This document summarizes a case series of 10 patients who presented with thrombotic microangiopathy associated with intravenous injection of reformulated Opana ER. The patients were treated at the University of Tennessee Medical Center between July 2012 and February 2013. Laboratory findings and clinical characteristics are described for each patient. Treatment included therapeutic plasma exchange for most patients. The total costs of treatment for this group was over $1 million. Reformulated Opana ER has been associated with distinctive thrombotic microangiopathy when injected intravenously, as seen in this case series.
A slide series to learn and appreciate the importance and the potential of Personalized/Individualized Genomic Medicine. It briefly goes through the idea of biotechnology and the advancements we have made in biology and technology. A series of applications for genomic medicine is then explored, not failing to mention the challenges we have to overcome as well, for the next medical revolution.
A case for personalized medicine is presented.
A slide series to learn and appreciate the importance and the potential of Personalized/Individualized Genomic Medicine. It briefly goes through the idea of biotechnology and the advancements we have made in biology and technology. A series of applications for genomic medicine is then explored, not failing to mention the challenges we have to overcome as well, for the next medical revolution.
A case for personalized medicine is presented.
A slide series to learn and appreciate the importance and the potential of Personalized/Individualized Genomic Medicine. It briefly goes through the idea of biotechnology and the advancements we have made in biology and technology. A series of applications for genomic medicine is then explored, not failing to mention the challenges we have to overcome as well, for the next medical revolution.
A case for personalized medicine is presented.
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
All manuscripts are subject to rapid peer review. Those of high quality (not previously published and not under consideration for publication in another journal) will be published without delay.
Rare Diseases: A Report on Orphan Drugs in the PipelinePhRMA
Rare diseases, when taken together, are not that rare at all. In fact, according to the National Institutes of Health (NIH), 30 million Americans have one of the nearly 7,000 diseases that are officially deemed “rare” because alone they each affect fewer than 200,000 people in the United States.
Nature medicine top ten advancements in biomedicine in 2020DoriaFang
In the field of biomedicine, which is closely related to human health, many innovative therapies have matured this year and promoted medical progress. Recently, the authoritative academic journal "Nature Medicine" published a series of articles reviewing ten remarkable advancements in 2020.
clinical distribution and molecular profiling on postoperative colorectal can...LucyPi1
Abstract
Background: Traditional Chinese medicine (TCM) syndrome, also named syndrome, are comprehensive and
integral analyses of clinical information which helps to guide different individualized treatment prescriptions.
Methods: Thirty healthy controls and 80 colorectal cancer (CRC) patients (including 33 Spleen Qi Deficiency
syndrome, 23 Dampness Heat syndrome, 17 Blood Stasis syndrome and 7 other syndrome) were enrolled into this
study. Human mRNAs were extracted from peripheral blood mononuclear cells. The gene expression for CRC
patients with different TCM syndrome was determined by microarray and qRT-PCR. Results: Spleen Qi Deficiency,
Dampness Heat and Blood Stasis were the most common syndromes in CRC patients. There is a significant
difference was found in mRNA expression levels (especially for PIK3CA, STAT3, SOX9 and KDM5C) among
Spleen Qi Deficiency, Dampness Heat and Blood Stasis syndrome groups. The higher mRNA levels of JNK1, TP53,
MLH1, MSH6, PMS2, SOCS3, TCF7L2, FAM123B, PSAP, FBXW7, SALL4 and the lower expression of
inflammatory cytokine IL-6 were found in Spleen Qi Deficiency group but not other syndrome types. The higher
mRNA levels of KRAS, MUC16, EGFR, GRASP65, PIK3CA, MAPK7, CD24, STAT3, SLC11A1, Bcl-2, TXNDC17
and some inflammatory cytokines (IL-6, IL-23, TNF-a, CXCR4) were found in Dampness Heat group but not other
syndrome types. Blood Stasis syndrome showed higher expression of SOX9, MLH1, MSH6, KDM5C, PCDH11X,
PSAP and SALL4, and lower mRNA levels of PIK3CA, CD24, STAT3, CXCR4, TXNDC17 and TP53. The CRC
patients with Dampness Heat syndrome might have a poor prognosis than other syndrome types. Conclusion: The
identification of syndrome conditions had different impacts on CRC prognosis, and which might be related with
different mRNA expression levels. Some oncogenes and pro-inflammatory cytokines were highly expressed in
Dampness Heat group but not other syndrome types, suggesting that the CRC patients with Dampness Heat
syndrome might have a poor prognosis. Our results prelimitarily uncovered the molecular basis of syndrome
differences in CRC prognosis, a better understanding for TCM treatment of CRC.
Dr. ihsan edan abdulkareem alsaimary
PROFESSOR IN MEDICAL MICROBIOLOGY AND MOLECULAR IMMUNOLOGY
ihsanalsaimary@gmail.com
mobile : 009647801410838
university of basrah - college of medicine - basrah -IRAQ
Prof. Milan Macek. Professor of Medical and Molecular Genetics Chairman of Department of Biology and Medical Genetics Division of Clinical Molecular Genetics and the National Cystic Fibrosis Centre- University Hospital Motol and 2nd School of Medicine -Charles University Prague- Czech Republic.
-----
There is an increasing need to manage cost-effectiveness issues of novel or relatively expensive technologies that are currently in use or being proposed for the treatment of rare diseases. Cystic fibrosis (CF), where so called „CFTR modulating therapies“ rendered by several novel orphan medicinal products (e.g. ivacaftor, lumacaftor) are rapidly being introduced into clinical practice, will be used as a model. Health-economic evaluations of rising pharmacotherapeutic costs, as the major driver of overall cost, have to be part of the cost analysis of chronic and progressive (rare) diseases like CF that may require lifelong therapy. Total costs include not only direct healthcare costs but also the cost of lost productivity by both patients and family caregivers. When considering the results of cost-effectiveness analysis of new technologies associated with the management of CF, it is unreasonable to expect that the incremental cost-effectiveness ratio to be less than the generally applied thresholds (willingness to pay) for other common diseases. This issue is further compounded by mutation specific therapies for a subset of the overal cohort of CF patients. Therefore, when assessing CF and other rare diseases, such analyses should include complex health technology assessment approaches, which evaluate comparative treatment effectiveness (novel and established), as well as wider social benefits and ethical aspects. We will present the experience of the Prague CF center in terms of costs of illness studies and pharmacoeconomical approaches to studying children and adolescents with this disease.
Abstract
This case report describes the diagnosis and management of a large mesenteric cyst in a 55 year old lady who presented with abdominal distension & with mass in the left upper quadrant. Mesenteric cysts are rare, benign, abdominal tumors to which <1000 cases have been reported in the literature. While 40% of cases are incidental findings found either through physical examination or imaging, they can cause non-specific abdominal symptoms including pain, altered bowel habits, nausea/vomiting or anorexia. Less commonly, 10% of cases can present with bowel obstruction, volvulus, torsion or shock. In general, the lack of characteristic clinical and radiological features presents as a diagnostic difficulty.
The mainstay in imaging is computerized tomography (CT). CT identifies and helps aid the decision to pursue a laparoscopic or open laparotomy approach, where complete surgical resection is the ultimate goal. In our patient a CT Abdomen & Pelvis showed a large, loculated cystic mass measuring 30cm in cranio-caudal length and 16cm in the transverse and anterior/posterior diameter. While different approaches have been described in the literature to surgically resect such cysts, our approach was largely reflective of size and adherence to surrounding structures in this case. A laparotomy was performed using an upper mid-line 7 cm incision; 4500cc of fluid was aspirated from the cyst which was found to originate from the small bowel mesentery. A complete resection of the multi-loculated cystic sac was done that included the resection of the middle mesenteric vein. The post-operative period was uneventful. The patient was discharged on post-operative day 2. The Histopathology identified the mass as a multi-loculated peritoneal inclusion-type cyst.
We report the case of a 74 year old female who presented with imaging concerning for an intramural hematoma of the ascending aorta. Despite multiple imaging modalities consistent with intramural hematoma, operative findings confirmed a peri-aortic lymphoma or what was once lymphoma.
