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Reliability and validity of the Newcastle Scales in relation to ICD-9-classification.

The assessment of endogenous depression by means of the Newcastle Scales (1965, 1971) has been validated by their correlation with biological findings in many previous studies. However, reliability and cross validation studies are lacking for these scales. We found the reliability of the Newcastle Scales to be sufficient or at least moderate in a sample of 70 inpatients with major depression. In order to cross validate both scales, the clinical classification according to ICD-9 and the assessment of the Newcastle Scales have been performed independently in a sample of 112 inpatients with Major Depressive Disorder (RDC). The rate of agreement between clinical diagnosis and classification according to the Newcastle Scales of endogenous depression is only fair. However, a modification of the diagnostic algorithm applied to the items of the Newcastle Scales I (1965) improves the rate of agreement considerably. The Newcastle Scale I turned out to represent a heterogenous concept without sufficient transferability. Modifications of both scales are proposed.

Adult↗

Role of ultrasound-guided core biopsy in the evaluation of spleen pathology.

Core biopsy has not traditionally been recommended in the study of spleen nodules due to the supposed fragility of this organ leading to a high risk of post-core biopsy complications. A total of 13 patients who presented solid spleen nodules, diffuse splenomegaly, or both on imaging studies (CT, MR, US) were biopsied under ultrasound control with 18G BioPince needles. Cytological (imprints and cytocentrifugates) and histological material were obtained for diagnosis in every case. Malignant lymphomas were the most commonly found pathology (four diffuse large B-cell lymphomas, two follicular lymphomas, one Hodgkin's disease, one B-cell lymphoma, NOS). In addition, there was one littoral-cell angioma, one well-differentiated neuroendocrine carcinoma, metastatic, and one haemangioma. The remaining two cases showed congestive features, and supposed spleen involvement by lymphoma in one of them was ruled out. On follow up, there were no complications related to the core biopsy. Splenectomy was performed in six cases, two diagnostic and four therapeutic. We conclude that core biopsy is a safe and efficient method in the diagnosis of spleen nodules that could be considered in the routine diagnostic algorithm of these lesions.

Adult↗

Flow-cytometric approach to the prompt laboratory diagnosis of TRALI: a case report.

OBJECTIVES: Transfusion-related acute lung injury (TRALI) is a rare but serious complication which can occur after transfusion of blood components. In this report we describe our flow-cytometry approach to the laboratory diagnosis of a case of TRALI in a recipient of fresh frozen plasma containing human leukocyte antigen (HLA) class II antibodies. METHODS: The post-transfusion reaction work-up included the direct and indirect Granulocyte Immunofluorescence Test (GIFT) on the recipient's neutrophils collected before and after the reaction and on the serum from the recipient and from all implicated donors; flow-cytometry bead-based screening and identification assay for HLA class I and II antibodies in donor sera and flow cytometry cross-matching on T and B patient's lymphocytes. Finally, we investigated the reactivity of one donor serum, containing HLA class II antibodies, with the patient's neutrophils activated in vitro to induce expression of HLA class II. RESULTS: We found an increased level of IgG bound on patient's granulocytes collected after TRALI, in the absence of detectable granulocyte and HLA class I antibodies in the five implicated donors. One of them showed HLA-DR 1 and -DR 51 antibodies, which determined a positive cross-match with patient's B lymphocytes and in vitro activated granulocytes. Both HLA class II antigens were present in the recipient and absent in the donor. CONCLUSIONS: In some pathological conditions, HLA class II antibodies can react with activated granulocytes expressing HLA-DR antigens, and activate TRALI reaction. HLA class II antibodies screening and flow cytometry cross-matching techniques should be added to the current diagnostic algorithm of TRALI.

Aged↗

Report: workshop on mediastinal grey zone lymphoma.

