scholarly journals International Fanconi Anemia Registry: relation of clinical symptoms to diepoxybutane sensitivity

Blood ◽  
1989 ◽  
Vol 73 (2) ◽  
pp. 391-396
Author(s):  
AD Auerbach ◽  
A Rogatko ◽  
TM Schroeder-Kurth
Keyword(s):  
Fanconi Anemia ◽  
Clinical Symptoms ◽  
Clinical Manifestations ◽  
Chromosomal Breakage ◽  
Scoring Method ◽  
Cellular Sensitivity ◽  
Progressive Pancytopenia ◽  
Clastogenic Effect ◽  
Blood Specimens ◽  
Stepwise Multivariate Logistic Regression

Fanconi anemia (FA) is characterized clinically by a progressive pancytopenia, diverse congenital abnormalities and increased predisposition to malignancy. Although a variable phenotype makes accurate diagnosis on the basis of clinical manifestations difficult in some patients, study of cellular sensitivity to the clastogenic effect of DNA cross-linking agents such as diepoxybutane (DEB) has been used to facilitate the diagnosis. Data from DEB-induced chromosomal breakage studies of 328 peripheral blood specimens from patients considered at risk for FA were analyzed using a stepwise multivariate logistic regression, in order to determine which method of representing the data best discriminated between DEB-sensitive (DEB+) and DEB-insensitive (DEB-) cases. Similar methods were applied to the data from the International Fanconi Anemia Registry (IFAR) to determine whether DEB+ and DEB- cases may be considered as distinct clinical entities, and if so, which variables provide the best discrimination between the two groups. We conclude that hypersensitivity to the clastogenic effect of DEB is a useful discriminator for FA. A simplified scoring method for classifying patients on the basis of eight clinical manifestations that are the best predictors for FA is presented. Our data indicate that the clinical diversity in FA is more widespread than previously recognized.

scholarly journals International Fanconi Anemia Registry: relation of clinical symptoms to diepoxybutane sensitivity

Blood ◽  
1989 ◽  
Vol 73 (2) ◽  
pp. 391-396 ◽  
Author(s):  
AD Auerbach ◽  
A Rogatko ◽  
TM Schroeder-Kurth
Keyword(s):  
Fanconi Anemia ◽  
Clinical Symptoms ◽  
Clinical Manifestations ◽  
Chromosomal Breakage ◽  
Scoring Method ◽  
Cellular Sensitivity ◽  
Progressive Pancytopenia ◽  
Clastogenic Effect ◽  
Blood Specimens ◽  
Stepwise Multivariate Logistic Regression

Abstract Fanconi anemia (FA) is characterized clinically by a progressive pancytopenia, diverse congenital abnormalities and increased predisposition to malignancy. Although a variable phenotype makes accurate diagnosis on the basis of clinical manifestations difficult in some patients, study of cellular sensitivity to the clastogenic effect of DNA cross-linking agents such as diepoxybutane (DEB) has been used to facilitate the diagnosis. Data from DEB-induced chromosomal breakage studies of 328 peripheral blood specimens from patients considered at risk for FA were analyzed using a stepwise multivariate logistic regression, in order to determine which method of representing the data best discriminated between DEB-sensitive (DEB+) and DEB-insensitive (DEB-) cases. Similar methods were applied to the data from the International Fanconi Anemia Registry (IFAR) to determine whether DEB+ and DEB- cases may be considered as distinct clinical entities, and if so, which variables provide the best discrimination between the two groups. We conclude that hypersensitivity to the clastogenic effect of DEB is a useful discriminator for FA. A simplified scoring method for classifying patients on the basis of eight clinical manifestations that are the best predictors for FA is presented. Our data indicate that the clinical diversity in FA is more widespread than previously recognized.

scholarly journals Diagnosis of Fanconi Anemia: Mutation Analysis by Next-Generation Sequencing

Anemia ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Najim Ameziane ◽  
Daoud Sie ◽  
Stefan Dentro ◽  
Yavuz Ariyurek ◽  
Lianne Kerkhoven ◽  
...  
Keyword(s):  
Fanconi Anemia ◽  
Clinical Symptoms ◽  
Massively Parallel Sequencing ◽  
Bone Marrow Failure ◽  
Genetic Diagnosis ◽  
Chromosomal Breakage ◽  
Developmental Defects ◽  
Pathogenic Mutations ◽  
High Cancer Risk ◽  
Generation Sequencing

