Differential Diagnostic Tool Research Articles

Postural responses to low-intensity, short-duration, galvanic vestibular stimulation as a possible differential diagnostic procedure

In this study we investigated the effect of polarity-related differences in short-duration very low-intensity galvanic vestibular stimulation (GVS), not perceived by the subject, by evaluating the minimal postural sway responses in healthy people. We also verified its possible usefulness as a differential diagnostic tool in patients with postural instability disturbances related to polyneuropathy or peripheral vertigo. We applied bimastoid opposite polarity direct current GVS (0.7 mA for 1 s) and recorded the induced postural response with an electromagnetic head position tracker. Latency, amplitude, velocity and an asymmetry index were measured between two reverse polarity sessions. The postural response was easily recorded and was statistically wider in amplitude and velocity in the polyneuropathy group than in the other groups. Postural responses were asymmetric only in the group with mild peripheral vertigo. These findings suggest that even weak GVS affects vestibular excitability: cathodal polarization increases whereas anodal GVS decreases excitability. Symmetry and amplitude or velocity of the postural responses, particularly in the eyes closed condition, can differentiate the three groups of subjects tested.

Recent Progress in the Management of Pulmonary Hypertension

Pulmonary hypertension (PH) is a fatal disease caused by small pulmonary artery obstruction from vascular proliferation and remodeling. PH is characterized by elevated pulmonary arterial pressure and increased pulmonary vascular resistance, frequently leading to right-sided heart failure and death. The classification of PH has been recently updated to include 5 major categories of the disorder, are as: Group 1, pulmonary arterial hypertension (PAH); Group 2, PH due to left heart disease; Group 3, PH due to lung diseases and/or hypoxia; Group 4, chronic thromboembolic PH (CTEPH); and Group 5, others. Recently, significant progress has been made in the understanding of the pathophysiology, diagnosis and treatment of PH. Regarding the pathophysiology of the disorder, direct evidence for Rho-kinase activation in the pulmonary artery from PAH patients has been provided. Regarding diagnosis, optical coherence tomography is useful as a new differential diagnostic tool for distal type CTEPH vs. PAH. Regarding treatment, in addition to the conventional therapy, several new drugs are under clinical trial, including fasudil (a Rho-kinase inhibitor), riosiguat (a soluble guanylate cyclase activator), and imatinib (a tyrosine kinase inhibitor). In addition, pulmonary angioplasty and intensive immunosuppressive therapy may be effective for CTEPH and connective tissue disease-associated PAH, respectively. We briefly review the recent progress in the management of PH.

Development of a real time PCR taqman assay based on the TPI gene for simultaneous identification of Clostridium chauvoei and Clostridium septicum

In the present study, a Taqman allelic discrimination assay based on three SNPs of the TPI gene is described. It was used as a differential diagnostic tool to detect blackleg and malignant edema. Sudden deaths of grazing ruminants, such as cattle, sheep and goats, which show clinical signs related to hyperacute infective processes, encouraged the development of a rapid and precise diagnostic molecular method. Specific primers and probes for Clostridium septicum and Clostridium chauvoei were designed on the basis of the TPI gene sequence. The multiplex PCR was tested on the DNA of a total of 57 strains, including 24 Clostridium chauvoei, 20 Clostridium septicum, 1 Bacillus anthracis and 12 other Clostridium spp. The DNA samples from Clostridium chauvoei and Clostridium septicum strains were amplified. Amplification of other DNA samples was not observed, with the exception of Clostridium tertium, which showed a weak positive signal. To avoid misdiagnosis, a confirmatory assay based on a Sybr green real time PCR was proposed. The authors confirmed the efficacy and the specificity of the test used in this study, which proved to be a useful tool for the diagnosis of clostridiosis that are often diagnosed using only traditional tools.

