Diseased Tonsils Research Articles

Spatially visualized single-cell pathology of highly multiplexed protein profiles in health and disease

Deep molecular profiling of biological tissues is an indicator of health and disease. We used imaging mass cytometry (IMC) to acquire spatially resolved 20-plex protein data in tissue sections from normal and chronic tonsillitis cases. We present SpatialViz, a suite of algorithms to explore spatial relationships in multiplexed tissue images by visualizing and quantifying single-cell granularity and anatomical complexity in diverse multiplexed tissue imaging data. Single-cell and spatial maps confirmed that CD68+ cells were correlated with the enhanced Granzyme B expression and CD3+ cells exhibited enrichment of CD4+ phenotype in chronic tonsillitis. SpatialViz revealed morphological distributions of cellular organizations in distinct anatomical areas, spatially resolved single-cell associations across anatomical categories, and distance maps between the markers. Spatial topographic maps showed the unique organization of different tissue layers. The spatial reference framework generated network-based comparisons of multiplex data from healthy and diseased tonsils. SpatialViz is broadly applicable to multiplexed tissue biology.

Sepsis- An unusual post tonsillectomy complication

Tonsillectomy is a commonly performed procedure in children. Disseminated sepsis is a rare complication of tonsillectomy. Patients usually present with hypotension, reduced oxygen saturation, tachycardia with high total count and reduced urine output. Our patient also required NIV (non-invasive ventilation), ionotropes and antibiotics with serial blood examinations. Early diagnosis and prompt treatment will help in better outcome. The tonsils contain T lymphocytes and macrophages as they serve immune defense mechanisms. Tonsillitis is most commonly caused by viral infection, 40% of cases are caused by bacterial infection. Immunological functions like antigen transport and antibody production are altered in diseased tonsils. The presence of various micro organisms in the open tonsillar bed during and after tonsillectomy acts as foci of infection. The tissue reaction and presence of micro-organisms is also due to different surgical techniques involved. Keywords: Tonsillectomy, Sepsis, Hypotension, Inflammation.

Toll-like receptor 2-mediated human B cell differentiation

Human B cells likely have a major role in the adjuvant activity of Toll-like receptor (TLR) 9 agonists by enhancing innate and adaptive immune responses. As several TLR2 ligands are promising vaccine adjuvant candidates, our aim was to characterize the effects of TLR2 stimulation on human B cell activation and differentiation using cells derived from healthy peripheral blood (PB), spleen, and diseased tonsils. We found a subset of partially differentiated TLR2+ PB and splenic B cells which responds to TLR2 agonists by mediating events involved in germinal center formation, such as upregulating CD77 and secreting chemokines. Furthermore, we show that TLR2-activated monocytes induce B cells to secrete significant quantities of IgM. Finally, activated TLR2+ B cells from tonsils are induced to secrete IgM directly by TLR2 ligands. Thus, TLR2 is likely involved in specific B cell-mediated functions and may be a viable vaccine adjuvant target in humans.

Anatomical evidence of microbial biofilms in tonsillar tissues: a possible mechanism to explain chronicity.

Bacteria within biofilms are resistant to host defenses and antibiotics. The presence of bacterial biofilms within the tissue and crypts of inflamed tonsils may explain the chronicity and recurrent characteristics of some forms of tonsillitis. To determine if microbial biofilms occur within clinically abnormal tonsils. In this study, we evaluated the histomorphological appearance of 19 human tonsils for evidence of biofilm formation using light and transmission electron microscopy. Human tissues were collected during surgical tonsillectomy. Fifteen specimens were removed because of a history of repeated infections, and 4 were removed because of hypertrophy and obstruction. No interventions were used in this study. Histological and ultrastructural evidence of bacterial biofilms within the crypts of tonsils. Gram-positive and gram-negative bacteria were seen within otherwise acellular deposits among crypts of 11 of 15 infected tonsils. Regions of accumulated bacteria possessed the ultrastructural appearance of typical amorphous polysaccharide biofilm matrix. Small clusters of bacterial colonies were seen in 3 of 4 tonsils removed because of hypertrophy. There is strong anatomical evidence for the presence of bacterial biofilms in chronically diseased tonsils. Because sessile bacteria within biofilms are resistant to host defenses and antibiotics, bacterial biofilms within tonsils may explain the chronicity and recurrent nature of some forms of tonsillitis.

