, J. Kong, D. Ko¨ nig, M. otze, A. Kourdouli, M. Kowal, A. Kraima, F. Kramer, M. Kryzauskas, I. Kuchynskyi, C. Kuemmerli, S. Kuiper, S. Kumar, A. Kumar, L. Kumar, H. Kumar, N. Kumar, S. Kumar Bandyopadhyay, P. Kumar Garg, S. Kumar Venkatappa, J. Kung, S. Kural, A. Kushairi, E. Kuuzie, M. Kvietkauskas, I. Kwek, J. 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Adult ,Male ,medicine.medical_specialty ,Biomedical Research ,Coronavirus disease 2019 (COVID-19) ,International Cooperation ,Practice Patterns ,Commission ,Global Health ,Health Services Accessibility ,Perioperative Care ,Education ,Surgeon ,COVID-19 ,surgery ,perioperative care ,Medical ,Pandemic ,Humans ,Medicine ,Practice Patterns, Physicians' ,Graduate ,Pandemics ,Surgeons ,Health Resource ,Infection Control ,Physicians' ,Surgical Procedures ,business.industry ,General surgery ,Middle Aged ,Operative ,Education, Medical, Graduate ,Surgical Procedures, Operative ,Perioperative care ,Health Resources ,Surgery ,Female ,business ,Human - Abstract
Background Coronavirus disease 2019 (COVID-19) was declared a pandemic by the WHO on 11 March 2020 and global surgical practice was compromised. This Commission aimed to document and reflect on the changes seen in the surgical environment during the pandemic, by reviewing colleagues’ experiences and published evidence. Methods In late 2020, BJS contacted colleagues across the global surgical community and asked them to describe how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had affected their practice. In addition to this, the Commission undertook a literature review on the impact of COVID-19 on surgery and perioperative care. A thematic analysis was performed to identify the issues most frequently encountered by the correspondents, as well as the solutions and ideas suggested to address them. Results BJS received communications for this Commission from leading clinicians and academics across a variety of surgical specialties in every inhabited continent. The responses from all over the world provided insights into multiple facets of surgical practice from a governmental level to individual clinical practice and training. Conclusion The COVID-19 pandemic has uncovered a variety of problems in healthcare systems, including negative impacts on surgical practice. Global surgical multidisciplinary teams are working collaboratively to address research questions about the future of surgery in the post-COVID-19 era. The COVID-19 pandemic is severely damaging surgical training. The establishment of a multidisciplinary ethics committee should be encouraged at all surgical oncology centres. Innovative leadership and collaboration is vital in the post-COVID-19 era.
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- 2021
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4. Elective cancer surgery in COVID-19–Free surgical pathways during the SARS-cov-2 pandemic: An international, multicenter, comparative cohort study
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J R Tan, A Thomas, P Whelan, A Anzak, A Banerjee, O Fuwa, F Hughes, J D Jayasinghe, C Knowles, H Kocher, I Leal Silva, F S Ledesma, A Minicozzi, L Navaratne, R Rahman, R Ramamoorthy, C Sohrabi, M Thaha, B Thakur, M Venn, V Yip, R Baumber, J Parry, S Evans, L Jeys, G Morris, M Parry, J Stevenson, N Ahmadi, G Aresu, Z M Barrett-Brown, A S Coonar, H Durio Yates, D Gearon, J Hogan, M King, A Peryt, I S Pradeep, C Smith, M Adishesh, R Atherton, K Baxter, M Brocklehurst, M Chaudhury, N Krishnamohan, J McAleer, G Owens, E Parkin, P Patkar, I Phang, A Aladeojebi, M Ali, B Barmayehvar, A Gaunt, M Gowda, E Halliday, M Kitchen, F Mansour, M Thomas, D Zakai, N Abbassi-Ghadi, H Assalaarachchi, A Currie, M Flavin, A Frampton, M Hague, C Hammer, J Hopper, J Horsnell, S Humphries, A Kamocka, T K Madhuri, S Preston, P Singh, J Stebbing, A Tailor, D Walker, F Aljanadi, M Jones, P Mhandu, C O'Donnell, R Turkington, Z Al-Ishaq, S Bhasin, A S Bodla, A Burahee, A Crichton, R Fossett, N Pigadas, S Pickford, E Rahman, D Snee, R Vidya, N Yassin, F Colombo, D Fountain, M T Hasan, K Karabatsou, R Laurente, O Pathmanaban, A Al-Mukhtar, S Brown, J Edwards, A Giblin, C Kelty, M Lee, G Lye, T Newman, A Sharkey, C Steele, N Sureshkumar Shah, E Whitehall, R Athwal, A Baker, L Jones, C Konstantinou, S Ramcharan, S Singh, J Vatish, R Wilkin, M Ethunandan, G K Sekhon, H Shields, R Singh, F Wensley, S Lawday, A Lyons, T Abbott, S Anwar, K Ghufoor, C Sohrabi, E Chung, R Hagger, A Hainsworth, A Karim, H Owen, A Ramwell, K Williams, C Baker, A Davies, J Gossage, M Kelly, W Knight, J Hall, G Harris, G James, C Kang, D J Lin, A D Rajgor, T Royle, R Scurrah, B Steel, L J Watson, D Choi, R Hutchison, A Jain, V Luoma, H Marcus, R May, A Menon, B Pramodana, L Webber, I A Aneke, P Asaad, B Brown, J Collis, S Duff, A Khan, F Moura, B Wadham, H Warburton, T Elmoslemany, M Jenkinson, C Millward, R Zakaria, S Mccluney, C Parmar, S Shah, J Allison, M S Babar, B Collard, S Goodrum, K Lau, A Patel, R Scott, E Thomas, H Whitmore, D Balasubramaniam, B Jayasankar, S Kapoor, A Ramachandran, A Elhamshary, Smb Imam, K Kapriniotis, V Kasivisvanathan, J Lindsay, S Rakhshani-Moghadam, N Beech, M Chand, L Green, N Kalavrezos, H Kiconco, R McEwen, C Schilling, D Sinha, J Pereca, J Singh, S Chopra, D Egbeare, R Thomas, T Combellack, Sef Jones, M Kornaszewska, M Mohammed, A Sharma, G Tahhan, V Valtzoglou, J Williams, P Eskander, K Gash, L Gourbault, M Hanna, T Maccabe, C Newton, J Olivier, S Rozwadowski, E Teh, D West, H Al-Omishy, M Baig, H Bates, G Di Taranto, K Dickson, N Dunne, C Gill, D Howe, D Jeevan, A Khajuria, K Martin-Ucar AMcEvoy, P Naredla, V Ng, S Robertson, M Sait, D R Sarma, S Shanbhag, T Shortland, S Simmonds, J Skillman, N Tewari, G Walton, M A Akhtar, A Brunt, J McIntyre, K Milne, M M Rashid, A Sgro, K E Stewart, A Turnbull, M Aguilar Gonzalez, S Talukder, C Boyle, D Fernando, K Gallagher, A Laird, D Tham, M Bath, P Patki, C Sohrabi, C Tanabalan, T Arif, C Magee, T Nambirajan, S Powell, R Vinayagam, I Flindall, A Hanson, V Mahendran, S Green, M Lim, L MacDonald, V Miu, L Onos, K Sheridan, R Young, F Alam, O Griffiths, C Houlden, R Jones, V S Kolli, A K Lala, S Leeson, R Peevor, Z Seymour, L Chen, E Henderson, A Loehrer, K Brown, D Fleming, A Haynes, C Heron, C Hill, H Kay, E Leede, K McElhinney, K Olson, E C Osterberg, C Riley, P Srikanth, M Thornhill, D Blazer, G DiLalla, E S Hwang, W Lee, M Lidsky, J Plichta, L Rosenberger, R Scheri, K Shah, K Turnage, J Visgauss, S Zani, J Farma, J Clark, D Kwon, E Etchill, H E Gabre-Kidan AJenny, A Kent, M Ladd, C Long, H Malapati, A Margalit, S Rapaport, J Rose, K Stevens, L Tsai, D Vervoort, P Yesantharao, A Dehal, D Klaristenfeld, K Huynh, L Brown, I Ganly, J Mullinax, N Gusani, J Hazelton, J Maines, J S Oh, A Ssentongo, P Ssentongo, M Azam, A Choudhry, W Marx, J Fleming, A Fuson, J Gigliotti, A Ovaitt, Y Ying, M K Abel, V Andaya, K Bigay, M A Boeck, L Chen, H Chern, C Corvera, I El-Sayed, A Glencer, P Ha, Bcs Hamilton, C Heaton, K Hirose, D M Jablons, K Kirkwood, L Z Kornblith, J R Kratz, R Lee, P N Miller, E Nakakura, B Nunez-Garcia, R O'Donnell, D Ozgediz, P Park, B Robinson, A Sarin, B Sheu, M Varma, K Wai, R Wustrack, M J Xu, D Beswick, J Goddard, J Manor, J Song, T Fullmer, C Gaskill, N Gross, K Kiong, C L Roland, S N Zafar, M Abdallah, A Abouassi, M Almasri, G Kulkarni, H Marwan, M Mehdi, S Aoun, V S Ban, H H Batjer, J Caruso, D Abbott, A Acher, T Aiken, J Barrett, E Foley, P Schwartz, S N Zafar, A Hawkins, A Maiga, J Laufer, S Scasso
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Aged, 80 and over ,Male ,Critical Care ,SARS-CoV-2 ,International Cooperation ,COVID-19 ,Middle Aged ,Cohort Studies ,Logistic Models ,Postoperative Complications ,Elective Surgical Procedures ,Neoplasms ,Outcome Assessment, Health Care ,Humans ,Female ,Epidemics ,Aged - Abstract
PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks.
