Anemia and stroke: Where do we stand?

Anemia seems to have a clear relationship with cerebrovascular events (CVEs), as there is a direct connection between central nervous system, blood supply, and tissue oxygen delivery. Anemia is considered a hyperkinetic state which disturbs endothelial adhesion molecule genes that may lead to thrombus formation. Furthermore, blood flow augmentation and turbulence may result in the migration of this thrombus, thus producing artery-to-artery embolism. It is for this reason that anemia is characterized as "the fifth cardiovascular risk factor." Anemia is consistently present in patients with acute stroke, ranging from 15% to 29%, while the mortality rate was significantly higher in patients suffering from anemia at the time of admission. Different types of anemia (sickle cell disease, beta thalassemia, iron deficiency anemia [IDA]) have been associated with increased cardiovascular and CVE risk. The relation between hemoglobin level and stroke would require further investigation. Unfortunately, treatment of anemia in cardiovascular and cerebrovascular disease still lacks clear targets and specific therapy has not developed. However, packed red blood cell transfusion is generally reserved for therapy in patients with CVEs. What is more, treatment of IDA prevents thrombosis and the occurrence of stroke; although iron levels should be checked, chronic administration favors thrombosis. Regarding erythropoietin (EPO), as there is lack of studies in anemic stroke patients, it would be desirable to utilize both neuroprotective and hematopoietic properties of EPO in anemic stroke patients. This review aims to clarify the poorly investigated and defined issues concerning the relation of anemia and CVEs.

Is management of hyperglycaemia in acute phase stroke still a dilemma?

INTRODUCTION: Close monitoring of blood glucose levels during the immediate post-acute stroke phase is of great clinical value, as there is evidence that the risk of neurological deterioration is associated with both hyper- and hypoglycaemia. The aim of this review paper is to summarise the evidence on post-stroke blood glucose management and its impact on clinical outcomes, during the early post-acute stage. FINDINGS: Post-stroke hyperglycaemia has been associated with increased cerebral oedema, haemorrhagic transformation, lower likelihood of recanalisation and deteriorating neurological state. Thus, hyperglycaemia during an acute stroke may result in poorer clinical outcomes, infarct progression, poor functional recovery and increased mortality rates. Although hypoglycaemia may also lead to poorer outcomes via further brain injury, it can be readily reversed by glucose administration. In most patients, the goal of regular treatment is euglycaemia and for acute-stroke patients, a reasonable approach is to target control of glucose level at 100-150 mg/dL. CONCLUSION: Both hypoglycaemia and hyperglycaemia may lead to further brain injury and clinical deterioration; that is the reason these conditions should be avoided after stroke. Yet, when correcting hyperglycaemia, great care should be taken not to switch the patient into hypoglycaemia, and subsequently aggressive insulin administration treatment should be avoided. Early identification and prompt management of hyperglycaemia, especially in acute ischaemic stroke, is recommended. Although the appropriate level of blood glucose during acute stroke is still debated, a reasonable approach is to keep the patient in a mildly hyperglycaemic state, rather than risking hypoglycaemia, using continuous glucose monitoring.

Simultaneous manifestation of pleural effusion and acute renal failure associated with dasatinib: a case report.

