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Tonsillar penetration of erythromycin and its 2'-acetyl ester in patients with chronic tonsillitis.

Concentrations of erythromycin and 2'-acetyl erythromycin were analysed in serum or plasma and tonsil tissue after repeated dosage of erythromycin acistrate (EA), a new erythromycin prodrug, in two separate studies in 61 young patients. The reference preparations were: (1) enterocoated tablets of erythromycin base (EB enterotablets, (2) erythromycin base as enterocoated pellets (EB enterocapsules) and (3) erythromycin stearate (ES). All drugs were given 500 mg tid for three days before scheduled tonsillectomy. Tonsils were removed about 3 h after intake of the last dose. Blood samples were collected at 0, 2 and 6 h and at the time of tonsillectomy. At all time points EA produced several-fold higher total drug (erythromycin + 2'-acetyl erythromycin) concentrations in serum or plasma than any of the reference preparations. Similarly, after EA the mean total antibiotic levels in tonsil tissue exceeded the erythromycin levels after the reference preparations by at least a factor of 3. Tonsil/serum or plasma ratios of the total antibiotic were quite similar with all preparations (means 38-50%). Peak erythromycin levels in circulation did not differ significantly from each other in spite of two nonabsorbers after EB enterotablets. The same was true of tonsil tissue. There were, however, 15 tonsils with undetectable erythromycin: 4/25 (16%) with EA, 5/12 (42%) with EB enterotablets, 2/12 (17%) with EB enterocapsules and 4/12 (33%) with ES. The degree of hydrolysis of 2'-acetyl erythromycin to erythromycin was 23-43% higher in tonsil tissue than in circulation.

Adolescent↗

The significance of recurrent tonsillitis in sickle cell disease.

Forty-five patients with homozygous sickle cell disease who had tonsillectomy for recurrent tonsillitis, when compared with 45 matched controls with haemoglobin genotype AA, showed significant differences in the clinical manifestations and complications of recurrent tonsillitis between the two groups. Although throat swabs in the sickle cell group were mostly negative because they were on prophylactic penicillin, all tonsils harboured Streptococcus pneumoniae when cultured. This study suggests the tonsils to be the more specific source of pneumococcal infection that causes systemic complications which increase morbidity and mortality in sickle cell disease. Although the sickle cell patients may be less clinically symptomatic with tonsillitis, the incidence of serious complications caused by pneumococcal infections, now shown to arise from the tonsils, is significant. Adenotonsillar hypertrophy is linked with an increased risk of a sleep apnoea which causes serious neurological complications such as cerebral infarction and stroke. Tonsillectomy has greatly reduced the incidence of complications from pneumococcal infections in the sickle cell group and should therefore be recommended for sickle cell patients taking prophylactic penicillin and still developing pneumococcal infections.

Anemia, Sickle Cell↗

Tonsillar distribution of IgA and IgG immunocytes and production of IgA subclasses and J chain in tonsillitis vary with the presence or absence of IgA nephropathy.

At the onset or in the course of IgA nephropathy (IgA NP), upper respiratory tract infections and tonsillitis are often followed by periods of gross haematuria. In a search for possible abnormalities in the tonsillar IgA- and IgG-cell system, the palatine tonsils from seven patients with IgA NP and eight controls, all 15 suffering from chronic recurrent tonsillitis, were subjected to an immunohistochemical study. Compared with the controls, tonsils of NP patients contained a significantly (P less than 0.001) increased proportion of IgA-producing cells (49.6% versus 35.7%). There was also an increase (P less than 0.001) in the ratio of IgA polymer- (J-chain-positive) to monomer-producing cells in NP tonsils compared with controls (35.0% versus 18.8%). Although the tonsillar IgA cells were generally producing mainly IgA1, this subclass was even more predominant in NP tonsils (P less than 0.03). These results are compatible with the hypothesis that in some patients with IgA NP, the polymeric IgA1 deposited in the mesangium may be of tonsillar origin.

B-Lymphocytes↗

Possible role of the anaerobe in tonsillitis.

