Abnormal Accumulation Of Fluid Research Articles

Lymphatic Endothelial Cells, Lymphedematous Lymphangiogenesis, and Molecular Control of Edema Formation

Lymphedema, defined as the abnormal accumulation of protein-rich fluid in soft tissues, results from the dysfunction of lymphatic system, an imbalance between lymph formation and its absorption into the initial lymphatics. Primary lymphedema occurs rarely on idiopathic or developmental abnormalities, especially hypoplasia or aplasia of lymphatics. Secondary lymphedema commonly develops when lymph transport is impaired due to lymphatic damage or resection of lymph nodes in surgery, infection, and radiation. Lymphatic endothelial cells (LECs) actively participate in the phenotypic consequences of a deranged lymphangiogenesis relating to tissue fluid accumulation in the pathogenesis of lymphedema. Recent insights into molecular genetic bases have shown an updated genotype-phenotype correlation between lymphangiogenesis, lymphatic function, and lymphedema. FOXC2, EphrinB2, VEGFR-3, VEGF-C, angiopoietin-2, Prox-1 and podoplanin have proved to be important factors of the genetic cascade linking to hereditary lymphedema, and embryonic and postnatal lymphatic development. FOXC2 may have a key role in regulating interactions between LECs and smooth muscle cells, and in the morphogenesis of lymphatic valves. Reduced VEGFR-3 tyrosine kinase activity and subsequent failure in transducing sufficient physiological VEGF-C/-D signals may affect LEC function and structure in the intercellular junctions and peri-lymphatic components. Identification of genetic markers in humans and animal models would facilitate the management of environmental factors influencing the expression and severity of lymphedema, and provide a basis for developing novel targeted therapies for the disease.

Postoperative chylous ascites: An institutional experience over two years

Chylous ascites is defined as the abnormal accumulation of chylous fluid in the abdominal cavity. This is an uncommon occurrence and is usually a result of disruption of the normal lymphatic channels during surgery at the base of mesentery, retroperitoneum or around the cisterna chyli. Chylous ascites is associated with significant morbidity such as malnutrition and ascitic distension, and may delay the commencement of chemotherapy in some patients. The authors performed a retrospective review of an institutional experience over 2 years (2005–2006), involving three cases of postoperative chylous ascites. Treatment modality and outcomes, as well as volume of chylous drainage were followed clinically. All three patients were treated successfully with non‐surgical means. All three had cessation of oral feeding, while the use of intravenous somatostatin led to early cessation of ascites in one case. The patients have been followed up and have not had recurrence or long‐term sequelae of chylous ascites. Chylous ascites is an uncommon condition for which early recognition and commencement of treatment is essential in preventing morbidity. In our experience, non‐surgical treatment of chylous ascites leads to favourable clinical outcomes.

Involvement of cystic fibrosis transmembrane conductance regulator in infection‐induced edema

Abnormal fluid accumulation in tissues, including the life-threatening cerebral and pulmonary edema, is a severe consequence of bacteria infection. Chlamydia (C.) trachomatis is an obligate intracellular gram-negative human pathogen responsible for a spectrum of diseases, causing tissue fluid accumulation and edema in various organs. However, the underlying mechanism for tissue fluid secretion induced by C. trachomatis and most of other infectious pathogens is not known. Here, we report that in mice C. trachomatis infection models, the expression of cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP activated chloride channel, is up regulated together with increased cytokine release and tissue fluid accumulation that can be reversed by treatment with antibiotic specific for C. trachomatis and CFTR channel blocker. However, C. trachomatis infection cannot induce tissue edema in CFTRtm1Unc mutant mice. Administration of exogenous IL-1beta to mice mimics the C. trachomatis infection-induced CFTR upregulation, enhanced CFTR channel activity and fluid accumulation, further confirming the involvement of CFTR in infection-induced tissue fluid secretion.

