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Hemiplegic shoulder pain: implications for occupational therapy treatment.

BACKGROUND: Hemiplegic shoulder pain is common after stroke causing hemiplegia. It adversely affects the recovery of arm function and independence in activities of daily living. Subluxation, abnormal tone and limited range of motion or capsular constrictions have been reported as potential causes. Other factors such as rotator cuff tears, brachial plexus injury, shoulder-hand syndrome and other pre-existing pathological conditions may also be associated with hemiplegic shoulder pain. The etiology remains unclear, but hemiplegic shoulder pain may result from a combination of the above factors. SCOPE: This literature review examines the possible causes of hemiplegic shoulder pain and discusses the implications for occupational therapy treatment. Occupational therapy interventions include proper positioning, facilitation of movement through purposeful therapeutic activities, increasing passive range of motion, implementation of external supports and treatment of shoulder-hand syndrome. PRACTICE IMPLICATIONS: Understanding the processes involved will assist with effective assessment, treatment and prevention of hemiplegic shoulder pain. This will facilitate clients' participation in rehabilitation programs and move them towards attainment of optimal function.

Hemiplegia↗

Nystatin prophylaxis in immunocompromised children.

In conclusion, the use of nystatin for fungal prophylaxis in hematology/oncology/bone marrow transplantation patients appears to convey little or no benefit over no therapy. Nystatin treatment significantly reduced the frequency of multiple-site colonization and of persistently positive oropharyngeal cultures, but was not able to prevent the occurrence of disseminated fungal infections. Other antifungal agents (e.g., ketoconazole, fluconazole, itraconazole, oral or intravenous amphotericin B) may be of benefit. Studies comparing nystatin with other agents are available in the literature but are beyond the scope of this review.

Agranulocytosis↗

PPARgamma and atherosclerosis.

BACKGROUND: Peroxisome proliferator-activated receptor (PPAR)gamma regulates a number of cellular processes that affect glucose homeostasis, endothelial function and vessel wall inflammation, as well as protecting against cardiovascular complications that occur in diabetes. Thiazolidinediones are PPARgamma agonists that are in clinical use for the treatment of type 2 diabetes. Accumulating evidence indicates that thiazolidinediones may exert cardioprotective effects at each stage of atherogenesis. SCOPE: This paper reviews preclinical and clinical evidence (identified from a search of MEDLINE databases) supporting a beneficial cardiovascular effect of thiazolidinediones and discusses the implications of these data for the optimal use of thiazolidinediones in clinical practice. FINDINGS: In vitro animal model and clinical studies indicate that thiazolidinediones correct endothelial dys function, suppress chronic inflammatory processes, reduce fatty streak formation, delay plaque evolution and vessel wall thickening and enhance plaque stabilization and regression. CONCLUSION: Thus, thiazolidinediones show potential as potent anti-inflammatory, antithrombotic agents that could both improve glucose levels and the long-term cardio vascular risk related to atherosclerosis in patients with type 2 diabetes.

Animals↗

Changing targets in the treatment of type 2 diabetes.

BACKGROUND: While correction of hyperglycemia remains central to the management of type 2 diabetes, current management approaches address an integrated constellation of disorders that predispose patients to the risk of microvascular and macrovascular complications. SCOPE: This paper reviews glycemic control targets and associated cardiovascular disease risk management in type 2 diabetes, as recommended by the American Diabetes Association (ADA), the International Diabetes Federation (IDF), and the UK National Institute for Clinical Excellence (NICE). It is based upon MEDLINE literature searches from January 1995 to April 2006. FINDINGS: Current guidelines recommend glycated hemoglobin (HbA1c) target levels of approximately 6.0-7.5%. However, European and US data suggest that HbA1c targets are achieved by only approximately one-third of patients with type 2 diabetes. Progression from pre-diabetic impaired glucose tolerance to type 2 diabetes has recently become a target for early intervention with pharmacological agents. The aggressive treatment of dyslipidemia towards defined target levels of triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol is recommended. The ADA and IDF recommend blood pressure targets of 130/80 mmHg in type 2 diabetes, and the use of aspirin for secondary cardiovascular disease prevention and primary prevention in patients at increased risk. Although inflammatory biomarkers, such as C-reactive protein, may predict type 2 diabetes risk, their role remains unclear. CONCLUSIONS: Concerted efforts are necessary to increase the proportion of patients achieving current treatment targets. Such measures must aim to educate patients and physicians, remove barriers due to health care organization and access, and improve the monitoring of cardiovascular disease risk indicators. The poly-pharmacy 'pill burden' may be alleviated through the use of drugs that are effective against multiple aspects of the metabolic syndrome, and by co-formulation of agents with established efficacy.