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- 2021
5. Mutations in NCAPG2 Cause a Severe Neurodevelopmental Syndrome that Expands the Phenotypic Spectrum of Condensinopathies
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Tahir N. Khan, Kamal Khan, Azita Sadeghpour, Hannah Reynolds, Yezmin Perilla, Marie T. McDonald, William B. Gallentine, Shahid M. Baig, Erica E. Davis, Nicholas Katsanis, Alexander Allori, Misha Angrist, Patricia Ashley, Margarita Bidegain, Brita Boyd, Eileen Chambers, Heidi Cope, C. Michael Cotten, Theresa Curington, Sarah Ellestad, Kimberley Fisher, Amanda French, William Gallentine, Ronald Goldberg, Kevin Hill, Sujay Kansagra, Sara Katsanis, Joanne Kurtzberg, Jeffrey Marcus, Marie McDonald, Mohammed Mikati, Stephen Miller, Amy Murtha, Carolyn Pizoli, Todd Purves, Sherry Ross, Edward Smith, and John Wiener
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Male ,0301 basic medicine ,Proband ,Microcephaly ,Chromosomal Proteins, Non-Histone ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Nephronophthisis ,Genetics ,medicine ,Animals ,Humans ,Abnormalities, Multiple ,Child ,Zebrafish ,Genetics (clinical) ,Adaptor Proteins, Signal Transducing ,Adenosine Triphosphatases ,Infant, Newborn ,Genetic disorder ,Infant ,Membrane Proteins ,Syndrome ,Zebrafish Proteins ,medicine.disease ,biology.organism_classification ,Phenotype ,Pedigree ,DNA-Binding Proteins ,Cytoskeletal Proteins ,030104 developmental biology ,Neurodevelopmental Disorders ,Child, Preschool ,Multiprotein Complexes ,Premature chromosome condensation ,Mutation ,Female ,Limb morphogenesis ,030217 neurology & neurosurgery - Abstract
The use of whole-exome and whole-genome sequencing has been a catalyst for a genotype-first approach to diagnostics. Under this paradigm, we have implemented systematic sequencing of neonates and young children with a suspected genetic disorder. Here, we report on two families with recessive mutations in NCAPG2 and overlapping clinical phenotypes that include severe neurodevelopmental defects, failure to thrive, ocular abnormalities, and defects in urogenital and limb morphogenesis. NCAPG2 encodes a member of the condensin II complex, necessary for the condensation of chromosomes prior to cell division. Consistent with a causal role for NCAPG2, we found abnormal chromosome condensation, augmented anaphase chromatin-bridge formation, and micronuclei in daughter cells of proband skin fibroblasts. To test the functional relevance of the discovered variants, we generated an ncapg2 zebrafish model. Morphants displayed clinically relevant phenotypes, such as renal anomalies, microcephaly, and concomitant increases in apoptosis and altered mitotic progression. These could be rescued by wild-type but not mutant human NCAPG2 mRNA and were recapitulated in CRISPR-Cas9 F0 mutants. Finally, we noted that the individual with a complex urogenital defect also harbored a heterozygous NPHP1 deletion, a common contributor to nephronophthisis. To test whether sensitization at the NPHP1 locus might contribute to a more severe renal phenotype, we co-suppressed nphp1 and ncapg2, which resulted in significantly more dysplastic renal tubules in zebrafish larvae. Together, our data suggest that impaired function of NCAPG2 results in a severe condensinopathy, and they highlight the potential utility of examining candidate pathogenic lesions beyond the primary disease locus.
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- 2019
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6. Late pancreatic panniculitis in a simultaneous pancreas kidney transplant patient with failed allografts
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Tim E. Taber, Jonathan A. Fridell, Mirza M. Baig, Asif Sharfuddin, and Muhammad S. Yaqub
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Graft Rejection ,Male ,medicine.medical_specialty ,Panniculitis ,medicine.medical_treatment ,030230 surgery ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Postoperative Complications ,Chronic allograft nephropathy ,Internal medicine ,medicine ,Immunology and Allergy ,Humans ,Pharmacology (medical) ,Kidney transplantation ,Transplantation ,medicine.diagnostic_test ,business.industry ,Pancreatic Diseases ,Immunosuppression ,Middle Aged ,medicine.disease ,Allografts ,Prognosis ,Kidney Transplantation ,Tacrolimus ,surgical procedures, operative ,medicine.anatomical_structure ,Skin biopsy ,Pancreatitis ,Pancreas Transplantation ,Pancreas ,business ,Immunosuppressive Agents - Abstract
We present a rare case of pancreatic panniculitis in a 59-year-old male simultaneous pancreas-kidney (SPK) recipient with failed allografts. The patient presented with fever and painful erythematous nodules on his leg 1 month after stopping all immunosuppression. A thorough infectious and rheumatological workup was negative. He had pancreas rejection 4 years after SKP transplant and was restarted on dialysis after 14 years when his renal allograft failed due to chronic allograft nephropathy. His chronic immunosuppression (tacrolimus, azathioprine) was stopped and prednisone was weaned over 3 months at that time. A skin biopsy revealed saponification of the subcutaneous fat with inflammation pathognomonic of pancreatic panniculitis. Concurrent allograft pancreatitis confirmed with elevated lipase and a computed tomography scan finding of peripancreatic graft stranding and atrophic native pancreas. He was started on pulse steroid therapy for 3 days followed by oral taper. This resulted in dramatic resolution of all skin lesions and normalization of lipase levels within 1 week, followed by resumption of low-dose tacrolimus and azathioprine. This is an extremely rare occurrence of panniculitis in pancreas allograft after 10 years of pancreatic failure associated with stopping immunosuppression.
- Published
- 2019
7. Value of Increasing Biopsy Cores per Target with Cognitive MRI-targeted Transrectal US Prostate Biopsy
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Linda Sugar, Farzad Khalvati, Laurent Milot, Sarah M Baig, Michelle Zhang, Laurence Klotz, Michelle R Downes, and Masoom A. Haider
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Adult ,Image-Guided Biopsy ,Male ,Subgroup analysis ,Magnetic Resonance Imaging, Interventional ,030218 nuclear medicine & medical imaging ,Lesion ,03 medical and health sciences ,0302 clinical medicine ,Prostate ,Biopsy ,Medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Ultrasonography, Interventional ,Aged ,Retrospective Studies ,Aged, 80 and over ,Index Lesion ,medicine.diagnostic_test ,business.industry ,Cancer ,Prostatic Neoplasms ,Magnetic resonance imaging ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Tumor Burden ,medicine.anatomical_structure ,Cross-Sectional Studies ,030220 oncology & carcinogenesis ,Biopsy, Large-Core Needle ,medicine.symptom ,Neoplasm Grading ,business ,Nuclear medicine - Abstract
Purpose To determine the increase in clinically significant cancer detection in the prostate with increasing number of core samples obtained by using cognitive MRI-targeted transrectal US biopsy. Materials and Methods This retrospective cross-sectional study included 330 consecutive patients (mean age, 64.3 years; range, 42-84 years) who underwent multiparametric prostate MRI from March 2012 to July 2017 and had an index lesion that subsequently underwent cognitive MRI-targeted biopsy using transrectal US with at least five core samples (which were sequentially labeled) per lesion. The detection rate of clinically significant cancer was calculated on sequential biopsy cores, comparing the first core alone versus three cores versus five cores per target. Clinically significant cancer was defined as International Society of Urological Pathology Grade Group 2 or higher. Results Increasing the number of biopsy core samples from one to three per target and from three to five per target increased the detection rate of clinically significant cancer by 6.4% (21 of 330) and 2.4% (eight of 330), respectively. The target yield for clinically significant cancer was 26% (87 of 330), 33% (108 of 330), and 35% (116 of 330) for one, three, and five cores, respectively. Subgroup analysis showed no significant difference in upgrade rates as a function of multiparametric MRI lesion size (P = .53-.59) or location (P = .28-.89). Conclusion More clinically significant prostate cancers are detected when increasing the number of core biopsy samples per index lesion from one to three and from three to five (6.4% and 2.4%, respectively) when performing cognitive MRI-targeted transrectal US biopsy. © RSNA, 2019 See also the editorial by Oto in this issue.
