Recurrence of carcinoma showing thymus-like differentiation (CASTLE) involving the thyroid gland.

BACKGROUND: Carcinoma showing thymus-like differentiation (CASTLE) in the thyroid gland is a rare disease with generally a favorable prognosis. Treatment with surgery and adjuvant radiotherapy has been shown to improve local control and long-term survival rates. In this report, we present a case of a recurrent thyroid gland CASTLE and review the literature on the diagnosis and treatment of this disease. CASE PRESENTATION: A 60-year-old woman, who was diagnosed with a CASTLE thyroid tumor in 2015, had a total thyroidectomy and was maintained on thyroid hormone replacement (levothyroxine). After 5 years, the patient had a recurrence, in an advanced stage unsuitable for surgery. As the patient declined to undergo radiotherapy, she was followed up without intervention and is currently stable after 15 months. CONCLUSIONS: CASTLE is a rare disease, diagnosed based on postoperative pathology and immunohistochemistry analysis, especially upon CD5 marker. In case of relapse, treatment options include surgery and radiotherapy; however conservative management without intervention is an acceptable alternative in some cases.

Over-under cartilage tympanoplasty: technique, results and a call for improved reporting.

OBJECTIVE: This study aimed to describe the microscopic over-under cartilage tympanoplasty technique, provide hearing results and detail clinically significant complications. METHOD: This was a retrospective case series chart review study of over-under cartilage tympanoplasty procedures performed by the senior author between January 2015 and January 2019 at three tertiary care centres. Cases were excluded for previous or intra-operative cholesteatoma, if a mastoidectomy was performed during the procedure or if ossiculoplasty was performed. Hearing results and complications were obtained. RESULTS: Sixty-eight tympanoplasty procedures met the inclusion criteria. The median age was 13 years (range, 3-71 years). The mean improvement in pure tone average was 6 dB (95 per cent confidence interval 4-9 dB; p < 0.0001). The overall perforation closure rate was 97 per cent (n = 66). Revision surgery was recommended for a total of 6 cases (9 per cent) including 2 post-operative perforations, 1 case of middle-ear cholesteatoma and 3 cases of external auditory canal scarring. CONCLUSION: Over-under cartilage tympanoplasty is effective at improving clinically meaningful hearing with a low rate of post-operative complications.

Identification and characterisation of conserved epitopes of E. ruminantium that activate Th1 CD4+ T cells: Towards the development of a multi-epitope vaccine.

Several studies have shown that cytotoxic T lymphocytes (CTL) require CD4 + Th1 epitopes to generate strong immune responses to intracellular pathogens. However, not much is known about Ehrlichia ruminantium epitopes, particularly those that can be considered potential candidates for inclusion in a multi-epitope vaccine. In order to identify CD4+ Th1 epitopes that induce IFNγ, a number of proteins previously identified as immunogenic were first screened to determine if they induce cellular immunity in tick infected immune sheep PBMC. Significant IFN-γ production and other Th1 cytokines were evident for 10 recombinant proteins in all sheep tested. Secondly, peptides (n = 246) derived from the top 10 E. ruminantium vaccine candidate proteins were assayed using enzyme linked immunospot (ELISPOT) assay, quantitative real-time PCR and flow cytometry. Of the 246 peptides, 23 peptides, Erum0660 (p0660-42), Erum1150 (p1150-18, p1150-19), Erum2540 (p2540-6, p2540-16, p2540-19, p2540-20, p2540-21), Erum5420 (p5420-13, p5420-14), Erum7140 (p7140-6, p7140-7, p7140-12, p7140-13, p7140-20), Erum7320 (p7320-8, p7320-9, p7320-21), Erum7350 (p7350-9), Erum7360 (p7360-8), Erum7620 (p7620-2, p7620-12) and Erum8010 (p8010-8) were identified that stimulate the best and different cell mediated immune responses. Amino acid sequences of these peptides except for p7140-12, p7140-13, p7140-20, and p7350-9 were conserved between 13 different local strains. These peptides could efficiently induce memory CD4+ T cells to rapidly proliferate and significantly increase IFN-γ production in immune sheep PBMC. The upregulation of pro-inflammatory cytokines, which include, IL-1α, IL-2, IL-12p40, TNF-α, IFN-γ, inducible nitric oxide synthase (iNOS) and granulocyte-macrophage colony stimulating factor (GM-CSF) was also detected. Our results show that these peptides could serve as promising candidates for a multi-epitope vaccine against E. ruminantium.

