scholarly journals Resolving a Multi-Generational Neuromuscular Mystery in a Family Presenting with a Variable Scapuloperoneal Syndrome in a c.464G>A, p.Arg155His VCP Mutation

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Nivedita U. Jerath
Keyword(s):  
Genetic Testing ◽  
Clinical Laboratory ◽  
Chronic Neck Pain ◽  
Pain Medication ◽  
Clinical Heterogeneity ◽  
Her Family ◽  
Scapuloperoneal Syndrome ◽  
High Degree ◽  
Work Up ◽  
Normal Work

Valosin containing protein (VCP) mutations have been reported to present with a high degree of variability and can be present in patients even if they may have an initial normal work up. A 55-year-old woman was labeled as “normal” and “pain medication seeking” after an unrevealing work up of clinical, laboratory, electrodiagnostic, radiographic, pathologic, and genetic testing. She continued to present with chronic neck pain, and had variable features of scapuloperoneal atrophy, which was also seen in her family. The patient and her family were found to have a known pathogenic c.464G>A, p.Arg155His (R155H) mutation in the VCP gene. Despite traditional thinking of attempting to localize neurological syndromes, VCP mutations are difficult to localize as they can present with significant clinical heterogeneity including a scapuloperoneal syndrome with variable neuropathic and myopathic features.

scholarly journals How I diagnose and treat splenic lymphomas

Blood ◽  
2011 ◽  
Vol 117 (9) ◽  
pp. 2585-2595 ◽  
Author(s):  
Emilio Iannitto ◽  
Claudio Tripodo
Keyword(s):  
Clinical Laboratory ◽  
Incidental Finding ◽  
Treatment Strategies ◽  
Systemic Diseases ◽  
Clinical Heterogeneity ◽  
Diagnostic Dilemma ◽  
Clinical Behavior ◽  
Lymphoid Malignancies ◽  
Pathologic Features ◽  
High Degree

Abstract The incidental finding of an isolated splenomegaly during clinical assessment of patients evaluated for unrelated causes has become increasingly frequent because of the widespread use of imaging. Therefore, the challenging approach to the differential diagnosis of spleen disorders has emerged as a rather common issue of clinical practice. A true diagnostic dilemma hides in distinguishing pathologic conditions primarily involving the spleen from those in which splenomegaly presents as an epiphenomenon of hepatic or systemic diseases. Among the causes of isolated splenomegaly, lymphoid malignancies account for a relevant, yet probably underestimated, number of cases. Splenic lymphomas constitute a wide and heterogeneous array of diseases, whose clinical behavior spans from indolent to highly aggressive. Such a clinical heterogeneity is paralleled by the high degree of biologic variation in the lymphoid populations from which they originate. Nevertheless, the presenting clinical, laboratory, and pathologic features of these diseases often display significant overlaps. In this manuscript, we present our approach to the diagnosis and treatment of these rare lymphomas, whose complexity has been so far determined by the lack of prospectively validated prognostic systems, treatment strategies, and response criteria.

Concealed cardiomyopathy as a frequent cause of idiopathic ventricular fibrillation in a representative Czech cohort of survivors of sudden cardiac arrest (SCA)

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
A Krebsova ◽  
P Votypka ◽  
P Peldova ◽  
J Haskova ◽  
T Tavacova ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Genetic Testing ◽  
Ventricular Fibrillation ◽  
Dna Sequencing ◽  
Clinical Diagnostics ◽  
Idiopathic Ventricular Fibrillation ◽  
Custom Made ◽  
Diagnostic Work ◽  
Work Up ◽  
Diagnostic Work Up

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministry of Health of the Czech Republic Introduction The complex diagnostic work up in SCA survivors often does not yield a concrete cardiological diagnosis. Moreover, there is conflicting evidence whether genetic testing could support or guide clinical diagnostics. Purpose To assess the molecular architecture of idiopathic ventricular fibrillation in cases without apparent evidence of specific structural or arrhythmic cardiac disease at initial diagnostic work up in a representative Czech cohort. Patients and Methods Between 2013 - 2020 we have ascertained 100 SCA survivors (54 M / 46 F; age range at cardiac arrest 5-69 years). Genetic counselling was followed by massively parallel DNA sequencing using custom-made panels comprising 100 cardiac conditions-related genes. Subsequently, thorough cardiological screening examinations in first degree relatives were carried out. Presence of pathogenic variants was validated by Sanger DNA sequencing and through family segregation analyses. Results Highly likely or certain molecular aetiology (i.e. based on the presence of Class 4 or 5 variants) was disclosed in 20/100 (20%) in PKP2 (3x), SCN5A (4x), RYR2 (3x), TTN (2x), PLN, FLNC, PRKAG2, KCNH2, KCNQ1, SLC4A, TNNT2, and DSP. Interestingly, the KCNE1 p.Asp85Asn (LQT 5 lite) variant, was detected in further 3/100 cases, representing a recognized risk factor for ventricular arrhythmias. Conclusions Genetic testing facilitates stratification of the cause of arrhythmia in a substantial portion of SCA survivors. The utility of positive outcomes of genetic testing was substantiated in 10/20 gene positive patients, where the genetic stratification led to diagnosis of concealed arrhythmogenic cardiomyopathy, whose extent of morphological changes was under the diagnostic sensibility of imaging modalities or ECG. Our results enable individualized care in SCA survivors and assure targeted preventive approaches in their relatives.