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- 2019
8. Homozygosity for a missense variant in COMP gene associated with severe pseudoachondroplasia
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M, Tariq, T N, Khan, L, Lundin, M, Jameel, T, Lönnerholm, S M, Baig, N, Dahl, and J, Klar
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Adult ,Male ,Adolescent ,Base Sequence ,Sequence Homology, Amino Acid ,Homozygote ,Mutation, Missense ,Cartilage Oligomeric Matrix Protein ,Achondroplasia ,Pedigree ,Consanguinity ,Phenotype ,Exome Sequencing ,Humans ,Female ,Genetic Predisposition to Disease ,Pakistan ,Amino Acid Sequence - Abstract
The phenotypic spectrum associated with heterozygous mutations in cartilage oligomeric matrix protein gene (COMP) range from a mild form of multiple epiphyseal dysplasia (MED) to pseudoachondroplasia (PSACH). However, the phenotypic effect from biallelic COMP variants is unclear. We investigated a large consanguineous Pakistani family with a severe form of PSACH in 2 individuals. Another 14 family members presented with a mild PSACH phenotype similar to MED. Using exome sequencing and subsequent segregation analysis, we identified homozygosity for a COMP missense variant [c.1423GA; p.(D475N)] in the 2 severely affected individuals, whereas family members with the mild PSACH phenotype were heterozygous. Our observations show for the first time that a biallelic COMP variant may be associated with pronounced and widespread skeletal malformations suggesting an additive effect of the 2 mutated alleles.
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- 2017
9. Human cervicovaginal mucus contains an activity that hinders HIV-1 movement
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Thomas J. Hope, Shetha Shukair, Eric J. Spongberg, Casey J. Gioia, Cassing Hammond, Meegan R. Anderson, Howard Y. Lakougna, Shannon A. Allen, Sarah M. Kauffman, Daniel J. Stieh, Patrick F. Kiser, Gianguido C. Cianci, Michael D. McRaven, and Samir M. Baig
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Male ,Immunology ,Human immunodeficiency virus (HIV) ,Biology ,medicine.disease_cause ,Article ,Facilitated Diffusion ,Cell Line ,03 medical and health sciences ,0302 clinical medicine ,Semen ,medicine ,Fluorescence microscope ,Humans ,Immunology and Allergy ,Barrier function ,030304 developmental biology ,0303 health sciences ,030219 obstetrics & reproductive medicine ,Unknown activity ,Mucin ,Virion ,Biological Transport ,Hydrogen-Ion Concentration ,Mucus ,Virology ,Molecular biology ,3. Good health ,Cervix Mucus ,HIV-1 ,Female ,Endocervix ,Ex vivo - Abstract
Cervical and vaginal epithelia are primary barriers against human immunodeficiency virus type I (HIV-1) entry during male-to-female transmission. Cervical mucus (CM) is produced by the endocervix and forms a layer locally as well as in the vaginal compartment in the form of cervicovaginal mucus (CVM). To study the potential barrier function of each mucus type during HIV-1 transmission, we quantified HIV-1 mobility in CM and CVM ex vivo using fluorescent microscopy. Virions and 200-nm PEGylated beads were digitally tracked and mean squared displacement was calculated. The mobility of beads increased significantly in CVM compared to CM, consistent with the known decreased mucin concentration of CVM. Unexpectedly, HIV-1 diffusion was significantly hindered in the same CVM samples in which bead diffusion was unhindered. Inhibition of virus transport was envelope-independent. Our results reveal a previously unknown activity in CVM that is capable of impeding HIV-1 mobility to enhance mucosal barrier function.
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- 2013
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10. Genetic heterogeneity in Pakistani microcephaly families revisited
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I, Ahmad, S M, Baig, A R, Abdulkareem, M S, Hussain, I, Sur, M R, Toliat, G, Nürnberg, N, Dalibor, A, Moawia, S S, Waseem, M, Asif, H, Nagra, M, Sher, M M A, Khan, I, Hassan, S Ur, Rehman, H, Thiele, J, Altmüller, A A, Noegel, and P, Nürnberg
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Male ,Homozygote ,Intracellular Signaling Peptides and Proteins ,Cell Cycle Proteins ,Nerve Tissue Proteins ,Pedigree ,Cytoskeletal Proteins ,Mutation ,Exome Sequencing ,Microcephaly ,Humans ,Female ,Genetic Predisposition to Disease ,Pakistan - Abstract
Autosomal recessive primary microcephaly (MCPH) is a rare and heterogeneous genetic disorder characterized by reduced head circumference, low cognitive prowess and, in general, architecturally normal brains. As many as 14 different loci have already been mapped. We recruited 35 MCPH families in Pakistan and could identify the genetic cause of the disease in 31 of them. Using homozygosity mapping complemented with whole-exome, gene panel or Sanger sequencing, we identified 12 novel mutations in 3 known MCPH-associated genes - 9 in ASPM, 2 in MCPH1 and 1 in CDK5RAP2. The 2 MCPH1 mutations were homozygous microdeletions of 164,250 and 577,594 bp, respectively, for which we were able to map the exact breakpoints. We also identified four known mutations - three in ASPM and one in WDR62. The latter was initially deemed to be a missense mutation but we demonstrate here that it affects splicing. As to ASPM, as many as 17 out of 27 MCPH5 families that we ascertained in our sample were found to carry the previously reported founder mutation p.Trp1326*. This study adds to the mutational spectra of four known MCPH-associated genes and updates our knowledge about the genetic heterogeneity of MCPH in the Pakistani population considering its ethnic diversity.
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- 2016
11. Comparison of the Functional Significance of Left Ventricular Hypertrophy in Hypertrophic Cardiomyopathy and Glycogenosis Type III
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William J. McKenna, John E. Deanfield, Michael Burch, James V. Leonard, Philip J. Lee, and Kamran M. Baig
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Heart disease ,Cardiomyopathy ,Left ventricular hypertrophy ,Glycogen storage disease type III ,Muscle hypertrophy ,Glycogen Storage Disease Type III ,Internal medicine ,medicine ,Humans ,cardiovascular diseases ,Child ,medicine.diagnostic_test ,business.industry ,Hypertrophic cardiomyopathy ,Infant ,Cardiomyopathy, Hypertrophic ,medicine.disease ,Blood pressure ,Echocardiography ,Child, Preschool ,Electrocardiography, Ambulatory ,Exercise Test ,cardiovascular system ,Cardiology ,Female ,Hypertrophy, Left Ventricular ,Cardiology and Cardiovascular Medicine ,business ,Electrocardiography - Abstract
A comparison of blood pressure response with exercise stress, thallium scintigraphy, and 24-hour electrocardiographic monitoring between 5 patients with left ventricular hypertrophy associated with glycogen storage disease type III and 10 matched patients with hypertrophic cardiomyopathy revealed normal results in the former group. These data highlight the importance of the etiology of left ventricular hypertrophy before the application of risk stratification.
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- 1997
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12. Creatine kinase isoforms as circulating markers of deterioration in idiopathic dilated cardiomyopathy
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K. M. Baig, WJ McKenna, PJ Keeling, D. W. Holt, JH Goldman, Alida L.P. Caforio, and M Hossein-Nia
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Adult ,Cardiomyopathy, Dilated ,Male ,medicine.medical_specialty ,Heart disease ,Cardiomyopathy ,Sudden death ,Death, Sudden ,Reference Values ,Internal medicine ,Idiopathic dilated cardiomyopathy ,Odds Ratio ,medicine ,Humans ,Clinical Investigation ,Myocardial infarction ,Creatine Kinase ,biology ,business.industry ,Myocardium ,Dilated cardiomyopathy ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,Isoenzymes ,Transplantation ,biology.protein ,Cardiology ,Heart Transplantation ,Female ,Creatine kinase ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers ,Follow-Up Studies - Abstract
Background: A proportion of patients with dilated cardiomyopathy (DCM) may have ongoing myocardial damage secondary to viral or immune mediated myocardial inflammation. Hypothesis: The prognostic determinants identify patients with decreased survival but do not provide a measure of myocardial damage. To obtain an objective assessment of myocardial damage in DCM, we measured plasma levels of creatine kinase (CK), its isoenzymes (CK-MM and CK-MB), and separated the isoforms of CK-MM and CK-MB. Methods: The cohort consisted of 77 consecutive patients (61 men, 16 women) with DCM (World Health Organization criteria), aged 49 ± 14 years (range 19–60). Patients had been symptomatic for 29 ± 38 months (range 0.5–200 months) with 48 in New York Heart Association class I/II and 29 in class III/IV at the time of diagnosis. During median follow-up of 27 months from diagnosis (range 0.6–165), 50 patients remained clinically stable and 27 had deteriorated. Results: A significantly higher proportion of patients with DCM had abnormal MB2/MB1 ratio compared with normal volunteers (11,14% vs. 1, 1%, p = 0.003). Patients who deteriorated had higher MB2/MB1 ratio, (1.22 ± 0.62 vs. 0.85 ± 0.56;p = 0.01), and more frequently had abnormal MB2/ MB1 ratio (8,30% vs. 3,6%;p=0.004) and CK and CK-MM activities (5, 19% vs. 2, 4%;p = 0.03) than those who remained stable. Patients with DCM with high CK-MB activity had 3.13-fold increased odds of sudden death or need for cardiac transplantation (95% confidence interval 1.53–6.40, p = 0.008). Thus, CK measurements, in particular CK-MB isoforms, are markers of myocardial damage in a subset of patients with DCM and could be useful in investigating the possibility of persistent myocardial damage in these patients.
