scholarly journals The pathophysiology of preeclampsia in view of the two-stage model

2012 ◽  
Vol 153 (30) ◽  
pp. 1167-1176 ◽  
Author(s):  
Bálint Alasztics ◽  
Zoltán Kukor ◽  
Zita Pánczél ◽  
Sándor Valent
Keyword(s):  
De Novo ◽  
Clinical Symptoms ◽  
Severe Disease ◽  
Multiple Organ ◽  
Common Denominator ◽  
Stage Model ◽  
Two Stage ◽  
Organ Systems ◽  
Stage 1 ◽  
Oxide Synthase

Preeclampsia is a common and severe disease in pregnancy, a major cause of maternal and fetal morbidity and mortality. The main features of the disease are de novo hypertension after the 20th gestational week and proteinuria, and it is frequently accompanied by edema and other subjective symptoms. The origin of the disease is the placenta, but its sequelae affect multiple organ systems. According to the two-stage model of preeclampsia, the abnormal and hypoperfused placenta (stage 1) releases factors to the bloodstream, which are responsible for the maternal symptoms (stage 2). Oxidative stress, impaired function of nitric-oxide synthase, cellular and humoral immunological factors play an important role in the pathophysiology of the placenta. Endothelial dysfunction is the common denominator of the clinical symptoms. The theory explains the origins of hypertension, proteinuria, edema and other symptoms as well. Orv. Hetil., 2012, 153, 1167–1176.

scholarly journals The Indirect Implication of SARS-CoV-2 Resulting in Kayexalate Toxicity in a Patient with Acute Kidney Injury

2021 ◽  
Vol 5 (1) ◽  
pp. 6-13
Author(s):  
Charles E. Middleton IV ◽  
William Daley ◽  
Neha Varshney
Keyword(s):  
Acute Kidney Injury ◽  
Virus Disease ◽  
Severe Disease ◽  
Kidney Injury ◽  
Multiple Organ ◽  
Subsequent Treatment ◽  
Gastrointestinal Complications ◽  
Treatment Regimens ◽  
Organ Systems ◽  
Life Threatening

The clinical features of corona virus disease 2019 (COVID-19) are variable, but the majority of patients experience mild flu-like symptoms. The cases of severe disease include complications such as progressive pneumonia, acute kidney injury, multi-organ failure, and even death. This paper explores the association between COVID-19 and its effect on multiple organ systems and how the subsequent treatment of this disease can itself lead to morbidity and mortality. We present a case which emphasizes the life threatening gastrointestinal complications associated with treatment of acute kidney injury (AKI) in a patient with COVID-19. We conclude that the patients whose treatment regimens utilize medical resins should be closely monitored for gastrointestinal complications so as to mitigate the known adverse effects associated with these drugs, such as colonic mucosal ulceration, perforation, or even death.

scholarly journals Insight into the Key Points of Preeclampsia Pathophysiology: Uterine Artery Remodeling and the Role of MicroRNAs

2021 ◽  
Vol 22 (6) ◽  
pp. 3132
Author(s):  
Katarzyna Pankiewicz ◽  
Anna Fijałkowska ◽  
Tadeusz Issat ◽  
Tomasz M. Maciejewski
Keyword(s):  
Uterine Artery ◽  
Clinical Symptoms ◽  
Multiorgan Failure ◽  
Endothelial Damage ◽  
Disease Stage ◽  
Stage Model ◽  
Two Stage ◽  
Placental Perfusion ◽  
Artery Remodeling

Preeclampsia affects about 3–8% of all pregnancies. It represents a complex and multifaceted syndrome with at least several potential pathways leading to the development of disease. The main dogma in preeclampsia is the two-stage model of disease. Stage 1 (placental stage) takes place in early pregnancy and is thought to be impaired placentation due to inadequate trophoblastic invasion of the maternal spiral arteries that leads to reduced placental perfusion and release of numerous biological factors causing endothelial damage and development of acute maternal syndrome with systemic multiorgan failure (stage 2—the onset of maternal clinical symptoms, maternal stage). Recently, in the light of the vast body of evidence, two-stage model of preeclampsia has been updated with a few novel pathways leading to clinical manifestation in the second part of pregnancy. This paper reviews current state of knowledge about pathophysiology of preeclampsia and places particular focus on the recent advances in understanding of uterine artery remodeling alterations, as well as the role of microRNAs in preeclampsia.

