Cytokine cascade in Kawasaki disease versus Kawasaki-like syndrome.

Kawasaki disease (KD) is a medium vessel systemic vasculitis that predominantly occurs in children below five years of age. It is an acute febrile condition in which coronary artery aneurysms and myocarditis are the most common cardiovascular complications. It is most often characterized by hypercytokinemia. The etiopathogenesis of KD is not fully understood. The present review synthesizes the recent advances in the pathophysiology and treatment options of KD. According to different studies, the genetic, infections and autoimmunity factors play a major role in pathogenesis. Several susceptibility genes (e.g. caspase 3) and cytokines (e.g. IL-2, IL-4, IL-6, IL-10, IFN-gamma and TNF-alpha) have been identified in KD. Patients with high cytokine levels are predisposed to KD shock syndrome. The importance of respiratory viruses in the pathogenesis of the disease is unclear. Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may induce in children and adults an abnormal systemic inflammatory response. This syndrome shares characteristics with KD. It has been called by many terms like MIS-C (Multisystem Inflammatory Syndrome in Children), PIMS-TS (pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2), hyperinflammatory shock syndrome, cytokine storm (cytokine release syndrome) or simply, Kawasaki-like syndrome. The cytokine's role in the development of KD or Kawasaki-like syndrome being triggered by COVID-19 is controversial. The presences of the antiendothelial cell autoantibodies (AECAs) together with the newly developed hypothesis of immunothrombosis are considered potential pathogenic mechanisms for KD. In consequence, the diagnosis and treatment of KD and Kawasaki-like syndrome, one of the most common causes of acquired heart disease in developed countries, are challenging without a clearly defined protocol.

Primary eosinophilic esophagitis in children and adults: new aspects for diagnosis.

Eosinophilic esophagitis (EoE) is a chronic, Th2-type immune-mediated disorder. During the past decade, the increasing prevalence of EoE has been recognized in pediatric and adult populations all over the world. EoE diagnosis can be frequent challenging. Three criteria must be met to diagnose EoE: clinical symptoms of esophageal dysfunction, an esophageal biopsy with a peak eosinophil count of at least 15 eosinophils per high-power microscopy field and exclusion of other possible causes of esophageal eosinophilia. Although eosinophils mediate the EoE pathogenesis, proinflammatory cytokines are also critically involved. In the past years biologic therapeutics have revolutionized treatment of EoE.

Eosinophilic esophagitis.

Eosinophilic esophagitis is a chronic, immune-mediated disorder, isolated to the esophagus. Current theory suggests that the former may be caused by cell-mediated food hypersensitivity or may be a subset of eosinophilic gastrointestinal disease, an autoimmune disorder. During the last decade, the increasing prevalence of EoE has been recognized in pediatric populations. Reports support the efficacy of dietary restriction or corticosteroid therapy. Aditional research is needed to determine etiology, allow earlier clinical recognition and improve treatment. Because no single symptom, endoscopic finding or histopathologic feature is pathognomonic, the diagnosis can frequently be challenging. The current article reviews the possible etiology, clinical presentation, diagnosis, and treatment of this disorder, which has been called not only allergic esophagitis (which may be the most important cause), but also eosinophilic esophagitis, primary eosinophilic esophagitis, and idiopathic eosinophilic esophagitis.

Immunological aspects predicting metastatic sentinel lymph node in early breast cancer patients.

Tumour antigens are poorly expressed, heterogeneous and they modulate rapidly. As a result, their recognition and elimination by the immune system is very difficult. There are several mechanisms, by means of which, the host can neutralize oncogenesis and prevent it from occurring. The sentinel lymph node concept has brought about a revolution in the surgical treatment of the regional lymphatic basin while preserving the prognostic value of the regional lymph node status in breast cancer. This prospective study included 93 women with early breast cancer with initial indication for surgery in whom the sentinel lymph node technique was employed. Cell immune response was assessed prior to surgery by means of in vitro mononuclear cells blastic transformation assay (BLT), of immunoglobulin (Ig) and interleukin 2 (IL-2) measurements. The results were correlated with tumour size, presence of positive sentinel lymph node, tumour proliferation and growth markers (Ki-67, c-erbB2, bcl-2). Even in its less advanced stages, breast cancer is more aggressive and associates with an increased rate of sentinel lymph node metastases in patients below 50 years old, the tumour size exceeds 20 mm, with the presence of peritumoral lymphocytic infiltrate, positive Ki-67 and bcl-2, an alteration of T helper (Th) lymphocytes function, increased immune suppression through IL-2 decrease, signalled by blastic transformation indexes modifications and a drop in IL-2 production (p<0.01).

Interleukin-2 alterations in the immune status of patients with mammary neoplasm.

