[The place of otorhinolaryngology in modern medicine].

This publication is devoted to the peculiar features of the development of otorhinolaryngology as an integral component of modern medical science and practice and the place it now occupies among other disciplines. Much attention is given to the formation of the scientific views of focal infections with special reference to tonsillitis, the role of immune pathology an allergic reactions in etiology and pathogenesis of ENT diseases. Also considered is the problem of the elaboration of the new surgical methods and their application for the treatment of ENT pathology.

Immunoglobulin and CD8⁺ T-cell distribution in histologically distinctive tonsils of individuals with tonsillar focal infection.

CONCLUSION: This study demonstrated that the common immunological mechanism, which involves aberration of immunoglobulin and T-cell distribution in histologically distinctive tonsils, may be associated with the pathogenesis of tonsillar focal infection. OBJECTIVES: Tonsillar focal infection comprises a group of relatively common diseases combined with chronic tonsillar infection, is associated with unusual immune responses in tonsils, and may cause lesions in another distant target organ. This study aimed to investigate the distribution of inflammatory T cells and T-cell regulatory elements, such as programmed cell death-1 (PD-1) and Fork head box protein 3 (Foxp3), immunoglobulin production, and histological characteristics in tonsils from patients with tonsillar focal infection. METHODS: Immunohistochemistry and reverse transcription-polymerase chain reaction (PCR) were used to compare the expression of CD8(+) T cells, immunoglobulins, and cytokines associated with immunoglobulin production in the tonsils of patients with IgA nephropathy (IgAN), palmoplantar pustulosis (PPP), rheumatoid arthritis (RA), and chronic tonsillitis. RESULTS: The overexpression of CD8(+) T cells combined with decreased expression of Foxp3 and PD-1 and the aberration of immunoglobulin production, which may be due to the elevated expression of activation-induced deaminase (AID), B-cell-activating factor of the TNF family (BAFF), supporting isotype switching, and B-cell survival in the histologically distinctive tonsils.

IgA production and tonsillar focal infection in IgA nephropathy.

IgA nephropathy (IgAN), the common primary glomerulonephritis, is a tonsillar focal infection characterized by the qualitative abnormality of IgA in circulation and IgA deposition in the renal mesangium. Mesangial deposition of IgA, which is composed predominantly of poorly galactosylated polymeric IgA1 (pIgA1), seems to be the initiating event in the pathogenesis of IgAN. The origin of poorly galactosylated IgA, however, remains unclear. Recent studies suggest that the mesangial polymeric IgA1 deposition could be derived from mucosally primed plasma cells. B cells may undergo IgA class switching to acquire the expression of IgA via T-cell-dependent or T-cell-independent pathways in mucosa-associated lymphoid tissue and then differentiate to IgA plasma cells or home in on systemic sites. Dendritic cells, including plasmacytoid dendritic cells and another type of antigen-retaining cell, follicular dendritic cells, have an irreplaceable role in IgA class-switch mechanisms by producing IgA-inducing signals. Furthermore, an increased number of pIgA1-secreting plasma cells in the bone marrow and tonsil, as well as increased IgA class switching, have been found in IgAN, providing a link between the mucosal immunity and IgAN. The favorable effect of tonsillectomy on patients with IgAN showed that tonsillar focal infection may be closely related to pIgA1 deposition in glomerular mesangium of patients with IgAN and at least a part of pIgA1 may originate from affected tonsils. Therefore, the indication for tonsillectomy should be considered in patients with IgA nephropathy, especially at a mild or early stage, to prevent future renal deterioration. In this paper, we focus on IgA class switching and the role of tonsils with focal infection in IgAN.

Tonsil-related skin diseases and possible involvement of T cell co-stimulation in chronic focal infection.

Some inflammatory skin diseases are known to be related to tonsil focal infection at their onset. Administration of antibiotics is adequate treatment in most acute or subacute cases. However, chronic focal infections in the tonsils could cause chronic skin diseases like pustulosis palmaris et plantaris (PPP), and it is our frequent experience that tonsillectomy leads to a dramatic and persistent improvement of PPP skin lesions. The expression of inducible co-stimulator (ICOS), a co-stimulatory receptor on activated T cells, was significantly higher in tonsil tissues from PPP patients than in tonsil tissues from non-PPP patients. Moreover, ICOS expression in tonsil tissues from 3 patients with psoriasis vulgaris that was strongly suspected to be related to tonsil focal infection was also high, suggesting that the activation of T cells via ICOS costimulation in focal infections likely triggers inflammation associated with tonsil-related skin diseases. PPP is notable today for paradoxically induced skin lesions in patients treated with TNF-α antagonists for rheumatoid arthritis, Crohn's disease, psoriasis and psoriatic arthritis. It is important to clarify the immunological milieu in PPP not only for the treatment approach but also for understanding these unexpected reactions.

Triggering role of focal infection in the induction of extra-palmoplantar lesions and pustulotic arthro-osteitis associated with palmoplantar pustulosis.