scholarly journals Assessment of Sperm Quality - A Light Microscope Study

2021 ◽  
Vol 10 (19) ◽  
pp. 1417-1421
Author(s):  
Jyothi A. Raj ◽  
Heera Sankar ◽  
Sagarika Mahapatra ◽  
Ashima Binny
Keyword(s):  
Light Microscope ◽  
Sperm Morphology ◽  
Clinical Laboratory ◽  
Sperm Quality ◽  
Semen Analysis ◽  
Complete Evaluation ◽  
Normal Sperm ◽  
Middle Piece ◽  
Sperm Counts ◽  
Work Up

BACKGROUND Semen analysis is an integral part of work up for infertility in men, with sperm morphology being an important qualitative parameter. Qualitative defects can affect any part of the sperm and are classified as defects in the head, middle piece, and tail, based on morphology. The focus of the study was to assess qualitative defects in sperms by light microscopy, in semen with normal sperm counts. METHODS This study is hospital based, descriptive, retrospective study. Of the semen samples received in the clinical laboratory, fifty with normal sperm counts were included in the study and processed according to standard protocol. For evaluation of qualitative defects by sperm morphology, smears were fixed in ethanol, stained with Papanicolaou stain [PAP], and assessed under light microscope. RESULTS The 50 semen samples included in the study had sperm counts ranging from 15 to 80 million / ml. Thirty samples had less than 10 % abnormal forms, fourteen samples had 11 - 20 % abnormal forms, five samples had 21 - 30 % abnormal forms and one sample had 40 % abnormal sperms. Qualitative defects were classified as morphological abnormalities in head, neck, and tail. Of the fifty cases, most defects were found in the head, followed by those in the neck and tail. Common defects noted were double head (44 %), abnormal sized heads, and bent neck (48 %). Coiling was a common defect noted in the tail (10 %). Most sperms showed a combination of defects. CONCLUSIONS Qualitative defects in sperm morphology are often seen in samples with normal sperm counts. Assessment of microscopic characteristics of human spermatozoa is as important as count and motility in the complete evaluation and work-up of semen samples in cases of infertility. KEY WORDS Semen, Sperm, Quality, Microscopy, Morphology

scholarly journals Audit of the Aetiological Investigations Performed in Children with Sensorineural Hearing Loss At Salford

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Saud K AlHajeri ◽  
Dr Mohammed Iqbal
Keyword(s):  
Hearing Loss ◽  
Genetic Testing ◽  
Sensorineural Hearing Loss ◽  
Genetic Counselling ◽  
Gold Standard ◽  
Sensorineural Hearing ◽  
British Association ◽  
Hearing Tests ◽  
Work Up

Objective: This project aims to look at the Audiovestibular Physician’s practice at Salford and how closely it aligns with the gold standard guidelines set in the protocol lately published by the British Association of Audiological Physicians. Method: An audit was done retrospectively on 20 patients suffering from sensorineural hearing loss. As such, patient notes were utilised to ascertain which aetiological investigations have been completed and which were not. Any inadequacy in the aetiological work up has been dissected to help know the underlying reasons. Results: All patients had a thorough history taken and were comprehensively physically examined. 95% of patients underwent imaging in the form of MRI/CT. 80% received CMV testing. 75% underwent ECG testing. 60% received family hearing tests. Only 35% had ophthalmology examinations and 25% underwent urine and genetic testing. Conclusion: In some cases, the low compliance rates were due to the Audiovestibular Physician not ordering the investigation as part of the aetiological work up. This could be improved with the use of a dedicated checklist to act as an aid to the physician. Moreover, genetic counselling has been proposed to attempt to boost the compliance rates with genetic testing and similarly, leaflets briefing patients’ families about the importance of undergoing hearing tests themselves is another promising proposition to help improve the adherence

Evaluation of a benchtop capillary gas chromatograph-mass spectrometer for clinical toxicology.