Bone marrow transplant (BMT) recipients often require parenteral nutrition (PN) to meet their nutrient needs. While general guidelines for the provision of PN support by nutrition support teams (NSTs) have been shown to decrease inappropriate PN use, recommendations for nutrition in BMT recipients are lacking. We reviewed the charts of patients status post BMT on PN to determine whether institutional guidelines for PN initiation and continuous supervision of NSTs could be applied in this population. With the Institutional Review Board (IRB) approval, charts of adult BMT recipients on PN between June 14, 2006 and June 30, 2007 were examined. Sixty-nine charts were reviewed. Indications for initiation of PN included severe mucositis, graft versus host disease (GVHD), and other transplant related side effects resulting in poor oral intake. Among 69 patients, 37 (54%) had severe mucositis, 12 (17%) had GVHD, 2 (3%) had both mucositis and GVHD, and 18 (26%) had other side effects. It was determined that all patients met the criteria for initiation of PN support, as outlined in the guidelines form. Comprehensive guidelines for initiating PN support, developed by NSTs can also be used for BMT recipients in order to optimize their nutritional status.
Abstract
Background: Olfactory neuroblastoma is a rare malignancy of the nasal cavity.
Methods: We describe a case of radiation-induced olfactory neuroblastoma in a patient with a history of radiation for Graves' ophthalmopathy. We also reviewed the literature and found four other cases of radiation-induced olfactory neuroblastoma reported since 2000, suggesting prior radiotherapy as one risk factor for this disease.
Results: We treated the patient with multimodality treatment consisting of surgery, radiotherapy and chemotherapy (6 cycles of cisplatin/ etoposide). Despite the previously irradiation, treatment was well tolerated without excessive short or long term radiation toxicity. The patient remains in long term remission with no evidence of loco-regional recurrence or systemic metastasis after 12 years of follow-up.
Conclusions: Prior radiotherapy appears to be a risk factor in a handful of cases of this rare malignancy. Although the literature is limited for radiation-related olfactory neuroblastoma, outcomes appear generally poorer for this group but highly variable. With careful patient selection, aggressive multi-modality therapy including post-operative radiotherapy may be feasible.
Journal of Proteomics & Geneomics (JPG) is an instructional journal providing a chance to researchers and scientists to explore the advanced and latest research developments within the field of Proteomics and Geneomics. Journal of Proteomics & Geneomics publishes the best quality scientific articles amalgamating broad vary of fields together with the fields associated with Proteomics & Geneomics.
A slide series to learn and appreciate the importance and the potential of Personalized/Individualized Genomic Medicine. It briefly goes through the idea of biotechnology and the advancements we have made in biology and technology. A series of applications for genomic medicine is then explored, not failing to mention the challenges we have to overcome as well, for the next medical revolution.
A case for personalized medicine is presented.
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
All manuscripts are subject to rapid peer review. Those of high quality (not previously published and not under consideration for publication in another journal) will be published without delay.
Rare Diseases: A Report on Orphan Drugs in the PipelinePhRMA
Rare diseases, when taken together, are not that rare at all. In fact, according to the National Institutes of Health (NIH), 30 million Americans have one of the nearly 7,000 diseases that are officially deemed “rare” because alone they each affect fewer than 200,000 people in the United States.
Nature medicine top ten advancements in biomedicine in 2020DoriaFang
In the field of biomedicine, which is closely related to human health, many innovative therapies have matured this year and promoted medical progress. Recently, the authoritative academic journal "Nature Medicine" published a series of articles reviewing ten remarkable advancements in 2020.
clinical distribution and molecular profiling on postoperative colorectal can...LucyPi1
Abstract
Background: Traditional Chinese medicine (TCM) syndrome, also named syndrome, are comprehensive and
integral analyses of clinical information which helps to guide different individualized treatment prescriptions.
Methods: Thirty healthy controls and 80 colorectal cancer (CRC) patients (including 33 Spleen Qi Deficiency
syndrome, 23 Dampness Heat syndrome, 17 Blood Stasis syndrome and 7 other syndrome) were enrolled into this
study. Human mRNAs were extracted from peripheral blood mononuclear cells. The gene expression for CRC
patients with different TCM syndrome was determined by microarray and qRT-PCR. Results: Spleen Qi Deficiency,
Dampness Heat and Blood Stasis were the most common syndromes in CRC patients. There is a significant
difference was found in mRNA expression levels (especially for PIK3CA, STAT3, SOX9 and KDM5C) among
Spleen Qi Deficiency, Dampness Heat and Blood Stasis syndrome groups. The higher mRNA levels of JNK1, TP53,
MLH1, MSH6, PMS2, SOCS3, TCF7L2, FAM123B, PSAP, FBXW7, SALL4 and the lower expression of
inflammatory cytokine IL-6 were found in Spleen Qi Deficiency group but not other syndrome types. The higher
mRNA levels of KRAS, MUC16, EGFR, GRASP65, PIK3CA, MAPK7, CD24, STAT3, SLC11A1, Bcl-2, TXNDC17
and some inflammatory cytokines (IL-6, IL-23, TNF-a, CXCR4) were found in Dampness Heat group but not other
syndrome types. Blood Stasis syndrome showed higher expression of SOX9, MLH1, MSH6, KDM5C, PCDH11X,
PSAP and SALL4, and lower mRNA levels of PIK3CA, CD24, STAT3, CXCR4, TXNDC17 and TP53. The CRC
patients with Dampness Heat syndrome might have a poor prognosis than other syndrome types. Conclusion: The
identification of syndrome conditions had different impacts on CRC prognosis, and which might be related with
different mRNA expression levels. Some oncogenes and pro-inflammatory cytokines were highly expressed in
Dampness Heat group but not other syndrome types, suggesting that the CRC patients with Dampness Heat
syndrome might have a poor prognosis. Our results prelimitarily uncovered the molecular basis of syndrome
differences in CRC prognosis, a better understanding for TCM treatment of CRC.
Dr. ihsan edan abdulkareem alsaimary
PROFESSOR IN MEDICAL MICROBIOLOGY AND MOLECULAR IMMUNOLOGY
ihsanalsaimary@gmail.com
mobile : 009647801410838
university of basrah - college of medicine - basrah -IRAQ
Prof. Milan Macek. Professor of Medical and Molecular Genetics Chairman of Department of Biology and Medical Genetics Division of Clinical Molecular Genetics and the National Cystic Fibrosis Centre- University Hospital Motol and 2nd School of Medicine -Charles University Prague- Czech Republic.
-----
There is an increasing need to manage cost-effectiveness issues of novel or relatively expensive technologies that are currently in use or being proposed for the treatment of rare diseases. Cystic fibrosis (CF), where so called „CFTR modulating therapies“ rendered by several novel orphan medicinal products (e.g. ivacaftor, lumacaftor) are rapidly being introduced into clinical practice, will be used as a model. Health-economic evaluations of rising pharmacotherapeutic costs, as the major driver of overall cost, have to be part of the cost analysis of chronic and progressive (rare) diseases like CF that may require lifelong therapy. Total costs include not only direct healthcare costs but also the cost of lost productivity by both patients and family caregivers. When considering the results of cost-effectiveness analysis of new technologies associated with the management of CF, it is unreasonable to expect that the incremental cost-effectiveness ratio to be less than the generally applied thresholds (willingness to pay) for other common diseases. This issue is further compounded by mutation specific therapies for a subset of the overal cohort of CF patients. Therefore, when assessing CF and other rare diseases, such analyses should include complex health technology assessment approaches, which evaluate comparative treatment effectiveness (novel and established), as well as wider social benefits and ethical aspects. We will present the experience of the Prague CF center in terms of costs of illness studies and pharmacoeconomical approaches to studying children and adolescents with this disease.
Abstract
This case report describes the diagnosis and management of a large mesenteric cyst in a 55 year old lady who presented with abdominal distension & with mass in the left upper quadrant. Mesenteric cysts are rare, benign, abdominal tumors to which <1000 cases have been reported in the literature. While 40% of cases are incidental findings found either through physical examination or imaging, they can cause non-specific abdominal symptoms including pain, altered bowel habits, nausea/vomiting or anorexia. Less commonly, 10% of cases can present with bowel obstruction, volvulus, torsion or shock. In general, the lack of characteristic clinical and radiological features presents as a diagnostic difficulty.
The mainstay in imaging is computerized tomography (CT). CT identifies and helps aid the decision to pursue a laparoscopic or open laparotomy approach, where complete surgical resection is the ultimate goal. In our patient a CT Abdomen & Pelvis showed a large, loculated cystic mass measuring 30cm in cranio-caudal length and 16cm in the transverse and anterior/posterior diameter. While different approaches have been described in the literature to surgically resect such cysts, our approach was largely reflective of size and adherence to surrounding structures in this case. A laparotomy was performed using an upper mid-line 7 cm incision; 4500cc of fluid was aspirated from the cyst which was found to originate from the small bowel mesentery. A complete resection of the multi-loculated cystic sac was done that included the resection of the middle mesenteric vein. The post-operative period was uneventful. The patient was discharged on post-operative day 2. The Histopathology identified the mass as a multi-loculated peritoneal inclusion-type cyst.