Comparison of the microanatomical distributions of macrophages and dendritic cells in normal and diseased tonsils.

The palatine tonsils play an important role in immunologic surveillance and resistance to infection in the upper aerodigestive tract. Dendritic cells and macrophages function to capture and process antigen and present it to T lymphocytes, a critical step in the early immune response. Few studies have characterized the distribution and phenotype of those antigen-presenting cells in the normal palatine tonsil, or determined how those parameters change with disease. Immunohistochemical analysis was performed to determine the microanatomical distribution, quantity, morphology, and phenotype of macrophages and dendritic cells in both normal and diseased tonsils. Differences were observed in macrophage and dendritic cell distribution, quantity, and phenotype in the surface and crypt epithelium. The number of macrophages was significantly increased in all compartments in all disease groups (p < .05), although the number of macrophages that expressed phenotypes of maturity and/or activation was not concomitantly increased. In the surface epithelium, Langerhans and interdigitating cells decreased significantly with disease (p < .05). Chronic infection may impose an immunosuppressive effect on responses within tonsil tissue, affecting the immunologic factors responsible for macrophage maturation and activation.

Quantitative Study of Germinal Center Area in Normal and Diseased Tonsils Using Image Analysis

The aim of this study was to measure the germinal center area of secondary follicles in a consistent and unbiased manner using image analysis. Tonsil specimens were obtained from children with clinical evidence of recurrent tonsillitis and/or idiopathic tonsillar hypertrophy. Normal control biopsy specimens were obtained from children with no history of ear, nose, or throat infections. The results show a significant increase in the germinal center area in tonsils exhibiting hypertrophy when compared to normal controls (p < .002). Image analysis is an important tool for making quantitative size comparisons in lymphoid tissues.

Pericoronitis and tonsillitis: Clinical and darkfield microscopy findings

Objectives Upper respiratory tract infections and tonsillitis and pharyngitis in particular increase the risk of lower third molar pericoronitis. This study was made to investigate clinical and microbiologic associations between pericoronitis and tonsillitis. Study designs The subjects were 20-year-old Finnish male conscripts. Thirty-eight patients had tonsillitis without and 33 patients had tonsillitis with a symptom-free erupting lower third molar; 27 patients had pericoronitis but healthy tonsils. All subjects were examined clinically. Bacterial samples were taken from healthy and diseased tonsils and from healthy and diseased third molar pericoronal pockets. The microbes were classified morphologically with the use of a darkfield microscope. Result Eighty-two percent of infected tonsils had deep crypts and 52% of them exudated pus compared with 36% ( p<0.001) and 0% ( p<0.001) in healthy tonsils, respectively. Infected lower third molars were less than half erupted and had on average 8.8 mm deep pericoronal pockets compared with pockets 5.5 mm deep recorded in symptom-free cases ( p<0.001). Spirochetes were more common in infected pockets than in symptom-free cases comprising 8.2% versus 3.0% of the total bacterial count ( p=0.044). Rods were more common in infected tonsils than in healthy ones (8.9% versus 4.8%, p=0.041). Conclusions There were similarities in morphologic microbiota of pericoronitis and tonsillitis. However, clinical findings of tonsils did not appear to link with the findings of third molars.

Qualitative and quantitative immunoglobulin production by specific bacteria in chronic tonsillar disease.

Tonsillar tissue lymphocyte (TTL) function as measured by immunoglobulin production was assessed in vitro in 60 tonsils, 51 diseased and 9 normal controls. The diseased specimens were from children (aged 3 to 10 years) clinically classified as having recurrent tonsillitis (RT), idiopathic tonsillar hyperplasia (ITH), or recurrent tonsillitis with hyperplasia (RT/H). TTLs were challenged with intact, heat-inactivated bacteria found in the core of diseased tonsils--Streptococcus pyogenes (SP) and Haemophilus influenzae type B (HIB) as well as the dominant bacterium (DB) grown from that particular tonsillar core. The phytomitogen, leukoagglutinin (LA), was used as a nonspecific activator. Qualitative immunoglobulin production was assessed for the immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA) classes. Immunoglobulin-specific production was quantified at the basal level, and at 2, 4, and 6 days following stimulation. Stimulation with HIB produced the greatest amount of IgG and IgM in TTLs from control tonsils. The DB was a relatively weak stimulator of normal (control) TTLs, yet produced relatively brisk IgG responses in the RT and ITH categories. It did, however, yield only marginal IgM secretion in these groups. IgA was consistently produced after stimulation in diseased TTLs, yet was not elicited from normal TTLs. The aforementioned findings suggest a differential qualitative and quantitative immunoglobulin response for healthy, recurrently infected, and hyperplastic tonsils. Lymphocyte hypofunction along with structural changes associated with hyperplasia may be central to the etiology of chronic tonsillar disease. The tonsillar immunologic response in disease and health is discussed.

