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Subacromial space measurement: a reliable method indicating fatty infiltration in patients with rheumatoid arthritis.

Proximal migration of the humeral head is thought to indicate fatty infiltration of the rotator cuff muscles or rotator cuff tears. We sought to evaluate the influence of these rotator cuff abnormalities on the subacromial space. Using anteroposterior radiographs, ultrasound, and computed tomography, we analyzed 54 shoulders in 29 patients with rheumatoid arthritis. The upward migration index was defined as proximal migration of the humeral head relative to its size. The mean muscle density from computed tomography images was used to indicate fatty infiltration. Fatty infiltration of the infraspinatus muscle showed the strongest correlation with proximal migration. After correcting for age, cuff tears, and rheumatoid disease, the partial correlation coefficient between both remained strong. A subdivision in proximal migration is proposed to screen for rotator cuff abnormalities. A large amount of fatty infiltration was indicated by an upward migration index less than 1.25, a medium amount by an upward migration index between 1.25 to 1.35, and a small amount by an upward migration index greater than 1.35. Measurement of proximal migration using the upward migration index provides a reliable screening method indicating fatty infiltration of the rotator cuff.

Acromion↗

Interleukin-1-dependent sequential chemokine expression and inflammatory cell infiltration in ischemia-reperfusion injury.

OBJECTIVE: Ischemia-reperfusion injury is known to cause organ failure, but the mechanisms of pathogenesis remain unclear. Inflammation is a factor in tissue destruction in ischemia reperfusion injury, and interleukin (IL)-1 is a key promoter of inflammation. DESIGN: Prospective, randomized, and controlled study. SETTING: University laboratory. SUBJECTS: Male mice 6-8 wks of age, in which genes for IL-1alpha and IL-1beta (IL-1alpha/beta deficient) and IL-1 receptor antagonist (IL-1RA deficient) are deleted by homologous recombination, and wild-type controls on a Balb/c background. INTERVENTIONS: In this study, the role of IL-1 on inflammatory cascades, including chemokine expression, inflammatory cell infiltration, and tissue destruction, was investigated in 45 mins of unilateral renal ischemic injury using IL-1alpha/beta-deficient mice and IL-1RA-deficient mice. In addition, the effects of IL-1 on chemokine expression in cultured tubular epithelial cells were investigated. MEASUREMENTS AND MAIN RESULTS: In vivo study revealed that the number of interstitial infiltrated neutrophils and macrophages, which accompanied the increase of the serum levels of keratinocyte-derived chemokine (KC) and macrophage inflammatory protein (MIP)-1alpha, respectively, significantly increased in IL-1RA-deficient mice. The number of interstitial infiltrated neutrophils correlated well with serum levels of KC at 24 hrs after reperfusion, whereas the number of interstitial infiltrated macrophages correlated well with the serum levels of MIP-1alpha and monocyte chemoattractant protein (MCP)-1 at 24 and 48 hrs after reperfusion, respectively. Likewise, in vitro study revealed that stimulation of tubular epithelial cells by IL-1beta and/or H2O2 sequentially induced KC, MIP-1alpha, and MCP-1 in both protein and messenger RNA levels, which is consistent with in vivo results. CONCLUSION: IL-1-dependent inflammatory cascades, followed by inflammatory cell infiltration and subsequent tissue destruction, may affect pathogenesis of renal ischemia-reperfusion injury.

Animals↗

Florid CD4+, CD56+ T-cell infiltrate associated with Herpes simplex infection simulating nasal NK-/T-cell lymphoma.

We report a case of Herpes simplex virus (HSV) infection of the nasopharynx associated with a dense CD4+, CD56+ T-cell infiltrate that simulated lymphoma on clinical, histologic, and immunophenotypic grounds. Histologic examination showed a tumorlike lymphoid infiltrate with extensive necrosis. Multinucleated giant cells with "ground-glass" nuclei characteristic of HSV were observed in necrotic areas but were not prominent. Immunohistochemical studies of the lymphoid infiltrate revealed a predominance of T cells, positive for CD3, CD4, CD5, and CD56. Immunohistochemical staining with HSV antibody was focally positive in the multinucleated giant cells. Molecular studies using PCR and Southern blot were positive for HSV Type II. PCR studies for T-cell receptor gamma and immunoglobulin heavy chain gene rearrangements showed no evidence of a clonal population. In situ hybridization studies for Epstein-Barr virus (EBV) were negative. The clinical presentation of a large fungating mass, the extent of the lymphoid infiltrate, and the expression of CD56 all raised the possibility of a nasal NK/T cell lymphoma. However, the presence of HSV, lack of angioinvasion and angiodestruction, absence of EBV, and polyclonal T-cell nature of the infiltrate argued against this diagnosis. Although prior studies have not fully characterized the immunophenotypic features of the lymphocyte response to HSV in infected tissues, we postulate that the CD56+, CD4+ T-cell reaction represents a florid antiviral immune response.

