Platelet function testing: methods of assessment and clinical utility

Platelets play a central role in the regulation of both thrombosis and haemostasis yet tests of platelet function have, until recently, been exclusively used in the diagnosis and management of bleeding disorders. Recent advances have demonstrated the clinical utility of platelet function testing in patients with cardiovascular disease. The ex vivo measurement of response to antiplatelet therapies (aspirin and clopidogrel), by an ever-increasing array of platelet function tests, is with some assays, predictive of adverse clinical events and thus, represents an emerging area of interest for both the clinician and basic scientist. This review article will describe the advantages and disadvantages of the currently available methods of measuring platelet function and discuss both the limitations and emerging data supporting the role of platelet function studies in clinical practice.     

Neuropathic pain: a narrative review of etiology,assessment, diagnosis,and treatment for primary care providers

Background: Neuropathic pain (NeP) is a distinct type of chronic pain that is a direct result of damage to the nervous system itself. Studies have shown that training on the topic of chronic pain in medical schools is lacking and many practitioners are not confident in their ability to effectively manage patients with such pain.

Aims: The purpose of this narrative review is to provide a brief high-level overview of NeP for primary healthcare providers that includes a discussion of mechanisms, prevalence, burden, assessment, and treatment. The information provided here should help primary care providers better understand this type of chronic pain.     

Platelet function during antihypertensive treatment with quinapril, a novel angiotensin converting enzyme inhibitor.

The effect of various antihypertensive medications on platelet function is of increasing interest. Conflicting effects of captopril on platelet function are reported and the impact of angiotensin converting enzyme (ACE) inhibitors not containing a sulfhydryl group such as enalapril, lisinopril, and quinapril on platelet function remains unstudied. Therefore, the aim of the present study was to examine the effect of antihypertensive treatment with quinapril, a novel ACE inhibitor not containing a sulfhydryl group, on platelet function. Ten white men (age range of 32-61 years) with untreated mild-to-moderate essential hypertension (supine diastolic blood pressure greater than 95 mm Hg) were treated with 4 weeks each of placebo and quinapril in a double-blind, randomized, crossover design. Quinapril (20 mg twice a day) significantly lowered systolic (p less than 0.01) and diastolic blood pressure (p less than 0.01) without any significant effect on heart rate or plasma catecholamines. No significant change was noted for in vitro platelet aggregation induced by epinephrine, ADP, or collagen. Plasma concentrations of the platelet release factors beta-thromboglobulin and platelet factor 4 did not change, nor did the platelet content of norepinephrine, platelet weight (mg/10 ml of blood), circulating platelet count, or platelet size. Thus, as assessed by a broad spectrum of platelet parameters, we found that antihypertensive treatment with quinapril has no significant effect on platelet function in patients with mild-to-moderate essential hypertension. These "platelet-neutral" properties of quinapril suggest that quinapril, both from a thromboembolic and a hemostatic point of view, may be a rather safe agent for treatment of hypertension.     

Platelet adenylate cyclase activity in depression and after clomipramine and lithium treatment: relation to serotonergic function

Adenylate cyclase activity was measured in platelet membranes from 10 healthy controls, 12 depressed patients, and the same patients after treatment with clomipramine (CMI) followed by lithium carbonate (Li) supplementation, in an attempt to determine whether any evidence for an effect on the serotonergic system could be obtained in peripheral cells. There were no differences in basal, NaF-, PGE₁-, or forskolin-stimulated activity either between the control subjects and depressed patients or between activities in the patients measured before treatment, after CMI, and after CMI+Li. The degree of inhibition of forskolin-stimulated adenylate cyclase by 5-HT, an effect putatively mediated by a 5-HT1A-like receptor, was not different in the depressed patients compared to controls or affected by CMI treatment, but was significantly reduced after Li supplementation.     

Problematic cybersex: Conceptualization,assessment, and treatment

Problematic involvement in cybersex is generally considered to be an excessive and uncontrolled use of online sexual activities associated with tangible negative outcomes and functional impairment. To date, there is no consensus in the literature regarding the conceptualization and labeling of this disorder, or of its diagnosis and assessment (e.g., screening questionnaires and diagnostic criteria). Through a systematic examination of the literature, we emphasize that problematic cybersex is an umbrella construct that regroups various types of distinct dysfunctional online behaviors. Despite a considerable increase in studies on problematic cybersex, no clear diagnostic guidelines exist for clinicians and researchers. Moreover, the factors involved in the development and maintenance of the disorder remain poorly examined, and the evidence regarding valid assessment and treatment are lacking.     

Pediatric asthma: natural history, assessment, and treatment

Wheezing and childhood asthma are not synonymous but rather comprise a heterogeneous group of conditions that have different outcomes over the course of childhood. Most infants who wheeze have a transient condition associated with diminished airway function at birth and have no increased risk of asthma later in life. However, children with persistent wheezing throughout childhood and frequent exacerbations represent the main challenge today. Studying the natural history of asthma is important for the understanding and accurate prediction of the clinical course of different phenotypes. To date, a great improvement has been achieved in reducing the frequency of asthma symptoms. However, neither decreased environmental exposure nor controller treatment, as recommended by the recent National Asthma Education And Prevention Program, can halt the progression of asthma in childhood or the development of persistent wheezing phenotype. This review focuses on the recent studies that led to the current understanding of asthma phenotypes in childhood and the recommended treatments.     