We report the case of a 74 year old female who presented with imaging concerning for an intramural hematoma of the ascending aorta. Despite multiple imaging modalities consistent with intramural hematoma, operative findings confirmed a peri-aortic lymphoma or what was once lymphoma.
Bone marrow transplant (BMT) recipients often require parenteral nutrition (PN) to meet their nutrient needs. While general guidelines for the provision of PN support by nutrition support teams (NSTs) have been shown to decrease inappropriate PN use, recommendations for nutrition in BMT recipients are lacking. We reviewed the charts of patients status post BMT on PN to determine whether institutional guidelines for PN initiation and continuous supervision of NSTs could be applied in this population. With the Institutional Review Board (IRB) approval, charts of adult BMT recipients on PN between June 14, 2006 and June 30, 2007 were examined. Sixty-nine charts were reviewed. Indications for initiation of PN included severe mucositis, graft versus host disease (GVHD), and other transplant related side effects resulting in poor oral intake. Among 69 patients, 37 (54%) had severe mucositis, 12 (17%) had GVHD, 2 (3%) had both mucositis and GVHD, and 18 (26%) had other side effects. It was determined that all patients met the criteria for initiation of PN support, as outlined in the guidelines form. Comprehensive guidelines for initiating PN support, developed by NSTs can also be used for BMT recipients in order to optimize their nutritional status.
Abstract
Background: Olfactory neuroblastoma is a rare malignancy of the nasal cavity.
Methods: We describe a case of radiation-induced olfactory neuroblastoma in a patient with a history of radiation for Graves' ophthalmopathy. We also reviewed the literature and found four other cases of radiation-induced olfactory neuroblastoma reported since 2000, suggesting prior radiotherapy as one risk factor for this disease.
Results: We treated the patient with multimodality treatment consisting of surgery, radiotherapy and chemotherapy (6 cycles of cisplatin/ etoposide). Despite the previously irradiation, treatment was well tolerated without excessive short or long term radiation toxicity. The patient remains in long term remission with no evidence of loco-regional recurrence or systemic metastasis after 12 years of follow-up.
Conclusions: Prior radiotherapy appears to be a risk factor in a handful of cases of this rare malignancy. Although the literature is limited for radiation-related olfactory neuroblastoma, outcomes appear generally poorer for this group but highly variable. With careful patient selection, aggressive multi-modality therapy including post-operative radiotherapy may be feasible.
Journal of Proteomics & Geneomics (JPG) is an instructional journal providing a chance to researchers and scientists to explore the advanced and latest research developments within the field of Proteomics and Geneomics. Journal of Proteomics & Geneomics publishes the best quality scientific articles amalgamating broad vary of fields together with the fields associated with Proteomics & Geneomics.
Abstract
A small set of amphetamines has been analyzed by gas chromatography (GC) high-resolution time-of-flight mass spectrometry (TOFMS) using a microplasma photoionization (MPPI) soft-ionization source. This plasma-based, wavelength selectable ionization source enables ionization of the test compounds and their corresponding derivatives at ~8-12 eV that is a softer alternative to electron ionization at 70 eV. Three plasma gases were used in this study: Xe plasma that emits photons at resonance lines of 9.57 eV and 8.44 eV; Kr plasma at 10.63 eV and 10.02 eV, and Ar plasma at 11.82 eV and 11.61 eV. Derivatization of the test compounds with trifluoroacetic anhydride and α-methoxy-α-(trifluoromethyl)-phenylacetyl pyrazole was evaluated because the MPPI mass spectra of the underivatized amphetamines yield primarily iminium ions, which make the identification of the test compounds by GC-TOFMS inconclusive. The MPPI mass spectra of the TFA-derivatized amphetamines yield abundant molecular ions, when using Xe as plasma gas, and enough fragment ions with the Ar plasma that can help in formula generation. The structure elucidation of two "known unknowns" designer drugs using this "tunable" soft-ionization source and a high-resolution TOF mass spectrometer is presented in this study.
Introduction
Cutaneous metastases from abdominal malignancies are rare and have been reported in less than 5% of patients [1]. Furthermore, metastases in patients suffering from colorectal neoplasia are even rarer entity. Tan et al, among 2538 of the new cases of colorectal cancer over the period of 6 years, reported only 3 cases (0.1%) with cutaneous deposits [1]. Presentation varies from cutaneous or subcutaneous small nodules, rash or large fungating lesions [1-4]. Inevitably, their presence implies the disease progression, and poor prognosis with the reported survival between 1 to 34 months [2,3,5].
We report a case of an elderly patient who initially was thought to present with a simple skin infection. Subsequently, the patient was diagnosed with the moderately differentiated mucinous adenocarcinoma and required the right hemicolectomy. This case highlights that a high index of suspicion is recommended in an unresolving skin erythema.
Abstract
An examination experiment has been carried out to investigate whether fingerprint powder and lifting technique can recover and transfer latent fingerprints from human skin surfaces of dead bodies. For recovery Swedish Black powder and for transfer White Fingerprint Gelatine were used.
Donors placed fingerprints on the human skin surfaces. Finger marks were then in all cases recovered with Swedish Black powder. The procedure was repeated after 2, 3, 4 and 5 hours. Treated finger marks were secured and preserved as latent fingerprint evidence by lifting process. We recovered 8% finger marks suitable for further examination of all deposited samples on the human skin surfaces.
Abstract
Hepatic angiosarcoma is a rare tumour that is often difficult to diagnose. Historically, most cases of hepatic angiosarcoma were seen in the setting of industrial epidemics caused by exposure of workers to toxins such as vinyl chloride. Cases associated with recognised exposure to carcinogens have fortunately been extremely rare for the last three or more decades. However, the tumour has by no means disappeared in the Australian community. In this case series, we describe three cases of hepatic angiosarcoma that were seen at our institution since 2002. The first case presented with cholestatic liver function tests and was found to have angiosarcoma on liver biopsy. In the second case, the patient was admitted for decompensated liver disease on a background of presumed hepatitis B cirrhosis. The diagnosis of hepatic angiosarcoma was made only at autopsy after the patient died from multi-organ failure. The third case presented with ascites and the diagnosis of disseminated angiosarcoma was again made at autopsy following a negative ante-mortem liver biopsy.
CLINICAL AND EXPERIMENTAL RESEARCH IN CARDIOLOGYAnnex Publishers
Journal of Clinical and Experimental Research in Cardiology (JCERC) is an international open access, scholarly peer-reviewed journal publishing high quality articles in all areas of cardiology related fields, especially current research, new concepts, novel methods, new therapeutic agents, and approaches for early detection and prevention of cardiac disorders and reporting new methods on basic and advanced clinical aspects of cardiology research.
Abstract
Metastatic gastric tumors (MGTs) mean the tumor cells that attack the stomach and grow there through blood vessel, lymph vessel, and other pathway, consistent with the primary tumor in phenotype, which are clinically uncommon, and information on MGTs is generally limited to single case reports. Here we present a clinical series of 8 cases with MGTs, in attention to discuss the clinical characteristics, diagnosis and treatment, and prognosis of MGTs. Our data showed that MGTs are rare, with a male predominance, and the cause of death was multiple organ metastases in most cases. Heterochromous MGTs showed a significantly better prognosis than simultaneous MGTs, and a long interval between initial radical excision of the primary tumor and appearance of gastric metastasis was found to be associated with good prognosis.
Journal of Gynecology Research (JGR) publishes original articles and research studies on, scientific advances, new medical and surgical techniques, obstetric management, and clinical evaluation of drugs and instruments and all aspects of gynecology including gynecological endoscopy, infertility, oncology contraception, urogynecology, fertility, and clinical practice and ultrasonography. It aims to publish the highest quality medical research in women's health, worldwide.
CLINICAL AND EXPERIMENTAL RESEARCH IN CARDIOLOGYAnnex Publishers
Journal of Clinical and Experimental Research in Cardiology (JCERC) is an international open access, scholarly peer-reviewed journal publishing high quality articles in all areas of cardiology related fields, especially current research, new concepts, novel methods, new therapeutic agents, and approaches for early detection and prevention of cardiac disorders and reporting new methods on basic and advanced clinical aspects of cardiology research.
Association between-stress-and-dietary-behaviours-among-undergraduate-student...Annex Publishers
Background: Studies have shown that a significant proportion of university students globally suffer from stress. Although many studies have reported an association between psychological stress and dietary behaviour, findings remain inconclusive. To date, no research in Kuwait has assessed the prevalence of stress and its relationship with dietary pattern among university students.
