Govan, Alasdair D. Publication Timeline. Most widely held works by Alasdair D. T Govan. Pathology illustrated by Alasdair D. T Govan Book 33 editions published between and in English and held by WorldCat member libraries worldwide Visual images are very important in the study of pathology where morphological changes are a major component.
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Synthetic glucocorticosteroids belong to a group of compounds which are derivatives of adrenal cortex hormones cortisone, cortisol, corticosterone. Due to their suggested and repeatedly proven strong anti-inflammatory, anti-allergic and immunosuppressive properties also when compared to natural compounds 1, 2 , these compounds are currently used in nearly all the medical fields and specialties.
They form the base of therapy for inflammatory diseases, including, among others, the numerous diseases of the respiratory system, like the allergic, seasonal or perennial rhinitis and nonallergic rhinitis In this case, the glucocorticosteroids, such as beclometasone, budesonide, fluticasone propionate or mometasone fuorate are administered locally in the form of nasal aerosols, inhalation powders and water solutions 1, 7.
Synthesizing glucocorticosteroids for localized treatment ensured strong, selective and simultaneously safe action, enabling high concentrations of the drug with a minimalized risk of side effects with the appropriate application technique and proper dosage even with long-term administration Modern treatment of rhinitis mainly concentrates on actions aiming to reduce the inflammation of nasal mucus.
Numerous reports show that the research on topical steroid drugs mainly concentrate on the clinical symptoms related to the nose, such as itching, rhinorrhea, obstruction, burning sensations, etc. Cytological assessment is concentrated on exogenous cells which determine the type of the inflammation, such as eosinophils or neutrophils Far less attention, however, is being paid to epithelial cells, which can determine the morphological effects of the ongoing inflammation process 16 or the administered treatment It should also be stressed that, depending on their type, glucocorticosteroids can have a diversified influence on the cells of nasal mucous membrane The available literature provides numerous conflicting information on this issue, which causes the mechanism of the anti-inflammatory action of glucocorticosteroids to remain partially unknown.
Special attention should be also given to the fact that, despite proper administration, applying such drugs in a localized manner, nasally, together with orally administered drugs, might change the cytological image of the nasal mucous membrane The goal of the study was to cytologically assess the influence of fluticasone on the cells of nasal mucous membrane, with a special attention to the changes in the morphology of pseudostratified epithelium cells, performed in vivo in standard treatment conditions.
The study group was 40 patients 17 women and 23 men , aged 5 — 30 median The patients were qualified to participate in the study by a doctor based on long-term, clinically homogenous symptoms, such as runny or stuffy nose, nasal mucosa swelling, itching of nose. The control group were 10 healthy people 5 women and 5 men aged 5 — 22 median Two smears were taken from each patient with the use of a sterile cytology brush, from the surface of the nasal mucous membrane exfoliative cytology , specifically from the inferior nasal concha 1 cm from its front edge.
The cells on the brush were spread by hand on the slide with a single movement parallel to the slide edges.
Changes in the nasal mucous membrane of patients with rhinitis were analyzed based on a control image obtained in smears taken from healthy people. The results of the control group corresponded to the description of healthy nasal mucosa published by Tarchalska-Krynska During the sample assessment, special attention was given to the morphological changes of epithelial cells.
These concerned the morphological profile of the nucleus change of size, karyorrhexis, non-nucleated form , cytoplasm structure, changes of staining, vacuolation and cell contour. In order to obtain the full picture, an assessment of the percentage of various types of cells in the smears was performed, according to the method of Tarchalska-Krynska The inflammatory cells counted were neutrophils and eosinophils, and the epithelial cells counted were columnar cells, goblet cells and squamous cells.
In the microscope field of view, all cell types epithelial and inflammatory cells , as well as the cells with morphological changes, were counted together, to a total of cells in the preparation. Determining cytograms for all patients enabled the emergence of 10 ill people 4 women and 6 men aged 5 — 20 median In this group, there were 7 people with symptoms of perennial rhinitis, accompanied by typical nasal symptoms.
Among the persons in 5 cases also demonstrated the profile of atopic diseases such as atopic dermatitis and asthma with symptoms from the conjunctiva tearing, itching, burning and the presence of allergen-specific immunoglobulin E for House Dust Mites D.
Dermatophagoides pteronyssinus and D. Dermatophagoides farinae. The remaining 3 people demonstrated characteristics of seasonal allergic rhinitis with typical nasal symptoms as well as the lack of extra-nasal symptoms and diseases associated and the presence of specific IgE to grass, birch, alder and hazel allergens.
The assessment of cytological image after fluticasone therapy was performed after 4 weeks of its use and compared to cytology taken from the same patients before treatment. The assessment of the morphology of the nasal mucous membrane of patients with rhinitis symptoms before treatment was performed in reference to the smear from the mucous membrane of patients from the control group, which was picked as correct Fig.