Ehrlichia ruminantium antigens and peptides induce cytotoxic T cell responses in vitro.

Since CD8+ T cells play an important role in resistance to infection with heartwater, effective vaccines against this disease will likely require identification of antigens that contain CD8+ T cell epitopes responsible for cytotoxic T lymphocyte (CTL) responses. With the use of the fluorescent antigen-transfected target cell (FATT)-CTL assay, IFN-γ ELISPOT and flow cytometry, peptides that induce CTL, proliferation of CD8 + T cells and IFN-γ production were identified as possible target antigens for vaccine development. Of particular relevance was the finding that different peptides from different antigens were able to elicit varied cytotoxic activities by immune peripheral blood mononuclear cells (PBMC) from heartwater immune tick-infected sheep. Several peptides derived from Erum0660, Erum2330, Erum2540, Erum2580 and Erum5000 induced CTL in immune sheep PBMC. Peptide Erum2540-6 was the only peptide that induced significant CTL, CD8+CD45RO+ and CD8+IFN-γ+ by PBMC from all three sheep, and Erum2540 and p2540-20 induced the highest % CTL response in all three outbred sheep. These results suggest that these epitopes may be of major importance in heartwater recombinant vaccine development.

Non-contrast magnetic resonance imaging for monitoring patients with acoustic neuroma.

OBJECTIVE: To assess the feasibility of non-contrast T2-weighted magnetic resonance imaging as compared to T1-weighted post-contrast magnetic resonance imaging for detecting acoustic neuroma growth. METHODS: Adult patients with acoustic neuroma who underwent at least three magnetic resonance imaging scans of the internal auditory canals with and without contrast in the past nine years were identified. T1- and T2-weighted images were reviewed by three neuroradiologists, and tumour size was measured. Accuracy of the measurements on T2-weighted images was defined as a difference of less than or equal to 2 mm from the measurement on T1-weighted images. RESULTS: A total of 107 magnetic resonance imaging scans of 26 patients were reviewed. Measurements on T2-weighted magnetic resonance imaging scans were 88 per cent accurate. Measurements on T2-weighted images differed from measurements on T1-weighted images by an average of 1.27 mm, or 10.4 per cent of the total size. The specificity of T2-weighted images was 88.2 per cent and the sensitivity was 77.8 per cent. CONCLUSION: The T2-weighted sequences are fairly accurate in measuring acoustic neuroma size and identifying growth if one keeps in mind the caveats associated with the tumour characteristics or location.

[Contribution of cooperative mechanisms of the thin filament activation to the myocardium contractile function. Assessment by a mathematical model].

We applied a mathematical model to compare the contributions to the myocardium mechanical activity of two a priori feasible variants of the cooperative effect of myosin cross-bridges on the calcium activation of sarcomere thin filaments. One of these variants implies that cross-bridge cooperative influence on the troponin C affinity to calcium is localized within the same functional cluster A7TmTn where the cross-bridge is attached. The second variant is based on the assumption that cross-bridges may affect the affinity of troponin C to calcium in other functional clusters A7TmTn as well (so that the nearer to the cross-bridge a cluster lies, the stronger the cross-bridge affects the affinity of CaTnC complex in this cluster). Each of these two variants and its contribution to the active mechanical performance of the heart muscle during the contraction-relaxation cycle were alternatively assessed in the model. It was found that only the second variant correctly simulates the mechanical activity of the muscle. Thus, the modeling suggests that just this variant of the cooperativity seems to be more feasible.

[Mechanisms of electromechanical function disturbances in cardiomyocytes overloaded with calcium. The theoretical study].