Adult↗

Frequency, histological, and immunohistochemical properties of massive inflammatory lymphocytic infiltration of leiomyomas of the uterus: an entity causing diagnostic difficulties.

Massive lymphocytic infiltration of the leiomyomas of the uterus is rare and causes diagnostic difficulties. The objective of this study is to estimate the frequency, to analyze the clinicopathologic features, to explore the possible pathogenetic factors, and to discuss the differential diagnosis of this entity. We reviewed the pathology reports of 379 patients who underwent surgery for leiomyomas at our institution, from 1999 until 2003, and we identified five cases of leiomyomas with massive lymphocytic infiltration. Thereafter, we reviewed the records of these five patients to identify the clinical, ultrasonographic, and surgical findings they had presented. Leiomyomas with lymphocytic infiltration were characterized by the presence of small lymphocytes, few plasma cells, and occasional germinal lymphocytes such as lymphoblasts confined into the leiomyoma. Immunohistochemistry was positive for desmin and leukocyte common antigen and showed a positive reaction to kappa and lambda light chains that is consistent with the polyclonal nature of an inflammatory infiltration. Gross appearance and ultrasonographic and color Doppler findings were the same as of a typical leiomyoma. Lymphocytic infiltration of leiomyomas is a rare histological entity. Although an inflammatory process seems to be the pathogenetic factor, other mechanisms such as an immunological or autoimmune response, a specific human leukocyte antigen alteration, or a viral infection could also be the cause of this entity. Differential diagnosis must be made from malignant lymphoma, pyomyoma, and inflammatory pseudotumor of the uterus, based on their special histological characteristics.

Adult↗

Reducing complications in cervicofacial rhytidectomy by tumescent infiltration: a comparative trial evaluating 678 consecutive face lifts.

Tumescent infiltration has been widely used in body-contouring surgery to facilitate dissection and reduce blood loss. Although its use in facial surgery has been suggested, there are presently no comparative studies of its efficacy. The aim of this study was to investigate the long-term outcome in a large series of consecutive face lifts performed with and without tumescence. During a 6-year period, 678 consecutive face lifts were performed: 449 without tumescence and 229 with tumescent infiltration using 200 ml on each side of the face. The spectrum of techniques included the extended superficial musculoaponeurotic system (SMAS) procedure, the lateral SMASectomy, the extended supraplatysmal plane lift, and the cutaneous face lift. Complications, such as hematoma, skin necrosis, alopecia, and scar quality, were compared between groups using Fisher's exact test. The use of tumescent infiltration facilitated dissection, particularly in the neck. Postoperative swelling and bruising were reduced in the tumescent group. In comparisons of major complications between groups, no difference was seen in hematoma rate (p > 0.5), although the incidence of other complications was significantly reduced by tumescent infiltration. Significant reduction was observed in the rate of skin necrosis (p = 0.03), alopecia (p = 0.006), hypertrophic scarring (p = 0.001), stretched scarring (p = 0.003), and scar revision (p < 0.001). This is the first comparative study of tumescent infiltration in facial rejuvenation surgery. Tumescence made dissection easier and significantly reduced the incidence of troublesome complications. The surgical technique and aesthetic implications for rejuvenation surgery are discussed.

Anesthetics, Local↗

Heating infiltration solutions used in tumescent liposuction: minimizing surgical risk.