Effect of specific bacteria on lymphocyte proliferation in diseased and nondiseased tonsils.

Tonsillar tissue lymphocyte (TTL) function as measured by lymphocyte proliferation was assessed in vitro in 38 tonsils--30 diseased and 8 normal controls. TTLs from diseased and control tonsils were challenged with intact, heat-inactivated bacteria which may be found in the core of diseased tonsils; these bacteria were Streptococcus pyogenes and Hemophilus influenzae type B (HIB), as well as the dominant bacterium (DB) grown from that particular tonsillar core. The phytomitogen leukoagglutinin (LA) was used as a nonspecific activator. Lymphocyte proliferation was quantified and reported using a stimulation index (SI) which was based upon viable cell counts at 2, 4, and 6 days following inoculation. Overall, the greatest degree of lymphocyte proliferation in diseased TTLs (SI = .91) was produced by HIB. However, both SP and HIB produced more lymphocyte proliferation in the nondiseased TTLs than in the diseased TTLs (P < .01). H influenzae (non-B) and group A beta-hemolytic streptococci were the pathogens most frequently cultured as the dominant bacteria from the core of diseased tonsils; Streptococcus viridans was most frequently cultured in nondiseased tonsils. The DB caused greater TTL proliferation in diseased (SI = .89) versus control (SI = .63) TTLs (P < .001). These findings suggest a differential proliferative response in vitro for diseased and nondiseased TTLs in response to specific bacteria. The role of possibly pathogenic bacteria and commensals, as well as the implications for clinical disease, are discussed.

The role of haemophilus influenzae in the pathogenesis of tonsillar hypertrophy in children

The role of specific bacteria in the pathogenesis of tonsillar hypertrophy in children in unknown. To determine the effect of specific bacteria on the presence and nature of tonsillar hypertrophy (measured both clinically and by tonsil weight), quantitative aerobic bacteriology was performed on 54 tonsil-core specimens from 54 children undergoing tonsillectomy for chronic tonsillitis and/or tonsillar hypertrophy. Twelve tonsil-core biopsies from 12 children with no history of tonsil disease served as controls. Haemophilus influenzae (HI), Streptococcus pyogenes (SP), Streptococcus pneumoniae (SPn), and Staphylococcus aureus (SA) were the most common microorganisms cultured from diseased tonsils. Few bacteria were cultured from the cores of controls. HI was cultured as the dominant aerobic bacteria in 15 of 54 tonsils (27%). For HI alone, the number of bacteria/gram tonsil showed a significant positive correlation to tonsil weight (p less than 0.05). Fourteen of 15 (94%) tonsils with HI were found in patients with clinical tonsillar hypertrophy, while only 6 of 10 patients (60%) with SP and SPn had tonsillar hypertrophy. Of the 38 tonsils removed for obstructive symptoms (clinical hypertrophy), 14 of 38 (37%) cultured HI as the dominant microorganisms, whereas only 6 of 38 (16%) cultured SP. Neither the type of HI (b vs. non-b) nor the presence of beta-lactamase production had a significant correlation to tonsil weight, bacterial load or the number of B- or T-cell subsets. The number of T-helper (Th), T-suppressor (Ts) and B-cells (per gram/tonsil) was markedly greater in all diseased tonsils than in controls. For both HI and SP the total number of bacteria/gram tonsil correlated positively to the number of Ts cells (p less than 0.003 and p less than 0.007, respectively). In patients with HI type b (HI-b), the tonsil weight correlated to an increase in Ts and B-cells (p less than 0.004 and p less than 0.007, respectively). An increased presence of the Ts and B-cells in the HI-b tonsils (and not in tonsils with HI non-b) suggests a differential response by the tonsil to these distinct but related bacteria. The above data strongly support an etiological role for HI in the pathogenesis of tonsillar hypertrophy in children. Alterations in the relationship between Th and Ts cells may affect normal B-cell function and be implicated in this phenomenon. Clinical implications for pathogenesis, antimicrobial therapy, and future directions for research are discussed.