Arrhythmias and mechanical disturbances are simulated in a mathematical model of cardiomyocyte electromechanical activity. The simulated pattern is similar to that observed for acute heart failure associated with calcium overloading of myocardium cells. Special attention was paid to the calcium overloading resulting from the reduced Na+,K+ pump activity. In the framework of the model, it was shown that mechanical factors could promote arrhythmia initiation when the pump activity reduced. Different approaches to electrical and mechanical function restoration during acute heart failure associated with calcium overloading were suggested and analyzed in the model.

[Modeling of mechanoelectric coupling in cardiomyocytes in norm and pathology].

We developed mathematical models of the electromechanical function of cardiomyocytes and the simplest mechanically heterogeneous myocardial systems, muscle duplexes. By means of these models we studied the contribution of mechanoelectric feedbacks to the contractile activity of the myocardium in norm and pathology. In particular, we simulated and clarified the effects of mechanical conditions on both the form and the duration of the action potential during contractions. From this standpoint different kinds of myocardium mechanical heterogeneity were analyzed. As we have established, the latter can play both a positive and a negative role, depending on the distribution of mechanical nonuniformity and the sequence of activation of heterogeneous myocardium system elements. By means of the same models, we studied the contribution of mechanical factors to the arrhythmogenicity in the case of the cardiomyocyte calcium overload caused by the attenuation of the sodium-potassium pump and outlined the ways for correcting the contractile function in these disturbances.

[The in vitro motility assay to study the calcium-mechanical relationship in skeletal and cardiac muscles].

In a series of experiments on regulated contractile systems (i.e., in vitro mobile systems with reconstructed thin filaments), the velocities of the movement of a thin filament on the surface covered by either rabbit skeletal or rat cardiac myosin at various concentrations of calcium ions in solution (in the pCa range from 4 to 8) were assessed. The corresponding "pCa-velocity" relationships were plotted, which proved to be of the sigmoid form. It was found that, at a saturating calcium concentration (pCa 4), the velocity of regulated thin filaments was 65% higher than for unregulated ones in the case of skeletal myosin and 87% higher than for unregulated thin filaments in the case of cardiac myosin. It was also found that the Hill coefficient was 1.95 and 2.5 for skeletal and cardiac myosins, respectively. The difference in the Hill coefficients for skeletal and cardiac myosins is discussed in terms of the difference in contribution of cooperativity mechanisms of contractile and regulatory proteins in the regulation of contraction in these types of muscles.

[Sydenham's chorea. A clinical analysis of 55 patients with a prolonged follow-up]. / Corea de Sydenham. Análisis clinico de 55 pacientes con seguimiento prolongado.

INTRODUCTION: Sydenham's chorea is permanently on the rise in developing countries and may suddenly reappear in developed nations. PATIENTS AND METHODS: We studied a prospective series of 55 cases, involving a total of 89 outbreaks with long-term follow-ups. All the cases were considered to be rheumatic from the outset, whether they were pure choreas or accompanied by the other signs from the Jones criterion, 38 and 17 respectively, in the first outbreak. Ages ranged between 7 and 22 years, with a mean of 15, at the time of the first outbreak; there was a predominance of females (87%). RESULTS: Hemichorea accounted for 54% of cases. Presentation under treatment was mild (60%), moderate (27%) and severe (13%). Duration ranged from 30 to 365 days. Most of the patients presented just one outbreak and only 18% had multiple outbreaks, between 2 and 10 in number. Ballism was observed in five patients, a state of chorea in two of them, another two had chorea mollis and corea gravidarum was found in five of the patients. Chorea was associated to hypotonia, incoordination, fatigue, postural disorders, motor impersistence, dysarthria and altered gait. Psychiatric disorders were frequent and varied, the most predominant being anguish, irritability, psychomotor restlessness, obsessive-compulsive traits and insomnia. The only important sequela involved the heart, with 10 cases, two of which required surgery. CONCLUSIONS: Crystalline penicillin was used to eradicate streptococcus, neuroleptic agents were employed to reduce involuntary movements and psychiatric symptoms, and benzathine was utilised as a prophylaxis for relapses and sequelae.