Stroke scans and radiation risk

Stroke scans and radiation risk

Recent developments in innervation imaging using iodine-123-metaiodobenzylguanidine scintigraphy in Lewy body diseases

Radiolabeled metaiodobenzylguanidine (MIBG) is an analog of guanethidine and is taken up by the postganglionic presynaptic nerve endings. MIBG uptake in the heart correlates with adrenergic function, which can be reduced in Lewy body diseases. We described the recent developments in innervation imaging using (123)I-MIBG scintigraphy in Lewy body diseases including Parkinson's disease and dementia with Lewy bodies. Particularly, we underlined the role of MIBG scintigraphy in differential diagnosis of movement disorders. As described by recent studies, MIBG scintigraphy is a valuable diagnostic tool for differentiation between Lewy body diseases and parkinsonian syndromes or other movement disorders with parkinsonism. Furthermore, this method may provide a powerful differential diagnostic tool between dementia with Lewy bodies and Alzheimer's disease. We also reported the results of clinical investigations about the correlation between characteristics of Parkinson's disease and myocardial MIBG uptake.

Expression of Galectin-3 in Renal Neoplasms: A Diagnostic, Possible Prognostic Marker

Galectin-3, a member of the lectin family, was shown to be expressed in normal distal tubular cells and in renal cell carcinomas (RCC). However, its diagnostic and prognostic significance in RCC is as yet undefined. To describe the expression of Galectin-3 among different histologic subtypes of renal neoplasms and to determine their diagnostic and prognostic significances. The expression of Galectin-3 was evaluated in 217 renal neoplasms by tissue microarray and immunohistochemistry with semiquantitative analysis. Strong expression of Galectin-3 was observed in 92 of 217 of renal neoplasms (42.4%). Although 22 of 23 oncocytomas (95.7%) and 19 of 21 chromophobe RCCs (90.5%) express Galectin-3, only 4 of 32 papillary RCCs (12.5%) and 47 of 137 clear cell RCCs (34.3%) express Galectin-3, suggesting that it may be used as a potential diagnostic marker. Galectin-3 expression was seen in 55% of high-grade (Fuhrman nuclear grades 3 and 4) versus 21% low-grade (grades 1 and 2) clear cell RCCs (P < .001). This study confirms that Galactin-3 is strongly overexpressed in renal cell neoplasms of distal tubular differentiation, that is, oncocytoma and chromophobe RCCs, suggesting it might be used as a possible differential diagnostic tool for renal cell neoplasm with oncocytic or granular cells. Furthermore, we observed a strong association of overexpression of Galectin-3 and high nuclear grade in clear cell RCC. These results also suggest a possible pivotal role for Galectin-3 in the differentiation and prognosis of clear cell RCC.

Positron Emission Tomography in Alzheimer‘s Disease: Early Prediction and Differentiation

The development of biomarkers for the preclinical detection of neurodegenerative diseases such as Alzheimer’s disease (AD) is a vital step in developing prevention therapies. One consistent feature of AD is a reduction in the cerebral metabolic rate of glucose (CMRglc), a measure of neuronal function. In vivo brain 2-[18F]fluoro-2-deoxy-D-glucose-PET imaging demonstrates consistent and progressive CMRglc reductions in AD patients, the extent and topography of which correlate with symptom severity. There is increasing evidence that CMRglc reductions occur at the preclinical stages of AD and predict decline years in advance of clinical symptoms. This review will give an overview of FDG-PET results in individuals at risk for developing dementia, including: presymptomatic individuals carrying mutations responsible for early-onset familial AD; patients with mild cognitive impairment, often a prodrome to late-onset sporadic AD; nondemented carriers of the ApoE ε4 allele, a strong genetic risk factor for late-onset AD; cognitively normal subjects with a family history of AD; subjects with subjective memory complaints; and normal elderly who were followed longitudinally until they expressed the clinical symptoms and later received postmortem confirmation of AD. We will then review the most recent studies using FDG-PET as an early differential diagnostic tool in AD.

Folicular and Diffuse Large B Cell Lymphoma Can Be Distinguished by 1H -Magnetic Resonance Spectroscopy.

