Epidural Abscess

A Foodborne Disease “Campylobacteriosis”: Global Epidemiology, Pathogenicity, Diagnosis and Treatment

Campylobacteriosis is a foodborne disease caused by Campylobacter, which is one of the leading causative agents of bacterial gastrointestinal diseases in developed and developing countries. According to WHO, Campylobacter species infects a hundred million people yearly. The bacterium is thermotolerant, cytochrome oxidase-positive, spiral-shaped, gram-negative, and microaerophilic, by exhibiting corkscrew motility it passes through the intestines of animals and birds. It is generally transmitted through the consumption of contaminated food associated with animal and their products. The main infectious species include C. coli, C. jejuni, C. fetus and C. upsaliensis. Infection symptoms can be mild to serious depending upon the patient's age and in some cases can lead to permanent neurological disorders. Detection of Campylobacter in food, clinical and environmental samples is accomplished with the help of combinatorial usage of selective enrichment and culture methods. Currently, there is no sole viable approach for infection management because of resistance emergence. In this review article, we discuss Campylobacter epidemiology, pathogenicity, various diagnostic methods and treatment of Campylobacteriosis.

Extensive Multifocal Emphysematous Osteomyelitis of Spine: A Rare Case and a Review of Literature

Background: Emphysematous osteomyelitis (EO) is an extremely rare form of osteomyelitis which is complicated mainly by infection with gas-forming organisms. The common causative agents of this disease are mainly members of Enterobacteriaceae family, the most common are Escherichia coli and Klebsiella pneumoniae along with anaerobes. A total of 48 cases of EO have been reported in the literature till now globally and none have documented the isolation of Corynebacterium amycolatum.

Case Presentation: We report a rare case of emphysematous osteomyelitis of the spine and pelvis due to Escherichia coli along with the isolation of Corynebacterium amycolatum from the same pus samples on two consecutive occasions in a 50-year-old female with uncontrolled diabetes mellitus, who was successively treated with antibiotics and drainage of pus. We also did a brief review of the literature of all cases reported till now.

Conclusion: The role of Corynebacterium amycolatum in the etiology of emphysematous osteomyelitis needs to be evaluated further in future studies as we cannot completely ignore its isolation in two consecutive samples as a mere contaminant.

The Virulent Hypothetical Proteins: The Potential Drug Target Involved in Bacterial Pathogenesis

Hypothetical proteins (HPs) are non-predicted sequences that are identified only by open reading frames in sequenced genomes, but their protein products remain uncharacterized by any experimental means. The genome of every species consists of HPs that are involved in various cellular processes and signaling pathways. Annotation of HPs is important as they play a key role in disease mechanisms, drug designing, vaccine production, antibiotic production, and host adaptation. In the case of bacteria, 25-50% of the genome comprises HPs, which are involved in metabolic pathways and pathogenesis. The characterization of bacterial HPs helps to identify virulent proteins that are involved in pathogenesis. This can be done using in-silico studies, which provide sequence analogs, physiochemical properties, cellular or subcellular localization, structure and function validation, and protein-protein interactions. The most diverse types of virulent proteins are exotoxins, endotoxins, and adherent virulent factors that are encoded by virulent genes present on the chromosomal DNA of the bacteria. This review evaluates virulent HPs of pathogenic bacteria, such as Staphylococcus aureus, Chlamydia trachomatis, Fusobacterium nucleatum, and Yersinia pestis. The potential of these HPs as a drug target in bacteria-caused infectious diseases, along with the mode of action and treatment approaches, has been discussed.

Intravenous Magnesium – Lidocaine - Ketorolac Cocktail for Postoperative Opioid Resistant Pain: A Case Series of Novel Rescue Therapy

Background: Severe postoperative pain is principally managed by opioids. While effective, opioids do not provide adequate relief in many patients and cause many side effects, including antinociceptive tolerance and opioid-induced hyperalgesia. To evaluate if a combination of intravenous Magnesium, Lidocaine, Ketorolac (MLK cocktail) is a useful rescue therapy through synergistic pharmacological mechanisms for acute pain relief. We present the intravenous combination of magnesium, lidocaine, and ketorolac (MLK cocktail) as a possible rescue for opioid insensitive severe post-operative pain.

Materials and Methods: The principal settings were the post-operative care unit (PACU) and the surgical ward. We retrospectively analyzed the electronic medical record and anesthesia documents of 14 patients experiencing severe postoperative pain, >7/10 visual-analogue pain score (VAS), despite receiving at least 8 mg of intravenous morphine milligram equivalents (MME) after arrival in the LAC+USC Medical Center PACU between September 2012 and January 2013. The data reviewed included patients’ demographics, disease etiology, surgical procedure, opioids received perioperatively, and visual-analogue pain scores before and after each analgesic received, and after the MLK cocktail. The a priori primary outcome and a posteriori secondary outcome of this study are mean visual-analogue pain score and morphine milligram equivalent dose administered per hour, respectively. The main tool evaluated has been VAS score.

Results: In patients who failed to respond to opioid analgesics, administration of the MLK cocktail improved the VAS pain scores immediately from 9.4 ± 1.0 to 3.6 ± 3.5. The MLK cocktail also decreased the MME doses/hour in the immediate 12 hours postoperative period from 12.4 ± 5.6 to 1.1 ± 0.9.

Conclusion: In patients experiencing opioid-resistant severe postoperative pain, the magnesium, lidocaine, and ketorolac combination may be an effective nonopioid rescue therapy. Additionally, magnesium, lidocaine, and ketorolac may be utilized in cases complicated by either antinociceptive tolerance or opioid-induced hyperalgesia and can restore opioid responsiveness.

Distinct Forms of Spinal Cysticercosis: A Vietnamese Case Series

Introduction: Neurocysticercosis (NCC), a major contributor to the burden of seizure disorders and epilepsy in the world, is one of the most common parasitic infections of the central nervous system, which is usually located in the brain. Medical therapy for NCC should initially cover appropriate symptom control and then the use of antiparasitic agents should be considered. Antiparasitic treatment is of benefit in most cases of viable and degenerating NCC. Nevertheless, cysticercosis of the spinal cord is very uncommon.

