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PubMed2004

A prospective analysis of intrathecal granuloma in chronic pain patients: a review of the literature and report of a surveillance study.

BACKGROUND: Over the past decade granulomas have been noted to occur at or near the tip of intrathecal catheters used for spinal infusions. The majority of cases involved morphine infusions, although other drugs have been implicated. Granulomas may be asymptomatic or cause significant neurological deficits. METHODS: Consecutive patients with intrathecal infusions were examined for the presence of intrathecal granulomas. MRI or CT was used to make the diagnosis. RESULTS: A total of 208 patients underwent imaging over a period of 34 weeks. Six patients (3%) were found to have a significant lesion. Five of the six patients were asymptomatic and one patient complained of radicular pain in the distribution of the catheter tip. The average catheter infusion time for patients with granulomas was 27 months, not significantly different from patients without granulomas. No specific characteristics, such as drugs or concentrations were identified. All six patients had percutaneous catheter revisions without complication. CONCLUSION: Intrathecal granulomas were identified in 3% of patients imaged in this series. Eighty percent of the patients were asymptomatic. MRI imaging remains the diagnostic method of choice for most patients, and can be done safely when scans are taken at the level of the catheter tip. Given the low incidence of granulomas with intrathecal catheters, routine imaging to identify granulomas is not warranted.

Journal Article↗
PubMed1996

[Characterization of structural and cellular components in pulmonary sarcoidosis granuloma].

Granulomas occurring in sarcoidosis with lung involvement are mostly located in the paravasal interstitium, pleura, bronchial mucosa and stroma. The phases and the activity of the disease process are characterised by different patterns from multicellular epitheloidcellular granulomas to marked hyalinisations and scarifications. For the purpose of histochemical characterisation of the composition of the cells and matrix of pulmonary granulomas in open and transbronchial lung biopsies of 15 patients suffering from sarcoidosis in different clinical stages, antibodies were employed against macrophages, neutrophil elastase, collagen types I and III, fibronectin, laminin, PCNA and against the tumour suppressor gene product P53. Identification was subsequently performed either by means of indirect immunofluorescence or the PAP technique. Multicellular granulomas showed, especially centrally, a specific fluorescence for macrophages involving also giant cells, whereas antibodies against neutrophil elastase could be mainly identified peripherally. PCNA and P53 protein were identified in the cytoplasm and partly also in the nuclei of giant cells. Collagen types I and III were mainly expressed pericentrally. Fibronectin was found in numerous multicellular epitheloid cellular granulomas not only in the peripheral collagen network but also centripetally oriented. The scarifying granulomas showed initially increased centripetal deposition of fibronectin followed by an addition of collagen types I and III. Laminin was always present in very small quantities only. The results obtained demonstrate a variable expression of matrix structures in sarcoidosis, dependent on the developmental stages of pulmonary granulomas, this expression being capable of control to some extent with the proportions of epitheloid cells, lymphocytes and macrophages that are present. Tumour suppressor gene p53 positive macrophage giant cells and adhesion molecules such as fibronectin participate in granuloma production to a varying extent.

Biopsy↗
PubMed1997

Cytokine patterns in tuberculous and sarcoid granulomas: correlations with histopathologic features of the granulomatous response.

Cytokines play an important role in granuloma formation, but the extent that cytokine profiles are similar in different granulomatous diseases and whether differences in the histopathologic features of the granulomatous response results from differences in cytokine production have not been evaluated. To investigate these questions, we used RT-PCR to quantify the expression of mRNAs coding for 16 cytokines in granulomatous lymph nodes from patients with tuberculosis and sarcoidosis and from control tissues, and we sought correlations between the level of expression of these cytokines and the histopathologic features of the granulomas. Expression of mRNAs coding for a number of cytokines (IL-1beta, IFN-gamma, TNF-alpha, granulocyte-macrophage (GM)-CSF, IL-12 (p40), and lymphotoxin-beta) was increased in tuberculous and sarcoid granulomas compared with that of control tissues. All sarcoid granulomas were shown to express a Th1 pattern of cytokine mRNAs, while tuberculous lymph nodes expressed either a Th1 or a Th0 profile. GM-CSF and lymphotoxin-beta mRNAs were more abundant in sarcoid than in tuberculous granulomas, whereas IL-8 mRNA was strongly expressed only in tuberculous lymph nodes. Strong expression of GM-CSF, TNF-alpha, and IL-8 by granulomas was shown to be correlated, respectively, with the presence of florid granulomatous lesions, the absence of central necrosis, and the presence of neutrophil infiltration. These results demonstrate that the formation of tuberculous and sarcoid granulomas in humans is associated with the expression of characteristic cytokine profiles and indicate that the expression of certain cytokines is associated with the development of specific pathologic features in the resulting granulomas.