WHAT IS KNOWN AND OBJECTIVE: Dasatinib is a novel second-generation inhibitor of multiple tyrosine kinases, indicated for the treatment for Philadelphia chromosome-positive (Ph+) chronic myeloid leukaemia (CML), acute lymphoblastic leukaemia (ALL) and lymphoid blast CML with resistance or intolerance to prior therapy. Although dasatinib is a potent, efficacious and generally well-tolerated drug, patients are also subject to various adverse effects. The most common pulmonary-related side effect is pleural effusion (PE). Renal failure has been reported rarely as a side effect of dasatinib treatment. We report the first case of a patient with imatinib-resistant CML who developed PE and acute renal failure (ARF) simultaneously, after being placed on dasatinib therapy. CASE SUMMARY: We report a 58-year-old female dasatinib-treated patient with Ph+ chronic phase CML who was admitted to our hospital due to persisted dyspnoea and fever. After reviewing the laboratory and clinical findings, we determined our patient as having simultaneously ARF and PE related to dasatinib therapy. Dasatinib was discontinued, and after 10 days of treatment with ampicillin-sulbactam, allopurinol, amlodipine, furosemide and methylprednisolone, she was discharged home effusion free and with ameliorated renal function. WHAT IS NEW AND CONCLUSION: PE is the most common extra-haematological toxicity observed during dasatinib treatment whose pathogenesis is still unclear. A possible role of cytokines, such as platelet-derived growth factor receptor (PDGFR)-ß and vascular endothelial growth factor (VEGF), in causing endothelial permeability has been suggested. The aetiology of renal failure is also unclear in these patients, but two different possible mechanisms have been suggested such as tumour lysis syndrome and toxic tubular damage. In conclusion, here we describe the first case of simultaneous manifestation of PE and ARF associated with dasatinib. Thus, in patients treated with tyrosine kinase inhibitors, especially those with predisposing nephrological or haematological factors, serum creatinine levels should be monitored routinely.

Adipokines and stroke: a review of the literature.

Stroke represents one of the most important menaces to public health. A number of modifiable and non-modifiable risk factors have been identified and studied in detail; among those, obesity, the new world epidemic, seems to be one of the most important in terms of prevention. The discovery of the secretory role of the adipose tissue and of adipokines has opened new fields of research. A number of studies have been published on their relation to cardiovascular risk and the potential of using them as prevention markers. In the present review the physiology of leptin, adiponectin and resistin is described and their role in the pathogenesis of stroke is examined.

Role of phytosterols in lipid-lowering: current perspectives.

The cholesterol-lowering effect of plant sterols was first discovered in the early 1950s. However, it is only recently that plant sterols have become clinically important, when advances in food-technology have made it possible to combine sterols with a variety of food products including margarines, yogurts, fruit juices and cereal bars. We review the clinical trial evidence of lipid-lowering efficacy of plant sterols and discuss their implications in routine clinical practice. To generate the evidence we searched the Pubmed database for English language literature, using relevant keywords and medical subject heading (MeSH) terms, and extracted the findings from recently published studies and meta-analyses on this topic. Our findings suggest that the short-term use of food supplements rich in plant sterols is a safe and effective strategy; to maximize the benefits of dietary and lifestyle therapy, either with or without statin therapy, among majority of dyslipidemic patients with need for additional lipid-lowering.

Amiodarone: pharmacological profile, animal-model experimental data and clinical use. How important is the vasodilating effect?

Amiodarone, the major representative of class III antiarrhythmic agents, is widely used in the treatment of ventricular and hyperventricular arrhythmias, being specifically useful in the therapy of patients suffering from life threatening ventricular arrhythmias. The combination of antianginal and antiarrthythmic actions of amiodarone is an extremely significant advantage regarding the treatment of patients with chronic atherosclerotic cardiopathy, as heart rate disorders are frequently fatal in coronary heart disease and, reversely, a high percentage of cardiac arrhythmias are caused by coronary heart disease. Since 1980s, several experimental in vitro and in vivo data, as well as clinical studies, regarding both systematic and coronary circulation, support the vasodilative effects of amiodarone. We have previously showed that amiodarone in vitro exerts a vasodilator effect in isolated vessel tissue, mainly via the activation of intracellular calcium binding mechanisms, a fact that differentiates this agent from other coronary vasodilative drugs, such as calcium channel blockers, that affect extracellular calcium ions entrance. Thus, the vasodilative, antianginal and antiarrhythmic actions of amiodarone may be further enhanced by the simultaneous supplementation of calcium channel blockers via synergistic mechanisms, supporting the clinical use of such drug combinations. Finally, as amiodarone and noradrenaline have been reported to exert antagonistic actions, the application of amiodarone is particularly indicated in pathologic conditions characterized by the stimulation of sympathetic nervous system (sympathicotonia).