Anaerobic bacteria were isolated from all tonsils removed from children at routine tonsillectomy; 75.6% of specimens yielded moderate to heavy growth and 80% of tonsils contained more than one anaerobic species. This recovery rate fell to 56% after a 10-day course of metronidazole before tonsillectomy--in only 14.6% of cases were anaerobes isolated in significant numbers. Surface swabbing of the tonsils permitted recovery of a similar spectrum of anaerobic bacteria but resulted in an overall loss of both aerobic and anaerobic pathogens. A comparison was made between the flora of acutely inflamed tonsils and "healthy' tonsils: over 90% of both groups yielded anaerobic bacteria, but they were present in significant numbers in 56.2% of swabs taken from acutely inflamed tonsils compared with 24% of swabs from "healthy' children. The isolation rate for anerobic pathogens was 37.5% and 16% respectively.

Acute Disease↗

An investigation into factors that may influence tonsil morphology.

To investigate whether tonsillar size was related to human morphology, age or duration of disease, 100 consecutive patients undergoing tonsillectomy for recurrent tonsillitis were investigated. The lengths, widths and volumes of each resected tonsil were measured and compared with patient characteristics ascertained on the day before surgery. The volume of tonsillar tissue was directly related to height (p = 0.46, P less than 0.001) and weight (p = 0.45, P less than 0.001) and age, but at any age (or body size) there was a wide range of tonsil size. A weak inverse relationship was found with the duration of recurrent tonsillitis. Tonsil size is of no relevance in the assessment of recurrent tonsillitis or adenoid hypertrophy.

Adenoids↗

Bacteriology of tonsil surface and core in children.

The tonsils of 97 children undergoing tonsillectomy were studied to determine the correlation between surface culture swab and culture of tonsillar core. In many cases, pathogenic organisms were found in the tonsil core, despite the fact that surface cultures revealed only normal respiratory flora. The tonsil core cultures showed a high incidence of Hemophilus influenzae and Staphylococcus aureus, which was rarely reflected on surface culture. The study indicates that pharyngeal swab cultures do not reliably reflect the presence of pathogens in the tonsil core. The value of parameters such as history of recurrent bouts of tonsillitis and presence of erythema or cryptic debris on physical examination for predicting the differential bacteriology of the tonsil is studied. The implications for treatment of children with adenotonsillar hypertrophy are discussed.

Bacteria↗

Expression and function of tight junctions in the crypt epithelium of human palatine tonsils.

The human palatine tonsils have surface and crypt stratified epithelium and may be initiated via the epithelium to mount immune responses to various presenting antigens. Here we investigated the expression and function of tight junctions in the epithelium of human palatine tonsils from patients with tonsillar hypertrophy or recurrent tonsillitis. Occludin, ZO-1, JAM-1, and claudin-1, -3, -4, -7, -8, and -14 mRNAs were detected in tonsillar hypertrophy. Occludin and claudin-14 were expressed in the uppermost layer of the tonsil surface epithelium, whereas ZO-1, JAM-1, and claudin-1, -4, and -7 were found throughout the epithelium. In the crypt epithelium, claudin-4 was preferentially expressed in the upper layers. In freeze-fracture replicas, short fragments of continuous tight junction strands were observed but never formed networks. In the crypt epithelium of recurrent tonsillitis, the tracer was leaked from the surface regions where occludin and claudin-4 disappeared. Occludin, ZO-1, JAM-1, and claudin-1, -3, -4, and -14, but not claudin-7, mRNAs were decreased in recurrent tonsillitis compared with those of tonsillar hypertrophy. These studies suggest unique expression of tight junctions in human palatine tonsillar epithelium, and the crypt epithelium may possess an epithelial barrier different from that of the surface epithelium.

Adolescent↗

Reduced lymphocyte activation in repeatedly inflamed human tonsils.

Tonsils of 20 patients with recurrent tonsillitis were investigated. Activated lymphocytes, that is lymphocytes with increased nuclear birefringence, were found in only 3 cases. The lack of lymphocyte activation is supposedly due to reduced antigen stimulation. Since antigens arrive at the tonsillar lymphoid tissue via the follicle-associated cells of the crypt epithelium, the ultrastructure of this epithelium was also studied in 5 cases. Tonsils of three dogs were used for comparison. In the repeatedly inflamed human tonsils the follicle-associated, so-called M cells contained fewer intracytoplasmic tubules and vesicles than those of the dogs. Moreover the frequency of these cells seemed to be reduced. Most of the crypts of inflamed tonsils were lined with a non-reticulated, stratified squamous epithelium. A hypothesis is presented on the pathomechanism of recurrent tonsillitis and suggestions are put forward about its pathohistology.