BACKGROUND: Liposuction, one of the most common operations performed by plastic surgeons, is not free of complications. One of the most common factors is patient hypothermia, a factor little studied but one capable of producing severe arrhythmias and cardiac arrest. A comparative clinical study was conducted to determine what effect using tumescent infiltration solutions at room temperature and at body temperature has on vital signs. METHODS: Two similar groups of 15 healthy female subjects were studied. In the first group (group A), subcutaneous solutions were infiltrated at room temperature (24 degrees C), and in the second group (group B), solutions were infiltrated at body temperature (37 degrees C). Vital signs (i.e., heart rate, respiratory rate, temperature, and blood pressure) were monitored every 15 minutes until the basal vital signs were attained. Variables such as age, body mass index, infiltrated and aspirated liquids, and surgery time were very similar for both groups. RESULTS: Although there were differences in heart rate, respiratory rate, and arterial pressure, they were not statistically significant. Nevertheless, the differences between groups A and B for body temperature (34.9 +/- 1.1 degrees C versus 35.7 +/- 1.3 degrees C, respectively) and for the time necessary to attain basal vital signs (120 +/- 8 minutes versus 69 +/- 4 minutes, respectively) were statistically significant (p < 0.05). CONCLUSIONS: Despite the existence of a significant change in the body temperature in healthy female subjects during manipulation of the temperature of the infiltration solution, this change had no important effect on the intraoperative hemodynamic values. Nevertheless, it could have a more significant effect on patients with greater surgical risk.

Adolescent↗

Analysis of major histocompatibility antigens and the mononuclear cell infiltrate in halo nevi.

A series of monoclonal antibodies was used to characterize the nevomelanocytes and the inflammatory infiltrate of 11 halo nevi in different stages of resolution, employing an immunoperoxidase technique. Three of the 11 halo nevi histologically showed signs of mild or moderate nevomelanocytic atypia. It was found that the vast majority of the nevomelanocytes in halo nevi with a dense inflammatory infiltrate markedly expressed HLA-A,B,C antigens, while expression was not demonstrable in nevocellular nests not adjacent to the mononuclear infiltrate. No difference in expression of HLA-A,B,C antigens was found between the 3 cases with mild or moderate nevomelanocytic atypia and the other cases lacking atypia. Expression of HLA-DR (Ia-like) antigens was found on few nevomelanocytes in only 2 of 11 lesions. The cellular composition of the mononuclear inflammatory infiltrate showed a predominance of T cells (80% or more) with a relatively high proportion of cytotoxic/suppressor T cells. Most of the T cells showed signs of activation as judged by staining for HLA-DR antigens. These results demonstrate that the expression of HLA-A,B,C antigens on the nevomelanocytes and the cellular composition of the mononuclear inflammatory infiltrate in halo nevi are very similar to that in malignant melanomas and dysplastic neiv. These findings also indicate the expression of HLA-A,B,C antigens on nevomelanocytes is primarily dependent on the presence of T-cell immune response and not necessarily related to the presence of nevomelanocytic atypia.

Adolescent↗

Characterization of cutaneous infiltrates in MRL/lpr mice monitored from onset to the full development of lupus erythematosus-like skin lesions.

The skin is a primary site injured in lupus erythematosus (LE), but it is still controversial whether the injury is due to cells of the mononuclear infiltrate and which immunocompetent cells play the major role in the development of cutaneous LE. To better characterize the role of immunocompetent cells, we performed an immunohistochemical examination of these cells in LE-like skin lesions in MRL/Mp-lpr/lpr (MRL/lpr) mice. Skin lesions in 60 female MRL/lpr mice were monitored from onset to full development. Skin specimens from each stage were stained for epidermal Ia+ Langerhans cells (Ia(+)-LC), for Thy-1+ dendritic epidermal cells (Thy-1+DEC), and for the phenotype of the mononuclear cell infiltrates. The numbers of Ia(+)-LC and Thy-1+DEC were decreased markedly in the skin lesions at the later stage. However, the numbers of Ia(+)-LC were increased significantly in the central portion of lesions at an early stage and in the peripheral portion of lesions later. L3T4+ cells were predominant, and the L3T4/Lyt-2 ratio was high in dermal infiltrates at an early stage. With advancing stage, the L3T4/Lyt-2 ratio gradually decreased in dermal infiltrates, whereas the Thy-1.2/Lyt-2 ratio in lymph nodes was reversed. L3T4+ cells were especially predominant in dermal infiltrates under the epidermis with increased numbers of Ia(+)-LC. This immunohistochemical analysis of a mouse model of cutaneous LE revealed changes in immunocompetent cell populations with the evolution of skin lesions, and we conclude that Ia(+)-LC and Thy-1+DEC, as well as L3T4+ and Lyt-2+ cells, may play pathogenic roles in the development of skin lesions.

