Publications by authors named "Ahmed Shah"

38 Publications

An approach to small lymph node biopsies: pearls and pitfalls of reporting in the real world.

J Am Soc Cytopathol 2021 May-Jun;10(3):328-337. Epub 2021 Mar 13.

Division of Anatomical Pathology, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON. Electronic address:

Recent advances in interventional radiology have resulted in the utilization of small lymph node biopsies, including fine-needle aspiration (FNA) and core needle biopsy (CNB) as an initial diagnostic tool in hematopathology. A major challenge to the utilization of FNA and CNB is the limited-to-scant tissue often available. We propose delegation of the task of handling biopsy specimens to the laboratory staff by the biopsy operators, in order to optimize the utilization of the specimen. Furthermore, in order to effectively diagnose hematolymphoid neoplasms a variety of ancillary tests including immunohistochemistry, flow cytometry, molecular analysis, florescence in situ hybridization (FISH) are necessary. We propose morphological evaluation coupled with careful utilization of ancillary studies along with clinical correlation to approach the correct diagnosis. Our morphological assessment considers the types of proliferating cell population: mainly small cells, sheets of large cells, or scattered large cells among small cells. This is followed by employment of the corresponding immunopanel to assess the differential diagnosis in each of the three categories. We also elaborate on the importance for pathologists to become proficient in understanding the limitations of small tissue biopsies as well as the differences in interpretation, and wording their reports to help clinicians and direct them to further investigate and/or to re-biopsy when necessary.
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http://dx.doi.org/10.1016/j.jasc.2020.12.006DOI Listing
March 2021

A Novel Metric System to Quantify Antibiotic Consumption in Paediatric Population: A Hospital Based, Biphasic Pilot Study.

Discoveries (Craiova) 2020 Dec 10;8(4):e119. Epub 2020 Dec 10.

Department of Pharmacology, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India.

Background: The Anatomical Therapeutic Chemical Classification / Defined Daily Dose (ATC/DDD) system recommended by World Health Organization is accepted worldwide as the standard method of quantification of drug consumption. However, owing to individual variation in body weight, the ATC/DDD system cannot be used for comparison across paediatric population.

Objective: This study aimed to develop a novel metric system for standard quantification of antibiotic consumption in paediatric population.

Method: The standard unit of drug quantification in adult population is DDD/100 patient days (PD). We conceived a new unit of DDD/1000 kg-days (KD) where KD is the product of the body weight and length of hospital stay of an individual patient. We simulated the quantification and comparison of drugs in a computer model of five virtual paediatric hospitals (H1 to H5, n=100, 200, 100, 100, 100 respectively). We re-applied the metric system on two, real world, hospital-based, time cohorts (TC) (TC18, n=38 and TC19, n=47) of 2 weeks each, in two consecutive years.

Results: The body weights (mean±SD) in H1-H5 were 5.7±3.0, 5.7±2.8, 25.3±8.5, 20.6±11.7 and 19.8±11.4 kg, respectively. The antibiotic consumption in terms of DDD/100 PD and DDD/1000 KD in the five hospitals was 1.26, 1.20, 5.52, 4.41 and 2.00, and 2.24, 2.14, 2.22, 2.17 and 1.06 respectively. In TC18 and TC19, the mean body weight, DDD/100 PD and DDD/1000 KD were 12.24±13.17, 30.93, 20.34 and 19.51±12.28, 11.99, 6.23, respectively.

Conclusion: DDD/1000 kg-days is a potential standard unit for drug quantification in paediatric population independent of weight distribution and size of the study sample. The universal application and comparison across diverse samples can generate useful information for resource allocation, anti-microbial stewardship, disease burden and drug use, and can help in taking policy decisions to improve healthcare delivery in the paediatric population.
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http://dx.doi.org/10.15190/d.2020.16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746476PMC
December 2020

Regression of the Left Ventricular Hypertrophy in Patients with Essential Hypertension on Standard Drug Therapy.

Discoveries (Craiova) 2020 Sep 30;8(3):e115. Epub 2020 Sep 30.

Department of General Medicine, All India Institute of Medical Sciences Bhopal, Madhya Pradesh, India.

 PURPOSE: The American College of Cardiology/ American Heart Association 2017 and European Society of Cardiology/European Society of Hypertension 2018 guidelines were a paradigm shift in hypertension management in contemporary medicine. Lowering of blood pressure to less than 130 (systolic) and 80 (diastolic) mm of Hg irrespective of cardiovascular risk is recommended. While intensive blood pressure control is commonly achievable with rational pharmacotherapy, the magnitude of left ventricular hypertrophy regression is an independent factor in improvement in cardiovascular health. The regression of left ventricular hypertrophy has been adjudged as a clinically useful surrogate marker that reflects the efficacy of hypertension treatment. Though angiotensin converting enzyme inhibitors/ angiotensin receptor blockers (ACEI/ARB) are the preferred initial drug for greater regression of left ventricular mass, the choice of add-on therapy, if required, is still debatable. Therefore, in our observational study, we sought to compare the reduction in left ventricular mass index in hypertensives with left ventricular hypertrophy on standard ACEI/ARB based drug therapy.  MATERIALS AND METHODS: The cohort (n=217) comprised of patients with uncontrolled hypertension (blood pressure>140/90 mm of Hg) and left ventricular hypertrophy (left ventricular mass index>115 and 95 gram/square meter in males and females respectively). The add-on drug in ACEI/ARB therapy was either thiazide diuretics (TD) or calcium channel blockers (CCB). Four sub-cohorts were constituted: mono-therapy - group A (n=70, ACEI/ARB), dual-therapy - group B (n=48, ACEI/ARB+TD) and  group C (n=51, ACEI/ ARB+CCB), triple therapy - group D (n=48, ACEI/ ARB+TD+CCB). Left ventricular mass index was determined using echocardiography at baseline and after 24 weeks of therapy.  RESULTS: There was no significant difference in baseline clinical or demographic variables between group B and group C. Baseline blood pressure and duration of hypertension was greater in group D compared to group A (P<0.001). The reduction in left ventricular mass index (mean ±SD) in the four groups (A to D) was 16.7±18.7, 21.0±20.8, 20.5±15.5  and 29.1±21.5 g/m2  respectively (D>A, P=0.011, B versus C, P=1.00). The corresponding change in blood pressure (systolic/diastolic) was 18.5±13.6/8.9±11.2, 27.5±19.2/12.2±9.3, 23.4±16.7/ 5.4±10.1, 26.6±19.5/10.7±12.8 mm of Hg respectively (systolic, B>A, P=0.027, D>A, P=0.048) (diastolic, B>C, P=0.013).  CONCLUSION: Anti-hypertensive treatment with angiotensin converting enzyme inhibitors/angiotensin receptor blockers-based therapy produced graded regression of left ventricular hypertrophy with monotherapy, dual therapy and triple therapy.  In dual therapy, add-on of either thiazide diuretics or calcium channel blockers to angiotensin converting enzyme inhibitors/angiotensin receptor blockers showed equal efficacy in regression of left ventricular hypertrophy independent of blood pressure reduction.
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http://dx.doi.org/10.15190/d.2020.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575414PMC
September 2020