Adolescent↗

Distribution and morphology of macrophages in palatine tonsils.

The distribution and morphology of macrophages were studied by immunohistochemical and electronmicroscopic methods in three diseases of the palatine tonsils: tonsillar hypertrophy, recurrent tonsillitis and tonsils with focal infection. We confirmed the presence of two types of macrophages in the tonsils, a monocyte-macrophage cell line and dendritic cells with subtypes, Langerhans' and interdigitating reticulum cells. In the lymphoepithelial symbiosis area and in the subepithelial area, the monocyte-macrophage cells and the dendritic cells had similar distributions and densities. Since these two types of cells were sometimes in contact with each other, they may function in close cooperation. In tonsils with focal infection, there were fewer dendritic cells in the lymphoepithelial symbiosis area, and the germinal centers were less well developed than in the other tonsillar diseases. These findings suggest that in tonsils with focal infection, insufficient amounts of antigen may be presented by the dendritic cells to helper T-lymphocytes.

Adolescent↗

Expanded primary T nodules in the palatine tonsils from patients with IgA nephropathy.

We designed a study to investigate the morphological expression of immune responses in the palatine tonsils from patients with IgA nephropathy. To distinguish between the histological characteristics of the tonsils in habitual tonsillitis (47 patients) and IgA nephropathy (11 patients), we studied the T nodules, B-lymphoid follicles, germinal centers, areas of mixed T and B lymphocytes, lacunar epithelium and connective tissues; then we compared patients with habitual tonsillitis and IgA nephropathy. The T nodules in patients with IgA nephropathy were enlarged, and this change was not accompanied by atrophy of B-lymphoid follicles. Morphologically, primary T nodules were predominant. In reactive lymph nodes, T nodules generally play an important role in the extra-follicular maturation of stimulated B lymphocytes into Ig-secreting plasma cells. Therefore the enlarged primary T nodules remind us that this maturation may occur more frequently in the tonsils of patients with IgA nephropathy than in those with habitual tonsillitis. This suggests that some immunoregulatory dysfunction exists in the secretory immune system of mucosa-associated lymphoid tissues in patients with IgA nephropathy.

Adult↗

Throat swab in the chronic tonsillitis: how reliable and valid is it?

INTRODUCTION: The diagnostic test of swabbing the surface of the tonsil as a culture specimen for the determination of the organism responsible for the tonsil infection is still in practice, despite controversy. To date there has been no reports of establishing the reliability and validity of this common diagnostic test by appropriate statistical test of Likelihood ratios taking into consideration the specificity and sensitivity. AIMS: To assess the reliability and validity of throat swab in the diagnosis of bacterial microflora in chronic tonsillitis. PATIENTS AND METHODS: A prospective study of 40 patients clinically diagnosed to have chronic tonsillitis undergoing tonsillectomy was undertaken. The reliability of the throat surface swab was then assessed and validated with the reference (gold) standard of tonsil core culture. RESULTS: The likelihood ratio of this diagnostic test being positive (LR +ve) was 0.84 to similar and 1.3 to general organism pathogen. CONCLUSION: Routine culture of the throat by surface swab in the accurate diagnosis of bacterial flora in chronic tonsillitis is neither reliable nor valid. The clinical implications of this investigation which is still very popular is discussed.

Adolescent↗

[Role of anaerobic streptococci in human pathology. Report I. Etiological significance of anaerobic streptococci in chronic tonsillitis].

The authors describe a method of isolation of anaerobic streptococci from the blood. A high seeding efficiency of anaerobic streptococci from the depth of the tonsils (75.1%) and from their surface (59.7%) and also from the blood (36%) pointed to the leading role of these microbes in the etiopathogenesis of chronic tonsillitis. In healthy individuals anaerobic streptococci are revealed (by culture method) on the surface of the tonsils but rarely (6%). Str. micros are the most incident in chronic tonsillitis (in 85.3% of cases-from the depth of the tonsils and in 77.5%-from the surface), whereas Str. anaerobius and Str. intermedius occur in individual cases only (8.4-7.5% and 6.3-15%, respectively). Pure culture of Str. micros was found in 36% of cases. Pathogenetic scheme of development of bacteriemia in chronic tonsillitis and rheumatism is presented. The isolated cultures were found to be resistant to the widely-used antibiotics.