Standardized arrangement for a guideline-driven treatment of the metabolic syndrome: the SAGE-METS study.

AIM: To substantially increase awareness, treatment and effective control of the metabolic syndrome (MetS) and its components. SUBJECTS AND METHODS: This is a pilot best practice implementation enhancement programme to reduce the estimated cardiovascular disease (CVD) risk in 628 MetS patients with or without diabetes or CVD by improving quality of care. A baseline visit was followed by action to improve adherence to lifestyle advice and drug treatment for CVD risk factors by physicians specifically trained to implement guidelines. Finally, after 6 months, a single-page form was completed, showing if patients were at CVD risk factor target. If not, there was an analysis of the reason why. RESULTS: The programme was effective in improving utilization of evidence-based treatment in 628 MetS patients. There was a substantially greater patient perception of MetS, an enhancement in compliance with lifestyle advice and increased prescription of evidence-based medication, leading to a 48% (p < 0.0001) improvement in estimated CVD risk. There was a substantial increase in the number of subjects on target for specific CVD risk factors. CONCLUSIONS: This is the first study to increase adherence to multiple interventions for all MetS components on an outpatient basis, in both primary care and teaching hospital settings. Physician and patient education, distribution of printed guidelines and brochures, and completion of a single-page form motivated both physicians and patients to achieve multiple CVD risk factor guideline goals. The absence of a control group is a limitation of this study. Further work is also needed to establish if the improvements observed are sustained on a long-term basis.

Implementation of strategy for the management of overt dyslipidemia: the IMPROVE-dyslipidemia study.

BACKGROUND: To assess the efficacy of a strategy aimed at improving vascular risk management in patients with dyslipidemia with or without cardiovascular disease (CVD). METHODS: This is a pilot implementation enhancement program that was evaluated in 1127 patients with dyslipidemia. There was a baseline visit, followed by a concerted effort from previously trained physicians to improve adherence to lifestyle advice and optimize drug treatment for all vascular risk factors. After 6 months the patients were re-evaluated. The PROspective-Cardiovascular-Munster (PROCAM) and Framingham trials risk engines were used to estimate CVD risk in primary prevention patients (n=609). RESULTS: This strategy induced a better compliance to lifestyle measures and use of evidence-based medication, focusing on statins. This resulted in a 45% (Framingham) to 63% (PROCAM) reduction in estimated CVD risk in primary prevention (both p<0.0001). There was also a substantial increase in the proportion of secondary prevention patients (n=518) achieving CVD risk factor targets (from 29% at baseline to 76% at 6 months, p<0.0001). CONCLUSIONS: This is the first study to increase the adherence to multiple interventions in patients with dyslipidemia, and other CVD risk factors, in both primary care and teaching hospital settings. Simple measures, such as educating physicians and patients, distributing printed guidelines and brochures, and completing a 1-page form, motivated physicians and patients to achieve multiple CVD risk factor goals.

Stroke and conditions that mimic it: a protocol secures a safe early recognition.

OBJECTIVE: Certain disorders may be falsely diagnosed as stroke. We examined the efficacy of the diagnostic protocol that is followed in our stroke unit and was designed in order to early differentiate more efficiently between stroke and conditions that mimic it. METHODS-PATIENTS: Three hundred sixty-two elderly patients (196 male, 166 female with average age 74.56 years), who were hospitalized at our stroke center between January of 2005 and June of 2007 and diagnosed at admission as stroke patients, were retrospectively studied in order to investigate if the final diagnosis agreed with the initial diagnosis of stroke on admission.Our diagnostic protocol included medical history of the patient, assessment of state of consciousness, blood pressure, electrocardiogram, complete blood cell count (hematocrit/hemoglobin, leukocytes, platelets), clotting mechanism (prothrombin time, activated partial thromboplastin time), glucose, electrolytes (Na, K, Ca), renal (blood urea nitrogen, creatinine) and liver function (SGOT, SGPT), as well as imaging methods like chest X-Ray and brain CT scan. RESULTS: In 95% of patients, the final diagnosis agreed with the initial diagnosis of stroke at admission. According to final diagnosis, 344 (95%) of them had stroke -either hemorrhagic or ischemic-, while from the rest 18 (5%), 12 (66.7%) were found to have metastatic neoplasm of brain, 3 (18.7%) had primal tumour of brain, whereas 3 (18.7%) suffered from other diseases (respiratory infection, meningoencephalitis, thyrotoxicosis). The principal symptoms of the conditions that mimicked a stroke were: aphasic disturbances (27.3%), dizziness/fainting (27.3%), headache/diplopia (11.1%), dysarthria (11.1%), hiccup and/or swallow disturbances (5.6%). CONCLUSION: Our diagnostic protocol seems to ensure a high degree of differential diagnosis between stroke and conditions that mimic it.