Palmoplantar pustulosis (PPP) is a chronic inflammatory disorder characterized by sterile pustules predominantly involving the palms and soles of middle-aged women. Whether PPP is the acral type of pustular psoriasis or a distinct entity has long been discussed; however, the clinical features of PPP are really heterogeneous and different between Asians and Caucasians, which may depend on the race with backgrounds of different HLAs. PPP is closely related with psoriasis, but considered to be a distinct entity in Japan. Although the pathogenesis of PPP is still poorly understood, PPP is a representative skin disorder showing a close relationship with focal infections such as tonsillitis, chronic sinusitis, and dental infection. In particular, tonsillitis often triggers or deteriorates PPP. In Japanese patients, regions other than the palms and soles are occasionally affected manifesting scaly erythemas which resemble psoriasis, and solitary pustules are also seen. Some of these extra-palmoplantar lesions are induced by the Koebner phenomenon or occur after focal infections. Further, arthralgia is also induced on the sternum, clavics, sacroiliac joints, and upper ribs following focal infections. This paper makes a focus on the triggering role of focal infection in the induction of extra-palmoplantar lesions as well as arthralgia (putulotic arthro-osteitis).

A case of infection-associated antiproteinase-3-negative cytoplasmic antineutrophil cytoplasmic antibody pauci-immune focal necrotizing glomerulonephritis.

We present the case of a man with Gram-negative sepsis and exposure to oral silica who developed pauci-immune focal necrotizing glomerulonephritis (PI-FNGN) in the setting of a subacute polymicrobial central venous line (CVL) infection. He developed a cytoplasmic antineutrophil cytoplasmic autoantibody (C-ANCA) that was antiproteinase-3 (PR-3) and antimyeloperoxidase (MPO) antibody negative. We believe this is the first reported case of Gram-negative sepsis-associated PI-FNGN. Chronic silica exposure is a leading environmental risk factor in the development of ANCA vasculitis. Oral silica is a common pharmaceutical additive and its bioavailability is being recognized. Oral silica, therefore, may also be a risk for development of autoreactivity. The PI-FNGN resolved with antibiotic therapy alone. The C-ANCA titer declined as the PI-FNGN resolved. The case supports experimental and observational research that environmental exposures act as adjuvants for an immune response and also provide epigenetic triggers for autoreactivity. The C-ANCA was negative for PR-3, its major antigen. C-ANCA antigen specificity may depend on the pathogenesis of the underlying disease, potentially elicited by a cross-reaction of an antibody to foreign and self target antigen sequence homology or alternatively elicited by antigenic epitope spread.

[Factors in the development of chronic infection foci in the nasopharynx]. / Vyvchennia faktoriv rozvytku khronichnykh vohnyshch infektsiï v nosohlottsi.

Antigens were studied of HLA system in always ailing patients presenting with the formed chronic focus of infection in the tonsils. A total of 56 patients with chronic decompensated tonsillitis who were assigned for tonsillectomy by clinical indications were examined together with 53 essentially healthy subjects. Tonsillitis patients revealed HLA-antigens B7, A1, associations A10B7, more frequently than controls, the difference being statistically significant. The data obtained are helpful in identification of risk groups in relation to formation in recurrent respiratory diseases of chronic focal pathology in the nasopharynx.

Detection of streptococcal class I M protein in psoriasis by confocal immunofluorescent microscopy.

Epidemiological evidence implicates Streptococcus pyogenes (group A) infection as a common triggering stimulus for psoriasis. Unequivocal demonstration of streptococcal antigens in psoriatic skin has been difficult due to cross-reactive antigens in both normal human tissue and group A streptococci, which complicate immunohistological analysis. In this study cryostat sections of involved psoriatic skin were stained with monoclonal antibody 111-15504 to group A streptococci. The epitope recognized by this antibody was found to be specific for group A streptococci and is associated with class I M protein. Streptococcal antigens were found in the dermal papillae and epidermis of psoriatic skin lesions of 20 out 38 patients. These findings indicate that specific S. pyogenes antigen, associated with class I M protein, is often present in psoriatic lesions. Such an antigen, originating from focal infection elsewhere could be responsible for T-lymphocyte inflammatory responses triggering the development of psoriatic lesions.

[The correction of immunity in adolescents and children with focal staphylococcal diseases]. / Korektsiia imunitetu u pidlitkiv i ditei z vohnyshchevymy stafilokokovymy zakhvoriuvanniamy.

The aim of the work done was to improve treatment options for focal Staphylococcus-induced diseases in adolescents and children with the aid of adsorbed staphylococcal anatoxin (ASA) concurrently with low-intensive EHF therapy. Overall fifty patients aged 3 to 17 years with Staphylococcus infection in tonsils, nose, ears were kept under medical surveillance. ASA and EHF therapies were instituted according to the developed schemes of such therapies. Positive dynamics was shown of clinical picture and parameters characterizing humoral and cell-mediated immunity. There were no unfavourable side-effects. The proposed mode of treatment can, we believe, be widely used in a clinical setting.

[The effect of antibodies to microorganisms in a focus of purulent inflammation]. / Vliianie antitel na mikroorganizmy v ochage gnoinogo vospaleniia.