Blood Glucose↗

Assessing glucose meter accuracy.

BACKGROUND: Self-monitoring of blood glucose plays an important role in the management of diabetes, particularly in patients treated with insulin. Blood glucose meters must have sufficient accuracy to allow patients and clinicians to monitor glycemic control and then modify treatment accordingly. Although several standards have been proposed, a consensus about how to measure glucose meter accuracy is not available. SCOPE: An informal review of recently published articles dealing with glucose meter accuracy was conducted to provide recommendations for evaluating accuracy relevant to the practicing clinician. FINDINGS: Whether in clinical practice or in accuracy studies, the accuracy of blood glucose meters is typically determined by comparing meter results to those obtained by a clinical laboratory method on samples collected from the same patient at the same time. However, multiple sample-related, analysis-related, and data display-related factors can have an impact on accuracy determination. Clinicians need to recognize these factors and take steps to minimize their impact when assessing the accuracy of glucose meters used by their patients. CONCLUSIONS: Although modern glucose meters show variable results with respect to analytical measures of accuracy, error grid analysis demonstrates that measurements deemed clinically acceptable approach 100%.

Blood Glucose Self-Monitoring↗

Serum biomarkers in acute respiratory distress syndrome an ailing prognosticator.

The use of biomarkers in medicine lies in their ability to detect disease and support diagnostic and therapeutic decisions. New research and novel understanding of the molecular basis of the disease reveals an abundance of exciting new biomarkers who present a promise for use in the everyday clinical practice. The past fifteen years have seen the emergence of numerous clinical applications of several new molecules as biologic markers in the research field relevant to acute respiratory distress syndrome (translational research). The scope of this review is to summarize the current state of knowledge about serum biomarkers in acute lung injury and acute respiratory distress syndrome and their potential value as prognostic tools and present some of the future perspectives and challenges.

Animals↗

Serum biomarkers in interstitial lung diseases.

The use of biomarkers in medicine lies in their ability to detect disease and support diagnostic and therapeutic decisions. New research and novel understanding of the molecular basis of the disease reveals an abundance of exciting new biomarkers who present a promise for use in the everyday clinical practice. The past fifteen years have seen the emergence of numerous clinical applications of several new molecules as biologic markers in the research field relevant to interstitial lung diseases (translational research). The scope of this review is to summarize the current state of knowledge about serum biomarkers in interstitial lung diseases and their potential value as prognostic and diagnostic tools and present some of the future perspectives and challenges.

Animals↗

Parasites.

Ill health related to food-borne infection transcends all geographical, political and cultural boundaries. The incidence of food-borne diseases continues to adversely affect the health and productivity of populations in most countries, especially non-industrialised ones. However, since the 1950s, the emphasis in the industrialised world had shifted away from addressing public health problems, to problems of chemical contaminants etc., but recently food-borne infections have again become of increasing concern to governments and the food industry. Improvements in international transportation means food can be distributed throughout the world, but so can the parasitic pathogens which contaminate foods. Alternatively, tourists are being affected abroad and possibly transmitting the pathogen to others at home. Thus, an increasing number of food-related illnesses are international in scope. In this review parasitic contamination of foods of animal origin, particularly meat and fish, will be discussed together with potential problems associated with water and unwashed fruits and vegetables.

Animals↗

Fluorescence correlation spectroscopy and its potential for intracellular applications.

