Contrast enhanced sonothrombolysis using streptokinase loaded phase change nano-droplets for potential treatment of deep venous thrombosis.

Current thrombolytic therapies for deep venous thrombosis are limited due to the wide side effect profile. Contrast mediated sonothrombolysis is a promising approach for thrombus treatment. The current study examines the effectiveness of in vitro streptokinase (SK) loaded phase-change nanodroplet (PCND) mediated sonothrombolysis at 7 MHz for the diagnosis of deep venous thrombosis. Lecithin shell and perfluorohexane core nanodroplets were prepared via the thin-film hydration method and morphologically characterized. Sonothrombolysis was performed at 7 MHz at different mechanical indexes of samples i.e., only sonothrombolysis, PCND mediated sonothrombolysis, sonothrombolysis with SK and SK loaded PCND mediated sonothrombolysis. Thrombolysis efficacy was assessed by measuring clot weight changes during 30 min US exposure, recording the mean gray intensity from the US images of the clot by computer software ImageJ, and spectrophotometric quantification of the hemoglobin in the clot lysate. In 15 minutes of sonothrombolysis performed at high mechanical index (0.9 and 1.2), SK loaded PCNDs showed a 48.61% and 74.29% reduction of mean gray intensity. At 0.9 and 1.2 MI, 86% and 92% weight loss was noted for SK-loaded PCNDs in confidence with spectrophotometric results. A significant difference (P < 0.05) was noted for SK-loaded PCND mediated sonothrombolysis compared to other groups. Loading of SK inside the PCNDs enhanced the efficacy of sonothrombolysis. An increase in MI and time also increased the efficacy of sonothrombolysis. This in vitro study showed the potential use of SK-loaded perfluorohexane core PCNDs as sonothrombolytic agents for deep venous thrombosis.

Novel Magnetic Elastic Phase-Change Nanodroplets as Dual Mode Contrast Agent for Ultrasound and Magnetic Resonance Imaging.

Recently, dual-mode imaging systems merging magnetic resonance imaging (MRI) and ultrasound (US) have been developed. Designing a dual-mode contrast agent is complex due to different mechanisms of enhancement. Herein, we describe novel phase change nanodroplets (PCNDs) with perfluoropentane encapsulated in a pre-polyglycerol sebacate (pre-PGS) shell loaded with polyethylene glycol (PEG)-coated iron oxide nanoparticles as having a dual-mode contrast agent effect. Iron oxide nanoparticles were prepared via the chemical co-precipitation method and PCNDs were prepared via the solvent displacement technique. PCNDs showed excellent enhancement in the in vitro US much more than Sonovue® microbubbles. Furthermore, they caused a susceptibility effect resulting in a reduction of signal intensity on MRI. An increase in the concentration of nanoparticles caused an increase in the MR contrast effect but a reduction in US intensity. The concentration of nanoparticles in a shell of PCNDs was optimized to obtain a dual-mode contrast effect. Biocompatibility, hemocompatibility, and immunogenicity assays showed that PCNDs were safe and non-immunogenic. Another finding was the dual-mode potential of unloaded PCNDs as T1 MR and US contrast agents. Results suggest the excellent potential of these PCNDs for use as dual-mode contrast agents for both MRI and US.

Assessment Of Carpal Tunnel Syndrome With Ultrasonography.

BACKGROUND: Carpal tunnel syndrome (CTS) is the most common nerve entrapment neuropathy caused by compression of median nerve at wrist as it passes through Osseo fibrous canal known as carpal tunnel. Epidemiological statistics shows one in every ten people develops the disease at any stage of life. CTS mostly affect females than males with mean age of 50. Clinical features are considered to be enough for establishing the diagnosis of carpal tunnel syndrome. However, nerve conduction studies give quantitative information regarding median nerve function therefore good at predicting outcome of intervention. Ultrasound being easily available, cost effective and real time is a promising modality for diagnosis and grading carpal tunnel syndrome. METHODS: This correlational study was conducted in collaboration of Neurology and Radiology Department of Pakistan Institute of Medical Sciences, Islamabad from January 2018 to January 2019. Total 50 patients with 85 wrists involved were included in the study. All patients with positive nerve conduction study were included. Patient with history of wrist trauma were not included. Detailed history and clinical features were recorded. All patients with positive result on nerve conduction studies underwent ultrasound examinations. Fifty control wrists were also included to establish the normal median nerve cross sectional area value in our study population. Results were recorded. Data was analyzed and appropriate statistical tests were applied by using SPSS v20. RESULTS: Mean cross sectional area of median nerve for controls was 6.34±1.23. Mean cross sectional area of median nerve for mild CTS was 8.05±1.72, moderate CTS was 11.15±2.32, severe was 17.49±4.93. Strong correlation was found between (r=0.76, p-value <0.0001) between increased cross-sectional area on Ultrasonography and severity of CTS on NCS. Other finding on Ultrasonography included flattening in 4 and fluid in 10 affected wrists. CONCLUSIONS: Increased cross-sectional area on Ultrasonography and severity of carpal tunnel syndrome on nerve conduction studies are very strongly correlated.