Development and validation of a mathematical model to quantify antibiotic consumption in paediatric population: A hospital-based pilot study.

J Clin Pharm Ther 2020 Dec 20;45(6):1349-1356. Epub 2020 Jul 20.

Department of Pharmacology, All India Institute of Medical Sciences Bhopal, Bhopal, Madhya Pradesh, India.

What Is Known And Objectives: A standard drug classification system and a fundamental measurement unit of drug consumption are prerequisites in a healthcare information system for generating quality data on drug use. Globally, the ATC/DDD (Anatomical Therapeutic Chemical Classification/Defined Daily Dose) system recommended by WHO is accepted as the international standard. However, owing to variability in body weight, it cannot be used directly in paediatric population. In our work, we aimed to develop a standard method of quantification of antibiotic consumption in paediatric population using a modified approach of the ATC/DDD system.

Method: We developed a mathematical model in a simulated paediatric cohort (n = 1000) and calculated antibiotic consumption in units of days of therapy (DOT) and DDD/100 patient days (PD). We validated the model in an observational cohort (n = 38) of inpatients admitted in Paediatric Department of a tertiary care centre.

Results: Model simulation showed near perfect positive correlation (R = .99-1.00) between DOT and DDD/100 PD in discrete weight based sub-cohorts (weight 1-10 kg). In the validation cohort, consumption of antibiotics was 121.76 and 33.16 in terms of DOT and DDD/100 PD respectively. Strong positive correlation between the two units (R = .73) was obtained. The correlation was better in predefined age and weight categories as compared to the uncategorised consumption (R = .78-.97). The model was proved validated when weight specific (in sub-cohorts of patients weighing 4, 5, 7 kg) DDD/100 PD and DOT also showed near perfect positive correlation (R = .96-.99).

What Is New And Conclusion: Weight specific DDD/100 PD can be explored further as a tool to standardise the quantification and comparison of consumption of drugs in paediatric population.
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http://dx.doi.org/10.1111/jcpt.13216DOI Listing
December 2020

Prediction of Left Ventricular Mass Index Using Electrocardiography in Essential Hypertension - A Multiple Linear Regression Model.

Med Devices (Auckl) 2020 11;13:163-172. Epub 2020 Jun 11.

Department of General Medicine, All India Institute of Medical Sciences Bhopal, Bhopal, Madhya Pradesh, India.

Background: Current electrocardiography (ECG) criteria indicate only the presence or absence of left ventricular hypertrophy (LVH). LVH is a continuum and a direct relationship exists between left ventricular mass (LVM) and cardiovascular event rate. We developed a mathematical model predictive of LVM index (LVMI) using ECG and non-ECG variables by correlating them with echocardiography determined LVMI.

Patients And Methods: The model was developed in a cohort of patients on treatment for essential hypertension (BP>140/90 mm of Hg) who underwent concurrent ECG and echocardiography. One hundred and forty-seven subjects were included in the study (56.38±11.84 years, 66% males). LVMI was determined by echocardiography (113.76±33.06 gm/m). A set of ECG and non-ECG variables were correlated with LVMI for inclusion in the multiple linear regression model. The model was checked for multicollinearity, normality and homogeneity of variances.

Results: The final regression equation formulated with the help of unstandardized coefficients and constant was =18.494+ 1.704 () + 0.969 () + 0.295 () + 15.406 () (aLL - sum of deflections in augmented limb leads; RaVL+SV3 - sum of deflection of (R wave in aVL + S wave in V3); MBP - mean blood pressure; IHD=1 for the presence of the disease, IHD=0 for the absence of the disease).

Conclusion: In the model, 50.4% of the variability in LV mass is explained by the variables used. The findings warrant further studies for the development of better and validated models that can be incorporated in microprocessor-based ECG devices. The determination of LVMI with ECG only will be a cost-effective and readily accessible tool in patient care.
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http://dx.doi.org/10.2147/MDER.S253792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295543PMC
June 2020

The Battle against COVID 19 Pandemic: What we Need to Know Before we "Test Fire" Ivermectin.

Drug Res (Stuttg) 2020 Aug 19;70(8):337-340. Epub 2020 Jun 19.