Objectives: This study was designed to determine the extent of stress among undergraduate students in Kuwait University and to examine the relationship between dietary behaviours and stress.
Methods: A total of 407 (164 males and 243 females) undergraduate students, aged ≥ 18 years, from 4 colleges of Kuwait University participated in this cross sectional study. Data were collected using a self-administered questionnaire consisting of three sections: socio demographic information, stress measures and a 7-day food frequency questionnaire.
Results: Of the total participants, 43% were found to suffer from some level of stress, with slightly more females (44%) than males (40.9%). When examined the severity of stress level, 28.4% of the females and 22% of the males had moderate to severe form of stress. Stressed female students were more likely to eat fast foods (OR 1.75; 95% CI: 1.02-3:00), snacks (OR 2.0; 95% CI: 1.16-3:43) and beverages (OR 2.28; 95% CI: 1.30-3.98) than unstressed female students. For male students, none of the food consumption groups were associated with stress.
Conclusions: These results show a clear difference in food selection patterns between stressed male and female students with stress being strongly associated with unhealthy food selection among female students than male students. These findings emphasize the importance for the development of specific intervention programs to decrease stress and improve healthy behaviour especially among female university students and thus reduce the potential negative implications of stress on health.
The updated-international-veterinary-anatomical-and-embryological-nomenclaturesAnnex Publishers
The international nomenclature of the anatomical, histological and embryological terms is known as Nomina Anatomica Veterinaria (N.A.V.), Nomina Histologica Veterinaria (N.H.V.) and Nomina Embryologica Veterinaria (N.E.V.).
This is the tripod of terms for the morphological sciences in our profession, a dictionary of terms used by all specialists in the basic and in the clinical sciences.
Abstract
The application of legal knowledge to psychiatry and of psychiatric knowledge to the legal issues is the subspecialty of psychiatry known as forensic psychiatry. In India, forensic psychiatry is still in its infancy. The legal issues pertaining to the mental health care in India appeared only after British Rule, with very minimal changes occurring post independence. Currently, the training of psychiatry postgraduates to the idea of an interface between law and psychiatry is poor. It is neglected, ignored, misinterpreted and misunderstood. To meet the standards of the developed world and international covenants, there is a pressing need by psychiatric community in the region to understand the existing legislation and to initiate changes through various agencies and regulatory bodies. This paper attempts to elucidate the interface of law and psychiatry in India in a nutshell.
Left ventricular-mural-thrombus-treated-with-dabigatranAnnex Publishers
Abstract
Novel oral anticoagulants may be effective and safe alternatives to conventional treatment for left ventricular (LV) mural thrombus. A case of left ventricular mural thrombus successfully treated with dabigatran etixelate is described, and the rationale for undertaking further systematic evaluation of novel anticoagulants for this indication discussed.
Abstract
Background: We set out to determine the possibility of radiographically evaluating the degree of marginal bone loss in humans after functional loading of implants at sites of guided bone regeneration (GBR) with autogenous tooth-based bone graft (ATBBG) material (AutoBT®, Korea Tooth Bank, Seoul, Korea).
Materials and Methods: Using ATBBG material, GBR procedures were performed on the extraction sockets with bone defects such as buccal dehiscence and 6 months of healing was allowed. Dental implants were installed and prosthetic procedures were done after another 6 months of healing. Marginal bone levels (MBLs) were radiographically measured following functional loading (mean duration, 10 months; range, 4–18 months) in 10 patients among 19 patients initially enrolled in this study (4 men and 6 women; age range, 39–65 years; mean age, 55.4 years) who maintained follow-up visits after entire surgical and prosthetic procedures.
Results: No significant MBL differences were noted immediately after GBR, implant placement and prosthesis delivery (F=0.245, P>0.05). Changes in the MBLs were not affected by gender.
Conclusion: The ATBBG material is viable for GBR and can yield a stable MBL even after functional loading of implants. The degree of marginal bone loss after loading with ATBBG is stable.
Background: Vegetarian diets are associated with reduced risk for diseases such as diabetes and cardiovascular disease. We aimed to determine the nutritional adequacy of usual food intake in a cohort of young vegetarians and omnivores who regularly exercise.
Methods: Five vegetarian (aged 21.7±2.0 yrs), three vegan (aged 31.3±7.5 yrs) and eight age and sex matched omnivore participants (aged 21.1±1.9 yrs) volunteered for this project. Participants completed diet diaries to determine usual intake of macronutrients such as protein and fat and micronutrients such as vitamin C and iron.
Results: All participants met or exceeded the recommended dietary intake (RDI) of protein, thiamine, riboflavin, niacin, vitamin B6 phosphorus, and vitamin C. Vegetarians and vegans consumed insufficient quantities of vitamin B12 and vegans consumed less the half the amount that omnivores managed (1.7μg compared to 4.5μg). Folate consumption was adequate amongst vegetarians and vegans (510μg and 696μg respectively) and vitamin C consumption was highest among the vegan group (>400% of the RDI). Zinc intake was lowest among the vegetarians while low iron and copper intakes were reported by omnivores. Calcium consumption was poor overall.
Conclusions: Nutritional inadequacies can arise from consuming omnivore, vegetarian and vegan diets. Over time such inadequacies may result in nutrient deficiencies thus it is important to consume a variety of nutrient rich foods to ensure nutrition requirements are being met
Abstract
A 53 year old man with a background of castrate-sensitive prostate cancer on intermittent androgen deprivation therapy (ADT) presented with right sixth nerve palsy secondary to a solitary right petroclival lesion involving adjacent dura and bone. The clinical and imaging characteristics of the lesion were consistent with a number of differential diagnoses (including metastatic prostate cancer, meningioma and chondrosarcoma). The patient initially declined biopsy and ADT was recommenced but the lesion continued to enlarge despite an excellent biochemical response. A subsequent biopsy of the petroclival mass demonstrated a WHO grade I meningioma and the patient proceeded to have definitive stereotactic radiotherapy. This case illustrates an unusual solitary skull base lesion in a man with prostate cancer. Whilst bony metastases, usually multiple, in the skeleton are common, solitary skull or brain lesions should be investigated as alternate diagnoses are likely in such circumstance.
ADVERSE DRUG REACTION | PHARMACY PRACTICE | PDF | SHIVAM DUBEY B PHARMA | PHA...MrHotmaster1
PHARMACY PRACTICE
SHIVAM DUBEY
BPYN1PY18041
ADVERSE DRUG REACTION Abstract
We define an adverse drug reaction as "an appreciably harmful or
unpleasant reaction
Un estudio sobre las caracteristicas del tratamiento sde la TB XDR en sudafrica y el pronostico de vida de los pacientes segun las estrategias terapeuticas
Introduction to ICSR Narrative Writing in Drug Safety & Pharmacovigilance in Pharmaceuticals, Bio-Pharmaceuticals, Medical Devices, Cosmeceuticals and Foods.
Contact:
"Katalyst Healthcares & Life Sciences"
South Plainfield, NJ, USA
info@KatalystHLS.com
The value of real-world evidence for clinicians and clinical researchers in t...Arete-Zoe, LLC
In the midst of a rapidly spreading global pandemic, real-world evidence can offer invaluable insight into the most promising treatments, risk factors, and not only predict but suggest how to improve outcomes. Despite overwhelming news coverage, significant knowledge gaps regarding COVID-19 persist. The current uncertainties regarding incidence and the case fatality rate can only be addressed by widespread testing. But the paucity of testing, and diversity of approaches implemented in different countries, particularly among the general asymptomatic public, perpetuates a lack of understanding about spread and infectivity. The essential indicators that would describe the pandemic more accurately can be obtained using real-world data (RWD). To that purpose, we designed a data collection tool to collect data from hospitals that treat COVID-19 patients. The captured data will enhance our understanding of the COVID-19 pandemic, identify risk factors relevant for triage, relate to other similar seasonal infections and gain insight into the safety and efficacy of experimental and off-label therapies. Knowledge derived from a focused data collection effort will enable clinicians to adjust rapidly clinical protocols and discontinue interventions that turn out to be ineffective or harmful. By deploying our elegantly designed survey to capture routine clinical indicators, we avoid placing an additional burden on practitioners. Systematically generating real-world evidence can decrease the time to insight compared to randomized clinical trials, improving the odds for patients in rapidly changing conditions.
Journal of Nutrition and Health Sciences is an open access journal that publishes peer reviewed research articles and short communications in all aspects of nutrition. This Journal encompasses the full spectrum of nutritional science including nutritional requirements, public health nutrition, epidemiology, dietary surveys, body composition, energetics, appetite, obesity, ageing and metabolic studies.