The analysis of smears from the nasal mucous membrane showed significant differences in the cytological image of patients with rhinitis before fluticasone treatment in comparison to the control group results. The statistically significant change was the presence of numerous cells of the stratified squamous epithelium.
These were large polygonal cells, with translucent cytoplasm and a small pyknotic nucleus without a visible chromatin structure or with nuclear shadows visible in the center Fig. Basophilic cells were present in a similar number: Some acidophilic cells were characterized by the presence of nuclei with signs of breakdown Fig.
Another significant change was the disturbed ratio of columnar to goblet cells, in favor of the goblet cells, caused by a statistically significant decrease in the number of columnar cells to Furthermore, fairly frequently occurring free nuclei of these cells with very clear nucleoli could be observed Fig.
The preparations also contained numerous bacteria, which were loosely distributed or adhered to the surface of squamous epithelial cells Fig. The dominant change was the statistically significant increase in the number of neutrophils to These granulocytes showed the characteristics of poorly differentiated cytoplasm and of cell nuclei contours. A statistically significant number No significant changes in the morphology of epithelial cells were shown, only the presence of 4.
Whereas the analysis of smears taken from the same patients after fluticasone therapy showed the presence of few bacteria, as well as a statistically significant reduction of the number of inflammatory cells such as neutrophils, to The studied granulocytes were showing characteristics of serious breakdown Figs.
At the same time, changes in the ratio of cells of pseudostratified epithelial cells were observed, in the form of a statistically significant increase in the number of columnar cells to A statistically significant increase in the number of basophilic cells of the stratified squamous epithelium was also shown, up to No significant changes were noted in relation to the number of basophils, lymphocytes and monocytes Fig.
Special attention was however drawn by the vacuolation changes in the form of one large vacuole or numerous small vacuoles in the cytoplasm of both columnar cells Fig.
A significant increase in the number of vacuolated cells can be seen, up to Among the cells with vacuolation changes, revealed the presence of forms with a perinuclear halo Fig.
Progress in diagnosing and treating allergic diseases is based on the improved understanding of the mechanisms of these diseases, the development of new drugs, as well as on the improvement and broadening of indications regarding drugs which are already in use The pathomechanism of inflammatory rhinitis is related to the inflow and activation of cells - mastocytes, basophils, eosinophils, T lymphocytes and neutrophils in the area of the inflammatory process 23, 24 , and its understanding allows us to correctly and justifiably use specific drugs and therapeutic methods The cytological assessment of the smear from the surface of the mucous membrane is, unlike the biopsy, a completely noninvasive method, which can often be used in routine ambulatory diagnostic.
It can be performed in every situation, in every patient of every age, and can be repeated numerous times in the same person The safety and lack of age limits are confirmed by cytological studies in infants 27, Since the picture obtained in cytological studies is a reflection of the processes taking place in the nasal mucous membrane, studies of this type provide many new and significant information about the type of the inflammatory reaction, as well allowing the monitoring of the effectiveness of the implemented treatment 24, 29 — Without glucocorticosteroid drugs it would certainly be difficult to imagine modern therapy of these diseases, the pathogenesis of which is associated with the activation of various inflammatory cells Besides nasal mucosa diseases they are commonly used in the treatment of asthma, Crohn's Disease or infant meconium aspiration syndrome MAS , where they, among other effects, significantly limit the influx of inflammatory cells It should be remembered that these drugs control numerous physiological processes in various organs and tissues and on many levels, from the proliferation and differentiation of cells, to the regulation of their metabolic activity and programmed death 37, The cellular reaction to glucocorticosteroids is very diverse and shows great variability in its specificity and sensitivity Glucocorticosteroids, independent on the form of administration, can change the cytological image of the mucous membrane, it should however be noted that these changes can be beneficial or undesirable The cytological studies preformed on a group of patients with rhinitis symptoms before their treatment, in comparison to the control smears, clearly show a disturbance in the biocenosis of the nasal mucous membrane.
The presence of numerous bacteria has been shown Fig. With the assumption that a cytogram described as correct should contain single neutrophils 13, 20, 25 , the presented change suggests a pathological state. Furthermore, the observed granulocytes display the characteristics of poorly differentiated cytoplasm, as well as contours of nuclei, which suggests a chronic state.
In acute inflammations granulocytes, existing as young forms, have clear and intensively staining nuclei and well differentiated cytoplasm Changes in the content of the cellular population of the nasal mucous membrane are also a confirmation of the pathological state. A disturbance in the ratio of columnar cells to goblet cells has been noted, to the benefit of the goblet cells Figs.