Adult↗
PubMed1991

A comparison of foreign body and hypersensitivity granuloma formation in the mouse: kinetic development, anergy, angiotensin converting enzyme levels, and response to captopril therapy.

Pulmonary granuloma size, anergy, serum and lung angiotensin converting enzyme (ACE) levels, and responsiveness to captopril therapy were measured in both pulmonary hypersensitivity granuloma (HSG) and foreign body granuloma (FBG) murine models. The kinetic development of the granuloma was similar in both models, peaking at 3 days and resolving by 14 days. The granuloma size of the FBG model was significantly larger than the HSG model at 1 and 3 days. The FBG model further differed from the HSG model in that anergy was observed at 3 days and lung ACE levels were increased at 1, 7, and 14 days. In the HSG model anergy was not observed and lung ACE levels were significantly elevated only at 1 and 7 days. Furthermore, the HSG model was shown to be responsive to captopril therapy whereas the FBG model was not. This study shows that two murine pulmonary granuloma models, although displaying similar growth and resolution kinetics, differ in terms of granuloma size, anergy, lung ACE activity, and responsiveness to captopril therapy, suggesting that the mechanism(s) involved in the inflammatory response of the two models may be different.

Animals↗
PubMed1994

Periocular granuloma annulare, nodular type. Occurrence in late middle age.

We describe the two oldest individuals with nodular granuloma annulare (pseudorheumatoid nodules) in the ophthalmologic literature and propose a unified classification scheme that recognizes pseudorheumatoid nodules to be granuloma annulare, nodular type. All lesions in both cases revealed so-called necrobiotic granulomas, characterized by an acellular central area containing mucin (hyaluronic acid) surrounded by palisading histiocytes (macrophages), diagnostic of granuloma annulare. These features are identical to those reported in the ophthalmologic and older general pathology literature as pseudorheumatoid nodules and the contemporary general and dermatologic pathology literature as granuloma annulare. We believe the diagnosis of nodular granuloma annulare should be employed for necrobiotic lesions displaying distinctive clinicopathologic features to unite the ophthalmologic, general, and dermatologic pathology literature. Granuloma annulare, nodular type, must also be considered in the differential diagnosis of ocular and periocular lesions at any age.

Eye↗
PubMed1978

Pulmonary granulomas induced by BCG.

BCG administered by the multiple-puncture technique has been used in a prospective, randomized study of the adjuvant treatment of patients with osteogenic sarcoma. Pulmonary granulomas were found in the lungs of four of five patients receiving BCG, that underwent thoracotomy for the diagnosis of pulmonary nodules within three weeks of the last BCG injection. Except for a single, foreign-body granuloma no pulmonary granulomas were seen in seven randomized patients who did not receive BCG. In addition, two patients receiving BCG had evidence of granulomas in bone marrow and in a mediastinal lymph node. BCG administered by the multiple-puncture technique is capable of causing granulomas at sites distant from that of the BCG application. BCG can cause pulmonary granulomas and these granulomas may be confused with pulmonary metastatic disease.

BCG Vaccine↗
PubMed1983

Regulation of fibroblast functions by products of schistosomal egg granulomas: potential role in the pathogenesis of hepatic fibrosis.