HGF and MET Mutations in Primary and Secondary Lymphedema

Lymphedema is the abnormal accumulation of protein-rich fluid in the interstitial space. Primary lymphedema is a rare genetic condition with both autosomal dominant and autosomal recessive modes of inheritance. Three genes, FLT4 (VEGFR3), FOXC2, and SOX18 cause varying forms of primary lymphedema. In industrialized countries, secondary lymphedema is usually associated with cancer therapy and/or trauma. Recent observations suggested that hepatocyte growth factor/high affinity hepatocyte growth factor receptor (HGF/MET) were new candidate lymphedema genes. The coding exons and flanking regions of HGF and MET were directly sequenced in 145 lymphedema probands, 59 unrelated women with secondary lymphedema following treatment for breast cancer, 21 individual patients with lymphedema and intestinal lymphangiectasia, and at least 159 unrelated ethnic matched control individuals. Mutations leading to truncation or missense changes in evolutionarily conserved residues of HGF and MET were identified. These mutations were not polymorphic in control individuals. The identification of HGF/MET mutations in primary lymphedema, lymphedema/lymphangiectasia, and breast cancer-associated secondary lymphedema suggests that the HGF/MET pathway is causal or alters susceptibility for a broad range of lymphedema phenotypes. The HGF/MET pathway provides a new target for the prevention and/or treatment of lymphedema.

Hydrops fetal no inmune

Non-immune hydrops fetalis (NIHF) is characterized by abnormal accumulation of serous fluid in the skin (edema) and body cavities (pericardial, pleural or ascitic effusions), without evidence of circulating antibodies against red blood cell antigens. This entity is caused by a heterogeneous group of disorders, including cardiovascular, gastrointestinal, pulmonary, chromosomal, hematological and infectious diseases. NIHF is an important cause of perinatal loss, with mortality ranging from 50% to 98%, depending on the etiology.

A novel microdevice for the treatment of hydrocephalus: design and fabrication of an array of microvalves and microneedles

We present an implantable, microfabricated device for the treatment of hydrocephalus. Hydrocephalus is a medical condition, in which an abnormal accumulation of cerebrospinal fluid (CSF, a water-like fluid that circulates around and protects the brain and spinal cord.) occurs in the brain. The novel microdevice presented here mimics the function of natural one-way valves, arachnoid villi, found in the human brain. Hence, we name it microfabricated arachnoid villi (MAV). The MAV consists of an array of one-way microvalves and hollow microneedles. The one-way microvalves control flow based on pressure differential. A Parylene microvalve array with a dome petal geometry was designed and fabricated. Initial flow tests demonstrated the desired low cracking pressure of the valve and a sufficient mechanical stability. The hollow microneedle array was designed to pierce the dura mater membrane (A tough fibrous membrane covering the brain and the spinal cord and lining the inner surface of the skull.) and provide a conduit for CSF. An SU-8 microneedle array was designed and successfully microfabricated. The innovative MAV may open a new era in the treatment of hydrocephalus.

The feasibility of using poroelastographic techniques for distinguishing between normal and lymphedematous tissues in vivo

Lymphedema is a common condition involving an abnormal accumulation of lymphatic fluid in the interstitial space that causes swelling, most often in the arm(s) and leg(s). Lymphedema is a significant lifelong concern that can be congenital or develop following cancer treatment or cancer metastasis. Common methods of evaluation of lymphedema are mostly qualitative making it difficult to reliably assess the severity of the disease, a key factor in choosing the appropriate treatment. In this paper, we investigate the feasibility of using novel elastographic techniques to differentiate between lymphedematous and normal tissues. This study represents the first step of a larger study aimed at investigating the combined use of elastographic and sonographic techniques for the detection and staging of lymphedema. In this preliminary study, poroelastographic images were generated from the leg (8) and arm (4) subcutis of five normal volunteers and seven volunteers having lymphedema, and the results were compared using statistical analyses. The preliminary results reported in this paper suggest that it may be feasible to perform poroelastography in different lymphedematous tissues in vivo and that poroelastography techniques may be of help in differentiating between normal and lymphedematous tissues.

Paracentesis in the management of ascites

Ascites is the abnormal accumulation of fluid in the peritoneal cavity. Men have little or no peritoneal fluid, but women may have up to 20 ml depending on the phase of the menstrual cycle. Ascites is a relatively common clinical finding with a range of malignant and non-malignant causes (Table 1). About 85% of ascites is caused by liver disease (Runyon, 2004), and cancer accounts for about 10% of cases (Smith and Jayson, 2003; Becker et al, 2006).

