The classification and diagnosis of erythrocytosis

An absolute erythrocytosis is present when the red cell mass is raised and the haematocrit is elevated above prescribed limits. Causes of an absolute erythrocytosis can be primary where there is an intrinsic problem in the bone marrow and secondary where there an event outside the bone marrow driving erythropoiesis. This can further be divided into congenital and acquired causes. There remain an unexplained group idiopathic erythrocytosis. Investigation commencing with thorough history taking and examination and then investigation depending on initial features is required. Clear simple criteria for polycythaemia vera are now defined. Those who do not fulfil these criteria require further investigation depending on the clinical scenario and initial results. The erythropoietin level provides some guidance as to the direction in which to proceed and the order and extent of investigation necessary in an individual patient. It should thus be possible to make an accurate diagnosis in the majority of patients.

Talking about colds and flu: The lay diagnosis of two common illnesses among older British people

This paper reports on a study of the ways in which 54 older people in South Wales (UK) talk about the symptoms and causes of cold and influenza (flu). The study was designed to understand why older people might reject or accept the offer of seasonal flu vaccine, and in the course of the interviews respondents were also asked to express their views about the nature and causes of the two key illnesses. The latter are among the most common infections in human beings. In terms of the biomedical paradigm the common cold is caused by numerous respiratory viruses, whilst flu is caused by the influenza virus. Medical diagnosis is usually made on clinical grounds without laboratory confirmation. Symptoms of flu include sudden onset of fever and cough, and colds are characterized by sneezing, sore throat, and runny nose, but in practice the symptoms often overlap. In this study we examine the degree by which the views of lay people with respect to both diagnosis and epidemiology diverge with that which is evident in biomedical discourse. Our results indicate that whilst most of the identified symptoms are common to lay and professional people, the former integrate symptoms into a markedly different observational frame from the latter. And as far as causation is concerned it is clear that lay people emphasize the role of 'resistance' and 'immunity' at least as much as 'infection' in accounting for the onset of colds and flu. The data are analyzed using novel methods that focus on the co-occurrence of concepts and are displayed as semantic networks. As well as reporting on its findings the authors draw out some implications of the study for social scientific and policy discussions concerning lay diagnosis, lay expertise and the concept of an expert patient.

Early diagnosis improves survival in kidney cancer

Kidney cancers account for 2-3% of all adult malignancies in the UK. Men are predominantly affected by renal cancer with an average age at diagnosis of 64 years. Renal (or clear) cell carcinoma (RCC) accounts for 90% of kidney cancers. Early diagnosis improves survival with five-year survival rates for renal cancer of 70-94% for localised tumours in the UK. RCC should be suspected in the presence of localising symptoms such as flank pain, a loin mass or haematuria; constitutional upset including weight loss, pyrexia and/or night sweats; or with unexplained laboratory tests. Smoking, obesity and hypertension are the most important and most common risk factors. Environmental exposure to asbestos, cadmium and trichloroethylene are less common risk factors. Patients on chronic dialysis and renal transplant recipients are at increased risk of RCC in their native kidneys. If kidney cancer is suspected on history, physical examination or initial screening tests then a red flag ultrasound examination of the renal tracts should be requested. Dipstick urinalysis is of great value as asymptomatic haematuria may be the only abnormal test in the presence of non-specific symptoms such as weight loss or loin pain. Visible or non-visible haematuria, in the absence of proteinuria, suggests an underlying structural abnormality is present in the kidneys, ureters or bladder. Surgical removal of RCCs, where feasible, may result in cure in up to 40-60% of cases. Individuals too frail for major surgery may benefit from thermal ablation and cryotherapy. Agents that target the VEGF and mTOR pathways are considered first line in the treatment of metastatic RCC. Sunitinib, recommended by NICE, is administered orally and acts by inhibiting the VEGF receptor.

