The role of serotonin and dopamine in schizophrenia

For many years schizophrenia was attributed to an overabundance of dopamine in the brain, and until recently conventional neuroleptics (dopamine-D₂ receptor antagonists) have been the mainstay of pharmacologic treatment for patients with this illness. The dopaminergic mechanism of action makes conventional neuroleptics effective for the positive symptoms of schizophrenia but not for the negative symptoms. It is now recognized that serotonin also plays an important role in the pathogenesis of schizophrenia. By blocking both dopamine and serotonin receptors, the newer antipsychotic agents such as clozapine, risperidone, and olanzapine are effective for both the positive and negative symptoms of schizophrenia and are less likely than conventional neuroleptics to cause extrapyramidal symptoms at prescribed doses. Although the newer antipsychotics are tolerated better than conventional neuroleptics, each of these newer drugs is associated with some adverse effects, such as hypotension and sedation. Further research into the neurobiology of schizophrenia may lead to the development of even more effective and safe antipsychotic medications for schizophrenia.     

Beyond the twelve-lead electrocardiogram: Diagnostic tests in the evaluation for suspected acute myocardial infarction in the emergency department, part I

On a daily basis the emergency physician is faced with the difficult task of determining whether or not a patient with acute chest pain is sustaining an acute myocardial infarction. In most cases, this is not a straightforward decision. Although observation units are being used more often for chest pain evaluations, many emergency physicians currently admit such patients to an intensive care setting. Because fewer than one-third of emergency department chest pain patients actually suffer an acute myocardial infarction, expensive resources are, in retrospect, used unnecessarily. Conversely, patients who are infarcting, and are inadvertently discharged home from the emergency department, have a worse prognosis than those admitted. This two-part series reviews the newer modalities available that may help the emergency physician arrive at a more accurate diagnosis. The current article, Part I, examines the use of myocardial imaging, computer assisted diagnostic protocols, and newer uses of the electrocardiogram. Part II reviews the use of biochemical assays of cardiac proteins and the Chest Pain Observation Unit.     

How do I transfuse platelets (PLTs) to reverse anti‐PLT drug effect? (CME)

Antiplatelet agents (APAs) are commonly used in clinical practice to either treat or prevent arterial thrombotic disorders in patients at high risk. The newer APAs are more potent with higher bleeding risk profiles. Patients who present with serious bleeds or need urgent surgical interventions while on APAs may require reversal of these agents' effect on PLTs. Currently, there are no guidelines for management of such patients. This article describes my approach to PLT transfusion or use of pharmacologic agents in such clinical scenarios based solely on personal experience and very limited published data.     

Safety and efficacy of glycopeptide antibiotics

It would be difficult to envision the practice of infectious diseases over the past 20 years without the availability of the glycopeptide antibiotics. The two agents currently in clinical use, vancomycin and teicoplanin, have proven remarkably versatile in many common applications. Several attributes of these agents account for this favourable profile: (i) their broad spectrum of activity against Gram-positive bacteria, including strains resistant to many other antimicrobials; (ii) their favourable pharmacokinetic properties that allow the once- or twice-daily dosing regimens that have made out-of-hospital therapy possible; and (iii) their generally good safety profiles which, along with their structural dissimilarity to beta-lactam and other antimicrobials, permits their use in many patients who are intolerant of other antibiotic regimens. It is not entirely surprising, therefore, that despite more than 40 years of clinical use and the interim appearance of bacterial strains resistant to this drug class, there remains continued interest in the development of newer members of the glycopeptide antibiotic class. This paper is intended to provide a global overview of the efficacy and safety of glycopeptide antibiotics currently in use, as background to understanding the need for and potential roles of new agents of this class.     

Herpes Simplex Virus Oncolytic Therapy for Pediatric Malignancies

Despite improving survival rates for children with cancer, a subset of patients exist with disease resistant to traditional therapies such as surgery, chemotherapy, and radiation. These patients require newer, targeted treatments used alone or in combination with more traditional approaches. Oncolytic herpes simplex virus (HSV) is one of these newer therapies that offer promise for several difficult to treat pediatric malignancies. The potential benefit of HSV therapy in pediatric solid tumors including brain tumors, neuroblastomas, and sarcomas is reviewed along with the many challenges that need to be addressed prior to moving oncolytic HSV therapy from the laboratory to the beside in the pediatric population.     