Monodisperse magnetic lecithin-PFP submicron bubbles as dual imaging contrast agents for ultrasound (US) and MRI.

Multimodal imaging is a recent idea of combining two or more imaging methods synergistically to overcome the weakness of individual imaging modalities and utilizing complementary benefits. Ultrasound (US) and magnetic resonance imaging (MRI) are widely used imaging techniques in healthcare and to fully utilize the potential of fusion imaging, dual-modal contrast agents are necessary to improve disease diagnosis by enhancing contrast resolution and reducing health risks associated with the dual dosage of contrast agents. In this study, magnetic microbubbles were synthesized by incorporating oleic acid stabilized superparamagnetic iron oxide nanoparticles (OA-SPIONs) into lecithin microbubbles, encapsulating the perfluoropentane (PFP) core. The magnetic microbubbles were characterized by FTIR, SEM, MFM, zeta potential, in vitro MRI, and ultrasound. Upon in vitro MRI, magnetic microbubbles showed a negative contrast effect by producing darker T2 weighted images. Magnetic microbubbles showed concentration-dependent response with a decrease in signal intensity with an increase in the concentration of OA-IONP in microbubbles. However, a decrease in acoustic enhancement was also observed with an increase in OA-IONP concentration, therefore concentration was optimized to achieve the best effect on both modalities. The magnetic lecithin microbubble with 10 mg SPIONs provided the best contrast on both US and MR imaging. The hemocompatibility testing resulted in hemolysis less than 7% with plasma recalcification time and thrombin time of 240 s and 6 s corresponding to excellent hemocompatibility. Thus the magnetic microbubbles with a phase convertible PFP core encapsulated by a lecithin shell loaded with OA-SPIONs can serve as a potential bimodal contrast agent for both US and MRI imaging.

Breast Hemangioma: Unique Presentation in a Patient with Klippel- Trenaunay-syndrome.

BACKGROUND: Klippel-Trénaunay-Syndrome (KTS) is characterized by a triad of varicose veins, port-wine stain and soft tissue or bony hypertrophy, and the diagnosis of KTS can be made if any two of these three features are present. Hemangiomas in various locations, e.g., skull, brain, epidural and vertebral hemangioma, mediastinal, colonic hemangioma, intraneural/intramuscular hemangiomas, are reported with KTS. CASE PRESENTATION: Benign vascular tumors may rarely develop malignant transformation as Bugarin- Estrada et al. reported breast angiosarcoma in a patient diagnosed as Klippel-Trenaunay-Syndrome. We reported a case of a 40-year-old female with a known case of Klipple-Trenaunay-Syndrome with left leg varicosities, cutaneous nevus, as well as unfortunate development of deep venous thrombosis and markedly enlarged right breast hemangioma. Due to low incidence or lack of early detection of breast hemangioma, its diagnosis is challenging. CONCLUSION: The history of the patient and multi-modality imaging utilization can help in early and accurate diagnosis of diseases leading to better prognosis.

Multimodality Imaging in Acute Ischemic Stroke.

Stroke is the most common cause of mortality and morbidity worldwide. The prognosis of stroke depends upon the area affected and its early treatment. Time is of the essence in the care of stroke patients as it is estimated that approximately 1.9 million neurons, 14 billion synapses, and 12 km myelinated nerve fibers are lost per minute. Therefore, early diagnosis and prompt treatment are necessary. The primary goal of imaging in acute stroke is to diagnose the underlying cause, estimate the area affected, predict response towards thrombolytic therapy and to exclude the conditions mimicking stroke. With advancements in radiology, multiple imaging modalities are available for diagnosis and predicting prognosis. None of them is considered alone to be perfect. In this era of multimodality imaging, the decision of choosing appropriate techniques depends upon purpose and availability. Non-Contrast Computed Tomography is time effective, and helps in excluding other causes, Trans Cranial Doppler is time-effective and cost-effective with wide availability, however, is operator dependent and less sensitive. It holds a great future in sonothrombolysis. Magnetic Resonance Imaging is so far considered to be the most superior one in terms of early diagnosis, planning for interventional treatment and predicting the response of treatment. However, it is limited due to high cost and lack of availability. The current review gives a detailed account of all imaging modalities available for imaging stroke and their associated pros and cons.