Fanconi anemia (FA) is a rare genetic instability syndrome characterized by developmental defects, bone marrow failure, and a high cancer risk. Fifteen genetic subtypes have been distinguished. The majority of patients (≈85%) belong to the subtypes A (≈60%), C (≈15%) or G (≈10%), while a minority (≈15%) is distributed over the remaining 12 subtypes. All subtypes seem to fit within the “classical” FA phenotype, except for D1 and N patients, who have more severe clinical symptoms. Since FA patients need special clinical management, the diagnosis should be firmly established, to exclude conditions with overlapping phenotypes. A valid FA diagnosis requires the detection of pathogenic mutations in a FA gene and/or a positive result from a chromosomal breakage test. Identification of the pathogenic mutations is also important for adequate genetic counselling and to facilitate prenatal or preimplantation genetic diagnosis. Here we describe and validate a comprehensive protocol for the molecular diagnosis of FA, based on massively parallel sequencing. We used this approach to identifyBRCA2,FANCD2,FANCIandFANCLmutations in novel unclassified FA patients.

scholarly journals Diagnostic Overlap between Fanconi Anemia and the Cohesinopathies: Roberts Syndrome and Warsaw Breakage Syndrome

Anemia ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Petra van der Lelij ◽  
Anneke B. Oostra ◽  
Martin A. Rooimans ◽  
Hans Joenje ◽  
Johan P. de Winter
Keyword(s):  
Fanconi Anemia ◽  
Bone Marrow Failure ◽  
Clinical Manifestations ◽  
Nijmegen Breakage Syndrome ◽  
Inherited Disease ◽  
Chromosomal Breakage ◽  
Metaphase Chromosomes ◽  
Roberts Syndrome ◽  
Premature Centromere Division ◽  
Multiple Symptoms

Fanconi anemia (FA) is a recessively inherited disease characterized by multiple symptoms including growth retardation, skeletal abnormalities, and bone marrow failure. The FA diagnosis is complicated due to the fact that the clinical manifestations are both diverse and variable. A chromosomal breakage test using a DNA cross-linking agent, in which cells from an FA patient typically exhibit an extraordinarily sensitive response, has been considered the gold standard for the ultimate diagnosis of FA. In the majority of FA patients the test results are unambiguous, although in some cases the presence of hematopoietic mosaicism may complicate interpretation of the data. However, some diagnostic overlap with other syndromes has previously been noted in cases with Nijmegen breakage syndrome. Here we present results showing that misdiagnosis may also occur with patients suffering from two of the three currently known cohesinopathies, that is, Roberts syndrome (RBS) and Warsaw breakage syndrome (WABS). This complication may be avoided by scoring metaphase chromosomes—in addition to chromosomal breakage—for spontaneously occurring premature centromere division, which is characteristic for RBS and WABS, but not for FA.

scholarly journals Diagnosis of Fanconi Anemia: Chromosomal Breakage Analysis

Anemia ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Anneke B. Oostra ◽  
Aggie W. M. Nieuwint ◽  
Hans Joenje ◽  
Johan P. de Winter
Keyword(s):  
Mitomycin C ◽  
Fanconi Anemia ◽  
Autosomal Recessive ◽  
Clinical Symptoms ◽  
Bone Marrow Failure ◽  
Blood Cultures ◽  
Chromosomal Breakage ◽  
Developmental Defects ◽  
Cycle Arrest ◽  
Laboratory Protocol

Fanconi anemia (FA) is a rare inherited syndrome with diverse clinical symptoms including developmental defects, short stature, bone marrow failure, and a high risk of malignancies. Fifteen genetic subtypes have been distinguished so far. The mode of inheritance for all subtypes is autosomal recessive, except for FA-B, which is X-linked. Cells derived from FA patients are—by definition—hypersensitive to DNA cross-linking agents, such as mitomycin C, diepoxybutane, or cisplatinum, which becomes manifest as excessive growth inhibition, cell cycle arrest, and chromosomal breakage upon cellular exposure to these drugs. Here we provide a detailed laboratory protocol for the accurate assessment of the FA diagnosis as based on mitomycin C-induced chromosomal breakage analysis in whole-blood cultures. The method also enables a quantitative estimate of the degree of mosaicism in the lymphocyte compartment of the patient.