Molecular diagnosis of the myeloproliferative neoplasms: UK guidelines for the detection of JAK2 V617F and other relevant mutations

Molecular genetic assays for the detection of the JAK2 V617F (c.1849G>T) and other pathogenetic mutations within JAK2 exon 12 and MPL exon 10 are part of the routine diagnostic workup for patients presenting with erythrocytosis, thrombocytosis or otherwise suspected to have a myeloproliferative neoplasm. A wide choice of techniques are available for the detection of these mutations, leading to potential difficulties for clinical laboratories in deciding upon the most appropriate assay, which can lead to problems with inter-laboratory standardization. Here, we discuss the most important issues for a clinical diagnostic laboratory in choosing a technique, particularly for detection of the JAK2 V617F mutation at diagnosis. The JAK2 V617F detection assay should be both specific and sensitive enough to detect a mutant allele burden as low as 13%. Indeed, the use of sensitive assays increases the detection rate of the JAK2 V617F mutation within myeloproliferative neoplasms. Given their diagnostic relevance, it is also beneficial and relatively straightforward to screen JAK2 V617F negative patients for JAK2 exon 12 mutations (in the case of erythrocytosis) or MPL exon 10 mutations (thrombocytosis or myelofibrosis) using appropriate assays. Molecular results should be considered in the context of clinical findings and other haematological or laboratory results.

The impact of sperm DNA damage in assisted conception and beyond: recent advances in diagnosis and treatment

Abstract Sperm DNA damage is a useful biomarker for male infertility diagnosis and prediction of assisted reproduction outcomes.
It is associated with reduced fertilization rates, embryo quality and pregnancy rates, and higher rates of spontaneous miscarriage
and childhood diseases. This review provides a synopsis of the most recent studies from each of the authors, all of whom have major
track records in the field of sperm DNA damage in the clinical setting. It explores current laboratory tests and the accumulating body
of knowledge concerning the relationship between sperm DNA damage and clinical outcomes. The paper proceeds to discuss the
strengths, weaknesses and clinical applicability of current sperm DNA tests. Next, the biological significance of DNA damage in
the male germ line is considered. Finally, as sperm DNA damage is often the result of oxidative stress in the male reproductive tract,
the potential contribution of antioxidant therapy in the clinical management of this condition is discussed. DNA damage in human spermatozoa is an important attribute of semen quality. It should be part of the clinical work up and properly controlled trials
addressing the effectiveness of antioxidant therapy should be undertaken as a matter of urgency.

'Leptorapide' - a one-step assay for rapid diagnosis of human leptospirosis

Leptospirosis is a globally important zoonotic infection caused by spirochaetes of the genus Leptospira. It is transmitted to humans by direct contact with infected animals or indirectly via contaminated water. It is mainly a problem of the resource-poor developing countries of the tropical and sub-tropical regions of the world but outbreaks due to an increase in travel and recreational activities have been reported in developed and more industrialized areas of the world. Current methods of diagnosis are costly, time-consuming and require the use of specialized laboratory equipment and personnel. The purpose of this paper is to report the validation of the 'Leptorapide®' test (Linnodee Ltd, Northern Ireland) for the diagnosis of human leptospirosis. It is a simple one-step latex agglutination assay performed using equal volumes of serum sample and antigen-bound latex beads. Evidence of leptospiral antibodies is determined within minutes. Agglutination is scored on a scale of 1-5 and the results interpreted using a score card provided with the kit. Validation has been performed with a large sample size obtained from individuals originating from various parts of the world including Brazil and India. The test has shown sensitivity and specificity values of 97·1% and 94·0%, respectively, relative to the microscopic agglutination test. The results demonstrate that Leptorapide offers a cost-effective and accurate alternative to the more historical methods of antibody detection.

Introducing EbolaCheck: potential for point-of-need infectious disease diagnosis

The 2013–2015 Ebolavirus disease humanitarian crisis has spurred the development of laboratory-free, point-of-care nucleic acid testing solutions. EbolaCheck is an international consortium of public health, academic and biotechnology industry stakeholders aiming to deliver clinical molecular diagnostic standard-of-care testing suitable for the West African milieu within 12 months. In this article, the current status of the EbolaCheck platform is discussed in the context of the current regulatory framework. Presented here are future goals to achieve differential diagnosis of hemorrhagic fever disease from <5-μl of whole blood samples or mucosal biofluids, in a single tube process, under 40 min and with minimal operator training requirements.