Journal of Obesity and Overweight (JOO) is a peer reviewed open access journal. It is dedicated to increase knowledge, fostering research, and promoting better treatment for people with obesity. It includes subjects like nutrition medicine, clinical nutrition medicine, genetics and nutrition, biophysics and lipid metabolism, etc. It aims to publish advanced research works related to public health and medical developments.
Journal of Computational Systems Biology (JCSB) is an open access online journal which aims to publish peer reviewed research articles and short communications in all aspects of computational biology and bioinformatics. JCSB comprehend the broad spectrum of computational bioscience including biological databases and bioalgorithms.
Journal of Biometrics and Its Applications (JBIA) is peer reviewed open access journal which addresses the fundamental areas in computer science that deal with biological measurements. It covers both the theoretical and practical aspects of human identification and verification. Biometrics based authentication, an integral component of identity science, is now being utilized in several applications playing a central role in personal, national and global security. Biometric refers to the field of development of statistical and mathematical methods applicable to data analysis problems in the biological sciences.
Journal of Genetic Mutations and Disorders (JGMD) is an open access, peer reviewed journal which provides advanced researches including Genetics of Infectious Diseases, Genealogical Tracing, Stem Cell Research, Gene mapping with three-point crosses, Genetic linkage and genetic maps. JGMD publishes original research, review articles in all aspects of genetic mutations and disorders
Journal of Bioequivalence Studies (JBS) is an open access, peer reviewed journal that publishes the most relevant and reliable researches with respect to the subject of Bioequivalence studies which includes pharmacokinetic and pharmcodynamic properties of a drug. JBS publishes original articles, review articles, case reports, short communications, etc.
Journal of Forensic Science & Criminology (JFSC) is an open access, significant and reliable source of contemporary knowledge on advancements in the field of forensic science. JFSC publishes peer reviewed research articles, critical reviews and short communications focused on forensic science and criminology. JFSC encompasses the full spectrum of forensic science including forensic biology, forensic chemistry, cyber forensics and crime scene investigation
Annex Publishers, as an Open Access publication model allows the dissemination of research articles to the worldwide community. We offer you the advantage of interaction with the most effective minds from the scientific community. All articles printed under open access will be accessed by anyone.
www.annexpublishers.com
JOURNAL OF VETERINARY SCIENCE & ANIMAL HUSBANDRYAnnex Publishers
Journal of Veterinary Science and Animal Husbandry (JVSAH) is a scientific journal which has topics associated with fundamental and aspects of veterinary science and animal husbandry. JVSAH has a special feature of publishing special issues in experimental clinical research, veterinary medicine and current research. At Annex Publishers, we tend to publish quality articles and try our best to provide the most effective analysis journal to the scientific community.
Anti arthritic-efficacy-and-safety-of-crominex-3+(trivalent-chromium-phyllant...Annex Publishers
Abstract
The present investigation was undertaken to evaluate the therapeutic efficacy and safety of Crominex® 3+ (a complex of trivalent chromium, Phyllanthus emblica (Amla) extract and purified Shilajit) in moderately arthritic dogs. Eleven client-owned moderately arthritic dogs in a randomized double-blinded study received placebo or Crominex® 3+ twice daily for a period of 150 days. On a monthly basis, each dog was evaluated for arthritis associated pain (overall pain, pain upon limb manipulation and pain after physical exertion) and a full physical exam (body weight, body temperature and heart rate). At the same time intervals, dogs serum samples were examined for biomarkers of kidney (BUN and creatinine), liver (bilirubin, ALT and AST) and heart and skeletal muscle (CK) functions. Findings of this investigation revealed that dogs receiving Crominex® 3+ (1000 μg chromium, 15 mg Amla extract and 15 mg purified Shilajit per day in two divided doses) exhibited a significant (P< 0.05) reduction in arthritic pain noted as early as after 90 days with a maximum reduction after 150 days of treatment. Pain level remained the same or slightly increased in the dogs receiving placebo. No significant change occurred in physical parameters or serum biomarkers in dogs on placebo or Crominex® 3+, which suggested that Crominex® 3+ was well tolerated by arthritic dogs. In conclusion, Crominex® 3+ significantly (P< 0.05) ameliorated arthritic pain and improved quality of life without causing any untoward effects in moderately arthritic dogs.
Abstract
The objectives of this retrospective study were 1. To determine the effect of three surgical techniques (right flank omentopexy, right flank omentoabomasopexy, and left flank abomasopexy), and 2. To determine the effect of concurrent disease on return to normal milk production. Return to normal milk production occurred in 86.3% of cows diagnosed with LDA. Results suggested that cattle diagnosed with LDA corrected via right flank omentopexy or left flank abomasopexy were significantly more likely to return to normal milk production as compared to those corrected via right flank omentoabomasopexy (p< 0.02). No significant difference in return to normal milk production was noted between surgical techniques for correction of RDA (p=1.000) and right abomasal volvulus (p=0.596). Concurrent disease diagnoses did not affect return to milk production. Reported complications were infrequent (n=11).
List of abbreviations: LDA- Left displaced abomasum; RDA- Right displaced abomasum; RAV- Right abomasal volvulus; RAOV- Right abomasal-omasal volvulus; RFO- Right flank omentopexy; RFOA- Right flank omentoabomasopexy; LFA- Left flank abomasopexy; DA – Displaced Abomasum
Abstract
Three surgical case reports are presented to demonstrate the clinical efficacy of using an improved aqueous solution of chlorine dioxide complex (160 ppm) as a topical antiseptic in the post operative management of serious wounds in dogs. In vitro studies are included to demonstrate the antiseptic properties of this new chlorine dioxide complex.
Keywords: Chlorine dioxide; Antiseptic; Antimicrobial; Wound management
Abbreviations: ClO2-Chlorine dioxide; Cl2-Chlorine; PPM-Parts Per Million; SPP-Species; TEM-Transmission Electron Micrograph
Abstract
Salmonella is a causative agent for a wide variety of pathological diseases in humans, cattle, poultry and other farm animals and hence Salmonella infections are a major cause of concern to humans, veterinary animals and to food industry. With characterization of over 2500 Salmonella serovars, the pathogen nearly infects all vertebrates but the severity of infection varies from one serovar to another depending upon their host specificity. Some Salmonella serovars are restricted to one or few hosts while others have a broad host spectrum. Thus the understanding of the mechanisms involving host preference by one serovar over another is very important. As our knowledge about host adaptability will then be instrumental in designing better vaccines. Furthermore, methods involving identification of genetic markers for host specificity will prove to be instrumental in determining virulence factors for other pathogenic bacteria that cause systemic infections.
Keywords: Host adaption; Evolution; Salmonella serovar; Horizontal gene transfer
Anti inflammatory-and-anti-arthritic-efficacy-and-safety-of-purified-shilajit...Annex Publishers
Abstract
The objective of this investigation was to evaluate the efficacy and safety of purified Shilajit in moderately arthritic dogs. Ten client-owned dogs in a randomized double-blinded study received either a placebo or Shilajit (500 mg) twice daily for a period of five months. Dogs were evaluated each month for physical condition (body weight, body temperature, heart rate, and respiration rate) and pain associated with arthritis (overall pain, pain from limb manipulation, and pain after physical exertion). Serum samples collected from these dogs were examined each month for biomarkers of liver (bilirubin, ALT, and AST), kidney (BUN and creatinine) heart and muscle (creatine kinase) functions. The findings of this study revealed that dogs receiving Shilajit (Group-II) showed a significant (P< 0.05) reduction in pain from limb manipulation by day 60, and overall pain and pain after physical exertion by day 120. Maximum pain reduction, using all three criteria, was observed on day 150. Pain level remained significantly unchanged in dogs receiving the placebo. Dogs in either group showed no significant change (P>0.05) in physical parameters or serum markers, suggesting that Shilajit was well tolerated by moderately arthritic dogs. It was concluded that Shilajit significantly (P< 0.05) reduced pain in osteoarthritic dogs and markedly improved their daily life without any side effects.
Keywords: Purified Shilajit; Osteoarthritis in canine; Shilajit safety; Anti-arthritic nutraceutical
The discovery of the presence of stem cells and precursors with high regenerative potential in the mammary gland, hypothetically maintained throughout the course of the productive life of the dairy cow sheds an interesting perspective in the research which is interested to clarify all physiological clues and possible solutions to increase or maintain longer the potential production of dairy cows during life span of lactation. In 2006, Connie Eaves' lab in Vancouver (Stingl et ., 2006) [1]
Abstract
Mitogen-Activated Protein Kinase (MAPK) pathway is a signal transduction pathway that functions in a wide range of physiological and pathophysiological cellular events including cell proliferation, differentiation, apoptosis, migration, inflammation, metabolic disorders and diseases. In skeletal muscle, it plays an essential role in muscle fiber specialization, muscle mass maintenance, damage induced muscle regeneration and muscle diseases. This review provides an overview of MAPK pathway and its pathophysiological role in skeletal muscle diseases with a primary focus on muscular dystrophy and atrophy.