Platelet function and signaling in diabetes mellitus

Diabetes mellitus is associated with the accelerated development of vascular disease and there is evidence that platelets actively contribute to this process. Certainly, platelets are able to modulate the function of endothelial and vascular smooth muscle cells via the direct release of growth factors and pro-inflammatory chemokines but also via the production of microparticles which function as a transcellular delivery system for micro RNAs. This article reviews the intracellular signaling mechanisms underlying the increased activation of diabetic platelets and the involvement of platelets in atherothrombosis development.     

Tick-borne encephalopathies : epidemiology, diagnosis, treatment and prevention

Tick-borne encephalopathies constitute a broad range of infectious diseases affecting the brain and other parts of the CNS. The causative agents are both viral and bacterial. This review focuses on the current most important tick-borne human diseases: tick-borne encephalitis (TBE; including Powassan encephalitis) and Lyme borreliosis. Rocky Mountain spotted fever (RMSF) and Colorado tick fever (CTF), less common tick-borne diseases associated with encephalopathy, are also discussed. TBE is the most important flaviviral infection of the CNS in Europe and Russia, with 10 000-12 000 people diagnosed annually. The lethality of TBE in Europe is 0.5% and a post-encephalitic syndrome is seen in over 40% of affected patients, often producing a pronounced impairment in quality of life. There is no specific treatment for TBE. Two vaccines are available to prevent infection. Although these have a good protection rate and good efficacy, there are few data on long-term immunity. Lyme borreliosis is the most prevalent tick-borne disease in Europe and North America, with >50 000 cases annually. Localised early disease can be treated with oral phenoxymethylpenicillin (penicillin V), doxycycline or amoxicillin. The later manifestations of meningitis, arthritis or acrodermatitis can be treated with oral doxycycline, oral amoxicillin or intravenous ceftriaxone; intravenous benzylpenicillin (penicillin G) or cefotaxime can be used as alternatives. The current use of vaccines against Lyme borreliosis in North America is under discussion, as the LYMErix vaccine has been withdrawn from the market because of possible adverse effects, for example, arthritis. RMSF and CTF appear only in North America. RMSF is an important rickettsial disease and is effectively treated with doxycycline. There is no treatment or preventative measure available for CTF.     

Pertussis resurgence: diagnosis, treatment, prevention, and beyond

The introduction of routine vaccination against Bordetella pertussis more than a half century ago led to a drastic decline in the number of reported cases of pertussis. It was originally believed that lifelong immunity was afforded after vaccination. Unfortunately, this belief is flawed, as the highest number of pertussis cases since 1959 was reported in 2004. This significant increase has led to additional research on immunity, vaccination, and treatment of B. pertussis in all age groups. We performed a MEDLINE search of literature from 1966-2006 to evaluate and review the existing data on immunity to and prevention or treatment of B. pertussis infections. Additional articles were identified from the bibliographies of reviewed literature. Numerous articles pertaining to these topics have been published recently. The most significant changes in the management of this infectious disease surround the new recommendations by the Advisory Committee on Immunization Practices for adult and adolescent immunizations to assist in preventing outbreaks of B. pertussis. The Centers for Disease Control and Prevention recently published guidelines updating the recommended pharmacologic agents for treatment or prevention of B. pertussis. Despite decades of successful vaccination programs, pertussis continues to be a problematic disease. Fortunately, data and vaccines are now available that make development of a pertussis booster vaccination campaign reasonable. However, until widespread compliance with such programs is achieved, clinicians need to maintain vigilance against pertussis.     

Pre-eclampsia, diagnosis and treatment

Pre-eclampsia is a multisystem disorder of pregnancy usually associated with raised blood pressure (BP) and proteinuria. The pathogenesis is not understood despite decades of research. Abnormal placentation related to immune mechanisms and maladaptation of the placenta may be the first step in the development of the disease. Although there are a number of risk factors and new innovatory tests (e.g., uterine artery Doppler) which can be used to predict pre-eclampsia, none fulfils standard diagnostic criteria. Of possible prophylactic value are antiplatelet agents, calcium supplementation and vitamins C and E. Prevention of eclampsia with magnesium sulfate is the subject of a current international randomised controlled trial (RCT), known as MAGPIE. Therapeutic strategies include avoidance of hypertensive injury and delivery of the baby and placenta. Further research into specific antihypertensive agents and conservative management strategies is required.     

Platelet membrane fluidity and treatment response in cognitively-impaired,depressed elderly: initial results

A prospective study of response to treatment with nortriptyline was carried out in a group of 14 inpatients with mixed symptoms of depression and dementia. Platelet membrane fluidity, as reflected by the fluorescence anisotropy of DPH labeled membranes, was determined for all 14 drug-free subjects prior to treatment by staff who were blind to clinical and demographic data. Patients who exhibited worsening of their cognitive impairment exhibited increased platelet membrane fluidity, an abnormality found in approximately 50% of patients with Alzheimer's disease.     