Fluorescence correlation spectroscopy (FCS) is a time-averaging fluctuation analysis of small molecular ensembles, combining maximum sensitivity with high statistical confidence. Among a multitude of physical parameters that are, in principle, accessible by FCS, it most conveniently allows to determine local concentrations, mobility coefficients, and characteristic rate constants of fast-reversible and slow-irreversible reactions of fluorescently labeled biomolecules at very low (nanomolar) concentrations, under equilibrium conditions and without physical separation. Its presently most popular instrumentation by confocal-microscope setups allows for a spatial resolution of fractions of femtoliters for the measurement volumes, containing sparse or even single molecules at any time, and encourages the adaptation of the solution-based technique for cellular applications. The scope of this review is thus, to introduce the FCS technique in particular to the reader with biological background, searching for new methods for a precise quantification of physical parameters governing cellular mechanisms and dynamics, especially if high sensitivity and fast dynamic resolution are required. After a short theoretical introduction, examples are given for the so far most important experimental applications, with respect to their implementation in cellular systems. As an interesting alternative to the confocal instrumentation, two-photon excitation will be introduced, offering a number of important advantages especially in cellular systems with high-noise and low-signal levels.

Cell Membrane↗

Liver stem cells: implications for hepatocarcinogenesis.

Numerous studies point to the fact that liver tumors are derived from single cells (monoclonal), but the important question is, which cell? Stem cell biology and cancer are inextricably linked. In continually renewing tissues such as the intestinal mucosa and epidermis, in which a steady flux of cells occurs from the stem cell zone to the terminally differentiated cells that are imminently to be lost, it is widely accepted that cancer is a disease of stem cells, as these are the only cells that persist in the tissue for a sufficient length of time to acquire the requisite number of genetic changes for neoplastic development. In the liver the identity of the founder cells for the two major primary tumors, hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC), is more problematic. The reason for this is that no such obvious unidirectional flux occurs in the liver, though it is held that the centrilobular hepatocytes may be more differentiated (polyploid) and closer to cell senescence than those cells closest to the portal areas. Moreover the existence of bipotential hepatic progenitor cells (HPCs), along with hepatocytes endowed with longevity and long-term repopulating potential suggests there may be more than one type of carcinogen target cell. Irrespective of which target cell is involved, cell proliferation at the time of carcinogen exposure is pivotal for "fixation" of the genotoxic injury into a heritable form. Taking this view, any proliferative cell in the liver can be susceptible to neoplastic transformation. Thus, hepatocytes are implicated in many instances of HCC, direct injury to the biliary epithelium implicates cholangiocytes in some cases of CC, whereas HPC/oval cell activation accompanies very many instances of liver damage irrespective of etiology, making such cells very likely carcinogen targets. Of course, we must qualify this assertion by stating that many carcinogens are both cytotoxic and cytostatic, and that HPC proliferation may be merely a bystander effect of this toxicity. An indepth discussion of causes of cancer in the liver are beyond the scope of this review, but infectious agents (e.g., hepatitis B and C viruses) play a major role, not just in transactivating or otherwise disrupting cellular proto-oncogenes (hepatitis B virus [HBV]), but in also causing chronic inflammation (hepatitis C virus [HCV] and HBV). Sustained epithelial proliferation in a milieu rich in inflammatory cells, growth factors, and DNA-damaging agents (reactive oxygen and nitrogen species produced to fight infection), will lead to permanent genetic changes in proliferating cells. The upregulation of the transcription factor nuclear factor kappaB (NF-kappaB) in transformed hepatocytes, through the paracrine action of tumor necrosis factor-alpha from neighboring endothelia and inflammatory cells, may be critical for tumor progression given the mitogenic and anti-apoptotic properties of proteins encoded by many of NF-kappaB's target genes.

Animals↗

The ubiquitin-mediated proteolytic pathway: mechanisms of action and cellular physiology.