Beyond the Twelve-Lead Electrocardiogram: Diagnostic Tests in the Evaluation for Suspected Acute Myocardial Infarction in the Emergency Department,Part II

On a daily basis the emergency physician is faced with the difficult task of determining whether or not a patient with acute chest pain is sustaining an acute myocardial infarction. In most cases this is not a straightforward decision. Although observation units are being used more often for chest pain evaluations, many emergency physicians currently admit such patients to an intensive care setting. Because fewer than one-third of emergency department chest pain patients actually suffer an acute myocardial infarction, expensive resources are, in retrospect, used unnecessarily. Conversely, patients who are infarcting, and are inadvertently discharged home from the emergency department, have a worse prognosis than those admitted. This two-part series reviews the newer modalities available that may help the emergency physician arrive at a more accurate diagnosis. This article, Part II, will review the use of biochemical assays of cardiac proteins and discuss the Chest Pain Observation Unit.     

What Do Primary Care Providers and Nurses Need to Know About Managing Chronic Pain?

Pain is the leading reason Americans seek health care access. Worldwide, more than 1.5 billion people are suffering from chronic pain. Unfortunately, providers are not equipped to manage patients with chronic pain as many advanced programs provide little to no education on pain management. Additionally, there are limited research articles on managing chronic pain, let alone regarding alternative treatment options for chronic pain. The patient presented in this case study is a 66-year-old woman who presents for a follow up regarding chronic pain. The case study outlines the success a patient found using alternative options other than opioid medication with lifestyle changes and a newer medication called low-dose Naltrexone (LDN). The purpose of this case study is to present a patient who has found success in managing chronic pain through alternative treatments and help the provider be able to educate patients on the importance of lifestyle changes to increase the prescribing and compliance of alternative treatment options.     

Antimicrobial resistance in community-acquired respiratory tract pathogens

Conclusion  In summary, the management of CAP has become more challenging given the emergence of antimicrobial resistance among respiratory tract pathogens. However, for most patients there are still many effective treatment options, including the third-generation cephalosporins, β-lactam/β-lactamase inhibitor combinations, the newer macrolides, and the newer fluoroquinolones. For documented infections with highly resistantS. pneumoniae, or in patients at high risk for drug-resistant pneumococci, the use of vancomycin, imipenem, or a newer quinolone should be considered.     

Herpes zoster: medical and nursing management

Herpes zoster, the latent descendent of the varicella zoster virus, commonly is seen in clinical practice. Healthcare providers must recognize and treat the virus to decrease the incidence of postherpetic neuralgic pain syndrome. Treatment with an antiviral medication regimen should be initiated rapidly for patients who have had lesions for up to 72 hours. Acyclovir has been the treatment of choice for herpes zoster in the past, but newer drugs, such as valacyclovir, a prodrug of acyclovir, and famciclovir, are as effective for treating the virus and have more convenient dosing regimens and decreased incidence of postherpetic neuralgia.     

Follow-up of nutritional and metabolic problems after bariatric surgery

Over the next several years, the number of patients who will have had bariatric surgery for morbid obesity will reach close to a million. Several well-described nutritional problems such as B12 and iron deficiency will be noted in these patients. Many of these patients will be lost to the original surgeon and will now be in the care of the "other physicians." These and other mineral and vitamin problems will need to be screened and treated. If these problems are left undiagnosed, severe and irreparable problems can result. Early problems, such as vomiting and dumping syndrome, will be easily recognized and treated, but other long-term problems, such as changes in bone metabolism, will need to be monitored. Again, if some of these long-term problems are not addressed in a timely fashion, then eventual treatment becomes much more difficult. This commentary will cover the common as well newer problems that are now developing in the patient who has had bariatric surgery. Patients who have undergone bariatric surgery require medical follow-up for reasons that are often determined by the type of surgical procedure performed. The majority of this review will deal with patients who have had the standard Roux-en-Y gastric bypass, which is a primarily restrictive procedure with a mild component of noncaloric malabsorption. At the end of this report, a short section will be devoted to the problems associated with the malabsorptive procedures.     

The potential role of natriuretic peptides and other biomarkers in heart failure diagnosis,prognosis and management

Heart failure (HF) is a complex disease process that is challenging to diagnose and manage. For more than 15 years, biomarkers have been used to diagnose and the guide the management of patients with this disease. The gold standard biomarkers for HF are B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP); both are used for diagnosis and prognosis. More recently, there has been an interest in use of BNP and NT-proBNP for HF management as well. Important aspects regarding production and clearance of BNP and NT-proBNP exist, which are vital for the clinician to understand. Beyond BNP or NT-proBNP, other newer biomarkers such as mid-regional pro-atrial natriuretic peptide, soluble ST2, highly sensitive troponin and renal biomarkers may add value for prognostication and possibly, patient management. In this article, the authors will discuss the established and evolving role of BNP and NT-proBNP in HF, along with consideration of select newer biomarkers in this setting.     