Recent observations suggest a molecular link between granuloma formation and hepatic fibrosis in schistosomiasis. Egg granulomas isolated from Schistosoma mansoni-infected mice, when cultured in serum-free medium, produce a variety of biologically active molecules that affect fibroblast function. One group of molecules--proteins with an estimated relative molecular mass (Mr) of 30 000--stimulate fibroblast proliferation in vitro. These molecules have interleukin (IL)-1-like activity when assayed in thymocyte cultures but are biochemically distinct from previously characterized murine IL-1. Fibroblast mitogenic activity is also produced by macrophages isolated from granulomas and by extracts of S. mansoni eggs. The egg-derived activity is distinct from the granuloma cell-derived material on the basis of Mr and isoelectric point determinations. Egg extracts also contain concanavalin A-binding substances which are not directly mitogenic for fibroblasts but can stimulate spleen cells from infected mice to produce fibroblast mitogenic activity in vitro. A large chemoattractant molecule (greater than 200 000 Mr) for fibroblasts has also been identified in supernatants from granuloma cultures and in supernatants from macrophages isolated from granulomas. This activity is abolished by treatment with anti-fibronectin antibody, suggesting that it is fibronectin or a cleavage product thereof. Molecules similar to or identical with the fibroblast mitogenic factors from the granulomas have been identified, and they inhibit the contraction of fibroblast-populated collagen lattices. These activities may be important in the pathogenesis of hepatic fibrosis in schistosomiasis, and pharmacological modification of their production or of their effects on target fibroblasts might theoretically prevent hepatic fibrosis in this disease.

Animals↗
PubMedDate not supplied

The incidence of spermatic granulomas and their relation to testis weight after vasectomy and vasovasostomy in Lewis rats.

The occurrence of spermatic granulomas of the vas deferens was studied in Lewis rats at intervals up to 7 months after vasectomy or vasectomy followed 3 months later by vasovasostomy. The incidence of granuloma progressed with time to involve one or both tracts in 100% of vasectomized rats. In addition, the majority of animals developed new granulomas after vasovasostomy, even though fluid flow through the reconnected vas deferens was demonstrated in vitro. When individual tracts were analyzed, the weight of the testis was related to ipsilateral spermatic granuloma formation in both vasectomy and vasovasostomy groups at 3 and 4 months after initial operation. Testes were small in the absence of a granuloma but similar to those of sham-operated rats if a granuloma was present. The possible protective effect of spermatic granuloma formation on the testis is discussed.

Animals↗
PubMed2007

Langhans giant cells from M. tuberculosis-induced human granulomas cannot mediate mycobacterial uptake.

Tuberculosis is characterized by a tight interplay between Mycobacterium tuberculosis (M. tb) and host cells within granulomas. These cellular aggregates restrain M. tb spreading but do not kill all bacilli, which persist for years. A more detailed investigation of the interaction between M. tb and granuloma cells is needed to improve our understanding of this persistence and to explain the physiopathology of tuberculosis. In the present study, a recently developed in vitro human model of tuberculous granulomas has been used to analyse the modulation of granuloma cell differentiation by M. tb, in comparison to poorly virulent mycobacteria, which do not persist. It is reported that whilst all mycobacteria species induce granuloma formation, only M. tb triggers the differentiation of granuloma macrophages into very large multinucleated giant cells (MGCs) that are unable to mediate any bacterial uptake. This loss of function is not due to cell quiescence, as MGCs still display NADPH oxidase activity, but it correlates with decreased expression of phagocytosis receptors. This phenomenon is specific for the virulent species of M. tuberculosis complex, as poorly virulent species only induce the formation of small multinucleated cells (MCs) with conserved mycobacterial uptake ability, which never reach the MGC differentiation stage. The phenotype of MGCs thus strongly resembles mature dendritic cells with a loss of microbial uptake ability, despite conserved antigen presentation. In M. tb-induced granulomas, MGCs thus seem to be devoted to the destruction of bacilli that have been ingested in previous differentiation stages, ie in macrophages and MCs.

Antigen-Presenting Cells↗
PubMed1996

Comparative study of CT and MRI in patients with seizures and a solitary cerebral cysticercus granuloma.