Neuropsychologically impaired alcoholics: assessment, treatment considerations, and rehabilitation

Recently there has been a resurgence of interest in the neuropsychological status of the alcoholic. The research documenting neuropsychological deficits has consistently shown impairments in abstract reasoning ability, visuospatial and visuomotor ability, and learning and memory skills. Despite these findings, it appears that many alcohol treatment clinicians interpret patient behavior from a psychological perspective and treatment programs make unwarranted assumptions about patients' ability to profit from standard treatment approaches. This paper discusses these issues, and presents an outline of an innovative cognitive rehabilitation program designed specifically to meet the needs of neuropsychologically impaired alcoholic patients.     

Nicotine dependence: diagnosis, pharmacology and treatment.

Nicotine dependence has been clearly documented as an addiction to nicotine. The development of tolerance and dependence to nicotine has been documented as well in studies in animals and humans. The morbidity and mortality from nicotine dependence continues to be widespread and significant in spite of some reduction in the prevalence of use. Various modalities of pharmacological and nonpharmacological treatments have been developed in recent years. These treatment methods may be used singularly or in combination. Although some success has been claimed with each form of treatment, more studies are needed to confirm their full efficacy.     

Late onset asthma: epidemiology, diagnosis and treatment

Asthma is common among older persons, affecting approximately 4 to 8% of those above the age of 65 years. Despite its prevalence, late onset asthma may be misdiagnosed and inadequately treated, with important negative consequences for the patient's health. The histopathology of late onset disease appears to be similar to that of asthma in general, with persistent airway inflammation a characteristic feature. It is less clear, however, that allergic exposure and sensitisation play the same role in the development of disease in adults as they do in children. Atopy is less common among those with late onset asthma, and the prevalence of elevated immunoglobulin E levels is lower among those aged over 55 years of age than younger patients. Occupational asthma is an aetiological consideration unique to adult onset disease, with important implications for treatment. The differential diagnosis for cough, wheeze, and dyspnoea in the elderly is broad, and includes chronic obstructive bronchitis, bronchiectasis, congestive heart failure, lung cancer with endobronchial lesion and vocal cord dysfunction. Keys to accurate diagnosis include a good history and physical examination, the demonstration of reversible airways obstruction on pulmonary function tests and a favorable response to treatment. Inhaled corticosteroid therapy is recommended for patients with persistent disease, and careful instruction in the use of metered-dose inhalers is particularly important for the elderly.     

Restless legs syndrome: pathophysiology, diagnosis and treatment

Restless legs syndrome (RLS) is clinically defined by the presence of (i) an urge to move the legs with or without an actual paraesthesia; (ii) a worsening of symptoms with inactivity; (iii) improvement with activity; and (iv) a worsening of symptoms in the evening and at night. Patients may use a variety of semantic phrases to describe their symptoms but all must have an urge to move. Most people with RLS also have periodic limb movements during sleep, although this is not part of the clinical diagnostic criteria. RLS is very common. About 10% of all Caucasian populations have RLS, although it may be mild in the majority of cases. Women generally outnumber men by about 2:1. As a general rule, RLS severity worsens through the first seven to eight decades of life, but may actually lessen in old age. The aetiology of RLS is only partly understood. There is a strong genetic component, and several genetic linkages and three causative genes have been identified worldwide. Several medical conditions, including renal failure, systemic iron deficiency and pregnancy, and possibly neuropathy, essential tremor and some genetic ataxias, are also associated with high rates of RLS. In all cases to date, the actual CNS pathology of RLS demonstrates reduced iron stores, in a pattern that suggests that the homeostatic control of iron is altered, not just that there is not enough iron entering the brain. The relationship between reduced CNS iron levels and the clinical phenotype or treatment response to dopaminergics is not known but generates promising speculation. Treatment of RLS is usually rewarding. Most patients respond robustly to dopamine receptor agonists. Over time, response may lessen, or the patients may develop 'augmentation', whereby they have a worsening of symptoms, usually in the form of an earlier onset. Other treatment options include gabapentin, or similar antiepileptic drugs, and opioids. High-dose intravenous iron is a promising but still experimental approach.     

基于超支化聚乙烯亚胺的磁共振成像造影剂研究进展

在过去10年中,分子成像技术迅速发展,并由此出现了很多有关影像检查的造影剂,其中基于超支化聚乙烯亚胺的磁共振成像造影剂展现出一些其他造影剂所没有的优异性。超支化聚乙烯亚胺价格相对低廉,可修饰性强,其研究开发得到了广泛的关注。基于超支化聚乙烯亚胺的良好理化性质和结构特点,综述了各类基于超支化聚乙烯亚胺的磁共振成像造影剂的制备及其生物医学应用进展,并展望此类磁共振成像造影剂在肿瘤早期诊断中的应用前景。