Case Series: In this article, we recorded 5 cases of extramedullary-intradural lumbar spinal cysticercosis, in which one case displayed cystic lesions in both brain and spine, one case showed an independent cystic lesion in the spine, and three remaining cases showed diffuse lesions in the spinal canal.

Conclusion: Thus, in any case of single or numerous cystic lesions or dispersed lesions entering the spinal canal, spinal cysticercosis should be considered.

T9-T10 Osteomyelitis, Epidural Abscess and Cord Compression Secondary to Mycobacterium abscessus: A Case Report

Background: We report a case of spinal abscess/osteomyelitis at the T9-T10 levels in a non-immunocompromised patient who presented with lower extremity weakness secondary to a Mycobacterium abscessus infection. This patient was successfully treated with surgical debridement with amikacin-tigecycline-imipenem triple therapy before and after her debridement. Outcomes and treatment with this rare cause of epidural abscess/osteomyelitis are not well defined at this time.

Case Report: Clinical Presentations with this species of mycobacterium are usually systemic with patients presenting with pulmonary and soft tissue infections. The primary presentation of spinal epidural abscess/osteomyelitis is unusual, especially when there is no primary focus such as a lung infection or concurrent bacteremia.

Conclusion: This paper presents a new case of spinal osteomyelitis without a primary source in addition to 10 previously reported M. abscessus cases. The treatment plans and outcomes suggest that surgical debridement along with a macrolide-based combination therapy should be considered a definitive treatment against Mycobacterium abscesses.

Organic Lesions in the Brain MRI of Children with Febrile Seizure

Objective: Seizure is the most common neurological disorders in children, where 4-10% of the cases experience at least one seizure before the age of 16. The most frequent causes of seizures in children are fever, epilepsy, infection and brain damage. The aim of this study was to investigate the frequency of organic lesions in MRI of children with seizures unrelated to fever.

Materials and Methods: This cross-sectional study included children presented with fever-unrelated seizures. The MRI was examined by a radiologist to identify abnormal findings in each patient. A researcher-made questionnaire including general information, history of head trauma, obstructed labor and the history of seizure was completed for the patients.

Results: Of 287 children with fever-related seizure, 127 (45.7%) were male and 151 (54.3%) were female. History of seizure, history of obstructed labor, abnormal MRI, complete delay, use of antiepileptic drug and history of trauma were 22(9.9%), 1 (0.4%), 11(4%), 5(1.8%), 259(93.2%) and 12 (4.3%), respectively. Of 11 patients with abnormal MRI, 4 had MTS lesions, 2 had tumor lesions, 2 had scarring trauma, 1 had an epidural abscess and 1 had meningitis. The frequency of organic lesions had no significant differences based on gender, use of antiepileptic drug and traumatic history, but it had a significant relation with obstructed labor andthehistory of seizure.

Conclusion: The results showed that organic brain lesions in children with fever-unrelated seizure had a significant relationship with the history of seizure and obstructed maternal labor.

Recent Advances in Pathophysiology of Traumatic Brain Injury

Background: Traumatic brain injury (TBI) constitutes the primary reason for mortality and morbidity in persons worldwide below 45 years of age. 1.7 million Traumatic events occur yearly in the United States alone, considering for 50,000 deaths. In severe traumatic brain injury sufferers, a considerable achievement attained in treating short-term consequences; but till date, huge failures are occurring in researcher’s capability to render severe traumatic brain injury sufferers to an elevated degree of performing.

Methods: Initial damage force results in Primary brain injury, causing tissue destruction and distortion in the early post-injury period. These secondary injuries from TBI cause changes in cell performance and dissemination of trauma via activities like free-radical generation, depolarization, and formation of edema, excitotoxicity, and disruption of blood brain barrier, calcium homeostasis, and intracranial hematoma. The expectation for developing effect in TBI sufferers is the best knowledge of these activities and enhancement of remedies that restrict secondary brain damage.

Results: The focal point of this study is on knowing the complex outburst of secondary impairments and studying the pathophysiology of TBI which provides alternative treatment benefits.

Conclusion: While injured persons demonstrate dissimilar levels of harm and every case is novel with specific recovery profiles, this article strengthens the recent pathophysiological sight of TBI mainly attention on oxidative stress, excitotoxicity, cerebral oxygenation and cerebral blood flow (CBF), development of edema, and inflammatory activities. For initial research acknowledgment of these recurring factors could permit clarification of possible beneficial targets.

CT and MR Imaging of the Encephalopathic Child

Background: Neonatal and paediatric encephalopathy can be a diagnostic challenge for clinicians. Potential aetiologies include hypoxic brain injury, stroke, infection, trauma, metabolic and electrolyte abnormalities, autoimmune conditions and drug ingestion. Radiology plays a key role in determining aetiology and, even when normal, directing further assessment.

Conclusion: We present a review of the neuroradiological manifestations of neonatal and paediatric encephalopathies which will aide paediatricians and radiologists in their assessment of children with this condition.

Bone Imaging in Metastatic Castration-resistant Prostate Cancer; Where do we Stand

Background and Objectives: We are witnessing an era of increased clinical interest in metastatic castration-resistant prostate cancer, both in terms of treatment and also in terms of imaging options. This surge of interest is attributed to the recent developments in treatments for metastatic prostate cancer that are able to confer a significant survival advantage. We are therefore, anticipating an increase in the number of patients that we need to treat at this disease stage. Imaging is undoubtedly crucial in monitoring disease response to treatment and progression.

Methods: We have reviewed the recent literature using the following search terms: “metastatic prostate cancer”, “castration-resistant”, “bone metastases”, “bone scan”, “abiraterone”, “enzalutamide”.

Results: Bone scintigraphy has evolved recently with new and more sensitive tracers that can accurately diagnose even low volume disease progression. MRI has an established role in the diagnosis of spinal cord compression.

Conclusion: Metastatic, castration-resistant prostate cancer is a discrete and different phase of prostate cancer with newer agents that have shown great promise in controlling the disease and offering a survival benefit for patients. Recommendations regarding the choice of imaging, trigger points for repeating imaging and intervals between imaging are still under development for this phase of the disease especially for patients treated with new androgen targeted agents.