Etiology and clinical features of epididymo-orchitis: A single-center study in Tehran, Iran

2020 ◽  
Vol 20 ◽  
Author(s):  
Sara Abolghasemi ◽  
Mohammad Alizadeh ◽  
Ali Hashemi ◽  
Shabnam Tehrani
Keyword(s):  
Chlamydia Trachomatis ◽  
Clinical Symptoms ◽  
Urine Culture ◽  
Clinical Manifestations ◽  
Urinary Frequency ◽  
Serological Tests ◽  
Duration Of Symptoms ◽  
Two Samples ◽  
History Of ◽  
Tract Infections

Introduction: Epididymo-orchitis is a common urological disease among men. Little is known about the clinical and epidemiological aspects of the disease in Iran. Thus, the present study was aimed to investigate the etiology, clinical sequelae and risk factors of patients with epididymo-orchitis in Tehran, Iran. Materials and Methods: Patients presenting with epididymo-orchitis were prospectively analyzed in order to study the etiology and pattern of the disease. Bacteriological, molecular and serological tests were undertaken to look for Chlamydia trachomatis, Neisseria gonorrhoeae, Brucella spp., Mycoplasma spp, and other bacteria. Results: Fifty patients with epididymo-orchitis were evaluated according to their clinical symptoms, duration of symptoms, physical examination, and laboratory studies. The mean age of the patients was 53 years. Fever, dysuria, pain in the flanks, urinary frequency and discharges occurred in 58.0%, 50.0%, 50.0%, 28.0% and 6.0%, respectively. Bacterial pathogen was identified in 26% (13/50) of patients by urine culture. Escherichia coli was the etiological agent in 11/13 patients (84.6%). Two out of 50 patients (4.0%) were also positive for Chlamydia trachomatis. Two samples were serologically positive for Brucella spp. High Mean age, fever, urinary frequency, history of the underlying disease and history of urinary tract infections were found to have a significant association with the positive bacteriologic urine culture (P<0.05). Conclusions: The most common clinical manifestations were fever, dysuria, and abdominal pain. E. coli and C. trachomatis were the major causative agents. Use of a set of diagnostic approaches including clinical symptoms, urine culture and more precise techniques such as PCR should be taken into consideration for the definitive diagnosis.

Scrub typhus (Orientia tsutsugamushi), A rapidly spreading epidemic in Chennai - A standalone lab experience

2016 ◽  
Vol 5 (09) ◽  
pp. 4896
Author(s):  
Sripriya C.S.* ◽  
Shanthi B. ◽  
Arockia Doss S. ◽  
Antonie Raj I. ◽  
Mohana Priya
Keyword(s):  
Scrub Typhus ◽  
Clinical Symptoms ◽  
Clinical Manifestations ◽  
Febrile Illness ◽  
Orientia Tsutsugamushi ◽  
The Past ◽  
Igm Elisa ◽  
The Mean ◽  
Specific Symptoms ◽  
Symptoms And Signs

Scrub typhus (Orientia tsutsugamushi), is a strict intracellular bacterium which is reported to be a recent threat to parts of southern India. There is re-emergence of scrub typhus during the past few years in Chennai. Scrub typhus is an acute febrile illness which generally causes non-specific symptoms and signs. The clinical manifestations of this disease range from sub-clinical disease to organ failure to fatal disease. This study documents our laboratory experience in diagnosis of scrub typhus in patients with fever and suspected clinical symptoms of scrub typhus infection for a period of two years from April 2014 to April 2016 using immunochromatography and IgM ELISA methods. The study was conducted on 648 patients out of whom 188 patients were found to be positive for scrub typhus. Results also showed that pediatric (0 -12 years) and young adults (20 – 39 years) were more exposed to scrub typhus infection and female patients were more infected compared to male. The study also showed that the rate of infection was higher between September to February which also suggested that the infection rate is proportional to the climatic condition. Statistical analysis showed that the mean age of the patients in this study was 37.6, standard deviation was 18.97, CV % was 50.45. 

scholarly journals Pediatric COVID-19 and the Factors That May Mitigate Its Clinical Course

2020 ◽  
Vol 10 (01) ◽  
pp. e137-e140
Author(s):  
Mosaad Abdel-Aziz ◽  
Nada M. Abdel-Aziz ◽  
Dina M. Abdel-Aziz ◽  
Noha Azab
Keyword(s):  
Clinical Features ◽  
Clinical Symptoms ◽  
Clinical Course ◽  
Clinical Manifestations ◽  
Gastrointestinal Symptoms ◽  
Angiotensin Converting Enzyme 2 ◽  
Compulsory Vaccination ◽  
Specific Factors ◽  
Novel Coronavirus ◽  
Radiographic Data