Anti-Bacterial Agents↗

[Comparative immunocytochemical studies of recurrent tonsillitis and infectious mononucleosis].

72 patients suffering from recurrent tonsillitis, and ten with infectious mononucleosis were compared by morphological and immunological studies. The distribution of Ig-containing plasma cells (IgA, IgG, IgM), lambda- and kappa-chains, lysozyme and Alpha-1-antitrypsin in tonsils was determined by the unlabelled antibody peroxidase-antiperoxidase method and correlated with the structure of the tonsils (follicles, interfollicular area, and reticular epithelium). While recurrent tonsillitis was associated with slight follicular hyperplasia, infectious mononucleosis was characterised by a marked distortion of the tonsillar architecture, reduction in the number of follicles and a mixed cellular proliferation. The cellular infiltration was composed of small, well differentiated lymphocytes, atypical lymphocytes (Downey cells), plasma cells, immunoblasts, and a variable number of pleomorphic immunoblasts (Reed-Sternberg-like-cells). The binucleated or multinucleated immunoblasts contained IgA, IgG, and IgM. Ig-producing cells occurred in all compartments. In recurrent tonsillitis most were found in the reticular epithelium, but in infectious mononucleosis their density was highest in the interfollicular area. There was a general prominence of IgG cells, confirming that the tonsils resemble lymph nodes more closely than the lymphoid tissue of the alimentary tract. Cells containing lambda and kappa chains were found in all follicle centres and extra-follicular areas. They gave evidence of polyclonality in both diseases. Lysozyme and Alpha-1-antitrypsin were present only in the vessels.

Humans↗

[The role of prostaglandins in the inflammation and immunity of human palatine tonsils].

It is well known that prostaglanding are biological mediators which are closely related to inflammation and immunity. To explore the role of PGE2 and PGF2 alpha in inflammation and immunity of human palatine tonsils, the levels of PGE2 and PGF2 alpha in diseased tonsils from 62 patients were measured. It is suggested that PGE2 and PGF2 alpha are present in the tonsillar tissue as inflammatory mediators. The levels of PGE2 and PGF2 alpha may be regarded as the major indicators of activation in chronic tonsillitis and represent the immunologic function of the palatine tonsils to a certain degree. The impairment of the ability of immunologic response in tonsils by inflammation may be related to PGE2. The more severe the inflammation, the more hazardous to the local immunologic defence of tonsils is. It is possible that PGE2 plays an important role in this respect.

Adolescent↗

Heritability of recurrent tonsillitis.

OBJECTIVE: To estimate the relative contribution of genetic and environmental effects on the variance in the liability of recurrent tonsillitis. DESIGN: Retrospective questionnaire data from a population-based cohort. SETTING: Population-based data from Norway. PARTICIPANTS: A total of 9479 Norwegian twins born between January 1, 1967, and December 31, 1979, identified through the Medical Birth Registry of Norway. Main Outcome Measure Recurrent tonsillitis. RESULTS: The lifetime prevalence of recurrent tonsillitis was 11.7% (95% confidence interval, 11.0%-12.3%), with a significant predominance of female cases. The tetrachoric correlations for monozygotic twins were 0.71 for males and 0.60 for females. For dizygotic twins, the correlations were 0.12 for males, 0.14 for females, and 0.24 for dizygotic pairs of opposite sex. Structural equation modeling indicated that genetic effects explained 62% of the variation in the liability of recurrent tonsillitis. The remaining variance was attributed to individual environmental effects. There was no evidence of sex-specific genetic effects on the liability of recurrent tonsillitis. CONCLUSION: There is evidence for a substantial genetic predisposition for recurrent tonsillitis.

Adult↗

In vitro studies on human IgD. I. Sources and characteristics of "externalized" IgD in tonsil lymphocyte cultures.