Animals↗

Infiltration of melanoma cells into the type I collagen gel.

Melanoma cells were cultured on type I collagen gel, and the infiltration of of those cells into the gel was observed. B16 murine melanoma cells initially adopted a spherical form on the gel, but they assumed a dendritic form after infiltration into the interior. The degree of infiltration increased very rapidly and was time-dependent. No correlations between the growth rate or melanogenic activity and infiltrative potential were observed. When Syrian hamster and human melanoma cell lines were cultured, the degrees of infiltration varied. This culture system using collagen gel is considered to be a useful in vitro model of tumor cell invasion.

Animals↗

Immunohistochemical studies of infiltrating cells in early and chronic lesions of psoriasis.

The expression of surface antigens on infiltrating cells, epidermal keratinocytes, and dendritic cells in biopsy specimens from 31 patients with psoriasis was examined immunohistochemically. The specimens were divided into early-phase and chronic-phase groups and then examined in a double blind manner. Among the infiltrating cells in the epidermis, CD4-positive cells were dominant in the early phase; CD8-positive cells were dominant in the chronic phase, resulting in a markedly decreased CD4/CD8 ratio in the latter. On the other hand, among the infiltrating cells in the dermal papillae, CD4-positive cells were dominant in both the early and chronic phases; both CD4-positive and CD8-positive cells were more dominant in the chronic phase than in the early one. However, the CD4/CD8 ratios were decreased in both the dermal papillae and the epidermis in the chronic phase. CD1-positive dendritic cells (probably Langerhans cells) were more numerous in the chronic phase than in the early phase. There were no significant differences between the early and chronic phases with regard to the expression of HLA-DR and HLA-DQ antigens on the infiltrating cells. However, the HLA-DR antigens and ICAM-1 (intracellular adhesion molecule-1) were more strongly expressed on epidermal keratinocytes in the chronic phase than in the early phase. LFA-1 alpha (lymphocyte function-associated antigen-1 alpha)-positive cells were also significantly more numerous in the chronic phase than in the early one, consistent with the expression of HLA-DR antigens and ICAM-1 on keratinocytes mentioned above. On the other hand, VLA-4 (integrin alpha 4 beta 1) positive cells were expressed more abundantly in the epidermis in the early phase than in the chronic phase. These results suggest, first, that the chronic phase of psoriasis is as immunologically active as or more active than the early phase. Second, CD4-positive T cells are more important than CD8-positive T cells in the early phase of psoriasis; CD8-positive rather than CD4-positive T cells are more important in the chronic phase. Third, the LFA-1/ICAM-1 pathway may play an important role with regard to cell adhesion of the infiltrating cells in the psoriatic lesions in disease exacerbation or prolongation, whereas the VLA-4/VCAM-1 (vascular cell adhesion molecule-1) pathway may be more important in disease onset.

Adolescent↗

Two distinct mechanisms involved in the infiltration of lymphocytes into tumors.

We have analyzed the mechanism controlling the infiltration of lymphocytes into tumor tissues. W3/25 (+) (helper/inducer phenotype) T cells obtained from tumor tissues of T-9 sensitized rats produced soluble factors. We demonstrated that the soluble factors were responsible for the infiltration of T lymphocytes into tumor tissues by using a modified Boyden chamber technique. We established a system in which we stained filters of the Boyden chamber by an immunoperoxidase technique, thus directly determining the phenotype of cells that had actually migrated into the filters in response to the soluble factors. Upon fractionation of soluble factors produced by W3/25 (+) T cells, four peaks of lymphocyte migration factor (LMF) activity were detected. Peaks B and C exhibited strong LMF activity and specifically attracted R1-10B5 (+) (suppressor/killer phenotype) T cells. Thus, the infiltration of R1-10B5 (+) T cells into tumor tissues was partly explained by LMF produced by tumor-infiltrating W3/25 (+) T cells. The expression of a putative receptor for LMF by lymphocytes may also influence the degree of lymphocyte infiltration into tumors.