Demonstrator, Department of Pharmacology, The West Bengal University of Health Sciences, College of Medicine and JNM Hospital, Kalyani, West Bengal, India.

The world is faced with the dire challenge of finding an effective treatment against the rampaging COVID 19 pandemic. Amidst the crisis, reports of in vitro inhibitory activity of ivermectin, an approved anthelmintic, against the causative SARSCoV2 virus, have generated lot of optimism. In this article, we have fished and compiled the needed information on the drug, that will help readers and prospective investigators in having a quick overview. Though the primordial biological action of the drug is allosteric modulation of helminthic ion channel receptor, its in vitro activity against both RNA and DNA viruses is known for almost a decade. In the past two years, efficacy study in animal models of pseudorabies and zika virus was found to be favourable and unfavourable respectively. Only one clinical study evaluated the drug in dengue virus infection without any clinical efficacy. However, the proposed mechanism of drug action, by inhibiting the importin family of nucleus-cytoplasmic transporters along with favourable pharmacokinetics, warrants exploration of its role in COVID 19 through safely conducted clinical trials. Being an available and affordable drug, enlisted in WHO List of Essential Medicine, and a long track record of clinical safety, the drug is already in clinical trials the world over. As the pandemic continues to ravage human civilisation with unabated intensity, the world eagerly waits for a ray of hope emanating from the outcome of the ongoing trials with ivermectin as well as other drugs.
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http://dx.doi.org/10.1055/a-1185-8913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417290PMC
August 2020

Colonic Goblet Cell Carcinoid: Rarity of a Rarity! A Case Report and Review of Literature.

Chirurgia (Bucur) 2020 Jan-Feb;115(1):102-111

Goblet cell carcinoids (GCC) are extremelyrare neuroendocrine tumours, and characterised by their unique combination of two types of cancer cells âÃÂ" neuroendocrine (carcinoid) and epithelial (adeno-carcinoma). In spite of the fact that GCC is regarded as Neuro-Endocrine Tumour (NET), it does not illicit carcinoid syndrome. GCC usually arises in the appendix and accounting for less than 14% of all appendiceal tumours.Primary extra-appendiceal GCC have been reported as stomach, duodenum, small intestine, colon and rectum. The paper presents a rare case of GCC of the ascending colon in a 57-year-old male.
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http://dx.doi.org/10.21614/chirurgia.115.1.102DOI Listing
March 2020

LncRNAs as Potential Therapeutic Targets in Thyroid Cancer.

Asian Pac J Cancer Prev 2020 Feb 1;21(2):281-287. Epub 2020 Feb 1.

Department of Clinical Oncology, Queen Elizabeth Hospital, 30 Gascoigne Road, Hong Kong, China.

Thyroid cancer (TC) is the most common cancer of endocrine system. TC can be subdivided into 4 different entities, papillary, follicular, medullary and anaplastic thyroid cancer. Among them, anaplastic thyroid cancer has the poorest prognosis. Exploring new therapeutic approach may entail favorable prediction as well as increasing overall survival rate of patients. Long non-coding RNAs (lncRNAs), have vast implications in different cancer types. Although they are not transcribed into proteins, they can act as a harness in regulating a plethora of biological functions. They have been implicated in a decisive role in gene expression via modulation of both coding and non-coding RNAs. This article discuss the multi-facet role of lncRNA in thyroid cancer biology.
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http://dx.doi.org/10.31557/APJCP.2020.21.2.281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332117PMC
February 2020

A comparative experimental study of analgesic activity of a novel non-steroidal anti-inflammatory molecule - zaltoprofen, and a standard drug - piroxicam, using murine models.

J Exp Pharmacol 2019 2;11:85-91. Epub 2019 Aug 2.

Department of Pharmacology, All India Institute of Medical Sciences Bhopal, Bhopal, Madhya Pradesh, India.

Purpose: Pain is an unpleasant sensation, but a protective mechanism of our body. It is the most common medical complaint requiring a visit to a physician. The new non-steroidal anti-inflammatory drug (NSAID) - zaltoprofen, is a preferential COX-2 inhibitor. It also inhibits bradykinin-induced nociceptive responses by blocking the B2 receptor-mediated pathway in the primary sensory neurons. The present study was conducted to evaluate and compare the anti-nociceptive activity of zaltoprofen with a conventional NSAID - piroxicam, in a mouse model of acute pain using hot plate and tail flick tests.

Materials And Methods: Twenty-four adult Swiss albino mice (20-25 g) of either sex were used in this study. Oral zaltoprofen and piroxicam were used as test and standard drugs respectively. Anti-nociceptive activity was evaluated and compared using hot plate and tail flick tests.

Results: In comparison to the control group (vehicle), zaltoprofen showed a significant increase in reaction time at various time periods in the hot plate and tail flick tests. In the hot plate method, zaltoprofen groups (15 and 20 mg/kg) showed a significant elevation in pain threshold in comparison to control group (vehicle) (<0.001). In the tail flick model also, zaltoprofen groups (15 and 20 mg/kg) showed a significant increase in the reaction time in comparison to control group (vehicle). In both the analgesiometer assays, zaltoprofen was found to be non-inferior compared to a standard drug - piroxicam (positive control).

Conclusion: Our study concludes that zaltoprofen is an effective analgesic agent in various pain models. Our results support that zaltoprofen has therapeutic potential for treating pain disorders and is non-inferior to a standard drug - piroxicam.
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http://dx.doi.org/10.2147/JEP.S212988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683967PMC
August 2019

Medication concordance in modern medicine - A critical appraisal from an Indian perspective.

J Family Med Prim Care 2019 Apr;8(4):1313-1318

Department of Pharmacology, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India.