The mechanism contributing to the increase of goblet cells is their over-proliferation, known as hyperplasia, which often accompanies inflammation in the respiratory epithelium 43, According to some authors, the hyperplasia of goblet cells can accompany inflammation in which the dominant cell is the neutrophil, like in the chronic inflammation of nasal mucous membrane and rhinosinusitis with the exclusion of nasal polyps It should also be stressed that the studied material showed the presence of free nuclei of columnar cells Fig.
The presence of very numerous cells of the squamous stratified epithelium has also been confirmed Figs. The prevalence of these cells, in different stages of development, with the assumption that the material was properly obtained, suggests a pathological state Since the analyzed smears showed a prevalence of cells originating from the deeper strata of the epithelium basophilic with a large round nucleus with a mildly granular structure , it suggests a damage to the upper layers of the epithelium The breakdown of the nucleus karyorrhexis observed in the basophilic cells is also, together with an enlargement and a dissolution karyolysis of this structure, a common occurrence in inflammation The obtained changes, especially the neutrophilic reaction, indicate a chronic infectious rhinitis, in which neutrophils can often be the only cells in the smear A comparison of the cytological image of patients with rhinitis before treatment and the same patients after treatment with fluticasone enabled the demonstration of significant differences in epithelial reaction and number of inflammatory cells.
The consequence of the drug activity was the decrease of inflammation of nasal mucosa, confirmed mainly through the reduction of the number of neutrophils Fig. The observed decrease of goblet cells, with a simultaneous, also statistically significant increase of the number of columnar cells the proper ratio of columnar to goblet cells shows a gradual regeneration of the nasal mucous membrane Figs. The confirmation of the results obtained in relation to goblet cells were the cytological studies of Lin et al.
Whereas the stimulating effect of glucocorticosteroids on columnar cells was shown in the research on mometasone performed by Tarchalska-Krynska 19 and Meltzer Another confirmation of the beneficial effect of topical glucocorticosteroid therapy on the proper proportion of columnar to goblet cells comes from the results of our own cytological studies on the use of budesonide 52, In comparison to the state before treatment, fluticasone therapy did not influence the general number of squamous stratified epithelial cells Fig.
However, special attention has been drawn by the increase of vacuolated epithelial cells Fig. Some cells were characterized by the presence of a single vacuole Fig. The intensified vacuolation of the cell cytoplasm might suggest an induction of autophagic processes. According to numerous reports, autophagy plays a significant role in numerous aspects of inborn and adaptive immunity, including, among others, the activation of the immunological system, survival of infected cells 54 or the elimination of intracellular pathogens, including bacteria and viruses 55, It should be stressed that according to numerous literature data, autophagy can be associated not only with macrophages, but also with cells not belonging to the immunological system Whereas the so called perinuclear halo effect, according to the available literature, appears because of karyoplasm shrinkage and can be the result of reversible cytoskeleton damage In our previous research we had confirmed the effectiveness of topical glucocorticosteroid therapy in the treatment of nasal mucosa diseases, however we have also revealed changes which require further study.
As described in professional literature 59 , the noninvasive study of nasal nitric oxide NO levels can be an excellent supplementation of the cytological studies both in the assessment of the inflammatory reaction of the nasal mucous membrane and the reaction to anti-inflammatory treatment.
As shown in professional literature 60 , the study design should also include the fact that the very use of hypertonic saline solution in nasal aerosol form can have a significant effect on the nasal NO levels.
Simultaneously, no harmful action of the applied glucocorticosteroid was observed, which was confirmed by the lack of significant changes in the number of squamous epithelial cells with a clearly increased number of columnar cells. Whereas the observed escalation in vacuolation of these cells, with a simultaneous lack of apoptosis characteristics, doesn't show the characteristics of degenerative changes, but might suggest an additional mechanism of glucocorticosteroids in nasal mucosa inflammation.
KROL 1 , T. The majority of cytological studies concern the influence of glucocorticosteroids on cells involved in creating and sustaining inflammation, such as eosinophils or neutrophils.
VIAF ID: 42488736 (Personal)
Synthetic glucocorticosteroids belong to a group of compounds which are derivatives of adrenal cortex hormones cortisone, cortisol, corticosterone. Due to their suggested and repeatedly proven strong anti-inflammatory, anti-allergic and immunosuppressive properties also when compared to natural compounds 1, 2 , these compounds are currently used in nearly all the medical fields and specialties. They form the base of therapy for inflammatory diseases, including, among others, the numerous diseases of the respiratory system, like the allergic, seasonal or perennial rhinitis and nonallergic rhinitis In this case, the glucocorticosteroids, such as beclometasone, budesonide, fluticasone propionate or mometasone fuorate are administered locally in the form of nasal aerosols, inhalation powders and water solutions 1, 7.