Ubiquitin modification of many protein targets within cells plays important roles in a variety of biological processes. Among these are regulation of gene expression, regulation of cell cycle and division, involvement in the cellular stress response, modification of cell surface receptors, DNA repair, import of proteins into mitochondria, uptake of precursors of neurotransmitters into synaptosomes, biogenesis of peroxisomes, assembly of ribosomes, and programmed cell death. The mechanisms that underlie these complex processes are poorly understood. The best studied modification occurs in the ubiquitin-mediated proteolytic pathway. Recent experimental evidence indicates that the ubiquitin system is involved in the degradation of mitotic cyclins, oncoproteins and tumor suppressors, in the removal of abnormal and otherwise damaged proteins, and in processing of antigens restricted to class I MHC molecules. Degradation of a protein via the ubiquitin system involves two discrete steps. Initially, multiple ubiquitin molecules are covalently linked in an ATP-dependent mode to the protein substrate. The targeted protein is then degraded by a specific, energy-dependent and high molecular mass protease complex into peptides and free amino acids, and free and reutilizable ubiquitin is released. In addition, stable mono-ubiquitin adducts are also found in the cell, for example, those involving nucleosomal histones. Despite the considerable progress that has been made in elucidating the mode of action and roles of the ubiquitin system, many problems remain unsolved. For example, little is known on the signals that target proteins for degradation. While a few proteins are targeted for degradation following recognition of their N-terminal amino acid residue, the vast majority of cellular proteins are targeted by other signals. The identity of the native cellular substrates of the system is another important, yet unresolved problem: only a few proteins have been recognized so far as substrates of the system in vivo. The scope of this review is to discuss the mechanisms involved in ubiquitin activation, selection of substrates for conjugation, and degradation of ubiquitin-conjugated proteins in the cell-free system. In addition, we shall summarize what is currently known of the physiological roles of ubiquitin-mediated proteolysis in vivo.

Adenosine Triphosphate↗

Pharmacological interventions for stroke: failures and future.

Given the few options currently available for patients following ischaemic stroke, the recent disappointing failures of several large-scale Phase III clinical trials has made the search for novel therapeutic approaches even more critical. Experimental evidence has suggested that the majority of stroke patients have a slow evolution of brain injury which can occur over several hours. Progressive microcirculatory failure following the initial onset of ischaemia may contribute to the expansion of brain injury. Included among the pathophysiological changes that are speculated to occur as a secondary response to the initial ischaemia are free radical production, excitotoxicity (for example, glutamate) disruption of ionic homeostasis (for example, sodium and calcium influx), enzymatic changes, stimulation of the inflammatory process, endothelin release, activation of platelets and leukocytes, delayed coagulation and endothelial dysfunction. All of these pathophysiological reactions could contribute to an increase in local vascular resistance and therefore cause progressive hypoperfusion of the brain following the onset of stroke. The scope of this review will focus on recent clinical failures in addition to agents currently in clinical development, comparing vascular targets to the common neuroprotective strategies.

Brain↗

Emerging therapies for human papillomavirus infection.

Human papillomavirus (HPV) is the most common sexually transmitted infection, with > 50% of sexually active women being affected. The virus causes a wide variety of benign and pre-malignant epithelial tumours and although most infections are transient, it is estimated that 1% of the sexually active population in the US have clinically apparent genital warts. A subset of genital HPVs, termed high-risk HPVs, is highly associated with the development of genital cancers including cervical carcinoma. Therapies for these HPV related cancers are however outside of the scope of this review. The absence of a simple monolayer cell culture system for analysis and propagation of the virus has substantially retarded progress in the development of diagnostic and therapeutic strategies for HPV infection. In spite of these difficulties, great progress has been made in the elucidation of the molecular controls of virus gene expression, replication and pathogenesis, and there has been some progress in the development of prophylactic and therapeutic vaccines and of other therapies.

Journal Article↗

[Epidemiological aspects of Helicobacter pylori infection in childhood and adolescence].

The scope of the review is to study the epidemiological aspects of Helicobacter pylori infection and its importance during childhood and adolescence, focusing on incidence, prevalence, transmission and risk factors. The study's references included the following databases: LILACS (PAHO/ Bireme), MEDLINE, the US's National Library of Medicine and the thesis developed at University of São Paulo for the period 1983 to 1999. It was noted that Helicobacter pylori infection is mainly acquired during childhood, age-related prevalence, main risk factors are associated to low socioeconomic status, and its transmission mechanism remains unclear.

