Publications by authors named "Fazal Arain"

15 Publications

  • Page 1 of 1

Prevalence of Malaria reported during Summer and Winter at a Tertiary Care Hospital in Karachi, Pakistan.

J Pak Med Assoc 2019 Nov;69(11):1721-1724

CDepartment of Pathology and Laboratory Medicine, Aga Khan University, Karachi, Pakistan.

This study was designed to determine the prevalence and type of malaria cases that presented throughout the year 2014 in a tertiary care hospital in Karachi, Pakistan. A total of 1099 cases, (377 females, 722 males) were reported. Plasmodium vivax (P. vivax) was discovered in 93.7% cases compared to 6.3% Plasmodium falciparum (P. falciparum). Based on the highest and lowest weather temperatures, in summer (June, July and August) and in winter (December, January and February) were differentiated. The number of cases were greater during summer months compared to winter. Interestingly, the ratio of P. falciparum to P. vivax during winter was greater compared to summer. Finally, there was a strong correlation between increasing humidity and number of malaria cases. These findings show that even though the incidence of malaria is higher in summer, malaria cases are still reported in winter. Furthermore, the probability of finding P. falciparum (which causes cerebral malaria ) is higher in winter.
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http://dx.doi.org/10.5455/JPMA.7805.DOI Listing
November 2019

Molecular and radiological characterization of glioblastoma multiforme using magnetic resonance imaging.

J Neurosurg Sci 2021 Feb 11;65(1):47-53. Epub 2019 Jul 11.

Department of Oncology, Aga Khan University, Karachi, Pakistan.

Background: Glioblastoma multiforme (GBM) is the most malignant, aggressive and common form of primary brain cancer. Currently, GBM is considered to be a homogenous mass as all its margins are treated equally at the time of resection. However, it is not known whether radiologically distinct regions of GBM are also distinct at molecular level. We conducted this study to see if radiologically distinct regions were also different at the molecular level.

Methods: In 20 patients, MRI derived variance known as Apparent Diffusion Coefficient (ADC) was plotted against Contrast Enhancement (CE). Four radiologically distinct regions were identified: 1) high ADC and low CE; 2) low ADC and low CE; 3) high ADC and high CE; and 4) low ADC and high CE. Biopsy samples were collected from these four regions of interest in each patient and immunohistochemistry was conducted to characterize cellular features and identify oncogene and stem cell marker expressing cells.

Results: Markedly increased nuclear pleomorphism, cellularity and necrosis were seen in region 2. Oncogene IDH was expressed in all regions, however, it was highest in region 4. Stem cell marker, CD44 expression was highest in region 1 and lowest in region 2 and 3. The expression of CD133 was highest in region 3.

Conclusions: This study shows that ADC/CE plot can divide GBM into four regions, whose heterogeneity is evidenced by differential expression of nuclear pleomorphism, necrosis, cellularity and mitotic rate as well as the expression of oncogene and stem cell markers.
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http://dx.doi.org/10.23736/S0390-5616.19.04760-XDOI Listing
February 2021

Flipped classroom instructional approach in undergraduate medical education.

Pak J Med Sci 2017 Nov-Dec;33(6):1424-1428

Syed Ather Enam, MD, PhD, FRCS, FRCS, FACS. Department of Surgery, The Aga Khan University, Karachi, Pakistan.

Objective: In this study we implemented the "flipped classroom" model to enhance active learning in medical students taking neurosciences module at Aga Khan University, Karachi.

Methods: Ninety eight undergraduate medical students participated in this study. The study was conducted from January till March 2017. Study material was provided to students in form of video lecture and reading material for the non-face to face sitting, while face to face time was spent on activities such as case solving, group discussions, and quizzes to consolidate learning under the supervision of faculty. To ensure deeper learning, we used pre- and post-class quizzes, work sheets and blog posts for each session. Student feedback was recorded via a likert scale survey.

Results: Eighty four percent students gave positive responses towards utility of flipped classroom in terms of being highly interactive, thought provoking and activity lead learning. Seventy five percent of the class completed the pre-session preparation. Students reported that their queries and misconceptions were cleared in a much better way in the face-to-face session as compared to the traditional setting (4.09 ±1.04).