The immunology of tonsils in children: The effect of bacterial load on the presence of b‐ and t‐cell subsets

Tonsil core specimens of 54 children, (3 to 12 years) with clinical evidence of chronic tonsillitis and/or "idiopathic" tonsillar hypertrophy, were studied for the effect of the magnitude of aerobic bacterial load on tonsil size and the absolute numbers of B- and T-cell subsets. Tonsillar core specimens obtained from ten children with no history of ear, nose, or throat infections and normal appearing tonsils served as controls. The findings of this study indicate that tonsil size was directly proportional to the mean bacterial load in colony forming units/g tonsil (CFU/g) even in the absence of a clinical history of infection (p less than 0.01). A mean bacterial load of 2.4 +/- 2.1 X 10(5) CFU/g tonsil was seen in diseased tonsils as compared to 1.6 +/- 2.4 X 10(4) CFU/g tonsil in normal controls (p less than 0.01). Hemophilus influenzae (type B and non-B), Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes were the most common pathogens recovered in the largest numbers from diseased tonsils; control tonsils harbored few bacteria in their cores. The absolute number of immunocompetent cells/g tonsil including T-helper, T-suppressor and B-cells (S-Ig+), were significantly greater in diseased tonsils than in controls (p less than 0.001). Increasing microbial load (CFU/g tonsil) correlated with increased numbers of T-helper (p less than 0.01) and B-cells (p less than 0.01). These data strongly support a bacterial etiology for chronic tonsillitis as well as "idiopathic" tonsillar hypertrophy. Bacterial induced proliferation of immunocompetent cells may be one underlying mechanism for chronic tonsillar disease in children.

Immunopathological alterations in tonsillar disease.

Inflammatory conditions continuing after the age of about 10 years usually seem to accelerate the aging process of palatine tonsils (PT). However, recurrent tonsillitis (RT) may significantly change the immunological competence of PT even before that age. The observed alterations may be irreversible since they were revealed in periods when the patients had been without inflammatory symptoms for at least 4 weeks. Altered immunological function may in fact contribute to recurrence of RT and a vicious circle may thereby develop. Nevertheless, considerable immunological activity persists in diseased tonsils so the functional changes cannot by themselves justify surgical removal of these organs.

Cardiopulmonary Changes Secondary to Chronic Adenotonsillitis

Thirty children with lower respiratory tract infection of varying degrees secondary to chronic tonsillitis and/or enlarged adenoids were studied clinically and roentgenographically. Symptoms and signs of alveolar hypoventilation and signs of cor pulmonale were present in two of them. These symptoms and signs improved markedly after adenoidectomy and tonsillectomy. The relationship of the lung changes to the incidence of cor pulmonale is discussed. The development of recurrent attacks of severe lower respiratory tract infection secondary to diseased tonsils and adenoids is believed to play an important role in the pathogenesis of cor pulmonale in children with upper respiratory tract obstruction due to chronically enlarged tonsils and adenoids.

OTITIS MEDIA-Reply

REPLY Dr. Fritz is entirely correct in saying that we did not address ourselves specifically to the correlation between indications for the removal of tonsils and adenoids when ignored and the occurrence and repetition of attacks of suppurative otitis media and serous otitis. Data on tonsils of Guamanian children were collected and studied but were omitted because no meaningful statement could be made on tonsular condition and otitis media. Enlarged, diseased tonsils were common but not significantly more so in those with serious hearing loss and otitis media. But Dr. Fritz's criticism is somewhat off the mark. The basic aim of the study was not to determine the cause of otitis media (certainly that is better pursued where experienced ear, nose, and throat personnel are available for prospective studies) but to determine the extent and causes of hearing loss . Having documented a formidable rate of hearing loss among Guamanians which

Blood loss during tonsillectomy.