Proton nuclear magnetic resonance spectroscopy (1H MRS) has proven useful in the metabolic characterization of neoplastic tissues both in vitro and in vivo. In vivo 1H MRS can be easily performed in conjunction with conventional MR imaging. Although 1H MRS studies of lymphoma have been performed both in cell lines and animal models, its usefulness as a differential diagnostic tool in lymphoma remains to be explored. T2-filtered high resolution proton magic-angle spinning (HRMAS) MRS of small tissue samples provides sufficient spectral resolution for the identification of chemical cell changes associated with malignancy. HRMAS data from 16 fresh frozen lymph nodes were studied. Histologically, 7 lymph nodes revealed grade I or II follicular lymphoma (FL) and 9 showed diffuse large B cell lymphoma (DLBCL). Each spectrum consisted of the accumulation of 64 scans with a CPMG sequence with an effective T2 delay of 32 ms and an overall experimental time of 6 minutes. Pattern recognition analysis was feasible in all cases except in one FL sample consisting almost exclusively of adipose tissue. Compared with DLBCL, FL cases showed increases in the signal intensity of resonances associted to taurine (3.43 ppm) and decreases in the signal intensity of resonances associated to alanine (1.47 ppm). The mean taurine/alanine ratio was 4.63 (95%SD 1.67) for FL and 1.41 (95%SD 0.69) for DLBCL (P = 0.004). The taurine/alanine ratio proved to be a powerful discriminator between FL and DLBCL at a 2.5 cutpoint, yelding a 90% specificity and an 83% sensitivity to identify DLBCL. Overlapping cases included a case of FL with a diffuse pattern and two cases of DLBCL evolving from indolent lymphomas. The 1H MRS assay proved that FL and DLBCL can be differentiated from a metabolomic standpoint and offers a unique way to explore the underlying biochemistry of malignant transformations. Unlike other techniques, MRS is potentially applicable in vivo and non-invasively in the diagnostic setting. The rapid assessment of nodes or masses before tissue sampling would allow preoperative decisions to be made more efficiently.

The Role of 123I-Metaiodobenzylguanidine Myocardial Scintigraphy in the Diagnosis of Lewy Body Disease in Patients with Dementia in a Memory Clinic

Reduction in cardiac ¹²³I-metaiodobenzylguanidine (MIBG) uptake is a characteristic feature of Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), and is useful in distinguishing them from other neurodegenerative disorders. The aim of this study was to investigate the role of this method of scintigraphy in the differential diagnosis of dementia in our Memory Clinic. We performed MIBG scintigraphy in patients with dementia referred to the Memory Clinic and compared the heart-to-mediastinum (H/M) ratio of MIBG uptake. Thirty out of 32 patients with DLB and all 9 PD with dementia patients had reduced H/M ratios, whereas 37 out of 40 patients with Alzheimer’s disease had normal H/M ratios. Most patients with vascular dementia, frontotemporal dementia, and other dementias had normal H/M ratios. The overall sensitivity to positively identify patients with Lewy body disease (including DLB and PD with dementia) was 95%, and the specificity to distinguish them from patients with other types of dementias was 87%. MIBG scintigraphy showed a high sensitivity for the detection of Lewy body disease, and also a high specificity for discrimination from other types of dementia. The scintigraphy may provide a valuable and adjunctive method in the diagnosis of Lewy body disease and a differential diagnostic tool for patients with dementias.

Novel Approach for Differential Diagnosis of HIV Infections in the Face of Vaccine-Generated Antibodies

Because increasing numbers of HIV vaccine candidates are being tested globally, it is essential to differentiate vaccine- from virus-induced antibodies. Most of the currently tested vaccines contain multiple viral components. As a result, many vaccine recipients give positive results in FDA-licensed HIV serodetection tests. We have identified conserved sequences in Env-gp41 and Gag-p6, which are recognized soon after infection but are not included in most HIV vaccine candidates. A new HIV serodetection assay, the HIV-SELECTEST, was established that distinguishes between vaccine-induced antibodies and seroconversion due to true HIV infections. It is important to make this assay globally relevant, because many clinical trials are conducted around the world where most HIV infections are due to non-B subtype HIV-1. Therefore, the current study examined the reactivity of plasma samples from >3,000 infections with diverse HIV subtypes worldwide. The HIV-SELECTEST performed at >99% specificity and sensitivity. Both recent and established infections with clades A, B, C, D, E, F, G, J, and CRFs were detected. Antibodies elicited by other vaccinations or infections endemic to the clinical trial sites did not react in this assay. Therefore, HIV-SELECTEST could be an important differential diagnostic tool for HIV vaccine trials, blood banks, and population screening worldwide.