As part of a broader analysis into the function of IgD, and especially into the role of human IgD-secreting cells, fresh human tonsil lymphocyte cultures were analyzed. The goals were to define the origins of "externalized" supernatant IgD and to examine its relationship to spontaneous Ig secretion of IgG, IgM and IgA. Assayable IgD was found by 24 h in cultures without added mitogens. "Externalized" IgD comprised a small fraction (1.6-1.8%) of supernatant Ig when compared to the fraction of IgD-containing cells (congruent to 10%): IgD appears to disappear rapidly in vitro. Initial experiments employing irradiation and chemical inhibitors of protein synthesis suggested that "externalized" IgD was produced de novo during culture rather than representing preformed or cytophilic Ig. Most significantly, tonsil cultures with higher IgD values (greater than 20 ng IgD/10(6) cells, day 7) showed convincing evidence that secreted IgD was a major source for "externalized" IgD. This evidence included the amount of "externalized" IgD depended on viable culture conditions; radioincorporated 35S appeared as a visible IgD band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gels; "higher" IgD cultures showed increased numbers of IgD-Ig-containing plasma cells, and IgD, lambda in excess of IgD, kappa; both events are associated with IgD secretion. In cultures producing high amounts of IgD, IgD secretion appeared to be spontaneous rather than induced and was independent of the polyclonal spontaneous Ig secretion of other Ig isotypes. Low titers of inhibitable IgD isotype anti-phosphorylcholine antibodies but not IgD isotype anti-polyribotol phosphate antibodies were present in tonsil supernatants: both were present in matched sera. Other laboratories have directed attention to the striking and possibly selective participation of human tonsil lymphocytes in IgD synthesis using other approaches. Present results supplement and expand earlier data and support the practical value of analysis of short-term cultured tonsil lymphocytes. Differentiation to IgD-secreting cells is suggested to be an active, underestimated and putatively an important part of the immune response in the human tonsil.

Antibodies, Anti-Idiotypic↗

Human tonsil, blood and bone marrow in vivo-induced B cells capable of spontaneous and high-rate immunoglobulin secretion in vitro: differences in the requirements for factors and for adherent and bone marrow stromal cells, as well as distinctive adhesion molecule expression.

Human B cells capable of spontaneous IgG secretion are commonly found in circulation and in lymphoid tissues such as tonsil and bone marrow (BM). The present study compares the mechanisms that regulate tonsil, blood and BM B cells capable of spontaneous IgG secretion. The BM cell subset produced IgG during a markedly longer period of time (14 days) than did tonsil and blood cell subsets (2-3 days). Blood and BM, but not tonsil, B cell IgG secretion depended on the presence of adherent cells, as demonstrated by adherent cell depletion and re-addition experiments. Stromal BM cells supported linear IgG secretion by non-adherent BM cells for 2 weeks, but were unable to prolong the short-term IgG secretion by tonsil and blood cells. Different factors induced IgG secretion in each of the three B cell populations as optimal IgG secretion by tonsil, blood or BM cell subsets required either tumor necrosis factor-alpha, interleukin-6 or fibronectin + interleukin-6, respectively. Finally, these populations also showed differences in the expression of adhesion molecules; the tonsilar cell subset was PNA+/- CD44+ CD49d+ CD49e- Leu-8+/-, the blood cell subset was PNA- CD44+/- CD49d+ CD49e- Leu-8+ and the BM cell subset was PNA- CD44+/- CD49d+ CD49e- Leu-8-. These results suggest that the mechanisms controlling the final differentiation and the expression of adhesion molecules in these B lymphocytes exhibit territorial specificity.

Antibody-Producing Cells↗

Influence of tonsils on velopharyngeal movements in children with craniofacial anomalies and hypernasality.

Velopharyngeal activity and tongue and tonsil movements were examined cineradiographically in the connected speech of 40 hypernasal children with craniofacial disorders--20 with small tonsils and 20 with large tonsils. The tonsils were defined as large when they obstructed two thirds or more of the pharyngeal space; they were considered small if the obstruction was one fourth or less of the pharyngeal space. In patients with small tonsils, consistent velopharyngeal activity was seen most of the time, regardless of the position of the back of the tongue during speech. An association between large tonsils and decreased velopharyngeal activity was found for speech sounds articulated in the back of the mouth. Therefore when examining velopharyngeal activity in hypernasal children, it is important that the speech material include syllables and words with speech sounds articulated in the back of the mouth.

Child↗