The neuroprotective role of erythropoietin in the management of acute ischaemic stroke: from bench to bedside.

Recombinant human erythropoietin was produced soon after the discovery of the erythropoietin gene in 1985 and since then, it is used in various clinical conditions such as chronic renal failure. Moreover, experimental studies have shown that erythropoietin exerts neuroprotective action as well. Recently, a clinical trial yielded promising results concerning the use of erythropoietin in stroke management. In this review, we summarize the main data which suggest that recombinant human erythropoietin and its analogues may indeed have a role in stroke treatment.

Parathyroid crisis as first manifestation of primary hyperparathyroidism.

We report the case of a 61-year-old woman who suffered a parathyroid crisis due to a parathyroid adenoma. The patient presented with the typical clinical symptoms of hypercalcemia. Ca(+2) and PTH were markedly increased. Initially, she was treated conservatively until Ca(+2) returned to normal levels. Then, she underwent surgical excision of a newly diagnosed parathyroid adenoma. Parathyroid crisis (PC), also known as parathyroid storm or acute primary hyperparathyroidism, is a rare and serious complication of primary hyperparathyroidism (PH). Fewer than 200 cases have been described in the literature. Prognosis is poor: mortality is 100% in non-operable cases and 20% in cases in which parathyroidectomy is performed. We emphasize the importance of early diagnosis and aggressive treatment.

Comparison of ciclopirox olamine 1% cream with ciclopirox 1%-hydrocortisone acetate 1% cream in the treatment of inflamed superficial mycoses.

The hydroxypyridone antifungal agent ciclopirox olamine cream 1% has been shown to be as effective in the treatment of inflamed, superficial fungal infections as a formulation in which ciclopirox 1% and hydrocortisone acetate 1% were combined. In a randomized, double-blind, parallel group comparison study, 138 patients with culture-confirmed superficial fungal diseases applied their assigned medication twice daily for 21 days. Clinical assessments were made at the baseline visit; at visits on days 4, 7, 14, and 21 during treatment; and on day 28 (one week posttreatment). Specimens for cultures were taken at baseline and on day 28. There were no differences for the 69 patients in either treatment group at any visit with respect to improvement in the signs/symptoms evaluated; mycological cures in the two treatment groups also were not significantly different.

[Galenic and clinico-pharmacologic studies of prednicarbate (Hoe 777)]. / Galenische und klinisch-pharmakologische Untersuchungen zu Prednicarbat (Hoe 777).

The corticoid prednicarbate (test name: Hoe 777) is derived from prednisolone having no halogenic groups (chemical name: prednisolone-17-ethyl carbonate-21-propionate). Because of the specific physical and chemical properties of prednicarbate, galenic research strove to optimize the vehicle. Further development was only performed on those drug-containing bases showing especially good drug release (granting the most favorable action) in a) the vasoconstriction test and b) the UV erythema test practiced on volunteers with healthy skin. Exemplarily dealing with the special preparations predicarbate cream, ointment, and greasy ointment, we give some details of studies on drug dosage, vehicle selection, and the optimum water/lipid ratio.