Effects of Maternal Obesity on Maternal and Fetal Health

Obesity, as defined by body mass index (BMI) is one of the biggest challenges facing health care system including maternity services today, particularly in the industrialized nations. Maternal obesity is linked with a number of pregnancy complications including gestational diabetes, preeclampsia, venous thromboembolism, caesarean delivery, postpartum haemorrhage, macrosomia, shoulder dystocia and poor perinatal outcomes. Obesity has also been shown to be independently associated with higher odds of dying from specific pregnancy complications. These risks increases with increasing BMI and are highest in women with BMI ≥ 50. The mechanisms underlying these pathologies remain unclear. All obese women in reproductive age group should be counselled about weight gain, exercise programmes, nutrition and food choices, longer term health risks and increased risk of maternal and fetal complications, ideally before contemplating pregnancy. They should also be supported to lose weight and optimise their health before conception. Obese pregnant women should receive routine care supplemented by specialist services and facilities that are specific to their needs, to improve maternal and perinatal outcomes.

Status Epilepticus: An Overview

Status epilepticus (SE) is an emergency situation, where immediate and effective treatment is required in least possible time as it is associated with neuronal damage, systemic complications, substantial morbidity and mortality depending on status type, duration, age and etiology. In the past few years, morbidity and mortality rate were improved, probably may be due to aggressive use of anti-epileptic drugs in emergency situations. Present literature gives an overview of the conditions leading to SE and its management guidelines in hospital and out of hospital setting emphasizing on the available drug therapies.

Maternal Sepsis: Current Approaches to Recognition and Clinical Management

Sepsis represents a leading cause of maternal morbidity and mortality in the United States and worldwide. Clinical management of sepsis in pregnancy must take into consideration the unique pathophysiology of pregnancy. Etiologies of sepsis in pregnant and post-partum women differ from a patient who is non-pregnant. Moreover, the clinical diagnosis of sepsis in pregnancy can be quite challenging due to the anticipated physiologic changes that occur in pregnancy, contributing to variability in recognition. Pre-existing maternal medical conditions and other demographic factors may also predispose certain women to developing sepsis. Prompt recognition and subsequent treatment of sepsis in pregnancy can improve both maternal and neonatal outcomes. In the present review, we will summarize the perinatal implications of sepsis in the obstetric population during the antepartum and postpartum periods. Further understanding of systemic inflammation leading to multi-system organ failure, non-obstetric and obstetric etiologies of sepsis, and subsequent perinatal complications will help to expeditiously identify and treat women with this life-threatening condition to ultimately improve outcomes.

Anesthesia Issues in Central Nervous System Disorders

Every year, millions of people affected by disorders of the central nervous system (CNS) undergo various diagnostic, therapeutic and surgical procedures requiring administration of anesthetic agents. Anesthetics exert their anesthetic, amnesic and analgesic effects by acting on multiple neuronal membrane proteins in the CNS. While some of the causal anesthetic targets have been identified, a large number of anesthetic targets remain unknown. The consequent longterm effect of anesthetic agents on expression of these various molecular targets has been implicated in mediating potentially long-lasting adverse effects. Recent work suggested that the effects of general anesthetics may not be entirely reversible, with animal studies demonstrating persistent changes in CNS protein expression post recovery from anesthesia. Age-associated or disease-induced alterations in the CNS can profoundly alter multiple aspects of brain structure, biochemistry, and function. Such maladaptive changes in the brain can render it increasingly vulnerable to the effects of various anesthetics. The selection of appropriate anesthesia drugs and protocol is mandatory, especially in individuals with pre-existing CNS disorders, so as to maximize anesthesia efficiency, avoid occurrence of adverse events, and ensure patient safety. This review aims to summarize and consider the effects and potential risks of commonly used anesthetic agents in patients with compromised CNS function. We provide a comprehensive review of the established as well as the implicated effects of anesthetic agents on the elderly as well as on the pathology and progression of common neurological conditions.

Non-Vitamin K Oral Anticoagulants (NOACs) A Review of Clinical Management and Laboratory Issues

The non-vitamin K oral anticoagulants (NOACs) are set to replace vitamin K antagonists (principally warfarin), unfractionated heparin and low molecular weight heparin as the leading antithrombotic prophylaxis in several medical and surgical settings. As a group, NOACs have a better safety profile and at least an equivalent (and sometimes superior) efficacy profile than their comparator. The objective of this review is to provide the practitioner with a comprehensive, balanced and contemporary view of these drugs and their applications. More specifically, it focuses on the evidence base for their licences, use in clinical practice (such as in renal dysfunction, orthopaedic surgery, atrial fibrillation, and venous thromboembolism, and the effects of co-medications), responses to actual or perceived haemorrhage, and the role of the laboratory.

Validity of Oxygen-Ozone Therapy as Integrated Medication Form in Chronic Inflammatory Diseases

The state-of-the-art of oxygen-ozone therapy is now clarified and all the mechanisms of action of medical ozone are within classical biochemistry and molecular biology. The outcomes of standard treatments in peripheral arterial occlusive disease (PAOD) and dry-form of age-related macular degeneration (AMD) have been compared with the documented therapeutic results achieved with ozonated autohemotherapy (O-AHT). On the other hand, the clinical data of O-AHT on stroke remain indicative. As the cost of O-AHT is almost irrelevant, its application in all public hospitals, especially those of poor Countries, would allow two advantages: the first is for the patient, who will improve her/his conditions, and the second is for Health Authorities burdened with increasing costs. The aim of this paper is to report to clinical scientists that O-AHT is a scientific-based therapeutic approach without side effects. The integration of O-AHT with effective approved drugs is likely to yield the best clinical results in several chronic inflammatory diseases.