The rats were infected with a suspension of dissociated or agglutinated Pseudomonas aeruginosa [correction of B. pynocyaneus]. Infection with the agglutinated agent drastically improved the clinical course, lowered the indices of the process generalization (mortality, metastatic foci, spread in the internal organs); no hemorrhages, necrosis or abscesses were noted. A rapid (within the first day) death of almost all agglutinated bacteria in the primary focus was observed, this not being due to phagocytosis or complement-dependent lysis.

[The prognostic significance of natural killers and dehydrogenases of the peripheral blood lymphocytes in patients with a suppurative inflammation]. / Prohnostychne znachennia pryrodnykh kileriv i dehidrohenza limfotsytiv peryferichnoï krovi u khvorykh z hniinym zapalenniam.

In patients with purulent inflammation foci of various location, reduction in the number of natural killers (NK) and in the activity of alpha-glycerophosphatedehydrogenase (alpha-GPDH) and adenosinetriphosphatase (ATP-ase) of lymphocytes was revealed. Maximum reduction in indices of NK, alpha-GPDH and ATP-ase was noted in patients with diffuse peritonitis, phlegmonous-gangrenous cholecystitis, destructive appendicitis. After treatment, the mentioned indices increased, but by the time of discharge of the patients from the hospital they were lower than the normal ones.

[The efficacy of leukinferon in suppurative-septic diseases]. / Effektivnost' leikinferona pri gnoino-septicheskikh zabolevaniiakh.

In the complex of treatment of purulent-septic diseases leukinferon at a dose of 300 IU/kg was used according to the following scheme: 3 injections with the 48 h interval between injections. The effect of leukinferon mainly on the function of neutrophil granulocytes and subpopulation of T-lymphocytes was established. Together with clinico-laboratory data indicative of the effectiveness of treatment, normalization of interferon status and decrease in the level of a circulating factor of tumour necrosis in seriously ill patients was observed.

Characterisation of the local inflammatory response in appendicitis.

In this study we have characterised the local inflammatory response in acute suppurative appendicitis (S), focal appendicitis (F), and normal appendices (C). Enumeration of lymphocyte subpopulations, cells expressing IL-2 receptor, natural killer (NK) cells, monocytes and plasma cell isotypes and subclasses infiltrating the lamina propria was carried out on all specimens using immunoperoxidase staining procedures. Total T cells were significantly increased in both acute suppurative appendicitis and focal appendicitis compared with controls (p < 0.001). Cells infiltrating the lamina propria expressed IL-2 receptor in all appendiceal specimens but were significantly increased in both acute and focal appendicitis (p < 0.01). IgG and IgA plasma cell isotypes were significantly increased in all S and F appendiceal specimens (p < 0.001). Monocyte and NK cell numbers, however, were only increased in acute suppurative appendiceal specimens. The increased lymphocyte and plasma cell isotypes seen in focal appendicitis occurred throughout the entire organ even through the inflammatory focus was confined to only three to seven serial sections. These results clearly show a differential pattern of cellular infiltration in focal appendicitis from that seen in acute suppurative appendicitis. The selective lymphocyte and plasma cell nature of the cellular infiltrate in the lamina propria of focal appendicitis may reflect the presence of a specific immune response to an as yet unidentified luminal antigen as a possible cause of appendicitis.

[A clinico-laboratory assessment of the efficacy of an Augmentin suspension in treating children with suppurative-inflammatory diseases caused by opportunistic bacteria]. / Kliniko-laboratornaia otsenka éffektivnosti Augmentin-suspenzii pri lechenii detei s gnoino-vospalitel'nymi zabolevaniiami, vyzvannymi uslovno-patogennymi bakteriiami.

Augmentin suspension (amoxycillin+clavulanic acid) was estimated in clinico-laboratory studies with respect to children suffering from pyoinflammatory diseases of various localization and its high efficacy was shown. Good and satisfactory results were recorded in 96.3 per cent of the cases in the treatment (monotherapy) and afterwards in the patients, adverse reactions such as nausea and vomiting being recorded only in 1 patient. The therapy with augmentin led to normalization of the microflora of the upper respiratory tract mucosa and a 1.5-fold increase in the neutrophil engulfment index.

[The immunomorphological characteristics of a focal staphylococcal infection against a background of long-term exposure to low doses of simazine]. / Immunomorfologicheskaia kharakteristika ochagovoi stafilokokkovoi infektsii na fone dlitel'nogo vozdeistviia malykh doz simazina.

State of immunologic and nonspecific resistance of the organism, ultra- and histostructure of the thymus, histopathology of the wall of experimental staph abscess reproduced in animals given low doses of the herbicide simazine for a long time have been studied. It is established that simazine induced the immunodeficiency state underlain by pathologic changes in the thymus. Against this background experimental abscesses developed more rapidly, alterative and exudative processes in their wall proceeding more intensively and proliferative ones--attenuating. This provides prolongation of the abscesses healing phase for an indefinite time and chronization of the process.