Modern medicine encompasses a holistic approach toward patient care that seeks to integrate the social, psychological, and pathological aspects of a disease. In line with this, the traditional model of improving treatment outcomes through improved compliance or adherence has given way to the concept of "concordance" that respects the integrity of the patient, autonomy, and self-determination. A self-conscious patient actively and equally participating in her or his comprehensive healthcare can bring a paradigm shift in the perceptions and functioning of the healthcare sector. Medication concordance can be expected to play a key role in improving patient well-being, clinical outcomes, and healthcare delivery. However, it is fraught with numerous questions to be addressed ranging from lack of clarity or standard protocol, medicolegal intricacies, cultural-linguistic barriers, illiteracy, shortage of time, infrastructure, and manpower. There are major challenges in the effective implementation of this initiative which has definite potential to prove beneficial in Indian healthcare settings. The success of this novel approach can only be accomplished by coordinated, inclusive, and persistent efforts from all participants of healthcare with fostering of a milieu of trust, belief, and communication. A systematic literature search was conducted using key words from relevant articles and MeSh terms on Google Scholar and PubMed. Data were abstracted according to their relevance to subheadings of the review and synthesis of concepts was done through multiple reviews by atleast two reviewers for any subsection.
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http://dx.doi.org/10.4103/jfmpc.jfmpc_176_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6510085PMC
April 2019

Effects of Different Biochars on Wheat Growth Parameters, Yield and Soil Fertility Status in a Silty Clay Loam Soil.

Molecules 2019 May 9;24(9). Epub 2019 May 9.

Department of Agronomy, Sindh Agriculture University, Tandojam 70060, Pakistan.

The conversion of organic wastes into biochar via the pyrolysis technique could be used to produce soil amendments useful as a source of plant nutrients. In this study, we investigated the effects of fruit peels and milk tea waste-derived biochars on wheat growth, yield, root traits, soil enzyme activities and nutrient status. Eight amendment treatments were tested: no amendment (CK), chemical fertilizer (CF), banana peel biochar 1% (BB1 + CF), banana peel biochar 2% (BB2 + CF), orange peel biochar 1% (OB1 + CF), orange peel biochar 2% (OB2 + CF), milk tea waste biochar 1% (TB1 + CF) and milk tea waste biochar 2% (TB2 + CF). The results indicated that chlorophyll values, plant height, grain yield, dry weight of shoot and root were significantly ( < 0.05) increased for the TB2 + CF treatment as compared to other treatments. Similarly, higher contents of nutrients in grains, shoots and roots were observed for TB2 + CF: N (61.3, 23.3 and 7.6 g kg), P (9.2, 10.4 and 8.3 g kg) and K (9.1, 34.8 and 4.4 g kg). Compared to CK, the total root length (41.1%), surface area (56.5%), root volume (54.2%) and diameter (78.4%) were the greatest for TB2 + CF, followed by BB2 + CF, OB2 + CF, TB1 + CF, BB1 + CF, OB1 + CF and CF, respectively. However, BB + CF and OB + CF treatments increased β-glucosidase and dehydrogenase, but not urease activity, as compared to the TB + CF amendment, while all enzyme activity decreased with the increased biochar levels. We concluded that the conversion of fruit peels and milk tea waste into biochar products contribute the benefits of environmental and economic issues, and should be tested as soil amendments combined with chemical fertilizers for the improvement of wheat growth and grain yield as well as soil fertility status under field conditions.
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http://dx.doi.org/10.3390/molecules24091798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540089PMC
May 2019

5-HT1A Receptor Function Makes Wound Healing a Happier Process.

Front Pharmacol 2018 11;9:1406. Epub 2018 Dec 11.

Sunnybrook Research Institute, Toronto, ON, Canada.

Skin wound healing is a multistage phenomenon that is regulated by cell-cell interplay and various factors. Endogenous serotonin is an important neurotransmitter and cytokine. Its interaction with the serotonin 1A receptor (5-HTR1A) delivers downstream cellular effects. The role of serotonin (5-hydroxytryptamine, 5-HT) and the 5-HT1A receptor has been established in the regeneration of tissues such as the liver and spinal motor neurons, prompting the investigation of the role of 5-HT1A receptor in skin healing. This study assessed the role of 5-HT1A receptor in excisional wound healing by employing an excisional punch biopsy model on 5-Ht1a receptor knockout mice. Post-harvest analysis revealed 5-Ht1a receptor knockout mice showed impaired skin healing, accompanied by a greater number of F4/80 macrophages, which prolongs the inflammatory phase of wound healing. To further unravel this phenomenon, we employed the 5-HT1A receptor agonist [(R)-(+)-8-Hydroxy-DPAT hydrobromide] as a topical cream treatment in an excisional punch biopsy model. The 5-HT1A receptor agonist treated group showed a smaller wound area, scar size, and improved neovascularization, which contributed to improve healing outcomes as compared to the control. Collectively, these findings revealed that serotonin and 5-HT1A receptor play an important role during the healing process. These findings may open new lines of investigation for the potential treatment alternatives to improve skin healing with minimal scarring.
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http://dx.doi.org/10.3389/fphar.2018.01406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6297675PMC
December 2018

Frequency of Ischemic Stroke Subtypes Based on Toast Classification at a Tertiary Care Center in Pakistan.

Asian J Neurosurg 2018 Oct-Dec;13(4):984-989

Department of Neurology, Shifa International Hospital, Islamabad, Pakistan.

Background: The purpose of this study was to determine the frequency of ischemic stroke subtypes based on Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification at a tertiary care center in Pakistan.

Materials And Methods: A cross-sectional study was conducted in Stroke Unit of Shifa International Hospital, Islamabad. We included 145 patients who presented to us from November 2015 to February 2016 with radiological confirmed neurological deficits consistent with ischemic stroke. The causes of ischemic stroke were classified according to TOAST criteria. Regression analysis and Chi-square test were used to compute value.