Treasures Hunt in Old Mines: Terminalia chebula-Based Traditional Herbal Medicinal Products

Traditional herbal medicinal products (THMPs) have served as a source of medicines as well as disease-preventive products; consequently, they became the major source of molecular medicines. Roughly 65% of the drugs in the current arsenal are based on natural products or derived from natural products. THMPs are regaining immense popularity in maintaining discovery of new drugs to cope with the challenges of sustaining drug efficacies and countering the emergence of drug resistance. Natural products are the main source for novel skeletons and drug candidate leads. Terminalia chebula, a plant habitant of sub- Himalaya region, is effectively being used against several diseases with no major reported side effects. Our Sci-Finder (CAS) literature search has shown ~2000 research reports on this single specie and ~74 THMPs based on T. chebula alone or in combination with other medicinal herbs. This review provides relevant knowledge covering these 74 THMPs derived from this miraculous cure, i.e. T. chebula and its major nature engineered bioactive chemical constituents. This is expected to make a meaningful contribution, especially: 1) Standardization, dosage and safety studies of these 74 THMPs of T. chebula; 2) its promising role in discovery of new, effective, novel and safer molecular drugs. T. chebula is a rich source of a variety of novel natural products, especially, its abundance in a wide range of tannins could be very important in modulating several biological disorders. T. chebula-derived THMPs are economical and are vastly being used throughout the world. It is important that their use, efficacy and side effects should be studied and documented properly to enhance the efficacy and reduce the adverse effects.

Chemotherapy Delivery Strategies to the Central Nervous System: neither Optional nor Superfluous

Malignant brain tumors including primary brain tumors (e.g., glioblastoma multiforme) and metastases, are aggressive and lethal entities for the majority of affected patients. Current standard treatments involving combinations of surgery, radiotherapy and systemic chemotherapy offer only modest improvements in survival. Faced with dismal survival, great efforts are deployed to find interesting treatment alternatives. However, the blood-brain barrier (BBB) and the blood-tumor barrier (BTB) remain great obstacles to significant drug delivery to brain tumors. The need to optimize delivery strategies for better patient outcome in the treatment of malignant brain tumors is well acknowledged. Certain interesting strategies use surgical or physical techniques to enhance the distribution of therapeutic agents to the central nervous system. The following strategies will be discussed in this review: intra-arterial delivery, osmotic BBB disruption, intranasal delivery, convection-enhanced delivery and osmotic pumps, implanted polymers, magnetic microspheres and ultrasound BBB disruption. The purpose of this paper is to review the importance of the BBB and the BTB and to review the current status and future perspectives of these delivery procedures.

Coccidioidomycosis Involving the Cranium: A Case Report and Review of Current Literature

We report a case of Coccidioidomycosis of the cranium that presented as a cystlike structure with adjoining bone destruction in a 40-year-old patient with underlying rheumatoid arthritis that was treated with a combination of lipid amphotericin B and longterm fluconazole. We also discuss the common risk factors and presentations of this unusual extra-pulmonary form of Coccidioidomycosis.

Catheter Related Line Sepsis Resulting from Mycobacterium chelonae Infection in an Immunocompromised Host

Almost any species of non tuberculosis mycobacterium [NTM], including M. chelonae may be associated with nosocomial infections including catheter related sepsis, pneumonia etc. We present a case of catheter related sepsis due to M. chelonae which was treated with appropriate therapy including removal of the catheter. This case serves as a reminder to include the NTM group in the differential diagnosis of these nosocomial infections.

Nanofibers Based Antibacterial Drug Design, Delivery and Applications

Infections caused by microorganisms like bacteria, fungi, etc. are the main obstacle in healing processes. Conventional antibacterial administration routes can be listed as oral, intravenous/intramuscular, topical and inhalation. These kinds of drug administrations are faced with critical vital issues such as; more rapid delivery of the drug than intended which can result in bacterial resistance, dose related systemic toxicity, tissue irritation and finally delayed healing process that need to be tackled. Recently, studies have been focused on new drug delivery systems, overcoming resistance and toxicological problems and finally localizing the molecules at the site of action in a proper dose. In this regard, many nanotechnological approaches such as nanoparticulate therapeutic systems have been developed to address accompanying problems mentioned above. Among them, drug loaded electrospun nanofibers propose main advantages like controlled drug delivery, high drug loading capacity, high encapsulation efficiency, simultaneous delivery of multiple drugs, ease of production and cost effectiveness for pharmaceutical and biomedical applications. Therefore, some particular attention has been devoted to the design of electrospun nanofibers as promising antibacterial drug carrier systems. A variety of antibacterials e.g., biocides, antibiotics, quaternary ammonium salts, triclosan, metallic nanoparticles (silver, titanium dioxide, and zinc oxide) and antibacterial polymers (chitosan, polyethyleneimine, etc.) have been impregnated by various techniques into nanofibers that exhibit strong antibacterial activity in standard assays. This review highlights the design and delivery of antibacterial drug loaded nanofibers with particular focus on their function in the fields of drug delivery, wound healing, tissue engineering, cosmetics and other biomedical applications.

Oral Inflammation and Bacteremia: Implications for Chronic and Acute Systemic Diseases Involving Major Organs

Gingivitis and periodontitis are both highly prevalent gum diseases characterized by an accumulation of a polymicrobial biofilm (dental plaque) around teeth and inflammation in adjacent soft tissues. During dental procedures, even tooth brushing, these bacteria and their components, such as endotoxin, can easily disseminate into the systemic circulation through minor or major gingival injuries. Particularly in immuno-compromised subjects or patients with preexisting pathologic conditions, bacteremia may lead to bacterial infection of distant organs, which may cause immunological reactions. Oral bacteria and endotoxins have been found in sepsis, infective endocarditis, lung infection, liver disease and many other potentially lethal disorders. This article presents a review of the possible pathologic consequences of bacteremia originating in the oral cavity and points out the most commonly affected organs as well as preventive and treatment measures. At the present time, plaque control by subjects and/or dental professionals is one of the most effective means to prevent the onset and progression of oral bacteremia-induced systemic diseases.

Delivery Systems of Opioid Analgesics for Pain Relief: A Review

Chronic pain is usually treated with pharmacological measures using opioids alone or in combination with adjuvant analgesics that play an important role in the treatment of pain not fully responsive to opioids administered alone, especially in neuropathic, bone and visceral colicky pain. The important part of the chronic pain treatment is the appropriate use of non-pharmacological measures along with psychosocial and spiritual support.