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- 1997
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13. Microduplications encompassing the Sonic hedgehog limb enhancer ZRS are associated with Haas-type polysyndactyly and Laurin-Sandrow syndrome
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S, Lohan, M, Spielmann, S C, Doelken, R, Flöttmann, F, Muhammad, S M, Baig, M, Wajid, W, Hülsemann, R, Habenicht, K W, Kjaer, S J, Patil, K M, Girisha, H H, Abarca-Barriga, S, Mundlos, and E, Klopocki
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Male ,Foot Deformities, Congenital ,Ectromelia ,Nose ,Regulatory Sequences, Nucleic Acid ,Toes ,Pedigree ,Fingers ,Polydactyly ,Gene Expression Regulation ,Gene Duplication ,Humans ,Abnormalities, Multiple ,Female ,Hedgehog Proteins ,Syndactyly ,Hand Deformities, Congenital ,Chromosomes, Human, Pair 7 - Abstract
Laurin-Sandrow syndrome (LSS) is a rare autosomal dominant disorder characterized by polysyndactyly of hands and/or feet, mirror image duplication of the feet, nasal defects, and loss of identity between fibula and tibia. The genetic basis of LSS is currently unknown. LSS shows phenotypic overlap with Haas-type polysyndactyly (HTS) regarding the digital phenotype. Here we report on five unrelated families with overlapping microduplications encompassing the Sonic hedgehog (SHH) limb enhancer ZPA regulatory sequence (ZRS) on chromosome 7q36. Clinically, the patients show polysyndactyly phenotypes and various types of lower limb malformations ranging from syndactyly to mirror image polydactyly with duplications of the fibulae. We show that larger duplications of the ZRS region (80 kb) are associated with HTS, whereas smaller duplications (80 kb) result in the LSS phenotype. On the basis of our data, the latter can be clearly distinguished from HTS by the presence of mirror image polysyndactyly of the feet with duplication of the fibula. Our results expand the clinical phenotype of the ZRS-associated syndromes and suggest that smaller duplications (80 kb) are associated with a more severe phenotype. In addition, we show that these small microduplications within the ZRS region are the underlying genetic cause of Laurin-Sandrow syndrome.
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- 2013
14. Association of TLL1 gene polymorphism (rs1503298, TC) with coronary heart disease in PREDICT, UDACS and ED cohorts
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Maryam, Zain, Fazli Rabbi, Awan, Jackie A, Cooper, Ka Wah, Li, Jutta, Palmen, Jay, Acharya, Philip, Howard, Shahid M, Baig, Robert S, Elkeles, Jeffrey W, Stephens, Helen, Ireland, and Steve E, Humphries
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Male ,Genotype ,Tolloid-Like Metalloproteinases ,Coronary Disease ,Middle Aged ,Polymorphism, Single Nucleotide ,United Kingdom ,Cohort Studies ,Logistic Models ,Diabetes Mellitus, Type 2 ,Gene Frequency ,Risk Factors ,Ethnicity ,Odds Ratio ,Humans ,Female ,Genetic Predisposition to Disease ,Taq Polymerase ,Alleles ,Aged - Abstract
To determine the sequence variant of TLL1 gene (rs1503298, TC) in three British cohorts (PREDICT, UDACS and ED) of patients with type-2 Diabetes mellitus (T2DM) in order to assess its association with coronary heart disease (CHD).Analytical study.UCL, London, UK. Participants were genotyped in 2011-2012 for TLL1 SNP. Samples and related information were previously collected in 2001-2003 for PREDICT, and in 2001-2002 for UDACS and ED groups.Patients included in PREDICT (n=600), UDACS (n=1020) and ED (n=1240) had Diabetes. TLL1 SNP (rs1503298, TC) was genotyped using TaqMan technology. Allele frequencies were compared using c2 test, and tested for Hardy-Weinberg equilibrium. The risk of disease was assessed from Odds ratios (OR) with 95% Confidence Intervals (95% CI). Moreover, for the PREDICT cohort, the SNP association was tested with Coronary Artery Calcification (CAC) scores.No significant association was found for this SNP with CHD or CAC scores in these cohorts.This SNP could not be confirmed as a risk factor for CHD in T2DM patients. However, the low power of thesmall sample size available is a limitation to the modest effect on risk. Further studies in larger samples would be useful.
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- 2013
15. Intersession reliability of the electromyographic signal during incremental cycle ergometry: quadriceps femoris
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Liesle A, Travis, Steven J, Arthmire, Ahmed M, Baig, Allon, Goldberg, and Moh H, Malek
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Adult ,Male ,Ergometry ,Electromyography ,Exercise Test ,Humans ,Reproducibility of Results ,Quadriceps Muscle - Abstract
The purposes of this investigation were to determine the: (1) reproducibility of the patterns of responses for electromyographic (EMG) amplitude and mean power frequency (MPF); and (2) intraclass correlation coefficient (ICC) of the EMG amplitude and MPF during three incremental cycle ergometer tests separated by 48 hours.Ten men performed incremental cycle ergometry tests to exhaustion on three separate occasions. Surface EMG signals were recorded simultaneously from the three superficial quadriceps muscles at each trial.Polynomial regression indicated that, for95% of the cases, the best-fit model was the same at each trial for EMG amplitude but not for EMG MPF. The ICC values were high for EMG amplitude but low for EMG MPF.These results indicate that EMG amplitude is a reliable measure of motor unit activation strategy during incremental cycle ergometry, whereas the EMG MPF was unreliable.
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- 2011
16. Association of GSTM1 and GSTT1 gene deletions with risk of head and neck cancer in Pakistan: a case control study
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M, Nosheen, M, Ishrat, F A, Malik, R M, Baig, and M A, Kayani
- Subjects
Adult ,Male ,Genotype ,Pharyngeal Neoplasms ,Middle Aged ,Case-Control Studies ,Odds Ratio ,Humans ,Female ,Mouth Neoplasms ,Pakistan ,Laryngeal Neoplasms ,Gene Deletion ,Glutathione Transferase - Abstract
Polymorphic deletions of GSTM1 and GSTT1 genes involved in the detoxification of potentially carcinogenic agents may be risk factors for various cancers, including head and neck cancer (HNC). In the present case-control study we aimed to access possible associations of HNC with GSTM1 and GSTT1 null genotypes in a Pakistani population. DNA was extracted from leukocytes of 388 cancer patients and 150 healthy controls by phenol-chloroform procedure. GSTM1 and GSTT1 deletion variants were genotyped by multiplex PCR assay with CYP1A1 as an internal control and further analyzed by primer specific PCR assay and sequencing. Mean age of cases and controls was 48 (±16.6) years with a male to female ratio of 1:1. Cancer of the oral cavity (57%) was most prevalent in the sampled population followed by pharynx and larynx (30% and 13% respectively). A statistically significant (P0.05) association was observed for both null genotypes in contribution to HNC as compared with the controls. The odds ratio (OR) for the GSTM1 null genotype was 2.3 with a 95% CI of 1.5-5.5 and for GSTT1 OR was 2.04 with 95% CI of 1.3-3.1. These results suggest that the GSTM1 and GSTT1 null genotypes are risk factors for HNC development among the Pakistani population.
- Published
- 2010
17. Post stroke seizures: descriptive study from a tertiary care centre in Pakistan
- Author
-
Bhojo A, Khealani, Sajjad, Ali, and Shahid M, Baig
- Subjects
Adult ,Male ,Epilepsy ,Adolescent ,Electroencephalography ,Middle Aged ,Stroke ,Recurrence ,Risk Factors ,Humans ,Epilepsy, Generalized ,Female ,Pakistan ,Epilepsies, Partial ,Aged ,Retrospective Studies - Abstract
To determine the frequency, mode of onset and outcome of post stroke seizures in a local setting.The retrospective (Aug 1999 to July 2001) and prospective (August 2001 to July 2002) data of patients aged 14 years and above, with post stroke seizures was collected from a tertiary care centre in a metropolitan city. The demographic, clinical, radiological, laboratory, neurophysiologic and outcome data was recorded and analyzed.During the three year period 1548 patients with stroke were admitted to the hospital. Four hundred thirty one (28%) had intracerebral haemorrhage (ICH) and 1117 (72%) had ischaemic stroke. One hundred seventeen (8%) of the 1548 had seizures. Their mean age was 63 +/- 12 (range; 15-70) years. Fifty-nine (50%) were men and 58 (50%) were women. Twenty of 431(5%) patients with ICH and 97/1117 (9%) with ischaemic stroke, developed seizures. Nine of 117 (8%) developed a seizure within 14 days of stroke and 108/117 (92%) developed seizures after 14 days of stroke. Twenty-six (22%) had partial and 91 (78%) had generalized seizures. Two patients expired early in the course. Twenty four (21%) of these continued to have seizures at one year follow up. Fifteen of 37 (40%) patients who had systemic infections early in the course continued to have seizures at one year as compared to 9/80 (11%) who did not (p = 0.001).Frequency of post stroke seizures is the same as reported in western literature. Post stroke seizures are more common in patients with ischaemic stroke. Generalized seizures are more common than partial seizures. Systemic infections early in the course are associated with recurrence of seizures at one year.