Screening for coronary artery disease in patients with diabetes

Coronary artery disease (CAD) accounts for a large fraction of the morbidity, mortality, and cost of diabetes. Recognizing this, nearly 10 years ago the American Diabetes Association published a consensus recommendation that clinicians consider a risk factor-guided screening approach to early diagnosis of CAD in both symptomatic and asymptomatic patients. Subsequent clinical trial results have not supported those recommendations. Since the prior consensus statement, newer imaging methods, such as coronary artery calcium scoring and noninvasive angiography with computed tomography (CT) techniques, have come into use. These technologies, which allow quantitation of atherosclerotic burden and can predict risk of cardiac events, might provide an approach to more widespread coronary atherosclerosis screening. However, over this same time interval, there has been recognition of diabetes as a cardiovascular disease (CVD) equivalent, clear demonstration that medical interventions should provide primary and secondary CVD risk reduction in diabetic populations, and suggestive evidence that percutaneous coronary revascularization may not provide additive survival benefit to intensive medical management in patients with stable CAD. This additional evidence raises the question of whether documenting asymptomatic atherosclerosis or ischemia in people with diabetes is warranted. More data addressing this issue will be forthcoming from the BARI 2-D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial. Until then, for patients with type 2 diabetes who are asymptomatic for CAD, we recommend that testing for atherosclerosis or ischemia, perhaps with cardiac CT as the initial test, be reserved for those in whom medical treatment goals cannot be met and for selected individuals in whom there is strong clinical suspicion of very-high-risk CAD. Better approaches to identify such individuals based on readily obtained clinical variables are sorely needed.     

Revisiting the Role of Ergots in the Treatment of Migraine and Headache

(Headache 2010;50:1353‐1361) The harmful side effects of the ergots described by early civilizations have been overcome with efficacious treatment for headaches including migraine, cluster, and chronic daily headache. Use of ergots contributed to initial theories of migraine pathogenesis and provided the substrate for development of the triptans. Triptans are very efficacious for many migraineurs, and since their widespread use, use of ergots has significantly declined. Unfortunately, there remain many migraineurs who benefit little from triptans, yet respond very well to ergots. Discoveries in migraine pathophysiology have given us better understanding of the complex processes involved, although there remain many unknown factors in migraine treatment. Additional, unrecognized therapeutic targets may exist throughout the neuronal connections of the brainstem, cortex, and cerebral vasculature. Ergots interact with a broader spectrum of receptors than triptans. This lack of receptor specificity explains potential ergot side effects, but may also account for efficacy. The role of ergots in headache should be revisited, especially in view of newer ergot formulations with improved tolerability and side effect profiles, such as orally inhaled dihydroergotamine. Redefining where in the headache treatment spectrum ergots belong and deciding when they may be the optimal choice of treatment is necessary.     

Perioperative and Intraoperative Pain and Anesthetic Care of the Chronic Pain and Cancer Pain Patient Receiving Chronic Opioid Therapy

Abstract:   The expanding role of the anesthesiologist as a "perioperative physician" places ever-increasing demands upon his or her clinical skills and knowledge. One area of growing concern for the anesthesiologist involves the perioperative assessment and management of the opioid-tolerant chronic pain patient. Opioids occupy a position of unsurpassed clinical utility for the treatment of many types of painful conditions. Coupled with noticeable shifts in physician attitudes that have occurred in recent years regarding the use of opioids for the treatment of benign and malignancy-related pain, many more patients are presenting for surgical procedures who are opioid tolerant. It is important therefore that the practicing anesthesiologist become familiar with the currently available opioid formulations, including drug interactions and side effects, in order to better plan the patient's perioperative anesthetic needs and management. Unfortunately, there is a lack of scientifically rigorous studies in this important area, and most of the information must be derived from anecdotal reports and personal experience of anesthesiologists working in this field. In this review, we shall discuss some aspects of current chronic pain management, the newer forms of opioid administration which may be unfamiliar to the anesthesiologist, as well as clinical aspects of opioid use and tolerance including the impact it may have on perioperative anesthetic management.     