Opioids may be administered by different routes; the most common and most convenient for majority of treated patients are oral and transdermal. However, in certain circumstances such as inability to swallow, lack of analgesic efficacy and intractable opioid-induced adverse effects parenteral routes (subcutaneous, intravenous) might be more useful. When these routes fail, in some patients intrathecal administration of opioids is required. Recently, more patients have been treated with short-acting opioids for breakthrough pain with sublingual, buccal and intranasal routes of opioid administration that may provide efficacy superior to oral and comparable to intravenous routes. Alternative routes comprise rectal, inhaled and topical administration of opioids. This article discusses various routes of opioid administration.

Cushing Syndrome and Giant Sterile Abscess Induced by Self Intramuscular Injection of Supra-therapeutic Doses of Triamcinolone

Objective: Corticosteroid are among the most commonly used medications for a wide range of inflammatory, autoimmune and neoplastic disorders. Therefore, it is important for the physician to be aware of their side effects, in relation to different forms and delivery, that occur more often with oral therapy.

Methods: A 33-year old professional drummer had been suffering from bilateral tenosynovitis of the wrists for three months. In order to accelerate the recovery and play drums again, he self-injected supra-therapeutic doses of triamcinolone acetonide (a total of injected drug > 2,400 mg was calculated) in his right gluteus.

Results: The intramuscular overuse of triamcinolone acetonide caused Cushing syndrome associated with a giant sterile abscess that involved the right gluteal muscles and the adjacent subcutaneous tissue.

Conclusion: A large intramuscular sterile abscess can be a side effect of supra-therapeutic intramuscular triamcinolone dose and this should be explained to the patient prior to initiation of treatment with triamcinolone.

Infection and Hemodialysis Access: An Updated Review.

The incidence of end-stage renal disease (ESRD) has almost doubled over past 2 decades. Despite decreasing overall hospital admission rates for ESRD population, the rate of infection-related hospitalizations has steadily increased. Infection remains the second most common cause of mortality in this patient population. Specifically, in the hemodialysis (HD) patients, the vascular access related infections are the most common identifiable source of infection. This concise review provides an update on the bacteremia related to vascular access primarily the catheters (Catheter Related Blood Stream Infection- CRBSI) in HD patients emphasizing on the determinants ranging from the epidemiology to pathogenesis, risk factors, cost implications and prevention. Staphylococcus aureus, coagulase negative Staphylococci, and Enterococci are the most common causative microorganisms implicated in CRBSI. The pathogenesis of CRBSI includes organism entry into the blood stream followed by adherence to catheter, colonization and biofilm formation. Vascular access type, catheter position, and prior bacteremic episodes are strongly associated with blood stream infection. Preventive measures should be multidisciplinary in nature and should include avoidance of central venous catheters, best practices for catheter care, surveillance, antimicrobial catheter lock solutions, and use of antibiotic impregnated catheters.

Antifungal Therapy of Aspergillosis of the Central Nervous System and Aspergillus Endophthalmitis

Cerebral Aspergillosis is the most lethal manifestation of infection due to Aspergillus species arising most commonly as hematogenous dissemination from a pulmonary focus, direct extension from paranasal sinus infection or direct inoculation through trauma and surgery of the central nervous system (CNS). Voriconazole is currently considered the standard of treatment of CNS aspergillosis with liposomal amphotericin B being the next best alternative. Neurosurgical resection of infected cerebral tissue in addition to antifungal therapy is frequently performed in patients with CNS aspergillosis to prevent neurological deficits and improve outcome.

Aspergillus endophthalmitis may occur endogenously mostly from a pulmonary focus or exogenously following eye surgery or trauma. Although amphotericin B is still described as the primary therapy, voriconazole is increasingly considered the first line treatment of Aspergillus endophthalmitis. Vitrectomy is recommended in most cases of Aspergillus endophthalmitis.

Clinical Presentations and Diagnosis of Brucellosis

Brucellosis is a worldwide zoonosis caused by Brucella species. The disease remains a significant economic and public health problem particularly in the Mediterranean countries. Clinical manifestations of brucellosis are variable and often nonspecific, simulating infectious and noninfectious diseases. Osteoarticular involvement is the most common focal complication of brucellosis and morbidity. Mortality rate due to brucellosis is low, mostly secondary to endocarditis and central nerve involvement of disease.

The diagnosis of brucellosis depends on the clinical presentations and laboratory tests. Detection of Brucella species by culture method is sometimes unsuccessful; therefore, serological tests are preferred. These tests are easy to perform, and results can be obtained within a short span of time. Several serologic tests have been developed for the diagnosis of human brucellosis, including the standard agglutination tube (SAT) test, anti-human globulin (Coombs) test, indirect fluorescence antibody (IFA) test, and enzyme-linked immunosorbent assay (ELISA). SAT is the primary test used in many clinical laboratories. IFA and ELISA are simple and reliable for the detection of immunoglobulin classes especially in complicated cases. Polymerase chain reaction (PCR) technique is highly sensitive and specific for the determination of Brucella spp. from peripheral blood and other tissues.

Recent patents are especially based on molecular assays in the diagnosis of brucellosis. However, PCR is still expensive and may not be appropriate for daily practice.

Immunopathology of Brucella Infection

In spite of the protean nature of the disease, inflammation is a hallmark of brucellosis and affected tissues usually exhibit inflammatory infiltrates. As Brucella lacks exotoxins, exoproteases or cytolysins, pathological findings in brucellosis probably arise from inflammation-driven processes. The cellular and molecular bases of immunopathological phenomena probably involved in Brucella pathogenesis have been unraveled in the last few years. Brucella-infected osteoblasts, either alone or in synergy with infected macrophages, produce cytokines, chemokines and matrixmetalloproteinases (MMPs), and similar phenomena are mounted by fibroblast-like synoviocytes. The released cytokines promote the secretion of MMPs and induce osteoclastogenesis. Altogether, these phenomena may contribute to the bone loss and cartilage degradation usually observed in brucellar arthritis and osteomyelitis. Proinflammatory cytokines may be also involved in the pathogenesis of neurobrucellosis. B. abortus and its lipoproteins elicit an inflammatory response in the CNS of mice, leading to astrogliosis, a characteristic feature of neurobrucellosis. Heat-killed bacteria (HKBA) and the L-Omp19 lipoprotein elicit astrocyte apoptosis and proliferation (two features of astrogliosis), and apoptosis depends on TNF-α signaling. Brucella also infects and replicates in human endothelial cells, inducing the production of chemokines and IL-6, and an increased expression of adhesion molecules. The sustained inflammatory process derived from the longlasting infection of the endothelium may be important for the development of endocarditis. Therefore, while Brucella induces a low grade inflammation as compared to other pathogens, its prolonged intracellular persistence in infected tissues supports a long-lasting inflammatory response that mediates different pathways of tissue damage. In this context, approaches to avoid the invasion of host cells or limit the intracellular survival of the bacterium may be suitable to prevent the pathological consequences of Brucella infections. The article presents some of the recent patents related to such approaches.