Results: Among the 145 patients diagnosed with ischemic stroke, there were 54.1% males and 45.9% females with a mean age of 65 ± 14 years. Nearly 62.7% patients had hypertension (HTN) as the most common risk factor, followed by 38.6% diabetes mellitus (DM), 27.5% heart failure, 19.3% valvular disease, 18.6% previous stroke, 16.4% smoking, 15.1% dyslipidemia, 13.7% ischemic heart disease, and 13.1% atrial fibrillation. HTN was significantly associated with large vessel disease ( = 0.028). DM was significantly associated with small vessel disease ( = 0.001). Smoking and atrial fibrillation both were associated with unknown etiology of stroke ( = 0.001 and = 0.039, respectively). Most common etiology of stroke was cardioembolism (40%), and atrial fibrillation is found to be the most common cause of cardioembolic stroke with 30.6% incidence.

Conclusion: Our study concludes that cardioembolic stroke is the most common cause of acute ischemic stroke in our stroke unit. Atrial fibrillation is found to be the most common cause of cardioembolic stroke.
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http://dx.doi.org/10.4103/ajns.AJNS_365_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6208235PMC
November 2018

Development of Criteria Highly Suggestive of Spinal Tuberculosis.

World Neurosurg 2018 Aug 31;116:e1002-e1006. Epub 2018 May 31.

Department of Neurosurgery, Aga Khan University Hospital, Karachi, Pakistan.

Background: In a developing country there is a need for development of criteria that can be used for the diagnosis of spinal tuberculosis, which is common in that region.

Methods: Demographic, clinical, and radiologic features of spinal tuberculosis and spinal epidural tumors have been compared statistically, and inferences have been drawn in terms of P values, sensitivity, specificity, positive predictive values, and negative predictive values.

Results: A statistically significant relationship was found between spinal tuberculosis and spinal pain, fever, gradually progressive lower limb weakness, contrast-enhancing epidural ± paravertebral lesions, continuous levels affected, spinal deformity, and raised erythrocyte sedimentation rate.

Conclusions: These relationships were considered the most probable criteria for the diagnosis of spinal tuberculosis.
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http://dx.doi.org/10.1016/j.wneu.2018.05.149DOI Listing
August 2018

The Role of Serotonin during Skin Healing in Post-Thermal Injury.

Int J Mol Sci 2018 Mar 29;19(4). Epub 2018 Mar 29.

Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.

Post-burn trauma significantly raises tissue serotonin concentration at the initial stages of injury, which leads us to investigate its possible role in post burn wound healing. Therefore, we planned this study to examine the role of serotonin in wound healing through in vitro and in vivo models of burn injuries. Results from in vitro analysis revealed that serotonin decreased apoptosis and increased cell survival significantly in human fibroblasts and neonatal keratinocytes. Cellular proliferation also increased significantly in both cell types. Moreover, serotonin stimulation significantly accelerated the cell migration, resulting in narrowing of the scratch zone in human neonatal keratinocytes and fibroblasts cultures. Whereas, fluoxetine (a selective serotonin reuptake inhibitor) and ketanserin (serotonin receptor 2A inhibitor) reversed these effects. Scald burn mice model (20% total body surface area) showed that endogenous serotonin improved wound healing process in control group, whereas fluoxetine and ketanserin treatments (disruptors of endogenous serotonin stimulation), resulted in poor reepithelization, bigger wound size and high alpha smooth muscle actin (α-SMA) count. All of these signs refer a prolonged differentiation state, which ultimately exhibits poor wound healing outcomes. Collectively, data showed that the endogenous serotonin pathway contributes to regulating the skin wound healing process. Hence, the results of this study signify the importance of serotonin as a potential therapeutic candidate for enhancing skin healing in burn patients.
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http://dx.doi.org/10.3390/ijms19041034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979562PMC
March 2018

Impact of pharmacist-led antibiotic stewardship program in a PICU of low/middle-income country.

BMJ Open Qual 2018 6;7(1):e000180. Epub 2018 Jan 6.

Department of Pediatrics and Child Health, Aga Khan University Hospital, Karachi, Pakistan.

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http://dx.doi.org/10.1136/bmjoq-2017-000180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5759741PMC
January 2018

Influences for gender disparity in dermatology in North America.

Int J Dermatol 2018 Feb;57(2):171-176

Department of Radiology, University of British Columbia, Vancouver, BC, Canada.

Background: Despite constituting half the population, women represent a minority of active physicians and hold a small proportion of faculty leadership positions in North America. However, dermatology is one of the few specialties where women comprise a substantial portion of the workforce. This study explores extent and contributors to gender disparity in academic dermatology faculty positions, leadership, and research.

Methods: We collected data on academic faculty including leadership from the websites of accredited U.S. and Canadian dermatology faculties. We used PubMed and SCOPUS to collect faculty research information including h-index, number of publications, citations, and years of active research.

Results: Although women constitute almost half of all dermatologists in the U.S. and Canada (47.9%), only one-fourth (26.1%) of all faculty heads are women. Furthermore, the proportion of women in higher faculty ranks (Assistant Professor, Associate Professors, and Professors) is much lower than males. Female dermatologists also have fewer publications, citations, and years of active research. Interestingly, having a female in a leadership position is associated with a higher proportion of female dermatologists in the faculty.

Conclusions: Gender disparity exists in academic dermatology, and the current academics fail to account for the enormous social challenges that women face, which may put them at a disadvantage to career advancement. Among other factors, better representation of female leadership may encourage and inspire women joining academic faculties in the future.
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http://dx.doi.org/10.1111/ijd.13875DOI Listing
February 2018

Calcification of the epiglottis presenting as foreign body sensation in the neck.