1985 ◽  
Vol 31 (5) ◽  
pp. 741-746 ◽  
Author(s):  
D G Deutsch ◽  
R J Bergert
Keyword(s):  
Mass Spectrometer ◽  
Clinical Laboratory ◽  
Ion Source ◽  
Clinical Toxicology ◽  
Gas Chromatograph ◽  
Degree Of Confidence ◽  
Routine Clinical Laboratory ◽  
High Degree ◽  
Drug Reference

Abstract We evaluated the Hewlett-Packard 5995B benchtop capillary gas chromatograph-mass spectrometer (GC-MS) for its ability to identify drugs commonly detected and (or) measured in the clinical toxicology laboratory. Initial experiments indicated that the instrument as originally configured, with an isolation valve between the gas chromatograph and mass spectrometer, was unsatisfactory for the identification of hypnotics-sedatives. However, with the capillary inserted directly into the ion source, we could detect 10 ng of these drugs on a total-ion chromatogram. The software programs cause the instrument to be highly automated. In terms of ease of operation and speed it was found suitable for use in a routine clinical laboratory. Chromatography of urine extracts on the capillary gas chromatograph-mass spectrometer yielded excellent resolution of parent compounds and metabolites (e.g., diphenhydramine together with approximately four metabolites and propoxyphene with four metabolites). However, the manufacturer's computer program used to evaluate the quality of the match between the experimental mass spectra and the 375 drug reference spectra was only moderately successful in identifying unknown compounds. The ability of this capillary GC-MS to identify most compounds with a high degree of confidence will be increased by enlarging the library to include more drugs and metabolites and by using a more reliable computerized matching program.

scholarly journals Impact of a Cancer Gene Variant Reclassification Program Over a 20-Year Period

2020 ◽  
pp. 944-954
Author(s):  
Lisa Esterling ◽  
Ranjula Wijayatunge ◽  
Krystal Brown ◽  
Brian Morris ◽  
Elisha Hughes ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Hereditary Cancer ◽  
Medical Management ◽  
Clinical Laboratory ◽  
Cancer Predisposition ◽  
Expert Committee ◽  
Variant Classification ◽  
Cancer Genetic ◽  
Time Period ◽  
Predisposition Genes

PURPOSE Hereditary cancer genetic testing can inform personalized medical management for individuals at increased cancer risk. However, many variants in cancer predisposition genes are individually rare, and traditional tools may be insufficient to evaluate pathogenicity. This analysis presents data on variant classification and reclassification over a 20-year period. PATIENTS AND METHODS This is a retrospective analysis of > 1.9 million individuals who received hereditary cancer genetic testing from a single clinical laboratory (March 1997 to December 2017). Variant classification included review of evidence from traditional tools (eg, population frequency databases, literature) and laboratory-developed tools (eg, novel statistical methods, in-house RNA analysis) by a multidisciplinary expert committee. Variants may have been reclassified more than once and with more than one line of evidence. RESULTS In this time period, 62,842 unique variants were observed across 25 cancer predisposition genes, and 2,976 variants were reclassified. Overall, 82.1% of reclassification events were downgrades (eg, variant of uncertain significance [VUS] to benign), and 17.9% were upgrades (eg, VUS to pathogenic). Among reclassified variants, 82.8% were initially classified as VUS, and 47.5% were identified in ≤ 20 individuals (allele frequency ≤ 0.001%). Laboratory-developed tools were used in 72.3% of variant reclassification events, which affected > 600,000 individuals. More than 1.3 million patients were identified as carrying a variant that was reclassified within this 20-year time period. CONCLUSION The variant classification program used by the laboratory evaluated here enabled the reclassification of variants that were individually rare. Laboratory-developed tools were a key component of this program and were used in the majority of reclassifications. This demonstrates the importance of using robust and novel tools to reclassify rare variants to appropriately inform personalized medical management.

scholarly journals Emerging Homogeneous DNA-based Technologies in the Clinical Laboratory

2001 ◽  
Vol 47 (6) ◽  
pp. 990-1000 ◽  
Author(s):  
Carole A Foy ◽  
Helen C Parkes
Keyword(s):  
Genetic Testing ◽  
Clinical Setting ◽  
Clinical Laboratory ◽  
Molecular Diagnostic ◽  
End User ◽  
Wide Range ◽  
And Performance ◽  
Diagnostic Technologies ◽  
Insight Into ◽  
Diagnostic Setting

Abstract Background: Advances in molecular diagnostic technologies have enabled genetic testing in single closed-tube reactions. The purpose of this review is to highlight some of the platforms and technologies currently available for the homogeneous detection of targets and the application of the technologies in the clinical setting. Validation issues surrounding the technologies, which may need to be addressed before they can become widely accepted, will also be discussed. Approach: This review discusses the principles of several of the major technologies available for performing homogeneous genetic analyses. Publications arising from the application of the technologies in a wide range of clinical areas are used to highlight and compare the potential advantages and shortcomings of the various technologies. Content: This review is descriptive and focuses on three areas: the technologies available for performing homogeneous analysis, the clinical applications where the technologies are being used, and validation issues surrounding the acceptance of the technologies in the general clinical setting. Summary: This review intends to give the reader a greater understanding of the various technologies available for performing homogeneous genetic testing in the clinical laboratory. Through insight into the principles and performance characteristics underlying these technologies, the end user can evaluate their value and limitations in the clinical diagnostic setting.