There are several indications that classical Hodgkin lymphoma (cHL) and at least a proportion of cases of Primary Mediastinal B cell Lymphoma (PMBL) are derived from B cells at similar stages of differentiation and share common pathogenic mechanisms. The first indication was the existence of mediastinal grey zone lymphomas as identified in the 4th International Symposium on HL, with clinical, histological and immunohistochemical features intermediate between cHL and PMBL. Second, both tumor types resemble a cell that is developmentally situated in-between the germinal center reaction and a plasma cell. Third, cHL and PMBL were found to have similar gene expression profiles, including the lack of immunoglobulin expression and low levels of B cell receptor signalling molecules, and the secretion of molecules like the chemokine TARC and the prominent expression of IL-13 receptors. Fourth, both entities were found to have common genomic aberrancies, notably in 2p15 and 9p24, the sites of the REL oncogene and the tyrosine kinase gene JAK2, respectively. Further comparison of both lymphoma types may provide further insight in the pathogenic mechanisms and allow the design of diagnostic algorithms to sort out the small number of so-called mediastinal grey zone lymphomas, that appear to be intermediate between PMBL and cHL.

B-Lymphocytes↗

Differential diagnosis of jaundice: a pocket diagnostic chart.

Based on extensive clinical and clinical chemical information (107 different items) from 1002 jaundiced patients, we developed a diagnostic algorithm which was evaluated on a test sample of another 110 jaundiced patients. A primary classification into categories of obstructive jaundice (probability of obstruction greater than or equal to 0.80), non-obstructive jaundice (probability of obstruction less than or equal to 0.20), and of doubtful causes of jaundice (probability of obstruction: 0.20-0.80) was attempted. Among 234 patients in the data base who were classified as obstructive, 220 (94%) proved to be so, as did 36 (97%) of 37 in the test sample. The corresponding figures for non-obstructive jaundice were 463 (96%) of 483 patients correctly classified in the data base and 47 (92%) of 51 patients in the test sample. Altogether 69% of the patients in the data base and 75% of those in the test sample were correctly classified, in 27% and 20% the cause of jaundice was doubtful, and only 4% and 5%, respectively, were misclassified. A slight majority of the patients in whom the algorithmic diagnoses were doubtful proved obstructive. A close correlation was found between the preliminary diagnoses made by the algorithm and by the clinicians. A secondary classification of the patients by the algorithm into benign versus malignant causes of obstructive jaundice performed equally well in the data base and the test sample.

Cholestasis↗

Overactive bladder: achieving a differential diagnosis from other lower urinary tract conditions.

Overactive bladder (OAB) is a debilitating condition characterised by an urgent need to urinate (urgency), often with urinary frequency and, in some cases, urgency incontinence and nocturnal frequency. Patients often adopt complex adaptive behaviours to cope with their symptoms as OAB can compromise all dimensions of a patient's quality of life. Most OAB patients present initially to their primary care physician. Diagnosis is based on presenting symptomatology and does not require any invasive tests. Direct questioning about symptoms is important in achieving a differential diagnosis. The most common condition to be considered when working towards a differential diagnosis is a urinary tract infection (UTI). However, some physicians have expressed concerns about identifying the small number of cases where bladder cancer is a potential underlying aetiology for the symptoms of OAB. In this review, we examine the prevalence and patient profiles for these bladder conditions and their presenting symptomatology. We also review tests that may be recommended to exclude a diagnosis of UTI or bladder cancer and present a diagnostic algorithm suitable for office-based primary care practice.

Algorithms↗

Myasthenia gravis: diagnosis and treatment.

PURPOSE: To provide information about myasthenia gravis (MG), including pathophysiology, differential diagnosis, treatments, diagnostic work up, patient teaching, and diagnostic algorithms for ptosis and weakness related to MG. DATA: Clinical and research journal articles, medical textbooks, and a patient with MG. CONCLUSIONS: Myasthenia Gravis is a very complex disease with many different signs and symptoms, which may be quite noticeable or vague. The presenting symptoms of ptosis and/or diplopia should cause the clinician to consider a work-up for MG. IMPLICATIONS FOR PRACTICE: Because of the low incidence MG (1 in 10,000) has in the U.S., a delay in diagnosis of one to two years is not uncommon. It is vital to diagnose this disease and begin treatment as soon as possible to decrease the signs and symptoms.

Humans↗

Constant and variable stiffness and damping of the leg joints in human hopping.