Immune control is achieved by the balance between tumour reduction mechanisms and the "immunological creeping" phenomenon. The purpose of this study was to look into the alterations of the immune effector component in the case of mammary tumours. The study included 42 cases of women with a clinical diagnosis of mammary tumour, initially referred for surgery, with a mean age of 45.07 (18-65 years of age). Neither radiotherapy nor chemotherapy had been given to the patients before surgery. Histopathological examination performed intraoperatively as well as later, under paraffin, revealed 12 cases of malign tumours. The control group consisted of 18 women (blood donors), apparently healthy, with a mean age of 41 (30-49 years of age). In both groups, the immune status was assessed by means of: lymphocyte counts, T-lymphocyte counts (TL), rosetting, lymphocyte blastic transformation test (BLT) under the action of polyclonal mitogens, immunoglobulin dosing and Interleukin-2 (IL-2) determination in lymphocyte cultures stimulated with mitogens. The conclusion of our results has been that even in the less advanced stages of mammary cancer, there occur alterations of the immune response represented by: A decrease in the total number of lymphocytes, especially through a decrease of the TL number; A decrease of the lymphocyte blastic transformation index on stimulation with PHA; A decrease of IL-2 concentration in cultures stimulated with mitogens through the impairment of the TL CD4+ (TL Helper) function. The decrease of IL-2 production capacity influences the transmission of the immune message to the cytotoxic TL and thus impairs the cytotoxic effector component whose role is to remove tumoral cells. Evidence of IL-2 involvement in the immunodeficiency of mammary cancer patients could prove useful for diagnosis purposes and could plead in favour of the therapeutic potential of this interleukin.

Morpho-functional aspects of the influence of procaine and diethylaminoethanol treatment on the immune system of rabbits.

Research was conducted in 24 male rabbits divided into three equal groups: 1) Controls; 2) Given daily i.m. injections with 15 mg/kg body weight of procaine for 30 days; 3) Given daily i.m. injections with 15 mg/kg body weight of diethylaminoethanol (DEAE) for 35 days. Blood samples were taken from the auricular vein to perform haematological investigations: before treatment, during treatment and for another 7 weeks after termination of treatment. At the end of the experiment, the animals were sacrificed in order to collect: 1) leukocytes, macrophages and lymphocytes from their spleen, for the purpose of immunological investigations, and 2) fragments of bone marrow (femur), thymus and spleen, for histopathological investigations. The result of haematological investigations indicated a statistically significant increase of circulating lymphocytes had occurred in rabbits treated with DEAE. There was an increase of percentage as well as of number of circulating lymphocytes. The increase occurred gradually in the course of treatment and continued after treatment was terminated. There were higher values than the initial ones by 44.4% and 66.4%, respectively, during the second and the fourth week after termination of treatment. Afterwards, the values started decreasing, so that by the end of the experiment (week 7 after termination), the values came close to those before treatment. Immunological findings indicated that T lymphocytes collected from rabbits treated with procaine or DEAE did not synthesize migration inhibition factors. Procaine and DEAE were found, in vitro, not to have a polyclonal stimulating effect over T lymphocytes. A study of blastic differentiation showed lymphocytes from treated rabbits to incorporate a larger amount of tritiated thymidine, by 52.6% in the procaine group and by 90% in the DEAE group, than those from non-treated rabbits. Histopathological examination indicated signs of a more intense activity in tissue formations involved in cell proliferation in the lymphoid organs collected from DEAE treated rabbits.

Analysis by flow cytometry of the subpopulations of lymphocytes from the peripheral blood of procain or diethylaminoethanol treated rabbits.

The authors worked on 3 groups of 8 male rabbits, New Zealand race: 1) controls; 2) procain injected i.m., 15 mg/kg body weight, daily, for 30 days; 3) i.m. injected with diethylaminoethanol (DEAE), 15 mg/kg body weight, daily, for 35 days. The expression of the MHC I, MHC II, CD43, CD4 and IgM antigenic markers on the plasmatic membrane of the lymphocytes was studied using flow cytometry and monoclonal antibodies. Procain or DEAE treatment reduced the percentage of lymphocytes expressing I MHC, from 99.06 in the control group, to 94.51 in procain group and to 96.91 in the DEAE group. The intensity of expression of MHC complexes of class II decreases from 160.94 in the control group, to 107.21 in the procain group and to 104.05 in the DEAE group. No significant differences were noticed between the three groups of rabbits concerning the rate of lymphocytes that have on their surface expressed markers for CD43 (lymphocytes T), CD4 (Th), or IgM (lymphocytes B). Lymphocytosis induced in rabbits as a result of the DEAE treatment took place without a change in the proportions of lymphocyte subpopulations. The authors consider that owing to their capacity to reduce the expression of antigens MHC of class I and class II on the membrane of lymphocytes, procain and DEAE can have benefic effects in some autoimmune, autoaggression and inflammatory diseases.

Immune mechanisms in the process of hepatopathies chronicization. Contribution and role of lymphokines.