Study on-efficiency-of-protein-extractants-employed-for-human-origin-determin...Annex Publishers
Abstract
Human origin determination is an important aspect of blood grouping analysis in forensic science laboratories. In the present study, protein extractants like gel buffer, ammonia and saline employed for origin determination were evaluated and compared qualitatively and quantitatively for their role in the extraction of proteins from dried blood stained materials of human origin at regular time intervals. Qualitative and quantitative methods employing counter immunoelectrophoresis (CIE) and rocket immunoelectrophoresis (RIE) respectively were used to study the protein extraction efficiency of extractants. Ammonia, compared to gel buffer and saline extracted the proteins effectively. Maximum extraction of proteins was observed in 2-3 hours of sample. CIE demonstrated sharp precipitin bands with all samples of ammonia extractant compared to the samples of counterparts. RIE also revealed greater concentration of proteins in the ammonia extract compared to extracts of gel buffer and saline. These results provide evidence that ammonia serves as a better protein extractant for rapid determination of human blood origin.
Keywords: Forensic science; Forensic serology; Blood origin; Electrophoresis; Protein extractants; Immunoprecipitation
Abstract
A person's stature is an identifying characteristic that is often used in forensic investigation. Footprint is the one of the valuable physical evidence encountered in the crime scenes and examination of barefoot impressions is important especially in developing countries like India, Malaysia where majority of the rural population like to walk barefooted because of socio-economic and climatic reasons. Foot impressions are still found at crime scenes, since offenders often tend to remove their footwear either to avoid noise or to gain better grip in climbing walls, etc., while entering or exiting. Most of the foot/foot print studies were conducted on mixed population. The researchers have cautioned that the people from different races and regions of a country bear different morphological features depending upon their geographical distribution and primary racial characteristics and hence a single formula cannot represent all parts of that country or world. The present study aims to estimate stature from bilateral footprints collected from 320 (160 males, 160 females) consenting adult Ibans, an indigenous group residing in Sarawak state, east Malaysia. Informed consent and Human Ethical Approval were obtained. The height of the individuals and footprints were collected following the standard procedure. The data obtained were analyzed with PASW 20 computer software and derived regression formulae to estimate stature from footprint lengths of Iban ethnics. The result of the investigation revealed that all footprint lengths exhibit statistically positive significant correlation with stature (p< 0.001). Correlation coefficient (R) values are found to be higher in the pooled sample (0.861–0.887) when compared with males (0.753–0.789) and females (0.728–0.790). The regression formulae derived for the pooled sample can be used to estimate stature when the sex of the footprint remains unknown, as in real crime scenarios.
Abstract
Programming scripts were written for the statistical analysis of genetic data from simple cases and complex cases of undetermined paternity. The methods presented here involve algorithms constructed with R, an open-source and increasingly popular programming language used for calculations and statistics; these methods also involve conditional probability analysis, Bayes’ Theorem, and pedigree analysis. Previous computer programs for assessing probable paternity in complex cases of undetermined paternity have been written; however, only minimal or generalized formulas are described in the papers presenting these programs. Therefore, these previously published programs are difficult to understand for most forensic researchers. Here, we present the details of the calculations used to evaluate probabilities of paternity and the details of the R scripts used execute these calculations. These scripts were constructed not only for standard trio case where DNA typing of the mother, child, and the alleged father are available, but also for more complex cases where DNA typing of the alleged father is absent. In these more complex cases, the putative genotype of the alleged father is determined from the genotypes of his parents, his siblings, his wife, children known to be his biological children, or some combination of these people. This report provides concrete and orderly descriptions of the calculations and the R scripts so that each facet of this method is easily understood. Furthermore, access to these scripts will enable individual researchers to develop calculation systems of their own.
Keywords: Forensic mathematics; Paternity testing; R; DNA typing
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
Seminar of U.V. Spectroscopy by SAMIR PANDASAMIR PANDA
Spectroscopy is a branch of science dealing the study of interaction of electromagnetic radiation with matter.
Ultraviolet-visible spectroscopy refers to absorption spectroscopy or reflect spectroscopy in the UV-VIS spectral region.
Ultraviolet-visible spectroscopy is an analytical method that can measure the amount of light received by the analyte.
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
Professional air quality monitoring systems provide immediate, on-site data for analysis, compliance, and decision-making.
Monitor common gases, weather parameters, particulates.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
THE IMPORTANCE OF MARTIAN ATMOSPHERE SAMPLE RETURN.Sérgio Sacani
The return of a sample of near-surface atmosphere from Mars would facilitate answers to several first-order science questions surrounding the formation and evolution of the planet. One of the important aspects of terrestrial planet formation in general is the role that primary atmospheres played in influencing the chemistry and structure of the planets and their antecedents. Studies of the martian atmosphere can be used to investigate the role of a primary atmosphere in its history. Atmosphere samples would also inform our understanding of the near-surface chemistry of the planet, and ultimately the prospects for life. High-precision isotopic analyses of constituent gases are needed to address these questions, requiring that the analyses are made on returned samples rather than in situ.
Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
1. Annex Publishers | www.annexpublishers.com
Volume 1 | Issue 4
Thrombotic Microangiopathy Associated with Intravenous Injection of Opana ER: University Medical Center Case Series.
Marcus R. Winkler1, Thomas C. Watkins1 and Christopher T. Clark*1
1University of Tennessee Graduate School of Medicine, Department of Pathology, 1924 Alcoa Highway, Knoxville, TN 37920, USA
*Corresponding author: Christopher T. Clark, Assistant Professor, University of Tennessee Graduate School of Medicine, Department of Pathology, 1924 Alcoa Highway, Knoxville, TN 37920, USA; Email: CClark@ utmck.edu
Citation: Marcus R. Winkler, Thomas C. Watkins, Christopher T. Clark (2014) Thrombotic Microangiopathy Associated with Intravenous Injection of Opana ER: University Medical Center Case Series. J Case Rep Stud 1(4): 401. doi: 10.15744/2348-9820.1.401
Case Report
Open Access
Volume 1 | Issue 4
Journal of Case Reports and Studies Abstract
In response to the rapidly rising intravenous opioid abuse epidemic, the United States Food and Drug Administration is currently promoting the development of prescription opioid tablets that are specifically formulated to deter abuse. Opana ER (Endo Pharmaceuticals) recently underwent reformulation to include a crush-resistant coating. Only recently described, illicit intravenous injection of reformulated Opana ER is associated with a distinctive clinical syndrome of thrombotic microangiopathy. Ten patients with the appropriate history and presenting symptoms were identified within an 8 month interval (July 2012 through February 2013) at the University of Tennessee Medical Center (UTMC) Knoxville with ICD-9 code of 446.6 (thrombotic microangiopathy) by electronic search. Review of laboratory data, electronic medical records, blood product usage, and total hospital admission charges were compiled for these individual patients. We report the clinicopathologic findings and correlating laboratory data for a group of patients presenting with thrombotic microangiopathy and documented recent history of intravenous Opana ER injection. We also report the economic impact and effect on blood product utilization by this study group. Keywords: 2-Thrombotic microangiopathy; opioid; therapeutic plasma exchange; plasma cryoprecipitate reduced Introduction
Opioid analgesics are a group of widely prescribed medications for post-operative, non-cancer and cancer-related pain. This class of medications is notable for the widely recognized potential for abuse, addiction and as an impetus for criminal behavior [1]. The United States Food and Drug Administration (FDA) recently reported an estimated 15,500 people died due to inappropriate use of prescription opioid drugs in 2009. The high number of deaths due to misuse of opioid drugs has increased 313 percent over the previous two decades. For each death, the FDA reports an additional 10 treatment-related hospital admissions, 32 emergency department visits and 825 illicit (non-medical) opioid drug users [2].
