Chen A.C.-H.,Massachusetts General Hospital |
Arany P.R.,Massachusetts General Hospital |
Arany P.R.,Harvard University |
Arany P.R.,Brigham and Women's Hospital |
And 16 more authors.
PLoS ONE | Year: 2011
Background: Despite over forty years of investigation on low-level light therapy (LLLT), the fundamental mechanisms underlying photobiomodulation at a cellular level remain unclear. Methodology/Principal Findings: In this study, we isolated murine embryonic fibroblasts (MEF) from transgenic NF-kB luciferase reporter mice and studied their response to 810 nm laser radiation. Significant activation of NF-kB was observed at fluences higher than 0.003 J/cm 2 and was confirmed by Western blot analysis. NF-kB was activated earlier (1 hour) by LLLT compared to conventional lipopolysaccharide treatment. We also observed that LLLT induced intracellular reactive oxygen species (ROS) production similar to mitochondrial inhibitors, such as antimycin A, rotenone and paraquat. Furthermore, we observed similar NF-kB activation with these mitochondrial inhibitors. These results, together with inhibition of laser induced NF-kB activation by antioxidants, suggests that ROS play an important role in the laser induced NF-kB signaling pathways. However, LLLT, unlike mitochondrial inhibitors, induced increased cellular ATP levels, which indicates that LLLT also upregulates mitochondrial respiration. Conclusion: We conclude that LLLT not only enhances mitochondrial respiration, but also activates the redox-sensitive NFkB signaling via generation of ROS. Expression of anti-apoptosis and pro-survival genes responsive to NFkB could explain many clinical effects of LLLT. © 2011 Chen et al.
Mroz P.,Massachusetts General Hospital |
Mroz P.,Harvard University |
Huang Y.-Y.,Massachusetts General Hospital |
Huang Y.-Y.,Harvard University |
And 25 more authors.
FASEB Journal | Year: 2010
Cutaneous malignant melanoma remains a therapeutic challenge, and patients with advanced disease have limited survival. Photodynamic therapy (PDT) has been successfully used to treat many malignancies, and it may show promise as an antimelanoma modality. However, high melanin levels in melanomas can adversely affect PDT effectiveness. Herein the extent of melanin contribution to melanoma resistance to PDT was investigated in a set of melanoma cell lines that markedly differ in the levels of pigmentation; 3 new bacteriochlorins successfully overcame the resistance. Cell killing studies determined that bacteriochlorins are superior at (LD50≈0.1 μM) when compared with controls such as the FDA-approved Photofrin (LD50≈10 μM) and clinically tested LuTex (LD50≈1 μM). The melanin content affects PDT effectiveness, but the degree of reduction is significantly lower for bacteriochlorins than for Photofrin. Microscopy reveals that the least effective bacteriochlorin localizes predominantly in lysosomes, while the most effective one preferentially accumulates in mitochondria. Interestingly all bacteriochlorins accumulate in melanosomes, and subsequent illumination leads to melanosomal damage shown by electron microscopy. Fluorescent probes show that the most effective bacteriochlorin produces significantly higher levels of hydroxyl radicals, and this is consistent with the redox properties suggested by molecular-orbital calculations. The best in vitro performing bacteriochlorin was tested in vivo in a mouse melanoma model using spectrally resolved fluorescence imaging and provided significant survival advantage with 20% of cures (P<0.01). © FASEB.
PubMed | Shaukat Khanum Memorial Cancer Hospital and Research Center, The Surgical Center, Aga Khan Medical College, Aga Khan University and Lahore Medical and Dental College
Type: Journal Article | Journal: Tumori | Year: 2016
Improving survival has been documented for oral squamous cell carcinoma in recent years. It is a common malignancy in Pakistan but survival outcomes have not been reported. The objective of this study was to determine survival and identify independent predictors in patients with oral squamous cell cancer in 2 different time periods.A retrospective review of patients who received treatment between 2003 and 2012 was performed. Patients were divided into two 5 year groups: group 1 (2003-2007) (n = 628) and group 2 (2008-2012) (n = 920). Demographics, risk factors, treatment approaches, and outcomes were compared. Disease-free and overall survival were calculated. Cox proportional hazard model was used to determine independent predictors of survival.A significant difference was present for ethnicity and grade and clinical T and N stage of tumors, with earlier presentation in group 2. More patients underwent surgery (p = 0.001) and had radical treatment intent (p<0.0001) in recent years. Induction chemotherapy (p<0.0001) and palliative chemotherapy (p<0.0001) were used more frequently. No significant difference in disease-free survival was observed but overall 5-year survival improved significantly (23% vs 42%) (p<0.0001). Use of palliative chemotherapy reduced risk of death significantly (hazard ratio [HR] 0.1, confidence interval [CI] 0.02-0.4, p = 0.003), while pathologic nodal positivity significantly increased the risk (HR 2.5, CI 1-5.9, p = 0.03).These results from a single cancer hospital demonstrate improvement in overall survival secondary to early detection, better patient selection, and use of palliative chemotherapy in the later period.
