Anasarca in an Infant – An Unusual Cause

Objectives Primary intestinal lymphangiectasia is a rare cause of protein losing enteropathy. It is usually seen in children less than 3 years of age. The disease is characterised by dilatation and engorgement of lymphatics in the small bowel due to congenital malformation of lymphatic channel or hypoplasia of lymphatics. Methods A 10 month old female child was admitted with a h/o persistent diarrhoea and generalised swelling of the body for 15 days. She was exclusively breastfed till 6 months, complementary feeding started thereafter. On examination, both eyelids were edematous with b/l pedal edema and abdominal distension. Investigations showed hypoalbuminemia, hypoproteinemia and thrombocytosis. Urine, stool examination and spot urine protein creatinine ratio were normal. USG abdomen showed mild ascites and edematous bowel loops. UGI endoscopy and biopsy showed multiple fragments of duodenal mucosa with subepithelium showing multiple dilated lymphatic spaces. The child was started on high protein, low fat diet with MCT, vitamin D, zinc and FFP transfusion. Child improved clinically with reduced edema and loose stools, hence discharged. I/v/o persistent thrombocytosis, we considered possibility of a rare syndrome, CHAPLE (Complement hyperactivation, Angiopathic Thrombosis and Protein losing enteropathy). However, CD55 level was normal and hence we also considered further evaluation for non -CHAPLE PIL but genetic work up could not be done. Results PIL should be considered as one of the differential diagnosis in a child presenting with anasarca. The main modality of treatment in our case was high protein, low fat diet and MCT supplements. Child was on regular follow up with pediatric gastroenterologist for about 3 months. Mother reported the baby had persistent loose stools and was treated at home and died before reaching a hospital. We have heard in literature about good outcomes in PIL as well as frequent relapses with chronicity. This acute life threatening event in PIL needs to be discussed regarding possibility of any thrombosis secondary to dehydration and thrombocytosis. Conclusions PIL is a rare condition seen in children less than 3 years. Early diagnosis with endoscopic visualization of the gut and biopsy of the small bowel may play a great role. Mainstay of treatment is high-protein, low fat diet with MCT supplement. Funding Sources None.

SWELLING OF THE SUBCUTANEOUS INTERSTITIUM UNDER THE INFLUENCE OF ISONIAZID AND DIFFERENT PH LEVELS

The article deals with the issues of interstitial conductivity for isoniazid and saline solution with different pH levels. Experimental studies were conducted to substantiate and explain the mechanisms of effectiveness of indirect endolymphatic drug administration. At the present stage, lymphotropic administration of anti-tuberculosis drugs occupies a worthy place in the complex therapy of patients with pulmonary and extrapulmonary tuberculosis. Lymphotropic therapy is an etio-pathogenetic method of treating patients and consists of regional subcutaneous injections of medicinal solutions with the use of lymphotropy factors, among which it is important to create an active functioning of the interstitial zones of lymphotropic administration, which determines the flow of drugs into the lymphatic channel. The influence of acidification and alkalinization of the medium on the hydrophilicity of the interstitium of the subcutaneous tissue of the parasternal zone, armpit, and interdigital spaces was studied. As incubation solutions, saline solution with pH 6.9, pH 7.4, pH 6.0 and 10% isoniazid solution (10%H) were used. It was found that the interstitial subcutaneous tissue of the lymphotropic injection zones is characterized by different intensity of swelling, which is probably due to the morphological features of the fiber, different content of loose connective and adipose tissues in it. The swelling coefficient is regulated by the pH level of incubation solutions and the chemical structure of the administered lymphotropically medicinal substance. Features of interaction between interstitial lymphotropic points and the drug should be taken into account when prescribing indirect endolymphatic therapy schemes. It is likely that the pH of the administered solutions must be maintained at the level of the physiological norm (7.4). Isoniazid in the lymphotropic points creates a depot that is more pronounced in the parasternal region.