High-pressure hydrocephalus: A novel analytical modeling approach

Hydrocephalus is an abnormal accumulation of cerebrospinal fluid (CSF) within ventricles and subarachnoid space (SAS) as a result of disturbances in secretion or absorption procedures. It is believed that arachnoid villi cells, which are microscopic projections of pia-arachnoid mater that extend into venous channels in sagittal sinus, are the main sites for CSF absorption, but it is tempting to speculate that a significant portion of CSF is removed from the SAS by nasal lymphatic vessels around olfactory nerve. Thus, in this paper, we propose an analytical model of CSF–lymphatic-blood circulation, in which these two output pathways for CSF absorption have been considered. Mathematical relations governing the pressures in different interacting compartments of the brain are considered. In addition, for increasing the similarity of our model to the physiological conditions, the bulk flow mechanism, which is supposed to occur during CSF absorption, has been considered in our model. We used our model to simulate hydrocephalus. The results indicate that the lymphatic disorders have more considerable effect in decreasing CSF absorption, compared to the disturbances in arachnoid villi cells. Based on our modeling, we believe that disorders in lymphatic pathway may be a cause of high-pressure hydrocephalus. Surely experimental studies are required to validate our hypothesis.

Exercise for Women With or at Risk for Breast Cancer–Related Lymphedema

Breast cancer accounts for approximately one third of all cancers diagnosed in American women. In 2005, it was estimated that 211,240 women would be diagnosed with invasive breast cancer in the United States and 58,490 would be diagnosed with in situ breast cancer.1 Although advancements in technology have led to early detection and a higher survival rate,2 approximately 40,410 US women were expected to die from this disease in 2005.1 Many women experience secondary complications of the disease and its treatments, including decreased quality of life (QOL), weight gain, sleep disturbances, poor body image, fatigue,3 increased risk for osteoporosis, cardiovascular disease, premature menopause, and lymphedema.4 Breast cancer is commonly treated by surgery, chemotherapy, or radiation. Axillary dissection or radiation can result in lymphedema due to obstruction, trauma, and inflammation of the lymphatic system.5 Lymphedema has been defined as an abnormal accumulation of protein-rich fluid,4,6 edema, and chronic inflammation5,7 and can elicit pain, tightness, and heaviness in the upper extremity (UE), as well as lead to recurrent skin infections.8 Lymphedema is classified into 3 stages based on severity. Stage I lymphedema is spontaneously reversible9 and typically involves pitting edema, an increase in UE girth, and heaviness.8 Stage II is marked by a spongy consistency of the tissue without signs of pitting edema. Tissue fibrosis causes limbs to harden and increase in size. Stage III, lymphostatic elephantiasis, is the most advanced stage but is rarely seen following breast cancer treatment.9 Management of lymphedema in women with breast cancer has been a subject of debate for many years. Treatment options include elevation, massage, compression garments, pneumatic compression pumps, and complex physical therapy.8 Traditionally, women who had been treated for breast cancer and those with pre-existing lymphedema …