Complications of Otitis Media

Otitis media is the most common reason for antibiotic prescription in the United States. Whether due to disease virulence or growing antimicrobial resistance, complications of otitis media seem to be seen more frequently. These complications may be difficult to identify and treat. This article focuses on the pathophysiology of these complications and address medical and surgical approaches to safe treatment.

Pain Management in Hematological Patients with Major Organ Dysfunctions and Comorbid Illnesses

Background: Organ dysfunctions and medical complications, such as renal failure, liver impairment, coagulation disorders, cardiovascular and respiratory illnesses, may hamper an adequate pain management in haematological patients.

Aim: To summarize current knowledge on pain management in hematological patients presenting major organ dysfunctions and comorbidity. We also attempted to provide recommendations to optimize analgesia and to minimize side effects in the setting of medically compromised and frail haematological patients.

Methods: A systematic search of the literature, using relevant key words, was conducted in PubMed.

Results and conclusions: Pain in hematological patients is a common symptom and is often multi-factorial. Most pharmacotherapeutic measures, including causal therapies, analgesics and adjuvant agents routinely applied in pain management, may also be used in the setting of clinical frailty and medical comorbidities; however, comprehensive clinical and functional patient’s evaluations and a careful consideration of expected benefits and potential adverse events are required.

30 Years Lost in Anesthesia Theory

The recent discovery of the “Stress Repair Mechanism” (SRM) enables the Unified Theory of Medicine postulated by Hans Selye. It confers cohesive theories of anesthesia, analgesia, and allostasis that enable the alteration of anesthetic technique to optimize surgical outcome. The SRM continuously maintains and repairs the vertebrate body in accord with stressful forces and stimuli. Three synergistic pathways activate the SRM: the spinal pathway, the cognitive pathway, and the tissue pathway. Emotional mechanisms modulate the cognitive pathway, which explains allostasis. Surgery simultaneously stimulates all three synergistic pathways, causing harmful SRM hyperactivity that manifests as the Surgical Stress Syndrome. Anesthesia inhibits the cognitive pathway. Analgesia inhibits the spinal pathway. Synergistic combinations of anesthesia and analgesia minimize SRM hyperactivity better than either alone. This principle improves outcome, simplifies anesthetic technique, and minimizes polypharmacy and drug toxicity. Once verified, stress theory will advance surgical safety, accelerate recovery, minimize complications, reduce costs, enhance patient comfort, and guide pharmaceutical development to discover treatments that inhibit the tissue pathway, and thereby eliminate surgical stress altogether.

Treatment of Central Nervous System Tuberculosis Infections and Neurological Complications of Tuberculosis Treatment

Tuberculosis (TB) with central nervous system (CNS) manifestation is a form of TB with a high mortality and morbidity. Tuberculous meningitis (TM) is the most common form of CNS-TB. Although diagnosis of CNS-TB can be challenging, early treatment of CNS-TB is related to a better outcome. If CNS-TB is suspected, even though the clinical picture is not specific, it should be immediately treated.

For the treatment of CNS-TB, knowledge of the penetration across the blood-brain barrier of the various antituberculosis agents used in TB treatment is important. These will be described here in order to serve as a guide in choosing a treatment for CNS-TB. Corticosteroids have an evidence-based value in the treatment of TM and so are recommended. As for thalidomide use in CNS-TB, sound evidence is still lacking. We will also include a description of the adverse neurotoxic effects of the various other agents including their psychiatric, ototoxic and ophthalmic adverse effects.

Critical Illness in Obstetric Patients: Venous Thromboembolism in Pregnancy

During pregnancy, the risk of venous thromboembolism (VTE) increases 2-5 fold and pulmonary embolism (PE) remains a leading cause of maternal mortality in developed countries.

For pregnant women with suspected deep vein thrombosis (DVT) or PE, the use of serial compression leg ultrasound (CUS) should be considered to exclude DVT whereas a normal ventilation perfusion lung scan likely excludes PE. A computer tomographic pulmonary angiogram (CTPA) could assist in ruling out PE in women who present with an abnormal chest radiograph.

Low molecular weight heparins (LMWH) are the agents of choice for treatment and thromboprophylaxis of pregnant patients with VTE but appropriate dosing changes throughout pregnancy remain uncertain.

Women with previously unprovoked VTE and those in whom VTE are provoked by previous pregnancies or use of oral contraceptive are at highest risk of VTE recurrence during pregnancy, and should be offered antepartum and postpartum thromboprophylaxis. On the other hand, women with prior VTE related to a transient risk factor would benefit from postpartum thromboprophylaxis. More research is needed to identify the absolute risk of VTE during pregnancy associated with more prevalent risk factors such as maternal age, obesity, and mode of delivery.

Maternal Sepsis 2010: Early Recognition and Aggressive Treatment with Early Goal Directed Therapy can Improve Maternal Outcomes

Maternal sepsis remains a major preventable cause of morbidity and mortality worldwide. The current epidemic of obesity, diabetes, and cesarean delivery will most certainly increase the risk of infectious morbidity and mortality. Women who undergo cesarean are three times more likely to develop sepsis. Early recognition of cases and prompt treatment are essential to improve outcomes. Most cases of maternal sepsis are due to direct obstetrical causes and should be treated with broad spectrum antibiotics and source control measures. Early goal directed therapies should be initiated according to standardized protocols. Patients should be transferred to a critical care unit if feasible. Optimal care for the septic patient requires a multidisciplinary team with expertise in all relevant areas including critical care, infectious disease, maternal fetal medicine, obstetrics, anesthesia, pharmacology, and neonatology. This article reviews the epidemiology, microbiology, pathophysiology and treatment of obstetrical sepsis.