J Radiol Case Rep 2017 Jun 30;11(6):1-5. Epub 2017 Jun 30.

Department of Radiology, Geisinger Medical Center, Danville, USA.

The epiglottis plays an important role in preventing food of different consistencies from entering the airway during swallowing. Calcification of epiglottis can, potentially, alter and limit its movement causing aspiration amongst other swallowing problems. Isolated calcification of the epiglottis and its clinical presentation remains a poorly understood entity for radiologists as well as clinicians. Therefore, it is important to recognize the imaging features of epiglottic calcification, and it's known clinical presentations to help clinicians with early diagnosis and management.
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http://dx.doi.org/10.3941/jrcr.v11i6.3093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5743143PMC
June 2017

The response of muscle progenitor cells to cutaneous thermal injury.

Stem Cell Res Ther 2017 10 17;8(1):234. Epub 2017 Oct 17.

Sunnybrook Research Institute, Sunnybrook's Trauma, Emergency & Critical Care (TECC) Program, Ross Tilley Burn Centre, M7-161, Lab: M7-140, 2075 Bayview Ave., Toronto, ON, M4N 3 M5, Canada.

Background: Severe burn results in a systemic response that leads to significant muscle wasting. It is believed that this rapid loss in muscle mass occurs due to increased protein degradation combined with reduced protein synthesis. Alterations in the microenvironment of muscle progenitor cells may partially account for this pathology. The aim of this study was to ascertain the response of muscle progenitor cells following thermal injury in mice and to enlighten the cellular cascades that contribute to the muscle wasting.

Methods: C57BL/6 mice received a 20% total body surface area (TBSA) thermal injury. Gastrocnemius muscle was harvested at days 2, 7, and 14 following injury for protein and histological analysis.

Results: We observed a decrease in myofiber cross-sectional area at 2 days post-burn. This muscle atrophy was compensated for by an increase in myofiber cross-sectional area at 7 and 14 days post-burn. Myeloperoxidase (MPO)-positive cells (neutrophils) increased significantly at 2 days. Moreover, through Western blot analysis of two key mediators of the proteolytic pathway, we show there is an increase in Murf1 and NF-κB 2 days post-burn. MPO-positive cells were also positive for NF-κB, suggesting that neutrophils attain NF-κB activity in the muscle. Unlike inflammatory and proteolytic pathways, the number of Pax7-positive muscle progenitor cells decreased significantly 2 days post-burn. This was followed by a recovery in the number of Pax7-positive cells at 7 and 14 days, suggesting proliferation of muscle progenitors that accompanied regrowth.

Conclusion: Our data show a biphasic response in the muscles of mice exposed to burn injury, with phenotypic characteristics of muscle atrophy at 2 days while compensation was observed later with a change in Pax7-positive muscle progenitor cells. Targeting muscle progenitors may be of therapeutic benefit in muscle wasting observed after burn injury.
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http://dx.doi.org/10.1186/s13287-017-0686-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5646146PMC
October 2017

Congenital neonatal scalp arteriovenous malformation: a very rare entity.

BMJ Case Rep 2017 Jun 30;2017. Epub 2017 Jun 30.

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

Congenital arteriovenous malformations (AVMs) of scalp are rare congenital vascular malformations. They are usually not symptomatic at birth and are often misdiagnosed as haemangiomas. To date, only two cases of symptomatic neonatal scalp AVM have been reported in literature. Pathophysiology of congenital AVM is not completely understood but genetic and acquired causes are implicated. Diagnosis and management are often difficult and require multidisciplinary approach. We report a rare case of symptomatic congenital scalp AVM in a 10-day-old neonate who was successfully managed at our unit.
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http://dx.doi.org/10.1136/bcr-2016-218756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5534721PMC
June 2017

The critical role of macrophages in the pathogenesis of hidradenitis suppurativa.

Inflamm Res 2017 Nov 27;66(11):931-945. Epub 2017 Jun 27.

Faculty of Medicine, University of Toronto, Toronto, Canada.

Introduction: Hidradenitis suppurativa (HS) is a painful chronic inflammatory disease with a prevalence between 1 and 4% of general population. The pathogenesis of HS long eluded scientists, but growing evidence suggests that it is a consequence of inflammatory dysregulation.

Findings: Recent studies suggest that dysregulated immune response to skin flora and overexpression of inflammatory cytokines leads to chronic skin inflammation seen in HS. Macrophages are the most numerous inflammatory cells found in HS infiltrates and release numerous pro-inflammatory cytokines such as IL-23, and IL-1β and TNF-α, exacerbating the inflammation and contributing to the pathogenesis of HS. Furthermore, in HS, there is dysregulated function of other immune players closely associated with macrophage function including: matrix metalloproteases (MMP) 2 and 9 overexpression, toll-like receptor upregulation, impaired Notch signalling, NLRP3 inflammasome upregulation, and dysregulated keratinocyte function. Lifestyle factors including obesity and smoking also contribute to macrophage dysfunction and correlate with HS incidence.

Conclusions: The overexpression of pro-inflammatory cytokines and subsequent efficacy of anti-cytokine biologic therapies highlights the importance of managing macrophage dysfunction. Future therapies should target key molecular drivers of macrophage dysfunction such as TLR2 and NLRP3 overexpression.
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http://dx.doi.org/10.1007/s00011-017-1074-yDOI Listing
November 2017

The Role of Phytochemicals in the Inflammatory Phase of Wound Healing.

Int J Mol Sci 2017 May 16;18(5). Epub 2017 May 16.

Department of Surgery, University of Toronto, Toronto, ON M5S 1A8, Canada.