Conclusion: Flipped classroom(FCR) teaching and learning pedagogy is an effective way of enhancing student engagement and active learning. Thus, this pedagogy can be used as an effective tool in medical schools.
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http://dx.doi.org/10.12669/pjms.336.13699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768837PMC
March 2018

Video Microscope Robotic Arm-Assisted, Neuronavigation-guided Glioma Resection and Regional Sampling.

Cureus 2017 Oct 2;9(10):e1738. Epub 2017 Oct 2.

Biomedical Sciences, The Aga Khan University.

High-grade gliomas possess internal pathological heterogeneity. Selective sampling of different tumor regions can help in the study of this heterogeneity. In this report, we have described the use of a novel navigation and optical system for the selective regional sampling of a high-grade glioma lesion. A 45-year-old gentleman presented to us with complaints of intermittent frontal headaches for past eight months. On examination, he had subtle pyramidal weakness in left upper and lower extremities. Magnetic resonance imaging (MRI) showed a large contrast-enhancing, space-occupying lesion in the right frontal lobe causing perilesional edema and midline shift. We marked four different regions on the preoperative MRI using apparent diffusion coefficient (ADC) mapping and contrast enhancement pattern in four different combinations using presurgical planning software (BrightMatter™ Plan) (Synaptive Medical, Inc., Toronto, Canada). These pre-identified areas were exported into BrightMatter™​​​​​​​ Servo (Synaptive Medical, Toronto, Canada), an integrated robotic video microscope with a neuronavigation system where these areas were selectively sampled and sent for analysis. The BrightMatter™​​​​​​​ Servo not only helped us to the target areas but also helped to identify a safe trajectory, respecting white matter tracts. Histopathology showed a neoplastic lesion composed of mononuclear round cells with the perinuclear halo in a fibrillary stroma with admixed mini-gemistocytes consistent with the diagnosis of a Grade 3 anaplastic astrocytoma. A selective regional sampling of the gliomas can be reliably performed using BrightMatter™​​​​​​​ technologies to study the pathological heterogeneity of these lesions.
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http://dx.doi.org/10.7759/cureus.1738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5711501PMC
October 2017

Building Bridges through Science.

Neuron 2017 Nov;96(4):730-735

The Scripps Research Institute, La Jolla, CA 92037, USA.

Science is ideally suited to connect people from different cultures and thereby foster mutual understanding. To promote international life science collaboration, we have launched "The Science Bridge" initiative. Our current project focuses on partnership between Western and Middle Eastern neuroscience communities.
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http://dx.doi.org/10.1016/j.neuron.2017.09.028DOI Listing
November 2017

Are animal models applicable for research on schizophrenia?

Asian J Psychiatr 2017 Dec 18;30:167-168. Epub 2017 Oct 18.

Department of Biological and Biomedical Sciences, The Aga Khan University, Stadium Road, P.O. Box 3500, Karachi, 74800, Pakistan. Electronic address:

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http://dx.doi.org/10.1016/j.ajp.2017.10.012DOI Listing
December 2017

Hemimegalencephaly with intractable epilepsy: A case report.

J Pak Med Assoc 2017 Sep;67(9):1444-1446

Biological and Biomedical Sciences, The Aga Khan University, Karachi, Pakistan.

Isolated Hemimegalencephaly (iHME) is a rare form of congenital malformation of cortical development.It is characterized by enlargement of all or part of one cerebral hemisphere. It typically presents with intractable seizures, mental retardation, developmental delay, contralateral hemiparesis and hemianopia. The patient was a five and half month's old baby girl who presented first with focal seizures at 10th day of life. No other physical or behavioral abnormality was noted. However, Initial EEG showed excessive sharp EEG transients more over the right hemisphere, repeated EEG showed spikes, polyspikes, sharps and slow wave discharges predominately over right hemisphere. MRI brain showed asymmetric enlargement of the right cerebral hemisphere, suggestive of hemimegalencephaly. Initial treatment with anti-epileptics was successful in controlling the seizures but later on the seizures became intractable even on polytherapy. Identification of this and similar cases of iHME can help us better understand this disorder and its associated symptoms and eventually help us develop better treatment options for it.
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September 2017

A species dependent response to the pro-epileptic drug pentylentetrazole in birds.