The study attempts to evaluate the role of interleukin-6 (IL-6) in the pathogenesis of chronic hepatitis. We have used EIA sensitive methods to determine the serum concentration in patients with chronic active hepatitis of HB (+) (CAH-HE Ag+) antigen, with chronic active hepatitis of HB(-) (CAH-HBAg-) antigen and in those with persistent chronic hepatitis of HB(+) (CPH-HBAg+) antigen, compared with a group of controls (blood donors) in whom HBAgs, antiHBs, HBAge, antiHBe and anti HBc were absent. Disease status diagnosis was given in accordance with international conventions, immunologic tests included. The fact that the T lymphocytes with a CD56 are present in the liver and that same marker is also encountered on the Kuppfer cells, but not on the T lymphocytes in circulation, shows that in the liver the interleukin 6 is produced by the activated T lymphocytes and by the Kuppfer cells. Therefore, in such conditions, LB stimulation and growth is performed rather by IL-6 and to a lesser extent by IL-8. This statement is also supported by the finding that in the lymphocyte cultures in the peripheral blood there is no difference in the response to polyclonal mitogens between patients with CAH-HBAg(+) and those with CAH-HBAg(-). Also, there are no significant differences in the total immunoglobulin concentrations, but there are differences in the IgM concentration (greater in CAH-HBAg(+). In our investigations, the serum level of IL-6 (40.1 +/- 6.8 pg/ml) was higher in those with higher immunoglobulin concentrations-both IgG, but more particularly IgM. The IgM increase was correlated with the presence of HBAg. Therefore, the highest IL-6 values were found in CAH with HBAg(+). Increases of serum IL-6 concentrations were found during intervals of severe hepatic aggression manifested in a cytolitic syndrome, with transaminase increase. In the case of determinations in dynamics, the values decreased as the enzyme titre decreased. We can state that the serum activity of IL-6 reflects the degree of liver inflammation and can be used as a parameter for monitoring the disease.

[Differentiated thyroid cancer]. / Cancerul tiroidian diferentiat.

In the interval 1979-1988, out of 1070 operated goiters 77 malignant thyroid tumors were recorded, 60 of them being differentiated: papillary--32 (53.4%), vesicular--12 (20%), mixed forms--16 (26.7%). The differentiated thyroid carcinomas had peculiar clinical biological and prognostic features and were framed: stage I--60%, stage II--23.4% and state III-IV--16.6%. Only 15 cases presented lymph node metastases. In 16 cases the thyroid tumor was associated with another thyropathy: Hashimoto's thyroiditis--5 cases, Basedow's disease--1 case. The surgical intervention was performed in two times: first total lobectomy or total lobo-isthmectomy [correction of lobioistectomy] with contralateral subtotal exeresis, then total thyroidectomy. It is insisted upon a careful surveillance of postoperative evolution (clinical, biological, scintigraphy) in order to detect the recurrence and apply a proper treatment.

[The "cold" thyroid nodule]. / Nodului tiroidian "rece".

The main problem posed by an (apparent) solitary thyroid nodule is cancer identification, present in about 10% of the nodules excised surgically. This percent might increase to 25-30% in the cold scintigraphic nodules. Therefore, a combination of all the methods for nodule assessment is necessary: anamnesis, physical examination, functional tests, therapeutic test with tyrosine and thyroid imaging, but mainly the intensive active exploration including puncture-biopsy with a fine needle and exeresis with extemporaneous and paraffin morphological checking. Starting from a two decades' experience of a group of endocrinologists, surgeons, anatomo-pathologists and specialists in nuclear medicine, in 2,289 thyropathies operated--of whom 1691 (poly)nodular goitres and 1,190 non-capturing nodules--the authors suggest an investigation algorithm for achieving a differentiated surgery in terms of the pre- and intraoperative morphological findings. This attitude permitted both the improvement of the surgeries of thyroid cancers and the exeresis of benign nodules under low-risk surgical conditions or avoidance of a "non-necessary" surgery.

[The surgery of intestinal obstruction in the elderly]. / Aspecte ale chirurgiei ocluziei intestinale la batrîni.

Out of 301 intestinal obstructions treated at the 1st Surgical Clinic of Iasi in the interval 1970-1987, 58 patients aged between 70 and 90 years (mean age 75 years) were recorded. Anatomo-clinically these 58 cases presented: strangulated hernia (19 cases), strangulated eventration (2 cases), strangulations on cords (4 cases), small intestine volvulus (8 cases), sigmoid colon volvulus (6 cases), volvulus of cecum (1 case), intestinal investigation (1 case), colorectal neoplasm (15 cases), peritoneal carcinomatosis (2 cases). The clinical and therapeutical aspects of these particular forms of obstruction in the elderly are discussed and the severity of their prognosis, given the terrain and late admission of such patients which sometimes make impossible a surgical intervention, is underlined. Ten deaths (17.1%) were recorded, representing a lower percentage as compared to other statistics published in the literature.

[Problems of therapeutic management of cancer of the superior pole of the stomach]. / Probleme de conduita terapeutica în cancerul polului superior al stomacului.

This cancer is rare (17-30%) and has the worst prognosis. In the interval 1970-1987 to the I-st Surgical Clinic of Iasi were admitted and treated 648 patients with gastric cancers of which 98 (15.2%) with adenocarcinomas of the cardiac end of the stomach. In most patients the diagnosis was late: stage II and III-40 patients; stage IV-58 patients. Given the extension of the tumoral process, the exeresis was possible but in 36 cases (36.7%), as compared to 26-70% mentioned in the literature. The therapeutical management of these cases and the obtained results are presented.