Alveolar fluid transport: a changing paradigm

UNLIKE OTHER EPITHELIAL TISSUES that transport large amounts of solutes and water, the alveolar epithelium is faced with a unique physiological challenge. To facilitate optimal gas exchange and to trap airborne particulate matter, it must maintain a thin layer of fluid on the luminal surface of its extensive alveolar network. However, the thickness of the fluid layer must be tightly regulated, since even slight increases in the fluid depth could adversely affect gas exchange, whereas dehydration of the surface would impair ciliary clearance. The alveolar flooding associated with acute respiratory distress syndrome or the airway dehydration in cystic fibrosis represents two pathological extremes of a failure to maintain proper airway fluid balance. Both of these conditions account for a significant burden of morbidity and mortality worldwide (16, 20). Extensive research done in the last two decades has shown that precise regulation of alveolar surface fluid layer is achieved through vectorial transport of solutes between the alveolar surface and interstitial spaces with active Na transport across the alveolar epithelium generating the osmotic force for movement of water (12, 17). The broadly accepted paradigm for Na transport in the alveoli involves a two-step process: movement of Na through cation channels in the apical cell membrane constitutes the first step, and extrusion of the excess Na thus acquired via basolateral Na-K-ATPase is the second step (19). However, despite extensive research using many different approaches that support this paradigm, gaps still exist in our understanding of how this fine balance is achieved in vivo (19). In particular, there are several unresolved questions that, when resolved, could significantly affect our view of alveolar fluid clearance. First, type 1 cells constitute 95% of the alveolar surface area, but their role in ion transport is not completely clear. If there are significant differences between the transport characteristics of type I and type II cells, the current paradigm describing alveolar fluid clearance would need to be modified. Second, although cation permeability pathways have been described fairly well, the precise pathways for movement of anions are unclear. The character of these channels is important since anion channels could form either co-ion pathways for the concomitant movement of Na and Cl or a secretory pathway to increase alveolar fluid. Finally, alveolar fluid clearance appears to consist of a basal and stimulated component of reabsorption. The relative contribution of different ion channels and different cell types to these two components of clearance is far from clear. These questions are all underscored by the differences between the robust increases in transport that can be produced by several different treatments in vitro and the often weak clearance response of the in vivo lung epithelium to the same treatments

Do the data obtained by the PiCCO system enable one to differentiate between direct ALI/ARDS and indirect ALI/ARDS?

It is known that measurement of the intrathoracic blood volume (ITBV) is a more accurate estimate of cardiac preload than pressure measurements using central venous or pulmonary artery occlusion pressures. Extravascular lung water (EVLW) is defined as the value of the intrathoracic thermal volume minus the ITBV. An increase in EVLW is the pathophysiological basis for the development of pulmonary edema (PE). There is evidence to suggest that therapy to reduce EVLW may improve outcome in the critically ill patient. The bedside assessment of EVLW may be very useful in identifying and quantifying PE, and hence in selecting patients who might benefit from a fluid restriction/depletion therapeutic strategy based on EVLW monitoring. The PiCCO (Pulsion, Munich, Germany) provides an estimate of the ITBV, EVLW, and permeability index (PI) via a single transpulmonary thermodilution technique. PE is defined as the abnormal accumulation of fluid in the extravascular space of the lung. ALI/ARDS is characterized by pulmonary edema. PE consists of increased hydrostatic PE (cardiogenic PE) and increased permeability PE (ALI/ARDS). Increased permeability PE (ALI/ARDS) is further classified into direct lung injury type and indirect lung injury type. PI was calculated as the ratio of EVLW to ITBV, which was previously shown to reflect permeability of the alveolar-capillary barrier. The early recognition and differential diagnosis of direct lung injury and indirect lung injury may be challenging.

Unusual findings during abdominal placement of a ventriculoperitoneal shunt

The authors present three cases of infants born with myelodysplasia. Each infant underwent closure of a myelomeningocele and within 2 to 4 days placement of a ventriculoperitoneal (VP) shunt. In each case, on opening the peritoneal cavity, the authors observed egress of a dark or creamy dark fluid. None of the patients had a history of abdominal birth trauma. The decision was made to continue the procedures and send samples of the unusual fluids to the laboratory for culture and analysis. The cultures proved to be nondiagnostic and the characteristics of the fluid samples were most consistent with those of blood-tinged chyle. The authors hypothesize that, occasionally, the mechanical tautness that is created with repair of myelomeningoceles is sufficient to rupture small lymphatic vessels and accompanying blood vessels of the abdomen. An alternative hypothesis is that abdominal compression due to closure of the myelomeningocele may temporarily compress the liver, leading to raised intraportal pressures and resulting in weeping of chyle from the gastrointestinal tract. This abnormal fluid accumulation did not lead to chronic ascites, VP shunt infection, or dysfunction at long-term follow-up examination and abdominal visceral function has not been an issue.