AbstractThe clinical manifestations of novel coronavirus disease 2019 (COVID-19) vary from mild flu-like symptoms to severe fatal pneumonia. However, children with COVID-19 may be asymptomatic or may have mild clinical symptoms. The aim of this study was to investigate clinical features of pediatric COVID-19 and to search for the factors that may mitigate the disease course. We reviewed the literature to realize the clinical features, laboratory, and radiographic data that may be diagnostic for COVID-19 among children. Also, we studied the factors that may affect the clinical course of the disease. Fever, dry cough, and fatigue are the main symptoms of pediatric COVID-19, sometimes flu-like symptoms and/or gastrointestinal symptoms may be present. Although some infected children may be asymptomatic, a recent unusual hyperinflammatory reaction with overlapping features of Kawasaki's disease and toxic shock syndrome in pediatric COVID-19 has been occasionally reported. Severe acute respiratory syndrome-coronvirus-2 (SARS-CoV-2) nucleic acid testing is the corner-stone method for the diagnosis of COVID-19. Lymphocyte count and other inflammatory markers are not essentially diagnostic; however, chest computed tomography is highly specific. Factors that may mitigate the severity of pediatric COVID-19 are home confinement with limited children activity, trained immunity caused by compulsory vaccination, the response of the angiotensin-converting enzyme 2 receptors in children is not the same as in adults, and that children are less likely to have comorbidities. As infected children may be asymptomatic or may have only mild respiratory and/or gastrointestinal symptoms that might be missed, all children for families who have a member diagnosed with COVID-19 should be investigated.

scholarly journals Gastric amyloidosis presenting as acute upper gastrointestinal bleeding: a case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Rachael Chan ◽  
Stephanie Carpentier
Keyword(s):  
Multiple Myeloma ◽  
Clinical Symptoms ◽  
Clinical Manifestations ◽  
Left Gastric Artery ◽  
Bleeding Complications ◽  
Al Amyloidosis ◽  
Gi Bleeding ◽  
Reduced Ejection Fraction ◽  
Repeat Endoscopy ◽  
Tertiary Center

Abstract Background Amyloidosis is characterized by extracellular tissue deposition of fibrils, composed of insoluble low-molecular-weight protein subunits. The type, location, and extent of fibril deposition generates variable clinical manifestations. Gastrointestinal (GI) bleeding due to amyloid deposition is infrequent. Previous literature describes upper GI bleeding (UGIB) in patients with known amyloid disease. Here, we describe a case of recurrent UGIB that ultimately led to a diagnosis of GI amyloidosis and multiple myeloma in a patient with no history of either. Case presentation A 76-year-old male presented to the emergency department with frank hematemesis, melena, and a decreased level of consciousness. Management required intensive care unit (ICU) admission with transfusion, intubation, and hemodynamic support. Upper endoscopy revealed gastritis with erosions and nodularity in the gastric cardia and antrum. Hemostasis of a suspected bleeding fundic varix could not be achieved. Subsequently, the patient underwent computerized tomography (CT) angiography and an interventional radiologist completed embolization of the left gastric artery to address potentially life-threatening bleeding. Complications included development of bilateral pleural effusions and subsegmental pulmonary emboli. Pleural fluid was negative for malignancy. He was transferred to a peripheral hospital for continued care and rehabilitation. Unfortunately, he began re-bleeding and was transferred back to our tertiary center, requiring re-admission to the ICU and repeat endoscopy. Repeat biopsy of the gastric cardial nodularity was reported as active chronic gastritis and ulceration. However, based on the unusual endoscopic appearance, clinical suspicion for malignancy remained high. He exhibited symptoms of congestive heart failure following standard resuscitation. Transthoracic echocardiogram (TTE) demonstrated a reduced ejection fraction of 35–40% and a strain pattern with apical sparing. Following discussions between the treating gastroenterologist, consulting cardiologist, and pathologist, Congo Red staining was performed, revealing submucosal amyloid deposits. Hematology was consulted and investigations led to diagnosis of multiple myeloma (MM) and immunoglobulin light-chain (AL) amyloidosis. The patient was treated for MM for four months prior to cessation of therapy due to functional and cognitive decline. Conclusions GI amyloidosis can present with various non-specific clinical symptoms and endoscopic findings, rendering diagnosis a challenge. This case illustrates GI amyloidosis as a potential—albeit rare—etiology of UGIB.

scholarly journals CD4+ CD25+ Foxp3+ Regulatory T Cells, Dendritic Cells, and Circulating Cytokines in Uncomplicated Malaria: Do Different Parasite Species Elicit Similar Host Responses?