We hypothesized that when contrast-enhanced CT reveals a solitary cerebral cysticercus granuloma, MRI would not usually provide additional information that might assist in management. We retrospectively compared visualisation of solitary cysticercus granulomas on contrast-enhanced CT and MRI in 16 patients presenting with seizures; gadolinium (Gd) enhancement was used in 6 patients. The granuloma was delineated well on both CT and MRI in 15 patients; in one patient, in whom CT was performed with 10-mm slices, it was seen only on contrast-enhanced MRI, CT and unenhanced MRI revealing only the surrounding oedema. On CT the granuloma was seen best on thin (2-5 mm) contrast-enhanced sections (in 10 patients). On MRI, Gd-enhanced images showed the granuloma best, as a ring-enhancing lesion, in all 6 patients. In the other 10 patients, the granuloma was seen only on T2-weighted images in 8 and on both T1- and T2-weighted images in 2. On T2-weighted images a characteristic low-signal ring with a high-signal centre was seen in 12 patients. Sensitivity of the imaging techniques was: contrast-enhanced CT (5 and 10 mm slices) 93.8% (15/16); thin (2-5 mm) section contrast-enhanced CT 100% (6/6); unenhanced MRI 93.8% (15/16). MRI did not reveal additional granulomas or cysts in any patient. In patients strongly suspected to be harbouring this lesion, when 10-mm contrast-enhanced CT reveals only oedema, thin (2-5 mm) slice CT is a cost-effective alternative to MRI.

Adolescent↗
PubMed1993

Identification of Schistosoma haematobium soluble egg antigens that elicit human granuloma formation in vitro.

Schistosoma haematobium soluble egg antigens (SH SEAs) induce intense granulomas in human hosts that often culminate in severe disease. In an attempt to identify the SH SEA fractions that are responsible for pathology, we combined T-cell Western blotting and an in vitro model of granuloma formation. Whole SH SEAs were dotted onto nitrocellulose pieces or were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrotransferred onto nitrocellulose paper. Horizontal strips bearing the separated antigens were solubilized in dimethylsulfoxide and precipitated in carbonate/bicarbonate buffer. Antigen-free and antigen-bearing particles were used to stimulate peripheral blood mononuclear cells (PBMCs) obtained from S. haematobium-infected patients and sex- and age-matched healthy controls to form granulomas in vitro. Whole SH SEA-bearing nitrocellulose particles elicited in vitro formation of granulomas by PBMCs from infected donors. The response was similar in sensitivity, specificity, and reproducibility to that evoked by SH SEA-bound polyacrylamide beads. The results obtained in samples form 30 patients and 10 controls tested with SH SEA-separated fractions revealed that SEA bands of 84,000, 63,000, 57,000, 55,000, 40,000, 30,000, and 28,000 Da elicited in vitro granuloma reactions by PBMCs of almost all infected patients. Conversely, separated soluble adult-worm antigens failed to stimulate PBMCs of infected patients to form granulomas. This study is the first to identify the SH SEA fractions that evoke in vitro granuloma formation and represents an initial step toward the development of an anti-urinary schistosomiasis pathology vaccine.

Adolescent↗
PubMed2003

The diagnostic difficulties of meningeal and intracerebral plasma cell granulomas--presentation of three cases.

Meningeal and intracerebral plasma cell granulomas are uncommon inflammatory lesions of unknown etiology. In this paper the diagnostic difficulties in two patients with meningeal plasma cell granuloma and one patient with intracerebral plasma cell granuloma are described. The first patient had an intracranial extra-axial lesion, which was first diagnosed as a meningioma. One and a half years later she underwent a second resection for recurrent tumor growth and the diagnosis of a meningeal plasma cell granuloma was made. The second patient was treated for a central nervous system B-cell lymphoma but proved to have an intracerebral plasma cell granuloma in retrospect 11 years later. In the third patient tuberculous meningitis was considered to be the most likely diagnosis because infratentorial contrast-enhanced thickened meninges (pachymeningitis) were found together with a high protein level in the cerebrospinal fluid and a positive Mantoux test. However, pathological examination of an extra-axial, cervical lesion that was operated upon revealed a meningeal plasma cell granuloma. These cases show the importance of diagnosing a meningeal or intracerebral plasma cell granuloma correctly, since it has both therapeutical and prognostic implications.