Adolescent↗

Surgical management of ureteropelvic junction obstruction in adults.

Ureteropelvic junction (UPJ) obstruction is a well-recognized entity that may present at any time - in fetal life, infancy, childhood, or early or late adulthood. As the most common site of obstruction in the upper urinary tract, the UPJ is an area with which urologists should be well familiar. There has been an improved understanding of the pathophysiology of primary congenital UPJ obstruction that has been reflected in the evolution of surgical options, from open surgical repair to minimally invasive surgery. Although the primary scope of this review is the surgical management of this condition, we will briefly review the pathogenesis, clinical presentation, and diagnosis of UPJ obstruction.

Journal Article↗

Current applications of polysaccharides in colon targeting.

Polysaccharides have over the years been used widely in pharmaceutical, chemical, and biochemical drug delivery. This family of natural polymers has an appeal to the area of drug delivery as it is comprised of polymers with a large number of derivatizable groups, a wide range of molecular weights, varying chemical compositions, and for the most part, a low toxicity and biodegradability, yet a high stability. The main scope of this review is to relate the polysaccharides available now to the rapidly growing field of colonic drug delivery. Polysaccharides have been applied to the area as controlled release coatings, matrices, macromolecular carriers, and biodegradable carriers. Bacterial sources of polysaccharidases as well as a detailed treatise of the enzymatic flora of the colonic region are discussed, followed by a presentation of the polysaccharides available for the purpose of colon-specific drug delivery. A final overview of the various approaches to obtain colon-specific delivery by using polysaccharides and a summary of available in vitro and in vivo testing methods will lead to the conclusion that polysaccharides at this point appear to be very promising compounds for use in obtaining colon-specific drug delivery systems.

Animals↗

IGF-binding protein-5: flexible player in the IGF system and effector on its own.

The multiple activities of IGF-I and -II are modulated by a family of IGF-binding proteins (IGFBP-1 to -6). Although structurally related, each IGFBP has unique properties and exerts specific functions. IGFBP-5 is the most conserved IGFBP across species and was identified as an essential regulator of physiological processes in bone, kidney and mammary gland. In addition, IGFBP-5 appears to play a decisive role in the control of proliferation of specific tumour cell types. In many situations IGFBP5 exerts biological activities in the absence of IGFs, indicating the existence of IGF-independent actions. This concept was supported by the unexpected localisation of IGFBP-5 in the nucleus and the description of IGFBP-5-specific membrane-bound IGFBP-5 receptor(s). The scope of this review is to summarise the available information about the structure of IGFBP-5 and the regulation of its expression. Furthermore, the potential significance of IGFBP-5 in the regulation of physiological processes will be critically analysed in the light of recent experimental data.

Animals↗

A guide to the safety of CNS-active agents during breastfeeding.

For most agents with CNS activity, there are limited data regarding their safety in breastfeeding. Any decision to institute treatment for a neurological or psychiatric disorder must weigh the benefits of maternal treatment against the potential harm to the breastfeeding mother of withholding medication which may improve her illness. For the neonate, one must balance the risk of medication exposure against the benefit of receiving breast milk. Most tricyclic antidepressants can be used in lactating women. Because of the limited data, selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors should only be used with due consideration of the potential adverse effects. Breastfeeding is best avoided by women who require lithium therapy, because of both the immature excretory systems in the infant and relatively high doses received by the infant. There is little information about the safety of antipsychotic medications in breastfeeding. Concerns include toxicity and abnormal neurological development in the infant. These agents may be used with caution. Most agents which cause depression of the CNS, including opiates and sedatives, can be used in small doses and for short courses in breastfeeding mothers. Most anticonvulsants can be used in lactating women. Reference texts and consultation with experts are useful adjuncts to discussion of the risks and benefits of therapy with the patient. The scope of this review is limited to drugs with therapeutic uses, thus drugs of abuse are not discussed, nor are caffeine and alcohol (ethanol).

Adult↗