Animals↗

Plasma catecholamine concentrations. The effects of infiltration with local analgesics and vasoconstrictors during nasal operations.

Plasma catecholamine concentrations were measured in 19 patients allocated randomly to receive submucous infiltration with 4 ml of either 0.5% lignocaine with adrenaline 1:200 000 or prilocaine 0.5% with octapressin 0.03 iu per ml. Venous blood samples were obtained before and at 2, 5, and 10 minutes following infiltration. Plasma adrenaline increased from 0.35 to 1.72 p mol/ml at 2 minutes infiltration with the former solution whilst there was little change in plasma noradrenaline concentration. No similar peak in adrenaline concentration occurred after infiltration with prilocaine/ octapressin solutions but with both solutions there was a small increase in plasma noradrenaline and adrenaline concentrations 10 minutes after infiltration, at the time of surgical stimulation.

Adolescent↗

In situ immunological characterization of the infiltrating cells in positive patch tests.

Skin biopsies from positive allergic patch tests were analysed by immunoenzymatic labelling of frozen sections with monoclonal antibodies. In seventeen patients the cellular infiltrate consisted of T cells admixed with Langerhans cells/indeterminate cells, but in two patients there were also many B lymphocytes. The B cells were accompanied by dendritic reticulum cells forming B-cell follicles, indistinguishable from those of normal and hyperplastic lymph nodes. There was no correlation between these two immunohistological staining patterns and the sensitizing antigen, the extent of local reaction or the time from epicutaneous application of allergen to examination (2 to 16 days). The ratio between T-helper and T-suppressor cells varied considerably, and showed no correlation with these variables. In all patients the infiltrating T cells expressed HLA-DR antigen. Transferrin receptors were identified on the infiltrating T cells in biopsies from nine patients. These data indicate activation of T cells in the infiltrate from positive patch tests, and support the functional significance of Langerhans cells in the initiation and maintenance of cutaneous contact allergy. An involvement of B cells and B-cell accessory cells in the pathogenesis of contact allergic reactions is also suggested. The presence of dendritic reticulum cells in skin infiltrates from positive patch tests may reflect a functional implication of the skin in the development of B-cell memory.

Adult↗

High incidence of lymphoid infiltration on labial salivary gland biopsy in non-Hodgkin's lymphomas: clinical implications.

Sjögren's syndrome (SS) is characterized by an increased risk of developing a non-Hodgkin's lymphoma (NHL). We performed labial salivary gland biopsy (LSGB) in 103 patients with untreated NHL, negative for human immunodeficiency virus. Median age was 58 years (range 21-79) and M/F 1.3. Using the Working Formulation, 37 patients had low-grade NHL and 66 had intermediate- or high-grade NHL. Dense lymphocytic infiltration (positive focus score 3 or 4) was found in 28 patients. 10 (35%) of these 28 patients fulfilled criteria for possible SS. 15/28 patients had an identical monotypic infiltrate on LSGB and NHL tissue (including two of the 10 patients with criteria for SS). The significance of the lymphoid infiltrate of LSGB was unknown in the five remaining patients with positive focus score. Significant correlations were found between positive focus score and presence of two or more extranodal sites of disease (P = 0.02), impaired performance status (P = 0.004), splenomegaly (P = 0.05), increased gammaglobulin level (P = 0.03), and beta 2 microglobulin (P = 0.004). Considering intermediate- or high-grade NHL, we found significant correlation between positive focus score and unfavourable prognosis according to the two Dana Farber Cancer Institute indexes (P < 0.04), to the LNH-84 index (P = 0.05), and to the international index (P = 0.003). In conclusion, systematic evaluation of LSGB in 103 patients with NHL found lymphoid infiltration in 28% of them, but possible SS could be considered in only 10%. This lymphoid infiltration, though not correlated with any particular histological subtypes, was associated with unfavourable clinical prognostic factors, especially in intermediate- or high-grade NHL.

Adult↗

Flow cytometric and functional analysis of mononuclear cells infiltrating the liver in experimental autoimmune hepatitis.

