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Karachi, Pakistan

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. Source

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. Source

Chen A.C.-H.,Massachusetts General Hospital | Arany P.R.,Massachusetts General Hospital | Arany P.R.,Harvard University | Arany P.R.,Brigham and Womens 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. Source

Afroze B.,Aga Khan University | Lakhani L.,Aga Khan Medical College | Naz F.,Aga Khan Medical College | Somani S.,Aga Khan Medical College | And 2 more authors.
Egyptian Journal of Medical Human Genetics | Year: 2016

Background: Pakistan is the sixth most populous country in the World. High rates of consanguinity and inter caste marriages have resulted in a substantial burden of inherited metabolic disorders (IMDs). Despite this load, there is a dearth of both medical genetic and clinical metabolic services in Pakistan. There are inadequate numbers of appropriately trained clinicians, ill-equipped laboratories, lack of scientists and technologists equipped with skills to deal with the challenging laboratory investigations involved in IMD and a health care infra-structure unable to support a service. Aim: We present the first five year experience of the first established metabolic unit at a tertiary care hospital in Pakistan and present the case for screening of parents, parents' siblings and antenatal diagnostic testing in subsequent pregnancies in order that families can make informed choices in preventing recurrence. Subjects and methods: This retrospective observational study comprising of patients' chart review was conducted in the Department of Paediatrics, AKUH Karachi in Pakistan for patients who presented to the Clinical Genetics unit from January 2008 to December 2012 seeking diagnosis and treatment for the underlying IMD. Results: We evaluated 426 children, of which, 333 (78%) had consanguineous parents. Most patients, 151 (35%). evaluated for IMD were between 1. year and 5. years of age. Developmental delay, seizures, hypotonia, microcephaly, neuroregression, dystonia, ataxia and encephalopathy were the most common reasons for referrals. Only 155 (36%) patients underwent metabolic biochemical testing. Among the investigated group of patients, diagnoses were established for 85 (55%) patients equivalent to only 19.8% of the total. Conclusion: Neonatal screening for IMDs and their treatment in the current situation is an unaffordable practical option in Pakistan. Screening parents, siblings and subsequent pregnancies, however, is likely to provide a cost effective and acceptable alternative in reducing the burden and enabling early, effective detection of affected progeny before the stage when neurometabolic changes become irreversible in developing countries like Pakistan with very limited resources. © 2016 Ain Shams University. Source

Bhatti A.B.H.,The Surgical Center | Jamshed A.,Shaukat Khanum Memorial Cancer Hospital and Research Center | Iqbal H.,The Surgical Center | Hafeez A.,Aga Khan University | And 4 more authors.
Tumori | Year: 2016

Aims and background: 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. Methods: 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. Results: 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). Conclusions: 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. © 2016 Wichtig Publishing. Source

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