The present study deals with the stiffness and damping profiles of the leg joints during the ground-contact phase of hopping. A two-dimensional (sagittal plane) jumping model, consisting of four linked rigid segments and including the paired feet, shanks, thighs, and the head-arms-trunk segment, was developed. The segments were interconnected by damped torsional springs, representing the action of the muscles, tendons and ligaments across the joint and of the other joint tissues. A regressive function was used to express stiffness and damping, and included second-order dependence on angle and first-order dependence on angular velocity. By eliminating redundancies in the numerical solution using multicollinearity diagnostic algorithms, the model results revealed that the correct and sufficient nonlinearity for the joint stiffness is of the first order. Damping was found negligible. The stiffness profiles obtained were bell-shaped with a maximum near midstance and nonzero edge values. In predicting the joint moments, the obtained variable joint stiffnesses provided a closer agreement compared to a constant stiffness model. The maximal stiffness was found to be in linear correlation with the initial stiffness in each joint, providing support to the of muscles' preactivation strategy during the flight phase of hopping. All stiffnesses increased with increasing hopping frequency. The model presented provides an effective tool for future designing of artificial legs and robots and for the development of more accurate control strategies.

Adult↗

Support vector machine for optical diagnosis of cancer.

We report the application of a support vector machine (SVM) for the development of diagnostic algorithms for optical diagnosis of cancer. Both linear and nonlinear SVMs have been investigated for this purpose. We develop a methodology that makes use of SVM for both feature extraction and classification jointly by integrating the newly developed recursive feature elimination (RFE) in the framework of SVM. This leads to significantly improved classification results compared to those obtained when an independent feature extractor such as principal component analysis (PCA) is used. The integrated SVM-RFE approach is also found to outperform the classification results yielded by traditional Fisher's linear discriminant (FLD)-based algorithms. All the algorithms are developed using spectral data acquired in a clinical in vivo laser-induced fluorescence (LIF) spectroscopic study conducted on patients being screened for cancer of the oral cavity and normal volunteers. The best sensitivity and specificity values provided by the nonlinear SVM-RFE algorithm over the data sets investigated are 95 and 96% toward cancer for the training set data based on leave-one-out cross validation and 93 and 97% toward cancer for the independent validation set data. When tested on the spectral data of the uninvolved oral cavity sites from the patients it yielded a specificity of 85%.

Algorithms↗

In vivo cancer diagnosis with optical spectroscopy and acoustically induced blood stasis using a murine MCa35 model.

Ultrasound-induced blood stasis has been observed for more than 30 years. Most of the literature has been focused on the health risks associated with this phenomenon and methods employed to prevent stasis from occurring during ultrasound imaging. To date, experimental observations have been either in vitro or invasive. The current work demonstrates ultrasound-induced blood stasis in murine normal leg muscle versus tumor-bearing legs, observed through noninvasive measurements of optical spectroscopy, and discusses possible diagnostic uses for this previously undesirable effect of ultrasound. We demonstrate that, using optical spectroscopy, effects of ultrasound can be used to differentiate tumor from normal leg muscle tissue in mice. Finally, we propose a novel diagnostic algorithm that quantitatively differentiates tumor from nontumor with maximum specificity 0.83, maximum sensitivity 0.79, and area under receiver-operating-characteristics curve 0.90.

Animals↗

Differentiation of clinical Mycobacterium tuberculosis complex isolates by gyrB DNA sequence polymorphism analysis.

The discriminatory power of gyrB DNA sequence polymorphisms for differentiation of the species of the Mycobacterium tuberculosis complex (MTBC) was evaluated by sequencing and restriction fragment length polymorphism (RFLP) analysis of a 1,020-bp fragment amplified from clinical isolates of M. tuberculosis, Mycobacterium bovis (pyrazinamide [PZA] resistant as well as PZA susceptible), Mycobacterium africanum subtypes I and II, and Mycobacterium microti types vole and llama. We found sequence polymorphisms in four regions described previously and at one additional position. These differences in the gyrB sequences allow an accurate discrimination of M. bovis, M. microti, and M. africanum subtype I. The PZA-susceptible subtypes of M. bovis shared the M. bovis-specific substitution at position 756 with the PZA-resistant strains, but can be unambiguously differentiated by a characteristic substitution at position 1311. As a drawback, M. tuberculosis and M. africanum subtype II showed an identical gyrB sequence that facilitates discrimination from the other species, but not from each other. A PCR-RFLP technique applying three restriction enzymes could be shown to be a rapid and easy-to-perform tool for the differentiation of the members of the MTBC. Based on these results, we present a clear diagnostic algorithm for the differentiation of species of the MTBC.

Animals↗

Capillary electrophoretic restriction fragment length polymorphism patterns for the Mycobacterial hsp65 gene.