2010 ◽  
Vol 78 (11) ◽  
pp. 4763-4772 ◽  
Author(s):  
Raquel M. Gonçalves ◽  
Karina C. Salmazi ◽  
Bianca A. N. Santos ◽  
Melissa S. Bastos ◽  
Sandra C. Rocha ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Parasite Species ◽  
Inflammatory Responses ◽  
Clinical Symptoms ◽  
Clinical Manifestations ◽  
Surface Expression ◽  
Interleukin 10 ◽  
Treg Cells ◽  
Experimental Models ◽  
Necrosis Factor Alpha

ABSTRACT Clearing blood-stage malaria parasites without inducing major host pathology requires a finely tuned balance between pro- and anti-inflammatory responses. The interplay between regulatory T (Treg) cells and dendritic cells (DCs) is one of the key determinants of this balance. Although experimental models have revealed various patterns of Treg cell expansion, DC maturation, and cytokine production according to the infecting malaria parasite species, no studies have compared all of these parameters in human infections with Plasmodium falciparum and P. vivax in the same setting of endemicity. Here we show that during uncomplicated acute malaria, both species induced a significant expansion of CD4+ CD25+ Foxp3+ Treg cells expressing the key immunomodulatory molecule CTLA-4 and a significant increase in the proportion of DCs that were plasmacytoid (CD123+), with a decrease in the myeloid/plasmacytoid DC ratio. These changes were proportional to parasite loads but correlated neither with the intensity of clinical symptoms nor with circulating cytokine levels. One-third of P. vivax-infected patients, but no P. falciparum-infected subjects, showed impaired maturation of circulating DCs, with low surface expression of CD86. Although vivax malaria patients overall had a less inflammatory cytokine response, with a higher interleukin-10 (IL-10)/tumor necrosis factor alpha (TNF-α) ratio, this finding did not translate to milder clinical manifestations than those of falciparum malaria patients. We discuss the potential implications of these findings for species-specific pathogenesis and long-lasting protective immunity to malaria.

CLINIC AND COMPLICATIONS OF COVID-19 CORONAVIRUS DISEASE WITH PATHOGENESIS ELEMENTS

2020 ◽  
pp. 72-79
Author(s):  
I. V. Аndrusovich
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Tract ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Clinical Symptoms ◽  
Clinical Course ◽  
Clinical Manifestations ◽  
Second Phase ◽  
Upper Respiratory Tract

The longer the COVID−19 coronavirus pandemic lasts, the more information about its clinical manifestations is accumulated. The incubation period of COVID−19 ranges from 2 to 14 days, rarely up to 3 weeks, but in a significant number of cases an infection is not accompanied with the appearance of clinical symptoms. Currently, the following variants of the clinical course of COVID−19 can be identified as follows: viral load; subclinical; slight; uncomplicated with damage to only the upper respiratory tract; mild pneumonia, severe pneumonia, acute respiratory distress syndrome, etc. The clinical course of COVID−19 depends on the severity, the criteria of which are the intoxication manifestation, the degree of fever and the dominant syndrome. Mild / moderate forms are manifested by frequent increase in body temperature up to 38 ° C, respiratory symptoms, headache, myalgias, palpitations and general malaise. Patients stop distinguishing smells and feel the taste of food. Approximately from the 7th to the 9th days of the disease there are problems with breathing, which indicates the impairment of the lower respiratory tract and the beginning of the second phase of the disease, and its course is regarded as severe. Severe forms of the disease can also be manifested by impaired coordination of movements, slurred speech. In 1 to 4 % of patients there is developed the psychosis in the form of hallucinations. In the elderly, COVID−19 may be accompanied by delirium, lowering blood pressure. The risks of adverse disease are associated with somatic diseases: cardiovascular and nervous systems, respiratory tract, hormonal disorders, etc. Otitis, sinusitis, sepsis, bronchopulmonary infection, thrombosis, myocarditis etc. can be the complications of COVID−19. Computer tomography is an instrumental test that demonstrates the damage of lungs with coronavirus and allows to assess its severity. Key words: coronavirus infection, COVID−19, clinical variants, severity, pneumonia, acute respiratory distress syndrome.

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