Historically, plant-based products have been the basis of medicine since before the advent of modern Western medicine. Wound dressings made of honey, curcumin and other phytochemical-rich compounds have been traditionally used. Recently, the mechanisms behind many of these traditional therapies have come to light. In this review, we show that in the context of wound healing, there is a global theme of anti-inflammatory and antioxidant phytochemicals in traditional medicine. Although promising, we discuss the limitations of using some of these phytochemicals in order to warrant more research, ideally in randomized clinical trial settings.
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http://dx.doi.org/10.3390/ijms18051068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454978PMC
May 2017

Bacterial contamination and stethoscope disinfection practices: a cross-sectional survey of healthcare workers in Karachi, Pakistan.

Trop Doct 2017 Jul 12;47(3):226-230. Epub 2017 Jan 12.

1 Graduate, Hamdard College of Medicine & Dentistry, Hamdard University, Karachi, Pakistan.

Stethoscopes routinely used for clinical examination of patients may potentially transfer micro-organisms and cause iatrogenic infections. This study was undertaken to detect the presence of microorganisms on stethoscopes used clinically in hospitals of Karachi, Pakistan and to ascertain the infection control practices of healthcare workers (HCWs). In a cross-sectional study, 118 samples were collected from public and private institutions. Samples were tested for the presence and sensitivity of pathogenic microorganisms. Microorganisms were found on diaphragms of 33/64 (51.6%) and 19/57 (33.3%) stethoscopes in public and private sector hospitals, respectively. Methycillin resistance was identified in all staphylococcally contaminated samples. Only 33 (18%) respondents reported cleaning their stethoscopes regularly. We highlight the need for more and better on-the-job routines for decontaminating stethoscopes among HCWs in Karachi.
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http://dx.doi.org/10.1177/0049475516686543DOI Listing
July 2017

Infraorbital nerve: a surgically relevant landmark for the pterygopalatine fossa, cavernous sinus, and anterolateral skull base in endoscopic transmaxillary approaches.

J Neurosurg 2016 12 4;125(6):1460-1468. Epub 2016 Mar 4.

Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and.

OBJECTIVE Endoscopic transmaxillary approaches (ETMAs) address pathology of the anterolateral skull base, including the cavernous sinus, pterygopalatine fossa, and infratemporal fossa. This anatomically complex region contains branches of the trigeminal nerve and external carotid artery and is in proximity to the internal carotid artery. The authors postulated, on the basis of intraoperative observations, that the infraorbital nerve (ION) is a useful surgical landmark for navigating this region; therefore, they studied the anatomy of the ION and its relationships to critical neurovascular structures and the maxillary nerve (V2) encountered in ETMAs. METHODS Endoscopic anatomical dissections were performed bilaterally in 5 silicone-injected, formalin-fixed cadaveric heads (10 sides). Endonasal transmaxillary and direct transmaxillary (Caldwell-Luc) approaches were performed, and anatomical correlations were analyzed and documented. Stereotactic imaging of each specimen was performed to correlate landmarks and enable precise measurement of each segment. RESULTS The ION was readily identified in the roof of the maxillary sinus at the beginning of the surgical procedure in all specimens. Anatomical dissections of the ION and the maxillary branch of the trigeminal nerve (V2) to the cavernous sinus suggested that the ION/V2 complex has 4 distinct segments that may have implications in endoscopic approaches: 1) Segment I, the cutaneous segment of the ION and its terminal branches (5-11 branches) to the face, distal to the infraorbital foramen; 2) Segment II, the orbitomaxillary segment of the ION within the infraorbital canal from the infraorbital foramen along the infraorbital groove (length 12 ± 3.2 mm); 3) Segment III, the pterygopalatine segment within the pterygopalatine fossa, which starts at the infraorbital groove to the foramen rotundum (13 ± 2.5 mm); and 4) Segment IV, the cavernous segment from the foramen rotundum to the trigeminal ganglion (15 ± 4.1 mm), which passes in the lateral wall of the cavernous sinus. The relationship of the ION/V2 complex to the contents of the cavernous sinus, carotid artery, and pterygopalatine fossa is described in the text. CONCLUSIONS The ION/V2 complex is an easily identifiable and potentially useful surgical landmark to the foramen rotundum, cavernous sinus, carotid artery, pterygopalatine fossa, and anterolateral skull base during ETMAs.
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http://dx.doi.org/10.3171/2015.9.JNS151099DOI Listing
December 2016

Clinical Efficacy, Safety, and Feasibility of Using Video Glasses during Interventional Radiologic Procedures: A Randomized Trial.

J Vasc Interv Radiol 2016 Feb 25;27(2):260-7. Epub 2015 Nov 25.

Department of Imaging Sciences, University of Rochester Medical Center, Rochester, NY 14642.

Purpose: To evaluate the clinical efficacy, safety, and feasibility of implementing video glasses in a variety of interventional radiologic (IR) procedures.

Materials And Methods: Between August 2012 and August 2013, 83 patients undergoing outpatient IR procedures were randomized to a control group (n = 44) or an experimental group outfitted with video glasses (n = 39). State-Trait Anxiety Inventory (STAI) scores, sedation and analgesia doses, mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), pain scores, and procedure times were obtained. Complications and adverse events related to the use of video glasses were recorded. Postprocedural staff surveys and patient satisfaction surveys were completed.