- Published
- 2008
18. Randomized, prospective comparison of precut vs surgeon-dissected grafts for descemet stripping automated endothelial keratoplasty
- Author
-
Kashif M. Baig, Jacob W. Brubaker, Francis W. Price, and Marianne O. Price
- Subjects
Male ,medicine.medical_specialty ,Visual acuity ,medicine.medical_treatment ,Visual Acuity ,Cell Count ,Fuchs' dystrophy ,Single Center ,Eye Banks ,Refraction, Ocular ,Specimen Handling ,Corneal Transplantation ,Double-Blind Method ,Microkeratome ,Cornea ,Ophthalmology ,medicine ,Humans ,Prospective Studies ,Prospective cohort study ,Descemet Membrane ,Corneal transplantation ,Aged ,business.industry ,Endothelium, Corneal ,Fuchs' Endothelial Dystrophy ,Eye bank ,medicine.disease ,eye diseases ,Surgery ,medicine.anatomical_structure ,Treatment Outcome ,Female ,sense organs ,medicine.symptom ,business - Abstract
Purpose To determine whether eye bank predissected corneal grafts provide outcomes comparable to surgeon-dissected grafts for Descemet stripping automated endothelial keratoplasty (DSAEK). Design Randomized, prospective, double-masked clinical trial. Methods Twenty pairs of donor corneas were harvested. One cornea from each pair was randomized to be precut at an eye bank for next-day use. The surgeon dissected the fellow cornea intraoperatively using a comparable microkeratome and protocol. The corneas were randomly assigned to 40 subjects having DSAEK at a single center. Subjects and evaluators were masked and statistical significance was assessed using the paired t test. Results Mean subject age was 71 ± 12 years and 90% had Fuchs dystrophy. Mean endothelial cell loss was 32% at six months and 34% at one year; the two groups did not differ by a statistically significant amount at either time point ( P = .10 and P = .79, respectively). Each group experienced two early dislocations (10%), and grafts were repositioned successfully with a second air bubble. At six months, 28 of 35 patients (80%) had best-corrected vision of 20/40 or better, excluding five patients (12%) with preexisting retinal problems ( P = .48). Both groups experienced a mild hyperopic shift ( P = .82), and neither had a statistically significant increase in mean refractive cylinder ( P = .63). Histology from one subject's eye postmortem demonstrated that endothelial cells had migrated over the exposed edge of the donor stroma a year after surgery. Conclusions Eye bank precut tissue provided similar endothelial cell loss, visual and refractive outcomes, and detachment rates compared with surgeon-dissected tissue.
- Published
- 2007
19. Clinical spectrum of Parkinson's disease from Pakistan
- Author
-
B A, Khealani and S M, Baig
- Subjects
Male ,Parkinson Disease ,Hypokinesia ,Middle Aged ,Severity of Illness Index ,Muscle Rigidity ,Antiparkinson Agents ,Hospitals, University ,Sex Factors ,Tremor ,Humans ,Female ,Pakistan ,Age of Onset ,Cognition Disorders ,Retrospective Studies - Abstract
Parkinson's disease is an idiopathic disorder of the extrapyramidal system. It has a worldwide prevalence but data from developing countries is scanty. We describe the clinical spectrum of the disease from Pakistan, a developing country.Patients with Parkinson's disease, over a period of 11 years, were identified by ICD-9 coding system of the hospital medical records. Demographical characteristics, clinical features, laboratory investigations and radiological investigations were recorded and analysed.A total of 80 patients were identified. 50 (63 percent) were males and 30 (37 percent) were females. Mean age of onset of the disease was 54 years. 47 (59 percent) patients had onset of illness during the sixth or seventh decade of life. Mean duration of illness at the time of presentation was five years. Rigidity, bradykinesia, tremors, hypomimia, primitive reflexes, difficulty in performing fine work and walking difficulty were the most common clinical features. 52 (65 percent) patients had stage I or II (Hoehn-Yahr staging) disease at the time of presentation. 56 (70 percent) patients had predominantly unilateral symptoms. 15 (19 percent) patients had cognitive impairment. Cognitive decline was more common in the elderly and in patients with disease duration of longer than ten years.Parkinson's disease is more common in males. Tremor, rigidity, walking difficulty, bradykinesia and difficulty in performing fine work are the commonest clinical features. Disease severity increases with duration of the disease. Cognitive impairment is not uncommon in these patients and is associated with disease duration and age of onset of the illness.
- Published
- 2006
20. Stroke-associated pneumonia: microbiological data and outcome
- Author
-
A, Hassan, B A, Khealani, S, Shafqat, M, Aslam, N, Salahuddin, N A, Syed, S M, Baig, and M, Wasay
- Subjects
Adult ,Aged, 80 and over ,Male ,Staphylococcus aureus ,Pneumonia ,Middle Aged ,Stroke ,Streptococcus pneumoniae ,Treatment Outcome ,Pseudomonas aeruginosa ,Humans ,Female ,Aged ,Retrospective Studies - Abstract
Pneumonia is a common complication after acute stroke. It affects the outcome adversely. However, data regarding microbiology of stroke-associated pneumonia and its effect on outcome is scarce.Stroke-associated pneumonia was identified through chart review of all ICD-9 identified adult stroke patients admitted to our hospital over a period of four years (1998-2001). The demographical, laboratory, radiological, microbiological data and outcome of patients with stroke-associated pneumonia were recorded and analysed.443 patients with stroke were admitted over the four-year period and 102 (23 percent) had stroke-associated pneumonia. Their ages range from 28 to 100 (mean 64+/-14) years. 69 (68 percent) were men. Median length of stay was nine days compared to four days for all stroke patients. 68 (67 percent) patients manifested pneumonia within 48 hours and 34 (33 percent) after 48 hours of admission. Yield of tracheal aspirate cultures was 38 percent and that of chest radiographs was 25 percent. Pseudomonas aeruginosa and Staphylococcus aureus were the most common organisms (12 percent each) followed by Streptococcus pneumoniae and Klebsiella pneumoniae (4 percent each). Patients with infiltrates on chest radiographs were more likely to have positive tracheal aspirate cultures (p-value is 0.003). 35 patients (34 percent) expired during hospital stay. Positive chest radiographs and tracheal aspirates were independent predictors of prolonged hospital stay (p-value is less than 0.005).Pneumonia is a common medical complication of stroke. It is associated with a high mortality and prolongs the hospital stay. The yield of chest radiographs and tracheal aspirates is low. However, these are independent predictors of prolonged hospital stay. Pseudomonas aeruginosa and Staphylococcus aureus are most common organisms in stroke-associated pneumonia.
- Published
- 2006
21. Abnormality of peptide YY and pancreatic polypeptide immunoreactive cells in colonic mucosa of patients with colonic inertia
- Author
-
Steven D. Wexner, Eric G. Weiss, Jay J. Singh, Sherry Woodhouse, Juan J. Nogueras, Rong Hua Zhao, and Khurrum M. Baig
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pathology ,Physiology ,Colon ,Population ,Pancreatic Polypeptide ,Gastroenterology ,Internal medicine ,Enterochromaffin Cells ,Medicine ,Pancreatic polypeptide ,Humans ,Large intestine ,Peptide YY ,Intestinal Mucosa ,education ,Retrospective Studies ,education.field_of_study ,biology ,business.industry ,Colonic inertia ,Chromogranin A ,Middle Aged ,Immunohistochemistry ,Staining ,medicine.anatomical_structure ,Case-Control Studies ,biology.protein ,Enterochromaffin cell ,Female ,business ,Constipation - Abstract
The etiopathology of colonic inertia remains unclear. Current studies show that pancreatic polypeptide-fold family members can serve as regulators of colonic motility and transit. Thus, the cells containing these peptides on colonic mucosa could be abnormal in patients with colonic inertia. We aimed to evaluate the immunocytochemical staining of peptide YY (PYY) and pancreatic polypeptide (PP) immunoreactive cells, and detect if alteration of these cells relates to an increase in enterochromaffin cells (EC) demonstrated by chromogranin A (CgA), in the colonic mucosa of patients with colonic inertia. Nineteen consecutive patients (18 female, 1 male; age, 43.7 ± 11.5 years) who underwent subtotal colectomy for colonic inertia were assessed. The control group consisted of 15 patients (all female; age, 50.7 ± 12.5 years) who underwent colonoscopic biopsies from the right and left colon for indications other than constipation, inflammatory bowel diseases, diarrhea, or neoplasm. Hollande’s-fixed, paraffin-embedded tissues of both right and left colons were collected. Immunocytochemical staining of PYY, PP, or CgA was performed on 4-μm tissue sections with the respective primary rabbit antibody, the biotinylated secondary antibody, and enzyme-labeled streptavidin. The average number of positive cells per microscopic field (200×) was calculated. Positive cells were classified as strongly, moderately, and weakly staining. The proportion of the variously stained cells is expressed as the percentage of the entire positive cell population. On both sides of the colon, the percentages of strongly and moderately stained PYY positive cells were higher in the patient group compared to the controls (right side, 10.6 and 27.3 vs. 6.1 and 18.7%, respectively; left side, 9.4 and 23.9 vs. 6.2 and 23.1%, respectively) (P&
- Published
- 2005
22. Mitochondrial DNA diversity in tribal and caste groups of Maharashtra (India) and its implication on their genetic origins
- Author
-
M M, Baig, A A, Khan, and K M, Kulkarni
- Subjects
Adult ,Male ,Genetics, Population ,Haplotypes ,Social Class ,Ethnicity ,Humans ,India ,DNA, Mitochondrial ,Anthropology, Physical ,Pedigree - Abstract
Genetic relationships among caste-groups are not uniform across the geographical regions of India. Many anthropologists have speculated on the tribal origin of some caste groups in Maharashtra and other states of India. To test this hypothesis, we used neutral mtDNA markers to study genetic relatedness among tribal and caste groups from Maharashtra. Descriptive statistics such as nucleotide diversity, gene diversity and average mismatches were found to be of the same magnitude. Phylogenetic network analysis exhibited a star-like expansion that may date back to the peopling of Eurasia, approximately 50,000 year ago. The reconstruction of mtDNA haplogroups showed that both the caste and tribal populations share similar branches of the tree. Also, the coalescence age estimation of caste and tribal populations suggests the persistence of maternal lineages with their root in early late Pleistocene. Our mtDNA analyses show some preliminary and significant evidence for the origin of prehistoric tribal and hierarchical caste societies of Maharashtra.