Diagnostic et traitement des infections d'implants orthopédiques [Update on implant related infections in orthopaedic surgery. Diagnosis and treatment]

Infections associated with implants are increasingly important in modem medicine. Biofilms are the cause that these infections are more difficult to diagnose and to cure. Particularly low-grade infections are difficult to distinguish from aseptic failure, because they often present with early loosening and persisting pain. For an accurate diagnosis, clinical signs and symptoms, laboratory markers of infection, microbiology, histology and imaging examinations are needed. The treatment goal is eradication of infection and an optimal functional result. Successful treatment requires adequate surgical procedure combined with long-term antimicrobial therapy, ideally with an agent acting on biofilms.

Microbial diagnosis of bloodstream infection: towards molecular diagnosis directly from blood.

When a bloodstream infection (BSI) is suspected, most of the laboratory results-biochemical and haematologic-are available within the first hours after hospital admission of the patient. This is not the case for diagnostic microbiology, which generally takes a longer time because blood culture, which is to date the reference standard for the documentation of the BSI microbial agents, relies on bacterial or fungal growth. The microbial diagnosis of BSI directly from blood has been proposed to speed the determination of the etiological agent but was limited by the very low number of circulating microbes during these paucibacterial infections. Thanks to recent advances in molecular biology, including the improvement of nucleic acid extraction and amplification, several PCR-based methods for the diagnosis of BSI directly from whole blood have emerged. In the present review, we discuss the advantages and limitations of these new molecular approaches, which at best complement the culture-based diagnosis of BSI.

Time misalignments in fault detection and diagnosis

El desalineamiento temporal es la incorrespondencia de dos señales debido a una distorsión en el eje temporal. La Detección y Diagnóstico de Fallas (Fault Detection and Diagnosis-FDD) permite la detección, el diagnóstico y la corrección de fallos en un proceso. La metodología usada en FDD está dividida en dos categorías: técnicas basadas en modelos y no basadas en modelos. Esta tesis doctoral trata sobre el estudio del efecto del desalineamiento temporal en FDD. Nuestra atención se enfoca en el análisis y el diseño de sistemas FDD en caso de problemas de comunicación de datos, como retardos y pérdidas. Se proponen dos técnicas para reducir estos problemas: una basada en programación dinámica y la otra en optimización. Los métodos propuestos han sido validados sobre diferentes sistemas dinámicos: control de posición de un motor de corriente continua, una planta de laboratorio y un problema de sistemas eléctricos conocido como hueco de tensión.

Simple telemedicine for developing regions: Camera phones and paper-based microfluidic devices for real-time, off-site diagnosis

This article describes a prototype system for quantifying bioassays and for exchanging the results of the assays digitally with physicians located off-site. The system uses paper-based microfluidic devices for running multiple assays simultaneously, camera phones or portable scanners for digitizing the intensity of color associated with each colorimetric assay, and established communications infrastructure for transferring the digital information from the assay site to an off-site laboratory for analysis by a trained medical professional; the diagnosis then can be returned directly to the healthcare provider in the field. The microfluidic devices were fabricated in paper using photolithography and were functionalized with reagents for colorimetric assays. The results of the assays were quantified by comparing the intensities of the color developed in each assay with those of calibration curves. An example of this system quantified clinically relevant concentrations of glucose and protein in artificial urine. The combination of patterned paper, a portable method for obtaining digital images, and a method for exchanging results of the assays with off-site diagnosticians offers new opportunities for inexpensive monitoring of health, especially in situations that require physicians to travel to patients (e.g., in the developing world, in emergency management, and during field operations by the military) to obtain diagnostic information that might be obtained more effectively by less valuable personnel.