Experimental autoimmune hepatitis was produced by immunizing Wistar rats with syngeneic liver proteins. Mononuclear cells infiltrating the liver tissue were identified by immunohistochemical techniques using monoclonal antibodies specific for subpopulations of rat lymphocytes. The strong infiltration of CD8+ cytotoxic T lymphocytes (CTL) were found in the portal areas. Subpopulations of mononuclear cells infiltrating the liver, spleen cells and peripheral blood lymphocytes were identified by flow cytometry. Flow cytometric analysis revealed the presence of CD5- and CD8+ lymphocytes in the liver tissues. Mononuclear cells infiltrating the liver were isolated from Wistar rats having autoimmune hepatitis to determine whether those exhibit cytotoxicity against syngeneic hepatocytes; they exhibited cytotoxicity against isolated syngeneic hepatocytes, but failed to lyse K562 cells, syngeneic concanavalin A-activated splenocytes and allogeneic hepatocytes. Depletion of CD8+ T cells significantly reduced the cytotoxic ability of mononuclear cells infiltrating into the liver against syngeneic hepatocytes. These findings support the idea that liver cell injury in experimental autoimmune hepatitis may at least in part be mediated by CTL.

Animals↗

Somatostatin is a specific inhibitor of SDF-1alpha-induced T cell infiltration.

The chemokine stromal cell-derived factor 1alpha (SDF-1alpha) is a potent stimulator of T cell infiltration into three-dimensional type I collagen matrices as demonstrated using T cells freshly isolated from blood and an activated T cell clone. The neuropeptide somatostatin selectively inhibits SDF-1alpha induced T cell infiltration by the same T cells including CD4 as well as CD8 positive cells, while somatostatin does not inhibit 'spontaneous' T cell infiltration. A number of other neuropeptides and opioids do not inhibit SDF-1alpha-induced T cell infiltration, indicating that the inhibitory effect is somatostatin-specific. The neuropeptide antagonist cyclosomatostatin abrogated the inhibitory effect of somatostatin on T cell infiltration, indicating that the effect of somatostatin is mediated via specific somatostatin receptors. Somatostatin does not inhibit SDF-1alpha-induced T cell attachment to the collagen substrate, which indicates that this neuropeptide specifically inhibits the process of chemokine-induced T cell penetration and migration through the collagen.

Cells, Cultured↗

Pagetoid infiltration in primary cutaneous melanoma.

Pagetoid infiltration of the epidermis by melanocytes, also termed 'buckshot spread', is regarded by some as being essential for the confident histopathological diagnosis of primary cutaneous melanoma. We have reviewed 340 melanomas received over a 23 year period to assess the frequency of pagetoid infiltration and whether its presence bears any relationship with other histopathological features. Conspicuous pagetoid infiltration was present in 32.1% of the lesions and occasional melanocytes were observed within the stratum spinosum in a further 23.5% of cases. However, no melanocytes could be seen above the basal layer in 44.4% of the melanomas. The presence of pagetoid infiltration showed inverse correlation with tumour thickness, level of invasion, growth phase and mitotic count, and positive correlation with the presence and severity of regression. No association was found with the site of the primary lesion, melanocytic dysplasia or lentigo maligna in the adjacent epidermis, or with the presence of residual benign naevus cells in the epidermis. Thus, pagetoid infiltration of the epidermis was commonest in in situ or thin horizontal growth phase melanomas, and was conspicuous in only one-third of cases. While its presence is useful in the diagnosis of melanoma, its absence should not preclude it.

Humans↗

Incidence of testicular mononuclear cell infiltrates in normal human males and in patients with germ cell neoplasia.

The incidence of mononuclear cell (MNC) infiltrates was studied in the testes of the following: 45 patients with carcinoma in situ (CIS) as the only lesion in the testis, CIS accompanied by an early invasion of CIS or CIS accompanied by invasive germ cell tumour (GCT) of the testis; 100 men and 146 boys who had died suddenly and unexpectedly, and 100 infertility patients. The results suggest that (1) the incidence of MNC infiltration increases with increasing severity of testicular malignant changes, (2) increased MNC infiltration is also evident in the contralateral testis where no malignant cells can be observed, (3) the incidence of MNC infiltration in men who died suddenly is not different from that in men who have had their testes biopsied because of infertility, and (4) the incidence of MNC infiltration is high in testes of boys younger than 1 year of age.

Adolescent↗