For over 2,000 years tonsillectomy has been the center of heated disputes involving both laymen and physicians. 1 The procedure has been praised, damned, disparaged, and advised, but, whether for or against or merely intrigued by some ramification of the problem, few of those interested have remained neutral or silent. Boies, 2 in reviewing the literature on tonsillectomy and the problems related to it, found over 100 papers a year recorded in the Quarterly Cumulative Index Medicus between 1942 and 1946, despite the marked decrease in medical writing brought about by the war. The question of whether or not to perform the tonsillectomy and adenoidectomy resolves itself into two opposing parts. On the one hand is the benefit to be expected from removal of the diseased tonsils and adenoids; on the other, the inherent risk involved. Indications for tonsillectomy and adenoidectomy have been discussed extensively by a wide range of

Specific Language Disability

PARENTS who take a child to a physician because of failure in school usually ask if the child needs thyroid, is below par or has poor vision or hearing or diseased tonsils; some physical cause is sought as the explanation of the trouble. In rare cases the cause may be organic, but failure in school is more likely to be related to emotional adjustment, interest or intelligence. In addition to those causes a significant number of children, perhaps as many as 10 per cent, fail because they are handicapped by what has come to be known as a specific language . . .

Studies on Rheumatic Fever: Observations on Tonsillar Carriers of Hemolytic Streptococci; The Effect of Tonsillectomy and the Administration of Penicillin on Rheumatic and Nonrheumatic Fever Patients

rheumatic fever. Most of these patients are 17 to 21 years of age, of relatively short naval experience, and have been transferred here from two large naval training centers in the north where the incidence of streptococcal infections has been extremely high. Veterans Administration patients from the surrounding area of roughly comparable age and history of tonsillitis, are also admitted to this hospital for tonsillectomy. The majority of rheumatic fever patients who have had appreciable amounts of tonsillary tissue present have been subjected to tonsillectomy prior to their discharge from this hospital. Neither a past history of chronic, recurrent tonsillitis nor the finding of grossly abnormal tonsils has been considered a necessary criterion in the selection of patients for tonsillectomy, but the number of men with chronically diseased tonsils would exceed those whose tonsils were rela-

Physical Impairments of Members of Low-Income Farm Families: 11,490 Persons in 2,477 Farm Security Administration Borrower Families, 1940: V. Defects of the Nasal Septum; And Chronic Respiratory Affections, Exclusive of Diseased Tonsils

Physical Impairments of Members of Low-Income Farm Families: 11,490 Persons in 2,477 Farm Security Administration Borrower Families, 1940: V. Defects of the Nasal Septum; And Chronic Respiratory Affections, Exclusive of Diseased Tonsils

ILLNESS HISTORY AND PHYSICAL GROWTH

It has become a commonplace generalization among physicians, public health workers and others that the growth of children is retarded by pathologic conditions. 1 Some consider that retardation of growth is most marked as a result of severity of illness, 2 while others believe it to be most marked as a result of mild illnesses of long duration. 3 Recourse to published studies shows that such generalizations are neither consistently nor extensively supported by experimental findings. Bowditch, 4 using 1 girl as his subject, reported 3 instances in which a small loss in weight was a precursor of disease. Woodbury, 5 using 57,977 children under 6 years of age, found stature and weight to be below average for those (203) with rachitis but not below average for those with a cardiac abnormality, diseased tonsils or adenoids. Turner, Lougee, Sarabia and Fuller, 6 using some 120 school children, found that the

RECOVERY FROM MULTIPLE RHEUMATOID ARTHRITIS COMPLICATED BY AMYLOIDOSIS IN A CHILD

An unusual and dangerous complication of rheumatoid arthritis is visceral amyloidosis. We have had the opportunity to study a child who recovered from severe multiple rheumatoid arthritis (Still's disease) complicated by generalized amyloidosis. Because of the paucity of records of similar cases we believe it important to report this case and to review the related literature. REPORT OF CASE R. B., was first admitted to the Mount Sinai Hospital when she was 14 years of age. Her illness dated from November 1935, when, at the age of 11, she entered another hospital complaining of sore throat, vomiting and pain in the joints of one week's duration. Tenderness and stiffness of the joints of the arms and legs were found, but there were no deformities. Therapy included two blood transfusions for mild anemia and removal of hypertrophied diseased tonsils. In the subsequent two years the patient had numerous exacerbations of severe