Online motor fault detection and diagnosis using a hybrid FMM-CART model

In this brief, a hybrid model combining the fuzzy min-max (FMM) neural network and the classification and regression tree (CART) for online motor detection and diagnosis tasks is described. The hybrid model, known as FMM-CART, exploits the advantages of both FMM and CART for undertaking data classification and rule extraction problems. To evaluate the applicability of the proposed FMM-CART model, an evaluation with a benchmark data set pertaining to electrical motor bearing faults is first conducted. The results obtained are equivalent to those reported in the literature. Then, a laboratory experiment for detecting and diagnosing eccentricity faults in an induction motor is performed. In addition to producing accurate results, useful rules in the form of a decision tree are extracted to provide explanation and justification for the predictions from FMM-CART. The experimental outcome positively shows the potential of FMM-CART in undertaking online motor fault detection and diagnosis tasks.

Validation of DNA methylation biomarkers for diagnosis of acute lymphoblastic leukemia

DNA methylation biomarkers capable of diagnosis and subtyping have been found for many cancers. Fifteen such markers have previously been identified for pediatric acute lymphoblastic leukemia (ALL). Validation of these markers is necessary to assess their clinical utility for molecular diagnostics. Substantial efficiencies could be achieved with these DNA methylation markers for disease tracking with potential to replace patient-specific genetic testing.

Motor fault detection and diagnosis using a hybrid FMM-CART model with online learning

In this paper, a hybrid online learning model that combines the fuzzy min-max (FMM) neural network and the Classification and Regression Tree (CART) for motor fault detection and diagnosis tasks is described. The hybrid model, known as FMM-CART, incorporates the advantages of both FMM and CART for undertaking data classification (with FMM) and rule extraction (with CART) problems. In particular, the CART model is enhanced with an importance predictor-based feature selection measure. To evaluate the effectiveness of the proposed online FMM-CART model, a series of experiments using publicly available data sets containing motor bearing faults is first conducted. The results (primarily prediction accuracy and model complexity) are analyzed and compared with those reported in the literature. Then, an experimental study on detecting imbalanced voltage supply of an induction motor using a laboratory-scale test rig is performed. In addition to producing accurate results, a set of rules in the form of a decision tree is extracted from FMM-CART to provide explanations for its predictions. The results positively demonstrate the usefulness of FMM-CART with online learning capabilities in tackling real-world motor fault detection and diagnosis tasks. © 2014 Springer Science+Business Media New York.

Frequency of Blastocystis hominis and other intestinal parasites in stool samples examined at the Parasitology Laboratory of the School of Pharmaceutical Sciences at the São Paulo State University, Araraquara

Blastocystis hominis é um protozoário, causador de infecção intestinal denominada blastocistose humana, cujo diagnóstico é realizado pelo exame coproparasitológico e por meio de técnicas de coloração permanente. Este estudo foi desenvolvido para avaliar a freqüência da infecção por Blastocystis hominis em habitantes da região de Araraquara/SP, bem como comparar diferentes métodos para a pesquisa desse protozoário em amostras de fezes. Foram estudadas 503 amostras de fezes submetidas ao exame direto a fresco, às técnicas de Faust e cols, Lutz e de Rugai e cols, além das colorações pela hematoxilina férrica, tricrômio e de Kinyoun modificada. Entre as 503 amostras examinadas, 174 (34,6%) apresentaram-se positivas para a presença de parasitas intestinais. O protozoário e o helminto mais freqüentes foram Entamoeba coli (14,6%) e Strongyloides stercoralis (6,7%), respectivamente. Blastocystis hominis foi observado em 23 (4,6%) amostras fecais com consistência predominantemente pastosa, não caracterizando quadro diarréico. Apesar da baixa freqüência de Blastocystis hominis encontrada na região de Araraquara, comparativamente a outras regiões brasileiras, é importante a realização do diagnóstico laboratorial desse protozoário. O encontro de Blastocystis hominis em material fecal é indicativo de contaminação de alimentos e água de consumo, desde que se admita a rota de transmissão oral-fecal desse parasita, o que implica na orientação da população sobre as medidas de saneamento básico e higiene como meio para se controlar problemas de saúde ocasionados pelos enteroparasitas.