MARFAN SYNDROME AND PREGNANCY: CLINICAL IMPLICATIONS AND MANAGEMENT

2010 ◽  
Vol 21 (3) ◽  
pp. 225-241
Author(s):  
ARIADNA C GRIGORIU ◽  
JACK COLMAN ◽  
CANDICE K SILVERSIDES ◽  
RACHEL WALD ◽  
SAMUEL C SIU ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Marfan Syndrome ◽  
Autosomal Dominant ◽  
De Novo ◽  
Connective Tissue Disorder ◽  
Multiple Organ ◽  
Clinical Implications ◽  
Organ Systems

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder that affects multiple organ systems, primarily the cardiovascular, ocular and skeletal. It is the most common inherited condition affecting the heart and the aorta, occurring in 1:5000–1:9800 people. There is no ethnic or gender predisposition; 20 to 35% of cases arise fromde novomutations.

scholarly journals Bezafibrate Improves Mitochondrial Fission and Function in DNM1L-Deficient Patient Cells

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 301 ◽  
Author(s):  
Liza Douiev ◽  
Ruth Sheffer ◽  
Gabriella Horvath ◽  
Ann Saada
Keyword(s):  
De Novo ◽  
Neurodevelopmental Disorder ◽  
Mitochondrial Fission ◽  
Fibroblast Cell ◽  
Multiple Organ ◽  
Mitochondrial Morphology ◽  
Main Role ◽  
Atp Production ◽  
Organ Systems ◽  
Mitochondrial Functions

Mitochondria are involved in many cellular processes and their main role is cellular energy production. They constantly undergo fission and fusion, and these counteracting processes are under strict balance. The cytosolic dynamin-related protein 1, Drp1, or dynamin-1-like protein (DNM1L) mediates mitochondrial and peroxisomal division. Defects in the DNM1L gene result in a complex neurodevelopmental disorder with heterogeneous symptoms affecting multiple organ systems. Currently there is no curative treatment available for this condition. We have previously described a patient with a de novo heterozygous c.1084G>A (p.G362S) DNM1L mutation and studied the effects of a small molecule, bezafibrate, on mitochondrial functions in this patient’s fibroblasts compared to controls. Bezafibrate normalized growth on glucose-free medium, as well as ATP production and oxygen consumption. It improved mitochondrial morphology in the patient’s fibroblasts, although causing a mild increase in ROS production at the same time. A human foreskin fibroblast cell line overexpressing the p.G362S mutation showed aberrant mitochondrial morphology, which normalized in the presence of bezafibrate. Further studies would be needed to show the consistency of the response to bezafibrate, possibly using fibroblasts from patients with different mutations in DNM1L, and this treatment should be confirmed in clinical trials. However, taking into account the favorable effects in our study, we suggest that bezafibrate could be offered as a treatment option for patients with certain DNM1L mutations.

scholarly journals Oral lesions as a clinical sign of systemic lupus erythematosus

2018 ◽  
Vol 51 (3) ◽  
pp. 147
Author(s):  
Eliza Kristina M. Munthe ◽  
Irna Sufiawati
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Clinical Symptoms ◽  
Organ Damage ◽  
Multiple Organ ◽  
Suspected Case ◽  
Oral Lesions ◽  
Systemic Lupus ◽  
Organ Systems ◽  
High Degree