Clinical relevance of antibodies against myelin oligodendrocyte glycoprotein in different clinical types of multiple sclerosis

Objective Myelin oligodendrocyte glycoprotein (MOG) is a highly immunogenic minor component on the outside surface of CNS myelin which is believed to be one of the autoantigens in multiple sclerosis. The aim of this study was to evaluate the diagnostic potential of anti-MOG IgG antibody levels in cerebrospinal fluid (CSF) and serum of patients with relapsing-remitting multiple sclerosis (RRMS), primary progressive multiple sclerosis (PPMS) and non-inflammatory neurological diseases (NIND) as markers for the different clinical types of multiple sclerosis. Patients and methods Consecutive serum and cerebrospinal fluid samples were taken from 21 patients with RRMS, 7 patients with PPMS and 19 patients with NIND. The antibody responses to MOG were determined in paired samples of these differrent clinical groups by enzyme-linked immunoassay using a recombinant human MOG protein. Results The performed analysis indicated that the differences in levels of anti-MOG IgG antibody in serum and cerebrospinal fluid from the patients with RRMS, PPMS or NIND were not statistically significant. Conclusion The assay is not sensitive or specific enough to be used as a differential diagnostic tool for the clinical types of MS, nor for MS itself.

Sequence analysis and distribution of an IS3-like insertion element isolated from Salmonella enteritidis.

The nucleotide sequence of a 3 kb region immediately upstream of the sef operon of Salmonella enteritidis was determined. A 1230 base pair insertion sequence which shared sequence identity (> 75%) with members of the IS3 family was revealed. This element, designated IS1230, had almost identical (90% identity) terminal inverted repeats to Escherichia coli IS3 but unlike other IS3-like sequences lacked the two characteristic open reading frames which encode the putative transposase. S. enteritidis possessed only one copy of this insertion sequence although Southern hybridisation analysis of restriction digests of genomic DNA revealed another fragment located in a region different from the sef operon which hybridised weakly which suggested the presence of an IS1230 homologue. The distribution of IS1230 and IS1230-like elements was shown to be widespread amongst salmonellas and the patterns of restriction fragments which hybridised differed significantly between Salmonella serotypes and it is suggested that IS1230 has potential for development as a differential diagnostic tool.

Comparative value of brain perfusion SPECT and [123I]MIBG myocardial scintigraphy in distinguishing between dementia with Lewy bodies and Alzheimer’s disease

Both decreased occipital perfusion on brain single-photon emission computed tomography (SPECT) and reduction in cardiac (123)I-metaiodobenzylguanidine (MIBG) uptake are characteristic features of dementia with Lewy bodies (DLB), and potentially support the clinical diagnosis of DLB. The aim of this study was to compare the diagnostic value of these two methods for differentiation of DLB from Alzheimer's disease (AD). The study population comprised 19 patients with probable DLB and 39 patients with probable AD who underwent both SPECT with N-isopropyl-p-[(123)I]iodoamphetamine and MIBG myocardial scintigraphy. Objective and quantitative measurement of perfusion in the medial occipital lobe, including the cuneus and lingual gyrus, was performed by the use of three-dimensional stereotactic surface projections. Medial occipital perfusion was significantly decreased in the DLB group compared with the AD group. The mean heart/mediastinum ratios of MIBG uptake were significantly lower in the DLB group than in the AD group. Although SPECT failed to demonstrate significant hypoperfusion in the medial occipital lobe in five patients with DLB, marked reduction of MIBG uptake was found in all patients with DLB. Receiver operating characteristic analysis revealed that MIBG myocardial scintigraphy enabled more accurate discrimination between DLB and AD than was possible with perfusion SPECT. MIBG myocardial scintigraphy may improve the sensitivity in the detection of DLB. In particular, this method may provide a powerful differential diagnostic tool when it is difficult to distinguish cases of DLB from AD using brain perfusion SPECT.