Changes in liver enzyme values after halothane and enflurane for surgical anesthesia

For over a decade there has been concern about hepatitis related to halothane anesthesia. No dose relationship or other direct cause has ever been established, and jaundice has been found to occur after other anesthetics for surgical operations. Enflurane is a newer halogenated compound with a remarkable record of safety, yet a few cases of hepatitis are reported to be associated with its administration. We have compared effects on the liver of the two anesthetics by testing hepatic serum enzymes and sulfobromophthalein in 12 patients who received halothane and 12 who received enflurane. No significant differences between the two groups were found. Both had similar but minimal elevations of the hepatic serum enzymes and retention of sulfobromophthalein. More than half the patients had enzyme increases over normal levels but reasons for this were not obvious. Since hepatic change may take place in many postoperative patients, it is not surprising to have an occasional one develop hepatitis. The exact cause is unknown and therefore it is impossible to predict the patient who will develop the disease, regardless of the anesthetic.     

Current medical management of diabetic foot infections

Foot infections are a serious complication of diabetes associated with substantial morbidity and occasional mortality. Antibiotic therapy for mild infections in patients who have not recently received antibiotic therapy can often be directed at just staphylococci and streptococci. Empiric therapy for infections that are chronic, moderate or severe, or that occur in patients who have failed previous antibiotic treatment, should usually be more broad spectrum. Bone infection also complicates a substantial percentage of diabetic foot wounds and increases the likelihood of treatment failure, requiring lower extremity amputation. An increasing body of evidence supports the effectiveness of nonsurgical treatment of diabetic foot osteomyelitis in selected patients, although the optimal choice of agent, route of administration and duration of therapy have yet to be defined. This article examines the potential role of standard and newer antibiotics that may be appropriate for treating diabetic foot infections, including ertapenem, vancomycin, moxifloxacin, daptomycin, telavancin and tigecycline, as well as several investigational agents, such as dalbavancin, ceftobiprole and nemonoxacin.     

Current medical management of diabetic foot infections

Foot infections are a serious complication of diabetes associated with substantial morbidity and occasional mortality. Antibiotic therapy for mild infections in patients who have not recently received antibiotic therapy can often be directed at just staphylococci and streptococci. Empiric therapy for infections that are chronic, moderate or severe, or that occur in patients who have failed previous antibiotic treatment, should usually be more broad spectrum. Bone infection also complicates a substantial percentage of diabetic foot wounds and increases the likelihood of treatment failure, requiring lower extremity amputation. An increasing body of evidence supports the effectiveness of nonsurgical treatment of diabetic foot osteomyelitis in selected patients, although the optimal choice of agent, route of administration and duration of therapy have yet to be defined. This article examines the potential role of standard and newer antibiotics that may be appropriate for treating diabetic foot infections, including ertapenem, vancomycin, moxifloxacin, daptomycin, telavancin and tigecycline, as well as several investigational agents, such as dalbavancin, ceftobiprole and nemonoxacin.     

Antidiabetic agents in patients with hepatic impairment

Chronic liver disease (CLD) often coexists with type 2 diabetes mellitus, making diabetes management a challenge to the clinician. It is well known that liver is the major site of drug metabolism, and, therefore, its impairment affects hepatic metabolism of many antidiabetic agents. Furthermore, patients with CLD have serious comorbidities such as impaired renal function, hypoalbuminemia, lactic acidosis, hypoglycemia and malnutrition, making their treatment even more difficult. On the other hand, most of the antidiabetic agents, with the exception of insulin, need dosage titration due to alterations to their pharmacokinetics in patients with CLD. For well-established antidiabetic treatments, like metformin and sulfonylureas there are studies regarding their dosage chance in these patients. However, despite the growing problem of management of diabetes in patients with CLD the existing literature data, especially on newer antidiabetic agents, are limited and, furthermore, no direct guidelines exist. Therefore, in the present review article we try to summarize the existing literature data regarding management of diabetes in patients with CLD.     

Percutaneous vertebroplasty: new treatment for vertebral compression fractures

Interventional radiologists have been performing image-guided spinal procedures for many years. Percutaneous vertebroplasty is a newer technique in which a medical grade cement is injected though a needle into a painful fractured vertebral body. This stabilizes the fracture, allowing most patients to discontinue or significantly decrease analgesics and resume normal activity. The impact of this procedure on the morbidity and expense associated with symptomatic osteoporotic vertebral compression fractures in the United States may be significant. Patients who are unresponsive to conservative therapy of bed rest, analgesics, and back bracing should be considered for vertebroplasty. This procedure is contraindicated in patients with active infection, untreated coagulopathy, and certain types of fracture morphology. Because many patients have multiple chronic fractures, there should be a strong correlation between the physical examination signs, symptoms, and cross-sectional imaging findings. The success rate for this procedure in treating osteoporotic fractures is 73 to 90 percent. Vertebroplasty can effectively treat aggressive hemangiomas of the vertebral body and may be palliative in patients with malignant pathologic fractures. Significant complications of the procedure are less than 1 percent.