PCR-restriction fragment length polymorphism (RFLP) analysis is a nonprobe method for the rapid identification of Mycobacterium species. We demonstrate the separation of DNA or restriction fragments digested from the mycobacterial gene encoding the 65-kDa heat shock protein (hsp65) by capillary electrophoresis (CE). By using a pair of unlabeled primers, Tb11 and Tb12, and only one restriction enzyme, HaeIII, we investigated a total of 52 reference and clinical strains encompassing 12 Mycobacterium species. The electrophoretic separation of high-resolution CE required <20 min and was capable of identifying fragments as small as 12 bp. A good agreement of measurement was observed between the sizes of restriction fragments resolved by CE, and the real sizes were deduced from the sequence analysis. Distinct differentiations were also well demonstrated between some species and subspecies by an extra HaeIII digestion site. With the advantage of the complete RFLP pattern available from CE, it appears to be more convenient to use an electropherogram rather than performing the cumbersome slab gel electrophoresis plus diagnostic algorithm to identify Mycobacterium species. Beyond the agarose and polyacrylamide gel electrophoresis, high-resolution CE provides an alternative for rapid identification of Mycobacterium species that is feasible for automation and routine use without the need for costly probes.

Bacterial Proteins↗

Diagnosis of and screening for cytomegalovirus infection in pregnant women.

No single diagnostic test for cytomegalovirus (CMV) infection is currently available for pregnant women at all stages of gestation. Improved accuracy in estimating the timing of primary infections can be used to identify women at higher risk of giving birth to congenitally infected infants. A diagnostic algorithm utilizing immunoglobulin G (IgG), IgM, and IgG avidity was used to prospectively screen serum from 600 pregnant women enrolled from two groups: < or =20 weeks gestation (n = 396) or >20 weeks gestation (n = 204). PCR testing of urine and/or blood was performed on all seropositive women (n = 341). The majority (56.8%) of women were CMV IgG seropositive, with 5.5% being also CMV IgM positive. In the IgM-positive women, 1.2% had a low-avidity IgG, indicating a primary CMV infection and a high risk of intrauterine transmission. Two infants with asymptomatic CMV infection were born of mothers who had seroconverted in the second trimester of pregnancy. Baseline, age-stratified CMV serostatus was established from 1,018 blood donors. Baseline seropositivity from a blood donor population increased with age from 34.9% seroprevalence at less than 20 years of age to 72% seroprevalence at 50 years of age. Women at high risk of intrauterine transmission of CMV were identified at all stages of gestation. Women infected with CMV during late gestation may be more likely to transmit the virus, so failure to detect seroconversions in late gestation may result in failure to detect infected neonates.

Adult↗

Internal transcribed spacer sequencing versus biochemical profiling for identification of medically important yeasts.

In this study, we established an in-house database of yeast internal transcribed spacer (ITS) sequences. This database includes medically important as well as colonizing yeasts that frequently occur in the diagnostic laboratory. In a prospective study, we compared molecular identification with phenotypic identification by using the ID32C system (bioMérieux) for yeast strains that could not be identified by a combination of CHROMagar Candida and morphology on rice agar. In total, 113 yeast strains were included in the study. By sequence analysis, 98% of all strains were identified correctly to the species level. With the ID32C, 87% of all strains were identified correctly to the species or genus level, 7% of the isolates could not be identified, and 6% of the isolates were misidentified, most of them as Candida rugosa or Candida utilis. For a diagnostic algorithm, we suggest a three-step procedure which integrates morphological criteria, biochemical investigation, and sequence analysis of the ITS region.

Candida albicans↗

Primary vesicoureteric reflux--how useful is postnatal ultrasound?

The presence or absence of pelvicalyceal dilatation on postnatal ultrasound continues to appear within diagnostic algorithms to select patients for micturating cystourethrography (MCU) in the investigation of antenatally diagnosed hydronephrosis. Postnatal ultrasound findings were assessed in a population diagnosed as having antenatal hydronephrosis due solely to primary vesicoureteric reflux (VUR) to see whether this is justified. The postnatal ultrasound and MCU findings in 177 patients with primary VUR detected as antenatal hydronephrosis were reviewed retrospectively. A total of 132 (75%) were boys. Reflux was unilateral in 103 cases and bilateral in 74 (42%). Altogether 37% of boys and 33% of girls with a renal pelvic diameter of < or = 10 mm had grade III-V VUR. Calyceal and/or ureteric dilatation had specificities of 87-96% for grade III-V VUR, but sensitivities of only 37-54%. Fifty eight per cent of male and 75% of female renal units with grade III VUR and 17% of male units with grade IV-V VUR were normal on ultrasound. Approximately 25% of ultrasonically normal renal units had grade III-V VUR on MCU. Postnatal ultrasound criteria correlate poorly with the presence and degree of VUR in children with antenatally diagnosed hydronephrosis and should not be used to direct the use of cystography.