[Activities of trypsin-like serine proteases and their inhibitors in blood and subretinal fluid of patients with different stages of proliferative vitreoretinopathy in rhegmatogenous retinal detachment]. / Izuchenie aktivnosti serinovykh proteinaz tipa tripsina i ikh ingibitorov v krovi i subretinal'noi zhidkosti u bol'nykh s razlichnymi stadiiami proliferativnoi vitreoretinopatii pri regmatogennoi otsloike setchatoi obolochki.

Concentrations of protein, trypsin-like and antitryptic activities, and the level of alpha 2-macroglobulin were measured in the subretinal fluid (SRF) and blood of patients with different stages of proliferative vitreoretinopathy (PVR). The content of protein in SRF of patients with retinal detachment with PVR was by an order of magnitude higher than in the vitreous body and increased from stage B to stage D1, which indicates increased permeability of the blood-eye barrier. Trypsin-like proteolytic enzymes and their main inhibitors are present in the SRF, and changes in their activity indicate augmentation of the inflammatory component of PVR from stage B to stage C3 and transition to a process similar to tissue cicatrization during stage D1. Changes in the proteinase-inhibitor balance in the peripheral blood in PVR are characteristic of a sluggish inflammatory process which activates from stage B to stage C and eventuates in stage D1. Increase in the blood level of alpha 2-macroglobulin during stages C3 and D1 seems to indicate the development of total autoimmune reaction. Antiinflammatory steroid therapy before surgery had a favorable impact on the course of the postoperative period.

[Liposomes and other nanoparticles as drug delivery systems]. / Liposomy i drugie nanochastitsy kak sredstvo dostavki lekarstvennykh veshchestv.

The basic principles of designing of nanoparticle drug delivery systems are considered. The special attention is paid to liposomes, because the greatest success has been achieved in this area. The modern condition in such intensively developing areas as antitumor and, antibacterials drugs, gene therapy, vaccines is reviewed.

[Clinical-immunological disorders in uveitis in patients with Behçet's syndrome]. / Kliniko-immunologicheskie narusheniia pri uveitakh u bol'nykh s sindromom Bekhcheta.

The results of comprehensive clinicoimmunologic examinations of 38 uveitis patients with Behçet's disease indicate that uveitis in the presence of Behçet's disease should be referred to multifactorial diseases to whose pathogenesis immunopathologic reactions in various combinations and genetic predisposition contribute much. Generalization of the process in the eye predominated in the clinical picture with involvement of the anterior and posterior segments, retinal vessels, this being combined with general somatic symptoms (aphthae on the buccal mucosa, genitals, arthritides, urethritis/cystitis symptoms, positive 'pricking' test). Study of the immunity status revealed depressed lymphocyte proliferative response to mitogen in 58.8% of patients, hyperimmunoglobulinemia of the A and M classes in 63.3%, impaired complex formation (increased levels of circulating immune complexes in 78.3% and cryoglobulin presence in 57.1%), and various combinations of these immunologic signs. The results indicated patients' infection with herpes virus, streptococcus, toxoplasma. An associative connection of Behçet's disease with A (II) red cell phenotype in 54.8% of patients (p < 0.05) suggests a relationship between genetic factors and the conditions of a specific geographic region. A variety of immunologic changes necessitated the use of corticosteroids, hemoperfusion, cytostatics, and immunity stimulants in the treatment of uveitis in Behçet's disease patients.

[Local fibrinolytic activity of the lacrimal fluid in patients with arterial hypertension]. / Issledovanie lokal'noi fibrinoliticheskoi aktivnosti sleznoi zhidkosti u bol'nykh arterial'noi gipertoniei.

Lacrimal fluid local fibrinolytic activity was measured in 101 patients with different variants of arterial hypertension. The studied parameter was found reduced in patients developing hypertensive retinopathy on the respective eye. A correlation was revealed between progress of hypertensive changes in the fundus oculi and reduction of lacrimal fluid local fibrinolytic activity. The results indicate that reduction of this parameter may be regarded as one of the prerequisites for the development of hypertensive retinopathy.

[Immunologic disorders in patients with idiopathic subretinal neovascular membrane]. / Immunologicheskie narusheniia u bol'nykh idiopaticheskoi subretinal'noi neovaskuliarnoi membranoi.