Increased cystic fibrosis transmembrane conductance regulator (CFTR) expression in the human hydrosalpinx

Hydrosalpinx (HSP), characterized by abnormal fluid accumulation in the Fallopian tube, is one of the main causes of infertility in women; however, the mechanism underlying the formation of hydrosalpinx fluid (HF) remains elusive. The present study investigated the possible involvement of cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-dependent chloride channel, in the pathogenesis of hydrosalpinx. Masson's trichrome staining was used to characterize epithelial transformation in human HSP; RT-PCR, immunohistochemistry and immunofluorescence staining were used for CFTR expression and localization. Masson's trichrome staining showed areas of epithelial transformation, focally attenuated and pseudostratified. Immunostaining showed enhanced CFTR immunoreactivity in the focally attenuated and pseudostratified areas of HSP epithelium. RT-PCR revealed that CFTR expression in HSP was significantly greater than that in normal Fallopian tubes. These results indicate that HSP epithelium undergoes epithelial transformation with elevated CFTR expression, which may lead to increased transepithelial electrolyte and fluid secretion resulting in HF formation. The present findings may lead to the development of new treatment strategies for infertile patients with HSP.

Perturbations in the Biochemical Composition of Fetal Fluids Are Apparent in Surviving Bovine Somatic Cell Nuclear Transfer Pregnancies in the First Half of Gestation1

Amniotic and allantoic fluid volumes and composition change dynamically throughout gestation. Cattle that are pregnant with somatic cell nuclear transfer (NT) fetuses show a high incidence of abnormal fluid accumulation (particularly hydrallantois) and fetal mortality from approximately midgestation. To investigate fetal fluid homeostasis in these pregnancies, Na, K, Cl, urea, creatinine, Ca, Mg, total PO(4), glucose, fructose, lactate, total protein, and osmolalities were measured in amniotic and allantoic fluids collected at Days 50, 100, and 150 of gestation from NT pregnancies and those generated by the transfer of in vitro-produced embryos or by artificial insemination. Deviations in fetal fluid composition between NT and control pregnancies were apparent after placental and fetal organ development, even when no gross morphological abnormalities were observed. Individual NT fetuses were affected to varying degrees. Elevated allantoic Na was associated with lower K and increased allantoic fluid volume or edema of the fetal membranes. Total PO(4) levels in NT allantoic and amniotic fluid were elevated at Days 100 and 150. This was not accompanied by hypophosphatemia at Day 150, suggesting that PO(4) acquisition by NT fetuses was adequate but that its readsorption by the kidneys may be impaired. Excessive NT placental weight was associated with low allantoic glucose and fructose as well as high lactate levels. However, the fructogenic ability of the NT placenta appeared to be normal. The osmolality of the fetal fluids was maintained within a narrow range, suggesting that the regulation of fluid composition, but not osmolality, was impaired in NT pregnancies.

Malignant Pericardial Effusion--An Uncommon Complication of Multiple Myeloma: Case Report

Multiple myeloma is a condition usually associated with lesions of the skeleton. However, under rare circumstances, the malignant plasma cells may infiltrate the pericardium, resulting in an effusion. If left untreated, the abnormal accumulation of pericardial fluid will result in cardiac tamponade, requiring drainage. The following report describes a multiple myeloma patient who developed secondary pericardial and pleural effusions, which were surgically drained via a pleuropericardial window.

The Problem of Post-Breast Cancer Lymphedema: Impact and Measurement Issues

Breast cancer treatment is recognized as the most common cause of secondary lymphedema (LE) in the developed countries of the world. LE occurs as both an acute and chronic health condition in which significant and persistent swelling is associated with an abnormal accumulation of protein-rich fluid. The impact of LE is significant on a wide range of daily activities and survivorship quality of life. Measurement and quantification of LE has been problematic despite the fact that various methods have been used to measure limb volume (LV). Perhaps in part because of difficulties in measurement and diagnosis, the reported incidence of LE varies greatly among persons treated with surgery and radiation for breast cancer. Through increased measurement accuracy, LE incidence and prevalence following current therapeutic approaches for breast cancer treatment cancer will be better understood, and more informed decisions about risk factors, treatment interventions, and recovery will be made. Further identification of epidemiological and clinical factors associated with risk and incidence will provide the necessary foundation for preventive intervention. Bilateral measurements at pre-op and over time are necessary to assess LV changes during follow-up, as it is important as part of the differential diagnosis to note whether volume change has occurred in the affected limb alone or in both limbs. Application of rigorous measurement protocols, assessment of symptom experience, and establishment of a data base on bilateral LV at pre-op for later comparison are essential components of a solid foundation for intervention studies. Through multidisciplinary collaboration with rigorous scientific approaches feasible to be carried out in the clinical setting, we have the opportunity to better target risk factors for development of LE, design data-based interventions, and improve post-treatment quality of life.