Precochlear Implant Assessment: Clinical Profile and Family History of Children with Severe Bilateral Prelingual Hearing Loss

Abstract Introduction The prevalence of deafness is high in Pakistan. Knowledge regarding the clinical features of patients with profound hearing loss will not only help identify the cause but will also help in the strategic planning for public health interventions. Objective The present study was conducted to cover in detail the clinical aspects of children with hearing loss, that is, age at presentation, associated deficits and disorders, possible cause of the disease, associated family history, and role of consanguineous marriage. Methods The present study was performed from November 2016 to September 2018. All of the patients under 6 years of age with profound bilateral hearing loss who would benefit from cochlear implantation were included in the study. Detailed history was taken. The developmental skills were assessed for all areas, and the patients were scored regarding their motor, manipulative, visual, language, social and self-care skills according to the Schedule of Growing Skills II. Detailed family history was taken from the parents of the affected children. The Statistical Package for the Social Sciences (SPSS) software, version 20.0, was used for the statistical analysis. Results The mean age of the children to be treated was 3.2 ± 1.25 years. Most patients (51.5%) had a positive family history of disease. Consanguineous marriage was common; the parents of 76.9% of the patients were first-degree relatives. Most patients (90.8%) had associated language impediments. In total, four (Ł3.07%) patients had global developmental delay. Conclusion Consanguineous marriage pattern plays an important role in diseases running in families. Development in these children is strongly linked to their age at the consultation.

Precochlear Implant Assessment: Clinical Profile and Family History of Children with Severe Bilateral Prelingual Hearing Loss.

Introduction The prevalence of deafness is high in Pakistan. Knowledge regarding the clinical features of patients with profound hearing loss will not only help identify the cause but will also help in the strategic planning for public health interventions. Objective The present study was conducted to cover in detail the clinical aspects of children with hearing loss, that is, age at presentation, associated deficits and disorders, possible cause of the disease, associated family history, and role of consanguineous marriage. Methods The present study was performed from November 2016 to September 2018. All of the patients under 6 years of age with profound bilateral hearing loss who would benefit from cochlear implantation were included in the study. Detailed history was taken. The developmental skills were assessed for all areas, and the patients were scored regarding their motor, manipulative, visual, language, social and self-care skills according to the Schedule of Growing Skills II. Detailed family history was taken from the parents of the affected children. The Statistical Package for the Social Sciences (SPSS) software, version 20.0, was used for the statistical analysis. Results The mean age of the children to be treated was 3.2 ± 1.25 years. Most patients (51.5%) had a positive family history of disease. Consanguineous marriage was common; the parents of 76.9% of the patients were first-degree relatives. Most patients (90.8%) had associated language impediments. In total, four (L3.07%) patients had global developmental delay. Conclusion Consanguineous marriage pattern plays an important role in diseases running in families. Development in these children is strongly linked to their age at the consultation.

Chitosan coated liposomes (CCL) containing triamcinolone acetonide for sustained delivery: A potential topical treatment for posterior segment diseases.

Drug delivery to the posterior eye is limited by epithelial and mucosal barriers limiting the topical administration of drugs leading to invasive modes of repeated long-term painful administration of drugs. Several constructs of liposomes have been prepared to counter this challenge yet are often limited by size and surface charge resulting in poor encapsulation efficiency, low retention time, and poor permeability. In the present study, chitosan coated liposomes (CCL) were prepared to address these challenges. Conventional liposomes encapsulating Triamcinolone Acetonide (TA) were compared with their chitosan coated counterpart for drug loading and release studies. CCL showed a higher encapsulation efficiency (74%), and a highly positive surface charge (+41.1Mv), increased retention time and sustained release. Choroidal neovascularization (CNV) rat models were generated to assess the efficiency of CCLs as nanocarriers in drug delivery. Significant amount of TA was found to be present and retaining in the eye after fifteen days of treatment with CCL, as shown by HPLC analysis. The results showed successful penetration of the construct via corneal mucosal barrier and its accumulation in vitreous body. The analysis shows that this chitosan based liposomal construct can be employed as a potential topical delivery system for treating posterior segment diseases.

Red flag symptoms: detailed account of clinicopathological features in young-onset colorectal cancer.

BACKGROUND/AIMS: Colorectal cancer has long been considered disease of the West, typically occurring in old age; however, the incidence is rising in Asia. The pattern of disease is quite different in Asia, occurring at a younger age and at an advanced stage. Recognition of disease at an early stage is still a challenge for physicians. Few data are available regarding young-onset colorectal cancer in Pakistan. We conducted this study to fill this gap and provide deeper insight into clinical symptoms and histopathological features of young-onset colorectal cancer. METHODS: We collected data regarding clinical features by directly interviewing patients and obtaining histopathological data from hospital records. Patients aged less than 50 years were included in the study. Statistical analysis was performed using IBM SPSS version 20.0. RESULTS: Results in 105 patients showed mean age at diagnosis was 35.90±9.39, with male predominance; the majority of patients had no family history of colorectal cancer. Most patients had left-sided tumors with advance stage and intermediate grade (grade 2). Mucinous histology was common. Rectal bleeding was the first symptom for left-sided tumors, whereas most of the right-sided lesions presented with sudden obstruction. CONCLUSIONS: Painless rectal bleeding in the early thirties should alert physicians to advise appropriate investigation, as the majority of young-onset colorectal cancer patients develop painless bleeding 2 to 3 years before appearance of other symptoms.