Hashmi J.T.,Massachusetts General Hospital |
Hashmi J.T.,Harvard University |
Huang Y.-Y.,Massachusetts General Hospital |
Huang Y.-Y.,Harvard University |
And 8 more authors.
PM and R | Year: 2010
This year marks the 50th anniversary of the discovery of the laser. The development of lasers for medical use, which became known as low-level laser therapy (LLLT) or photobiomodulation, followed in 1967. In recent years, LLLT has become an increasingly mainstream modality, especially in the areas of physical medicine and rehabilitation. At first used mainly for wound healing and pain relief, the medical applications of LLLT have broadened to include diseases such as stroke, myocardial infarction, and degenerative or traumatic brain disorders. This review will cover the mechanisms of LLLT that operate both on a cellular and a tissue level. Mitochondria are thought to be the principal photoreceptors, and increased adenosine triphosphate, reactive oxygen species, intracellular calcium, and release of nitric oxide are the initial events. Activation of transcription factors then leads to expression of many protective, anti-apoptotic, antioxidant, and pro-proliferation gene products. Animal studies and human clinical trials of LLLT for indications with relevance to neurology, such as stroke, traumatic brain injury, degenerative brain disease, spinal cord injury, and peripheral nerve regeneration, will be covered. © 2010 by the American Academy of Physical Medicine and Rehabilitation.
Faqah A.,Aga Khan Medical College |
Moiz B.,Aga Khan Medical College |
Shahid F.,Aga Khan Medical College |
Ibrahim M.,Dow University of Health Sciences |
Raheem A.,Aga Khan University
Transfusion and Apheresis Science | Year: 2015
Objective: Theory of Planned Behavior proposes a model which can measure how human actions are guided. It has been successfully utilized in the context of blood donation. We employed a decision-making framework to determine the intention of blood donation among medical students who have never donated blood before the study. Methods: Survey responses were collected from 391 medical students from four various universities on a defined questionnaire. The tool composed of 20 questions that were formulated to explain donation intention based on theory of planned behavior. The construct included questions related to attitude, subjective norm and perceived behavior control, descriptive norm, moral norm, anticipated regret, donation anxiety and religious norm. Pearson's correlational relationships were measured between independent and dependent variables of intention to donate blood. ANOVA was applied to observe the model fit; a value of 0.000 was considered statistically significant. A multiple regression analysis was conducted to explore the relative importance of the main independent variables in the prediction of intention. Multi-collinearity was also evaluated to determine that various independent variables determine the intention. The reliability of measures composed of two items was assessed using inter-item correlations. Results: Three hundred and ninety-one medical students (M:F; 1:2.2) with mean age of 21.96 years±1.95 participated in this study. Mean item score was 3.8±0.83. Multiple regression analysis suggested that perceived behavioral control, anticipated regret and attitude were the most influential factors in determining intention of blood donation. Donation anxiety was least correlated and in fact bore a negative correlation with intention. ANOVA computed an F value of 199.082 with a p-value of 0.000 indicating fitness of model. The value of R square and adjusted R square was 0.811 and 0.807 respectively indicating strong correlation between various independent and dependent variables. Conclusions: Medical students as novice blood donors showed a positive attitude toward blood donation. Theory of planned behavior can be successfully utilized in determining the antecedents toward blood donation behavior. © 2015 Elsevier Ltd.