Initial otolaryngological manifestations of severe acute respiratory syndrome in Taiwan.

To provide a clue for screening severe acute respiratory syndrome (SARS), a highly transmissible disease with health care workers at particular risk, in the early stage from an otolaryngological perspective. Prospective study. Community hospital. Between April 17 and April 26, 2003, 32 consecutive patients with SARS were encountered. Investigation consisted of local examination of ear, nose, and throat fields; palpation of the nuchal areas; and plain chest radiography. Analyses of throat swab samples using reverse transcription-polymerase chain reaction were conducted. Clinical manifestations included fever in 31 patients (97%), followed by cough, dyspnea, chill, headache, sore throat, diarrhea, rhinorrhea, and otalgia. Neither the pharyngeal wall nor the tonsillar area demonstrated hyperemia. There was no lymphadenopathy in the neck. Plain chest radiographs revealed consolidation in 25 (78%) of 32 patients. Results of reverse transcription-polymerase chain reaction analysis targeting the novel coronavirus present in throat swab samples were positive in 19 (66%) of 29 patients tested. Twenty-eight patients required supplemental oxygen, and 14 patients were intubated with mechanical ventilation. Twenty-eight patients survived and 4 patients died. When presented with a patient with flulike symptoms such as fever and/or cough, but no pharyngeal hyperemia or neck lymphadenopathy, physicians should be alerted to the possibility of SARS. In contrast, evidence of inflammatory signs in the otolaryngological field may explain the flulike symptoms, and serve as a differential diagnostic tool between influenza and SARS.

Measuring the impact of diagnostic decision support on the quality of clinical decision making: development of a reliable and valid composite score

ObjectiveFew previous studies evaluating the benefits of diagnostic decision support systems have simultaneously measured changes in diagnostic quality and clinical management prompted by use of the system. This report describes a reliable and valid scoring technique to measure the quality of clinical decision plans in an acute medical setting, where diagnostic decision support tools might prove most useful. DesignSets of differential diagnoses and clinical management plans generated by 71 clinicians for six simulated cases, before and after decision support from a Web-based pediatric differential diagnostic tool (ISABEL), were used. MeasurementsA composite quality score was calculated separately for each diagnostic and management plan by considering the appropriateness value of each component diagnostic or management suggestion, a weighted sum of individual suggestion ratings, relevance of the entire plan, and its comprehensiveness. The reliability and validity (face, concurrent, construct, and content) of these two final scores were examined. ResultsTwo hundred fifty-two diagnostic and 350 management suggestions were included in the interrater reliability analysis. There was good agreement between raters (intraclass correlation coefficient, 0.79 for diagnoses, and 0.72 for management). No counterintuitive scores were demonstrated on visual inspection of the sets. Content validity was verified by a consultation process with pediatricians. Both scores discriminated adequately between the plans of consultants and medical students and correlated well with clinicians' subjective opinions of overall plan quality (Spearman ρ 0.65, p<0.01). The diagnostic and management scores for each episode showed moderate correlation (r=0.51). ConclusionThe scores described can be used as key outcome measures in a larger study to fully assess the value of diagnostic decision aids, such as the ISABEL system.

A multiplex polymerase chain reaction for a differential diagnosis of Plasmodium falciparum and Plasmodium vivax

A multiplex PCR was designed for the differential diagnosis of the two parasite species by targeting the 18S rRNA gene with a set of primer combinations, amplifying DNA fragments of 1451-bp and 833-bp for P. falciparum and P. vivax, respectively. The sensitivity of this PCR test was high, as minimal as 0.1 parasite per one microliter of blood sample and a minimum of four copies of the target gene could be detected. For the diagnosis of mixed infection of two Plasmodium spp., there were no apparent competition or cross-reaction between the majority and minority Plasmodium species. The multiplex PCR was evaluated on 210 clinical samples and 60 normal controls. The PCR test yielded highly concordant results with microscopic examination, with the only one exception of a mixed ( P. falciparum plus P. vivax) infection case, which was diagnosed as a single infection of P. falciparum by microscopy. We propose that the multiplex PCR is a sensitive, specific, and rapid tool that can serve as a useful differential diagnostic tool for detecting P. falciparum and P. vivax.