Female↗

Diagnostic assessment of haemorrhagic rash and fever.

AIMS: To establish criteria for early distinction between meningococcal disease and other conditions with similar clinical features, and to identify other causes for haemorrhagic rashes accompanied by fever. METHODS: In a prospective study, 264 infants and children hospitalised with fever and skin haemorrhages were studied. RESULTS: We identified an aetiological agent in 28%: 15% had meningococcal disease, 2% another invasive bacterial infection, 7% enterovirus infection, and 4% adenovirus infection. Five clinical variables distinguished between meningococcal disease and other conditions on admission: (1) skin haemorrhages of characteristic appearance; (2) universal distribution of skin haemorrhages; (3) maximum diameter of one or more skin haemorrhages greater than 2 mm; (4) poor general condition (using a standardised observation scheme); and (5) nuchal rigidity. If any two or more of these clinical variables were present, the probability of identifying a patient with meningococcal disease was 97% and the false positive rate was only 12%. This diagnostic algorithm did not identify children in whom septicaemia was caused by other bacterial species.

Adenovirus Infections, Human↗

Interrater reproducibility of clinical tests for rotator cuff lesions.

BACKGROUND: Rotator cuff lesions are common in the community but reproducibility of tests for shoulder assessment has not been adequately appraised and there is no uniform approach to their use. OBJECTIVE: To study interrater reproducibility of standard tests for shoulder evaluation among a rheumatology specialist, rheumatology trainee, and research nurse. METHODS: 136 patients were reviewed over 12 months at a major teaching hospital. The three assessors examined each patient in random order and were unaware of each other's evaluation. Each shoulder was examined in a standard manner by recognised tests for specific lesions and a diagnostic algorithm was used. Between-observer agreement was determined by calculating Cohen's kappa coefficients (measuring agreement beyond that expected by chance). RESULTS: Fair to substantial agreement was obtained for the observations of tenderness, painful arc, and external rotation. Tests for supraspinatus and subscapularis also showed at least fair agreement between observers. 40/55 (73%) kappa coefficient assessments were rated at >0.2, indicating at least fair concordance between observers; 21/55 (38%) were rated at >0.4, indicating at least moderate concordance between observers. CONCLUSION: The reproducibility of certain tests, employed by observers of varying experience, in the assessment of the rotator cuff and general shoulder disease was determined. This has implications for delegation of shoulder assessment to nurse specialists, the development of a simplified evaluation schedule for general practitioners, and uniformity in epidemiological research studies.

Adult↗

Epidemiological profile of symptomatic osteoarthritis in older adults: a population based study in Dicomano, Italy.

OBJECTIVES: To assess the prevalence of hand, hip, and knee osteoarthritis (OA) in an older Italian community dwelling population and its association with disability. METHOD: A cross sectional survey of the whole community aged 65 years and over, was carried out in Dicomano, a small rural town in Tuscany, Italy. Subjects were screened by geriatricians for major chronic conditions, including hip, knee, and hand OA, using diagnostic algorithms based on the American College of Rheumatology (ACR) clinical criteria. A rheumatologist examined subjects who screened positive. Disability was assessed by a World Health Organisation questionnaire. RESULTS: 697 of 864 eligible subjects (81% of the eligible population) were screened. OA of the knee, hand, or hip was identified by clinical ACR criteria respectively in 159, 139, and 81 subjects, and was confirmed by the rheumatologist in 158/182 (87%), 75/101 (74%), and 63.2% of cases. The estimated prevalence was 29.8%, 14.9%, and 7.7%, respectively. Only hip OA was significantly associated with disability in basic activities of daily living. CONCLUSIONS: About one third of community dwelling older people are affected by symptomatic peripheral OA. Hip OA was strongly associated with disability.

Activities of Daily Living↗