Background: Oral lesions represent one of the most important clinical symptoms of systemic lupus erythematosus (SLE), an autoimmune disease with a high degree of clinical variability rendering it difficult to arrive at a prompt and accurate diagnosis. There are many unknown causes and multiple organ systems involved, with the result that permanent organ damage may occur before treatment commences. Purpose: The purpose of this case report is to discuss the importance of recognizing the lesions related to SLE which may help dentists to make an early diagnosis. Case: A 17-year-old female patient was referred by the Internal Medicine Department with a suspected case of SLE. Prior to admittance to the hospital, the patient was diagnosed with tuberculosis. A subsequent extraoral examination revealed ulceration with a blackish crust on the upper lip. An intraoral examination showed similar ulceration covered with a blackish crust on the labial mucosa accompanied by central erythema in the hard palate. Blood tests indicated decreased levels of hemoglobin, hematocrit and platelets, but increased levels of leukocytes. A diagnosis of oral lesions associated with SLE and angioedema was formulated. Case management: The patient was given 1% hydrocortisone and vaseline album for extraoral lesions, while 0.2% chlorhexidine gluconate and 0.1% triamcinolone acetonide was used to treat intraoral lesions. An improvement in the oral lesions manifested itself after two weeks of treatment. Conclusion: Early detection of oral lesions plays a significant role in diagnosing SLE. It is important for the dentist to recognize the presentation of diseases that may be preceded by oral lesions. A multidisciplinary approach and appropriate referrals are necessary to ensure comprehensive medical and dental management of patients with SLE.

scholarly journals Bezafibrate Improves Mitochondrial Fission and Function in DNM1L Deficient Patient Cells

2019 ◽  
Author(s):  
Liza Douiev ◽  
Ruth Sheffer ◽  
Gabriella Horvath ◽  
Ann Saada
Keyword(s):  
De Novo ◽  
Neurodevelopmental Disorder ◽  
Mitochondrial Fission ◽  
Multiple Organ ◽  
Mitochondrial Morphology ◽  
Main Role ◽  
Atp Production ◽  
Organ Systems ◽  
Mitochondrial Functions ◽  
And Function

Mitochondria are involved in many cellular processes and their main role is cellular energy production. They constantly undergo fission and fusion, and these counteracting processes are under strict balance. The cytosolic dynamin-related protein 1, Drp1 or dynamin-1-like protein (DNM1L) mediates mitochondrial and peroxisomal division. Defects in the DNM1L gene results in a complex neurodevelopmental disorder with heterogeneous symptoms affecting multiple organ systems. Currently there is no curative treatment available for this condition. We have previously described a patient with a de novo heterozygous c.1084G>A (p.G362S) DNM1L mutation and studied the effects of a small molecule, Bezafibrate, on mitochondrial functions in this patient’s fibroblasts compared to controls. Bezafibrate normalized growth on glucose-free medium, ATP production, oxygen consumption and s improved mitochondrial morphology in patient’s fibroblasts, albeit concomitantly causing a mild increase ROS production. Further studies would be needed to show the consistency of the response to Bezafibrate, possibly using fibroblasts from patients with different mutations in DNM1L, and this treatment should be confirmed in clinical trials. However, taking into account the favorable effects in our study, we suggest that Bezafibrate could be a possible treatment option for patients with certain DNM1L mutations.

scholarly journals Patient with H syndrome, cardiogenic shock, multiorgan infiltration, and digital ischemia

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Laura Ventura-Espejo ◽  
Inés Gracia-Darder ◽  
Silvia Escribá-Bori ◽  
Eva Regina Amador-González ◽  
Ana Martín-Santiago ◽  
...  
Keyword(s):  
Cardiogenic Shock ◽  
Clinical Symptoms ◽  
Heart Function ◽  
Systolic Dysfunction ◽  
Severe Disease ◽  
Invasive Mechanical Ventilation ◽  
Multiple Organ ◽  
Antibody Detection ◽  
Digital Ischemia ◽  
Liver And Kidney