ISABEL: a web-based differential diagnostic aid for paediatrics: results from an initial performance evaluation

Aims: To test the clinical accuracy of a web based differential diagnostic tool (ISABEL) for a set of case histories collected during a two stage evaluation. Methods: Setting: acute paediatric...

Low prevalence of GAD and IA2 antibodies in schoolchildren from a village in the southwestern section of The Netherlands

Glutamic acid decarboxylase (GAD) and insulinoma antigen 2 (IA2) antibodies are increasingly used as a tool to predict type I diabetes in children and as a differential diagnostic tool to distinguish type I and type II diabetes in adults. However, the background frequency of these antibodies in the general population has not been extensively studied and may differ between countries. The current study aims to establish the frequency of GAD and IA2 antibodies in an unselected population of schoolchildren and confirm the previously reported low prevalence of islet cell antibodies (ICA) in the general Dutch population. The study population consisted of 1403 unselected schoolchildren. All children were tested for GAD antibodies, and 1085 children were analyzed for IA2 antibodies by radiobinding assay. Development of diabetes was recorded during a 7-year follow-up. Five children (0.4%) were positive for GAD antibodies, one child (0.1%) was positive for IA2 antibodies. Two children developed diabetes during follow-up, one was positive for GAD antibodies only, the second was positive for both GAD and IA2 antibodies. The frequency of GAD and IA2 antibodies in the southwestern part of The Netherlands is low. This observation is in concordance with earlier studies on ICA in Dutch schoolchildren. For future diabetes prediction and intervention trials it is important to establish the background frequencies and predictive power of antibody screening in different populations.

Sangramento uterino disfuncional

Baseado em longa experiência clínica, o autor faz uma análise crítica da terminologia e conceituação das perdas sangüíneas uterinas irregulares. Destaca a freqüente confusão acadêmica entre os termos sangramento uterino disfuncional e sangramento uterino anormal, o que gera discussões acerca do diagnóstico e tratamento destas patologias. Procura racionalizar e simplificar a investigação clínica, enfatizando os recursos disponíveis em qualquer serviço ou consultório. Para tal, procura responder basicamente a duas questões: 1) O sangramento é de causa orgânica ou endócrina? 2) Se for de causa endócrina, é ovulatório ou anovulatório? Da mesma forma, limita o tratamento a dois ou três esquemas simples e eficazes, que funcionam também como diagnóstico diferencial ou tratamento de prova, pois, se um esquema racional, baseado no conhecimento da fisiopatologia do processo, não corrigir o sangramento, ele certamente não terá uma causa endócrina. Este fato nos obrigará a aprofundar a nossa propedêutica para identificar a causa orgânica.

Head Tilt Suppression Test as a Differential Diagnostic Tool in Vertiginous Patients

The head tilt suppression test has been known to be a diagnostic tool to distinguish between centrally originating dizziness and peripheral vertigo, as the latter enhances the natural spontaneous firing rate of the velocity storage system and decreases the time constant; however, the otolith organ is now considered to be a cause of head tilting effect. Therefore we questioned whether the head tilt suppression test is still worth differential diagnostic tool. We measured the time constant and initial eye velocity of pre- and post-rotatory nystagmus in a velocity step test in nine healthy adults. The time constant was significantly affected by head tilting ( p = 0.001), pre- and post-rotatory nystagmus ( p = 0.020) and the compounding interaction between them ( p < 0.000). The initial eye velocity was also significantly affected by pre- and post-rotatory nystagmus ( p = 0.016) and the compounding interaction ( p < 0.000), but not by head tilting (Wilks' Lambda=0.054). The head tilt suppression test is a useful method for the differential diagnosis of vertiginous patients. It is affected by pre- and post-rotatory nystagmus and their interaction, however, other central parameters in vestibular function testing should also be considered in order to obtain an exact differential diagnosis.