Adult↗
PubMed2006

Sarcoid-like lesions associated with the immune restoration inflammatory syndrome in AIDS: absence of polymerase chain reaction detection of Mycobacterium tuberculosis in granulomas isolated by laser capture microdissection.

Highly active antiretroviral therapy (HAART)-treated human immunodeficiency virus (HIV)-positive patients can develop granulomatous lesions within the first few weeks of initiating therapy. This immune syndrome, called immune restoration inflammatory syndrome (IRIS), can induce sarcoid-like lesions in tissues. The pathogenesis of these granulomas is currently unknown because no pathogen has been identified to date in the lesions using morphological and/or microbiological approaches. However, the role of certain microbes, such as Mycobacterium tuberculosis, is still debated. The aim of this study was to look for the presence of M. tuberculosis in sarcoid-like lesions occurring in 14 AIDS patients treated with HAART. We used the PCR DNA amplification method in granulomas microdissected from sections stained by hematoxylin-eosin from formalin-fixed, paraffin-embedded specimens. Results were compared to those obtained from microdissected tuberculosis (TB) granulomas (15 patients) and from microdissected sarcoidosis granulomas (12 patients). M. tuberculosis DNA was undetectable from the microdissected sarcoid-like granulomas, whereas DNA from M. tuberculosis was isolated in all the microdissected TB granulomas and was absent in the microdissected sarcoidosis granulomas. Taken together, these data showed that M. tuberculosis DNA is not associated with the presence of sarcoid-like lesions occurring in HIV-positive patients treated with HAART.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Expression of intercellular adhesion molecule-1 and lymphocytefunction-associated antigen-1 in experimental Schistosoma mansoni infection and in synchronous periparticular hepatic granulomas in mice: immunohistochemistry, confocal laser scanning microscopy, and immunoelectron microscopy.

Adhesion molecules play an important role in inflammatory and immunological responses. We assessed the expression pattern of intercellular adhesion molecule-1 (ICAM-1) and lymphocytefunction-associated antigen-1 (LFA-1) in the livers of mice experimentally infected with Schistosoma mansoni and in synchronous hepatic granulomas induced by injection of soluble egg antigen (SEA)-coupled Sepharose beads in a mesenteric vein of mice. By immunohistochemistry, confocal laser scanning microscopy, and immunoelectron microscopy, ICAM-1 was localized on endothelial cells, sinusoidal-lining cells (Kupffer cells and sinusoidal endothelium), the hepatocyte cell membrane facing Disse's space, and inflammatory cells in the granuloma. LFA-1 was visualized on the inflammatory cells of the granuloma and on phagocytic sinusoidal-lining cells, most likely Kupffer cells. ICAM-1- and LFA-1-immunoreactive cells were present in the granuloma as early as at 3 days after injection of SEA-coupled beads and persisted with time. As granulomas became older, nonimmunoreactive granuloma cells appeared. We conclude that adhesion molecules play an important role in the genesis of the schistosomal granuloma.

Animals↗
PubMed1988

Influence of the acyl-CoA: cholesterol O-acyltransferase inhibitor, CL 277082, on cholesteryl ester accumulation in rabbit macrophage-rich granulomas and hepatic tissue.