Opana ER (Endo Pharmaceuticals) is an extended-release form of oxymorphone, a potent opioid pain reliever. Opana ER rapidly rose in popularity following the reformulation of OxyContin (Purdue Pharma). The reformulated version of OxyContin was designed to prevent crushing, dissolving and subsequent intravenous (IV) injection [1]. The immediate-release and extended-release versions of Opana were initially released onto the market in 2006 [3]. Opana ER manufacturer developed a crush-resistant pill which was FDA-approved in late 2011. In 2012, the production of Opana ER’s original formulation ceased in lieu of the new crush-resistant formulation [1]. Many websites and chat rooms have since emerged detailing methods to circumvent the new tamper-resistant coating of Opana ER. The illicit IV use of opioid prescription medications has become a nationwide epidemic [1,2,4]. The choice illicit drug of abuse has progressively gone through a transition to the current favorite: opioids [1,4]. While acknowledging this rise to popularity, one must recognize the socioeconomic burden on society. In an effort to deter illicit opioid abuse, the FDA has advocated reformulated, tamper-resistant opioids, made changes in labeling to include risk for abuse, and increased prescriber education through outreach with key members of the prescribing community. Namely, the FDA mandated a Risk Evaluation and Mitigation Strategy for extended-release and long-acting opioids. This program requires the manufacturers to make educational materials about the safe use of opioids available to patients as well as having training programs available to prescribers [2].
Received Date: January 11, 2014 Accepted Date: February 21, 2014 Published Date: February 24, 2014
ISSN: 2348-9820
2. Annex Publishers | www.annexpublishers.com
Volume 1 | Issue 4
Journal of Case Reports and Studies
2
Only recently described by the Centers for Disease Control and Prevention (CDC) in January 2013 is a distinctive clinical syndrome of TTP-like symptoms associated with illicit IV injection of reformulated Opana ER [3]. We present a University-based hospital’s experience of a series of ten patients with characteristic clinical and laboratory findings of Thrombotic Microangiopathy (TMA) and documented recent history of illicit IV Opana ER use. This article describes the clinical and laboratory findings of each patient, as well as the utilization of blood products, and the economic impact by our case series. Results
We identified a total of 18 patients in an 8 month time frame (July 2012 through February 2013) at the University of Tennessee Medical Center (UTMC) Knoxville with ICD-9 code of 446.6 (thrombotic microangiopathy) by search of hospital electronic medical records. Chronic TMA was noted in the electronic medical record of 6 patients who presented for routine clinical follow- up with no treatment during our study time frame. An additional 2 patients were treated with Therapeutic Plasma Exchange (TPE) for TMA unrelated to Opana ER use (one pregnant patient with placenta accreta; one patient with Wegener’s granulomatosis, end-stage renal disease and pneumonia). One patient with history of end-stage cirrhosis was treated with TPE for TMA and had positive toxicology screen for opiates at admission; however, there is no documentation of IV Opana ER use. This is the only patient who expired during this time frame.
Documentation of IV Opana ER use was identified in 10 patients with TMA, by their own verbal report and noted in the electronic medical record. This patient population was selected as our study group and further investigated. The patient age ranged from 20 to 41 years (mean 28.2) with 40% male and 60% female. All patients were Caucasian. The listed home county address for 9 of the patients is within Eastern Tennessee and one from Central Tennessee, but all within a 170 mile radius. The Tennessee counties include: Fentress (1), Hamblen (2), Hawkins (2), Knox (1), Scott (2), and Sevier (2). The average length of stay for the initial admissions ranged from 6 to 28 days (average 15.2). The final inpatient fees determined by UTMC billing department generated for these patients during the 8 month time period (initial and readmissions) totaled $1,025,382. The individual fees for the initial admission ranged from $29,021 (no apheresis patient) to $149,270 per admission. The initial admission fees for all 10 patients totals $851,714 with 3 patients having re-admission fees totaling $173,688 [Table 1].
10
9
8
7
6
5
4
3
2
1
Patient Number
21
21
21
21
21
41
26
21
35
31
Age (years)
M
F
M
F
M
F
M
F
F
F
Sex
C
C
C
C
C
C
C
C
C
C
Race
Sc
Fe
Sc
Haw
Se
Se
Knox
Haw
Haw
Haw
TN County
1
2
2
1
1
3
1
1
1
2
Number of Hospital Admissions
8
20
4
6
11
12
10
7
28
23
14
20
19
Length of Stay (initial admission/ readmission)
29,021
101,357
15,549
45,007
73,081
72,038
55,258
18,464
113,093
141,180
149,270
72,322
139,655
Total Fees (US dollars)
Initial Admission
Readmission
F = Female, M = Male, C = Caucasian, Fe = Fentress, Haw = Hawkins, Ham = Hamblen, Sc = Scott, Se = Sevier
Table 1:
An additional 10 month follow-up revealed 3 of the 10 patients were re-admitted. Patient # 8 was re-admitted within 1 week of this study period with a length of stay of 76 days and additional final bill of $457,059. This patient was also re-admitted 5 additional times within 8 months of our study period. Patient # 5 was re-admitted 2 additional times. Patient # 6 was re-admitted two additional times and expired due to complications of sepsis and endocarditis.
All patients were negative for HIV antibodies; however, 7 patients were positive for hepatitis C antibodies and 1 positive for hepatitis B core IgM antibody while being negative for hepatitis B surface antigen (patient # 1). Likely sepsis was reported in 6 patients. D-Dimer was reported positive in 4 patients. Only 1 of the 6 female patients was recently pregnant. This female patient was transferred to our facility following recent intrauterine demise in addition to symptoms of TMA (patient # 3). Urine toxicology screens at admission were positive in all patients (5 opiates only, 1 opiates and benzodiazepines, 2 benzodiazepines, 1 opiates and cannabinoids, 1 benzodiazepines and cannabinoids). The ADAMTS13 activity levels ranged from 33 to 77% (average 61%, normal ref. range > 66%). The platelet count at admission ranged from 18 to 150 (average 54.3, ref. range 130 – 400 x 109/L). The platelet count at discharge ranged from 113 to 381 (average 221). Lactate Dehydrogenase (LDH) levels at admission were elevated in 9 of 10 patients (average 791.3, ref. range 110-250 IU/L). All patients were anemic at admission with average hematocrit of 23.83% (range 15.3% - 31.6%, ref. range 37.0 – 47.0%). Schistocytes were documented on the peripheral blood smear of 6 patients. Elevated serum creatinine levels were noted in 8 patients (range 1.6 to 11.22, average 3.19, ref. range 0.60 - 1.30 mg/dL). Fever was reported at admission in 2 patients and 5 had reported neurologic symptoms [Table 2].
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10
9
8
7
6
5
4
3
2
1
Patient Number
75%
51%
54%
45%
73%
33%
70%
77%
77%
55%
ADAMTS13 RR: >66% (Percent Activity)
45/181
150/381
66/145
51/113
62/202
31/166
60/236
19/250
18/378
41/149
Platelet Count Admit/ Discharge RR: 130-400 (Plt Ct x 109/L)
417/178
430/120
338/232
794/308
397/168
1685/231
1890/205
1382/160
217/199
363/218
LDH Admit/Discharge RR: 110-250 (IU/L)
8.2
10.2
6.8
7.3
8.6
8.1
8.9
4.7
6.7
9.2
Hemoglobin, Admission RR: M= 14-18 F= 12-16 (g/dL)
Yes
Yes
Yes
Yes
Yes
Yes
NP†
NP†
NP†
No
Schistocytes (PB)
1.55
5.74
3.08
11.22
1.19
1.02
1.6
3.2
1.55
1.7
Serum Creatinine, Admission RR: 0.60-1.30 (mg/dL)
Yes
No
Yes
No
Yes
Yes
Yes
No
No
No
Neurologic Sx.
No
No
No
No
Yes
No
Yes
No
No
No
Fever
No
Yes
Yes
No
Yes
No
Yes
No
Yes
Yes
Likely Sepsis
Neg.
Neg.
Neg.
Neg.
Neg.
Neg.
Neg.
Neg.
Neg.
Neg.
HIV AB Screen
Pos.
Pos.
Pos.
Pos.
Pos.
Pos.
Neg.
Neg.
Neg.
Pos.
Hepatitis C AB Screen
RR = Reference Range, (PB) = Peripheral Blood, Sx. = Symptoms,
AB = Antibodies, Neg. = Negative, Pos. = Positive
† Not performed; Peripheral blood smear not reviewed
Table 2:
TPE was utilized in 9 patients and 1 patient was treated with serial thawed plasma transfusions. Only 2 of the 10 patients required dialysis treatments (patients # 7 and 8). During initial admissions, a total of 77 TPE procedures were performed with total overall volume of apheresis of 272,757 mL. TPE performed during re-admissions in this time frame totaled 36 procedures with a total overall volume of apheresis of 60,895 mL. No significant complications of TPE were reported in the electronic medical record. The total blood products utilized during this time frame included: 47 red blood cell units, 3 apheresis platelet units, 120 thawed plasma units, and 653 units (189,068 mL) of plasma cryoprecipitate reduced [Table 3].