PubMed | Dow University of Health Sciences, Aga Khan Medical College and Aga Khan University
Type: Journal Article | Journal: Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis | Year: 2015
Theory of Planned Behavior proposes a model which can measure how human actions are guided. It has been successfully utilized in the context of blood donation. We employed a decision-making framework to determine the intention of blood donation among medical students who have never donated blood before the study.Survey responses were collected from 391 medical students from four various universities on a defined questionnaire. The tool composed of 20 questions that were formulated to explain donation intention based on theory of planned behavior. The construct included questions related to attitude, subjective norm and perceived behavior control, descriptive norm, moral norm, anticipated regret, donation anxiety and religious norm. Pearsons correlational relationships were measured between independent and dependent variables of intention to donate blood. ANOVA was applied to observe the model fit; a value of 0.000 was considered statistically significant. A multiple regression analysis was conducted to explore the relative importance of the main independent variables in the prediction of intention. Multi-collinearity was also evaluated to determine that various independent variables determine the intention. The reliability of measures composed of two items was assessed using inter-item correlations.Three hundred and ninety-one medical students (M:F; 1:2.2) with mean age of 21.96 years 1.95 participated in this study. Mean item score was 3.8 0.83. Multiple regression analysis suggested that perceived behavioral control, anticipated regret and attitude were the most influential factors in determining intention of blood donation. Donation anxiety was least correlated and in fact bore a negative correlation with intention. ANOVA computed an F value of 199.082 with a p-value of 0.000 indicating fitness of model. The value of R square and adjusted R square was 0.811 and 0.807 respectively indicating strong correlation between various independent and dependent variables.Medical students as novice blood donors showed a positive attitude toward blood donation. Theory of planned behavior can be successfully utilized in determining the antecedents toward blood donation behavior.
PubMed | Jinnah Postgraduate Medical Institute, Aga Khan University, Sultan Qaboos University and Aga Khan Medical College
Type: Journal Article | Journal: Indian journal of cancer | Year: 2017
Breast cancer is the most common cancer in Pakistani women. We report the presenting features, treatment patterns and survival of breast cancer from a University Hospital in Southern Pakistan and compare the data with international population based studies.Medical records of patients diagnosed to have breast cancer between January 1999 and November 2008 were reviewed retrospectively.A total of 845 patients were identified. Median age of diagnosis was 48 years (range 18-92). Clinical stage was as follows: Stage I 9.9%; Stage II 48.5%; Stage III 26.2%; Stage IV 13.8%; data not available 1.5%. Approximately, half (51.6%) were estrogen receptor (ER) positive and 17.5% over-expressed Her2/neu. Nearly 23% patients received neo-adjuvant chemotherapy while 68.9% received adjuvant chemotherapy. Anthracycline based treatment was the most common treatment until 2003 while later on, patients also received taxanes and trastuzumab based therapy. Age, stage, tumor size, lymph node status, tumor grade, ER status, treatment with hormonal therapy and radiation were the major predictive factors for overall survival (OS). We report an impressive 5 year OS of 75%, stage specific survival was 100%, 88% and 58% for Stages I, II and III respectively.The majority of patients present at a younger age and with locally advanced disease. However, short term follow-up reveals that the outcomes are comparable with the published literature from developed countries. Long-term follow-up and inclusion of data from population-based registries are required for accurate comparison.
Almas A.,Aga Khan University |
Godil S.S.,Aga Khan Medical College |
Lalani S.,Aga Khan Medical College |
Samani Z.A.,Aga Khan Medical College |
Khan A.H.,Aga Khan University
BMC Research Notes | Year: 2012
Background: According to the National Health survey only 3% of the population has controlled hypertension. This study was designed to elucidate the knowledge about hypertension in hypertensive patients at three tertiary care centers in Karachi. Secondly we sought to compare the knowledge of those with uncontrolled hypertension and controlled hypertension. Methods. It was a cross-sectional study conducted at The Aga Khan University hospital (AKUH), Ziauddin Hospital (ZH) and Civil hospital, Karachi (CHK. All diagnosed Hypertensive patients (both inpatients and outpatients) coming to a tertiary care hospital in Pakistan aged > 18 years were included. Patients were categorized into 2 groups: controlled and uncontrolled hypertension based on their initial BP readings on presentation Uncontrolled Hypertension was defined as average BP ≥ 140/90 mm Hg in patients on treatment. Controlled Hypertension (HTN) was defined as average BP <140/90 mm Hg in patients on treatment. Standardized methods were used to record BP in the sitting position. Knowledge was recorded as a15 item question. Primary outcome was knowledge about hypertension. Results: A total of 650 participants were approached and consented 447 were found eligible. 