- Published
- 2004
23. Predictors of ischemic versus hemorrhagic strokes in hypertensive patients
- Author
-
Bhojo A, Khealani, Nadir A, Syed, Sabeen, Maken, Uzma U, Mapari, Bilal, Hameed, Sajjad, Ali, Rizwana, Qureshi, Naveed, Akhter, Ali, Hassan, Aziz B, Sonawalla, Shahid M, Baig, and Mohammed, Wasay
- Subjects
Cohort Studies ,Male ,Stroke ,Risk Factors ,Hypertension ,Humans ,Female ,Middle Aged ,Intracranial Hemorrhages ,Brain Ischemia - Abstract
To identify the factors that predispose to ischemic versus hemorrhagic stroke in hypertensive patients.Cohort study.The study was conducted at the Aga Khan University Hospital (AKUH), Karachi, from August 1999 to May 2001.All the hypertensive patients, who were registered in AKUH acute stroke outcome data base, over a period of 22 months, were identified and from this cohort the patients with first ever stroke were selected. The data regarding demographics, stroke type (ischemic vs. hemorrhagic), pre-existing medical problems, laboratory and radiological investigations was recorded and analyzed.Five hundred and nineteen patients with either ischemic stroke or parenchymal hemorrhage were registered over a period of 22 months. Three hundred and forty-eight patients (67%) had hypertension and of these, 250 had first ever stroke at the time of admission. Presence of diabetes mellitus (OR: 3.76; CI:1.67-8.46) and ischemic heart disease (OR: 6.97; CI:1.57-30.98) were found to be independent predictors of ischemic strokes.Presence of diabetes mellitus and ischemic heart disease predict ischemic stroke in a patient with hypertension.
- Published
- 2004
24. Ischemic stroke subtypes in Pakistan: the Aga Khan University Stroke Data Bank
- Author
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N A, Syed, B A, Khealani, S, Ali, A, Hasan, N, Akhtar, H, Brohi, T, Mozaffar, N, Ahmed, A, Hameed, S M, Baig, and M, Wasay
- Subjects
Adult ,Male ,Stroke ,Age Distribution ,Incidence ,Humans ,Female ,Pakistan ,Prospective Studies ,Middle Aged ,Sex Distribution ,Aged - Abstract
Frequency of ischemic stroke subtypes is influenced by ethnic and geographic variables. Our objective was to identify various stroke subtypes and its determinants at a tertiary care hospital.We prospectively collected data on ischemic stroke subtypes admitted to The Aga Khan University Hospital in Karachi.A total of 596 patients were enrolled in 22 months in the Aga Khan Universtiy Stroke Registry. These included 393 patients with Ischemic stroke, 126 patients with intracerebral hemorrhage, 50 patients with subarachnoid hemorrhage and others. The ischemic stroke group was classified according to the TOAST criteria and comprised of lacunar 168/393 (42.7%); large artery atherosclerosis 106/393 (26.9%); cardioembolic 24/393 (6.1%); undetermined 80/393 (20.3%); and other determined types 15/393 (3.8%). The high proportion of lacunar strokes in our population may be due to high burden of inadequately treated hypertension and diabetes. Clear cut cardioembolic stroke was relatively infrequent in our population.Lacunar stroke is the most common subtype of stroke in our patient population. This is most likely secondary to uncontrolled hypertension.
- Published
- 2004
25. Spectrum of complications and mortality of bacterial meningitis: an experience from a developing country
- Author
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M A, Rabbani, A A, Khan, S S, Ali, B, Ahmad, S M, Baig, M A, Khan, and M, Wasay
- Subjects
Adult ,Causality ,Male ,Humans ,Female ,Pakistan ,Middle Aged ,Meningitis, Bacterial ,Retrospective Studies - Abstract
The aim of this study was to obtain data on predisposing factors, causative organisms and their associated mortality and complications related to acute bacterial meningitis.The chart review of all patients in whom acute bacterial meningitis was diagnosed at The Aga Khan University Hospital from January 1995 through December 2001.One hundred ninety-four patients were included in study. There were 146 males and 48 females. The mean age of our study population was 41 +/- 12.3 years. One hundred and ninety (97.9%) patients had community-acquired meningitis; only 4 (2.0%) patients developed meningitis nosocomially. The two most common predisposing factors were diabetes mellitus (13.9%) and otitis media (7.7%) among all 194 patients. A significant proportion of patients with complications had diabetes mellitus (24.6%, p0.001). CSF and blood cultures were positive in 53 (27.3%) and 42 (21.6%) patients respectively; there was no statistical difference found. The most common organisms isolated were Streptococcus pneumoniae in 35 (36.8%) patients followed by Neisseria meningitides in 30 (31.5%) patients. Approximately 68% of positive cultures yielded S. pneumoniae and N. meningitides (p0.0001). The overall mortality rate was 22.1%. The mortality rate for Streptococcus pneumoniae was 17.1%. The highest mortality was observed in patients with Pseudomonal meningitis where all four patients expired followed by mortality rate of 85.7% in Escherichia coli afflicted patients (p0.001). Complications occurred in 73 (37.6%) patients with persistent complications in 31 (42.4%) patients. Complications resolved in 34 (46.5%) patients. The most common complications were seizures (12.8%) and cranial nerve palsies (11.3%). Seizures were more likely to occur in older patients (p0.05) whereas hydrocephalus was more common in younger patients (p0.05).Bacterial Meningitis remains a serious disease associated with substantial morbidity and mortality. Most cases are community acquired with S. Pneumoniae being the most common pathogen. Old age, diabetes mellitus, a positive culture, seizures as a complication and late stage in the disease are the important predictors of a poor outcome.
- Published
- 2004
26. Should carotid endarterectomy be performed for symptomatic carotid stenosis in Pakistan?
- Author
-
N A, Syed, A, Zakaria, B A, Khealani, M, Wasay, S M, Baig, and Z, Sophie
- Subjects
Adult ,Aged, 80 and over ,Male ,Endarterectomy, Carotid ,Middle Aged ,Risk Assessment ,Stroke ,Postoperative Complications ,Humans ,Carotid Stenosis ,Female ,Pakistan ,Coronary Artery Bypass ,Aged ,Retrospective Studies - Abstract
The risk of stroke and death associated with carotid endarterctomy is operator dependant. Data regarding risks of this procedure are not available in Pakistan and therefore it is difficult to make accurate risk benefit analysis for individual patients. Our objective was to determine safety of carotid endarterectomy at an academic tertiary care center in Pakistan.Patients who underwent carotid endarterectomy (CEA) at our hospital during a ten-year period were identified through ICD-9 coding system of the hospital medical records. Demographic features, associated medical problems and immediate postoperative complications were recorded and analyzed.Sixty-three carotid endarterectomies were performed on 59 patients. Ages range from 43 to 80 (mean 61 +/- 8) years; 53 were male and 10 were female. Common associated diseases among these patients were hypertension; 38 (64.4%), ischemic heart disease; 26 (44%), diabetes mellitus; 24 (40.7%), dyslipidemia; 19 (32.2%) and renal insufficiency; 13 (22%). Most common complication was neuropraxia (transient neuropathy); 5 (7.9%), followed by pneumonia and stroke; each in 3 (4.8%) patients. None of the strokes related to the surgical procedure were disabling. Two of the patients who had stroke, recovered fully within 17 weeks and one recovered partly but was independent in all daily activities of living (ADLs). One patient died following simultaneous coronary artery bypass graft (CABG) and CEA. The risk of stroke or death for patients undergoing CEA was high with simultaneous CABG (3/11, 27%) and low for patients undergoing CEA alone (1/52, 2%).Carotid endarterectomy is a safe procedure in patients with symptomatic carotid stenosis at our hospital and should be performed, when indicated.