Number of Apheresis Platelet Units
Number of RBC Units
Number Thawed Plasma Units
Number of CPP Units (mL)
Volume of Apheresis Procedures (mL)
Number of Therapeutic ApheresisProcedures
Patient Number
0
0
2
0
2
0
166 (47,145)
113 (31,878)
76,488
60,895
16
9
1
Readmit
1
8
0
56 (16,189)
28,935
10
2
2
9
0
109 (32,525)
61,840
18
3
0
5
0
40 (11,761)
21,404
7
4
0
0
4
1
1
18
51 (14,670)
0
16,537
0
7
0
5
Readmit
0
4
4
33 (9,828)
21,511
5
6
0
5
4
41 (12,217)
23,608
8
7
0
2
5
32 (9,381)
17,630
4
8
0
0
3
0
0
0
12 (3,474)
0
4,804
0
2
0
9
Readmit
0
4
35
0
0
0
10
3
0
T = 3
46
1
T = 47
51
69
T = 120
540
113
T = 653
272,757
60,895
T = 333,652
77
36
T = 113
Totals
Initial
Readmit
Overall
CPP = Cryo-poor plasma (plasma cryoprecipitate reduced), RBC = red blood cell
Table 3: Discussion and Conclusion
Tamper-resistant tablets to prevent crushing and dissolving were developed in an attempt to reduce misuse of prescription drugs. Despite this, there are numerous websites and chat rooms with information about ways to circumvent these efforts. Some techniques
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suggested in web-based chat rooms include: use of nail file to remove outer layer, microwaving, use of acid base extraction, and use of a solvent with filtration [5,6]. The new formulation of Opana ER was FDA approved in late 2011 and released in February 2012. The CDC first reported cases of “TTP-like illness associated with IV Opana ER abuse” in August 2012. The CDC report notes 15 patients in Tennessee reported through October 2012 [3]. We found 10 cases at our institution from July 2012 through February 2013, which extends beyond the time frame of the CDC report, but we are unsure if any of our patient population was included in the cases reported by the CDC. The tamper-resistant tablets are coated with inactive ingredients including Polyethylene Oxide (PEO); a compound similar to Polyethylene Glycol (PEG) with a higher molecular weight [3,7]. Used as an inactive ingredient in many other drug formulations, PEO confers tablet hardness and aids in controlling the release of the active ingredient, oxymorphone. PEO is a polymer and the molecular weight is highly variable [7]. However, PEG has been used in certain IV medications with very few studies on toxicity. It does appear the major target organ for toxicity was the kidney when high doses of PEG were given to laboratory animals [8]. The disparity in molecular weights between the PEG used in this study of toxicokinetics and the PEO used in Opana ER could possibly contribute to systemic manifestations [7,8]. To our knowledge, studies involving the IV injection of PEO have not been performed. Therefore, it is difficult to predict the pharmacokinetics as well as toxicity and organ damage for this route of administration. It is interesting to note that re-formulated OxyContin contains PEO; however, no cases of TMA associated with the IV use of re-formulated OxyContin have been reported [3]. These drugs are produced by different manufacturers; therefore, there may be variation in the ingredients and/or manufacturing process of the tamper-resistant forms. In addition, this may represent a shift in the prescription practice from re-formulated OxyContin to Opana ER. In April 2010, re-formulated OxyContin was FDA approved. An alert issued by Nassau County Department of Social Services, Long Island, New York reported that between August 2010 and February 2011, there was a 43% decrease in Medicaid prescriptions for OxyContin with a 45% increase in Opana ER [9].
There is overlap in our patient population, as well as in the CDC case-control study group, with some of the known associations with TMA, such as Hepatitis C infection and clinical features of sepsis. The CDC case-control study reports a strong association between injection of re-formulated Opana ER and “TTP-like illness” (OR=35.0; CI=3.9-312.1) [3]. The exact underlying cause for this association is unknown and is likely multifactoral. Decreased levels of ADAMTS13 is a proposed etiologic mechanism for TMA and patients with Hepatitis C infection and IV drug abusers are known to have decreased levels [10]. The interaction and relationship of the re-formulated PEO coating and ADAMTS13 activity is unknown. One possible mechanism is formation of an inhibitor and/or autoantibody to ADAMTS13 contributing to the clinical symptoms of TMA as the tablets are altered for injection. Unfortunately, our patient population was not tested for ADAMTS13 autoantibodies and the method of altering the tablets is unknown. It would be of interest to know exactly how the drugs were altered by the abusers in our population since the mechanism utilized to alter the tablets may be a contributing factor. Since our patient population was concentrated in a relatively small geographic region, and some are immediate family members, it is likely that our patient population may be using a similar technique to alter the tablets for injection.
In addition to the clinical novelty, the impact of this method of drug abuse on the health care system is quite significant. At our institution, we saw 2 cases of TMA requiring TPE that were unrelated to IV Opana abuse and 1 patient with an undocumented drug history. In contrast, we had 10 patients within this time frame with TMA and documented IV Opana ER abuse, which is 77% of TMA patients requiring treatment during this time frame. Four of our ten patients were re-admitted during this study time frame. Two patients had similar findings of the initial presentation of TMA and reported continued use of IV Opana ER. One patient received additional TPE and one received serial thawed plasma transfusions. The other two admissions were for reasons other than TMA. During this time frame, these 10 patients generated over 1 million dollars in fees. IV Opana ER abuse is not only a social issue, but greatly impacts the available medical resources in our community, including availability of staffing and equipment.
In addition to the financial impact, there is a potential impact on the available blood supply which at times can already be limited. During our 8-month study period, a significant number of blood products were utilized. Our local blood supplier could not meet the demand for plasma cryoprecipitate reduced units for these apheresis treatments and many units had to be acquired and shipped from outside blood donor centers. Within 10 months following our study period, 3 of the 10 patients were re-admitted. One patient was re-admitted within 1 week of this study period requiring 27 TPE procedures and utilizing 12 red blood cell units, 11 units thawed plasma and 198 units plasma cryoprecipitate reduced (55,511 mL). Only 1 of 10 patients is known to have expired with cause of death listed as complications of sepsis and endocarditis.
This case report illustrates at least some aspects of the growing epidemic of prescription drug abuse and its potential impact on the medical community and society at large. The exact cause for TMA in this patient population is unknown and will require further investigation. We did not identify any unique clinical symptom or laboratory findings in our patient population that would alert clinicians of possible IV Opana ER use when patients present with TMA. Questioning patients who present with TMA about their illicit drug use may reveal more reports and associations with IV Opana ER. Due to the novel nature of our report, long- term sequalae have not been clearly defined at this time. Long-term patient follow-up may be needed to fully characterize the emphasized aspects of this report.
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Journal of Case Reports and Studies References
1. Stanos SP, Bruckenthal P, Barkin RL, (2012) Strategies to Reduce the Tampering and Subsequent Abuse of Long-acting Opioids: Potential Risks and Benefits of Formulations with Physical or Pharmacologic Deterrents to Tampering. Mayo Clin Proc. 87: 683-94.
2. United States Food and Drug Administration (2013) FDA’s Efforts to Address the Misuse and Abuse of Opioids.
3. Centers for Disease Control and Prevention (2013) Thrombotic Thrombocytopenic Purpura (TTP)-Like Illness Associated With Intravenous Opana ER Abuse – Tennessee, 2012. MMWR Morb Mortal Wkly Rep 62: 1-4.
4. Substance Abuse and Mental Health Services Administration (2013) Drug Abuse Warning Network, 2011: National Estimates of Drug-Related Emergency Department Visits.
5. Tutorial How To IV Opana ER (2013).
6. How To Prep A Specific Generic Opana 5 mg IR for IV (2013).
7. Food and Drug Administration Advisory Committee on Reformulated OxyContin (2009).
8. Li BQ, Dong X, Fang SH, Gao JY, Yang GQ, et al. (2011) Systemic toxicity and toxicokinetics of a high-dose of polyethylene glycol 400 in dogs following intravenous injection. Drug Chem Toxicol 34: 208-12.
9. Mangano Issues Dependency Public Health Alert on Increasing Usage of the Narcotic Drug Opana (2013).
10. Yagita M, Uemura M, Nakamura T, Kunitomi A, Matsumoto M, et al. (2005) Development of ADAMTS13 inhibitor in a patient with hepatitis C virus-related liver cirrhosis causes thrombotic thrombocytopenic purpura. J Hepatol 42: 420-1.