Brain Res Bull 2017 Sep 9;134:189-194. Epub 2017 Aug 9.

Department of Biological and Biomedical Sciences, The Aga Khan University, Pakistan. Electronic address:

Epilepsy is common disorder that affects over 50 million people worldwide. Birds remain a promising yet largely under-explored model of epilepsy. This study reports the comparison of the response of two species of birds, Australian Parrots (APs) and Sparrows (SPs), to a pro-epileptic drug, Pentylenetetrazole (PTZ). PTZ injections caused myoclonic jerks (MCJs) and tonic clonic seizures (TCSs) in both species. The frequency of MCJs in APs was greater at the dose of 75mg/kg compared to both 50mg/kg and 25mg/kg while it was not significantly different in SPs. The comparison of APs and SPs showed that the frequency of MCJs was greater in APs compared to SPs at 25mg/kg and 75mg/kg while its latency was reduced at 25mg/kg and 50mg/kg. Interestingly SPs had a reduced latency of TCSs compared to APs at 75mg/kg. Glutamatergic and Gabaergic cell count was conducted to determine an association with the epileptic response to PTZ. The Glutamatergic cell counts for SPs was significantly greater than APs and conversely the Gabaergic cell counts in APs was higher compared to SPs. The reason for this difference in findings needs to be further investigated. This study shows that birds, and APs and SPs in particular, are a valid, interesting and under-explored model of epilepsy that should be further explored in order to understand the mysteries of epilepsy.
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http://dx.doi.org/10.1016/j.brainresbull.2017.08.003DOI Listing
September 2017

Challenges of conducting animal based research and teaching in medical colleges of Karachi, Pakistan.

J Pak Med Assoc 2017 Mar;67(3):487

Department of Biological and Biomedical Sciences, The Aga Khan University, Karachi.

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March 2017

Hereditary Sensory Autonomic Neuropathy II, a rare disease in a large Pakistani family.

J Pak Med Assoc 2015 Oct;65(10):1128-30

Department of Pediatric Neurology, The Aga Khan University, Karachi.

Hereditary Sensory Autonomic Neuropathy II (HSAN II) is a rare genetic disorder, characterized by severe loss of pain, temperature and touch sensation. Injuries in these patients can progress to necrosis and shedding of digits and limbs. Here we report two cases of HSAN II belonging to a Pakistani family. Individual 1, a forty five year old man, had complete loss of pain sensation since birth. Self-mutilation and complication of injuries resulted in the shedding of all the digits and right foot and surgical amputation of left leg. Individual 2, a five year old girl,had delay in healing of wounds and self-mutilation. Examination showed a complete lack of pain sensation throughout her body and hyporeflexia. As the genetic cause of HSAN II is unknown, identification of more patients will allow further research on this disease and possibly develop a cure.
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October 2015

The developmental evolution of the seizure phenotype and cortical inhibition in mouse models of juvenile myoclonic epilepsy.

Neurobiol Dis 2015 Oct 6;82:164-175. Epub 2015 Jun 6.

Department of Neurology, Vanderbilt University, Nashville, TN 37232-8552 USA. Electronic address:

The GABA(A) receptor (GABA(A)R) α1 subunit mutation, A322D, causes autosomal dominant juvenile myoclonic epilepsy (JME). Previous in vitro studies demonstrated that A322D elicits α1(A322D) protein degradation and that the residual mutant protein causes a dominant-negative effect on wild type GABA(A)Rs. Here, we determined the effects of heterozygous A322D knockin (Het(α1)AD) and deletion (Het(α1)KO) on seizures, GABA(A)R expression, and motor cortex (M1) miniature inhibitory postsynaptic currents (mIPSCs) at two developmental time-points, P35 and P120. Both Het(α1)AD and Het(α1)KO mice experience absence seizures at P35 that persist at P120, but have substantially more frequent spontaneous and evoked polyspike wave discharges and myoclonic seizures at P120. Both mutant mice have increased total and synaptic α3 subunit expression at both time-points and decreased α1 subunit expression at P35, but not P120. There are proportional reductions in α3, β2, and γ2 subunit expression between P35 and P120 in wild type and mutant mice. In M1, mutants have decreased mIPSC peak amplitudes and prolonged decay constants compared with wild type, and the Het(α1)AD mice have reduced mIPSC frequency and smaller amplitudes than Het(α1)KO mice. Wild type and mutants exhibit proportional increases in mIPSC amplitudes between P35 and P120. We conclude that Het(α1)KO and Het(α1)AD mice model the JME subsyndrome, childhood absence epilepsy persisting and evolving into JME. Both mutants alter GABA(A)R composition and motor cortex physiology in a manner expected to increase neuronal synchrony and excitability to produce seizures. However, developmental changes in M1 GABA(A)Rs do not explain the worsened phenotype at P120 in mutant mice.
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http://dx.doi.org/10.1016/j.nbd.2015.05.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4641014PMC
October 2015