Abstract Background H syndrome (HS) is a rare autoinflammatory disease caused by a mutation in the solute carrier family 29, member 3 (SCL29A3) gene. It has a variable clinical presentation and little phenotype-genotype correlation. The pathognomonic sign of HS is cutaneous hyperpigmentation located mainly in the inner thighs and often accompanied by other systemic manifestations. Improvement after tocilizumab treatment has been reported in a few patients with HS. We report the first patient with HS who presented cardiogenic shock, multiorgan infiltration, and digital ischemia. Case presentation 8-year-old boy born to consanguineous parents of Moroccan origin who was admitted to the intensive care unit during the Coronavirus Disease-2019 (COVID-19) pandemic with tachypnoea, tachycardia, and oliguria. Echocardiography showed dilated cardiomyopathy and severe systolic dysfunction compatible with cardiogenic shock. Additionally, he presented with multiple organ dysfunction syndrome. SARS-CoV-2 polymerase chain reaction (PCR) and antibody detection by chromatographic immunoassay were negative. A previously ordered gene panel for pre-existing sensorineural hearing loss showed a pathological mutation in the SCL29A3 gene compatible with H syndrome. Computed tomography scan revealed extensive alveolar infiltrates in the lungs and multiple poor defined hypodense lesions in liver, spleen, and kidneys; adenopathy; and cardiomegaly with left ventricle subendocardial nodules. Invasive mechanical ventilation, broad antibiotic and antifungal coverage showed no significant response. Therefore, Tocilizumab as compassionate use together with pulsed intravenous methylprednisolone was initiated. Improvement was impressive leading to normalization of inflammation markers, liver and kidney function, and stabilising heart function. Two weeks later, he was discharged and has been clinically well since then on two weekly administration of Tocilizumab. Conclusions We report the most severe disease course produced by HS described so far in the literature. Our patient’s manifestations included uncommon, new complications such as acute heart failure with severe systolic dysfunction, multi-organ cell infiltrate, and digital ischemia. Most of the clinical symptoms of our patient could have been explained by SARS-CoV-2, demonstrating the importance of a detailed differential diagnosis to ensure optimal treatment. Although the mechanism of autoinflammation of HS remains uncertain, the good response of our patient to Tocilizumab makes a case for the important role of IL-6 in this syndrome and for considering Tocilizumab as a first-line treatment, at least in severely affected patients.

scholarly journals Diagnosis and management of mastocytosis: an emerging challenge in applied hematology

Hematology ◽  
2015 ◽  
Vol 2015 (1) ◽  
pp. 98-105 ◽  
Author(s):  
Peter Valent
Keyword(s):  
Clinical Symptoms ◽  
Systemic Mastocytosis ◽  
Organ Damage ◽  
Multiple Organ ◽  
High Dose ◽  
Molecular Defects ◽  
Vasoactive Mediators ◽  
Organ Systems ◽  
Novel Drugs ◽  
The Individual

Abstract Mastocytosis is a unique and rare neoplasm defined by abnormal expansion and accumulation of clonal mast cells (MCs) in one or multiple organ systems. Most adult patients are diagnosed to have systemic mastocytosis (SM). Based on histological findings and disease-related organ damage, SM is classified into indolent SM (ISM), smoldering SM (SSM), SM with an associated hematologic non-MC-lineage disease (SM-AHNMD), aggressive SM (ASM), and MC leukemia (MCL). The clinical picture, course, and prognosis vary profoundly among these patients. Nonetheless, independent of the category of SM, neoplastic cells usually exhibit the KIT point-mutation D816V. However, in advanced SM, additional molecular defects are often detected and are considered to contribute to disease progression and drug resistance. These lesions include, among others, somatic mutations in TET2, SRSF2, ASXL1, CBL, RUNX1, and RAS. In SM-AHNMD, such mutations are often found in the “AHNMD component” of the disease. Clinical symptoms in mastocytosis result from (1) the release of proinflammatory and vasoactive mediators from MCs, and (2) SM-induced organ damage. Therapy of SM has to be adjusted to the individual patient and the SM category: in those with ISM and SSM, the goal is to control mediator secretion and/or mediator effects, to keep concomitant allergies under control, and to counteract osteoporosis, whereas in advanced SM (ASM, MCL, and SM-AHNMD) anti-neoplastic drugs are prescribed to suppress MC expansion and/or to keep AHNMD cells under control. Novel drugs directed against mutated KIT and/or other oncogenic kinase targets are tested currently in these patients. In rapidly progressing and drug-resistant cases, high-dose polychemotherapy and stem cell transplantation have to be considered.