Results: Women had greater preprocedural anxiety than men (P = .0056), and patients undergoing vascular interventions had greater preprocedural anxiety than those undergoing nonvascular interventions (P = .0396). When assessed after the procedure, patients who wore video glasses had significantly reduced levels of anxiety (-7.7 vs -4.4, respectively; P = .0335) and average MAP (-6.3 vs 2.1, respectively; P = .0486) compared with control patients. There was no significant difference in amount of sedation and analgesia, HR, RR, pain score, or procedure time between groups. No significant adverse events related to the use of video glasses were observed. Postprocedural surveys showed that video glasses were not distracting and did not interfere or pose a safety issue during procedures. Patients enjoyed using the video glasses and would use them again for a future procedure.

Conclusions: Video glasses can be safely implemented during IR procedures to reduce anxiety and improve a patient's overall experience.
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http://dx.doi.org/10.1016/j.jvir.2015.09.023DOI Listing
February 2016

Predictors of postpericardiotomy syndrome.

Am J Emerg Med 2015 Sep 30;33(9):1320. Epub 2015 May 30.

Cardiology Division, Mercer University School of Medicine, Macon, GA.

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http://dx.doi.org/10.1016/j.ajem.2015.05.038DOI Listing
September 2015

Preservation of Glucagon-Like Peptide-1 Level Attenuates Angiotensin II-Induced Tissue Fibrosis by Altering AT1/AT 2 Receptor Expression and Angiotensin-Converting Enzyme 2 Activity in Rat Heart.

Cardiovasc Drugs Ther 2015 Jun;29(3):243-55

Department of Cardiology, Shanxi Medical University, Shanxi Dayi Hospital, Taiyuan, Shanxi, China.

Purpose: The glucagon-like peptide-1 (GLP-1) has been shown to exert cardioprotective effects in animals and patients. This study tests the hypothesis that preservation of GLP-1 by the GLP-1 receptor agonist liraglutide or the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin is associated with a reduction of angiotensin (Ang) II-induced cardiac fibrosis.

Methods And Results: Sprague-Dawley rats were subjected to Ang II (500 ng/kg/min) infusion using osmotic minipumps for 4 weeks. Liraglutide (0.3 mg/kg) was subcutaneously injected twice daily or linagliptin (8 mg/kg) was administered via oral gavage daily during Ang II infusion. Relative to the control, liraglutide, but not linagliptin decreased MAP (124 ± 4 vs. 200 ± 7 mmHg in control, p < 0.003). Liraglutide and linagliptin comparatively reduced the protein level of the Ang II AT1 receptor and up-regulated the AT2 receptor as identified by a reduced AT1/AT2 ratio (0.4 ± 0.02 and 0.7 ± 0.01 vs. 1.4 ± 0.2 in control, p < 0.05), coincident with the less locally-expressed AT1 receptor and enhanced AT2 receptor in the myocardium and peri-coronary vessels. Both drugs significantly reduced the populations of macrophages (16 ± 6 and 19 ± 7 vs. 61 ± 29 number/HPF in control, p < 0.05) and α-SMA expressing myofibroblasts (17 ± 7 and 13 ± 4 vs. 66 ± 29 number/HPF in control, p < 0.05), consistent with the reduction in expression of TGFβ1 and phospho-Smad2/3, and up-regulation of Smad7. Furthermore, ACE2 activity (334 ± 43 and 417 ± 51 vs. 288 ± 19 RFU/min/μg protein in control, p < 0.05) and GLP-1 receptor expression were significantly up-regulated. Along with these modulations, the synthesis of collagen I and tissue fibrosis were inhibited as determined by the smaller collagen-rich area and more viable myocardium.

Conclusion: These results demonstrate for the first time that preservation of GLP-1 using liraglutide or linagliptin is effective in inhibiting Ang II-induced cardiac fibrosis, suggesting that these drugs could be selected as an adjunctive therapy to improve clinical outcomes in the fibrosis-derived heart failure patients with or without diabetes.
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http://dx.doi.org/10.1007/s10557-015-6592-7DOI Listing
June 2015

Wearing the mask of ST-elevation myocardial infarction: postpericardiotomy syndrome.

Am J Emerg Med 2015 Aug 2;33(8):1115.e5-7. Epub 2015 Feb 2.

Cardiology Division, Mercer University School of Medicine, Macon, GA.

Introduction: Postpericardiotomy syndrome (PPS) is an inflammatory process, affecting 15% to 20% of patients, after surgery involving pleura, pericardium, or both. The role of electrocardiogram (ECG) in diagnosing PPS is uncertain because ECG is rarely normal (especially after cardiac surgery). We report a case of PPS that presented initially with localized ST-segment elevation and also discuss proposed mechanisms.

Clinical Case: A 60-year-old White man presented to the emergency department (ED) after having chest pain, shortness of breath, and palpitation for approximately 2 hours. Patient had known coronary artery disease, status postcoronary artery bypass graft a month earlier with a graft to right coronary artery, and 2 grafts to marginal arteries. In the ED, ECG revealed localized ST-segment elevations in leads II, III, and aVF. Coronary angiography did not reveal significant coronary artery stenosis, and all the grafts were found to be patent. Following ECG showed PR depression along with diffuse ST elevation consistent with pericarditis. Patient was started on nonsteroidal anti-inflammatory drugs and colchicine with significant improvement of his symptoms in a few days.

Discussion: In our patient, injury or surgical manipulation to the area perfused by right coronary artery might have initiated a process, initially localized to the inferior wall with subsequent diffuse involvement of the entire pericardium. The presentation of our patient shortly after the development of chest pain and availability of 2 ECGs a few minutes apart may have shed light on the pathophysiology of PPS.
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http://dx.doi.org/10.1016/j.ajem.2015.01.048DOI Listing
August 2015

Defining hyponatraemia: a call for action.

Eur J Heart Fail 2012 Oct 31;14(10):1085-6. Epub 2012 Aug 31.

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http://dx.doi.org/10.1093/eurjhf/hfs140DOI Listing
October 2012