Altered cortical GABAA receptor composition, physiology, and endocytosis in a mouse model of a human genetic absence epilepsy syndrome.

J Biol Chem 2013 Jul 6;288(29):21458-21472. Epub 2013 Jun 6.

From the Department of Neurology, Vanderbilt University, Nashville, Tennessee 37232. Electronic address:

Patients with generalized epilepsy exhibit cerebral cortical disinhibition. Likewise, mutations in the inhibitory ligand-gated ion channels, GABAA receptors (GABAARs), cause generalized epilepsy syndromes in humans. Recently, we demonstrated that heterozygous knock-out (Hetα1KO) of the human epilepsy gene, the GABAAR α1 subunit, produced absence epilepsy in mice. Here, we determined the effects of Hetα1KO on the expression and physiology of GABAARs in the mouse cortex. We found that Hetα1KO caused modest reductions in the total and surface expression of the β2 subunit but did not alter β1 or β3 subunit expression, results consistent with a small reduction of GABAARs. Cortices partially compensated for Hetα1KO by increasing the fraction of residual α1 subunit on the cell surface and by increasing total and surface expression of α3, but not α2, subunits. Co-immunoprecipitation experiments revealed that Hetα1KO increased the fraction of α1 subunits, and decreased the fraction of α3 subunits, that associated in hybrid α1α3βγ receptors. Patch clamp electrophysiology studies showed that Hetα1KO layer VI cortical neurons exhibited reduced inhibitory postsynaptic current peak amplitudes, prolonged current rise and decay times, and altered responses to benzodiazepine agonists. Finally, application of inhibitors of dynamin-mediated endocytosis revealed that Hetα1KO reduced base-line GABAAR endocytosis, an effect that probably contributes to the observed changes in GABAAR expression. These findings demonstrate that Hetα1KO exerts two principle disinhibitory effects on cortical GABAAR-mediated inhibitory neurotransmission: 1) a modest reduction of GABAAR number and 2) a partial compensation with GABAAR isoforms that possess physiological properties different from those of the otherwise predominant α1βγ GABAARs.
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http://dx.doi.org/10.1074/jbc.M112.444372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774412PMC
July 2013

Decreased viability and absence-like epilepsy in mice lacking or deficient in the GABAA receptor α1 subunit.

Epilepsia 2012 Aug 19;53(8):e161-5. Epub 2012 Jul 19.

Department of Neurology, Vanderbilt University, Nashville, Tennessee 37232-8552, USA.

Autosomal dominant mutations S326fs328X and A322D in the GABA(A) receptor α1 subunit are associated with human absence epilepsy and juvenile myoclonic epilepsy, respectively. Because these mutations substantially reduce α1 subunit protein expression in vitro, it was hypothesized that they produce epilepsy by causing α1 subunit haploinsufficiency. However, in a mixed background strain of mice, α1 subunit deletion does not reduce viability or cause visually apparent seizures; the effects of α1 subunit deletion on electroencephalography (EEG) waveforms were not investigated. Here, we determined the effects of α1 subunit loss on viability, EEG spike-wave discharges and seizures in congenic C57BL/6J and DBA/2J mice. Deletion of α1 subunit caused strain- and sex-dependent reductions in viability. Heterozygous mice experienced EEG discharges and absence-like seizures within both background strains, and exhibited a sex-dependent effect on the discharges and viability in the C57BL/6J strain. These findings suggest that α1 subunit haploinsufficiency can produce epilepsy and may be a major mechanism by which the S326fs328X and A322D mutations cause these epilepsy syndromes.
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http://dx.doi.org/10.1111/j.1528-1167.2012.03596.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3418418PMC
August 2012

General practitioner's knowledge regarding the diagnosis and drug therapy for acute myocardial infarction.