Microprobe analysis of inclusion bodies related to two benzofuran derivatives

1987 ◽  
Vol 45 ◽  
pp. 672-673
Author(s):  
T. L. Benning ◽  
P. Ingram ◽  
J. D. Shelburne
Keyword(s):  
Inclusion Bodies ◽  
Uranyl Acetate ◽  
Multiple Organ ◽  
High Dose ◽  
En Bloc ◽  
Tissue Samples ◽  
Transmission Electron ◽  
Organ Systems ◽  
Dense Inclusion ◽  
Melanin Complex

Two benzofuran derivatives, chlorpromazine and amiodarone, are known to produce inclusion bodies in human tissues. Prolonged high dose chlorpromazine therapy causes hyperpigmentation of the skin with electron-dense inclusion bodies present in dermal histiocytes and endothelial cells ultrastructurally. The nature of the deposits is not known although a drug-melanin complex has been hypothesized. Amiodarone may also cause cutaneous hyperpigmentation and lamellar lysosomal inclusion bodies have been demonstrated within the cells of multiple organ systems. These lamellar bodies are believed to be the product of an amiodarone-induced phospholipid storage disorder. We performed transmission electron microscopy (TEM) and energy dispersive x-ray microanalysis (EDXA) on tissue samples from patients treated with these drugs, attempting to detect the sulfur atom of chlorpromazine and the iodine atom of amiodarone within their respective inclusion bodies.A skin biopsy from a patient with hyperpigmentation due to prolonged chlorpromazine therapy was fixed in 4% glutaraldehyde and processed without osmium tetroxide or en bloc uranyl acetate for Epon embedding.

Impairment Rating and Spinal Cord Injuries: Revisiting the Guides

2010 ◽  
Vol 15 (3) ◽  
pp. 1-7
Author(s):  
Richard T. Katz
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injuries ◽  
Functional Independence ◽  
Outcome Data ◽  
Multiple Organ ◽  
Loss Of Function ◽  
Sixth Edition ◽  
Organ Systems ◽  
Cord Injury ◽  
Impairment Ratings

Abstract This article addresses some criticisms of the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides) by comparing previously published outcome data from a group of complete spinal cord injury (SCI) persons with impairment ratings for a corresponding level of injury calculated using the AMA Guides, Sixth Edition. Results of the comparison show that impairment ratings using the sixth edition scale poorly with the level of impairments of activities of daily living (ADL) in SCI patients as assessed by the Functional Independence Measure (FIM) motor scale and the extended FIM motor scale. Because of the combinations of multiple impairments, the AMA Guides potentially overrates the impairment of paraplegics compared with that of quadriplegics. The use and applicability of the Combined Values formula should be further investigated, and complete loss of function of two upper extremities seems consistent with levels of quadriplegia using the SCI model. Some aspects of the AMA Guides contain inconsistencies. The concept of diminishing impairment values is not easily translated between specific losses of function per organ system and “overall” loss of ADLs involving multiple organ systems, and the notion of “catastrophic thresholds” involving multiple organ systems may support the understanding that variations in rating may exist in higher rating cases such as those that involve an SCI.

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