The Adult Patient with Eisenmenger Syndrome: A Medical Update after Dana Point Part III: Specific Management and Surgical Aspects

Eisenmenger syndrome is the most severe form of pulmonary arterial hypertension and arises on the basis of congenital heart disease with a systemic-to-pulmonary shunt. Due to the chronic slow progressive hypoxemia with central cyanosis, adult patients with the Eisenmenger syndrome suffer from a complex and multisystemic disorder including coagulation disorders (bleeding complications and paradoxical embolisms), renal dysfunction, hypertrophic osteoarthropathy, heart failure, reduced quality of life and premature death. For a long time, therapy has been limited to symptomatic options or lung or combined heart-lung transplantation. As new selective pulmonary vasodilators have become available and proven to be beneficial in various forms of pulmonary arterial hypertension, this targeted medical treatment has been expected to show promising effects with a delay of deterioration also in Eisenmenger patients. Unfortunately, data in Eisenmenger patients suffer from small patient numbers and a lack of randomized controlled studies. To optimize the quality of life and the outcome, referral of Eisenmenger patients to spezialized centers is required. In such centers, specific interdisciplinary management strategies of physicians specialized on congenital heart diseases and PAH should be warranted. This medical update emphasizes the current diagnostic and therapeutic options for Eisenmenger patients with particularly focussing on specific management and surgical aspects.

Perioperative Considerations in Diabetic Patients

Diabetes mellitus is an increasingly common disease that affects people of all ages, resulting in significant morbidity and mortality. Diabetic patients require more frequent hospitalization, have greater lengths of stay, and cost more to manage than non-diabetics. The major risk factors for diabetics undergoing surgery are the end-organ diseases associated with diabetes: cardiovascular disease, autonomic neuropathy and immune deficiency. Physicians should pay extra attention to preoperative and preprocedure evaluation and treatment of these diseases to ensure optimal perioperative management. Furthermore, these patients unexpectedly develop hemodynamic instability in response to vasopressor or vasodilator administration during anesthesia, this being of particular importance in patients with concurrent ischemic heart disease in whom it may have a direct effect on mortality. Recent studies have shown that tight glycemic control in diabetic patients undergoing major surgery has been shown to improve perioperative morbidity and mortality.

A Stress Repair Mechanism That Maintains Vertebrate Structure During Stress

Based on Capillary Gate Theory and Tissue Repair Theory, this paper describes the “Stress Repair Mechanism” (SRM) that maintains and repairs vertebrate tissues. It accounts for most of the mysterious manifestations of allostasis that remain unexplained by Hypothalamic-Pituitary-Axis (HPA) hormones and thereby enables the Universal Theory of Medicine predicted by Hans Selye. SRM activity explains hemodynamic physiology, capillary hemostasis, infarction, Korotkoff sounds, blood pressure, hypertension, diabetes, allostasis, allostatic load, anesthesia, analgesia, atherosclerosis, apoptosis, malignancy, eclampsia, sepsis, Multi-System Organ Failure (MSOF), the surgical stress syndrome, the fight or flight response, and numerous other manifestations of physiology and pathology. SRM function comprises the autonomic nervous system, the vascular endothelium, and the dynamic enzymatic interaction of blood-borne hepatic Factors VII, VIIIC, IX and X that produces thrombin, soluble fibrin and insoluble fibrin, whose combined effects account for all SRM manifestations. The vascular endothelium is a diaphanous neuroendocrine organ that lines all blood vessels and is the sole constituent of capillary walls. It secretes tissue factor into extravascular tissues, and insulates those tissues from the hepatic enzymes, so that tissue disruption exposes tissue factor to the enzymatic interaction and activates tissue repair. The vascular endothelium also releases nitric oxide and von Willebrand Factor into blood in accord with autonomic balance to regulate the enzymatic interaction to govern tissue perfusion and organ function. Therefore, continuously fluctuating combinations of nervous stimuli that affect autonomic balance and forces that disrupt tissues determine SRM activity.

Non-Surgical Treatment Options for Symptomatic Uterine Leiomyomas

Uterine leiomyomas (or uterine fibroids), benign tumors of the uterine smooth muscle cells, can cause significant morbidity and impair quality of life in many women. For those who are asymptomatic, watchful waiting constitutes appropriate management. For women with symptomatic fibroids, hysterectomy and myomectomy are traditionally the standard treatments. In the last two decades, many alternatives to surgery for the management of fibroids have been developed. Most of the current medical treatments involve hormone manipulation. Newer treatments such as mifepristone, asoprisnil and aromatase inhibitors show promising results in fibroid symptom and size reduction; however, larger studies are needed. A safe and effective therapy as an alternative to hysterectomy is uterine artery embolization (UAE), which offers shorter recovery times and fewer major complications, though fertility and pregnancy outcomes after a UAE may be affected. Limited data are available for the efficacy and safety of temporary uterine artery occlusion. Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is the newest treatment option for uterine fibroids. It also shows promising results for symptom relief. The degree of symptom relief depends significantly on the amount of fibroid volume that is non-perfused after treatment and the experience of the physician performing the procedure.

Noninvasive Monitoring of Intracranial Pressure

Increased intracranial pressure (ICP) is one of the major causes of secondary brain ischemia that accompanies a variety of pathological conditions, most notably, traumatic brain injury (TBI), stroke, and intracranial hemorrhages. However, aside from a few Level I trauma centers, ICP monitoring is rarely a part of the clinical management of patients with these conditions because of the invasiveness of the standard monitoring methods (which require insertion of a catheter into the cranium), additional risks they present for patients, high costs associated with the procedure, and the limited access to trained personnel, i.e., a neurosurgeon. Alternative methods have therefore been sought with which ICP can be measured noninvasively. This article reviews nearly 30 such methods patented over the past 25 years, which included ultrasound “time-of-flight” techniques, transcranial Doppler, methods based on acoustic properties of the cranial bones, EEG, MRI, tympanic membrane displacement, oto-acoustic emission, ophthalmodynamometry, and ultrasound measurements of optic nerve sheath diameter. At present, none of the methods is sufficiently accurate to allow for routine clinical use although several hold promise. Future developments should integrate further refinements of the existing methods, combined use of multiple sensors and/or technologies, and large clinical validation studies on relevant populations.