- Published
- 2004
27. Moyamoya disease: an elusive diagnosis
- Author
-
K B, Asumal, N, Akhtar, N A, Syed, S, Shafqat, and S M, Baig
- Subjects
Adult ,Male ,Adolescent ,Age Factors ,Infant ,Electroencephalography ,Prognosis ,Risk Assessment ,Severity of Illness Index ,Stroke ,Child, Preschool ,Humans ,Female ,Pakistan ,Registries ,Moyamoya Disease ,Child ,Tomography, X-Ray Computed ,Magnetic Resonance Angiography ,Retrospective Studies - Abstract
Moyamoya disease is an idiopathic vasculopathy of circle of Willis. Stroke is a common presentation. We describe clinical and radiological features of moyamoya disease in four patients.Tertiary care center in a metropolitan city.Patients with moyamoya disease were identified by ICD-9 coding system of the hospital medical records. Demographic characteristics, clinical features/presentation, laboratory investigations and radiological investigations were recorded and analyzed.Four patients (three children and one adult) presented with hemiparesis. One patient expired during hospital stay. Two patients underwent surgery (synangiosis). EEGs of three patients showed focal abnormalities. Neuroimaging showed ischemic infarctions in all patients. Findings on four vessel digital substraction angiography and/or magnetic resonance angiography were compatible with moyamoya disease.Moyamoya disease should be considered in all young patients, especially children, presenting with stroke.
- Published
- 2003
28. Ischemic stroke in young adults of South Asia
- Author
-
A A, Razzaq, B A, Khan, and S M, Baig
- Subjects
Adult ,Male ,Adolescent ,Arteriosclerosis ,Middle Aged ,Magnetic Resonance Imaging ,Brain Ischemia ,Stroke ,Echocardiography ,Risk Factors ,Humans ,Carotid Stenosis ,Female ,Pakistan ,Hospital Mortality ,Retrospective Studies - Abstract
To study the risk factors, etiology and management of ischemic stroke in young adults in a South Asian population.Retrospective study conducted at a large tertiary hospital in Karachi. One hundred and eighteen patients between fifteen and forty-five years admitted over a five year period with a diagnosis of ischemic infarct constituted the study population. The study variables included the full clinical spectrum, spanning historical, laboratory, radiological and outcome parameters.Forty-three percent of patients were hypertensive and 30% were diabetic. The combination of diabetes and hypertension was found in 19.5% of patients, intra-cranial and carotid artherosclerosis in 22% and embolism in 11% of the cases. The in-hospital mortality was 11%. The outcome was excellent in 27%, good in 50% and poor in 23% of patients.The risk factors for artherosclerosis and the contribution of intra and extra-cranial artherosclerosis were found to be much higher than those from the Western Hemisphere.
- Published
- 2003
29. Hypercalcaemia: a clue to Mycobacterium avium intracellulare infection in a patient with AIDS
- Author
-
E S, Aly, M, Baig, D, Khanna, and M A, Baumann
- Subjects
Diagnosis, Differential ,Male ,Acquired Immunodeficiency Syndrome ,AIDS-Related Opportunistic Infections ,Hypercalcemia ,Humans ,Middle Aged ,Mycobacterium avium-intracellulare Infection - Abstract
Hypercalcaemia is uncommon in HIV-infected patients and should suggest a different priority for differential diagnosis than would be considered in other settings. Although hypercalcaemia has long been associated with granulomatous diseases including tuberculosis, it has only recently been recognised that patients with illness due to Mycobacterium avium intracellulare (MAI) may develop it. We report a patient with AIDS in whom unexplained hypercalcaemia was the harbinger of clinically significant MAI infection. Patients with AIDS who develop hypercalcaemia should be closely evaluated for underlying MAI infection.
- Published
- 2000
30. Carotid Doppler ultrasonography in young stroke patients
- Author
-
A A, Razzaq, B A, Khan, C K, Jadoon, and S M, Baig
- Subjects
Adult ,Male ,Stroke ,Carotid Arteries ,Adolescent ,Arteriosclerosis ,Risk Factors ,Humans ,Carotid Stenosis ,Female ,Pakistan ,Ultrasonography, Doppler ,Retrospective Studies - Abstract
The present study focuses on the role of carotid doppler ultrasonography (CDUS) in the diagnosis and management of carotid stenosis in young stroke patients.The findings of carotid doppler in 45 ischemic stroke patients between 15-45 years of age were reviewed retrospectively. The variables of interest for this study included risk factors for atherosclerotic disease, primary abnormality detected on carotid doppler ultrasonography (ulceration vs. stenosis), degree of stenosis and the type of plaque (soft vs. calcified).The prevalence of hypertension and diabetes was 50% and 35% respectively. The rate of carotid stenosis in the study population was found to be 31%. The degree of stenosis was mild in 35% and moderate in 21%. High-grade stenosis was found in 21% of patients. The plaque was soft in the majority of cases (43%).The proportion of carotid stenosis in young stroke patients was relatively high compared with previous studies. This may be due to an increase in the risk factors for atherosclerotic disease in developing countries.
- Published
- 1999
31. Circulating cardiac-specific autoantibodies as markers of autoimmunity in clinical and biopsy-proven myocarditis. The Myocarditis Treatment Trial Investigators
- Author
-
A L, Caforio, J H, Goldman, A J, Haven, K M, Baig, L D, Libera, and W J, McKenna
- Subjects
Adult ,Male ,Biopsy ,Autoimmunity ,Enzyme-Linked Immunosorbent Assay ,Middle Aged ,Myosins ,Coronary Angiography ,Myocarditis ,Immunoglobulin G ,Humans ,Female ,Fluorescent Antibody Technique, Indirect ,Biomarkers ,Autoantibodies - Abstract
Myocarditis and dilated cardiomyopathy may be phases of an organ-specific autoimmune disease of the myocardium. To provide evidence for autoimmune involvement in myocarditis, cardiac autoantibodies were detected in patient sera from the Myocarditis Treatment Trial.Cardiac antibody status was assessed by indirect immunofluorescence and by anti-alpha-myosin enzyme-linked immunosorbent assay in 53 patients from the Myocarditis Treatment Trial (35 males, aged 42 +/- 15 years); all had clinical myocarditis, but only 24 were classified as having histological myocarditis (Dallas criteria). By immunofluorescence, cardiac antibodies were more common in myocarditis (13/53) than in ischaemic (11/186, P = 0.0001) or in normal controls (24/270, P = 0.001). Abnormally raised anti-alpha-myosin antibodies were also more frequent in myocarditis (9/53) than in ischaemic (4/92, P = 0.01) or normal controls (4/203, P = 0.001); 34% of myocarditis patients were positive with one or both tests. Similar proportions of patients with and without histological myocarditis had antibodies by immunofluorescence (8/24 vs 5/29, P = ns) and by enzyme-linked immunosorbent assay (4/24 vs 5/29, P = ns).The detection of disease-specific cardiac autoantibodies supports autoimmune involvement in a subset of patients with clinical myocarditis. The lack of correlation of antibody with biopsy features suggests that diagnosis of myocarditis should not be made on histology alone. Autoimmune markers may provide adjunct diagnostic tools and identify patients in whom immunosuppression is of potential benefit.
- Published
- 1997
32. Prenatal diagnosis of beta-thalassaemia and sickle cell anaemia in Turkey
- Author
-
S, Tüzmen, G O, Tadmouri, A, Ozer, S M, Baig, H, Ozçelik, S, Başaran, and A N, Başak
- Subjects
Male ,Parents ,Genotype ,Turkey ,DNA Mutational Analysis ,beta-Thalassemia ,Anemia, Sickle Cell ,Fetal Diseases ,Chorionic Villi Sampling ,Pregnancy ,Prenatal Diagnosis ,Humans ,Female ,Genetic Testing - Abstract
This paper reports our experience of molecular analysis and diagnosis of beta-thalassaemia and sickle cell anaemia (HbS) in 70 prospective parents of Turkish descent and their fetuses. Molecular screening was carried out by allele-specific oligonucleotide (ASO) hybridization of amplified DNA to the 12 most common mutations in the Turkish population. By using this approach, we were able to define the mutation in 95 per cent of chromosomes investigated. Genomic sequencing led to the additional detection of three rare mutations: Cd 44 (-C), IVS-I-5 (G-C), and IVS-I-116 (T-G). All diagnoses were successfully accomplished and no misdiagnosis occurred. Consanguineous marriage appears to contribute significantly to the frequency of affected births in Turkey. Out of the 14 homozygous fetuses, six were the result of close consanguinity. This study indicates that fetal diagnosis of beta-thalassaemia and HbS may be obtained in practically all cases, even in a heterogeneous population like the Turkish population, when early methods of fetal sampling are combined with polymerase chain reaction (PCR)-based techniques. Until gene therapy becomes a reality, the only approaches to the control of haemoglobinopathies are prevention and avoidance. The most relevant and common aspects of the programmes, which have been very effective in reducing the birth rate of beta-thalassaemia major in several at-risk areas of the Mediterranean basin, are the continuous educational campaigns directed at the population at large, the voluntary basis, and non-directive counselling. The most important challenge for the eradication of the haemoglobinopathies in Turkey is the organization of a nation-wide and comprehensive genetic preventive programme based on DNA technology.