scholarly journals Causes of brain dysfunction in acute coma: a cohort study of 1027 patients in the emergency department

2019 ◽  
Vol 27 (1) ◽  
Author(s):  
Wolf Ulrich Schmidt ◽  
Christoph J. Ploner ◽  
Maximilian Lutz ◽  
Martin Möckel ◽  
Tobias Lindner ◽  
...  
Keyword(s):  
Hospital Mortality ◽  
Clinical Laboratory ◽  
Brain Dysfunction ◽  
University Hospital ◽  
Unknown Etiology ◽  
Efficient Management ◽  
Observational Study Design ◽  
Diagnostic Work ◽  
Work Up ◽  
Diagnostic Work Up

Abstract Background Coma of unknown etiology (CUE) is a major challenge in emergency medicine. CUE is caused by a wide variety of pathologies that require immediate and targeted treatment. However, there is little empirical data guiding rational and efficient management of CUE. We present a detailed investigation on the causes of CUE in patients presenting to the ED of a university hospital. Methods One thousand twenty-seven consecutive ED patients with CUE were enrolled. Applying a retrospective observational study design, we analyzed all clinical, laboratory and imaging findings resulting from a standardized emergency work-up of each patient. Following a predefined protocol, we identified main and accessory coma-explaining pathologies and related these with (i.a.) GCS and in-hospital mortality. Results On admission, 854 of the 1027 patients presented with persistent CUE. Their main diagnoses were classified into acute primary brain lesions (39%), primary brain pathologies without acute lesions (25%) and pathologies that affected the brain secondarily (36%). In-hospital mortality associated with persistent CUE amounted to 25%. 33% of patients with persistent CUE presented with more than one coma-explaining pathology. In 173 of the 1027 patients, CUE had already resolved on admission. However, these patients showed a spectrum of main diagnoses similar to persistent CUE and a significant in-hospital mortality of 5%. Conclusion The data from our cohort show that the spectrum of conditions underlying CUE is broad and may include a surprisingly high number of coincidences of multiple coma-explaining pathologies. This finding has not been reported so far. Thus, significant pathologies may be masked by initial findings and only appear at the end of the diagnostic work-up. Furthermore, even transient CUE showed a significant mortality, thus rendering GCS cutoffs for selection of high- and low-risk patients questionable. Taken together, our data advocate for a standardized diagnostic work-up that should be triggered by the emergency symptom CUE and not by any suspected diagnosis. This standardized routine should always be completed - even when initial coma-explaining diagnoses may seem evident.

Result of Genetic Testing in 856 Consecutive Unrelated Patients Referred for Long QT Syndrome in a Clinical Laboratory

Heart Rhythm ◽  
2011 ◽  
Vol 8 (11) ◽  
pp. 1826
Author(s):  
K.V.V. Lieve ◽  
L. Williams ◽  
A. Daly ◽  
G. Richard ◽  
S. Bale ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Long Qt Syndrome ◽  
Clinical Laboratory ◽  
Long Qt ◽  
Qt Syndrome

scholarly journals Schwannomas along Different Segments of Facial Nerve: Case Series with Review of Literature

2011 ◽  
Vol 2 (2) ◽  
pp. 103-108 ◽  
Author(s):  
Deepa Nair ◽  
Prathamesh S Pai ◽  
Shawn T Joseph ◽  
Aliasgar V Moiyadi
Keyword(s):  
Facial Nerve ◽  
English Literature ◽  
Case Series ◽  
Review Of Literature ◽  
Delay In Diagnosis ◽  
Clinical Presentations ◽  
Early Imaging ◽  
Facial Nerve Schwannoma ◽  
High Degree ◽  
Work Up

ABSTRACT Facial nerve schwannomas are rare conditions which can mimic many other conditions. A series of patients with facial nerve schwannomas were treated in our department, all of whom had a delay in diagnosis resulting in a significant morbidity. This prompted us to present this rare case series of schwannomas along different segments of facial nerve and also review the literature on such tumors—the different presentations, work-up issues in management and rehabilitation. A wide text and PubMed English literature-based search was done on the existing literature on facial nerve schwannomas and the summary presented. Facial nerve schwannomas can have multiple clinical presentations with or without a facial paresis. Only a high degree of clinical suspicion and early imaging can lead to this diagnosis. An early diagnosis of facial nerve schwannoma is important as the morbidity associated with the condition as well as the surgery increases with the delay in diagnosis.

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