Eye Movement Disorders in Hydrocephalus and Increased Intracranial Pressure

Hydrocephalus is an abnormal accumulation of cerebrospinal fluid that causes enlargement of cerebral ventricles and increased intracranial pressure. Hydrocephalus and increased intracranial pressure are associated with many neurologic disorders in children and adults. There are numerous ocular findings described in patients with increased intracranial pressure. The purpose of this paper is to discuss several eye movement disorders associated with hydrocephalus and increased intracranial pressure.

INJURY OF THE COLLATERAL LIGAMENTS OF THE DISTAL INTERPHALANGEAL JOINT DIAGNOSED BY MAGNETIC RESONANCE

We describe the clinical, imaging, and necropsy findings of two horses with severe injury of the collateral ligaments of the distal interphalangeal (DIP) joint diagnosed using magnetic resonance (MR) imaging. In MR images it was possible to examine the collateral ligaments of the DIP joint from the origin at the middle phalanx to the insertion on the distal phalanx. Both horses in this report had abnormal high signal intensity within the collateral ligaments of the DIP joint, and one horse had abnormal high signal intensity within the bone of the distal phalanx on short tau inversion recovery (STIR) and T2-weighted imaging sequences. High signal intensity on STIR and T2-weighted images represents abnormal fluid accumulation indicative of inflammation, within ligament, tendon, or bone on these imaging sequences. Abnormalities were confirmed on necropsy in both horses. Injury of the collateral ligaments of the DIP joint should be considered as a source of pain in horses with lameness localized to the foot.

Immunotherapy with the trifunctional antibody removab leads to significant elimination of tumor cells from malignant ascites in ovarian cancer: Results of a phase I/II study

2504 Background: Malignant ascites is the abnormal accumulation of fluid within the peritoneal cavity due to the peritoneal spread of the tumor. It is associated with a poor prognosis and low quality of life. Currently available treatment methods are of limited success. In a phase I/II study we investigated a new concept of ascites treatment based on the intraperitoneal application of the trifunctional antibody removab. Via its two binding arms specific for EpCAM and CD3, and its Fc region, removab binds simultaneously to tumor cells, T cells and antigen-presenting cells resulting in a significant tumor cell killing. Methods: For evaluation of treatment success, we developed an immunofluorescence detection method for monitoring effects on tumor cells within the ascites fluid. Cytospins were prepared from fresh ascites samples before, during and after removab treatment. Tumor cell reduction was monitored with a fluorescence double staining (EpCAM; CK8, 18,19). In addition, tumor cell/leukocyte ratio was determined by EpCAM/CD45 double staining. Results: 23 women with ascites in ovarian cancer (stage IIIb, IIIc and IV) were treated with up to 5 intraperitoneal removab infusions within 13 days using increasing dosages of 5–200 μg. During the treatment, a drastic and continuous decrease of tumor cells within the ascites fluid from 540,000 /10e6 total cells to a mean of 35 /10e6 total cells was observed. Remarkably, the tumor cell/leukocyte ratio was completely reversed after the first low-dose (10 μg) removab infusion. After the last removab infusion, all patients had tumor cell counts below 0.1% to 0%. These findings were associated with a strong reduction of ascites flow from a median of 105 ml/h to 23 ml/h. By the end of observation (day 37), 22/23 patients had no need for further paracentesis. Conclusions: The trifunctional antibody removab may provide a promising tumor targeted option for treatment of malignant ascites. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Trion Research GmbH Trion Pharma GmbH