The authors analyze the results of comprehensive clinical and immunologic examinations of 52 patients with this condition (SNVM) in its active and inactive phases, angiographically confirmed, aged 19 to 46; 32 of these were women (61.5%), 20 (38.4%) men. A complex of immunologic methods was employed to reveal the etiology of the condition and the immune status of SNMV patients. The origin of the condition was identified in 44.2% of patients; it was toxoplasmic in 19.2, autoimmune in 15.4, tuberculous in 7.7, and mixed toxoplasmic and tuberculous in 1.9% of cases. T lymphocyte functional activity was inhibited in 37.5% of patients with the exudative hemorrhagic phase of SNMV and in 16.7% of those in the cicatrization phase. Changes in the humoral immunity presenting as gammapathies were detected in 34% of patients, those manifesting by hyperconcentrations of circulating immune complexes in 66.7%, and of cryoglobulins in 37.8% of patients. Krypton laser coagulation was employed in multiple-modality treatment of patients with SNMV. The remissions persisted for 3-5 years.

[Determination of antiplatelet antibodies on the surface of platelets by direct radioimmune method in patients with different types of immune thrombocytopenia]. / Opredelenie antitrombotsitarnykh antitel na poverkhnosti trombotsitov bol'nykh s razlichnymi formami immunnoi trombotsitopenii priamym radioimmunnym metodom.

Direct radioimmune assay (RIA) have been developed for detection of antibodies associated wild platelet membrane. Platelets from 12 patients with idiopathic thrombocytopenic purpura (ITP) and 27 patients with chronic lymphocytic leukemia (CLL) (platelet count (100,000 in 1 microliters) have been tested. Antibodies on platelets surface have been detected in all 12 patients with ITP and in 21 patients with CLL. In 6 CLL patients the number of immunoglobulins associated with platelets surface does not increase control level. It is possible, that in some CLL patients development of thrombocytopenia is mediated not only by platelet associated antibodies but by other mechanisms, one of which can be linked with the depression of megakaryocytes growth in bone marrow. Direct RIA for measurement of antibodies on platelet surface detect antiplatelet antibodies with higher frequency than indirect enzyme-linked-immunosorbent-assay (ELISA), developed earlier for assessment of antiplatelet antibodies in serum. Increase of platelet count in CLL patients after steroid and cytostatic treatment correlated with the decrease of platelet surface associated antibodies.

[Comparative study of lymph node gangliosides and blood serum of normal and T-lymphotrophic baboons]. / Sravnitel'noe izuchenie gangliozidov limfaticheskikh uzlov i syvorotki krovi pavianov-gamadrilov v norme i pri T-kletochnykh limfomakh.

The gangliosides from the lymph nodes and blood sera of normal and T-lymphomic baboons were studied. In lymph nodes the major gangliosides were identified as GM3 and GD3, those in blood sera--as GM3, GM1 and GD3. Gangliosides GM3 and GD3 contained N-acetyl as well as N-glycoloyl neuraminic acids. In gangliosides isolated from lymph nodes and blood sera of T-lymphomic baboons the levels of N-glycoloyl neuraminic acid markedly exceeded that in normal tissues. In tumour lymph nodes the GM3/GD3 ratio was shifted towards GD3.

[Immunologic disorders in young patients with retinal vein thrombosis]. / Immunologicheskie narusheniia pri trombozakh ven setchatki v molodom vozraste.

Immunologic shifts in 53 patients with retinal vein thrombosis, aged 20 to 41, were under study. Present-day immunologic methods were employed to investigate the status of the humoral and cellular immunity and define the infection rate. The results were assessed functionally and immunologically. The authors have revealed the contribution of infection to the development of retinal vein thrombosis in young patients, analyzed for the first time the immunity status of such patients, detected the signs of humoral immunodeficiency are senting as gammapathies and impaired complex formation, showed the relationship between thromboses and genetic predisposition and the role of the erythrocytic phenotype in the development of a cyst-like edema; this permitted them develop recommendations on the disease source and outcome prediction and on the choice of drugs.