Morphogenesis of limph nodes in Muscovy ducks during early posnatal onthogenesis

The dynamics of mass and linear parameters of lymph nodes of ducks is a direct reflection of structural and functional transformations of their lymphatic parenchyma. The peculiarities of quantitative dynamics of tissue components of peripheral lymphatic organs at early stages of postnatal ontogenesis are to a great extent determined by advanced growth rates of their absolute mass against the background of sharp increase of their antigenic stimulation intensity. Parenchyma of lymph nodes of newborn ducklings is characterized by relatively low degree of differentiation and is represented by diffuse lymphatic tissue with no pronounced signs of its division into separate functional zones. Internally, the lymphatic channel is represented by only two lymphatic sinuses - the central one, which is located in the central part of the organ and occupies a large relative area and a discrete edge sinus, which borders on the node capsule and has a much smaller relative area and, accordingly, is located at its periphery. The organ parenchyma is a diffuse cluster of stromal and lymphatic cells in the enlarged lymphatic vessel between the central (inner) and edge (outer) lymphatic sinuses, without signs of its division into cortical and brain matter. Among the lymphatic tissue of the lymph node, reticular stroma cells and the population of small lymphocytes have the largest relative amount.

MORPHOLOGICAL TRANSFORMATION OF INTESTINAL GRAFT AFTER CYSTECTOMY WITH ORTHOTOPIC PLASTIC OF THE URINARY BLADDER

Introduction.The histomorphological state and mechanisms of transformation of the intestinal epithelium of the orthotopic urinary bladder are unexplored.Purpose of research.The study the morphological adaptive and compensatory changes in the intestinal graft wall (IGW) and their relationship with homeostasis at various stages after surgical treatment. Materials and methods. The morphological state of the intestinal graft wall (IGW) was studied in 42 patient’s cystectomy undergoing with the formation of an orthotopic intestinal bladder (15-ileum, 27-sigmoid) at terms from 1 to 6.5 months and 1 year or more after the treatment.Results.Morphological changes occurring in the IGW wall begin with the moment of urine entering the lumen, which occurs in combination with changes in the stereotyped dynamics of the organ. Expressed changes are observed in all parts of the wall of the small and large intestine. There is regeneration and restructuring of the epithelium, expressed in atrophy and a decrease in the number of suction cylindrical cells and an increase in the number of mucus-forming goblet elements, terminating by 12 months and more after the operation. This combined with a decrease in the number and size of villi and crypts, reduction of the lymphatic channel and sclerosis of the blood vessels and stroma blocks suction. An increase in the number of mucus-forming goblet cells provides a barrier that protects the IGW mucosa from the effects of urine.Conclusion.Morphological changes occurring in the IGW wall under the influence of urine contribute to the preservation of homeostasis and are identical in the thick and thin-intestinal variant of plastic of the bladder.Disclosure: The study did not have sponsorship. The authors have declared no conflicts of interest

Pathogenic variant in EPHB4 results in central conducting lymphatic anomaly

Central conducting lymphatic anomaly (CCLA) is one of the complex lymphatic anomalies characterized by dilated lymphatic channels, lymphatic channel dysmotility and distal obstruction affecting lymphatic drainage. We performed whole exome sequencing (WES) of DNA from a four-generation pedigree and examined the consequences of the variant by transfection of mammalian cells and morpholino and rescue studies in zebrafish. WES revealed a heterozygous mutation in EPHB4 (RefSeq NM_004444.4; c.2334 + 1G>C) and RNA-Seq demonstrated that the EPHB4 mutation destroys the normal donor site, which leads to the use of a cryptic splice donor that results in retention of the intervening 12-bp intron sequence. Transient co-expression of the wild-type and mutant EPHB4 proteins showed reduced phosphorylation of tyrosine, consistent with a loss-of-function effect. Zebrafish ephb4a morpholino resulted in vessel misbranching and deformities in the lymphatic vessel development, indicative of possible differentiation defects in lymphatic vessels, mimicking the lymphatic presentations of the patients. Immunoblot analysis using zebrafish lysates demonstrated over-activation of mTORC1 as a consequence of reduced EPHB4 signaling. Strikingly, drugs that inhibit mTOR signaling or RAS-MAPK signaling effectively rescued the misbranching phenotype in a comparable manner. Moreover, knock-in of EPHB4 mutation in HEK293T cells also induced mTORC1 activity. Our data demonstrate the pathogenicity of the identified EPHB4 mutation as a novel cause of CCLA and suggesting that ERK inhibitors may have therapeutic benefits in such patients with complex lymphatic anomalies.