- Published
- 1996
33. The role of tryptophan, 5-hydroxy indole-3-acetic acid and their protein binding in uremic patients
- Author
-
G A, Qureshi and S M, Baig
- Subjects
Adult ,Male ,Muscles ,Tryptophan ,Hydroxyindoleacetic Acid ,Middle Aged ,Sensitivity and Specificity ,Catecholamines ,Peritoneal Dialysis, Continuous Ambulatory ,Humans ,Female ,Chromatography, High Pressure Liquid ,Serum Albumin ,Aged ,Protein Binding ,Uremia - Abstract
An on-line high performance liquid chromatography (HPLC) method of analysis with electrochemical detection was developed to quantitate catecholamines, tryptophan (Trp) and 5-hydroxy indoleacetic acid (5-HIAA) in muscle and plasma samples from healthy subjects and uraemic patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Equilibrium dialysis was performed on the plasma samples from 14 healthy and 14 uraemic subjects for the separation of free Trp and its metabolites from bound Trp. The results demonstrate abnormal Trp-albumin binding probably with accumulation of indolic metabolites and abnormally high muscle Trp concentration in uraemic patients.
- Published
- 1993
34. Application of high performance liquid chromatography in study of sulphur amino acid metabolism in uremic patients
- Author
-
G A, Qureshi and S M, Baig
- Subjects
Male ,Methionine ,Peritoneal Dialysis, Continuous Ambulatory ,Renal Dialysis ,Taurine ,Muscles ,Humans ,Kidney Failure, Chronic ,Reproducibility of Results ,Female ,Cysteine ,Middle Aged ,Aged - Abstract
High-performance liquid chromatography (HPLC) was used for the quantitation of the free amino acids in plasma and muscle samples from 34 patients with chronic renal failure; of these patients, 18 were treated by hemodialysis (HD) and 16 by continuous ambulatory peritoneal dialysis (CAPD). Depletion of taurine was observed in plasma and muscle of uremic patients, whereas methionine was normal. Cysteine sulphinic acid was present in plasma of all uremic patients. The results suggest that taurine depletion is due to decreased endogenous synthesis in uremic patients.
- Published
- 1993
35. Impact of the long term supply of iodized salt to the endemic goitre area
- Author
-
A, Ali, M M, Khan, Z U, Malik, B A, Charania, F A, Bhojani, and S M, Baig
- Subjects
Male ,Time Factors ,Prevalence ,Humans ,Female ,Pakistan ,Sodium Chloride ,Sodium Chloride, Dietary ,Goiter, Endemic ,Iodine - Abstract
The study was designed to assess the impact of the supplementation levels of iodine in salt supplied since the last 12 years to Gilgit and Hunza, an endemic goitre area of Pakistan. The overall prevalence of visible goitre is reduced from 61.36% to 4.68%. Results of urinary excretion of iodine (UEI) indicate severe to mild iodine deficiency among 70.41% of the randomly surveyed households. Severely deficient are 3%, moderate 29.54% and mild 37.87%, criteria of UEI being less than 2.0 micrograms/dl, 2-5 micrograms/dl and 5-10 micrograms/dl respectively. Levels of iodine supplementation in 267 iodized salt samples at production (n = 128) and consumption (n = 139) points are compared with a mean +/- SD are 70.86 +/- 29.73 ppm and 37.24 +/- 20.47 ppm respectively, representing 566.8 +/- 237.8 micrograms and 297.9 +/- 163.7 micrograms of iodine per 8.0 gram of salt. It is suggested to replace common salt with iodized salt in the goitre area to ensure the use by all households and quality control measures for iodination of salt should strictly be adhered so that uniform and consistent supply of iodine be ensured. The magnitude of contributory factors other than iodine deficiency, i.e., environmental and hereditary should be monitored and considered when levels of iodine supplementation are adjusted.
- Published
- 1992
36. Changes in circulating levels of immunoreactive follicle stimulating hormone, luteinizing hormone, and testosterone during sexual development in the rhesus monkey, Macaca mulatta
- Author
-
M, Arslan, S, Mahmood, S, Khurshid, S M, Naqvi, M A, Afzal, and S M, Baig
- Subjects
Gonadotropin-Releasing Hormone ,Male ,Radioimmunoassay ,Animals ,Macaca ,Testosterone ,Sexual Maturation ,Follicle Stimulating Hormone ,Luteinizing Hormone ,Macaca mulatta - Abstract
Basal serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) and the responsiveness of these hormones to a challenge dose of luteinizing hormone releasing hormone (LHRH), were determined in juvenile, pubertal, and adult rhesus monkeys. The monkey gonadotrophins were analyzed using RIA reagents supplied by the World Health Organization (WHO) Special Programme of Human Reproduction. The FSH levels which were near the assay sensitivity in immature monkeys (2.4 +/- 0.8 ng/ml) showed a discernible increase in pubertal animals (6.4 +/- 1.8 ng/ml). Compared to other two age groups, the serum FSH concentration was markedly higher (16.1 +/- 1.8 ng/ml) in adults. Serum LH levels were below the detectable limits of the assay in juvenile monkeys but rose to 16.2 +/- 3.1 ng/ml in pubertal animals. When compared to pubertal animals, a two-fold increase in LH levels paralleled changes in serum LH during the three developmental stages. Response of serum gonadotrophins and T levels to a challenge dose of LHRH (2.5 micrograms; i.v.) was variable in the different age groups. The present data suggest: an asynchronous rise of FSH and LH during the pubertal period and a temporal correlation between the testicular size and FSH concentrations; the challenge dose of LHRH, which induces a significant rise in serum LH and T levels, fails to elicit an FSH response in all the three age groups; and the pubertal as compared to adult monkeys release significantly larger quantities of LH in response to exogenous LHRH.
- Published
- 1986
37. A study of major causes of mortality and their trend from 1921 to 1971 in Pune Cantonment
- Author
-
B D, Varma, M M, Baig, B M, Aiyanna, D P, Achar, and T C, Sarma
- Subjects
Male ,Humans ,India ,Female ,Mortality - Abstract
The authors present a study of mortality in Pune cantonment, India, which had a population of around 78,000 in 1971. Data are from death registration records. Changes in mortality by sex and cause are analyzed over time
- Published
- 1980
38. Prevalence of autoantibodies in Saudi population
- Author
-
M M, Baig and S J, Shere
- Subjects
Adult ,Male ,Adolescent ,Age Factors ,Saudi Arabia ,Infant ,Autoimmune Diseases ,Sex Factors ,Reference Values ,Antibodies, Antinuclear ,Child, Preschool ,Humans ,Female ,Child ,Autoantibodies - Abstract
The demonstration of autoantibodies in sera from patients is diagnostic of autoimmune diseases. A prerequisite to such diagnostic undertaking and interpretation, the availability of serologic data pertaining to normal controls in a given population, is an absolute must. To achieve this, we determined the prevalence of antinuclear antibodies in an apparently healthy Saudi population. Of the total of 664 serum samples tested, 4.2% were found to be positive. Throughout life, the prevalence of autoantibodies was found to be higher in females than in age matched males, and increased with age in both sexes.
- Published
- 1989
39. Hypocholesterolemic agents: a comparison of the relative effectiveness of cholestyramine and pectin in rats
- Author
-
M M, Baig, C W, Burgin, and J J, Cerda
- Subjects
Cholesterol, Dietary ,Male ,Anticholesteremic Agents ,Cholesterol, HDL ,Cholestyramine Resin ,Animals ,Pectins ,Rats, Inbred Strains ,Cholesterol, LDL ,Triglycerides ,Rats - Abstract
Studies were carried out to evaluate the comparative effectiveness of cholestyramine and pectin as hypocholesterolemic agents. Circulating levels of serum cholesterol and lipoprotein-associated cholesterol were measured in rats fed high cholesterol diet supplemented with either cholestyramine or pectin. When compared with controls, a significant decrease in the level of total cholesterol was observed in rats fed either cholestyramine or pectin (p less than 0.001, 43% reduction in cholesterol, and p less than 0.04, 25% reduction in cholesterol, respectively) and this was due exclusively to the lowering of low density lipoprotein. Further statistical evaluation of data revealed no significant difference between the cholesterol levels of rats fed either cholestyramine or pectin (p greater than 0.07). The data acquired in this study suggest that both cholestyramine and pectin are comparable and effective hypocholesterolemic agents and the observed hypocholesterolemic effect of these agents is mediated through lowering of cholesterol associated with the low density lipoprotein.
- Published
- 1985
40. Isolation of mucin from human submaxillary secretions
- Author
-
M M, Baig, R J, Winzler, and W M, Rennert
- Subjects
Male ,Immunodiffusion ,Submandibular Gland ,Mucins ,Hemagglutination Inhibition Tests ,Electrophoresis, Disc ,Molecular Weight ,Polysaccharides ,Chromatography, Gel ,Humans ,Female ,Amino Acids ,Saliva ,Hexoses - Published
- 1973
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