284(63.5%) were from Aga Khan University, 101(22.6) from Dow University of health sciences and 62(13.9) were from Ziauddin University. Mean (SD) age of participants was 57.7(12) years, 50.1(224) were men. Controlled hypertension was present in 323(72.3) and uncontrolled hypertension was present in 124(27.4). The total mean (SD) Knowledge score was 20.97(4.93) out of a maximum score of 38. On comparison of questions related to knowledge between uncontrolled and controlled hypertension, there was statistically significant different in; meaning of hypertension (p <0.001), target SBP(p0.001), target DBP(p 0.001), importance of SBP versus DBP, improvement of health with lowering of blood pressure (p 0.002), high blood pressure being asymptomatic (p <0.001), changing lifestyle improves blood pressure(p 0.003),hypertension being a lifelong disease (<0.001), lifelong treatment with antihypertensives(<0.001) and high blood pressure being part of aging(<0.001). On comparison of knowledge as a composite score between uncontrolled and controlled hypertensive; Mean (SD) score was 21.85(4.74) v18.67 (4.70) (p value: < 0.001). On multivariate analysis; gender β (95% CI) 1.67(0.75, 2.59) p <0.001, uncontrolled blood pressure; -2.70(-3.76,-1.67) p <0.001, Sindhi ethnicity; -1.79(-3.25,-3.27) p 0.01 and pukhtoon ethnicity; -2.72(-4.13,-1.32) p <0.001 were significantly associated with knowledge score. Conclusion: Knowledge about hypertension in hypertensive patients is not adequate and is alarmingly poor in patients with uncontrolled hypertension. More emphasis needs to be made on target blood pressure and need for taking antihypertensives for life to patients by physicians. © 2012 Almas et al.; licensee BioMed Central Ltd.
Raza A.,Aga Khan University |
Ghanchi N.K.,Aga Khan University |
Thaver A.M.,Aga Khan Medical College |
Jafri S.,Aga Khan University |
Beg M.A.,Aga Khan University
Malaria Journal | Year: 2013
Background: Plasmodium vivax is the prevalent malarial species accounting for 70% of malaria burden in Pakistan; however, there is no baseline data on the circulating genotypes. Studies have shown that polymorphic loci of gene encoding antigens pvcsp and pvmsp1 can be used reliably for conducting molecular epidemiological studies. Therefore, this study aimed to bridge the existing knowledge gap on population structure on P. vivax from Pakistan using these two polymorphic genes. Methods. During the period January 2008 to May 2009, a total of 250 blood samples were collected from patients tested slide positive for P. vivax, at the Aga Khan University Hospital, Karachi, or its collection units located in Baluchistan and Sindh Province. Nested PCR/RFLP was performed, using pvcsp and pvmsp1 markers to detect the extent of genetic diversity in clinical isolates of P. vivax from southern Pakistan. Results: A total of 227/250 (91%) isolates were included in the analysis while the remainder were excluded due to negative PCR outcome for P.vivax. Pvcsp analysis showed that both VK 210 (85.5%, 194/227) and VK 247 type (14.5%, 33/227) were found to be circulating in P. vivax isolates from southern Pakistan. A total of sixteen and eighty-seven genotypes of pvcsp and pvmsp-1 were detected respectively. Conclusion: This is the first report from southern Pakistan on characterization of P. vivax isolates confirming that extensively diverse pvcsp and pvmsp1 variants are present within this region. Results from this study provide valuable data on genetic diversity of P. vivax that will be helpful for further epidemiological studies. © 2013 Raza et al.; licensee BioMed Central Ltd.
PubMed | Indus Hospital, Aga Khan Medical College and Aga Khan University
Type: Journal Article | Journal: JPMA. The Journal of the Pakistan Medical Association | Year: 2016
In a developing country like Pakistan, laparoscopic surgeries are not considered favourable by many, possibly because of high costs or a lack of expertise. It is an established fact that laparoscopic surgery offers better surgical treatments with a shorter hospital stay and fewer complications. The current retrospective study was conducted at a tertiary care hospital in Karachi and comprised of laparoscopy cases performed by a single surgeon from March 2012 to September of 2014. A total of 100laparoscopic surgeries were performed; mostly appendectomies 49(49%) and undescended testes (UDTs) 34(34%). Overall, there were 70(70%) male patients. The mean age of the patients was 7.1 years and standard deviation (SD) of 2. Four (4%) patients had cellulitis. Laparoscopy paediatric surgery offered advantages of fewer wound-associated complications, less incisional pain, a shorter recovery time, and improved cosmesis.