The influence of the acyl-CoA: cholesterol O-acyltransferase (ACAT) inhibitor, CL 277082, on macrophage cholesteryl ester accumulation in a rabbit carrageenan granuloma macrophage-foam cell model was studied. Diets were supplemented with 0.3% cholesterol and 6% peanut oil with or without the inhibitor (0.25%) for 4 weeks prior to granuloma induction, and macrophage-rich granuloma tissue was harvested 14 days after carrageenan injection. Serum cholesterol was monitored biweekly, and plasma lipoproteins were isolated terminally. Total, free and esterified cholesterol contents were measured in hepatic and granuloma tissue. In hepatic tissue, administration of CL 277082 resulted in an 80% reduction in the content of total cholesterol, a 37% decrease in free cholesterol, and a 90% decrease in esterified cholesterol. Similarly, in macrophage-rich granuloma tissue, total cholesterol content was decreased by 44%, and esterified cholesterol content by 61%, with no change in free cholesterol. Additionally, CL 277082 was shown to inhibit granuloma tissue ACAT activity by 45%, VLDL mass was decreased slightly, LDL mass increased 3.4-fold and HDL mass was similar in both the inhibitor-treated and control animals. CL 277082 resulted in a 57% decrease in VLDL cholesteryl ester content and a 4.5-fold increase in triacylglycerol. Cholesteryl ester content in LDL was decreased by 31% and LDL triacylglycerol was increased 5.2-fold, while the only change in HDL composition was a 3.5-fold increase in triacylglycerol. The reductions in both hepatic tissue and macrophage-rich granuloma tissue esterified cholesterol accumulation are considered to be due largely to cellular ACAT inhibition, and the altered distribution and composition of the plasma lipoproteins.

Animals↗
PubMed1990

Macrophages within the granulomas of murine Schistosoma mansoni are a source of a somatostatin 1-14-like molecule.

Inflammatory cells secrete some neuropeptides that function as immunomodulators. Somatostatin has immunoregulatory properties. It is unknown whether immune cells make somatostatin. Intricate intercellular communications govern the granulomas of murine Schistosoma mansoni. These granulomas synthesize several neuropeptides. Thus, it was determined whether somatostatin is in these inflammatory lesions. Granulomas, which were isolated from the livers of infected mice, contained somatostatin 1-14 as shown by radioimmunoassay and chromatography. Immunostaining localized immunoreactive somatostatin and pre-prosomatostatin to granuloma macrophages. Granuloma macrophages cultured in vitro released immunoreactive somatostatin. Calcium ionophore A23187, which promotes macrophage secretion, increased somatostatin in the culture supernatants. Thus, the granulomas have a molecule with somatostatin 1-14-like properties that is possibly a secretory product of the granuloma macrophage.

Animals↗
PubMed1985

Arachidonic acid, an in vivo inhibitor of carrageenin induced granulomas in the rat.

Arachidonic acid (AA) injected locally into carrageenin/sponge granulomas, but not if given orally, inhibited granuloma growth. Granuloma macrophage (M0) infiltration was inhibited, and prostaglandin E2 (PGE2) synthesis (ng/100 mg granuloma dry weight) stimulated, by AA treatment. M0 adenosine 3',5'-cyclic monophosphate (cAMP) levels and granuloma exudate volume were not affected. Granuloma M0s incubated in vitro with arachidonic acid synthesised thromboxane B2 (Txb2), 6-ketoprostaglandin F1 alpha (6-ketoPGF1 alpha), and preferentially, PGE2. The AA inhibition of granuloma growth was possibly mediated via the synthesis of PGE2.

6-Ketoprostaglandin F1 alpha↗
PubMedDate not supplied

Suppression of pulmonary hypersensitivity granulomas in mice by superoxide dismutase.

Pulmonary hypersensitivity granulomas were induced in immunized mice by the intratracheal injection of antigen-coupled agarose beads. Foreign body lung granulomas were induced in mice by the intratracheal injection of dextran beads. Both lesions developed within 1 day, reached peak intensity within 3 days, and gradually declined in size thereafter. Hypersensitivity granulomas were much larger than foreign body lesions. The lung extracts prepared from mice with hypersensitivity lung granulomas, but not foreign body lesions, contained high levels of superoxide dismutase (SOD) and thiobarbiturate-reactive substances including lipid peroxides. SOD activity and levels of thiobarbiturate-reactive substances in the extracts correlated with sizes of hypersensitive lesions. Hypersensitivity granulomas, but not foreign body lesions, were inhibited by the administration of recombinant human SOD (rh-SOD). Thiobarbiturate-reactive substances were decreased in the lung extracts of mice bearing hypersensitivity granulomas injected with rh-SOD. These results suggest that reactive oxygen intermediates such as superoxide anion may play an important role in the development of hypersensitivity granulomas and that rh-SOD is capable of inhibiting the lesions by its antioxidant action.

Acetylglucosaminidase↗