Mechanisms of Action and Chemical-Biological Interactions Between Ozone and Body Compartments: A Critical Appraisal of the Different Administration Routes

After a long initial stage obscured by empirism and misconceptions, oxygen-ozonetherapy has now become a scientific discipline where the reactions between ozone and human blood are within the realm of orthodox biochemistry, physiology and pharmacology. Most of the basic mechanisms of action have been clarified and ozone can be considered a pro-drug, which almost instantaneously reacts with antioxidants and unsaturated fatty acids. These reactions generate the actual ozone messengers represented by either hydrogen peroxide as a fast acting compound or a variety of lipid oxidation products as late effectors. While ozone is totally consumed, micromolar amounts of these messengers are able to enhance the delivery of oxygen via erythrocyte activation, the immune system by a bland leukocyte stimulation and most of the remaining body cells by up-regulating the antioxidant system. The hazard of ozone toxicity has been dispelled by using the gas only within a dose range perfectly calibrated against the potent blood antioxidant capability. Ozonetherapy can be very useful in patients with chronic vascular disorders and ischemic problems and should be extensively used by official medicine. An extraordinary facet of ozone is its medical application versatility, as represented by several administration routes, and the minimal cost of this drug.

Back Pain in Children and Adolescents: Etiology, Clinical Approach and Treatment

The purpose of this systematic review is to investigate back pain as a clinical presentation in childhood and adolescence providing the clinician with a comprehensive approach, which will enable for an early recognition of those spinal disorders in need of more aggressive medical intervention. The current literature suggests that young people have a fairly high incidence of non-specific back pain, which seems to be much more frequent than traditionally reported. In schoolchildren, low back pain is mainly associated with psychosocial factors and seems to be mostly benign and selflimiting, therefore, only occasionally requiring medical attention. However, young patients who seek medical assistance, have a higher incidence of organic conditions that can manifest with spinal pain as their predominant symptom. The evaluation of a child or adolescent presenting with back pain can be a challenging task and requires skilled clinical expertise and a high index of suspicion. The physician should have a carefully planned strategy for assessing the pediatric spine patient, which should be accurate, reliable, consistent, and easily reproducible in delineating spinal pathologies. This should include a detailed history, physical examination, radiographic imaging, and appropriate diagnostic laboratory studies. A specific diagnosis will be established in at least 50% of the patients. In certain cases, an exact diagnosis cannot be made, and it is always advisable to re-evaluate the child after a period of initial observation. By then more serious problems will advance and become more obvious while minor symptoms not linked to an underlying pathology will resolve spontaneously. The authors did not receive grants or outside funding in support of their research or preparation of this manuscript. They did not receive payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or non-profit organization with which the authors are affiliated or associated.

Inflammatory Mediators as Potential Therapeutic Targets in the Spine

Inflammation plays a variable part in the pathogenesis of several spinal disorders. Ankylosing spondylitis is a chronic inflammatory arthropathy of the spine and rheumatoid arthritis, whilst affecting predominantly limb joints, also affects the cervical spine in a significant proportion of people. Inflammation is also involved in disorders such as disc herniation and sciatica, which have previously been thought of as being primarily mechanical or degenerative. Anti-inflammatory agents which have been shown to be effective elsewhere in the body are discussed in this review as possible therapeutic agents in the spine. As the inflammatory cascade and immunopathology of these conditions continue to be elucidated, it has become apparent that individual molecules may be potential targets for inactivation or down-regulation. Candidates include pro-inflammatory cytokines, such as TNF-α, cytokines, e.g. IL-1 and IL-15, or enzymes enhancing the inflammation pathway such as the cyclooxygenases. Hence treatments based on inactivation of these molecules by various mechanisms, including antibodies, receptor antagonists, enzyme inhibitors or gene therapy, are being introduced. However, the mode of action of a particular molecule can be complex and sometimes apparently contradictory. For example, TNF-α is known to play an important role in promoting inflammation by upregulating expression of cell adhesion molecules on endothelial cells and stimulating the production of reactive oxygen intermediates, nitric oxide and prostaglandins. However, it can also have an immunosuppressive and anti-inflammatory role after prolonged release. Therefore, although inhibitors of many of these molecules are now in clinical application and trials (many with promising results in rheumatoid arthritis), it is important to remain vigilant and monitor long-term outcomes particularly when these treatments are used in clinical syndromes with relatively poorly defined immunopathology such as spinal disorders.

Drug Delivery to Captive Asian Elephants - Treating Goliath

Captive Asian elephants have been maintained in captivity by humans for over 4000 years. Despite this association, there is little published literature on the treatment of elephant diseases or methods of drug administration to these animals. Elephants in captivity are generally healthy and require few therapeutic interventions over the course of their lifetime. However, when they become acutely ill, treatment becomes a serious issue. The successful and consistent administration of therapeutics to elephants is formidable in an animal that presents significant limitations in drug delivery options. The single most important factor in administering drugs to an elephant is the animals cooperation in accepting the medication. Working around elephants can be very dangerous and this is magnified when working around sick or injured animals where the elephant is subject to increased stress, pain, and unusual situations associated with treatment. The large body size of the Asian elephant produces a separate set of issues. In this paper, methods of drug administration and their associated limitations will be reviewed. Considerations of medicating such large animals can serve to highlight the problems and principles of treatment that are inherent in these species.

Nerve Injury Associated with Regional Anesthesia

Neural damage is a possible consequence of general anesthesia, central nervous system blockade, and regional anesthesia. Damage may be caused by ischaemic and mechanical or chemical factors, which may occur either alone or in combination. Neural damage may be secondary to prolonged and severe arterial hypotension compromising blood supply to the cord, a spinal haematoma whose main etiological factor is a coagulation abnormality, an intraneural injection, and peripheral neuropathy related to perioperative positioning. Mechanical trauma by the needle bevel is an important factor contributing to neuropathy. Neurological complications may also result from a direct neurotoxic effect of local anesthetic agents, which is concentration and dose-dependent. A better understanding of these mechanisms will provide a reliable basis for the development of improved pharmaceutical therapy.