J Pak Med Assoc 2009 Feb;59(2):118-22

Department of Community Health Sciences, The Aga Khan University, Karachi, Pakistan.

Objective: To assess the general practitioners (GP) knowledge regarding the diagnosis and initial drug therapy for acute myocardial infarction (AMI).

Methods: A questionnaire-based survey was conducted in randomly selected GPs of Karachi. Doctors working in community as GPs who were registered medical practitioners having a Bachelor of Medicine & Bachelor of Surgery degree were included in the study. Doctors working at tertiary care facilities or having a post graduate degree or post graduate training in a specialty other than family medicine were excluded from the study.

Results: A total of 186 GPs participated in our study. GPs who studied research journals were 2.33 times more likely to investigate serum cardiac troponins levels for the diagnosis of AMI compared to those who did not study research journals (P = 0.02). Twenty six percent of the GPs said that they would refer a patient with suspected AMI without treatment, while 76% said that they would consider some treatment prior to referral. Fifty eight percent of the GPs identified ST segment elevation myocardial infarction (STEMI) of < 12 hours duration as an indication of thrombolysis while 28% identified posterior wall AMI as a thrombolytic indication.

Conclusion: GPs, although adequately aware of the presenting features of AMI, were lacking in knowledge regarding the means for confirmation of diagnosis, initial drug therapy and were less likely to carry management steps in their practice.
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February 2009

The juvenile myoclonic epilepsy GABA(A) receptor alpha1 subunit mutation A322D produces asymmetrical, subunit position-dependent reduction of heterozygous receptor currents and alpha1 subunit protein expression.

J Neurosci 2004 Jun;24(24):5570-8

Department of Neurology, Vanderbilt University, Nashville, Tennessee 37212, USA.

Individuals with autosomal dominant juvenile myoclonic epilepsy are heterozygous for a GABA(A) receptor alpha1 subunit mutation (alpha1A322D). GABA(A) receptor alphabetagamma subunits are arranged around the pore in a beta-alpha-beta-alpha-gamma sequence (counterclockwise from the synaptic cleft). Therefore, each alpha1 subunit has different adjacent subunits, and heterozygous expression of alpha1(A322D), beta, and gamma subunits could produce receptors with four different subunit arrangements: beta-alpha1-beta-alpha1-gamma (wild type); beta-alpha1(A322D)-beta-alpha1-gamma (Het(betaalphabeta)); beta-alpha1-beta-alpha1(A322D)-gamma (Het(betaalphagamma));beta-alpha1(A322D)-beta-alpha1(A322D)-gamma (homozygous). Expression of a 1:1 mixture of wild-type andalpha1(A322D) subunits with beta2S and gamma2S subunits (heterozygous transfection) produced smaller currents than wild type and much larger currents than homozygous mutant transfections. Western blot and biotinylation assays demonstrated that the amount of total and surface alpha1 subunit from heterozygous transfections was also intermediate between those of wild-type and homozygous mutant transfections. alpha1(A322D) mutations were then made in covalently tethered triplet (gamma2S-beta2S-alpha1) and tandem (beta2S-alpha1) concatamers to target selectively alpha1(A322D) to each of the asymmetric alpha1 subunits. Coexpression of mutant and wild-type concatamers resulted in expression of either Het(betaalphabeta) or Het(betaalphagamma) receptors. Het(betaalphabeta) currents were smaller than wild type and much larger than Het(betaalphagamma) and homozygous currents. Furthermore, Het(betaalphabeta) transfections contained less beta-alpha concatamer than wild type but more than both Het(betaalphagamma) and homozygous mutant transfections. Thus, whole-cell currents and protein expression of heterozygous alpha1(A322D)beta2Sgamma2S receptors depended on the position of the mutant alpha1 subunit, and GABA(A) receptor currents in heterozygous individuals likely result primarily from wild-type and Het(betaalphabeta) receptors with little contribution from Het(betaalphagamma) and homozygous receptors.
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http://dx.doi.org/10.1523/JNEUROSCI.1301-04.2004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6729321PMC
June 2004
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